Validation of a simple body map to measure widespread pain in urologic chronic pelvic pain syndrome: A MAPP Research Network study.

PURPOSE: In patients with urologic chronic pelvic pain syndrome (UCPPS), the presence of widespread pain appears to identify a distinct phenotype, with a different symptom trajectory and potentially different response to treatment than patients with pelvic pain only. MATERIALS AND METHODS: A 76-site body map was administered four times, at weekly intervals, to 568 male and female UCPPS participants in the MAPP Network protocol. The 76 sites were classified into 13 regions (1 pelvic region and 12 nonpelvic regions). The degree of widespread pain was scored from 0 to 12 based on the number of reported nonpelvic pain regions. This continuous body map score was regressed over other measures of widespread pain, with UCPPS symptom severity, and with psychosocial variables to measure level of association. These models were repeated using an updated body map score (0-12) that incorporated a threshold of pain ≥ 4 at each site. RESULTS: Body map scores showed limited variability over the 4 weekly assessments, indicating that a single baseline assessment was sufficient. The widespread pain score correlated highly with other measures of widespread pain and correlated with worsened UCPPS symptom severity and psychosocial functioning. Incorporating a pain severity threshold ≥4 resulted in only marginal increases in these correlations. CONCLUSIONS: These results support the use of this 13-region body map in the baseline clinical assessment of UCPPS patients. It provides reliable data about the presence of widespread pain and does not require measurement of pain severity, making it relatively simple to use for clinical purposes.

Reliability and Validity of Pain and Urinary Symptom Severity Assessment in Urological Chronic Pelvic Pain: A MAPP Network Analysis.

PURPOSE: We assessed the reliability and validity of an efficient severity assessment for pelvic pain and urinary symptoms in urological chronic pelvic pain syndrome, which consists of interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome. MATERIALS AND METHODS: A total of 578 patients were assessed using brief, empirically derived self-report scales for pelvic pain severity (PPS) and urinary symptom severity (USS) 4 times during a 1-month period and baseline clinic visit that included urological, pain and illness-impact measures. Mild, moderate and severe categories on each dimension were examined for measurement stability and construct validity. RESULTS: PPS and USS severity categories had adequate reliability and both discriminant validity (differential relationships with specific clinical and self-report measures) and convergent validity (common association with nonurological somatic symptoms). For example, increasing PPS was associated with pelvic tenderness and widespread pelvic pain, whereas USS was associated with urgency during a bladder filling test and increased sensory sensitivity. PPS and USS categories were independently associated with nonurological pain and emotional distress. A descriptive analysis identified higher likelihood characteristics associated with having moderate to severe PPS or USS or both. Lack of sex interactions indicated that the measures are comparable in interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome. CONCLUSIONS: Women and men with urological chronic pelvic pain syndrome can be reliably subgrouped using brief self-report measures of mild, moderate or severe pelvic pain and urinary symptoms. Comparisons with a broad range of clinical variables demonstrate the validity and potential clinical utility of these classifications, including use in clinical trials, health services and biological research.

Cross-situational consistency of trait expressions and injunctive norms among Asian Canadian and European Canadian undergraduates.

OBJECTIVE: In the current paper, we sought to clarify when and why Asian Americans/Canadians and European Americans/Canadians differ in self-consistency (the consistency of personality traits across situations). METHOD: European Canadian (n = 220) and second-generation Asian Canadian (n = 166) undergraduates (Mage = 19 years) described the traits they expressed and the traits others wanted them to express (i.e., injunctive norms, or injunctions) in four different social situations (i.e., with parents, with friends, with siblings, and with professors). RESULTS: Self-consistency was greater among European Canadians than Asian Canadians, but only when comparing behavior with parents versus with peers (i.e., friends and siblings). The same pattern was found for injunctive consistency (cross-situational consistency of trait injunctions). Injunctions strongly predicted the behavior of both Asian and European Canadians, but because the injunctions from parents versus peers diverged more for Asian Canadians, so did their behaviors. Controlling for the effect of inconsistent injunctions across situations eliminated the ethnic difference in self-consistency. Finally, Asian Canadians who perceived their immigrant parents as embracing a Canadian identity were as cross-situationally consistent as European Canadians because they tended to behave-and believe their parents approved of their behaving-with parents similarly to how they behaved with peers (e.g., more carefree and outspoken). CONCLUSION: Contrary to previous theorizing, cultural influences on broad cognitive or motivational dispositions (e.g., dialecticism, collectivism) alone cannot explain the observed pattern of ethnic differences in consistency. To understand when bicultural individuals are less consistent across situations also requires an understanding of the specific situations across which they tend to encounter divergent social norms. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Interpersonal Circumplex Profiles Of Persistent Depression: Goals, Self-Efficacy, Problems, And Effects Of Group Therapy.

OBJECTIVES: We assessed severely and persistently depressed patients' interpersonal self-efficacy, problems, and goals, plus changes in interpersonal functioning and depression during 20 weeks of group therapy. METHOD: Outpatients (32 female, 26 male, mean age = 45 years) completed interpersonal circumplex measures of goals, efficacy, and problems before completing 20 weeks of manualized group therapy, during which we regularly assessed depression and interpersonal style. RESULTS: Compared to normative samples, patients lacked interpersonal agency, including less self-efficacy for expressive/assertive actions; stronger motives to avoid conflict, scorn, and humiliation; and more problems with being too submissive, inhibited, and accommodating. Behavioral Activation and especially Cognitive Behavioral Analysis System of Psychotherapy interventions produced improvements in depression and interpersonal agency, with increases in "agentic and communal" efficacy predicting subsequent decreases in depression. CONCLUSIONS: While severely and persistently depressed patients were prone to express maladaptive interpersonal dispositions, over the course of group therapy, they showed increasingly agentic and beneficial patterns of cognitions, motives, and behaviors.

Examining the Process of Responding to Circumplex Scales of Interpersonal Values Items: Should Ideal Point Scoring Methods Be Considered?

The Circumplex Scales of Interpersonal Values (CSIV) is a 64-item self-report measure of goals from each octant of the interpersonal circumplex. We used item response theory methods to compare whether dominance models or ideal point models best described how people respond to CSIV items. Specifically, we fit a polytomous dominance model called the generalized partial credit model and an ideal point model of similar complexity called the generalized graded unfolding model to the responses of 1,893 college students. The results of both graphical comparisons of item characteristic curves and statistical comparisons of model fit suggested that an ideal point model best describes the process of responding to CSIV items. The different models produced different rank orderings of high-scoring respondents, but overall the models did not differ in their prediction of criterion variables (agentic and communal interpersonal traits and implicit motives).

Synthesis and biological evaluation of novel pyrrolidine acid analogs as potent dual PPARα/γ agonists.

The design, synthesis and structure-activity relationships of a novel series of 3,4-disubstituted pyrrolidine acid analogs as PPAR ligands is outlined. In both the 1,3- and 1,4-oxybenzyl pyrrolidine acid series, the preferred stereochemistry was shown to be the cis-3R,4S isomer, as exemplified by the potent dual PPARα/γ agonists 3k and 4i. The N-4-trifluoromethyl-pyrimidinyl pyrrolidine acid analog 4i was efficacious in lowering fasting glucose and triglyceride levels in diabetic db/db mice.

Trait-specificity versus global positivity: A critical test of alternative sources of assumed similarity in personality judgments.

For decades, a recurring question in person perception research has been whether people's perceptions of others' personality traits are related to how they see themselves on these traits. Indeed, evidence for such "assumed similarity" effects has been found repeatedly, at least for certain characteristics. However, recent research suggests that these findings may be an artifact of individual differences in how positively or negatively perceivers see others in general, irrespective of trait-specific content. Overcoming the limitations of prior studies, the present work provides a critical test of trait-specificity versus global positivity as sources of assumed similarity in personality judgments. In two large studies (Ns = 2,287 and 3,563) with preregistered hypotheses and analyses, perceivers rated 10 targets (strangers) each on the honesty-humility, emotionality, extraversion, agreeableness, conscientiousness, and openness to experience; HEXACO (Study 1) and Big Five (Study 2) dimensions to capture their perceptions of the "average other" (i.e., perceiver effects). We then computed "positivity-corrected" assumed similarity effects using trait-based and profile-based approaches. Although controlling for global positivity considerably reduced the strength of assumed similarity, perceiver effects were still positively related to self-reports. As predicted, these assumed similarity effects occurred foremostly for traits strongly linked to values. Specifically, in Study 1, positivity-corrected assumed similarity was observed only for honesty-humility and openness to experience, albeit meaningful effects merely occurred on one of the two self-report measures. In Study 2, traits' value-relatedness remained a unique moderator of assumed similarity after accounting for traits' positivity (i.e., social desirability). These findings demonstrate that assumed similarity is indeed, to some extent, trait-specific. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Widespread Pain Phenotypes Impact Treatment Efficacy Results in Randomized Clinical Trials for Interstitial Cystitis/Bladder Pain Syndrome: A MAPP Network Study.

Clinical trials of pain are notoriously difficult and inefficient in demonstrating efficacy even for known efficacious treatments. Determining the appropriate pain phenotype to study can be problematic. Recent work has identified the extend of widespread pain as an important factor in the likelihood of response to therapy, but has not been tested in clinical trials. Using data from three previously published negative studies of the treatment of interstitial cystitis/ bladder pain with data on the extent of widespread pain, we examined the response of patients to different therapies base on the amount of pain beyond the pelvis. Participants with predominately local but not widespread pain responded to therapy targeting local symptoms. Participants with widespread and local pain responded to therapy targeting widespread pain. Differentiating patients with and without widespread pain phenotypes may be a key feature of designing future pain clinical trials to demonstrate treatments that are effective versus not.

Quantitation of the results of abdominal liposuction.

BACKGROUND: There are few objective techniques to accurately measure the outcome of liposuction. Consequently, there is also a paucity of data quantifying the results of this procedure. OBJECTIVES: The authors compare changes in abdominal volume and circumference with several objective measurement techniques in a relatively homogeneous group of individuals undergoing liposuction in a single, defined abdominal region. METHODS: This clinical study enrolled 23 patients with a body mass index (BMI) <25 kg/m(2) who had a localized anterior abdominal contour defect. Patients underwent standard suction-assisted tumescent liposuction. Changes in abdominal volume and circumference in the operative area (60 mm above to 80 mm below the umbilicus) preoperatively and 10 weeks postoperatively were assessed using a 3-dimensional (3D) digital photographic system and a standardized constant-tension manual tape measure procedure. RESULTS: The majority of the patients in this study were Caucasian women with a mean age of 42 years, a mean weight of 65.8 kg, and a mean BMI of 23.8 kg/m(2). In the study population, mean abdominal volume and umbilical circumference were reduced by 231.0 mL (~30% of subcutaneous fat) and 1.7 cm, respectively, at 10 weeks postoperatively as determined by 3D digital imaging. Fat volume in the surgical aspirate (mean = -183.3 mL) was a poor predictor of individual outcome, as assessed 10 weeks postoperatively by both the 3D digital imaging and multilevel constant-tension tape measure assessment tools. CONCLUSIONS: Both 3D digital photographic imaging and a standardized manual tape measurement procedure proved to be reliable tools for objectively assessing changes in abdominal circumference and volume produced by standard liposuction of a single, defined abdominal region.

An efficient and accurate distributed learning algorithm for modeling multi-site zero-inflated count outcomes.

Clinical research networks (CRNs), made up of multiple healthcare systems each with patient data from several care sites, are beneficial for studying rare outcomes and increasing generalizability of results. While CRNs encourage sharing aggregate data across healthcare systems, individual systems within CRNs often cannot share patient-level data due to privacy regulations, prohibiting multi-site regression which requires an analyst to access all individual patient data pooled together. Meta-analysis is commonly used to model data stored at multiple institutions within a CRN but can result in biased estimation, most notably in rare-event contexts. We present a communication-efficient, privacy-preserving algorithm for modeling multi-site zero-inflated count outcomes within a CRN. Our method, a one-shot distributed algorithm for performing hurdle regression (ODAH), models zero-inflated count data stored in multiple sites without sharing patient-level data across sites, resulting in estimates closely approximating those that would be obtained in a pooled patient-level data analysis. We evaluate our method through extensive simulations and two real-world data applications using electronic health records: examining risk factors associated with pediatric avoidable hospitalization and modeling serious adverse event frequency associated with a colorectal cancer therapy. In simulations, ODAH produced bias less than 0.1% across all settings explored while meta-analysis estimates exhibited bias up to 12.7%, with meta-analysis performing worst in settings with high zero-inflation or low event rates. Across both applied analyses, ODAH estimates had less than 10% bias for 18 of 20 coefficients estimated, while meta-analysis estimates exhibited substantially higher bias. Relative to existing methods for distributed data analysis, ODAH offers a highly accurate, computationally efficient method for modeling multi-site zero-inflated count data.

Synthesis and structure-activity relationships of 2-aryl-4-oxazolylmethoxy benzylglycines and 2-aryl-4-thiazolylmethoxy benzylglycines as novel, potent PPARalpha selective activators- PPARalpha and PPARgamma selectivity modulation.

The synthesis and follow-up SAR studies of our development candidate 1 by incorporating 2-aryl-4-oxazolylmethoxy and 2-aryl-4-thiazolylmethoxy moieties into the oxybenzylglycine framework of the PPARalpha/gamma dual agonist muraglitazar is described. SAR studies indicate that different substituents on the aryloxazole/thiazole moieties as well as the choice of carbamate substituent on the glycine moiety can significantly modulate the selectivity of PPARalpha versus PPARgamma. Potent, highly selective PPARalpha activators 2a and 2l, as well as PPARalpha activators with significant PPARgamma activity, such as 2s, were identified. The in vivo pharmacology of these compounds in preclinical animal models as well as their ADME profiles are discussed.

Beyond paging: building a web-based communication tool for nurses and physicians.

INTRODUCTION: The traditional means of communication between nurses and physicians is through paging. This method is disruptive to the workflow of both professions and is too non-specific to be used for all types of messages. AIMS: We undertook a quality improvement project to streamline communication between nurses and trainees for urgent and non-urgent matters. We assessed user uptake and satisfaction with the new method. SETTING: A General Internal Medicine teaching unit in a tertiary care academic centre. METHODS: Through collaborative techniques, we developed a novel communication method that sends non-urgent messages to a Web-based task list and urgent messages to an alphanumeric pager. We implemented this new technology using a collaborative process between nurses and physicians to address all concerns. EVALUATION: Post-implementation surveillance indicated a high degree of uptake of the new practice. User surveys and focus groups showed a high level of satisfaction and a perceived decrease in interruptions to the workflow of both nurses and physicians with the new system. Usage data indicated that the new system may increase overall non-urgent communication. CONCLUSION: A Web-based system to triage urgent and non-urgent messages between nurses and physicians was developed collaboratively and implemented successfully to improve workflow for both groups.

Design, synthesis and structure-activity relationships of azole acids as novel, potent dual PPAR alpha/gamma agonists.

The design, synthesis and structure-activity relationships of a novel series of N-phenyl-substituted pyrrole, 1,2-pyrazole and 1,2,3-triazole acid analogs as PPAR ligands are outlined. The triazole acid analogs 3f and 4f were identified as potent dual PPARalpha/gamma agonists both in binding and functional assays in vitro. The 3-oxybenzyl triazole acetic acid analog 3f showed excellent glucose and triglyceride lowering in diabetic db/db mice.

Development and Validation of a Circumplex Measure of the Interpersonal Culture in Work Teams and Organizations.

Interpersonal circumplex (IPC) inventories assess a range of dispositions but can condense and compare their findings within a circular model defined by two factors: agency and communion. Whereas other IPC inventories assess individuals, the current research introduces IPC inventories assessing the interpersonal culture (interaction and communication norms) characterizing an entire organization or team-namely, the Circumplex Culture Scan (CCS) and Circumplex Team Scan (CTS). Across an initial development sample (n = 1676), online validation sample (CCS, n = 808; CTS, n = 832), and onsite validation sample (CCS, n = 516 respondents from 21 organizations; CTS, n = 347 respondents from 38 teams), the eight 8-item CCS/CTS octant scales demonstrated good internal consistencies, circumplex properties, reliable within-group agreement and between-group variance (thus justifying aggregation across an organization/team), and convergent, discriminant, and incremental validity in relation to other measures. According to their members, the organizations/teams with the most satisfied members and customers/clients were organizations/teams with considerably stronger communal (e.g., being open and respectful) than uncommunal (e.g., being rude and guarded) norms and somewhat stronger agentic (e.g., being eager and assertive) than unagentic (e.g., being cautious and quiet) norms. The CCS/CTS complements existing IPC and organizational culture measures and helps bridge the IPC and organizational literatures.

ENHANZE® drug delivery technology: a novel approach to subcutaneous administration using recombinant human hyaluronidase PH20

ENHANZE® drug delivery technology is based on the proprietary recombinant human hyaluronidase PH20 enzyme (rHuPH20; Halozyme Therapeutics, Inc.) that facilitates the subcutaneous (SC) delivery of co-administered therapeutics. rHuPH20 works by degrading the glycosaminoglycan hyaluronan (HA), which plays a role in resistance to bulk fluid flow in the SC space, limiting large volume SC drug delivery, dispersion, and absorption. Co-administration of rHuPH20 with partner therapies can overcome administration time and volume barriers associated with existing SC therapeutic formulations, and has been shown to reduce the burden on patients and healthcare providers compared with intravenous formulations. rHuPH20 (as HYLENEX® recombinant) is currently FDA-approved for subcutaneous fluid administration for achieving hydration, to increase the dispersion and absorption of other injected drugs, and in subcutaneous urography for improving resorption of radiopaque agents. rHuPH20 is also co-formulated with two anticancer therapies, trastuzumab (i.e. Herceptin® SC) and rituximab (i.e. RITUXAN HYCELA®/RITUXAN® SC/MabThera® SC) and dosed sequentially with human immunoglobin to treat primary immunodeficiency (i.e. HyQvia®/HYQVIA®). This article reviews pharmaceutical properties of rHuPH20, its current applications with approved therapeutics, and the potential for future developments.

Novel peroxisome proliferator-activated receptor alpha agonists lower low-density lipoprotein and triglycerides, raise high-density lipoprotein, and synergistically increase cholesterol excretion with a liver X receptor agonist.

The first generation peroxisome proliferator-activated receptor (PPAR) alpha agonist gemfibrozil reduces the risk of major cardiovascular events; therefore, more potent PPARalpha agonists for the treatment of cardiovascular diseases have been actively sought. We describe two novel, potent oxybenzylglycine PPARalpha-selective agonists, BMS-687453 [N-[[3-[[2-(4-chlorophenyl)-5-methyl-4-oxazolyl]methoxy]phenyl]methyl]-N-(methoxycarbonyl)-glycine] and BMS-711939 N-[[5-[[2-(4-chlorophenyl)-5-methyl-4-oxazolyl]methoxy]-2-fluorophenyl]methyl]-N-(methoxycarbonyl)-glycine], that robustly increase apolipoprotein (Apo) A1 and high-density lipoprotein cholesterol in human ApoA1 transgenic mice and lower low-density lipoprotein-cholesterol and triglycerides in fat-fed hamsters. These compounds have much lower potency against mouse PPARalpha than human PPARalpha; therefore, they were tested in PPARalpha-humanized mice that do not express murine PPARalpha but express human PPARalpha selectively in the liver. We developed hepatic gene induction as a novel biomarker for efficacy and demonstrate hepatic gene induction at very low doses of these compounds. BMS-711939 induces fecal cholesterol excretion, which is further increased upon cotreatment with a liver X receptor (LXR) agonist. It is surprising that this synergistic increase upon coadministration is also observed in mice that express PPARalpha in the liver only. BMS-711939 also prevented the LXR agonist-induced elevation of serum triglycerides. Such PPARalpha agonists could be attractive candidates to explore for the treatment of cardiovascular diseases, especially in combination with a suitable LXR agonist.

Design, synthesis, and structure-activity relationships of piperidine and dehydropiperidine carboxylic acids as novel, potent dual PPARalpha/gamma agonists.

Several series of substituted dehydropiperidine and piperidine-4-carboxylic acid analogs have been designed and synthesized as novel, potent dual PPARalpha/gamma agonists. The SAR of these series of analogs is discussed. A rare double bond migration occurred during the basic hydrolysis of the alpha,beta-unsaturated dehydropiperidine esters 12, and the structures of the migration products were confirmed through a series of 2D NMR experiments.

Discovery of azetidinone acids as conformationally-constrained dual PPARalpha/gamma agonists.

A novel class of azetidinone acid-derived dual PPARalpha/gamma agonists has been synthesized for the treatment of diabetes and dyslipidemia. The preferred stereochemistry in this series for binding and functional agonist activity against both PPARalpha and PPARgamma receptors was shown to be 3S,4S. Synthesis, in vitro and in vivo activities of compounds in this series are described. A high-yielding method for N-arylation of azetidinone esters is also described.

Interpersonal Self-Efficacy, Goals, and Problems of Persistently Depressed Outpatients: Prototypical Circumplex Profiles and Distinctive Subgroups.

Severely and persistently depressed outpatients ( n = 138) completed interpersonal circumplex measures of self-efficacy, problems, and values/goals. Compared with normative samples, patients showed deficits in agency: They reported less self-efficacy, especially for being assertive, tough, and influential; stronger goals, especially to avoid conflict or humiliation; and more problems, especially with being too timid, inhibited, and accommodating. Circular and structural summary indices suggested greater variability among patients in goal profiles than in efficacy or problem profiles; nonetheless, latent profile analyses identified coherent subgroups of patients with distinct patterns of efficacy (e.g., lacking confidence for speaking up vs. setting boundaries) and problems (e.g., being overly inhibited vs. self-sacrificing) as well as goals (e.g., to be included vs. unobtrusive). Women and those with more severe symptoms were overrepresented in the least agentic groups. The results show how observing patients through multiple circumplex surfaces simultaneously can help clarify their interpersonal dispositions and inform interventions.