We describe a most straightforward synthetic method for preparing neurokinin‐1 (NK1) receptor antagonist derivatives by asymmetric hydrogenation of 3‐amido‐2‐arylpyridinium salts using dinuclear iridium complexes with enantiopure diphosphine ligands, affording the corresponding chiral piperidines in high cis‐diastereoselectivity (>95:5) and moderately high enantioselectivity (up to 86%). Deprotection treatments afforded the NK‐1 receptor antagonist (+)‐CP‐99,994 (83% ee). In addition, we observed unique additive effects of 10‐camphorsulfonic acid in the asymmetric hydrogenation of 3‐amido‐2‐arylpyridinium salts.

Significant differences in the adjusted risk of stress incontinence among Hispanic, white, black and Asian-American women suggest the presence of additional, as yet unrecognized, risk or protective factors for stress incontinence.

Purpose-We compared the impact of mixed, stress and urge urinary incontinence on quality of life in middle-aged or older women.Materials and Methods-We analyzed cross-sectional data from a population based cohort of 2,109 ethnically diverse middle-aged or older women. Among participants reporting weekly incontinence, clinical type of incontinence was assessed by self-reported questionnaires and disease specific quality of life impact was evaluated using the Incontinence Impact Questionnaire. Multivariable logistic regression was used to compare the odds of greater quality of life impact from incontinence, defined as an Incontinence Impact Questionnaire score in the 75th percentile or greater in women with stress, urge and mixed incontinence.Results-More than 28% (598) of women reported weekly incontinence, including 37% with stress, 31% with urge and 21% with mixed incontinence. Unadjusted Incontinence Impact Questionnaire scores were higher for women with mixed vs urge or stress incontinence (median score 29 vs 17 and 13, respectively, p <0.01). Adjusting for age, race/ethnicity, health status and clinical incontinence severity, women with mixed incontinence were more likely to report a greater overall quality of life impact compared to those with stress incontinence (OR 2.5, 95% CI 1.4-4.3), as well as a greater specific impact on travel (OR 2.2, 95% CI 1.3-3.7) and emotional (OR 1.8, 95% CI 1.0 -3.4) Incontinence Impact Questionnaire domains. The overall impact of urge incontinence did not differ significantly from that of stress (urge vs stress OR 1.6, 95% CI 0.9 -2.7) or mixed incontinence (mixed vs urge OR 1.6, 95% CI 0.9 -2.8) in adjusted models.Conclusions-In middle-aged or older women mixed incontinence is associated with a greater quality of life impact than stress incontinence independent of age, race, health or incontinence severity. Identification of women with mixed incontinence symptoms may be helpful in discovering which women are most likely to experience functional limitations and decreased well-being from incontinence. Urinary incontinence is a common problem in middle-aged or older women, with up to 25% of reproductive age women and 50% of postmenopausal women reporting at least weekly incontinence. 1 While incontinence does not lead to death it can have a profound effect on quality of life 2,3 comparable to that of stroke, arthritis and chronic obstructive pulmonary disease. 4 In addition, incontinence accounts for more than $20 billion in annual expenditures in the United States, an amount greater than the annual direct costs of breast, ovarian, cervical and uterine cancers combined. 5 KeywordsTo date, most studies examining the impact of incontinence on quality of life have not distinguished among stress, urge and mixed incontinence. Additionally, many prior studies have been limited by a focus on specialized clinical populations 3,6,7 or the use of quality of life instruments that are not disease specific 6,8 and, thus, are less sensitive in measuring the specific impact of incont...

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Patients who deteriorate in the hospital outside the intensive care unit (ICU) have higher mortality and morbidity than those admitted directly to the ICU. As more hospitals deploy comprehensive inpatient electronic medical records (EMRs), attempts to support rapid response teams with automated early detection systems are becoming more frequent. We aimed to describe some of the technical and operational challenges involved in the deployment of an early detection system. This 2-hospital pilot, set within an integrated healthcare delivery system with 21 hospitals, had 2 objectives. First, it aimed to demonstrate that severity scores and probability estimates could be provided to hospitalists in real time. Second, it aimed to surface issues that would need to be addressed so that deployment of the early warning system could occur in all remaining hospitals. To achieve these objectives, we first established a rationale for the development of an early detection system through the analysis of risk-adjusted outcomes. We then demonstrated that EMR data could be employed to predict deteriorations. After addressing specific organizational mandates (eg, defining the clinical response to a probability estimate), we instantiated a set of equations into a Java application that transmits scores and probability estimates so that they are visible in a commercially available EMR every 6 hours. The pilot has been successful and deployment to the remaining hospitals has begun.