Publications

OBJECTIVE: To evaluate the association between pharmacologic therapy for urgency urinary incontinence (UUI) and sleep quality.

METHODS: We conducted a planned secondary data analysis of sleep outcomes in a previously conducted multicenter, double-blind, 12-week randomized trial of pharmacologic therapy for urgency-predominant incontinence among community-dwelling women self-diagnosed using the 3-Incontinence Questions questionnaire. Participants (N=645) were assigned randomly to 4-8 mg antimuscarinic therapy daily or placebo. At baseline and 12 weeks, participants completed a validated voiding diary to evaluate incontinence and voiding symptoms, the Pittsburgh Sleep Quality Index to evaluate sleep quality, and the Epworth Sleepiness Scale to evaluate daytime sleepiness.

RESULTS: Mean (SD) age was 56 (±14) years, 68% were white, and 57% had poor sleep quality (Pittsburgh Sleep Quality Index score greater than 5). Mean frequency of any urinary incontinence and UUI was 4.6 and 3.9 episodes/d, respectively. After 12 weeks, women randomized to the antimuscarinic group reported greater decrease compared with the placebo group in UUI frequency (0.9 episodes/d; P<.001) and diurnal and nocturnal voiding frequency (P<.05). As compared with the placebo group, women in the antimuscarinic group also reported greater improvement in sleep quality (total Pittsburgh Sleep Quality Index score 0.48; P=.02) with greater improvement in sleep duration and sleep efficiency subscales (P<.05). The intervention did not affect daytime sleepiness.

CONCLUSION: Pharmacologic treatment of UUI is associated with decreased incontinence frequency and nocturia and improvement in overall sleep quality, sleep duration, and sleep efficiency.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT00862745.

OBJECTIVE: To study the resources available for cancer patients once referred for fertility preservation.

MATERIALS AND METHODS: Cross-sectional study clinics that are members of the Society for Assisted Reproductive Technology assess support for fertility preservation.

RESULTS: Surveys were distributed to a total of 1135 members at 394 Society for Assisted Reproductive Technology clinics. Responses were received from 99 individuals representing a total of 84 unique clinics (21.3%). Most clinics (76%) are able to see new cancer patients within 24 to 48 hours after a referral. Clinics most commonly offer oocyte freezing and embryo freezing (96% and 98%, respectively), with a significantly smaller portion of clinics offering ovarian tissue freezing (26%). Although most clinics offer fertility preservation for breast cancer, hematologic cancers and ovarian cancer, only 31% of clinics offer fertility preservation for pediatric premenarchal cancers. Clinics that receive >20 referrals from oncology centers annually are more likely to be in the Northeast and have an academic affiliation. These clinics are more likely to provide support for patients during their cancer treatment, more likely to have long-term follow-up with cancer patients and similarly more likely to have cancer patients return to take advantage of their treatment.

CONCLUSIONS: There are significant geographic and clinic variations in support for fertility preservation. Clinics overall are able to expeditiously see patients to avoid delays in oncologic treatment. Clinics that provide additional support and long-term care tend to have a larger oncologic volume and have more patients who utilize their fertility treatment upon completion of cancer therapy.

OBJECTIVE: The objective of this study was to examine the strength and direction of the association between urinary symptoms and both poor quality sleep and daytime sleepiness among women with urgency urinary incontinence.

METHODS: A planned secondary analysis of baseline characteristics of participants in a multicenter, double-blinded, 12-week randomized controlled trial of pharmacologic therapy for urgency-predominant urinary incontinence in ambulatory women self-diagnosed by the 3 Incontinence Questions was performed. Urinary symptoms were assessed by 3-day voiding diaries. Quality of sleep was assessed using the Pittsburgh Sleep Quality Index (PSQI) and daytime sleepiness using the Epworth Sleepiness Scale.

RESULTS: Of the 640 participants, mean (SD) age was 56 (±14) years and 68% were white. Participants reported an average of 3.9 (±3.0) urgency incontinence episodes per day and 1.3 (±1.3) episodes of nocturia per night. At baseline, 57% had poor sleep quality (PSQI score, >5) and 17% reported daytime sleepiness (Epworth Sleepiness Scale score, >10). Most women (69%) did not use sleeping medication during the prior month, whereas 13% reported use of sleeping medication 3 or more times per week. An increase in total daily incontinence episodes, total daily urgency incontinence episodes, total daily micturitions, and moderate to severe urge sensations were all associated with higher self-report of poor sleep quality according to the PSQI (all P ≤ 0.01). Higher scores on the Bother Scale and the Health-Related Quality of Life for overactive bladder on the Overactive Bladder Questionnaire were similarly associated with higher rates of poor sleep quality (both P ≤ 0.01). In subgroup analysis of those who took sleeping medications less than twice a week, there was still a significant relationship between incontinence measures and quality of sleep as measured by the PSQI. In multivariable analyses, greater frequency of nighttime urgency incontinence was associated with poor sleep quality (P = 0.03).

CONCLUSIONS: Among ambulatory women with urgency urinary incontinence, poor sleep quality is common and greater frequency of incontinence is associated with a greater degree of sleep dysfunction. Women seeking urgency urinary incontinence treatment should be queried about their sleeping habits so that they can be offered appropriate interventions.

OBJECTIVE: The aim of this study was to identify clinical and demographic characteristics that moderate response to treatment with fesoterodine among women with a diagnosis of urgency-predominant urinary incontinence.

METHODS: A multicenter, double-blinded, 12-week randomized controlled trial of pharmacologic therapy for urgency-predominant urinary incontinence in community-dwelling women diagnosed by the 3-item Incontinence Questionnaire (3IQ) was previously performed. Participants (N = 645) were randomized to fesoterodine therapy (4-8 mg daily; n = 322) or placebo (n = 323). Urinary incontinence was assessed by 3-day voiding diaries. In this secondary analysis, a "responder" was defined as reduction of 50% or greater in overall incontinence episode frequency compared with baseline. Clinical and demographic characteristics that may moderate treatment response were assessed by testing for interaction between characteristics and intervention in logit models of responders, adjusting for clinical site.

RESULTS: Participants' ages were a mean of 56 (SD, 14) years, 68% were white race, and they had a mean of 3.9 (SD, 3.0) urgency incontinence episodes per day. There were no baseline differences in demographic, clinical, or incontinence characteristics between treatment and placebo groups or between responders and nonresponders. There was an increase in the proportion of responders to fesoterodine with increasing age (P = 0.04) and parity (0.04) and among married women (P = 0.03), but no effect modification was observed by race/ethnicity, body mass index, education, employment status, or alcohol or tobacco use.

CONCLUSIONS: In ambulatory women with urgency-predominant urinary incontinence, older age, being married, and higher parity significantly moderated and potentiated the effects of pharmacologic therapy on incontinence frequency. This study identifies certain populations who may have increased responsiveness to treatment with antimuscarinic therapy and may be used to inform and guide future therapy.

INTRODUCTION: Infertility affects approximately 6.7 million women in the United States. Couples with infertility have significantly more anxiety, depression, and stress. This is compounded by the fact that almost 40% of couples undergoing assisted reproduction technology still cannot conceive, which can have an ongoing effect on quality of life, marital adjustment, and sexual impact.

AIM: To assess the sexual impact of infertility in women undergoing fertility treatment.

METHODS: This study is a cross-sectional analysis of women in infertile couples seeking treatment at academic or private infertility clinics. Basic demographic information was collected. Respondents were surveyed regarding sexual impact and perception of their infertility etiology. Multivariate regression analyses were used to identify factors independently associated with increased sexual impact.

MAIN OUTCOME MEASURE: Sexual impact of perceived fertility diagnosis.

RESULTS: In total, 809 women met the inclusion criteria, of whom 437 (54%) agreed to participate and 382 completed the sexual impact items. Most of the infertility was female factor only (58.8%), whereas 30.4% of infertility was a combination of male and female factors, 7.3% was male factor only, and 3.5% was unexplained infertility. In bivariate and multivariate analyses, women who perceived they had female factor only infertility reported greater sexual impact compared with woman with male factor infertility (P = .01). Respondents who were younger than 40 years experienced a significantly higher sexual impact than respondents older than 40 years (P < .01). When stratified by primary and secondary infertility, respondents with primary infertility overall reported higher sexual impact scores.

CONCLUSION: In women seeking fertility treatment, younger age and female factor infertility were associated with increased sexual impact and thus these women are potentially at higher risk of sexual dysfunction. Providers should consider the role young age and an infertility diagnosis plays in a women's sexual well-being.

PURPOSE: To study the perspectives of the United States population towards the use of preimplantation genetic diagnosis (PGD) in various clinical scenarios.

METHODS: Online cross-sectional population based questionnaire of a nationally representative sample according to age, gender, race/ethnicity, income, education and religion.

RESULTS: A total of 1006 completed the questionnaire with an overall response rate of 94%. A majority supported PGD for diseases fatal early in life or those causing lifelong disability (72.9 and 66.7%, respectively); only 48.0% supported PGD for diseases that manifest late in life. Respondents were more supportive of PGD for genetic diseases if they were aware of PGD prior to the survey (OR = 1.64; CI = 1.13-2.39). However, a small proportion were in favor of genetically-based trait selection: 21.1% supported PGD for sex selection, 14.6% for physical traits and 18.9% for personality traits. Compared to women, men were nearly two- to three-fold more supportive of PGD for sex selection (OR = 1.65; CI = 1.20-2.78), physical traits (OR = 2.38; CI = 1.60-3.48) and personality traits (OR = 2.31; CI =  .64-3.26). Compared to Caucasians, Asians (OR = 3.87; CI = 1.71-8.78) and African Americans (OR = 1.61; CI = 1.04-2.74) were more supportive of PGD for sex selection.

CONCLUSIONS: In a nationally representative sample, a majority supported PGD to identify early onset diseases. We noted significant variation in opinions by sex, race, and education. There was more support among those with prior knowledge of PGD suggesting that education about PGD may foster favorable opinions. This study identifies public knowledge and attitudes that may be used to shape future research hypotheses and clinical policies.

PURPOSE: Religion and/or spirituality (R/S) have increasingly been recognized as key elements in patients' experience of advanced illness. This study examines the relationship of spiritual concerns (SCs) to quality of life (QOL) in patients with advanced cancer.

PATIENTS AND METHODS: Patients were recruited between March 3, 2006 and April 14, 2008 as part of a survey-based study of 69 cancer patients receiving palliative radiotherapy. Sixteen SCs were assessed, including 11 items assessing spiritual struggles (e.g., feeling abandoned by God) and 5 items assessing spiritual seeking (e.g., seeking forgiveness, thinking about what gives meaning in life). The relationship of SCs to patient QOL domains was examined using univariable and multivariable regression analysis.

RESULTS: Most patients (86%) endorsed one or more SCs, with a median of 4 per patient. Younger age was associated with a greater burden of SCs (β = -0.01, p = 0.006). Total spiritual struggles, spiritual seeking, and SCs were each associated with worse psychological QOL (β = -1.11, p = 0.01; β = -1.67, p < 0.05; and β = -1.06, p < 0.001). One of the most common forms of spiritual seeking (endorsed by 54%)–thinking about what gives meaning to life–was associated with worse psychological and overall QOL (β = - 5.75, p = 0.02; β = -12.94, p = 0.02). Most patients (86%) believed it was important for health care professionals to consider patient SCs within the medical setting.

CONCLUSIONS: SCs are associated with poorer QOL among advanced cancer patients. Furthermore, most patients view attention to SCs as an important part of medical care. These findings underscore the important role of spiritual care in palliative cancer management.

The complex molecular communications that occur between neoplastic and stromal cells within the tumor microenvironment play an integral role in breast cancer pathogenesis. Carcinoma-associated fibroblasts (CAF) produce tumor-enhancing factors and have been strongly implicated in breast cancer development. Similar to the way in which tumors have been compared with "wounds that never heal," CAFs have been equated to activated fibroblasts, which are present in inflammatory environments, in which they aid in wound healing through tissue remodeling and repair. Matrix metalloproteinase-1 (MMP-1) and G protein-coupled receptor, CXCR4, are elevated in these activated fibroblasts, in which they facilitate angiogenesis and matrix degradation, processes that are also vital to breast cancer metastasis. In this study, we investigated MMP-1 and CXCR4 expression in normal human mammary fibroblasts (HMF) exposed to soluble breast cancer factors. Historically, elevated CXCR4 expression is associated with breast cancer cells. However, we show that soluble factors secreted by SUM102 breast cancer cells stimulated the expression of MMP-1 and CXCR4 in HMFs. As a result, these stromal cells acquired an invasive and migratory phenotype. To confirm the clinical relevancy of our findings, we analyzed CAFs obtained from primary breast cancers. These cells also displayed elevated MMP-1 and CXCR4 levels compared with counterpart fibroblasts, and were more invasive and migratory. Together, our data suggest that soluble breast cancer factors initiate the transdifferentiation of normal HMFs to tumor-promoting CAFs, and that through the induction of MMP-1 and CXCR4 levels, these cells exhibit an invasive and migratory phenotype.