Nonbiologic factors that impact management in women with urinary incontinence: review of the literature and findings from a National Institute of Diabetes and Digestive and Kidney Diseases workshop.

INTRODUCTION AND HYPOTHESIS: Urinary incontinence (UI)-defined as a complaint of involuntary loss of urine-is common in women, with major public health, financial, and quality of life (QoL) implications. Despite the high toll of UI and the availability of effective conservative treatments, many women with UI do not seek care. Those who do often continue to experience symptoms. Improving UI treatment may require a comprehensive approach to urology research, including a broad set of potentially influential factors beyond biologic. METHODS: To explore the effects of nonbiologic factors (NBF) on UI management and treatment response, the National Institute of Diabetes and Digestive and Kidney Diseases convened a workshop for clinical and psychosocial researchers. Participants proposed a UI treatment pathway: recognizing the problem, willingness to seek treatment, access to care, receiving quality treatment, engaging in self-management, and adhering to chosen treatments; discussed potential NBFs that may affect the pathway; and identified areas for future research. After the meeting, a rapid literature review was conducted to assess the current state of research on NBFs in women with UI. RESULTS: Participants identified several patient-level NBFs that may influence the UI management pathway, including QoL and perceived bother; stigma, shame, and embarrassment; knowledge and perceptions; social determinants of health; cultural and language characteristics; personal characteristics and skills; and physical abilities. Additionally, participants acknowledged that provider- and system-level factors also play a role and likely interact with patient-level factors. CONCLUSIONS: NBFs that potentially affect the UI management pathway are not well understood, and a comprehensive, interdisciplinary approach to research is needed to understand and appropriately support effective UI treatment.

Health related quality of life in adolescents with bladder exstrophy-epispadias as measured by the Child Health Questionnaire-Child Form 87.

PURPOSE: We determined health related quality of life as reported by adolescents with bladder exstrophy or epispadias using a validated generic instrument. MATERIALS AND METHODS: Adolescents age 11 to 18 years with bladder exstrophy or epispadias (57) completed a validated, generic, health related quality of life instrument, the CHQ-CF87 (Child Health Questionnaire-Child Form 87). Urinary incontinence, catheterization status, and medical and surgical history data were also obtained. Mean summary scores and 95% CIs for each subdomain of the CHQ-CF87 were calculated, and descriptively compared to 2 population based samples. In our sample health related quality of life outcomes by continence status were compared using univariate and multivariate analysis. However, this analysis was limited by a small sample size. RESULTS: Mean age of the 49 patients with bladder exstrophy and the 8 with epispadias was 14.3 years, 67% were male and 81% were Caucasian. There were 31 participants who reported incontinence and the median number of lifetime surgeries was 9. The exstrophy population scored well in all subdomains of the instrument when descriptively compared to 2 large samples of adolescent populations. In our sample incontinent patients had lower scores by multivariate analysis in 7 of 10 domains and better scores in 3 of 10 domains, although these differences were not statistically significant. CONCLUSIONS: Adolescents with bladder exstrophy and epispadias reported relatively good scores on the CHQ-CF87 when descriptively compared to other reference populations. This finding suggests that these children adapt well to the challenges of their condition. Analysis of the association of incontinence with health related quality of life was limited by the small sample size.

Urological disorders in chronic kidney disease in children cohort: clinical characteristics and estimation of glomerular filtration rate.

PURPOSE: Urological disorders are the most common cause of pediatric chronic kidney disease. We determined the characteristics of children with urological disorders and assessed the agreement between the newly developed bedside glomerular filtration rate estimating formula with measured glomerular filtration rate in 586 patients in the Chronic Kidney Disease in Children study. MATERIALS AND METHODS: The Chronic Kidney Disease in Children study is a prospective, observational cohort of children recruited from 48 sites in the United States and Canada. Eligibility requirements include age 1 to 16 years and estimated glomerular filtration rate by original Schwartz formula 30 to 90 ml/min/1.73 m(2). Baseline demographics, clinical variables and glomerular filtration rate were assessed. Bland-Altman analysis was conducted to assess agreement between estimated and measured glomerular filtration rates. RESULTS: Of the 586 participants with at least 1 glomerular filtration rate measurement 348 (59%) had an underlying urological diagnosis (obstructive uropathy in 118, aplastic/hypoplastic/dysplastic kidneys in 104, reflux in 87 and other condition in 39). Among these patients median age was 9 years, duration of chronic kidney disease was 7 years and age at first visit with a urologist was less than 1 year. Of the patients 67% were male, 67% were white and 21% had a low birth weight. Median height was in the 24th percentile. Median glomerular filtration rate as measured by iohexol plasma disappearance was 44.8 ml/min/1.73 m(2). Median glomerular filtration rate as estimated by the Chronic Kidney Disease in Children bedside equation was 44.3 ml/min/1.73 m(2) (bias = -0.5, 95% CI -1.7 to 0.7, p = 0.44). CONCLUSIONS: Underlying urological causes of chronic kidney disease were present in 59% of study participants. These children were diagnosed early in life, and many had low birth weight and growth delay. There is good agreement between the newly developed Chronic Kidney Disease in Children estimating equations and measured glomerular filtration rate in this population.

Parent perspectives of health related quality of life for adolescents with bladder exstrophy-epispadias as measured by the child health questionnaire-parent form 50.

PURPOSE: Few groups have examined health related quality of life for adolescents with bladder exstrophy-epispadias. We studied parent reported health related quality of life for adolescents with bladder exstrophy-epispadias using the Child Health Questionnaire-Parent Form 50. MATERIALS AND METHODS: We recruited 11 to 17-year-old participants with bladder exstrophy-epispadias and their parents. Parents served as proxy respondents for the adolescents by self-administering a validated generic health related quality of life instrument, the Child Health Questionnaire-Parent Form 50. We collected urinary incontinence, catheterization status, and medical and surgical history data. Mean questionnaire scores were compared to population based norms. RESULTS: Median age of the 55 patients was 14 years, 69% were male and 84% were white. Diagnoses included bladder exstrophy in 48 cases and epispadias in 7. Of the participants 29 (53%) reported urinary incontinence. The median number of lifetime surgeries was 9. Although physical and psychosocial summary measure scores were comparable to norms, the mean general health perception score was significantly worse than that of a population based sample (65.8 points, 95% CI 61.4-70.2 vs 73, 95% CI 71.3-74.7, p = 0.004). Mean family activity and parent emotional impact scores were also significantly worse than in a population based sample (83.6 points, 95% CI 79.3-88.0 vs 89.7, 95% CI 87.9-91.5, p = 0.02 and 67.7, 95% CI 61.9-73.6 vs 80.3, 95% CI 78.4-82.2, p <0.0001, respectively). Comparison of incontinent to continent children revealed a lower mean score on the parent emotional impact scale (62.6 points, 95% CI 55.5-69.8 vs 73.4, 95% CI 63.9-82.9), which approached significance (p = 0.06). CONCLUSIONS: Although overall adolescent quality of life was comparable to norms, parents reported significantly impaired adolescent general health and family activity as well as a negative parental emotional impact. Further research is needed to identify interventions that can decrease the adverse impact of bladder exstrophy-epispadias on family activity and parent emotional distress.

Urinary incontinence in the CKiD cohort and health related quality of life.

PURPOSE: Many children with chronic kidney disease have urinary incontinence due to urological disorders and/or a urine concentrating defect. We determined the prevalence and impact of incontinence on health related quality of life in children with chronic kidney disease. MATERIALS AND METHODS: The Chronic Kidney Disease in Children study is a prospective, observational cohort of children recruited from 47 sites in the United States and Canada. Eligibility requirements are age 1 to 16 years and an estimated glomerular filtration rate of 30 to 90 ml per minute per 1.73 m(2). Demographics, continence status, glomerular filtration rate and physical examination were assessed at study entry. Health related quality of life was measured using the parent and child versions of PedsQL. PedsQL scores in participants 5 years old or older were compared among children who were toilet trained and not bed-wetting, bed-wetting or not toilet trained using multivariate linear regression. RESULTS: Overall median age of the 329 participants was 12.5 years, 61.4% were male, 70% were white and 55.5% had a urological disorder. Of participants 71.4% were toilet trained at study enrollment, 23.1% had bed-wetting and 5.5% were not toilet trained. Children who were not yet toilet trained had an average total score that was 13.5 points lower (95% CI -25.2, -1.8) on the PedsQL child report than in those who were toilet trained (p = 0.02). Physical functioning (-15.0, 95% CI -28.2, -1.9) and school functioning (-15.3, 95% CI -29.8, -0.8) were also lower in this group (p = 0.03 and 0.04, respectively). On the PedsQL parent proxy report physical functioning (-14.2, 95% CI -26.7, -1.6) was similarly affected by child incontinence (p = 0.03). CONCLUSIONS: Urinary incontinence is common in pediatric patients with chronic kidney disease and associated with lower health related quality of life on the PedsQL child and parent proxy reports. Early recognition of and treatment for urinary incontinence may improve health related quality of life in this population.

Formative research for a healthy diet intervention among inner-city adolescents: the importance of family, school and neighborhood environment.

OBJECTIVES: To understand influences on diet among low-income African-American adolescents in East Baltimore. METHODS: Formative research was conducted for a food store-centered healthy diet intervention targeted to inner-city youth. Family, school and neighborhood influences on eating habits and health concepts were explored. RESULTS: Family structure, economic resources and past experiences influence what food means to adolescents. Healthy food in school and local stores is limited. Terminology to categorize foods was identified, including the term "home foods". CONCLUSIONS: Suggested adolescent nutritional interventions include promotion of home-based eating, improving availability of healthy foods in school and neighborhood stores, and targeted educational materials.

Parent perspectives of health related quality of life in adolescents with chronic kidney disease due to underlying urological disorders: an assessment using the Child Health Questionnaire-Parent Form 50.

PURPOSE: Little is known about health related quality of life in adolescents with chronic kidney disease due to urological anomalies. We assessed generic health related quality of life in this population using a validated parent proxy instrument. MATERIALS AND METHODS: In this multicenter prospective cohort study the Child Health Questionnaire-Parent Form 50, a generic health related quality of life parent proxy instrument, was administered to 92 parents of adolescents 10 to 18 years old with chronic kidney disease. Mean summary measure and scale scores in adolescents with urological anomalies were compared to scores in those with other causes of kidney disease and in a representative American population sample. RESULTS: The cohort included 35 adolescents with an underlying diagnosis of congenital urological anomaly and 57 with another cause of kidney disease. There were no significant differences in mean scale or summary measure scores between the 2 diagnostic groups. When compared to a representative population sample, adolescents with congenital urological anomalies scored significantly worse on the questionnaire physical summary measure (44.5, 95% CI 39.9-49.1 vs 52.0, 95% CI 51.1-52.9, p = 0.002), and on the Child Health Questionnaire scales physical functioning, role physical, general health perceptions, family activities and parental emotional impact. CONCLUSIONS: As assessed by Child Health Questionnaire-Parent Form 50, parents reported that adolescents with chronic kidney disease due to urological disorders scored lower on the physical summary measure than a population based reference sample and they reported a negative effect on family activities and parental emotional well-being. These findings suggest that the Child Health Questionnaire-Parent Form 50 could provide a family based assessment of generic health related quality of life in adolescents with urological disorders.

Health related quality of life in adolescents with abnormal bladder function: an assessment using the Child Health and Illness Profile-Adolescent Edition.

PURPOSE: We studied the impact of abnormal bladder function due to congenital urological disorders on health related quality of life in children. A reliable patient based method is needed to assess the impact of these conditions in children and the interventions used to treat them. MATERIALS AND METHODS: Participants 11 to 17 years old with bladder exstrophy-epispadias complex, spina bifida or other causes of abnormal bladder function self-administered the Child Health and Illness Profile-Adolescent Edition, a generic health related quality of life instrument. They also responded to questions about incontinence, catheterization status and bother level. Mean scores on the profile were compared to population based norms. RESULTS: Mean age of the 50 participants was 14.9 years, 62% were male and 82% were white. Diagnoses included bladder exstrophy-epispadias complex in 37 patients, spina bifida in 10 and other in 3. The mean +/- SD score on the disorders domain of 14.2 +/- 6.3 was significantly worse than the population norm of 20. Mean scores on the satisfaction, discomfort, resilience, risks and achievement domains were comparable to or better than the population based norm of 20. A total of 29 participants reported incontinence and 31 performed catheterization. CONCLUSIONS: In this study of adolescents with congenital causes of abnormal bladder function Child Health and Illness Profile-Adolescent Edition generic health related quality of life scores were significantly worse in the disorders domain but largely comparable to or better than those of the general population in other domains. This suggests that the profile may discern between adolescents with structural urological disease and norms but it may not be sensitive enough to fully detect the impact of the condition. Alternatively adolescents may adapt well to the challenges of urological disease.

Use of Bladder Antimuscarinics in Older Adults with Impaired Cognition.

OBJECTIVE: To examine the use of antimuscarinics for treating urinary incontinence (UI) in older adults with varying levels of cognition. DESIGN: Cross-sectional. SETTING: National Alzheimer's Coordinating Center from 2005 through 2015. PARTICIPANTS: Community-dwelling men and women aged 65 and older (N = 24,106). MEASUREMENTS: Clinicians and staff evaluated each participant's dementia status during annual in-person assessments. Participants or their informants reported all medications taken in the 2 weeks before each study visit. RESULTS: Overall, 5.2% (95% confidence interval (CI) = 4.9-5.5%) of the cohort took a bladder antimuscarinic. Participants with impaired cognition were more likely to be taking an antimuscarinic than those with normal cognition. Rates of bladder antimuscarinic use were 4.0% (95% CI = 3.6-4.4%) for participants with normal cognition, 5.6% (95% CI = 4.9-6.3%) for those with mild cognitive impairment, and 6.0% (95% CI = 5.5-6.4%) for those with dementia (p < .001). Of 624 participants with dementia who took antimuscarinics, 16% (95% CI = 13-19%) were simultaneously taking other medicines with anticholinergic properties. CONCLUSION: Use of bladder antimuscarinics was more common in older adults with impaired cognition than in those with normal cognition. This use is despite guidelines advising clinicians to avoid prescribing antimuscarinics in individuals with dementia because of their vulnerability to anticholinergic-induced adverse cognitive and functional effects. A substantial proportion of cognitively impaired individuals who took antimuscarinics were simultaneously taking other anticholinergic medications. These findings suggest a need to improve the treatment of UI in individuals with impaired cognition.

Outcomes of delayed hypospadias repair: implications for decision making.

PURPOSE: The current American Academy of Pediatrics recommendation is to perform hypospadias repair at age 6 to 12 months. Primary hypospadias repair at adolescence or beyond is uncommon, and there is little reported about the postoperative course of such patients. We report the outcomes for a series of patients who underwent primary hypospadias repair at age 10 years or older. MATERIALS AND METHODS: We identified patients seen at our institution between 1979 and 2002 who underwent primary hypospadias repair at age 10 years or older. Electronic and paper charts were abstracted for baseline demographics, degree of hypospadias, surgical technique, complications and reoperation. RESULTS: A total of 31 patients were identified, with a median available followup of 14 months. Median patient age at first hypospadias surgery was 13 years. The location of the urethral meatus was distal in 19 patients, mid shaft in 7, proximal in 4 and undetermined in 1. A variety of techniques were used, including meatal advancement and glanuloplasty, meatal based flaps, island onlay flaps, Snodgrass repair and staged procedures. Complications were noted in 48% of patients (15 of 31), including fistula (10), stricture (4), hematoma (2) and other complications (2). CONCLUSIONS: Although retrospective in nature, these data suggest that delay of primary hypospadias repair into the teen years or beyond may result in more complications than currently accepted for infant hypospadias repair.

An assessment of health related quality of life using the child health and illness profile-adolescent edition in adolescents with chronic kidney disease due to underlying urological disorders.

PURPOSE: We examined health related quality of life in adolescents with congenital urological disease causing kidney disease using a generic health related quality of life instrument. We then compared the results to those in adolescents with medical kidney disease and to population based norms. MATERIALS AND METHODS: The Child Health and Illness Profile-Adolescent Edition was administered to 113 patients 10 to 18 years old with chronic kidney disease. Mean domain and subdomain scores for adolescents with urological disease were compared to those of adolescents with medical kidney disease and to population based norms. RESULTS: The cohort included adolescents with an underlying diagnosis of congenital urological anomaly (37 patients) or other causes of kidney disease (76). Compared to adolescents with kidney disease caused by other factors, those with congenital urological disease scored statistically significantly better in the Child Health and Illness Profile-Adolescent Edition subdomain of Limitations of Activity (mean 22.3 [SD 2.5] vs 20.4 [SD 5.0], p = 0.04). Compared to population norms, adolescents with congenital disorders scored lower in the Disorders domain (mean 16.5, 95% CI 14.2 to 18.9) but better in the Risks domain (mean 25.9, 95% CI 25.1 to 26.6) and in the Home Safety and Health subdomain (mean 25.2, 95% CI 23.7 to 26.6). CONCLUSIONS: As assessed by the Child Health and Illness Profile-Adolescent Edition generic health status questionnaire, adolescents with kidney disease due to underlying congenital urological disease had fewer limitations of activity compared to those with underlying medical kidney disease. Except for low scores in the Disorders domain, children with underlying urological disease did not have significant impairments in any other domain compared to population based norms.

A systematic review of vitamin D receptor gene polymorphisms and prostate cancer risk.

PURPOSE: Polymorphisms in the vitamin D receptor gene have been hypothesized to alter the risk of prostate cancer. However, studies investigating the associations between specific vitamin D receptor polymorphisms and prostate cancer risk have yielded inconsistent results. MATERIALS AND METHODS: We performed a meta-analysis of 26 studies evaluating the association between vitamin D receptor TaqI, poly(A), BsmI, ApaI, and/or FokI polymorphisms, and prostate cancer risk. RESULTS: The studies were heterogeneous in terms of study design, selection of cases and controls, and racial composition. Random effects models were used to estimate the pooled OR and 95% CI of each vitamin D receptor polymorphism under codominant, additive, dominant and recessive genetic models. Overall we did not find evidence to support an association between any of the vitamin D receptor polymorphisms and the risk of prostate cancer. For TaqI, which is the most studied vitamin D receptor polymorphism with 18 studies (total of 2,727 cases and 3,685 controls), the pooled OR was 1.00 (95% CI 0.85 to 1.18) for the Tt vs TT genotypes, 0.94 (95% CI 0.78 to 1.13) for the tt vs TT genotypes and 0.89 (95% CI 0.71 to 1.10) for the recessive model (tt vs Tt plus TT). ORs for the poly(A) microsatellite, BsmI, ApaI and FokI polymorphisms were similar. CONCLUSIONS: The results of this meta-analysis suggest that the vitamin D receptor TaqI, poly(A), BsmI, ApaI and FokI polymorphisms are not related to prostate cancer risk.

Poor predictability of prenatal ultrasonography for a nonfunctional kidney.

We present 2 cases in which the diagnosis of a unilateral nonfunctioning kidney was not anticipated. The first case appeared to be simple, antenatally diagnosed, unilateral hydronephrosis with adequate parenchyma. However, at 3 months postnatally, it was found to be nonfunctional, most likely secondary to early high-grade obstruction. The second case presented prenatally as a left hydronephrotic kidney with parenchymal cysts, and the right kidney showed only mild parenchymal cystic changes. By 6 months, however, the right kidney was nonfunctional. These cases emphasize the need for coordinated prenatal and postnatal care. The sonographic appearance of renal dysplasia is variable (in size, number of cysts, and degree of hydronephrosis), depending on the point at which it is evaluated during the disease course. Subtle signs of dysplasia, such as increased echogenicity, may be the only warning sign of a nonfunctioning kidney, for which one should have a high index of suspicion.

Clinical and molecular characterization of the bladder exstrophy-epispadias complex: analysis of 232 families.

OBJECTIVE: To identify genetic and nongenetic factors contributing to the risk of bladder exstrophy-epispadias complex (BEEC). PATIENTS AND METHODS: In all, 285 families with BEEC were invited to participate in the study, and 232 of them were recruited. Epidemiological information was obtained from 151 of the consenting families, with a detailed clinical genetic examination of 94 probands. In all, 440 DNA samples were collected from 163 families for molecular analysis. RESULTS: Most of the cases were sporadic and had no family history of BEEC. Among patients, 95% were Caucasian, and males were more common in both the epispadias group (M/F, 2.2, 29 patients) and the classic bladder-exstrophy group (M/F 1.8, 164), but in the cloacal exstrophy group the sex ratio was close to unity (1.1, 15). There was a statistically significant association with advanced parental age (P < 0.001). Birth weight, gestational age and maternal reproductive history did not appear to be significantly different from those in the general population. Information on exposures to tobacco, alcohol and drugs was collected but none appeared to act as a risk factor. Karyotype analysis on 37 cases detected two chromosomal abnormalities, i.e. 46XY t(8;9)(p11.2; q13) and 47XYY. Molecular analysis of the HLXB9 gene, which causes Currarino syndrome, did not detect mutations in the blood or bladder DNA of 10 patients with bladder or cloacal exstrophy. CONCLUSIONS: BEEC most commonly occurs as an isolated sporadic birth defect with a recurrence risk of << 1%. There was no evidence of a single-gene effect or common environmental factor in this study population. In addition to race and advanced parental age, birth order may be a risk factor for BEEC. We suggest somatic mutations in a gene(s) within the pathway regulating bladder development may be the cause of BEEC.

Integrin alpha(v) and coxsackie adenovirus receptor expression in clinical bladder cancer.

OBJECTIVES: To evaluate the expression of the coxsackie and adenovirus receptor (CAR) and alpha(v) integrins in clinical specimens of bladder cancer to determine the susceptibility to adenoviral gene therapy. Efficient adenovirus-based gene therapy requires binding of the virus to CAR and involves the alpha(v) integrins. Studies on bladder cancer cell lines have shown that low adenoviral transduction rates were associated with low-level expression of CAR. Integrin alpha(v) expression increases in various tumors suggest its importance in differentiation, proliferation, and migration. CAR is structurally a member of the Ig-type superfamily of cell-cell adhesion molecules, suggesting that its expression may also be related to the state of tumor differentiation. METHODS: We performed immunohistochemistry for CAR and integrin alpha(v) expression in bladder cancer specimens in 50 paraffin-embedded tumor-normal pairs and confirmed the results by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of 11 separate bladder tumors and 4 separate normal bladder controls. RESULTS: Immunochemistry demonstrated a stage and grade-dependent decrease in CAR expression (90.0%, 83.3%, and 31.3% of normal urothelium and superficial and invasive transitional cell carcinoma [TCC] and 83.3% and 39.5% of low and high-grade TCC, respectively). Furthermore, we found a stage and grade-dependent increase in alpha(v) integrin expression (13.3%, 46.0%, and 56.3% of normal urothelium, superficial TCC, and invasive TCC and 25% and 52.6% of low and high-grade TCC, respectively). Quantitative RT-PCR analysis confirmed a downregulation at the CAR gene expression level. CONCLUSIONS: This down-regulation may have a major impact on developing adenoviral-based gene therapy modalities. In addition, we propose that loss of CAR expression decreases rigid cell adhesion, possibly increasing the migratory potential. Loss of CAR expression correlates with the invasive phenotype in our analysis of bladder cancer. Simultaneously, the finding of increased alpha(v) expression in invasive cancer suggests a pathogenesis that involves heterophilic adhesion and migration of these cells on various extracellular ligands.