Presence of Obstructive Symptoms and Absence of Perianal Crohn Disease Is Predictive of Surgery After Endoscopic Balloon Dilation.

BACKGROUND: Patients with Crohn disease (CD) often develop strictures that require surgery. Endoscopic balloon dilation (EBD) is an alternative treatment that can be safe and effective. The objective of this study was to assess factors associated with the need for repeat EBD and surgery after initial EBD for stricturing CD. METHODS: Patients with stricturing CD who underwent EBD from 2007 to 2017 were identified. Demographic and clinical information was obtained from the electronic medical record. A Cox proportional hazards regression model and Kaplan-Meier curves were generated for variables associated with repeat EBD and surgical resection. RESULTS: Ninety-nine patients underwent a total of 240 EBD proedures; 35% had a history of perianal disease, and 63% were on a biologic at the time of initial EBD. Fifty-one percent of patients had obstructive symptoms at the time of initial EBD, and 75% of the EBDs were successful. Complications occurred in 8 EBDs (3.3%). Repeat intervention after EBD was more likely in patients on biologics at baseline EBD (76% vs 54%; P = 0.029). Thirty-three percent of patients had surgical resection at a median of 5 months (interquartile ratio = 2.0-13.0 months) after initial EBD. The presence of obstructive symptoms at the time of EBD was associated with surgical resection (hazard ratio = 3.18; 95% confidence interval, 1.28-7.86). Conversely, a history of perianal disease was negatively associated with surgical resection (hazard ratio = 0.27; 95% confidence interval, 0.10-0.68). CONCLUSIONS: Patients on biologic treatment at the time of EBD are more likely to need an intervention in the future. Patients with obstructive symptoms at the time of initial EBD and those without a history of perianal involvement are more likely to undergo surgical intervention.

Prognostic factors for human papillomavirus-positive and negative oropharyngeal carcinomas.

OBJECTIVES/HYPOTHESIS: Human papillomavirus (HPV)-positive and HPV-negative oropharyngeal squamous cell carcinoma (OPSCC) are distinct disease entities. Prognostic factors specific to each entity have not been adequately explored. Goals for this study were: 1) to determine whether HPV-positive and HPV-negative OPSCCs have distinct prognostic factors, and 2) to explore the prognostic significance of sex and race in OPSCC after HPV stratification STUDY DESIGN: Retrospective case series. METHODS: A retrospective review of 239 incident OPSCC patients from 1995 to 2012, treated at Johns Hopkins and University of California-San Francisco was conducted. Women and nonwhite races were oversampled. All analyses were stratified by tumor HPV in situ hybridization status. The effects of sex and race on survival were considered in Kaplan-Meier and unadjusted and adjusted Cox regression models. RESULTS: One hundred thirty-four (56.1%) OPSCC patients were HPV positive. On univariate analysis, women had better overall survival than men among HPV-positive (hazard ratio [HR]: 0.47, 95% confidence interval [CI]: 0.20-1.07; P = .06) but not HPV-negative (HR: 0.73, 95% CI: 0.43-1.24; P = .24) OPSCCs. On multivariate analysis, women with HPV-positive OPSCCs remained at lower risk of death (adjusted hazard ratio [aHR]: 0.34, 95% CI: 0.12-0.96; P = .04). Survival did not vary significantly by race among HPV-positive patients. Among HPV-negative patients, Hispanic patients had significantly better survival in unadjusted (HR: 0.27, 95% CI: 0.08-0.91; P = .04) but not adjusted (aHR: 0.93, 95% CI: 0.11-7.36; P = .94) analysis. CONCLUSIONS: Women with HPV-positive OPSCC may have improved overall survival compared to men. Sex does not play a prognostic role in HPV-negative OPSCC. There are no differences in prognosis by race among HPV-positive or HPV-negative patients. LEVEL OF EVIDENCE: 4 Laryngoscope, E287-E295, 2018.

Human papillomavirus (HPV) 16 antibodies at diagnosis of HPV-related oropharyngeal cancer and antibody trajectories after treatment.

OBJECTIVES: Despite the fact that HPV-driven oropharyngeal cancer (HPV-OPC) has relatively low recurrence rates, intensive post-therapy monitoring remains the standard of care. Post-treatment biomarkers are needed to risk stratify HPV-OPC patients for more individualized surveillance intensity and which remain at higher recurrence risk. MATERIALS AND METHODS: 115 HPV-OPC patients (ascertained by p16 immunohistochemistry and/or in-situ hybridization) from a multicenter prospective case study (HOTSPOT) had blood collected at diagnosis, and 64 of these also had blood collected at post-treatment follow-up visits for up to two years. Samples were centrally tested for antibodies to the L1, E1, E2, E4, E6, and E7 proteins of HPV16. RESULTS: At diagnosis, most HPV-OPC cases were seropositive to HPV16 E6 (85%). In post therapeutic samples, HPV16 antibody level decreased slowly over time, but only 3 (of 51 cases seropositive at enrollment) dropped low enough to be classified as seronegative. At 3years after diagnosis, cumulative risk of recurrence was 10.2% and 0% in HPV16 E6 seropositive and E6 seronegative HPV-OPC cases, respectively (p=0.18). Risk of recurrence was increased, although not statistically significant, in those with higher HPV16 E6 antibody levels at diagnosis (per log antibody level, hazard ratio [HR]=1.81, 95%CI=0.47-6.92). CONCLUSION: This study confirms the high seroprevalence of HPV oncogenic antibodies at diagnosis of HPV-OPC. HPV16 E6 antibody levels decrease after treatment, but most cases remain seropositive for up to two years. HPV16 E6 antibody levels at diagnosis did not appear to be a strong predictor of recurrence.

The prognostic role of sex, race, and human papillomavirus in oropharyngeal and nonoropharyngeal head and neck squamous cell cancer.

BACKGROUND: Human papillomavirus (HPV) is a well-established prognostic marker for oropharyngeal squamous cell cancer (OPSCC). Because of the limited numbers of women and nonwhites in studies to date, sex and racial/ethnic differences in prognosis have not been well explored. In this study, survival differences were explored by the tumor HPV status among 1) patients with OPSCCs by sex and race and 2) patients with nonoropharyngeal (non-OP) head and neck squamous cell cancers (HNSCCs). METHODS: This retrospective, multi-institution study included OPSCCs and non-OP HNSCCs of the oral cavity, larynx, and nasopharynx diagnosed from 1995 to 2012. Race/ethnicity was categorized as white non-Hispanic, black non-Hispanic, Asian non-Hispanic, and Hispanic of any race. Tumors were centrally tested for p16 overexpression and the presence of HPV by HPV16 DNA and high-risk HPV E6/E7 messenger RNA in situ hybridization. Kaplan-Meier and Cox proportional hazards models were used to evaluate overall survival (OS). RESULTS: The study population included 239 patients with OPSCC and 621 patients with non-OP HNSCC with a median follow-up time of 3.5 years. After adjustments for the tumor HPV status, age, current tobacco use, and stage, the risk of death was lower for women versus men with OPSCC (adjusted hazard ratio, 0.55; P = .04). The results were similar with p16. In contrast, for non-OP HNSCCs, HPV positivity, p16 positivity, and sex were not associated with OS. CONCLUSIONS: For OPSCC, there are differences in survival by sex, even after the tumor HPV status has been taken into account. For non-OP HNSCC, the HPV status and the p16 status are not of prognostic significance. Cancer 2017;123:1566-1575. © 2017 American Cancer Society.

Differences in the Prevalence of Human Papillomavirus (HPV) in Head and Neck Squamous Cell Cancers by Sex, Race, Anatomic Tumor Site, and HPV Detection Method.

IMPORTANCE: Human papillomavirus (HPV) causes an increasing proportion of oropharyngeal squamous cell carcinomas (OPSCCs), particularly in white men. The prevalence of HPV among other demographic groups and other anatomic sites of HNSCC is unclear. OBJECTIVE: To explore the role of HPV tumor status among women and nonwhites with OPSCC and patients with nonoropharyngeal head and neck squamous cell carcinoma (non-OP HNSCC). DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study at 2 tertiary academic centers including cases diagnosed 1995 through 2012, oversampled for minorities and females. A stratified random sample of 863 patients with newly diagnosed SCC of the oral cavity, oropharynx, larynx, or nasopharynx was used. MAIN OUTCOMES AND MEASURES: Outcomes were HPV status as measured by p16 immunohistochemical analysis, HPV16 DNA in situ hybridization (ISH), and high-risk HPV E6/E7 mRNA ISH. RESULTS: Of 863 patients, 551 (63.9%) were male and median age was 58 years (interquartile range, 51-68 years). Among 240 OPSCCs, 144 (60%) were p16 positive (p16+), 115 (48%) were HPV16 DNA ISH positive (ISH16+), and 134 (56%) were positive for any oncogenic HPV type (ISH+). From 1995 to 2012, the proportion of p16+ OPSCC increased significantly among women (from 29% to 77%; P = .005 for trend) and men (36% to 72%; P < .001 for trend), as well as among whites (39% to 86%; P < .001 for trend) and nonwhites (32% to 62%; P = .02 for trend). Similar results were observed for ISH+ OPSCC (P ≤ .01 for all). Among 623 non-OP HNSCCs, a higher proportion were p16+ compared with ISH positive (62 [10%] vs 30 [5%]; P = .001). A high proportion (26 of 62 [42%]) of these p16+ non-OP HNSCCs were found in sites adjacent to the oropharynx. The proportion of p16+ and ISH+ non-OP HNSCCs were similar by sex. Over time, the proportion of non-OP HNSCCs that were p16+ (or ISH+) increased among whites (P = .04 for trend) but not among nonwhites (each P > .51 for trend). Among OPSCCs, p16 had high sensitivity (100%), specificity (91%), and positive (93%) and negative predictive value (100%) for ISH positivity. In non-OP HNSCCs, p16 had lower sensitivity (83%) and positive predictive value (40%) but high specificity (94%) and negative predictive value (99%) for ISH positivity. CONCLUSIONS AND RELEVANCE: During 1995 through 2012, the proportion of OPSCCs caused by HPV has increased significantly. This increase was not restricted to white men but was a consistent trend for women and men, as well as for white and nonwhite racial groups. Few non-OP HNSCCs were HPV related. P16 positivity was a good surrogate for ISH+ tumor status among OPSCC, but not a good surrogate for non-OP HNSCC.

The association of medication use with clearance or persistence of oral HPV infection.

PURPOSE: Persistent oral human papillomavirus (HPV) infection increases risk for oropharyngeal carcinoma, and people living with HIV have higher rates of oral HPV infection and related cancers. Some prescription medications have immunomodulatory effects, but the impact of medication use on oral HPV natural history is unknown. METHODS: Scope® oral rinse-and-gargle samples were collected semi-annually from 1,666 participants and tested for 37 types of oral HPV DNA using PCR; 594 HPV-infected participants with 1,358 type-specific oral HPV infections were identified. Data were collected on recent (past 6 months) use of medications. The relationship between medication use and oral HPV clearance was evaluated using Wei-Lin-Weissfeld regression, adjusting for biologic sex, prevalent versus incident infection, age, HIV status and CD4+ T cell count. RESULTS: Out of 11 medications examined, oral HPV clearance was significantly reduced in participants reporting recent use of antipsychotics (HR 0.75, 95% CI 0.57-0.99), anxiolytics/sedatives (HR 0.78, 95% CI 0.63-0.96) and antidepressants (HR 0.82, 95% CI 0.67-0.999). Among antipsychotics users, effect modification by HIV status was observed, with reduced clearance in HIV-infected (HR 0.67, 95% CI 0.49-0.91), but not HIV-uninfected participants (p-interaction = 0.009). After adjusted analysis, antipsychotic use remained significantly associated with reduced oral HPV clearance overall (aHR 0.75, 95% CI 0.57-0.99), and when restricted to only HIV-infected participants (aHR 0.66, 95% CI 0.48-0.90). After adjustment, anxiolytic/sedative use and antidepressant use were no longer significantly associated with reduced oral HPV clearance. CONCLUSIONS: Some medications were associated with decreased oral HPV clearance, most notably antipsychotic medications. These medications are prescribed for conditions that may have immunomodulating effects, so characteristics of underlying illness may have partially contributed to reduced oral HPV clearance.

Using a Mystery-Caller Approach to Examine Access to Prostate Cancer Care in Philadelphia.

PURPOSE: Prior work suggests that access to health care may influence the diagnosis and treatment of prostate cancer. Mystery-caller methods have been used previously to measure access to care for health services such as primary care, where patients' self-initiate requests for care. We used a mystery-caller survey for specialized prostate cancer care to assess dimensions of access to prostate cancer care. MATERIALS AND METHODS: We created an inventory of urology and radiation oncology practices in southeastern Pennsylvania. Using a 'mystery caller' approach, a research assistant posing as a medical office scheduler in a primary care office, attempted to make a new patient appointment on behalf of a referred patient. Linear regression was used to determine the association between time to next available appointment with practice and census tract characteristics. RESULTS: We successfully obtained information on new patient appointments from 198 practices out of the 223 in the region (88.8%). Radiation oncology practices were more likely to accept Medicaid compared to urology practices (91.3% vs 36.4%) and had shorter mean wait times for new patient appointments (9.0 vs 12.8 days). We did not observe significant differences in wait times according to census tract characteristics including neighborhood socioeconomic status and the proportion of male African American residents. CONCLUSIONS: Mystery-caller methods that reflect real-world referral processes from primary care offices can be used to measure access to specialized cancer care. We observed significant differences in wait times and insurance acceptance between radiation oncology and urology practices.

Association of serum cytokines with oral HPV clearance.

BACKGROUND: Initial studies suggest higher serum levels of some pro-inflammatory cytokines may be associated with decreased cervical human papillomavirus (HPV) clearance. However, the relationship of cytokines with oral HPV clearance has not been explored. METHODS: From 2010 to 2014, oral rinse and serum samples were collected semi-annually from 1601 adults. Oral rinse samples were tested for HPV DNA using PCR. Based on oral HPV results, 931 serum samples were selected for cytokine evaluation to include a roughly equal number of prevalent (n=307), incident (n=313), and no oral HPV infections (n=311). Electrochemiluminescence multiplex assays were used to determine the concentrations of IL-6, IL-8, TNF-α, IFN-γ, IL-1ß, IL-2, IL-4, IL-10, IL-12 and IL-13. The relationship between serum cytokine concentrations (categorized into quartiles) and oral HPV clearance was evaluated with Wei-Lin-Weissfeld regression models, adjusting for HPV infection type (prevalent vs. incident), age, HIV status, and CD4 T cell count. RESULTS: Higher TNF-α concentration was associated with decreased clearance in men (highest vs. lowest quartile, adjusted hazard ratio [aHR]=0.52, 95% CI=0.34-0.79) and women (aHR=0.76, 95% confidence interval [CI]=0.55-1.04), with stronger associations in men than women (p-interaction=0.049). Higher IL-2 concentration was associated with reduced clearance in men (aHR=0.69, 95% CI=0.50-0.95), but not women (p-interaction=0.058). Results were similar within CD4 T cell strata (CD4⩾500 or CD4<500 cells/µl) among HIV-infected participants. No other cytokines were associated with clearance. CONCLUSION: High serum TNF-α is associated with reduced clearance of oral HPV infection.

Sex Differences in Risk Factors and Natural History of Oral Human Papillomavirus Infection.

UNLABELLED: Oral human papillomavirus genotype 16 (HPV16) infection causes oropharyngeal squamous cell carcinoma (SCC), and the prevalence of oropharyngeal SCC is higher among men than women in the United States. In a cohort study of oral HPV infection among 409 individuals aged 18-25 years, the risk among men but not among women significantly increased as the number of recent (ie, within the prior 3 months) oral sex partners increased (Pinteraction = .05). In contrast, the risk among women but not among men significantly decreased as the lifetime number of vaginal sex partners increased (Pinteraction = .037). Men were also significantly less likely than women to clear oral HPV infection. Our data contribute to understanding sex differences in risk for HPV-positive oropharyngeal SCC. CLINICAL TRIALS REGISTRATION: NCT00994019.

Anal Cancer Screening in Men Who Have Sex With Men in the Multicenter AIDS Cohort Study.

OBJECTIVE: To evaluate the prevalence of anal cytology (ACyt) abnormalities among HIV-infected and HIV-uninfected men who have sex with men (MSM). DESIGN: Multicenter cohort study of 723 HIV-infected and 788 HIV-uninfected MSM with ACyt, with a second ACyt collected 2 years later. A referral for high-resolution anoscopy was suggested for abnormal ACyt. METHODS: ACyt samples were collected using a polyester swab and liquid cytology media and read in a central laboratory. RESULTS: Prevalence of any abnormal ACyt was 25% in HIV-uninfected MSM and increased to 38%, 41%, and 47% among HIV-infected MSM with current CD4 T-cell counts ≥500, 350-499, and <350 cells/mm (P < 0.001), respectively. Anal HPV16 DNA was also more common in HIV-infected than HIV-uninfected MSM (25% versus 16%, P < 0.001). Abnormal baseline ACyt together with prevalent HPV16 DNA detection was present in only 7% of HIV-uninfected MSM compared to 18% of HIV-infected MSM with current CD4 < 350, P < 0.001. Among HIV-infected men, 56% of the men with atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesions ASCs-US/LSILs and 81% of men with atypical squamous cells cannot exclude high-grade (ASC-H/)/high-grade squamous intraepithelial lesions (HSIL) had lower grade ACyt findings 18-30 months later ("regressed"). However, 19% of untreated HIV-infected men with ASC-H/HSIL cytology maintained that same grade of cytology in their second test approximately 2 years later, and 15% with ASC-US/LSIL "progressed" to ASC-H/HSIL. Abnormal ACyt had high sensitivity (96%) but low specificity (17%) for biopsy-proven HSIL. CONCLUSIONS: Prevalence of abnormal ACyt remains elevated in HIV-infected men during the current antiretroviral therapy era.

Prevalence of and Risk Factors for Oral Human Papillomavirus Infection among HIV-Positive and HIV-Negative People Who Inject Drugs.

BACKGROUND: Human papillomavirus (HPV) causes most oropharyngeal cancers in the United States. Oral HPV prevalence is associated with immunosuppression, and drug use can be immunosuppressive, but the epidemiology of oral HPV among people who use drugs is not well described. METHODS: We enrolled men and women with a current or prior history of injection drug use in this cross-sectional sub-study within the AIDS Linked to the Intravenous Experience (ALIVE) cohort. We tested oral rinse samples for 37 types of HPV DNA and collected self-reported risk factor information. We compared oral HPV prevalence across categories using chi-squared statistics and multivariable logistic regression. RESULTS: Among 199 subjects, 32% were HIV-positive (median CD4 count 384 cells/µL), 90% were Black, 56% had less than a high school education, 17% had recently used injection drugs, and the median age was 54 years. Most had performed oral sex (82%) but had fewer than 5 lifetime partners (58%). The prevalence of any oral HPV was 29%, and of any oncogenic oral HPV was 13%. Oral HPV prevalence was high among both heterosexual men (30%) and women (20%). After adjustment, odds of oral HPV were increased among HIV-positive individuals with a low CD4 count (<350 cells/µl, aOR = 2.7, 95%CI = 1.2-6.4, vs. HIV-negative individuals), but not among HIV-positive individuals with a higher CD4 cell count. Odds were also elevated for those who had recently performed oral sex on a woman (aOR = 2.2, 95%CI = 1.01-4.6) and, even after this adjustment, among bisexual/lesbian females (aOR = 5.6, 95%CI = 1.4-23, vs. heterosexual females). Oral HPV prevalence was not associated with vaginal sex, performing oral sex on a man, or recent drug use. CONCLUSIONS: Recent drug use was not associated with oral HPV prevalence in our study. However, despite modest numbers of sexual partners, the prevalence of oral HPV among this largely Black population with lower socioeconomic status was high.

Prognostic Implication of Persistent Human Papillomavirus Type 16 DNA Detection in Oral Rinses for Human Papillomavirus-Related Oropharyngeal Carcinoma.

IMPORTANCE: Human papillomavirus-related oropharyngeal carcinoma (HPV-OPC) is increasing in incidence in the United States. Although HPV-OPC has favorable prognosis, 10% to 25% of HPV-OPCs recur. Detection of human papillomavirus (HPV) DNA in oral rinses is associated with HPV-OPC, but its potential as a prognostic biomarker is unclear. OBJECTIVE: To determine whether HPV DNA detection in oral rinses after treatment for HPV-OPC is associated with recurrence and survival. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of patients with incident HPV-OPC diagnosed from 2009 to 2013 at 4 academic tertiary referral cancer centers in the United States. Oral rinse samples were collected at diagnosis and after treatment (9, 12, 18, and 24 months after diagnosis), and evaluated for HPV DNA. Among an initial cohort of 157 participants with incident HPV-OPC treated with curative intent, 124 had 1 or more posttreatment oral rinses available and were included in this study. MAIN OUTCOMES AND MEASURES: Disease-free survival (DFS) and overall survival (OS) were estimated by the Kaplan-Meier method, and the association of HPV DNA detection in oral rinses with survival was evaluated using Cox regression analysis. RESULTS: Oral HPV type 16 (HPV16) DNA was common at diagnosis (67 of 124 participants [54%]). In contrast, oral HPV16 DNA was detected in only 6 participants after treatment (5%), including 5 with HPV16 DNA also detected at diagnosis (persistent oral HPV16 DNA). Two-year DFS and OS were 92% (95% CI, 94%-100%) and 98% (95% CI, 93%-99%). Persistent oral HPV16 DNA was associated with worse DFS (hazard ratio, 29.7 [95% CI, 9.0-98.2]) and OS (hazard ratio, 23.5 [95% CI, 4.7-116.9]). All 5 participants with persistent oral HPV16 DNA developed recurrent disease, 3 with local disease involvement. In contrast, just 9 of 119 participants (8%) without persistent oral HPV16 DNA developed recurrent disease, only 1 (11%) with local disease involvement. Median (range) time from earliest posttreatment oral HPV16 DNA detection to recurrence was 7.0 (3.7-10.9) months. CONCLUSIONS AND RELEVANCE: Human papillomavirus type 16 DNA in oral rinses is common at diagnosis but rare after treatment for HPV-OPC. Our data suggest that, although infrequent, persistent HPV16 DNA in posttreatment oral rinses is associated with poor prognosis and is a potential tool for long-term tumor surveillance, perhaps more so for local recurrence.

Oral Human Papillomavirus (HPV) Infection among Unvaccinated High-Risk Young Adults.

Oral HPV infection, the cause of most oropharyngeal cancer in the U.S., is not well studied among high-risk young adults. Men (n = 340) and women (n = 270) aged 18-25 years attending Baltimore County STD clinics were recruited if they declined HPV vaccination. Each participant had a 30-second oral rinse and gargle sample tested for 37 types of HPV DNA, and a risk-factor survey. Factors associated with prevalent infection were explored using log binomial regression. Men had higher prevalence of any oral HPV (15.3% vs. 7.8%, p = 0.004) and vaccine-type oral HPV (i.e., HPV16/18/6/11: 5.0% vs. 1.1%, p = 0.007) infection than women. In multivariate analysis, male gender (aPR = 1.93, 95% CI = 1.10-3.39), number of recent oral sex partners (p-trend = 0.013) and having ever performed oral sex on a woman (aPR = 1.73, 95% CI = 1.06-2.82) were associated with increased oral HPV prevalence. Performing oral sex on a woman may confer higher risk of oral HPV acquisition than performing oral sex on a man.

Neurocognitive functioning of children and adolescents with mild-to-moderate chronic kidney disease.

BACKGROUND AND OBJECTIVES: Few data exist on the neurocognitive functioning of children with mild-to-moderate chronic kidney disease (CKD). The primary objectives of this paper are (1) to determine the neurocognitive status in this population and (2) to identify sociodemographic and health-status variables associated with neurocognitive functioning. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a cross-sectional study of 368 children, aged 6 to 16 years, from the Chronic Kidney Disease in Children (CKiD) cohort. Median iGFR was 43 ml/min per 1.73 m(2), and the median duration of CKD was 8.0 years. Approximately 26% had underlying glomerular disease. Measures of intelligence, academic achievement, attention regulation, and executive functioning were obtained at study entry. The prevalence of neurocognitive deficits was determined by comparing participant scores on each measure of neurocognitive functioning with normative data. The association between hypothesized predictors of neurocognitive dysfunction was evaluated using multivariate regression analyses. RESULTS: Neurocognitive functioning was within the average range for the entire group; however, 21% to 40% of participants scored at least one SD below the mean on measures of intelligence quotient (IQ), academic achievement, attention regulation, or executive functioning. Higher iohexol-based GFR (iGFR) predicted a lesser risk for poor performance on measures of executive function. Participants having elevated proteinuria (i.e., urine protein/creatinine >2) scored lower on verbal IQ, full-scale IQ, and attention variability than those without elevated proteinuria. CONCLUSIONS: Whereas most children with mild-to-moderate CKD have no major neurocognitive deficits, a substantial percentage did show neurocognitive dysfunction that places them at risk for poor long-term educational and occupational outcomes.

Health-related quality of life of children with mild to moderate chronic kidney disease.

OBJECTIVE: To compare the health-related quality of life (HRQoL) of children with chronic kidney disease (CKD) with healthy children; to evaluate the association between CKD severity and HRQoL; and to identity demographic, socioeconomic, and health-status variables that are associated with impairment in HRQoL in children with mild to moderate CKD. METHODS: This was a cross-sectional assessment of HRQoL in children who were aged 2 to 16 and had mild to moderate CKD using the Pediatric Inventory of Quality of Life Core Scales (PedsQL). Overall HRQoL and PedsQL domain means for parents and youth were compared with previously published norms by using independent sample t tests. Study participants were categorized by kidney disease stage (measured by iohexol-based glomerular filtration rate [iGFR]), and group differences in HRQoL were evaluated by using analysis of variance and Cuzick trend tests. The association between hypothesized predictors of HRQoL and PedsQL scores was evaluated with linear and logistic regression analyses. RESULTS: The study sample comprised 402 participants (mean age: 11 years, 60% male, 70% white, median iGFR: 42.5 mL/min per 1.73 m(2), median CKD duration: 7 years). Youth with CKD had significantly lower physical, school, emotional, and social domain scores than healthy youth. iGFR was not associated with HRQoL. Longer disease duration and older age were associated with higher PedsQL scores in the domains of physical, emotional, and social functioning. Older age was associated with lower school domain scores. Maternal education > or =16 years was associated with higher PedsQL scores in the domains of physical, school, and social functioning. Short stature was associated with lower scores in the physical functioning domain. CONCLUSIONS: Children with mild to moderate CKD, in comparison with healthy children, reported poorer overall HRQoL and poorer physical, school, emotional, and social functioning. Early intervention to improve linear growth and to address school functioning difficulties is recommended.

Sleep and fatigue symptoms in children and adolescents with CKD: a cross-sectional analysis from the chronic kidney disease in children (CKiD) study.

BACKGROUND: Although symptoms of sleepiness and fatigue are common in adults with chronic kidney disease (CKD), little is known about the prevalence of these symptoms in children with CKD. STUDY DESIGN: Cross-sectional analysis within a cohort study. SETTING & PARTICIPANTS: We describe the frequency and severity of sleep problems and fatigue and assess the extent of their association with measured glomerular filtration rate (mGFR) and health-related quality of life (HRQOL) in 301 participants of the Chronic Kidney Disease in Children cohort. OUTCOMES & MEASUREMENTS: Sleep and fatigue-related items from the Pediatric Quality of Life Inventory 4.0 Generic Scales and the CKD-related Symptoms List were used. RESULTS: Median mGFR was 42.0 mL/min/1.73 m(2) (25th-75th percentiles, 31.2-53.2), and median age was 13.9 years (25th-75th percentiles, 10.8-16.2). Children with mGFR of 40-<50, 30-<40, or <30 mL/min/1.73 m(2) had 2.07 (95% CI, 1.05-4.09), 2.35 (95% CI, 1.17-4.72), and 2.59 (95% CI, 1.15-5.85) higher odds of having more severe parent reports of low energy than children with mGFR > or = 50 mL/min/1.73 m(2). Compared with participants with mGFR > or = 50 mL/min/1.73 m(2), those with mGFR < 30 mL/min/1.73 m(2) had 3.92 (95% CI, 1.37-11.17) higher odds of reporting more severe weakness, and those with mGFR of 40-<50 mL/min/1.73 m(2) had 2.95 (95% CI, 1.26-6.88) higher odds of falling asleep during the day. Low energy, trouble sleeping, and weakness were associated with lower HRQOL scores. LIMITATIONS: Symptoms of sleep and fatigue represent the child's or parent's perception of symptom severity, whereas individual items can lead to imprecise measurements of sleep and fatigue. CONCLUSIONS: Lower mGFR was associated with increased weakness, low energy, and daytime sleepiness. Furthermore, a strong association between trouble sleeping, low energy, and weakness with decreases in overall HRQOL was observed. Detection and treatment of poor sleep and fatigue may improve the development and HRQOL of children and adolescents with CKD.

Quantifying morbidity associated with the abuse and misuse of opioid analgesics: a comparison of two approaches.

BACKGROUND: Due to the rising nonmedical use of opioid analgesics, methods are needed to quantify the associated health-related consequences. METHODS: Using opioid analgesic intentional exposure reports from poison control centers from January 2003-June 2004, we calculated quarterly rates for 7 opioids at the 3-digit ZIP code level using population- and patient-based denominators. RESULTS: Hydrocodone was the most widely prescribed opioid (maximum: 5,321,390 patients per quarter), with the largest intentional exposure caseload (range: 498-1,290), and the highest aggregate population-based rate (maximum of 13.61 cases per 1,000,000 individuals). Methadone had the highest aggregate patient-based rate (maximum 2.03 cases per 1,000 patients). CONCLUSION: Population- and patient-based rates are complementary tools that address different public health questions. Population-based rates describe the health-related burden of nonmedical opioid analgesic use on the community as a whole, while patient-based rates show this burden ("risk") in relation to the level of corresponding medicinal use ("benefit") within a given area.

Neurocognitive outcomes in children with chronic kidney disease: Current findings and contemporary endeavors.

Given the rise in chronic kidney disease (CKD) in both children and adults, CKD has recently been targeted as a public health priority. Childhood onset kidney disease is generally a noncurable and progressive condition that leads to kidney failure by early adulthood. Fortunately, improved identification of kidney problems allows for early intervention, which is thought to slow progression toward end-stage renal disease. In addition, medical interventions for pediatric end-stage renal disease have also improved, allowing children to take advantage of lifesaving renal replacement treatments such as dialysis and kidney transplantation. In spite of improvements in identification and treatment, CKD causes both direct and indirect insults to a variety of organ systems. This paper reviews recently published studies pertaining to the neurocognitive and psychosocial impact of CKD on children of various ages and at various stages of kidney failure. Specific attention is focused on summarizing peer reviewed research that describes associations between kidney functioning and cognitive functioning, language acquisition, visual spatial abilities, memory, and executive functioning. In addition, peer reviewed research describing psychosocial outcomes associated with CKD related to academic achievement, social-behavioral functioning, and quality of life are summarized. The authors also identified disease-specific factors that likely mediate neurocognitive outcomes (e.g., anemia, hypertension, cardiovascular) and endorse the importance of continued interdisciplinary research collaborations that will provide a better understanding of the mechanisms responsible for improved neurocognitive functioning after transplantation. The authors conclude this review by describing a multicenter, prospective, longitudinal, National Institutes of Health funded study that is currently examining the developmental outcomes of children with mild to moderate CKD. The authors speculate that the Chronic Kidney Disease in Children Prospective Cohort Study (CKiD) findings will provide additional evidence-based guidance for clinicians and researchers working with children and adolescents with deteriorating kidney function to improve medical and developmental outcomes.