Alicia Wentz

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 m2, 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 ≥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.

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.

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

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).

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 childs or parents 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.

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.

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.

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.

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.

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.

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.