Stephanie Kliethermes

The Epidemiology of Cirrhosis in the United States: A Population-based Study.

Background and Aims: Liver cirrhosis is an important public health concern in the United States and a significant source of morbidity and mortality. However, the epidemiology of cirrhosis is incompletely understood. The aims of this study were to estimate the prevalence of cirrhosis in the general US population, determine characteristics of affected Americans with a focus on health disparities, and calculate excess mortality attributable to cirrhosis. Methods: National Health And Nutrition Examination Survey data conducted between 1999 and 2010 were used to estimate cirrhosis prevalence and factors associated with cirrhosis. The National Center for Health Statistics-linked death certificate data from the National Death Index were linked to the National Health And Nutrition Examination Survey database for the years 1999 to 2004, and attributable mortality was calculated using propensity score adjustment. Cirrhosis was ascertained by aspartate aminotransferase-to-platelet ratio of >2 and abnormal liver function tests. Results: The prevalence of cirrhosis in the United States was approximately 0.27%, corresponding to 633,323 adults. Sixty-nine percent reported that they were unaware of having liver disease. The prevalence was higher in non-Hispanic blacks and Mexican Americans, those living below the poverty level, and those with less than a 12th grade education. Diabetes, alcohol abuse, hepatitis C and B, male sex, and older age were all independently associated with cirrhosis, with a population attributable fraction of 53.5% from viral hepatitis (mostly hepatitis C), diabetes, and alcohol abuse. Mortality was 26.4% per 2-year interval in cirrhosis compared with 8.4% in propensity-matched controls. Conclusions: The prevalence of cirrhosis is higher than previously estimated. Many cases may be undiagnosed, and more than half are potentially preventable by controlling diabetes, alcohol abuse, and viral hepatitis. Public health efforts are needed to reduce this disease burden, particularly among racial/ethnic minorities and individuals at lower socioeconomic status.

The Female Urinary Microbiome: a Comparison of Women with and without Urgency Urinary Incontinence

ABSTRACT Bacterial DNA and live bacteria have been detected in human urine in the absence of clinical infection, challenging the prevailing dogma that urine is normally sterile. Urgency urinary incontinence (UUI) is a poorly understood urinary condition characterized by symptoms that overlap urinary infection, including urinary urgency and increased frequency with urinary incontinence. The recent discovery of the urinary microbiome warrants investigation into whether bacteria contribute to UUI. In this study, we used 16S rRNA gene sequencing to classify bacterial DNA and expanded quantitative urine culture (EQUC) techniques to isolate live bacteria in urine collected by using a transurethral catheter from women with UUI and, in comparison, a cohort without UUI. For these cohorts, we demonstrated that the UUI and non-UUI urinary microbiomes differ by group based on both sequence and culture evidences. Compared to the non-UUI microbiome, sequencing experiments revealed that the UUI microbiome was composed of increased Gardnerella and decreased Lactobacillus. Nine genera (Actinobaculum, Actinomyces, Aerococcus, Arthrobacter, Corynebacterium, Gardnerella, Oligella, Staphylococcus, and Streptococcus) were more frequently cultured from the UUI cohort. Although Lactobacillus was isolated from both cohorts, distinctions existed at the species level, with Lactobacillus gasseri detected more frequently in the UUI cohort and Lactobacillus crispatus most frequently detected in controls. Combined, these data suggest that potentially important differences exist in the urinary microbiomes of women with and without UUI, which have strong implications in prevention, diagnosis, or treatment of UUI. IMPORTANCE New evidence indicates that the human urinary tract contains microbial communities; however, the role of these communities in urinary health remains to be elucidated. Urgency urinary incontinence (UUI) is a highly prevalent yet poorly understood urinary condition characterized by urgency, frequency, and urinary incontinence. Given the significant overlap of UUI symptoms with those of urinary tract infections, it is possible that UUI may have a microbial component. We compared the urinary microbiomes of women affected by UUI to those of a comparison group without UUI, using both high-throughput sequencing and extended culture techniques. We identified statistically significant differences in the frequency and abundance of bacteria present. These differences suggest a potential role for the urinary microbiome in female urinary health. New evidence indicates that the human urinary tract contains microbial communities; however, the role of these communities in urinary health remains to be elucidated. Urgency urinary incontinence (UUI) is a highly prevalent yet poorly understood urinary condition characterized by urgency, frequency, and urinary incontinence. Given the significant overlap of UUI symptoms with those of urinary tract infections, it is possible that UUI may have a microbial component. We compared the urinary microbiomes of women affected by UUI to those of a comparison group without UUI, using both high-throughput sequencing and extended culture techniques. We identified statistically significant differences in the frequency and abundance of bacteria present. These differences suggest a potential role for the urinary microbiome in female urinary health.

The Clinical Urine Culture: Enhanced Techniques Improve Detection of Clinically Relevant Microorganisms

ABSTRACT Enhanced quantitative urine culture (EQUC) detects live microorganisms in the vast majority of urine specimens reported as “no growth” by the standard urine culture protocol. Here, we evaluated an expanded set of EQUC conditions (expanded-spectrum EQUC) to identify an optimal version that provides a more complete description of uropathogens in women experiencing urinary tract infection (UTI)-like symptoms. One hundred fifty adult urogynecology patient-participants were characterized using a self-completed validated UTI symptom assessment (UTISA) questionnaire and asked “Do you feel you have a UTI?” Women responding negatively were recruited into the no-UTI cohort, while women responding affirmatively were recruited into the UTI cohort; the latter cohort was reassessed with the UTISA questionnaire 3 to 7 days later. Baseline catheterized urine samples were plated using both standard urine culture and expanded-spectrum EQUC protocols: standard urine culture inoculated at 1 μl onto 2 agars incubated aerobically; expanded-spectrum EQUC inoculated at three different volumes of urine onto 7 combinations of agars and environments. Compared to expanded-spectrum EQUC, standard urine culture missed 67% of uropathogens overall and 50% in participants with severe urinary symptoms. Thirty-six percent of participants with missed uropathogens reported no symptom resolution after treatment by standard urine culture results. Optimal detection of uropathogens could be achieved using the following: 100 μl of urine plated onto blood (blood agar plate [BAP]), colistin-nalidixic acid (CNA), and MacConkey agars in 5% CO2 for 48 h. This streamlined EQUC protocol achieved 84% uropathogen detection relative to 33% detection by standard urine culture. The streamlined EQUC protocol improves detection of uropathogens that are likely relevant for symptomatic women, giving clinicians the opportunity to receive additional information not currently reported using standard urine culture techniques.

Clinical and genetic features of hearing loss in facioscapulohumeral muscular dystrophy

Objective: To describe the hearing loss in facioscapulohumeral muscular dystrophy (FSHD) and examine the relationship to genotype. Methods: Medical records of all individuals with FSHD seen at the University of Iowa neuromuscular clinic between July 2006 and July 2012 (n = 59) were reviewed. Eleven had significant hearing loss and no non-FSHD cause. All available audiology records for these individuals were analyzed. The relationship between the FSHD mutation (EcoRI/BlnI fragment size) and hearing loss was evaluated using a logistic regression analysis. Results: In patients with hearing loss, recalled age at onset of facial weakness ranged from birth to 5 years and shoulder weakness was 3 to 15 years. The age at diagnosis of hearing loss ranged from birth to 7 years. Only 2 were identified by newborn hearing screen. Most audiograms demonstrated a bilateral, sloping, high-frequency sensorineural hearing loss. Of the 4 patients with more than 5 years of data, 3 had progression of hearing loss. Logistic regression showed statistically significant negative association between the presence of hearing loss and EcoRI/BlnI fragment size (p = 0.0207). Conclusions: FSHD with a small EcoRI/BlnI fragment is associated with a bilateral, progressive, sloping, high-frequency hearing loss with onset in childhood. Patients with FSHD and small EcoRI/BlnI fragment sizes should have hearing screened, even if the child passed newborn hearing screening.

Evaluation of the urinary microbiota of women with uncomplicated stress urinary incontinence

BACKGROUND: Female urinary microbiota are associated with urgency urinary incontinence and response to medication. The urinary microbiota of women with stress urinary incontinence has not been described. OBJECTIVE: We sought to study the cross‐sectional relationships between urinary microbiota features and demographic and clinical characteristics of women undergoing stress urinary incontinence surgery. STUDY DESIGN: Preoperative urine specimens were collected from women without urinary tract infection and were available from 197 women (174 voided, 23 catheterized) enrolled in a multicenter prospective randomized trial, the Value of Urodynamic Evaluation study. Demographic and clinical variables were obtained including stress and urgency urinary incontinence symptoms, menopausal status, and hormone use. The bacterial composition of the urine was qualitatively assessed by sequencing the bacterial 16S ribosomal RNA gene. Phylogenetic relatedness and microbial alpha diversity were compared to demographics and symptoms using generalized estimating equation models. RESULTS: The majority of 197 urine samples (86%) had detectable bacterial DNA. Bacterial diversity was significantly associated with higher body mass index (P = .02); increased Medical, Epidemiologic, and Social Aspects of Aging urge index score (P = .04); and hormonal status (P < .001). No associations were detected with stress urinary incontinence symptoms. Increased diversity was also associated with a concomitant lower frequency of Lactobacillus in hormone‐negative women. CONCLUSION: Women undergoing stress urinary incontinence surgery have detectable urinary microbiota. This cross‐sectional analysis revealed that increased diversity of the microbiota was associated with urgency urinary incontinence symptoms, hormonal status, and body mass index. In contrast, the female urinary microbiota were not associated with stress urinary incontinence symptoms.

Speech intonation and melodic contour recognition in children with cochlear implants and with normal hearing.

Background Cochlear implant (CI) users have difficulty perceiving some intonation cues in speech and melodic contours because of poor frequency selectivity in the cochlear implant signal. Objectives To assess perceptual accuracy of normal hearing (NH) children and pediatric CI users on speech intonation (prosody), melodic contour, and pitch ranking, and to determine potential predictors of outcomes. Hypothesis Does perceptual accuracy for speech intonation or melodic contour differ as a function of auditory status (NH, CI), perceptual category (falling versus rising intonation/contour), pitch perception, or individual differences (e.g., age, hearing history)? Method NH and CI groups were tested on recognition of falling intonation/contour versus rising intonation/contour presented in both spoken and melodic (sung) conditions. Pitch ranking was also tested. Outcomes were correlated with variables of age, hearing history, HINT, and CNC scores. Results The CI group was significantly less accurate than the NH group in spoken (CI, M = 63.1%; NH, M = 82.1%) and melodic (CI, M = 61.6%; NH, M = 84.2%) conditions. The CI group was more accurate in recognizing rising contour in the melodic condition compared with rising intonation in the spoken condition. Pitch ranking was a significant predictor of outcome for both groups in falling intonation and rising melodic contour; age at testing and hearing history variables were not predictive of outcomes. Conclusion Children with CIs were less accurate than NH children in perception of speech intonation, melodic contour, and pitch ranking. However, the larger pitch excursions of the melodic condition may assist in recognition of the rising inflection associated with the interrogative form.

High Frequency of Active HCV Infection Among Seropositive Cases in West Africa and Evidence for Multiple Transmission Pathways

BACKGROUND Sub-Saharan Africa (SSA) has one of the highest global hepatitis C virus (HCV) prevalence estimates. However, reports that suggest high rates of serologic false positives and low levels of viremia have led to uncertainty regarding the burden of active infection in this region. Additionally, little is known about the predominant transmission risk factors in SSA. METHODS We prospectively recalled 363 past blood donors (180 who were rapid screen assay [RSA] positive and 183 who were RSA negative at time of donation) to identify the level of active infection and risk factors for infection at a teaching hospital in Kumasi, Ghana. Participants had repeat blood testing and were administered a questionnaire on risk factors. RESULTS The frequency of HCV active infection ranged from 74.4% to 88% depending on the criteria used to define serologically positive cases. Individuals with active disease had biochemical evidence of liver inflammation and median viral loads of 5.7 log copies/mL. Individuals from the northern and upper regions of Ghana had greater risks of infection compared with participants from other areas. Additional risk factors included traditional circumcision, home birth, tribal scarring, and hepatitis B virus coinfection. CONCLUSIONS Viremic infection was common among serologically confirmed cases. Attention to testing algorithms is needed in order to define the true HCV burden in SSA. These data also suggest that several transmission modes are likely contributing to the current HCV epidemic in Ghana and that the distribution of these practices may result in substantial regional variation in prevalence.

Postoperative Atrial Fibrillation Predicts Long-Term Cardiovascular Events after Radical Cystectomy

PURPOSE Postoperative atrial fibrillation after radical cystectomy occurs in 2% to 8% of cases. Recent evidence suggests that transient postoperative atrial fibrillation leads to future cardiovascular events. The long-term cardiovascular implications of postoperative atrial fibrillation in patients undergoing radical cystectomy are largely unknown. MATERIALS AND METHODS The Healthcare Cost and Utilization Project State Inpatient Databases for California and Florida were used to identify patients who underwent radical cystectomy between 2007 and 2010. After excluding patients with a history of atrial fibrillation, coronary artery disease and/or stroke, patients were matched using propensity scoring on age, race, insurance status and preexisting comorbidities. Adjusted Kaplan-Meier time-to-event analysis and Cox proportional hazards models were used to assess the effect of postoperative atrial fibrillation on cardiovascular events (acute myocardial infarction and stroke) during postoperative year 1. RESULTS Radical cystectomy was performed in 4,345 patients who met the study inclusion criteria, of whom 210 (4.8%) had postoperative atrial fibrillation. There was a significantly higher cumulative incidence of cardiovascular events during the first postoperative year in patients in whom postoperative atrial fibrillation developed (24.8% vs 10.9%, adjusted log rank p=0.007). Cox proportional hazards regression demonstrated an increased risk of cardiovascular events in patients with postoperative atrial fibrillation (HR 10, p=0.02). CONCLUSIONS Our results demonstrate that patients undergoing radical cystectomy in whom transient postoperative atrial fibrillation develops are at significantly increased risk for cardiovascular events in the first postoperative year. Physicians should be vigilant in assessing postoperative atrial fibrillation, even when transient, and establish appropriate followup given the increased risk of cardiovascular morbidity.

Accuracy of Cochlear Implant Recipients in Speech Reception in the Presence of Background Music

Objectives: This study examined speech recognition abilities of cochlear implant (CI) recipients in the spectrally complex listening condition of 3 contrasting types of background music, and compared performance based upon listener groups: CI recipients using conventional long-electrode devices, Hybrid CI recipients (acoustic plus electric stimulation), and normal-hearing adults. Methods: We tested 154 long-electrode CI recipients using varied devices and strategies, 21 Hybrid CI recipients, and 49 normal-hearing adults on closed-set recognition of spondees presented in 3 contrasting forms of background music (piano solo, large symphony orchestra, vocal solo with small combo accompaniment) in an adaptive test. Outcomes: Signal-to-noise ratio thresholds for speech in music were examined in relation to measures of speech recognition in background noise and multitalker babble, pitch perception, and music experience. Results: The signal-to-noise ratio thresholds for speech in music varied as a function of category of background music, group membership (long-electrode, Hybrid, normal-hearing), and age. The thresholds for speech in background music were significantly correlated with measures of pitch perception and thresholds for speech in background noise; auditory status was an important predictor. Conclusions: Evidence suggests that speech reception thresholds in background music change as a function of listener age (with more advanced age being detrimental), structural characteristics of different types of music, and hearing status (residual hearing). These findings have implications for everyday listening conditions such as communicating in social or commercial situations in which there is background music.

Standardized Reporting of Microscopic Renal Tumor Margins: Introduction of the Renal Tumor Capsule Invasion Scoring System

Purpose: Renal tumor enucleation allows for maximal parenchymal preservation. Identifying pseudocapsule integrity is critically important in nephron sparing surgery by enucleation. Tumor invasion into and through the capsule may have clinical implications, although it is not routinely commented on in standard pathological reporting. We describe a system to standardize the varying degrees of pseudocapsule invasion and identify predictors of invasion. Materials and Methods: We performed a multicenter retrospective review between 2002 and 2014 at Indiana University Hospital and Loyola University Medical Center. A total of 327 tumors were evaluated following removal via radical nephrectomy, standard margin partial nephrectomy or enucleation partial nephrectomy. Pathologists scored tumors using our i‐Cap (invasion of pseudocapsule) scoring system. Multivariate analysis was done to determine predictors of higher score tumors. Results: Tumor characteristics were similar among surgical resection groups. Enucleated tumors tended to have thinner pseudocapsule rims but not higher i‐Cap scores. Rates of complete capsular invasion, scored as i‐Cap 3, were similar among the surgical techniques, comprising 22% of the overall cohort. Papillary histology along with increasing tumor grade was predictive of an i‐Cap 3 score. Conclusions: A capsule invasion scoring system is useful to classify renal cell carcinoma pseudocapsule integrity. i‐Cap scores appear to be independent of surgical technique. Complete capsular invasion is most common in papillary and high grade tumors. Further work is warranted regarding the relevance of capsular invasion depth as it relates to the oncologic outcome for local recurrence and disease specific survival.