Renal outcomes in patients with type 1 diabetes and macroalbuminuria.

Macroalbuminuria, defined as urine albumin excretion rate (AER)≥300 mg/d, has long been considered a stage of irreversible kidney damage that leads reliably to GFR loss. We examined the long-term renal outcomes of persons with type 1 diabetes who developed incident macroalbuminuria during the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study. One hundred fifty-nine participants developed incident macroalbuminuria and were subsequently followed for a median duration of 9 years (maximum of 25 years). At the time of macroalbuminuria diagnosis, mean (SD) age was 37 (9) years, mean (SD) duration of diabetes was 17 (5) years, median AER was 524 mg/d, and mean (SD) eGFR was 108 (20) ml/min per 1.73 m(2). Ten years after macroalbuminuria diagnosis, the cumulative incidence of a sustained reduction in AER to <300 mg/d was 52%, mostly but not entirely under treatment with renin-angiotensin system inhibitors. The cumulative incidence of impaired GFR (sustained eGFR<60 ml/min per 1.73 m(2)) 10 years after macroalbuminuria diagnosis was 32%, including 16% who developed ESRD. Lower hemoglobin A1c and BP and regression to AER<300 mg/d were associated with reduced risk of developing impaired GFR. In conclusion, people with type 1 diabetes who develop macroalbuminuria are at high risk of progressive kidney disease. However, through at least 10 years of follow-up, AER could often be controlled, and GFR frequently remained in the normal range.

The burden of influenza-associated critical illness hospitalizations.

OBJECTIVE: Influenza is the most common vaccine-preventable disease in the United States; however, little is known about the burden of critical illness due to influenza virus infection. Our primary objective was to estimate the proportion of all critical illness hospitalizations that are attributable to seasonal influenza. DESIGN: Retrospective cohort study. SETTING: Arizona, California, and Washington from January 2003 to March 2009. PATIENTS: All adults hospitalized with critical illness, defined by International Classification of Diseases, 9th Edition, Clinical Modification diagnosis and procedure codes for acute respiratory failure, severe sepsis, or in-hospital death. MEASUREMENTS AND MAIN RESULTS: We combined the complete hospitalization discharge databases for three U.S. states, regional influenza virus surveillance, and state census data. Using negative binomial regression models, we estimated the incidence rates of adult influenza-associated critical illness hospitalizations and compared them with all-cause event rates. We also compared modeled outcomes to International Classification of Diseases, 9th Edition, Clinical Modification-coded influenza hospitalizations to assess potential underrecognition of severe influenza disease. During the study period, we estimated that 26,760 influenza-associated critical illness hospitalizations (95% CI, 14,541, 47,464) occurred. The population-based incidence estimate for influenza-associated critical illness was 12.0 per 100,000 person-years (95% CI, 6.6, 21.6) or 1.3% of all critical illness hospitalizations (95% CI, 0.7%, 2.3%). During the influenza season, 3.4% of all critical illness hospitalizations (95% CI, 1.9%, 5.8%) were attributable to influenza. There were only 2,612 critical illness hospitalizations with International Classification of Diseases, 9th Edition, Clinical Modification-coded influenza diagnoses, suggesting influenza is either undiagnosed or undercoded in a substantial proportion of critical illness. CONCLUSIONS: Extrapolating our data to the 2010 U.S. population, we estimate that about 28,000 adults are hospitalized for influenza-associated critical illness annually. Influenza in many of these critically ill patients may be undiagnosed. Critical care physicians should have a high index of suspicion for influenza in the ICU, particularly when influenza is known to be circulating in their communities.

Population-based incidence estimates of influenza-associated respiratory failure hospitalizations, 2003 to 2009.

RATIONALE: The incidence of influenza-associated acute respiratory failure is unknown. OBJECTIVES: To estimate the population-based incidence of influenza-associated acute respiratory failure hospitalizations. METHODS: This is a cohort study from January 2003 through March 2009 using hospitalization databases for Arizona, California, and Washington from the Healthcare Cost and Utilization Project and influenza surveillance data for regions encompassing these states. Acute respiratory failure requiring mechanical ventilation was defined by International Classification of Diseases-9-CM code. We used negative-binomial regression modeling to estimate the incidence of influenza-associated events. MEASUREMENTS AND MAIN RESULTS: The incidence of influenza-associated acute respiratory failure was 2.7 per 100,000 person-years (95% confidence interval, 0.2-23.5), and during the influenza season, 3.8% of all respiratory failure hospitalizations were attributable to influenza. Compared with adults aged 18-49 years, the incidence rate ratio for influenza-associated acute respiratory failure was lower among children aged 1-4 (0.9) and 5-17 years (0.3); however, it was higher among adults aged 50-64 (4.8), 65-74 (10.4), 75-84 (19.9), and 85 years and older (33.7). Results were similar with more sensitive and specific outcome definitions and in a sensitivity analysis using only Arizona-specific outcome and surveillance data. CONCLUSIONS: Our data indicate that influenza was an important contributor to respiratory failure hospitalizations during 2003-2009. Clinicians should maintain a high index of suspicion for influenza among hospitalized patients with acute respiratory illness when influenza is circulating in a community. Influenza has a greater effect on respiratory failure in the elderly, for whom better prevention measures are needed.

Rhombencephalosynapsis: a hindbrain malformation associated with incomplete separation of midbrain and forebrain, hydrocephalus and a broad spectrum of severity.

Rhombencephalosynapsis is a midline brain malformation characterized by missing cerebellar vermis with apparent fusion of the cerebellar hemispheres. Rhombencephalosynapsis can be seen in isolation or together with other central nervous system and extra-central nervous system malformations. Gómez-López-Hernández syndrome combines rhombencephalosynapsis with parietal/temporal alopecia and sometimes trigeminal anaesthesia, towering skull shape and dysmorphic features. Rhombencephalosynapsis can also be seen in patients with features of vertebral anomalies, anal atresia, cardiovascular anomalies, trachea-oesophageal fistula, renal anomalies, limb defects (VACTERL) association. Based on a comprehensive evaluation of neuroimaging findings in 42 patients with rhombencephalosynapsis, we propose a spectrum of severity, ranging from mild (the partial absence of nodulus, anterior and posterior vermis), to moderate (the absence of posterior vermis with some anterior vermis and nodulus present), to severe (the absence of posterior and anterior vermis with some nodulus present), to complete (the absence of the entire vermis including nodulus). We demonstrate that the severity of rhombencephalosynapsis correlates with fusion of the tonsils, as well as midbrain abnormalities including aqueductal stenosis and midline fusion of the tectum. Rhombencephalosynapsis is also associated with multiple forebrain abnormalities including absent olfactory bulbs, dysgenesis of the corpus callosum, absent septum pellucidum and, in rare patients, atypical forms of holoprosencephaly. The frequent association between rhombencephalosynapsis and aqueductal stenosis prompted us to evaluate brain magnetic resonance images in other patients with aqueductal stenosis at our institution, and remarkably, we identified rhombencephalosynapsis in 9%. Strikingly, subjects with more severe rhombencephalosynapsis have more severely abnormal neurodevelopmental outcome, as do subjects with holoprosencephaly and patients with VACTERL features. In summary, our data provide improved diagnostic and prognostic information, and support disruption of dorsal-ventral patterning as a mechanism underlying rhombencephalosynapsis.

Association of socio-demographic factors and parental education with depressive symptoms among older African Americans and Caribbean Blacks.

OBJECTIVE: The purpose of this study was to examine ethnic variation in the relationship between individual socio-demographic factors, parental educational level, and late-life depressive symptoms in older African Americans and Caribbean Blacks. METHOD: This cross-sectional study used data from the National Survey of American Life. A subsample of older African Americans (N = 837) and Caribbean Blacks (N = 271) was analyzed using multiple regression analysis. RESULTS: Findings suggest differences in predictors of depressive symptoms for the two ethnic groups. Among older African Americans, lower educational attainment and lower income were predictive risk factors for higher depressive symptoms. Findings among older Caribbean Blacks suggest that nativity and income were significantly associated with depressive symptoms. This study did not find support for any association between parental education and late-life depressive symptoms. CONCLUSION: This study adds new information by considering ethnic variation in an examination of depressive symptoms in older Black Americans. The results contribute to the growing awareness of the older Caribbean Black population in the United States.

Perceived discrimination and social networks among older African Americans and Caribbean blacks.

The relationship between perceived discrimination and depressive symptoms among older black American populations is poorly understood. Although a small number of studies have examined the relationship between stress and social support, few have examined the association between perceived discrimination, social networks, and depressive symptoms among a representative sample of older racial and ethnic groups. This study examines (a) the relationship between sociodemographic factors, perceived discrimination and depressive symptoms and (b) social networks as a potential moderator in the perceived discrimination and depressive symptom relationship between 2 groups of older black Americans. This was a cross-sectional study using data from the National Survey of American Life with a sample of older African Americans (N = 837) and Caribbean blacks (N = 271). Depressive symptoms were assessed using the 12-item Center for Epidemiological Studies Depression scale. Linear regression analyses were used to predict depressive symptoms. The relationship between perceived discrimination and depressive symptoms was significant in both groups. Social networks contributed as a protective factor for depressive symptoms for both groups. However, there was no significant moderation effect. Results suggest that regardless of ethnic affiliation, the experience of perceived discrimination is similar in both groups and is a risk factor for depressive symptoms. Future research is needed in this area to better understand the associations between sociodemographic factors, perceived discrimination, social networks, and their impact on depressive symptoms.

Temporal trends in the prevalence of diabetic kidney disease in the United States.

CONTEXT: Diabetes is the leading cause of kidney disease in the developed world. Over time, the prevalence of diabetic kidney disease (DKD) may increase due to the expanding size of the diabetes population or decrease due to the implementation of diabetes therapies. OBJECTIVE: To define temporal changes in DKD prevalence in the United States. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional analyses of the Third National Health and Nutrition Examination Survey (NHANES III) from 1988-1994 (N = 15,073), NHANES 1999-2004 (N = 13,045), and NHANES 2005-2008 (N = 9588). Participants with diabetes were defined by levels of hemoglobin A(1c) of 6.5% or greater, use of glucose-lowering medications, or both (n = 1431 in NHANES III; n = 1443 in NHANES 1999-2004; n = 1280 in NHANES 2005-2008). MAIN OUTCOME MEASURES: Diabetic kidney disease was defined as diabetes with albuminuria (ratio of urine albumin to creatinine ≥30 mg/g), impaired glomerular filtration rate (<60 mL/min/1.73 m(2) estimated using the Chronic Kidney Disease Epidemiology Collaboration formula), or both. Prevalence of albuminuria was adjusted to estimate persistent albuminuria. RESULTS: The prevalence of DKD in the US population was 2.2% (95% confidence interval [CI], 1.8%-2.6%) in NHANES III, 2.8% (95% CI, 2.4%-3.1%) in NHANES 1999-2004, and 3.3% (95% CI, 2.8%-3.7%) in NHANES 2005-2008 (P <.001 for trend). The prevalence of DKD increased in direct proportion to the prevalence of diabetes, without a change in the prevalence of DKD among those with diabetes. Among persons with diabetes, use of glucose-lowering medications increased from 56.2% (95% CI, 52.1%-60.4%) in NHANES III to 74.2% (95% CI, 70.4%-78.0%) in NHANES 2005-2008 (P <.001); use of renin-angiotensin-aldosterone system inhibitors increased from 11.2% (95% CI, 9.0%-13.4%) to 40.6% (95% CI, 37.2%-43.9%), respectively (P <.001); the prevalence of impaired glomerular filtration rate increased from 14.9% (95% CI, 12.1%-17.8%) to 17.7% (95% CI, 15.2%-20.2%), respectively (P = .03); and the prevalence of albuminuria decreased from 27.3% (95% CI, 22.0%-32.7%) to 23.7% (95% CI, 19.3%-28.0%), respectively, but this was not statistically significant (P = .07). CONCLUSIONS: Prevalence of DKD in the United States increased from 1988 to 2008 in proportion to the prevalence of diabetes. Among persons with diabetes, prevalence of DKD was stable despite increased use of glucose-lowering medications and renin-angiotensin-aldosterone system inhibitors.

Integrative analysis of DNA copy number and gene expression in metastatic oral squamous cell carcinoma identifies genes associated with poor survival.

BACKGROUND: Lymphotropism in oral squamous cell carcinoma (OSCC) is one of the most important prognostic factors of 5-year survival. In an effort to identify genes that may be responsible for the initiation of OSCC lymphotropism, we examined DNA copy number gains and losses and corresponding gene expression changes from tumor cells in metastatic lymph nodes of patients with OSCC. RESULTS: We performed integrative analysis of DNA copy number alterations (CNA) and corresponding mRNA expression from OSCC cells isolated from metastatic lymph nodes of 20 patients using Affymetrix 250 K Nsp I SNP and U133 Plus 2.0 arrays, respectively. Overall, genome CNA accounted for expression changes in 31% of the transcripts studied. Genome region 11q13.2-11q13.3 shows the highest correlation between DNA CNA and expression. With a false discovery rate < 1%, 530 transcripts (461 genes) demonstrated a correlation between CNA and expression. Among these, we found two subsets that were significantly associated with OSCC (n = 122) when compared to controls, and with survival (n = 27), as tested using an independent dataset with genome-wide expression profiles for 148 primary OSCC and 45 normal oral mucosa. We fit Cox models to calculate a principal component analysis-derived risk-score for these two gene sets ('122-' or '27-transcript PC'). The models combining the 122- or 27-transcript PC with stage outperformed the model using stage alone in terms of the Area Under the Curve (AUC = 0.82 or 0.86 vs. 0.72, with p = 0.044 or 0.011, respectively). CONCLUSIONS: Genes exhibiting CNA-correlated expression may have biological impact on carcinogenesis and cancer progression in OSCC. Determination of copy number-associated transcripts associated with clinical outcomes in tumor cells with an aggressive phenotype (i.e., cells metastasized to the lymph nodes) can help prioritize candidate transcripts from high-throughput data for further studies.

A genetic expression profile associated with oral cancer identifies a group of patients at high risk of poor survival.

PURPOSE: To determine if gene expression signature of invasive oral squamous cell carcinoma (OSCC) can subclassify OSCC based on survival. EXPERIMENTAL DESIGN: We analyzed the expression of 131 genes in 119 OSCC, 35 normal, and 17 dysplastic mucosa to identify cluster-defined subgroups. Multivariate Cox regression was used to estimate the association between gene expression and survival. By stepwise Cox regression, the top predictive models of OSCC-specific survival were determined and compared by receiver operating characteristic analysis. RESULTS: The 3-year overall mean+/-SE survival for a cluster of 45 OSCC patients was 38.7+/-0.09% compared with 69.1+/-0.08% for the remaining patients. Multivariate analysis adjusted for age, sex, and stage showed that the 45 OSCC patient cluster had worse overall and OSCC-specific survival (hazard ratio, 3.31; 95% confidence interval, 1.66-6.58 and hazard ratio, 5.43; 95% confidence interval, 2.32-12.73, respectively). Stepwise Cox regression on the 131 probe sets revealed that a model with a term for LAMC2 (laminin gamma2) gene expression best identified patients with worst OSCC-specific survival. We fit a Cox model with a term for a principal component analysis-derived risk score marker and two other models that combined stage with either LAMC2 or PCA. The area under the curve for models combining stage with either LAMC2 or PCA was 0.80 or 0.82, respectively, compared with 0.70 for stage alone (P=0.013 and 0.008, respectively). CONCLUSIONS: Gene expression and stage combined predict survival of OSCC patients better than stage alone.

Serum phosphorus concentrations in the third National Health and Nutrition Examination Survey (NHANES III).

BACKGROUND: Higher serum phosphorus concentrations within the normal laboratory range have been associated with cardiovascular events and mortality in large prospective cohort studies of individuals with and without kidney disease. Reasons for interindividual variation in steady-state serum phosphorus concentrations are largely unknown. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: 15,513 participants in the Third National Health and Nutrition Examination Survey. PREDICTORS: Demographic data, dietary intake measured by means of 24-hour dietary recall and food-frequency questionnaire, and established cardiovascular risk factors. OUTCOME & MEASUREMENTS: Serum phosphorus concentration. RESULTS: Mean serum phosphorus concentrations were significantly greater in women (+0.16 mg/dL versus men; P < 0.001) and people of non-Hispanic black and Hispanic race/ethnicity (+0.06 and +0.07 mg/dL versus non-Hispanic white, respectively; P < 0.001). Dietary intakes of phosphorus and phosphorus-rich foods were associated only weakly with circulating serum phosphorus concentrations, if at all. Higher serum phosphorus levels were associated with lower calculated Framingham coronary heart disease risk scores, which are based on traditional atherosclerosis risk factors. In aggregate, demographic, nutritional, cardiovascular, and kidney function variables explained only 12% of the variation in circulating serum phosphorus concentrations. LIMITATIONS: Results may differ with advanced kidney disease. CONCLUSIONS: Serum phosphorus concentration is weakly related to dietary phosphorus and not related to a diverse array of phosphorus-rich foods in the general population. Factors determining serum phosphorus concentration are largely unknown. Previously observed associations of serum phosphorus concentrations with cardiovascular events are unlikely to be a result of differences in dietary intake or traditional cardiovascular risk factors.

Urinary porphyrin excretion in children with mercury amalgam treatment: findings from the Casa Pia Children's Dental Amalgam Trial.

Increases in the urinary concentrations of pentacarboxyl- and coproporphyrins and the appearance of the atypical precoproporphyrin have been defined in relation to mercury (Hg) body burden in animal studies, and this change in the porphyrin excretion pattern has been described as a biomarker of occupational Hg exposure and toxicity in adult human subjects. In the present studies, urinary porphyrins were determined in relation to Hg exposure in children and adolescents, 8-18 yr of age, over the 7-yr course of a clinical trial designed to evaluate the neurobehavioral and renal effects of dental amalgam in children. Subjects were randomized to either dental amalgam or composite resin treatments. Urinary porphyrins and creatinine concentrations were measured at baseline and annually in all subjects. Results were evaluated using linear regression analysis. No significant differences between treatment groups (amalgam versus composite) were found when comparing all subjects for any of the porphyrins of interest. However, incipent amalgam treatment-specific increases were observed in the mean concentrations of penta-, precopro- and coproporphyrins especially when the analyses were restricted to younger subjects (8 to 9 yr old at baseline), and these increases were most apparent during yr 2 through 3 of follow-up, the period of highest mercury exposure from amalgam treatment. Based on the mean number of amalgam fillings received by children in this group (17.8), the renal Hg concentration associated with incipient increases in urinary porphyrins was estimated to be approximately 2.7 microg/g renal cortex. This value corresponds to an observed mean urinary Hg concentration of 3.2 microg/g creatinine, which is approximately fivefold less than that at which renal damage from Hg exposure is estimated to occur in children. These findings are consistent with growing evidence supporting the sensitivity of urinary porphyrins as a biological indicator of subclinical Hg exposure in children.

Risk interval analysis of emergency room visits following colonoscopy in patients with inflammatory bowel disease.

BACKGROUND AND AIMS: Prior studies suggest that colonoscopy may exacerbate inflammatory bowel disease (IBD) symptoms. Thus, our study aimed to determine risk of emergency room (ER) visits associated with colonoscopy among IBD patients and evaluate potential modifiers of this risk. METHODS: The study population included IBD patients in the Multi-Payer Claims Database who were >20 years old and had a colonoscopy from 2007-2010. We used a self-controlled risk interval design and mixed-effects Poisson regression models to calculate risk ratios (RR) and 95% confidence intervals (CI) comparing the incidence of ER visits in the 1-4 weeks following colonoscopy (risk interval) to the incidence of ER visits in the 7-10 weeks after colonoscopy (control interval). We also conducted stratified analyses by patient characteristics, bowel preparation type, and medication. RESULTS: There were 212,205 IBD patients with at least 1 colonoscopy from 2007-2010, and 3,699 had an ER visit during the risk and/or control interval. The risk of an ER visit was higher in the 4-week risk interval following colonoscopy compared to the control interval (RR = 1.24; 95% CI: 1.17-1.32). The effect was strongest in those <41 years old (RR = 1.60; 95% CI: 1.21-2.11), in women (RR = 1.32; 95% CI: 1.21-1.44), and in those with sodium phosphate bowel preparation (RR = 2.09; 95% CI: 1.02-4.29). Patients using immunomodulators had no increased risk of ER visits (RR = 0.75; 95% CI: 0.35-1.59). CONCLUSIONS: Our results suggest that there is an increased risk of ER visits following colonoscopy among IBD patients, but that immunomodulators and mild bowel preparation agents may mitigate this risk.

Biomarkers of kidney integrity in children and adolescents with dental amalgam mercury exposure: findings from the Casa Pia children's amalgam trial.

Mercury is toxic to the kidney, and dental amalgam is a source of mercury exposure. Few studies have evaluated the effects of dental amalgam on kidney function in a longitudinal context in children. Here, we evaluated urinary concentrations of glutathione S-transferases (GSTs) alpha and pi as biomarkers of renal proximal and distal tubular integrity, respectively, and albumin as a biomarker of glomerular integrity in children and adolescents 8-18 years of age over a 7-year course of dental amalgam treatment. Five hundred seven children, 8-12 years of age at baseline, participated in a clinical trial to evaluate the neurobehavioral and renal effects of dental amalgam in children. Subjects were randomized to either dental amalgam or resin composite treatments. Urinary GSTs alpha and pi, albumin, and creatinine concentrations were measured at baseline and annually in all subjects. Results were evaluated using linear regression analysis. GST-alpha concentrations were similar between treatment groups and in each sex and race (white vs. non-white) group in each follow-up year. GST-pi levels tended upward over the course of follow-up by four- to six-fold. This increase was seen in all groups irrespective of the treatment, race, or gender. Females had GST-pi levels approximately twice those of males at all ages. Albumin concentrations were constant throughout the follow-up period and did not differ by treatment, although females had 39% higher albumin levels than males. Additionally, we found no significant effects of amalgam treatment on the proportion of children with microalbuminuria (>30 mg/g creatinine). These findings are relevant within the context of children's health risk assessment as relates to the safety of mercury exposure from dental amalgam on kidney function. These data also provide normative values for sensitive indices of renal functional integrity that may serve in the evaluation of children and adolescents with renal disorders.

Third-molar extraction as a risk factor for temporomandibular disorder.

BACKGROUND: Although third-molar extraction is common in the U.S., there are few reports on the relationship between third-molar extraction and temporomandibular disorder (TMD). The aim of this study was to investigate this potential association. METHODS: The authors enrolled study subjects on their 15th birthdays and followed them continuously for a minimum of five years. The authors ascertained exposure (third-molar extraction) and outcome (TMD) via electronic dental insurance records. A survival analysis design estimated the relative risk of experiencing TMD after third-molar extraction. They considered sex, dental care utilization and other potentially confounding variables in the analyses. RESULTS: A total of 34,491 subjects met the inclusion criterion. Fifty percent of all subjects had third molars removed by the age of 20 years, and 391 subjects had claims indicating TMD. The adjusted relative risk of experiencing TMD after third-molar extraction was 1.6 (95 percent confidence interval, 1.3 to 2.0). Calculation of the population risk indicated that 23 percent of all TMD cases in this age group might be due to third-molar extraction. CONCLUSIONS: Third-molar extraction appears to be a risk factor for TMD. CLINICAL IMPLICATIONS: Dental providers should be aware of the risk of experiencing TMD related to third-molar extraction and take measures to minimize trauma to the joint during extraction.

Two Hundred Thirty-Six Children With Developmental Hydrocephalus: Causes and Clinical Consequences.

Few systematic assessments of developmental forms of hydrocephalus exist. We reviewed magnetic resonance images (MRIs) and clinical records of patients with infancy-onset hydrocephalus. Among 411 infants, 236 had hydrocephalus with no recognizable extrinsic cause. These children were assigned to 1 of 5 subtypes and compared on the basis of clinical characteristics and developmental and surgical outcomes. At an average age of 5.3 years, 72% of children were walking independently and 87% could eat by mouth; in addition, 18% had epilepsy. Distinct patterns of associated malformations and syndromes were observed within each subtype. On average, children with aqueductal obstruction, cysts, and encephaloceles had worse clinical outcomes than those with other forms of developmental hydrocephalus. Overall, 53% of surgically treated patients experienced at least 1 shunt failure, but hydrocephalus associated with posterior fossa crowding required fewer shunt revisions. We conclude that each subtype of developmental hydrocephalus is associated with distinct clinical characteristics, syndromology, and outcomes, suggesting differences in underlying mechanisms.

Using Internet to recruit immigrants with language and culture barriers for tobacco and alcohol use screening: a study among Brazilians.

Limited English proficient (LEP) individuals face disparities in accessing substance abuse treatment, but little is known on how to reach this population. This study aimed to test online recruitment methods for tobacco and alcohol screening among LEP Portuguese speakers. The study was advertised in Portuguese using Facebook, Google, online newsletters and E-mail. Participants clicked ads to consent and access a screening for tobacco and alcohol dependence. Ads yielded 690 screening responses in 90 days. Respondents had a mean age of 42.7 (SD 12), with a higher proportion of women than men, 95% born in Brazil with high levels of LEP and low levels of acculturation. Facebook ads yielded 41.4% of responses, and were the lowest cost recruitment channel ($8.9, $31.10 and $20.40 per respondent, hazardous drinker and smoker, respectively). Online recruitment of LEP populations is feasible. Future studies should test similar strategies in other LEP groups.

Visits to US emergency departments by 20- to 29-year-olds with toothache during 2001-2010.

BACKGROUND: Visits to emergency departments (EDs) for dental symptoms are on the rise, yet reliance on EDs for dental care is far from ideal. ED toothache visits represent opportunities to improve access to professional dental care. METHODS: This research focuses on 20- to 29-year-olds, who account for more ED toothache visits than do other age groups. The authors analyzed publicly available ED visit data from the National Hospital Ambulatory Medical Care Survey (NHAMCS) from 2001 through 2010. They assessed trends in ED toothache visit rates compared with back pain and all cause ED visits during the past decade. The authors used NHAMCS data for years 2009 and 2010 to characterize the more recent magnitude, relative frequency, and independent risk factors for ED toothache visits. Statistical analyses accounted for the complex sampling design. RESULTS: The average annual increase in ED visit rates among 20- to 29-year-olds during 2001-2010 was 6.1% for toothache, 0.3% for back pain, and 0.8% for all causes of ED visits. In 2009 and 2010, 20- to 29-year-olds made an estimated 1.27 million ED visits for toothaches and accounted for 42% of all ED toothache visits. Toothache was the fifth most common reason for any ED visit and third most common for uninsured ED visits by 20- to 29-year-olds. Independent risk factors for ED toothache visits were being uninsured or Medicaid-insured. CONCLUSIONS: Younger adults increasingly rely on EDs for toothaches-likely because of barriers to accessing professional dental care. Expanding dental coverage and access to affordable dental care could increase options for timely dental care and decrease ED use for dental symptoms. PRACTICAL IMPLICATIONS: Though additional research is needed to better understand why younger adults disproportionately use the ED for toothaches, findings from this study suggest the importance of maintaining access to a dental home from childhood through adolescence and subsequently into early adulthood.

A 13-gene signature prognostic of HPV-negative OSCC: discovery and external validation.

PURPOSE: To identify a prognostic gene signature for patients with human papilloma virus (HPV)-negative oral squamous cell carcinomas (OSCC). EXPERIMENTAL DESIGN: Two gene expression datasets were used: a training dataset from the Fred Hutchinson Cancer Research Center (FHCRC, Seattle, WA; n = 97) and a validation dataset from the MD Anderson Cancer Center (MDACC, Houston, TX; n = 71). We applied L1/L2-penalized Cox regression models to the FHCRC data on the 131-gene signature previously identified to be prognostic in patients with OSCCs to identify a prognostic model specific for patients with high-risk HPV-negative OSCCs. The models were tested with the MDACC dataset using a receiver operating characteristic (ROC) analysis. RESULTS: A 13-gene model was identified as the best predictor of HPV-negative OSCC-specific survival in the training dataset. The risk score for each patient in the validation dataset was calculated from this model and dichotomized at the median. The estimated 2-year mortality (± SE) of patients with high-risk scores was 47.1% (± 9.24%) compared with 6.35% (± 4.42) for patients with low-risk scores. ROC analyses showed that the areas under the curve for the age, gender, and treatment modality-adjusted models with risk score [0.78; 95% confidence interval (CI), 0.74-0.86] and risk score plus tumor stage (0.79; 95% CI, 0.75-0.87) were substantially higher than for the model with tumor stage (0.54; 95% CI, 0.48-0.62). CONCLUSIONS: We identified and validated a 13-gene signature that is considerably better than tumor stage in predicting survival of patients with HPV-negative OSCCs. Further evaluation of this gene signature as a prognostic marker in other populations of patients with HPV-negative OSCC is warranted.

Examining palliative care team involvement in automatic consultations for children on extracorporeal life support in the pediatric intensive care unit.

BACKGROUND: Extracorporeal life support (ECLS) is an advanced form of life-sustaining therapy that creates stressful dilemmas for families. In May 2009, Seattle Children's Hospital (SCH) implemented a policy to involve the Pediatric Advanced Care Team (PACT) in all ECLS cases through automatic referral. OBJECTIVE: Our aim was to describe PACT involvement in the context of automatic consultations for ECLS patients and their family members. METHODS: We retrospectively examined chart notes for 59 consecutive cases and used content analysis to identify themes and patterns. RESULTS: The degree of PACT involvement was related to three domains: prognostic uncertainty, medical complexity, and need for coordination of care with other services. Low PACT involvement was associated with cases with little prognostic uncertainty, little medical complexity, and minimal need for coordination of care. Medium PACT involvement was associated with two categories of cases: 1) those with a degree of medical complexity but little prognostic uncertainty; and 2) those that had a degree of prognostic uncertainty but little medical complexity. High PACT involvement had the greatest medical complexity and prognostic uncertainty, and also had those cases with a high need for coordination of care. CONCLUSIONS: We describe a framework for understanding the potential involvement of palliative care among patients receiving ECLS that explains how PACT organizes its efforts toward patients and families with the highest degree of need. Future studies should examine whether this approach is associated with improved patient and family outcomes.

Human sinonasal explant system for testing cytotoxicity of intranasal agents.

BACKGROUND: Intranasal agents play a critical role in the management of sinonasal disorders. There are ongoing efforts to develop new intranasal medications to combat sinonasal disease. Some intranasal agents, however, can have cytotoxic effects on human sinonasal tissue. In order to facilitate safe drug discovery, we developed a simple and reliable in vitro screening assay using human sinonasal explants to measure the cytotoxic profiles of intranasal agents. METHODS: We obtained sinonasal tissues from several regions of the nasal cavity from 12 patients undergoing endoscopic sinonasal surgery. These tissues were cultured on polytetrafluoroethylene membrane in serum-free growth medium. We determined the biochemical properties of these explants by measuring extracellular lactate dehydrogenase (LDH) levels and performing histological analyses over a period of 1 to 2 weeks. We then examined the cytotoxic profiles of 13 intranasal agents by measuring extracellular LDH levels using the human sinonasal explant system. RESULTS: Sinonasal explants exhibited a rapid reduction in extracellular LDH levels indicating stabilization in the culture environment within 2 days. Histological analysis showed maintenance of good cellular architecture for up to 2 weeks. The explants displayed intact epithelium and expressed ßIII-tubulin and Ki-67. Of the 13 tested intranasal agents, 1% zinc sulfate (ZnSO(4) ), 5% ZnSO(4) , and Zicam application were cytotoxic. CONCLUSION: Based on the unique biochemical properties of the human nasal explant culture system, we developed a simple and reliable in vitro screening assay to determine the cytotoxic profiles of various intranasal agents by examining extracellular LDH levels and histopathology.