H. Lester Kirchner

Frequency of voice problems among teachers and other occupations.

This study describes the frequency of reporting vocal problems among a random sample of elementary and high school teachers (n = 554) compared to individuals working in other occupations (n = 220). Teachers were more likely to define themselves as ever having a voice problem (32% versus. 1%, p < .05); having a tired, weak, or effortful voice (p < .05 each); and having a higher frequency of symptoms of physical discomfort with speaking (p < .05). They also were more likely to perceive that their voice problem negatively affected current job performance (p < .05) and limited options regarding change in work (p < .05). About 20% of teachers but only 4% of nonteachers had missed work due to their voice. These findings suggest that teachers are at high-risk for disability from voice disorders and that this health problem may have significant work-related and economic effects.

Increased risk of death and de novo chronic kidney disease following reversible acute kidney injury

Acute kidney injury increases mortality risk among those with established chronic kidney disease. In this study we used a propensity score-matched cohort method to retrospectively evaluate the risks of death and de novo chronic kidney disease after reversible, hospital-associated acute kidney injury among patients with normal pre-hospitalization kidney function. Of 30,207 discharged patients alive at 90 days, 1610 with reversible acute kidney injury that resolved within the 90 days were successfully matched across multiple parameters with 3652 control patients who had not experienced acute kidney injury. Median follow-up was 3.3 and 3.4 years (injured and control groups, respectively). In Cox proportional hazard models, the risk of death associated with reversible acute kidney injury was significant (hazard ratio 1.50); however, adjustment for the development of chronic kidney injury during follow-up attenuated this risk (hazard ratio 1.18). Reversible acute kidney injury was associated with a significant risk of de novo chronic kidney disease (hazard ratio 1.91). Thus, a resolved episode of hospital-associated acute kidney injury has important implications for the longitudinal surveillance of patients without preexisting, clinically evident kidney disease.

Voice problems among teachers: Differences by gender and teaching characteristics

This study describes the effects of teaching activities on voice problems in male (n = 274) and female teachers (n = 280). Over 38% of the teachers studied complained that teaching had an adverse impact on their voice and 39% of those had cut back teaching activities as a result. Compared to males, female teachers more frequently reported a voice problem (38% vs. 26%, p<.05), acute (p<.05), and chronic (p<.05) voice problems, six specific voice symptoms, and five symptoms of physical discomfort. However, there were no gender differences in the perception that a voice problem adversely affected their current or future teaching career. For every type of course taught, women had a higher probability of reporting voice problems compared to men: odds ratio (OR) = 1.7-2.1. Compared with other courses, the teaching of physical education also was associated with an increased risk of developing a voice problem (OR = 3.7, 95% CI: 1.4-9.4) independent of gender, age, hours/day, or years taught. This is the first study to show that in the same occupation, females report a higher frequency of vocal symptoms than males even when teaching characteristics and years employment are similar.

Variation of C-Reactive Protein Levels in Adolescents Association With Sleep-Disordered Breathing and Sleep Duration

Background—There is increasing evidence that sleep-disordered breathing (SDB) is an independent risk factor for cardiovascular disease (CVD) in adults. C-reactive protein (CRP), a marker of systemic inflammation, is an important predictor of future cardiovascular events. The goal of this study was to quantify the associations of SDB, sleep duration, and CRP in adolescents to better understand the role of SDB in CVD risk. Methods and Results—Adolescents (n=143; age, 13 to 18 years; 36% black; 50% female) with a wide range of SDB severity underwent polysomnography and measurement of high-sensitivity CRP. SDB was quantified with the apnea hypopnea index (AHI) and oxygen desaturation measures. Sleep duration was estimated from 7-day actigraphy. The independent and dose-response associations of SDB with CRP were addressed through linear mixed-effects models. Forty-eight percent were overweight or obese, and 12% had SDB (AHI ≥5). CRP levels varied with increasing body mass index and SDB. After adjustment for body mass index, age, sex, and race, mean CRP levels were 0.50, 0.43, 0.97, and 1.66 mg/L for SDB severity levels of AHI <1, 1 to 4.9, 5 to 14.9, and ≥15, respectively (P=0.0049, AHI ≥15 versus <1). Adjusted mean CRP levels demonstrated a dose response with SDB above a threshold AHI of 5. This association was partially explained by overnight hypoxemia and less so by sleep duration. Conclusions—In adolescents free of known CVD, an AHI ≥5 is associated with increasing levels of CRP, suggesting that pediatric SDB may confer additional CVD risk beyond that of obesity.

Human papillomavirus and risk of oral cancer

Although human papillomavirus (HPV), a sexually transmitted virus, is established as a necessary cause for more than 95% of cervical carcinomas, the association with oral squamous cell carcinoma is less well delineated. The purpose of this study was to determine the frequency and types of HPV in squamous cells of a group of patients with newly diagnosed oral or pharyngeal cancer (n = 93) compared with an age‐and gender‐frequency‐matched control group of patients with no history of oral cancer (n = 205). HPV was evaluated from a mouth rinse collection of cells in the oral cavity and tested by 32P‐labeled HPV generic probes and DNA sequencing for HPV types. HPV was identified in 15% of the oral cancer cases but in fewer than 5% of the controls (P < .05). The risk of cancer associated with HPV infection was independent of tobacco and alcohol use (adjusted odds ratio [OR] = 3.70; 95% confidence interval [CI]: 1.47–9.32; P < .05). HPV types included similar and other types not identified previously in the genital tract. There was no statistically significant increased risk of cancer among former tobacco users (former vs. never users: adjusted OR = 0.67, 95% CI: 0.31–1.44, P < .05), but the risk was significantly increased for current users (current vs. never: adjusted OR = 2.63; 95% CI: 1.22–5.71; P < .05). Likewise, former alcohol users were not at increased risk of disease (former vs. never: adjusted OR = 1.78; 95% CI: 0.87–3.67), whereas current alcohol users were (current vs. never: adjusted OR = 2.57; 95% CI: 1.22–5.42; P < .05). HPV‐related genital lesions (14.3% vs. 10.6%), oral‐genital sexual behavior (42.4% vs. 45.2%), and number (11 or more) of sexual partners (23% v. 17%) were not significantly different between cases and controls. These data suggest that in addition to tobacco and alcohol, HPV plays a role in the development of oral cancer.

Reduction in asthma morbidity in children as a result of home remediation aimed at moisture sources.

Objective Home dampness and the presence of mold and allergens have been associated with asthma morbidity. We examined changes in asthma morbidity in children as a result of home remediation aimed at moisture sources. Design In this prospective, randomized controlled trial, symptomatic, asthmatic children (n = 62), 2–17 years of age, living in a home with indoor mold, received an asthma intervention including an action plan, education, and individualized problem solving. The remediation group also received household repairs, including reduction of water infiltration, removal of water-damaged building materials, and heating/ventilation/air-conditioning alterations. The control group received only home cleaning information. We measured children’s total and allergen-specific serum immuno-globulin E, peripheral blood eosinophil counts, and urinary cotinine. Environmental dust samples were analyzed for dust mite, cockroach, rodent urinary protein, endotoxin, and fungi. The follow-up period was 1 year. Results Children in both groups showed improvement in asthma symptomatic days during the preremediation portion of the study. The remediation group had a significant decrease in symptom days (p = 0.003, as randomized; p = 0.004, intent to treat) after remodeling, whereas these parameters in the control group did not significantly change. In the postremediation period, the remediation group had a lower rate of exacerbations compared with control asthmatics (as treated: 1 of 29 vs. 11 of 33, respectively, p = 0. 003; intent to treat: 28.1% and 10.0%, respectively, p = 0.11). Conclusion Construction remediation aimed at the root cause of moisture sources and combined with a medical/behavioral intervention significantly reduces symptom days and health care use for asthmatic children who live in homes with a documented mold problem.

Sleep Disordered Breathing and Impaired Glucose Metabolism in Normal Weight and Overweight/Obese Individuals: The Sleep Heart Health Study

OBJECTIVE—To characterize the association between sleep-disordered breathing (SDB) and impaired fasting glucose (IFG), impaired glucose tolerance (IGT), combined IFG and IGT, and occult diabetes in individuals of different body habitus. RESEARCH DESIGN AND METHODS—Cross-sectional analysis of 2,588 participants (aged 52–96 years; 46% men) without known diabetes. SDB was defined as respiratory disturbance index ≥10 events/h. IFG, IGT, occult diabetes, and body weight were classified according to recent accepted guidelines. Participants with and without SDB were compared on prevalence and odds ratios for measures of impaired glucose metabolism (IGM), adjusting for age, sex, race, BMI, and waist circumference. RESULTS—SDB was observed in 209 nonoverweight and 1,036 overweight/obese participants. SDB groups had significantly higher adjusted prevalence and adjusted odds of IFG, IFG plus IGT, and occult diabetes. The adjusted odds ratio for all subjects was 1.3 (95% CI 1.1–1.6) for IFG, 1.2 (1.0–1.4) for IGT, 1.4 (1.1–2.7) for IFG plus IGT, and 1.7 (1.1–2.7) for occult diabetes. CONCLUSIONS—SDB was associated with occult diabetes, IFG, and IFG plus IGT, after adjusting for age, sex, race, BMI, and waist circumference. The magnitude of these associations was similar in nonoverweight and overweight participants. The consistency of associations across all measures of IGM and body habitus groups and the significant association between SDB and IFG plus IGT, a risk factor for rapid progression to diabetes, cardiovascular disease, and mortality, suggests the importance of SDB as a risk factor for clinically important levels of metabolic dysfunction.

Comparison of racemic albuterol and levalbuterol for treatment of acute asthma

OBJECTIVE To determine whether levalbuterol resulted in fewer hospital admissions than racemic albuterol when used for treatment of acute asthma. Study design A randomized, double-blind, controlled trial was conducted in the emergency department (ED) and inpatient asthma care unit of an urban tertiary childrens hospital. Children age 1 to 18 years (n=482) provided a total of 547 enrollments. Patients received a nebulized solution of either 2.5 mg racemic albuterol or 1.25 mg levalbuterol every 20 minutes (maximum six doses). Patients admitted to the asthma care unit were treated in a standardized fashion by using the same blinded drug assigned in the ED. Hospitalization rate was the primary outcome. RESULTS Hospitalization rate was significantly lower in the levalbuterol group (36%) than in the racemic albuterol group (45 %, P=.02). The adjusted relative risk of admission in the racemic group compared with the levalbuterol group was 1.25 (95% confidence interval, 1.01-1.57). Hospital length of stay was not significantly shorter in the levalbuterol group (levalbuterol, 44.9 hours; racemic albuterol, 50.3 hours; P=.63). No significant adverse events occurred in either group. CONCLUSIONS Substituting levalbuterol for racemic albuterol in the ED management of acute asthma significantly reduced the number of hospitalizations.

Hydroxychloroquine use associated with improvement in lipid profiles in rheumatoid arthritis patients

Cardiovascular disease (CVD) is the leading cause of death in patients with rheumatoid arthritis (RA). Disease‐modifying therapies that improve risk factors for CVD, such as dyslipidemia, are desired. This study used an electronic health record to determine if hydroxychloroquine (HCQ) use was associated with an improvement in lipid levels in an inception RA cohort.

Genetic and Pharmacologic Inactivation of ANGPTL3 and Cardiovascular Disease

BACKGROUND Loss‐of‐function variants in the angiopoietin‐like 3 gene (ANGPTL3) have been associated with decreased plasma levels of triglycerides, low‐density lipoprotein (LDL) cholesterol, and high‐density lipoprotein (HDL) cholesterol. It is not known whether such variants or therapeutic antagonism of ANGPTL3 are associated with a reduced risk of atherosclerotic cardiovascular disease. METHODS We sequenced the exons of ANGPTL3 in 58,335 participants in the DiscovEHR human genetics study. We performed tests of association for loss‐of‐function variants in ANGPTL3 with lipid levels and with coronary artery disease in 13,102 case patients and 40,430 controls from the DiscovEHR study, with follow‐up studies involving 23,317 case patients and 107,166 controls from four population studies. We also tested the effects of a human monoclonal antibody, evinacumab, against Angptl3 in dyslipidemic mice and against ANGPTL3 in healthy human volunteers with elevated levels of triglycerides or LDL cholesterol. RESULTS In the DiscovEHR study, participants with heterozygous loss‐of‐function variants in ANGPTL3 had significantly lower serum levels of triglycerides, HDL cholesterol, and LDL cholesterol than participants without these variants. Loss‐of‐function variants were found in 0.33% of case patients with coronary artery disease and in 0.45% of controls (adjusted odds ratio, 0.59; 95% confidence interval, 0.41 to 0.85; P=0.004). These results were confirmed in the follow‐up studies. In dyslipidemic mice, inhibition of Angptl3 with evinacumab resulted in a greater decrease in atherosclerotic lesion area and necrotic content than a control antibody. In humans, evinacumab caused a dose‐dependent placebo‐adjusted reduction in fasting triglyceride levels of up to 76% and LDL cholesterol levels of up to 23%. CONCLUSIONS Genetic and therapeutic antagonism of ANGPTL3 in humans and of Angptl3 in mice was associated with decreased levels of all three major lipid fractions and decreased odds of atherosclerotic cardiovascular disease. (Funded by Regeneron Pharmaceuticals and others; ClinicalTrials.gov number, NCT01749878.)