Hepatitis C virus screening at a Veterans Administration Hospital in New York City.

BACKGROUND: Asymptomatic hepatitis C virus (HCV) infection has the highest prevalence in "baby boomers" born in 1945 through 1965. New York State mandates that all persons born during this period be screened at least once for hepatitis C. LOCAL PROBLEM: Military veteran HCV screening is often missed during primary care visits. METHODS: After baseline screening, provider education with and without an HCV education dashboard of information in the Electronic Medical Record system was used to determine if screening proportions could be improved. The Chi-square and Z-test for independent proportions compared after with before education screening. The odds ratio compared after versus before screening odds. INTERVENTIONS: Two interventions were tested. One was provider education with a 30-minute lecture. The second was the lecture with addition of an HCV education computer dashboard. RESULTS: The Chi-square test and Z-test comparing the month immediately after provider education was significant for increased screening (p < .01) compared with baseline. There was a 2.04-fold (95% confidence interval, 1.31-3.20) greater odds of screening in the month after education. If two or more months went by after education, the effect of education no longer improved screening proportions. Provider education plus the use of HCV education dashboard did not improve screening from baseline to the month immediately after screening (p = .95). CONCLUSION: Provider education significantly improved HCV screening the month immediately after education, then regressed toward baseline. Adding an HCV education dashboard to education did not improve screening. To maintain elevated screening proportions, provider screening education must be reinforced on a frequent basis for sustained effect.

A Case of Right Ventricular Dysfunction with Right Ventricular Failure Secondary to Obesity Hypoventilation Syndrome.

BACKGROUND Obesity hypoventilation syndrome (OHS) is characterized by a body mass index (BMI) ≥30 kg/m², daytime hypercapnia, an arterial carbon dioxide tension ≥45 mmHg, and obstructive sleep apnea (OSA). OHS can lead to pulmonary hypertension. It has not been clearly demonstrated that OHS with pulmonary hypertension can lead to right ventricular dysfunction and right heart failure. A case is presented of right ventricular dysfunction and right ventricular failure secondary to OHS. CASE REPORT A 53-year-old man, who was morbidly obese with a BMI of 75 kg/m², presented with shortness of breath (SOB) and hypercapnia. He had never smoked but had a history of severe OSA and hypertension. On examination, the patient was obese with normal lung auscultation and mild pitting edema of the lower extremities. A spiral computed tomography (CT) angiogram showed no evidence of pulmonary embolism or interstitial lung disease. Pulmonary function testing showed no obstructive airway disease and a normal diffusion capacity. Two-dimensional transthoracic echocardiogram (TTE) showed normal left ventricular function and a dilated right ventricle (RV) with a flattened septal wall, moderate tricuspid regurgitation, and an estimated right ventricular systolic pressure of 55-60 mmHg. The patient was discharged on continuous positive airway pressure (CPAP) and oxygen at night, and as needed during the day. CONCLUSIONS This report has shown that OHS without underlying causes of alveolar hypoventilation can result in isolated right ventricular dysfunction and right ventricular failure.

Creatinine Excretion as a Determinant of Accelerated Skeletal Muscle Loss with Critical Illness.

OBJECTIVE: The 24-h urinary creatinine excretion rate has been used as an approximation of the skeletal muscle (SM) mass in non-intensive care unit (ICU) settings. The study goal or aim was to determine reductions in SM mass in patients with recurrent critical illness who are admitted to a medical ICU. METHODS: Retrospective ICU patient records between 2013 and 2015 were reviewed. Inclusion of ICU patients with repeat 24-h urinary creatinine excretion levels at two different ICU admissions done routinely as part of care. The study design is a case series with patients as their own control. RESULTS: Three patients were found to have data on two separate ICU admissions. The reduction in creatinine excretion among ICU patients was correlated with estimated SM mass. All patients had >50% reduction in creatinine excretion and ≥47% reduction in estimated SM mass over 4 months. All patients were bed-bound after the first ICU admission and met the definition of sarcopenia by the second ICU admission; all patients died during the second ICU admission. The final SM mass in all patients was <4 kg m-2. CONCLUSION: Patients with chronic critical illness admitted to the medical ICU, who become bed bound, can experience up to 50% reduction in SM mass as gleaned from creatinine excretion within 4 months. Low SM mass may predispose patients to increased mortality. Measurement of 24-h urinary creatinine excretion may be a useful ICU biomarker to determine SM mass for diagnostic and prognostic purposes.

Dyspnoea as a predictor of cause-specific heart/lung disease mortality in Bangladesh: a prospective cohort study.

BACKGROUND: The spectrum of mortality outcomes by cause in populations with/without dyspnoea has not been determined. The study aimed to evaluate whether dyspnoea, a symptom, predicts cause-specific mortality differences between groups. The hypothesis was that diseases that result in chronic dyspnoea, those originating from the heart and lungs, would preferentially result in heart and lung disease mortality in those with baseline dyspnoea (relative to no dyspnoea) when followed over time. METHODS: A population-based sample of 11 533 Bangladeshis was recruited and followed for 11-12 years and cause-specific mortality evaluated in those with and without baseline dyspnoea. Dyspnoea was ascertained by trained physicians. The cause of death was determined by verbal autopsy. Kaplan-Meier survival curves, the Fine-Gray competing risk hazards model and logistic regression models were used to determine group differences in cause-specific mortality. RESULTS: Compared to those not reporting dyspnoea at baseline, the adjusted HRs were 6.4 (3.8 to 10.7), 9.3 (3.9 to 22.3), 1.8 (1.2 to 2.8), 2.2 (1.0 to 5.1) and 2.8 (1.3 to 6.2) for greater risk of dying from chronic obstructive pulmonary disease (COPD), asthma, heart disease, tuberculosis and lung cancer, respectively. In contrast, there was a similar risk of dying from stroke, cancer (excluding lung), liver disease, accidents and other (miscellaneous causes) between the dyspnoeic and non-dyspnoeic groups. In addition, the HR was 2.1 (1.7 to 2.5) for greater all-cause mortality in those with baseline dyspnoea versus no dyspnoea. CONCLUSIONS: Dyspnoea, ascertained by a single question with binary response, predicts heart and lung disease mortality. Individuals reporting dyspnoea were twofold to ninefold more likely to die of diseases that involve the heart and/or lungs relative to the non-dyspnoeic individuals. Therefore, in those with chronic dyspnoea, workup to look for the five common dyspnoeic diseases resulting in increased mortality (COPD, asthma, heart disease, tuberculosis and lung cancer), all treatable, should reduce mortality and improve the public health.

Dyspnea as an independent predictor of mortality.

BACKGROUND AND AIM: Dyspnea is a common and easily elicited presenting complaint in patients seen by physicians who evaluate and take care of chronic respiratory disorders. Although dyspnea is subjective and tends to increase with age or reduced lung function, it appears to be reproducible as a symptom and often signifies serious underlying disease. METHODS: Systematic review of longitudinal studies with dyspnea as the exposure and mortality as the outcome; age, smoking and lung function had to be controlled for to be included in the review. In addition, a minimum sample size at baseline of 500 subjects was required for each study. RESULTS: From over 3000 potential references, 10 longitudinal studies met all criteria and were included. All 10 studies suggested that dyspnea was an independent predictor of mortality with point estimates by odds ratio, rate ratio or hazard ratios ranging from 1.3 up to 2.9-fold greater than baseline. All 10 studies had actual or implied 95% confidence interval bands greater than the null value of one. CONCLUSION: Dyspnea, a symptom, predicts mortality and is a proxy for underlying diseases, most often of heart and lung. Therefore, chronic dyspnea needs to be evaluated as to etiology to allow for treatment to minimize morbidity and mortality when possible.

Dipstick proteinuria as a predictor of all-cause and cardiovascular disease mortality in Bangladesh: A prospective cohort study.

OBJECTIVE: Baseline, persistent, incident, and remittent dipstick proteinuria have never been tested as predictors of mortality in an undeveloped country. The goal of this study was to determine which of these four types of proteinuria (if any) predict mortality. METHODS: Baseline data was collected from 2000 to 2002 in Bangladesh from 11,121 adults. Vital status was ascertained over 11-12years. Cox models were used to evaluate proteinuria in relation to all-cause and cardiovascular disease (CVD) mortality. CVD mortality was evaluated only in those with baseline proteinuria. Persistent, remittent, and incident proteinuria were determined at the 2-year exam. RESULTS: Baseline proteinuria of 1+ or greater was significantly associated with all-cause (hazard ratio (HR) 2.87; 95% C.I., 1.71-4.80) and CVD mortality (HR: 3.55; 95% C.I., 1.81-6.95) compared to no proteinuria, adjusted for age, gender, arsenic well water concentration, education, hypertension, BMI, smoking, and diabetes mellitus. Persistent 1+ proteinuria had a stronger risk of death, 3.49 (1.64-7.41)-fold greater, than no proteinuria. Incident 1+ proteinuria had a 1.87 (0.92-3.78)-fold greater mortality over 9-10years. Remittent proteinuria revealed no increased mortality. CONCLUSIONS: Baseline, persistent, and incident dipstick proteinuria were predictors of all-cause mortality with persistent proteinuria having the greatest risk. In developing countries, those with 1+ dipstick proteinuria, particularly if persistent, should be targeted for definitive diagnosis and treatment. The two most common causes of proteinuria to search for are diabetes mellitus and hypertension.

Arsenic exposure from drinking water and dyspnoea risk in Araihazar, Bangladesh: a population-based study.

Bangladesh has high well water arsenic exposure. Chronic arsenic ingestion may result in diseases that manifest as dyspnoea, although information is sparse. Baseline values were obtained from an arsenic study. Trained physicians ascertained data on dyspnoea among 11,746 subjects. Data were collected on demographic factors, including smoking, blood pressure and arsenic exposure. Logistic regression models estimated odds ratios and confidence intervals for the association between arsenic exposure and dyspnoea. The adjusted odds of having dyspnoea was 1.32-fold (95% CI 1.15-1.52) greater in those exposed to high well water arsenic concentrations (≥ 50 µg · L(-1)) compared with low-arsenic-exposed nonsmokers (p<0.01). A significant dose-response relationship was found for arsenic (as well as smoking) in relation to dyspnoea. In nonsmokers, the adjusted odds of having dyspnoea were 1.36, 1.96, 2.34 and 1.80-fold greater for arsenic concentrations of 7-38, 39-90, 91-178 and 179-864 µg · L(-1), respectively, compared with the reference arsenic concentration of <7 µg · L(-1) (p<0.01; Chi-squared test for trend). Arsenic exposure through well water is associated with dyspnoea, independently of smoking status. This study suggests that mandated well water testing for arsenic with reduction in exposure may significantly reduce diseases that manifest as dyspnoea, usually cardiac or pulmonary.

Association between arsenic exposure from drinking water and proteinuria: results from the Health Effects of Arsenic Longitudinal Study.

BACKGROUND: Proteinuria has been recognized as a marker for an increased risk of chronic renal disease. It is unclear whether arsenic (As) exposure from drinking water is associated with proteinuria. METHODS: We evaluated the association between As exposure from drinking water and proteinuria in 11,122 participants in the Health Effects of Arsenic Longitudinal Study (HEALS). Proteinuria was detected by urinary dipstick tests at baseline and at 2-year intervals. As exposure variables included baseline well As and changes in urinary As during follow-up modelled as time-dependent variables in the analyses. RESULTS: At baseline, well As was positively related to prevalence of proteinuria; prevalence odds ratios (PORs) for proteinuria in increasing quintiles of well As (≤ 7, 8-39, 40-91, 92-179 and 180-864 µg/l) were 1.00 (ref), POR 0.99 [95% confidence interval (CI) 0.77-1.27], POR 1.23 (95% CI 0.97-1.57), POR 1.50 (95% CI 1.18-1.89) and POR 1.59 (95% CI 1.26-2.00) (P for trend <0.01). Hazard ratios for incidence of proteinuria were POR 0.83 (95% CI 0.67-1.03) and POR 0.91 (95% CI 0.74-1.12) for participants with a decreasing level of >70 and 17-70 µg/l in urinary As over time, respectively, and were POR 1.17 (95% CI 0.97-1.42) and POR 1.42 (95% CI 1.16-1.73) for participants with an increasing level of 16-68 and >68 µg/l in urinary As over time, respectively, compared with the group with relatively little changes in urinary As as the reference group (urinary As -16 to 15 µg/l). CONCLUSION: The findings suggest that there are adverse effects of As exposure on the risk of proteinuria and the effects are modifiable by recent changes in As exposure.

Comparison of the ATS versus EU Mini Wright peak flow meter in normal volunteers.

OBJECTIVES: The American Thoracic Society (ATS) and European Union (EU) have precise and accurate Mini Wright peak flow meters. The purpose of this investigation was to compare both 1) for accuracy using a pneumotachometer, 2) in volunteers to determine whether they are interchangeable, and 3) to spirometrically predicted peak flows. METHODS: Lab testing: A pneumotachometer was connected in series with each peak flow meter and varying flows pushed through both meters for comparison. Human subjects: Nonsmoking adult volunteers did three standing peak flows. The order of peak flow meter used was random. The best of three efforts was used for analysis. The t-test, concordance correlation coefficient (CCC), Deming regression, and Bland-Altman plot were the analytic strategies used to determine agreement. Peak flow results were compared to spirometrically predicted values. RESULTS: Fifty-seven volunteers, average age 37 ± 12 years and mean BMI 24.9 ± 2.5 years, were included. The average peak flows were different at 541 ± 114 and 526 ± 112 L/min for the ATS and EU meters, respectively (p < .01). Both peak flow meter values were significantly different than spirometrically predicted values of 483 ± 86 L/min (p < .01). The CCC was 0.98 (0.97-0.99) and regression revealed a slope and y-intercept consistent with 1 and 0, respectively. The Bland-Altman plot revealed no increase in scatter of values over the range of peak flows versus the difference with a mean bias of 15 ± 15 L/min. Laboratory testing revealed that the ATS and EU peak flow meters read 3.0 ± 2.1% above and -2.0 ± 1.5% below the comparison pneumotachometer, respectively. The pneumotachometer comparison was significantly different for both meters at p < .01, paired t-test. CONCLUSIONS: The ATS peak flow meter reads 2.8% higher than the EU peak flow meter across a range of flows. Both meters have similar accuracy with a different bias compared with a pneumotachometer. Finally, both peak flow meters read slightly and significantly higher than spirometrically derived peak flows. Therefore, the peak flow meters are not interchangeable and both may obtain slightly higher values than those determined using current spirometrically derived prediction equations.

Peak expiratory flow in normals: comparison of the mini Wright versus spirometric predicted peak flows.

OBJECTIVES: U.S. prediction equation estimated peak flows were obtained spirometrically and may not correctly predict actual peak flows that are obtained using a peak flow meter. The purpose of this investigation was to compare actual Mini Wright peak flows in normal volunteers as compared with spirometric predicted values to determine whether they are similar. METHODS: Nonsmoking, nonobese adult volunteers with no history of lung disease underwent peak flow testing with an American Thoracic Society (ATS) Mini Wright peak flow meter. All subjects did three peak flows by taking a maximal deep breath and expiring as hard and fast as possible while in the standing position. The best of three efforts was taken as the peak flow value for analysis and compared with prediction equation estimates. The paired t test compared differences between actual and predicted values. The concordance correlation coefficient evaluated whether the actual peak flows were interchangeable with predicted. RESULTS: Seventy-two volunteers, average age 44 +/- 10 years and mean BMI 25.2 +/- 2.9, were included. The Mini Wright peak flow values of 508 +/- 113 L/min were significantly different than the predicted values of 471 +/- 84 (p < 0.01). The predicted values were reduced on average by 7.3 percent compared to actual values. The concordance correlation coefficient was 0.72 (95% C.I.; 0.60 - 0.80) suggesting the actual and predicted values are not interchangeable. CONCLUSIONS: The ATS Mini Wright peak flow values are slightly higher than spirometrically derived predicted peak flow values in subjects without lung disease. This suggests that predicted peak flow values should be generated by a peak flow meter and would be higher than current spirometrically predicted values.

Total lung capacity: single breath methane dilution versus plethysmography in normals.

OBJECTIVE AND BACKGROUND: Methane is an inert tracer gas used to obtain TLC estimates during single breath diffusion capacity (DL(CO)) measurements. The aim of this study was to assess the accuracy of methane dilution TLC in normal subjects undergoing single breath diffusion capacity measurements using plethysmography as the gold standard comparison method. METHODS: Fifty non-smoking adults underwent lung function testing. Total lung volume was obtained by both plethysmography and methane dilution during a single breath DL(CO) measurement. Deming regression and the concordance correlation coefficient, r(ccc), were used to determine agreement between methods for TLC. Bias was the mean difference between methods and limits of agreement were the mean difference between methods +/- 1.96 (SD). All values are mean +/- SD unless otherwise stated. RESULTS: Plethysmography and methane dilution TLC values were not significantly different. The r(ccc) was 0.87 (95% confidence interval (CI) 0.78-0.92). Deming regression revealed a slope of 0.93 (P = 0.17, H(o): beta = 1.0; 95% CI 0.84-1.03) and a y-intercept of 0.20 (P = 0.39, H(o): alpha = 0; 95% CI -0.27-0.70). The bias was 0.11 L favouring plethysmography. Limits of agreement varied as 0.11 +/- 0.92 L. CONCLUSIONS: There is statistical agreement between methods suggesting the average TLC by methane could substitute for plethysmography in normals at the population level. At the individual level, a normal methane dilution value indicates a normal TLC whereas values below the normal range should be validated using plethysmography.

Smoking affects response to inhaled corticosteroids or leukotriene receptor antagonists in asthma.

RATIONALE: One-quarter to one-third of individuals with asthma smoke, which may affect response to therapy and contribute to poor asthma control. OBJECTIVES: To determine if the response to an inhaled corticosteroid or a leukotriene receptor antagonist is attenuated in individuals with asthma who smoke. METHODS: In a multicenter, placebo-controlled, double-blind, double-dummy, crossover trial, 44 nonsmokers and 39 light smokers with mild asthma were assigned randomly to treatment twice daily with inhaled beclomethasone and once daily with oral montelukast. MEASUREMENTS AND MAIN RESULTS: Primary outcome was change in prebronchodilator FEV(1) in smokers versus nonsmokers. Secondary outcomes included peak flow, PC(20) methacholine, symptoms, quality of life, and markers of airway inflammation. Despite similar FEV(1), bronchodilator response, and sensitivity to methacholine at baseline, subjects with asthma who smoked had significantly more symptoms, worse quality of life, and lower daily peak flow than nonsmokers. Adherence to therapy did not differ significantly between smokers and nonsmokers, or between treatment arms. Beclomethasone significantly reduced sputum eosinophils and eosinophil cationic protein (ECP) in both smokers and nonsmokers, but increased FEV(1) (170 ml, p = 0.0003) only in nonsmokers. Montelukast significantly increased a.m. peak flow in smokers (12.6 L/min, p = 0.002), but not in nonsmokers. CONCLUSIONS: In subjects with mild asthma who smoke, the response to inhaled corticosteroids is attenuated, suggesting that adjustments to standard therapy may be required to attain asthma control. The greater improvement seen in some outcomes in smokers treated with montelukast suggests that leukotrienes may be important in this setting. Larger prospective studies are required to determine whether leukotriene modifiers can be recommended for managing asthma in patients who smoke.

The Predicting Response to Inhaled Corticosteroid Efficacy (PRICE) trial.

BACKGROUND: Although guidelines recommend anti-inflammatory therapy for persistent asthma, recent studies suggest that 25% to 35% of patients with asthma may not improve lung function with inhaled corticosteroids. OBJECTIVE: To evaluate potential biomarkers of predicting short-term (6-week) response to inhaled corticosteroid with subsequent evaluation of responders and nonresponders to asthma control over a longer interval (16 additional weeks). METHODS: Eighty-three subjects with asthma off steroid were enrolled in this multicenter study. Biomarkers and asthma characteristics were evaluated as predictors of inhaled corticosteroid response over a 6-week trial for changes in FEV(1) and methacholine PC(20). After this, an additional 4-month trial evaluated asthma control. RESULTS: Although multiple baseline predictors had significant correlations with improvements for short-term inhaled steroid success, the only strong correlations (r >or= +/- 0.6) were albuterol reversibility (r = 0.83; P < .001), FEV(1)/forced vital capacity (r = -0.75; P < .001), and FEV(1) % predicted (r = -0.71; P < .001). Dividing the subjects in the short-term inhaled steroid trial into responders (>5% FEV(1) improvement) and nonresponders (

Combination therapy with a long-acting beta-agonist and a leukotriene antagonist in moderate asthma.

RATIONALE: Long-acting beta-agonists (LABAs) and inhaled corticosteroids administered together appear to be complementary in terms of effects on asthma control. The elements of asthma control achieved by LABAs (improved lung function) and leukotriene receptor antagonists (LTRAs; protection against exacerbations) may be complementary as well. OBJECTIVE: We sought to determine whether the combination of the LTRA montelukast and the LABA salmeterol could provide an effective therapeutic strategy for asthma. METHODS AND MEASUREMENTS: In a randomized, placebo-controlled, crossover study of 192 subjects with moderate asthma, we compared the clinical efficacy of regular treatment over 14 weeks with the combination of montelukast and salmeterol to that with the combination of beclomethasone and salmeterol in moderate asthma. The primary efficacy outcome was time to treatment failure. MAIN RESULTS: Three months after the randomization of the last subject, the Data and Safety Monitoring Board determined that the primary research question had been answered and terminated the trial. The combination of montelukast and salmeterol was inferior to the combination of beclomethasone and salmeterol as judged by protection against asthma treatment failures (p = 0.0008), lung function (26 L/min difference in a.m. peak expiratory flow rate, p = 0.011), asthma control score (0.22 difference in Asthma Control Questionnaire score, p = 0.038), and markers of inflammation and airway reactivity. CONCLUSIONS: Patients with moderate asthma similar to those we studied should not substitute the combination of an LTRA and an LABA for the combination of inhaled corticosteroid and an LABA.

Abnormal predicted diffusion capacities in healthy Asians: an inequality with a solution.

BACKGROUND: Asian lung volumes are 10-15% less than those of Caucasians. OBJECTIVES: To test the hypothesis that healthy Asians might be labeled as abnormal using three commonly used Caucasian-derived prediction equation estimates (PEE) of DLCO currently used. In addition, a Chinese-derived PEE of DLCO was tested to determine its validity in non-Chinese Asians. METHODS: Forty-one healthy Asians underwent DLCO testing. Controls consisted of the PEE and 12 healthy Caucasians. Measured DLCO was compared with the Miller, Knudson, Crapo and one Chinese PEE. Abnormal was defined as a DLCO <80% predicted. Gas dilution and plethysmography estimated alveolar volume. Proportions in parentheses in the results below are DLCO adjusted for alveolar volume. RESULTS: The average Asian DLCO was 25.75 +/- 5.55 ml/min/mm Hg, no different than the predicted DLCO of 25.29 +/- 5.53 seen with Chinese PEE. This was different (p < 0.01) than the predicted DLCO of 27.82 +/- 5.09, 33.66 +/- 6.29, and 31.64 +/- 5.33 for the Miller, Knudson, and Crapo equations, respectively. This resulted in 4/41 (0/41), 27/39 (2/39), 21/41 (3/41) and 1/41 (0/41) DLCO measurements being defined as abnormal using Miller, Knudson, Crapo and Chinese PEE, respectively. In Caucasians, the measured DLCO was similar to the Miller but significantly lower than the Knudson and Crapo PEE. Measured lung volumes were significantly smaller compared to predicted for the three Caucasian PEE in Asians, with no difference in Caucasians. There was no difference in measured lung volumes and Chinese PEE. CONCLUSIONS: Current Caucasian PEE for DLCO when used in healthy Asians result in an abnormal reading that is incorrect from 10 to 50% of the time. This PEE failure is related to a reduction in lung volume not accounted for. The Chinese PEE for DLCO works for non-Chinese Asians and should replace Caucasian PEE in the US in all Asians.