Normal Lung Function and Mortality in World Trade Center Responders and National Health and Nutrition Examination Survey III Participants.

Rationale: Low FEV1 is a biomarker of increased mortality. The association of normal lung function and mortality is not well described. Objectives: To evaluate the FEV1-mortality association among participants with normal lung function. Methods: A total of 10,999 Fire Department of the City of New York (FDNY) responders and 10,901 Third National Health and Nutrition Examination Survey (NHANES III) participants, aged 18-65 years with FEV1 ⩾80% predicted, were analyzed, with FEV1 percent predicted calculated using Global Lung Function Initiative Global race-neutral reference equations. Mortality data were obtained from linkages to the National Death Index. Cox proportional hazards models estimated the association between FEV1 and all-cause mortality, controlling for age, sex, race/ethnicity, smoking history, and, for FDNY, work assignment. Cohorts were followed for a maximum of 20.3 years. Measurements and Main Results: We observed 504 deaths (4.6%) of 10,999 for FDNY and 1,237 deaths (9.4% [weighted]) of 10,901 for NHANES III. Relative to FEV1 ⩾120% predicted, mortality was significantly higher for FEV1 100-109%, 90-99%, and 80-89% predicted in the FDNY cohort. In the NHANES III cohort, mortality was significantly higher for FEV1 90-99% and 80-89% predicted. Each 10% higher predicted FEV1 was associated with 15% (hazard ratio, 0.85; 95% confidence interval, 0.80-0.91) and 23% (hazard ratio, 0.77; 95% confidence interval, 0.71-0.84) lower mortality for FDNY and NHANES III, respectively. Conclusions: In both cohorts, higher FEV1 is associated with lower mortality, suggesting higher FEV1 is a biomarker of better health. These findings demonstrate that a single cross-sectional measurement of FEV1 is predictive of mortality over two decades, even when FEV1 is in the normal range.

Interstitial Lung Disease and Progressive Pulmonary Fibrosis: a World Trade Center Cohort 20-Year Longitudinal Study.

PURPOSE: World Trade Center (WTC) exposure is associated with obstructive airway diseases and sarcoidosis. There is limited research regarding the incidence and progression of non-sarcoidosis interstitial lung diseases (ILD) after WTC-exposure. ILD encompasses parenchymal diseases which may lead to progressive pulmonary fibrosis (PPF). We used the Fire Department of the City of New York's (FDNY's) WTC Health Program cohort to estimate ILD incidence and progression. METHODS: This longitudinal study included 14,525 responders without ILD prior to 9/11/2001. ILD incidence and prevalence were estimated and standardized to the US 2014 population. Poisson regression modeled risk factors, including WTC-exposure and forced vital capacity (FVC), associated with ILD. Follow-up time ended at the earliest of incident diagnosis, end of study period/case ascertainment, transplant or death. RESULTS: ILD developed in 80/14,525 FDNY WTC responders. Age, smoking, and gastroesophageal reflux disease (GERD) prior to diagnosis were associated with incident ILD, though FVC was not. PPF developed in 40/80 ILD cases. Among the 80 cases, the average follow-up time after ILD diagnosis was 8.5 years with the majority of deaths occurring among those with PPF (PPF: n = 13; ILD without PPF: n = 6). CONCLUSIONS: The prevalence of post-9/11 ILD was more than two-fold greater than the general population. An exposure-response gradient could not be demonstrated. Half the ILD cases developed PPF, higher than previously reported. Age, smoking, and GERD were risk factors for ILD and PPF, while lung function was not. This may indicate that lung function measured after respirable exposures would not identify those at risk for ILD or PPF.

Serum Th-2 cytokines and FEV1 decline in WTC-exposed firefighters: A 19-year longitudinal study.

BACKGROUND: Accelerated-FEV1 -decline, defined as rate of decline in FEV1 > 64 ml/year, is a risk factor for asthma and chronic obstructive pulmonary disease in World Trade Center (WTC)-exposed firefighters. Accelerated-FEV1 -decline in this cohort is associated with elevated blood eosinophil concentrations, a mediator of Th-2 response. We hypothesized that an association exists between Th-2 biomarkers and FEV1 decline rate in those with accelerated-FEV1 -decline. METHODS: Serum was drawn from Fire Department of the City of New York (FDNY) firefighters 1-6 months (early) (N = 816) and 12-13 years (late) (N = 983) after 9/11/2001. Th-2 biomarkers IL-4, IL-13, and IL-5 were assayed by multiplex Luminex. Individual FEV1 decline rates were calculated using spirometric measurements taken: (1) between 9/11/2001 and 9/10/2020 for the early biomarker group and (2) between late measurement date and 9/10/2020 for the late biomarker group. Associations of early and late Th-2 biomarkers with subsequent FEV1 decline rates were analyzed using multivariable linear regression controlling for demographics, smoking status, and other potential confounders. RESULTS: In WTC-exposed firefighters with accelerated-FEV1 -decline, IL-4, IL-13, and IL-5 measured 1-6 months post-9/11/2001 were associated with greater FEV1 decline ml/year between 9/11/2001 and 9/10/2020 (-2.9 ± 1.4 ml/year per IL-4 doubling; -8.4 ± 1.2 ml/year per IL-13 doubling; -7.9 ± 1.3 ml/year per IL-5 doubling). Among late measured Th-2 biomarkers, only IL-4 was associated with subsequent FEV1 decline rate (-4.0 ± 1.6 ml/year per IL-4 doubling). CONCLUSIONS: In WTC-exposed firefighters with accelerated-FEV1 -decline, elevated serum IL-4 measured both 1-6 months and 12-13 years after 9/11 is associated with greater FEV1 decline/year. Drugs targeting the IL-4 pathway may improve lung function in this high-risk subgroup.

Splenectomy is not associated with a higher tricuspid regurgitant jet velocity in people with sickle cell anemia.

BACKGROUND: Vascular complications such as pulmonary hypertension (PH) occur at an increased rate following splenectomy in patients with various hemolytic blood disorders including thalassemia. The goal of this retrospective cross-sectional analysis was to assess the independent association of splenectomy with an elevated tricuspid regurgitation velocity (TRV) in people with homozygous sickle cell disease (HbSS). TRV is a noninvasive screening test for PH and a surrogate marker of prognosis in sickle cell disease (SCD). PROCEDURE: Data were obtained from the multicenter Walk-PHaSST (treatment of pulmonary hypertension and sickle cell disease with sildenafil therapy) study of PH (NCT00492531). We compared TRV in the cohort of patients with HbSS who were surgically splenectomized with patients who were not surgically splenectomized. RESULTS: We found no significant differences in TRV between the two groups. CONCLUSIONS: The lack of difference in TRV between the two groups is most likely because members of the comparator nonsurgical group in many cases experienced autoinfarction of the spleen in childhood. Splenectomy does not seem to confer additional risk for the development of a higher TRV in HbSS, unlike in patients with thalassemia or other hemolytic anemias. This could be an important consideration when weighing the risks and benefits of splenectomy in patients with HbSS.

Risk factors for post-9/11 chronic rhinosinusitis in Fire Department of the City of New York workers.

OBJECTIVES: Chronic rhinosinusitis (CRS) has high socioeconomic burden but underexplored risk factors. The collapse of the World Trade Center (WTC) towers on 11 September 2001 (9/11) caused dust and smoke exposure, leading to paranasal sinus inflammation and CRS. We aim to determine which job tasks are risk factors for CRS in WTC-exposed Fire Department of the City of New York (FDNY) firefighters and emergency medical services (EMS) workers. METHODS: This cohort study included a 16-year follow-up of 11 926 WTC-exposed FDNY rescue/recovery workers with data on demographics, WTC exposure, job tasks and first post-9/11 complete blood counts. Using multivariable Cox regression, we assessed the associations of WTC exposure, work assignment (firefighter/EMS), digging and rescue tasks at the WTC site and blood eosinophil counts with subsequent CRS, adjusting for potential confounders. RESULTS: The rate of CRS was higher in firefighters than EMS (1.80/100 person-years vs 0.70/100 person-years; p<0.001). The combination of digging and rescue work was a risk factor for CRS (HR 1.54, 95% CI 1.23 to 1.94, p<0.001) independent of work assignment and WTC exposure. CONCLUSIONS: Compared with EMS, firefighters were more likely to engage in a combination of digging and rescue work, which was a risk factor for CRS. Chronic irritant exposures associated with digging and rescue work may account for higher post-9/11 CRS rates among firefighters.

Incidence and prevalence of antibody to hepatitis C virus in FDNY first responders before and after work at the World Trade Center disaster site.

BACKGROUND: The goals of this study were to assess the impact of work at the World Trade Center (WTC) site in relation to new, post-9/11/2001 (9/11) antibody to hepatitis C Virus (anti-HCV); and, evaluate secular trends in WTC-exposed male Fire Department of New York City (FDNY) Firefighters and Emergency Medical Services (EMS) responders. METHODS: FDNY monitors responder health through physical exams and routine blood work. We used descriptive statistics to compare trans-9/11 and post-9/11 incidence and to assess trends in prevalence from 2000 to 2012. RESULTS: Trans-9/11 incidence of new anti-HCV was 0.42 per 100 persons compared with post-9/11 incidence of 0.34 (P = 0.68). Overall seroprevalence was 1.3%; rates declined from 1.79 per 100 to 0.49 per 100 over time (P < 0.0001). CONCLUSIONS: Work at the WTC was not associated with new infection. Biennial seroprevalence in responders declined over time, supporting the FDNY decision to discontinue routine annual testing in this cohort.

An age dependent response to hydroxyurea in pediatric sickle cell anemia patients with alpha thalassemia trait.

Hydroxyurea (HU) is a key drug therapy for individuals with sickle cell anemia (SCA), yet its clinical and hematologic responses can be variable. Various studies have reported the role of α-thalassemia as one of the most prevalent heritable traits that may modify HU response. We provide data from 62 pediatric and adolescent patients with SCA, 26 with co-inherited α-thalassemia trait. Our data suggest that altered hematologic and clinical responses to HU therapy are noted in adolescent SCA individuals with co-inherited α-thalassemia trait. Adolescent patients who co-inherited α-thalassemia trait had a greater reduction in vaso-occlusive episodes compared to those without α-thalassemia, despite a less robust fetal hemoglobin induction as well as a lower maximum HU dose. This clinical improvement was associated with a lower MCH and higher RBC count. Responses to HU in younger SCA children (ages 5-11years) with co-inherited α-thalassemia trait, compared to those without α-thalassemia trait, did not show any difference in number vaso-occlusive episodes, fetal hemoglobin induction and change in MCH and RBC count.

Post-9/11/2001 lung function trajectories by sex and race in World Trade Center-exposed New York City emergency medical service workers.

OBJECTIVE: To determine whether lung function trajectories after 9/11/2001 (9/11) differed by sex or race/ethnicity in World Trade Center-exposed Fire Department of the City of New York emergency medical service (EMS) workers. METHOD: Serial cross-sectional study of pulmonary function tests (PFTs) taken between 9/11 and 9/10/2015. We used data from routine PFTs (forced expiratory volume in 1 s (FEV1) and FEV1% predicted), conducted at 12-18 month intervals. FEV1 and FEV1% predicted were assessed over time, stratified by sex, and race/ethnicity. We also assessed FEV1 and FEV1% predicted in current, former and never-smokers. RESULTS: Among 1817 EMS workers, 334 (18.4%) were women, 979 (53.9%) self-identified as white and 939 (51.6%) were never-smokers. The median follow-up was 13.1 years (IQR 10.5-13.6), and the median number of PFTs per person was 11 (IQR 7-13). After large declines associated with 9/11, there was no discernible recovery in lung function. In analyses limited to never-smokers, the trajectory of decline in adjusted FEV1 and FEV1% predicted was relatively parallel for men and women in the 3 racial/ethnic groups. Similarly, small differences in FEV1 annual decline between groups were not clinically meaningful. Analyses including ever-smokers were essentially the same. CONCLUSIONS: 14 years after 9/11, most EMS workers continued to demonstrate a lack of lung function recovery. The trajectories of lung function decline, however, were parallel by sex and by race/ethnicity. These findings support the use of routine, serial measures of lung function over time in first responders and demonstrate no sex or racial sensitivity to exposure-related lung function decline.

Can Discrepancies Between Coronary Computed Tomography Angiography and Cardiac Catheterization in High-Risk Patients be Overcome With Consensus Reading?

OBJECTIVE: To assess the incidence and cause of discrepancies between coronary computed tomography angiography (CTA) and catheterization in a high-risk, diverse, predominantly overweight inner-city population. METHODS: Ninety-two patients who underwent coronary CTA and catheterization on March 2007 to December 2012 were retrospectively identified. Clinical coronary CTA interpretation and reinterpretation by a review panel was compared with catheterization results. RESULTS: Severe stenosis was present on catheterization in 65% (60/92). Clinical coronary CTA was concordant with catheterization for severe stenosis in 78% (72/92), whereas panel interpretation was concordant in 77% (70/91). Sensitivity and specificity of clinical and panel coronary CTA interpretations were 92% (55/60) and 53% (17/32) versus 82% (48/59) and 68% (22/32), respectively. CONCLUSIONS: Both coronary CTA interpretations were concordant with catheterization for severe stenosis in three quarters of patients. However, the diagnostic profile of the 2 interpretations differed, with higher sensitivity for the clinical report. This supports the clinical practice, which favored overestimation of difficult to quantify stenoses.

Treatment of Vitamin D Deficiency in Predominantly Hispanic and Black Adolescents: A Randomized Clinical Trial.

OBJECTIVES: To compare 3 different treatment regimens for vitamin D deficiency in minority adolescents and to explore factors that impact treatment efficacy. STUDY DESIGN: We conducted an 8-week, prospective, open-label, randomized clinical trial in an urban, academic, children's hospital. A total of 183 vitamin D-deficient adolescents, mean 25-hydroxyvitamin D or 25(OH)D 13.7 ± 3.9 ng/mL; mean age 16.6 ± 2.2 years, were randomized into 3 vitamin D3 (cholecalciferol) treatment arms: 50,000 IU/wk; 5000 IU/d; and 1000 IU/d. Serum 25(OH)D and vitamin D binding protein (VDBP) levels were measured pre-and posttreatment; 122 (67%) participants completed posttreatment measures. Complete-case and multiple-imputation, intention-to-treat analyses were performed. RESULTS: Mean change in 25(OH)D level posttreatment was significantly different among the 3 arms, 24.9 ± 15.1 vs 21.0 ± 15.2 vs 6.2 ± 6.5 ng/mL, for 50,000 IU, 5000 IU, and 1000 IU doses, respectively, P < .001. Both high-dose treatments were effective in increasing the 25(OH)D level out of deficiency range (≥ 20 ng/mL) in more than 80% of participants, and 60% remained deficient after low-dose treatment. Only 72%, 56%, and 2% achieved vitamin D sufficiency (>30 ng/mL) with 50,000 IU, 5000 IU, and 1000 IU doses, respectively, P < .001. Obese participants had substantially less mean change in 25(OH)D level after treatment than normal-weight participants, 13.7 ± 10.7 vs 21.9 ± 16.9 ng/mL, P < .001. Mean baseline VDBP level was almost twice as high in Hispanic compared with black participants (P < .001) and did not alter treatment response or change with treatment. CONCLUSIONS: Adult-sized adolescents require 8 weeks of high-dose cholecalciferol, at least 5000 IU/d, to correct deficiency. Obese adolescents have poorer response to treatment and may need higher doses than nonobese youth. Hispanic and black adolescents have different VDBP levels but similar treatment responses. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01784029.

Association of spinal degenerative disc disease with thyroid autoimmunity.

OBJECTIVES: Autoimmune thyroiditis (ATD) has been linked to various forms of arthritis. The relationship with spinal degenerative disc disease (DDD) is not known. We studied the association between ATD and spinal DDD. METHODS: We performed a cross-sectional analysis of patients who had data on both anti-thyroid peroxidase antibodies (TPOAb) and anti-thyroglobulin antibodies (TgAb) from January 1997 to January 2014 in Clinical Looking Glass (CLG), a data analysis software platform. Spinal DDD was confirmed by radiological diagnosis. RESULTS: Of the 7698 patients for whom the TPOAb and TgAb values were available, 4383 patients with complete data for the following covariates; age, gender, race, ethnicity, smoking, diabetes, body mass index and thyroid stimulating hormone (TSH) levels, were included. Thirty-three percent had ATD, while 67% did not. The unadjusted odds ratio (OR) of having spinal DDD with ATD was 1.5 (95% confidence interval (CI)1.3, 1.7), p<0.001. After adjustment for covariates, ATD remained associated with a higher frequency of spinal DDD, OR 1.8 (95% CI 1.6, 2.2), p<0.001. Stratifying by BMI and TSH levels showed similar results. Additional analyses excluding patients with known connective tissue diseases and spondyloarthritis (SpA) also showed consistent results. CONCLUSIONS: ATD is associated with increased frequency of spinal DDD independent of BMI and TSH levels, and among those without connective tissue diseases or SpA. This finding suggests that there may be an important link between thyroid autoimmunity and spinal DDD.

Daytime Versus Nighttime Extubations: A Comparison of Reintubation, Length of Stay, and Mortality.

PURPOSE: Despite studies regarding outcomes of day versus night medical care, consequences of nighttime extubations are unknown. It may be favorable to extubate patients off-hours, as soon as weaning parameters are met, since this could decrease complications and shorten length of stay (LOS). Conversely, nighttime extubation could be deleterious, as staffing varies during this time. We hypothesized that patients have similar reintubation rates, irrespective of extubation time. METHODS: A retrospective cohort study performed at 2 hospitals within a tertiary academic medical center included all adult intensive care unit (ICU) patients extubated between July 01, 2009 and May 31, 2011. Those extubated due to withdrawal of support were excluded. The nighttime group included patients extubated between 7:00 pm and 6:59 am and the daytime group included patients extubated between 7:00 am and 6:59 pm. RESULTS: Of 2240 extubated patients, 1555 were extubated during the day and 685 were extubated at night. Of these, 119 (7.7%) and 26 (3.8%), respectively, were reintubated in 24 hours with likelihood of reintubation significantly lower for nighttime than daytime after multivariable adjustment (odds ratio [OR] = 0.5, 95% confidence interval [CI] 0.3-0.9, P = .01), with a similar trend for reintubation within 72 hours (OR = 0.7, 95% CI = 0.5-1.0, P = .07). There was a trend toward decreased mortality for patients extubated at night (OR = 0.6, 95% CI = 0.3-1.0, P = .06). There was also a significantly lower LOS for patients extubated at night (P = .002). In a confirmatory frequency-matched analysis, there was no significant difference in reintubation proportion or mortality, but LOS was significantly less in those extubated at night. CONCLUSIONS: Intensive care unit extubations at night did not have higher likelihood of reintubation, LOS, or mortality compared to those during the day. Since patients should be extubated as soon as they meet parameters in order to potentially decrease complications of mechanical ventilation, these data provide no support for delaying extubation until daytime.

Persistent neutrophilia is a marker for an increased risk of venous thrombosis.

In patients with cancer and myeloproliferative disorders, leukocytosis has been associated with an increased venous thromboembolic (VTE) risk. Our goal was to determine whether persistent neutrophilia (PN), not associated with known causes such as malignancies, infections or steroids, is independently associated with VTE. All adult patients with >3 outpatient complete blood counts (CBCs) within 3 years were included. PN was defined as having an absolute neutrophil count >95 % (>2SD) of the population (≥7.8 × 10(9)/L) on at least three CBCs, at least 2 months apart. Separate analyses for neutrophil counts ≥9 × 10(9)/L and ≥10 × 10(9)/L were also performed. Blood counts from inpatients were excluded. Primary outcome was diagnosis of VTE, as determined by ICD-9 codes. Odds ratios were adjusted for diabetes, smoking, obesity, gender, and age. Charlson score was utilized as a morbidity measure. Data on 43,538 outpatients were collected. Although there was no association of VTE with neutrophil counts ≥7.8 × 10(9)/L, patients with ≥9.0 × 10(9)/L neutrophils were twice as likely to be diagnosed with VTE compared to those with normal neutrophil counts (OR 2.0, 95 % CI 1.3, 3.1; p = 0.003). Patients with neutrophil counts ≥10.0 × 10(9)/L were at an even higher risk (OR 2.3, 95 % CI 1.2, 4.8; p = 0.019). Charlson scores significantly modified this risk when incorporated into analysis. Elevated neutrophil counts are associated with an increased risk of venous thrombosis even when they are not due to cancer, infection or steroids. In patients with significant comorbidities, neutrophilia may be a marker of VTE risk.

Unplanned Repeat Echocardiography with Sedation in Children: Patient Risk Factors.

Patient selection criteria for echocardiography with sedation in children are not well defined. We attempted to identify predictors of unplanned repeat echocardiography with sedation. This was a single-center, case-control study of echocardiograms performed in children aged 1-36 months. Cases underwent unplanned repeat examinations with sedation, while controls did not. Patient variables and study indications were compared. Logistic regression identified the most significant predictors. Cases (n = 104, median time to repeat echocardiogram 17 days, median age 12.9 months) were older than controls (n = 212, median age 5.0 months, P < 0.001). Significantly more cases than controls had structural cardiac disease (64 vs. 23 %) and anatomic complexity ≥moderate (38 vs. 5 %, P < 0.001 for both). Cases more often had Kawasaki disease (11 vs. 2 %), and controls more often had murmur (56 vs. 11 %, P < 0.001 for both). Logistic regression identified age 6 months to <2 years (OR 3.26, 95 % CI 1.70-6.28, P < 0.001), Kawasaki disease (OR 5.20, 95 % CI 1.46-18.50, P = 0.01), and known pre-echocardiogram anatomic complexity ≥moderate (OR 3.99, 95 % CI 1.64-9.66, P = 0.002) as significant risk factors. An indication for murmur was protective (OR 0.32, 95 % CI 0.13-0.76, P = 0.01). We identified several risk factors for unplanned repeat echocardiography with sedation in children, including age 6 months to <2 years, higher anatomic complexity, and Kawasaki disease. Murmur was a protective factor. These results may help pediatric echocardiography laboratories establish criteria for sedation.

Who's misbehaving? Perceptions of unprofessional social media use by medical students and faculty.

BACKGROUND: Social media use by physicians offers potential benefits but may also be associated with professionalism problems. The objectives of this study were: 1) to examine and compare characteristics of social media use by medical students and faculty; 2) to explore the scope of self- and peer-posting of unprofessional online content; and 3) to determine what actions were taken when unprofessional content was viewed. METHODS: An anonymous, web-based survey was sent to medical students and faculty in October, 2013 at the Albert Einstein College of Medicine in Bronx, New York. RESULTS: Three-quarters of medical students reported using social media "very frequently" (several times a day), whereas less than one-third of faculty did so (p < .001). Medical students reported using privacy settings more often than faculty (96.5 % v. 78.1 %, p < .001). Most medical students (94.2 %) and faculty (94.1 %) reported "never" or "occasionally" monitoring their online presence (p = 0.94). Medical students reported self-posting of profanity, depiction of intoxication, and sexually suggestive material more often than faculty (p < .001). Medical students and faculty both reported peer-posting of unprofessional content significantly more often than self-posting. There was no association between year of medical school and posting of unprofessional content. CONCLUSION: Medical students reported spending more time using social media and posting unprofessional content more often than did faculty.

Single-dose intravenous gammaglobulin can stabilize neutrophil Mac-1 activation in sickle cell pain crisis.

Intravenous immunoglobulin (IVIG) decreases neutrophil adhesion to endothelium and red blood cell-neutrophil interactions in sickle cell mice undergoing vaso-occlusion. In this Phase I clinical trial of sickle cell anemia (SCA) patients admitted with pain crisis, we evaluated the status of adhesion molecules on neutrophils in control and IVIG-treated subjects pre- and post-infusion up to 800 mg/kg, the same dose used in murine studies. Mac-1 function significantly decreased from baseline in the low-dose IVIG (200-400 mg/kg) cohorts. IVIG-related adverse events may have occurred in the high-dose (600-800 mg/kg) cohorts. There were no significant increases in neutrophil and leukocyte counts, suggesting that IVIG may more selectively inhibit Mac-1 function as opposed to neutrophil adhesion. This study provides the first in-human validation of pre-clinical murine studies that IVIG can decrease Mac-1 function.

Spontaneous pain-like behaviors are more sensitive to morphine and buprenorphine than mechanically evoked behaviors in a rat model of acute postoperative pain.

BACKGROUND: Nonevoked spontaneous pain is most problematic for postoperative patients. Physicians assess this form of pain using the human visual analog scale or verbal numeric rating scale. Recent studies have proposed that spontaneous foot-lifting (SFL) behaviors are an expression of spontaneous pain in animals after spinal nerve injury or adjuvant-induced inflammation. In the current study, we characterize SFL behaviors in a rat model of acute postoperative pain, which includes comparisons with evoked behaviors to analgesic treatments. METHODS: SFL was manually recorded over four 5-minute periods with 10-minute intervals between each testing session. Paw-withdrawal thresholds were subsequently measured with an electronic von Frey esthesiometer. To evaluate the effects of age, rats were tested in different age groups: 2, 7, and >26 months. The effects of buprenorphine and morphine were tested in a separate group of animals, which received intraperitoneal injections of saline, morphine (0.01, 0.1, 1, or 2 mg/kg), or buprenorphine (0.001, 0.01, or 0.1 mg/kg) before testing. RESULTS: SFL behaviors peaked at 3 hours after incision and significantly recovered by the 3rd or 4th postoperative day (P < 0.0001). The presentation of these behaviors did not significantly vary with animal age (2, 7, and >26 months old; P = 0.30). SFL behaviors, with the exception of rapid SFL at 3 hours after incision, did not show significant correlation with paw-withdrawal threshold behaviors. The median effective dose of buprenorphine for reversal of mechanical hyperalgesia (0.0452 mg/kg; 95% CI, 0.0259-0.0787) was significantly larger than for reversing rapid (0.0027 mg/kg; 95% CI, 0.0009-0.0083; P < 0.0001) and prolonged (0.0004 mg/kg, 95% CI, 0.0000, 0.0035; P = 0.001) SFL at 3 hours after incision. Similarly, the median effective dose of morphine for reversal of mechanical hypersensitivity behaviors (2.901 mg/kg; 95% CI, 1.132-7.436) was larger than for SFL count (0.4044 mg/kg; 95% CI, 0.1048-1.561; P = 0.0103) and SFL duration (0.0309 mg/kg; 95% CI, 0.0095-0.0998; P < 0.0001) at 3 hours after incision. CONCLUSIONS: The present study demonstrates that a hindpaw plantar incision induces SFL behaviors in rats and that these behaviors have higher bioassay sensitivity to analgesic interventions with morphine and buprenorphine compared with mechanically evoked behaviors.

Serial Measurement of Amino-Terminal Pro-B-Type Natriuretic Peptide Predicts Adverse Cardiovascular Outcome in Children With Primary Myocardial Dysfunction and Acute Decompensated Heart Failure.

OBJECTIVES: In children, elevated amino-terminal pro-B-type natriuretic peptide levels are associated with impaired heart function. The predictive value of serial monitoring of amino-terminal pro-B-type natriuretic peptide levels in acute decompensated heart failure is unclear. DESIGN: Prospective observational study. SETTING: Single, tertiary referral pediatric critical care unit. PATIENTS: Patients aged 0-21 years with primary myocardial dysfunction and acute decompensated heart failure. INTERVENTIONS: Amino-terminal pro-B-type natriuretic peptide levels were obtained on enrollment, day 2, and day 7. Clinical, laboratory, and imaging data were collected on enrollment. Adverse cardiovascular outcome was defined as heart transplant, ventricular assist device placement, extracorporeal membrane oxygenation, or death at 1 year after admission. Aminoterminal pro-B-type natriuretic peptide levels and the percent change from day 0 to day 2 and day 0 to day 7 were calculated and compared between those with and without adverse cardiovascular outcome. MEASUREMENTS AND MAIN RESULTS: Sixteen consecutive patients were enrolled. Adverse cardiovascular outcome occurred in six patients (37.5%, four heart transplant and two ventricular assist device). In patients with an adverse cardiovascular outcome, median amino-terminal pro-B-type natriuretic peptide levels at day 7 were significantly higher (7,365 vs 1,196 pg/mL; p = 0.02) and the percent decline in amino-terminal pro-B-type natriuretic peptide was significantly smaller (28% vs 73%; p = 0.02) compared with those without an adverse cardiovascular outcome. Receiver operating curve analysis revealed that a less than 55% decline in amino-terminal pro-B-type natriuretic peptide levels at day 7 had a sensitivity and specificity of 83% and 90%, respectively, in predicting an adverse cardiovascular (area under the curve, 0.86; 95% CI, 0.68-1.0; p = 0.02). CONCLUSIONS: In conclusion, children with primary myocardial dysfunction and acute decompensated heart failure, a persistently elevated amino-terminal pro-B-type natriuretic peptide, and/or a lesser degree of decline in amino-terminal pro-B-type natriuretic peptide during the first week of presentation were strongly associated with adverse cardiovascular outcome. Serial amino-terminal pro-B-type natriuretic peptide monitoring may allow the early identification of children at risk for worse outcome.

What Is the Appropriate Use of Renal Sonography in an Inner-City Population With New-Onset Acute Kidney Injury?

OBJECTIVES: We aimed to determine the prevalence of hydronephrosis in patients who underwent renal sonography for new-onset acute kidney injury (AKI) and to identify clinical factors predictive of hydronephrosis. In patients with hydronephrosis, we sought to investigate how routine renal sonography affects patient treatment, including performance of interventional procedures. METHODS: A retrospective chart review identified 274 adults with AKI who underwent renal sonography at an urban teaching hospital from January through July 2011. The prevalence of hydronephrosis was determined. Electronic medical records were reviewed for comorbidities, including risk factors for hydronephrosis such as a pelvic mass, prior renal or pelvic surgery, and neurogenic bladder, and for subsequent interventions and outcomes. RESULTS: Sonography showed hydronephrosis in 28 patients (10%); 5 (18%) had subsequent interventions. In a multivariable logistic regression model with the outcome being hydronephrosis, all considered risk factors (pelvic mass, prior renal or pelvic surgery, and neurogenic bladder) were significantly associated with hydronephrosis (odds ratio, 6.4; 95% confidence interval, 2.7-15.4; P < .001) when adjusting for age and diabetes mellitus. Diabetes had a negative predictive value for hydronephrosis. No diabetic patients younger than 85 years and without clinical risk factors had hydronephrosis. CONCLUSIONS: Hydronephrosis is infrequently seen on sonograms in hospitalized patients with AKI who lack risk factors for urinary tract obstruction. Deferral of sonography pending a trial of medical treatment is safe and will reduce medical costs. Adoption of clinical guidelines to assess patients' risk levels for hydronephrosis is critical to avoid unnecessary imaging.

Arrhythmias in the paediatric intensive care unit: a prospective study of the rates and predictors of arrhythmias in children without underlying cardiac disease.

OBJECTIVE: Arrhythmias are common in patients admitted to the paediatric intensive care unit. We sought to identify the rates of occurrence and types of arrhythmias, and determine whether an arrhythmia was associated with illness severity and paediatric intensive care unit length of stay. DESIGN: This is a prospective, observational study of all patients admitted to the paediatric intensive care unit at the Children's Hospital at Montefiore from March to June 2012. Patients with cardiac disease or admitted for the treatment of primary arrhythmias were excluded. Clinical and laboratory data were collected and telemetry was reviewed daily. Tachyarrhythmias were identified as supraventricular tachycardia, ventricular tachycardia, and arrhythmias causing haemodynamic compromise or for which an intervention was performed. RESULTS: A total of 278 patients met the inclusion criteria and were analysed. There were 97 incidences of arrhythmia in 53 patients (19%) and six tachyarrhythmias (2%). The most common types of arrhythmias were junctional rhythm (38%), premature atrial contractions (24%), and premature ventricular contractions (22%). Tachyarrhythmias included three supraventricular tachycardia (50%) and three ventricular tachycardia (50%). Of the six tachyarrhythmias, four were related to placement or migration of central venous lines and two occurred during aminophylline infusion. Patients with an arrhythmia had longer duration of mechanical ventilation and paediatric intensive care unit stay (p<0.001). In multivariate analysis, central venous lines (odds ratio 3.1; 95% confidence interval 1.3-7.2, p=0.009) and aminophylline use (odds ratio 5.1; 95% confidence interval 1.7-14.9, p=0.003) were independent predictors for arrhythmias. CONCLUSIONS: Arrhythmias were common in paediatric intensive care unit patients (19%), although tachyarrhythmias occurred rarely (2%). Central venous lines and use of aminophylline were identified as two clinical factors that may be associated with development of an arrhythmia.