Evaluating the Efficacy of Chronic Galantamine on Sustained Attention and Cholinergic Neurotransmission in A Pre-Clinical Model of Traumatic Brain Injury.

Cholinergic disruptions underlie attentional deficits following traumatic brain injury (TBI). Yet, drugs specifically targeting acetylcholinesterase (AChE) inhibition have yielded mixed outcomes. Therefore, we hypothesized that galantamine (GAL), a dual-action competitive AChE inhibitor and α7 nicotinic acetylcholine receptor (nAChR) positive allosteric modulator, provided chronically after injury, will attenuate TBI-induced deficits of sustained attention and enhance ACh efflux in the medial prefrontal cortex (mPFC), as assessed by in vivo microdialysis. In Experiment 1, adult male rats (n = 10-15/group) trained in the 3-choice serial reaction time (3-CSRT) test were randomly assigned to controlled cortical impact (CCI) or sham surgery and administered GAL (0.5, 2.0, or 5.0 mg/kg; i.p.) or saline vehicle (VEH; 1 mL/kg; i.p) beginning 24-h post-surgery and once daily thereafter for 27 days. Measures of sustained attention and distractibility were assessed on post-operative days 21-25 in the 3-CSRT, following which cortical lesion volume and basal forebrain cholinergic cells were quantified on day 27. In Experiment 2, adult male rats (n = 3-4/group) received a CCI and 24 h later administered (i.p.) one of the three doses of GAL or VEH for 21 days to quantify the dose-dependent effect of GAL on in vivo ACh efflux in the mPFC. Two weeks after the CCI, a guide cannula was implanted in the right mPFC. On post-surgery day 21, baseline and post-injection dialysate samples were collected in a temporally matched manner with the cohort undergoing behavior. ACh levels were analyzed using reverse phase high-performance liquid chromatography (HPLC) coupled to an electrochemical detector. Cortical lesion volume was quantified on day 22. The data were subjected to ANOVA, with repeated measures where appropriate, followed by Newman-Keuls post hoc analyses. All TBI groups displayed impaired sustained attention versus the pooled SHAM controls (p's < 0.05). Moreover, the highest dose of GAL (5.0 mg/kg) exacerbated attentional deficits relative to VEH and the two lower doses of GAL (p's < 0.05). TBI significantly reduced cholinergic cells in the right basal forebrain, regardless of treatment condition, versus SHAM (p < 0.05). In vivo microdialysis revealed no differences in basal ACh in the mPFC; however, GAL (5.0 mg/kg) significantly increased ACh efflux 30 min following injection compared to the VEH and the other GAL (0.5 and 2.0 mg/kg) treated groups (p's < 0.05). In both experiments, there were no differences in cortical lesion volume across treatment groups (p's > 0.05). In summary, albeit the higher dose of GAL increased ACh release, it did not improve measures of sustained attention or histopathological markers, thereby partially supporting the hypothesis and providing the impetus for further investigations into alternative cholinergic pharmacotherapies such as nAChR positive allosteric modulators.

A bridge to recovery: Acute amantadine prior to environmental enrichment after brain trauma augments cognitive benefit.

Environmental enrichment (EE) facilitates motor and cognitive recovery after traumatic brain injury (TBI). Historically, EE has been provided immediately and continuously after TBI, but this paradigm does not model the clinic where rehabilitation is typically not initiated until after critical care. Yet, treating TBI early may facilitate recovery. Hence, we sought to provide amantadine (AMT) as a bridge therapy before commencing EE. It was hypothesized that bridging EE with AMT would augment motor and cognitive benefits. Anesthetized adult male rats received a cortical impact (2.8 mm deformation at 4 m/s) or sham surgery and then were housed in standard (STD) conditions where they received intraperitoneal AMT (10 mg/kg or 20 mg/kg) or saline vehicle (VEH; 1 mL/kg) beginning 24 h after surgery and once daily during the 6-day bridge phase or once daily for 19 days for the non-bridge groups (i.e., continuously STD-housed) to compare the effects of acute AMT plus EE vs. chronic AMT alone. Abbreviated EE, which was presented to closer emulate clinical rehabilitation (e.g., 6 h/day), began on day 7 for the AMT bridge and chronic EE groups. Motor (beam-walking) and cognition (acquisition of spatial learning and memory) were assessed on days 7-11 and 14-19, respectively. Cortical lesion volume and hippocampal cell survival were quantified on day 21. EE, whether provided in combination with VEH or AMT, and AMT (20 mg/kg) + STD, benefitted motor and cognition vs. the STD-housed VEH and AMT (10 mg/kg) groups (p < 0.05). The AMT (20 mg/kg) + EE group performed better than the VEH + EE, AMT (10 mg/kg) + EE, and AMT (20 mg/kg) + STD groups in the acquisition of spatial learning (p < 0.05) but did not differ in motor function (p > 0.05). All groups receiving EE exhibited decreased cortical lesion volumes and increased CA3 neuron survival relative to the STD-housed groups (p < 0.05) but did not differ from one another (p > 0.05). The added cognitive benefit achieved by bridging EE with AMT (20 mg/kg) supports the hypothesis that the temporal separation of combinational therapies is more effective after TBI.

Efficacy of a music-based intervention in a preclinical model of traumatic brain injury: An initial foray into a novel and non-pharmacological rehabilitative therapy.

Traumatic brain injury (TBI) causes neurobehavioral and cognitive impairments that negatively impact life quality for millions of individuals. Because of its pernicious effects, numerous pharmacological interventions have been evaluated to attenuate the TBI-induced deficits or to reinstate function. While many such pharmacotherapies have conferred benefits in the laboratory, successful translation to the clinic has yet to be achieved. Given the individual, medical, and societal burden of TBI, there is an urgent need for alternative approaches to attenuate TBI sequelae and promote recovery. Music based interventions (MBIs) may hold untapped potential for improving neurobehavioral and cognitive recovery after TBI as data in normal, non-TBI, rats show plasticity and augmented cognition. Hence, the aim of this study was to test the hypothesis that providing a MBI to adult rats after TBI would improve cognition, neurobehavior, and histological endpoints. Adult male rats received a moderate-to-severe controlled cortical impact injury (2.8 mm impact at 4 m/s) or sham surgery (n = 10-12 per group) and 24 h later were randomized to classical Music or No Music (i.e., ambient room noise) for 3 h/day from 19:00 to 22:00 h for 30 days (last day of behavior). Motor (beam-walk), cognitive (acquisition of spatial learning and memory), anxiety-like behavior (open field), coping (shock probe defensive burying), as well as histopathology (lesion volume), neuroplasticity (BDNF), and neuroinflammation (Iba1, and CD163) were assessed. The data showed that the MBI improved motor, cognitive, and anxiety-like behavior vs. No Music (p's < 0.05). Music also reduced cortical lesion volume and activated microglia but increased resting microglia and hippocampal BDNF expression. These findings support the hypothesis and provide a compelling impetus for additional preclinical studies utilizing MBIs as a potential efficacious rehabilitative therapy for TBI.

Enriching adult male rats prior to traumatic brain injury does not attenuate neurobehavioral or histological deficits.

Environmental enrichment (EE) confers significant increases in neurobehavioral and cognitive recovery and decreases histological damage in various models of traumatic brain injury (TBI). However, despite EE's pervasiveness, little is known regarding its prophylactic potential. Thus, the goal of the current study was to determine whether enriching rats prior to a controlled cortical impact exerts protection as evidenced by attenuated injury-induced neurobehavioral and histological deficits relative to rats without prior EE. The hypothesis was that enrichment prior to TBI would be protective. After two weeks of EE or standard (STD) housing, anesthetized adult male rats received either a controlled cortical impact (2.8 mm deformation at 4 m/s) or sham injury and then were placed in EE or STD conditions. Motor (beam-walk) and cognitive (spatial learning) performance were assessed on post-operative days 1-5 and 14-18, respectively. Cortical lesion volume was quantified on day 21. The group that was housed in STD conditions before TBI and received post-injury EE performed significantly better in motor, cognitive, and histological outcomes vs. both groups in STD conditions regardless of whether having received pre-injury EE or not (p < 0.05). That no differences in any endpoint were revealed between the two STD-housed groups after TBI suggests that enriching rats prior to TBI does not attenuate neurobehavioral or histological deficits and therefore does not support the hypothesis.

Recombinant interleukin-21 plus sorafenib for metastatic renal cell carcinoma: a phase 1/2 study.

BACKGROUND: Despite the positive impact of targeted therapies on metastatic renal cell carcinoma (mRCC), durable responses are infrequent and an unmet need exists for novel therapies with distinct mechanisms of action. We investigated the combination of recombinant Interleukin 21 (IL-21), a cytokine with unique immunostimulatory properties, plus sorafenib, a VEGFR tyrosine kinase inhibitor. METHODS: In this phase 1/2 study, 52 mRCC patients received outpatient treatment with oral sorafenib 400 mg twice daily plus intravenous IL-21 (10-50 mcg/kg) on days 1-5 and 15-19 of each 7-week treatment course. The safety, antitumor activity, pharmacokinetic and pharmacodynamic effects of the combination were evaluated. RESULTS: In phase 1 (n = 19), the maximum tolerated dose for IL-21 with the standard dose of sorafenib was determined to be 30 mcg/kg/day; grade 3 skin rash was the only dose-limiting toxicity. In phase 2, 33 previously-treated patients tolerated the combination therapy well with appropriate dose reductions; toxicities were mostly grade 1 or 2. The objective response rate was 21% and disease control rate was 82%. Two patients have durable responses that are ongoing, despite cessation of both IL-21 and sorafenib, at 41+ and 30+ months, respectively. The median progression-free survival in phase 2 was 5.6 months. The pharmacokinetic and pharmacodynamic properties of IL-21 appeared to be preserved in the presence of sorafenib. CONCLUSION: IL-21 plus sorafenib has antitumor activity and acceptable safety in previously treated mRCC patients. IL-21 may represent a suitable immunotherapy in further exploration of combination strategies in mRCC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00389285.

Vitamin A status after prophylactic intramuscular vitamin A supplementation in extremely low birth weight infants.

BACKGROUND: Vitamin A supplementation (VAS) is recommended to prevent bronchopulmonary dysplasia (BPD). Our objective was to evaluate the effect of VAS on vitamin A (VA) status. We hypothesized that VAS would improve VA status in extremely low birth weight (ELBW) infants. MATERIALS AND METHODS: Retrospective chart review of infants 1 year before and after initiation of VAS (5000 IU 3 times a week intramuscularly [IM]; total 12 doses). Linear regression was used to model impact of VAS on VA status (retinol level and retinol/retinol binding protein [RBP] ratio). Models were adjusted for time and generalized estimating equations were used to account for intraindividual correlation. RESULTS: Sixty-seven infants (mean gestational age 26 ± 2 weeks; mean body weight 803 ± 142 g) were included; 35 received VAS and 32 did not (no-VAS). Both groups had similar baseline characteristics. Infants who received VAS had mean retinol levels that were 9.0 mcg/dL (95% confidence interval [CI], 4.9-13.2; P < .001) higher and mean retinol/RBP ratios that were 0.21 (95% CI, 0.07-0.36; P = .005) higher than the no-VAS group. Retinol and retinol/RBP ratio increased with time (P < .001). Fewer infants in the VAS group had VA deficiency (retinol/RBP ratios <0.7) compared with the no-VAS group. Culture-positive sepsis was more common in the VAS group (48% vs 12%; P = .002). CONCLUSIONS: VA status in ELBW infants was improved and maintained over the first month of life with IM VAS. Because of concerns for potential risks of repeated injections, further studies are indicated to evaluate the optimal mode of VA delivery in preterm infants.

The utility of adding expiratory or decubitus chest radiographs to the radiographic evaluation of suspected pediatric airway foreign bodies.

STUDY OBJECTIVE: This study aimed to compare test characteristics of standard (lateral and posteroanterior or anteroposterior) chest radiographs with and without special views (expiratory or bilateral decubitus) in the emergency department evaluation of children with suspected airway foreign bodies. METHODS: From 1997 to 2008, 328 patients with a suspected airway foreign body had standard and special view chest radiographs: 192 with left and right decubitus views, 133 with expiratory views, and 3 with both. Patients were excluded for cardiorespiratory disease, chest wall deformity, visible airway foreign bodies on standard views, or spontaneously expelled airway foreign bodies. After blinded radiologist review, standard plus special view test characteristics were compared to standard views. RESULTS: Nine upper airway and 70 tracheobronchial airway foreign bodies were identified by direct visualization or bronchoscopy, and the remainder were ruled out by bronchoscopy (50 patients) or clinically (199 patients). The sensitivity and specificity of the radiographs were, respectively, decubitus cohort, standard views, 56% and 79% and standard+decubitus views, 56% and 64%; expiratory radiograph cohort, standard views, 33% and 70% and standard+expiratory views, 62% and 72%. For standard plus decubitus views versus standard views alone, the relative sensitivity was 1.0 (0.56/0.56; 95% confidence interval [CI] 0.81 to 1.23) and the relative 1-specificity was 1.76 (0.36/0.21; 95% CI 1.3 to 2.37). For standard plus expiratory views versus standard views alone, the relative sensitivity was 1.87 (0.62/0.33; 95% CI 1.23 to 2.83) and the relative 1-specificity was 0.93 (0.28/0.3; 95% CI 0.6 to 1.44). CONCLUSION: The addition of decubitus to standard views increases false positives without increasing true positives and lacks clinical benefit. The addition of expiratory to standard views increases true positives without increasing false positives, but test accuracy remains low and the clinical benefit is uncertain.

Maternal risk factors for congenital urinary anomalies: results of a population-based case-control study.

OBJECTIVE: Epidemiologic data addressing maternal risk factors for congenital urinary tract anomalies (CUTA) are limited, with conflicting results for preexisting diabetes mellitus, gestational diabetes, and tobacco and alcohol use. The purpose of this study was to examine the association between maternal risk factors and CUTA in a population-based case-control study. METHODS: A case-control analysis was performed using linked birth-hospital discharge records from Washington state for 1987-2007 to evaluate the association between maternal risk factors and CUTA. Cases were children with International Classification of Diseases, Ninth Revision, Clinical Modification codes for urinary anomalies. Controls without urinary tract anomalies were selected from Washington State birth records and matched by birth year in a ratio of 4:1. Logistic regression was performed to evaluate the association between maternal factors and CUTA. RESULTS: A total of 4673 cases and 18,692 controls were studied. In the multivariate analysis, gestational diabetes (OR 1.42, 95% CI 1.09-1.85), preexisting diabetes (OR 3.46, 95% CI 2.17-5.54), and maternal renal disease (OR 5.31, 95% CI 2.40-11.72) were all associated with an increased risk of kidney anomalies. Advanced maternal age (OR 1.20, 95% CI 1.06-1.35), gestational diabetes (OR 1.25, 95% CI 1.01-1.56), maternal renal disease (OR 4.06, 95% CI 1.95-8.46), and non-Caucasian race (OR 0.82, 95% CI .74-.91) were all associated with the risk of ureter, bladder, and urethra anomalies in multivariate analysis. CONCLUSION: Several maternal factors are associated with the risk of CUTA, including diabetes mellitus and maternal renal disease. This information can be used for prenatal counseling and management of women with these risk factors.

The optimal timing of referral to an intestinal failure program: the relationship between hyperbilirubinemia and mortality.

PURPOSE: Multidisciplinary treatment of pediatric intestinal failure has shown promising results. However, there are limited data as to the optimal time frame for referral of patients to intestinal failure programs. The aim of this study was to explore the relationship of hyperbilirubinemia at referral with patient outcomes in a multidisciplinary program. METHODS: A retrospective analysis was performed of a prospectively collected database from a multidisciplinary intestinal failure program. Multivariable logistic regression adjusted for age at referral was used to model the association between the conjugated bilirubin at referral and risk of mortality. Median values with range are reported. RESULTS: Sixty-two patients were referred from 2005 to 2009. Patients presented at age 6.4 months (0.4-261.4 months) and were followed up for 16.8 (0.3-53.0) months. Nine subjects (14.5%) died, and 12 subjects (19.4%) were listed for combined liver-intestine transplant. A 50% mortality was seen in patients referred with a conjugated bilirubin ≥ 7.2 mg/dL (n = 12), whereas mortality at referral bilirubin levels <7.2 mg/dL was 6%. After adjusting for age at referral, patients with a conjugated bilirubin ≥ 7.2 mg/dL at referral were 15.4 times more likely to die than patients who presented with lower bilirubin levels (P = .001; 95% confidence interval, 2.8-83.4). CONCLUSION: Within a pediatric intestinal failure program, mortality is associated with the degree of hyperbilirubinemia at time of referral. These data strongly suggest that these patients should be referred to a multidisciplinary program early in the evolution of their liver disease.

Lidocaine pretreatment with tourniquet versus lidocaine-propofol admixture for attenuating propofol injection pain: a randomized controlled trial.

OBJECTIVE: Findings from studies investigating optimal techniques for attenuating propofol-related injection pain are inconsistent. In previous studies, lidocaine pretreatment using a tourniquet has been reported to be superior, inferior, or equivalent to a lidocaine-propofol admixture for reducing pain. This discordance could represent either no meaningful difference in the treatments or underlying methodological differences in the previous studies. We hypothesized that tourniquet-controlled pretreatment with lidocaine would be superior to lidocaine-propofol admixture for reducing propofol injection pain. METHODS: This randomized controlled trial compared 3 groups-a control group (saline pretreatment/saline admixture; n = 50), a pretreatment group (lidocaine pretreatment/saline admixture; n = 51), and an admixture group (saline pretreatment/lidocaine admixture; n = 50). The primary outcome was verbal pain score after injection. The incidence of pain on injection was explored as a secondary outcome. RESULTS: The median (interquartile range) verbal pain score after study solution injection were as follows-control group: 3 (0-6), pretreatment group: 0 (0-0), and admixture group: 0 (0-2). The pretreatment group had significantly lower pain scores when compared with the admixture group (P = 0.016), and both groups were superior to the control group. The pretreatment group had fewer subjects experiencing any injection pain than did the admixture group (20% vs. 44%, respectively; P = 0.024). CONCLUSIONS: Tourniquet-controlled pretreatment with lidocaine is statistically superior to admixing lidocaine with propofol for reducing propofol injection pain intensity, but the clinical importance of this small effect is questionable. However, pretreatment more effectively eliminates injection pain.

The lateral capitellohumeral angle in normal children: mean, variation, and reliability in comparison to Baumann's angle.

BACKGROUND: Angular deformity is the most common complication of supracondylar humerus fracture. Baumann's angle (BA) is an established radiographic measure of coronal plane deformity after this injury. Numerous radiographic methods have been used to assess sagittal plane deformity, however, the mean, variability, and reliability of these measures has not been established. The purpose of this study was to determine the mean, SD, and intraobserver/interobserver reliability of the lateral capitellohumeral angle (LCHA) in children without evidence of fracture and compare them with those of BA. METHODS: Seventy-one sets of anteroposterior and lateral elbow radiographs were selected and stratified into 6-year age categories with equal number of males and females in each category. Five physicians performed 3 separate measurements of LCHA and BA on each film set. Statistical calculations were performed to determine mean, SD, measurement reliability, and differences between patients groups. RESULTS: The mean LCHA ±1 SD and BA ± 1 SD measurements were 50.8 ± 6 degrees and 71.5 ± 6.2 degrees, respectively, and did not vary significantly by age, side, or sex (P>0.05). The LCHA showed good intraobserver (correlation coefficient 0.67) and fair interobserver (0.37) reliability, whereas BA showed excellent intraobserver (0.86) and interobserver (0.80) reliability. The expected SD for repeated measurement of a radiograph by a single observer was 2.6 degrees for BA and 5.2 degrees for LCHA. CONCLUSIONS: The LCHA is a simple measurement to perform using digital tools. In normal elbows, the mean angle is 51 ± 6 degrees and does not vary by age, side, or sex. LCHA variability in normal elbow radiographs is similar to BA. Its reliability is inferior to BA, but improves with age. Sagittal angulation abnormality of at least 12 degrees (<39 or >63 degrees) is necessary to be confident that the change is not because of measurement error alone. Further research is needed to better define the relationship of sagittal plane angular deformity to clinical outcome. LEVEL OF EVIDENCE: Diagnostic study with poor reference standard, Level IV.

Pulmonary exacerbations are associated with subsequent FEV1 decline in both adults and children with cystic fibrosis.

BACKGROUND: Patients with cystic fibrosis (CF) frequently experience pulmonary exacerbations that may lead to a faster subsequent decline in pulmonary function; however, this relationship has not been clearly established. The purpose of this study was to determine the association between the frequency of pulmonary exacerbations and subsequent forced expiratory volume in 1 sec (FEV(1) ) decline in adults and children with CF. METHODS: Cohort study of subjects followed in the Cystic Fibrosis Foundation Patient Registry from 2003 through 2006. Mixed effects modeling was used to estimate differences in rates of decline in FEV(1) in 2004-2006 for patients with 0, 1, 2, or 3+ pulmonary exacerbation(s) in 2003. RESULTS: Of 8,490 subjects who met inclusion criteria, 60% had 0 exacerbations, 23% had 1, 10% had 2, and 7% had 3+ exacerbations in 2003. Compared to children with no pulmonary exacerbations in 2003, children with one or more exacerbations experienced a significantly (P < 0.001) greater rate of FEV(1) decline in 2004-2006. In contrast, among adults, only those with 3+ exacerbations in 2003 had a significantly (P = 0.01) greater rate of FEV(1) decline in 2004-2006 than those with no exacerbations in 2003. CONCLUSIONS: There is a strong association between the frequency of pulmonary exacerbations and subsequent decline in pulmonary function. In adults, having 3+ exacerbations, and among children, having any exacerbations is associated with a greater rate of decline in the ensuing 3 years. Improved prevention, identification, and treatment of pulmonary exacerbations are likely to have long-term benefits for patients with CF, especially children.

Subclinical viremia increases risk for chronic allograft injury in pediatric renal transplantation.

The impact of subclinical viral infection on chronic allograft injury in the pediatric renal transplant population is not well defined. We prospectively assessed cytomegalovirus (CMV) and Epstein-Barr virus (EBV) DNAemia by monthly PCR in 55 pediatric renal transplant recipients for the first 2 years after transplantation. Subclinical CMV and EBV infection occurred in 22 and 36%, respectively. Multivariable linear regression analysis suggested that both subclinical CMV and EBV infection independently associate with significant declines in GFR during the first 2 years after transplantation. CMV seronegativity associated with a significantly greater decline in GFR than seropositivity (P < 0.01). Subclinical CMV infection and subclinical EBV infection each associated with approximately fourfold greater odds of histologic evidence of chronic allograft injury (odds ratio 4.61 [95% confidence interval 1.18 to 18.07] and odds ratio 4.33 [95% confidence interval 1.34 to 14.00], respectively). An increase in viral load of CMV or EBV also associated with increased risk for moderate to severe chronic allograft injury. Taken together, these results demonstrate an association between subclinical CMV and EBV infections, which occur despite standard antiviral prophylaxis, and chronic allograft injury in pediatric renal transplant recipients.

Performance of rheumatoid arthritis disease activity measures and juvenile arthritis disease activity scores in polyarticular-course juvenile idiopathic arthritis: Analysis of their ability to classify the American College of Rheumatology pediatric measures of response and the preliminary criteria for flare and inactive disease.

OBJECTIVE: To measure the abilities of the continuous measures of disease activity used in rheumatoid arthritis (RA) and the 3 versions of the Juvenile Arthritis Disease Activity Score (JADAS; based upon 10-, 27-, and 71-joint counts) to accurately classify the American College of Rheumatology (ACR) pediatric measures of response, flare, and inactive disease in polyarticular-course juvenile idiopathic arthritis (JIA). METHODS: We conducted a secondary analysis of a randomized trial of infliximab in polyarticular-course JIA. Disease activity was calculated at baseline and weeks 14, 28, and 52 using the Disease Activity Score (DAS), DAS in 28 joints, Simplified Disease Activity Index, Clinical Disease Activity Index, and JADAS. The ability of the RA measures and JADAS to classify each ACR pediatric measure, flare, and inactive disease was measured by areas under the receiver operating characteristic curve (AUCs). Positive predictive values (PPVs) for inactive disease were calculated. RESULTS: Data from 97 participants were available. The AUCs for the RA scores for each ACR pediatric measure were 0.73-0.89. The AUCs of the JADAS for the ACR pediatric measures were 0.75-0.92. The PPVs of the RA scores for inactive disease were 0.33-0.67. The PPVs of the JADAS for inactive disease were each 0.93. Based on the RA and JADAS scores, the percentage of visits misclassified as inactive disease ranged from 7-67%. CONCLUSION: The RA measures and JADAS versions showed acceptable to excellent ability to classify participants for each pediatric outcome measure, but the clinical significance of differences between AUCs for these scores could not be assessed. Misclassification of active disease versus inactive disease by the RA and JADAS scores was not uncommon in this cohort.

Failure to recover to baseline pulmonary function after cystic fibrosis pulmonary exacerbation.

RATIONALE: Patients with cystic fibrosis periodically experience pulmonary exacerbations. Previous studies have noted that some patients' lung function (FEV(1)) does not improve with treatment. OBJECTIVES: To determine the proportion of patients treated for a pulmonary exacerbation that does not recover to spirometric baseline, and to identify factors associated with the failure to recover to spirometric baseline. METHODS: Cohort study using the Cystic Fibrosis Foundation Patient Registry from 2003-2006. We randomly selected one pulmonary exacerbation treated with intravenous antibiotics per patient and compared the best FEV(1) in the 3 months after treatment with the best FEV(1) in the 6 months before treatment. Recovery to baseline was defined as any FEV(1) in the 3 months after treatment that was greater than or equal to 90% of the baseline FEV(1). Multivariable logistic regression was used to estimate associations with the failure to recover to baseline FEV(1). MEASUREMENTS AND MAIN RESULTS: Of 8,479 pulmonary exacerbations, 25% failed to recover to baseline FEV(1). A higher risk of failing to recover to baseline was associated with female sex; pancreatic insufficiency; being undernourished; Medicaid insurance; persistent infection with Pseudomonas aeruginosa, Burkholderia cepacia complex, or methicillin-resistant Staphylococcus aureus; allergic bronchopulmonary aspergillosis; a longer time since baseline spirometric assessment; and a larger drop in FEV(1) from baseline to treatment initiation. CONCLUSIONS: For a randomly selected pulmonary exacerbation, 25% of patients' pulmonary function did not recover to baseline after treatment with intravenous antibiotics. We identified factors associated with the failure to recover to baseline, allowing clinicians to identify patients who may benefit from closer monitoring and more aggressive treatment.

Hydroscopic properties of organic objects that may present as aural foreign bodies.

BACKGROUND: Organic foreign bodies swell when irrigated with water, potentially making extraction more difficult. As the degree and rate of swelling of different types of organic foreign bodies has not been established, we aimed to analyze the hydroscopic properties of different organic foreign bodies in body temperature water. METHODS: Dry kidney beans, brown beans, peas, popcorn kernels, and dried fruits were soaked in a body temperature (37C) water bath. Volume of these organic materials was measured hourly to 8 hours, then at 12, 16, 24, 28, 36 and 48 hours. RESULTS: All dried fruits and beans increased in volume over time. The volume increase from baseline at 6 hours was between 43% (popcorn kernels) and 383% (kidney beans). Peas, popcorn, and raisins did not increase volume further after 6 hours. Kidney and brown beans had the greatest increase in volume overall (1268% and 482% respectively), and the greatest continued increase after 24 hours. CONCLUSIONS: Many organic substances that frequently present as aural foreign bodies may swell enough in water to lodge tightly in the ear canal. Typical popcorn kernels and dried peas will not swell sufficiently to lodge tightly in the ear canal of a typical child one year or older. A retained organic foreign body in a moist ear canal may cause inflammation until the foreign body can be removed. These risks may be offset by the advantages of successful removal with irrigation. KEYWORDS: Foreign body; Irrigation; Organic; Ear; Hydroscopic; Procedure; Removal.

Compliance with multiple-dose vaccine schedules among older children, adolescents, and adults: results from a vaccine safety datalink study.

OBJECTIVES: We studied compliance with multiple-dose vaccine schedules, assessed factors associated with noncompliance, and examined timeliness of series completion among older children, adolescents, and adults. METHODS: We conducted a large, multisite, retrospective cohort study of older children, adolescents, and adults in the Vaccine Safety Datalink population from 1996 through 2004. We quantified the rates of completion of all required doses for varicella, hepatitis A, and hepatitis B vaccines according to their recommended schedules. RESULTS: Among those who received a first dose of varicella (n = 16 075), hepatitis A (n = 594 917), and hepatitis B (n = 590 445) vaccine, relatively few completed the series (55%-65% for hepatitis B vaccine and 40%-50% for hepatitis A and varicella vaccines in most age groups). Compliance was lowest among adolescents (35.9%) and Medicaid recipients (29.7%) who received varicella vaccine and among younger adult age groups who received hepatitis A vaccine (25%-35% across those age groups). Even among series completers, there was a relatively long interval of undervaccination between the first and last doses. CONCLUSIONS: Compliance with multiple-dose vaccine series among older children, adolescents, and adults is suboptimal. Further evaluations of strategies to improve compliance in these populations are needed.

Impact of the introduction of pneumococcal conjugate vaccine on rates of community acquired pneumonia in children and adults.

Pneumococcal conjugate vaccine use among young children has led to significant declines in invasive pneumococcal disease in the United States, but the impact on community-acquired pneumonia is unknown. We conducted population-based pneumonia surveillance among 794,282 Group Health members before and after infant vaccine introduction in 2000. We presumptively identified pneumonia episodes using diagnosis codes assigned to medical encounters and confirmed 17,513 outpatient and 6318 hospitalized events by reviewing chest radiograph reports or hospitalization records. There was evidence for a decline in rates of both outpatient and hospitalized pneumonia in children less than 1 year of age following vaccine introduction but there were no consistent reductions in pneumonia rates among older children and adults.