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2.  Survey of injuries among West End performers 
OBJECTIVES: To obtain more information about injuries of West End performers. METHODS: A retrospective survey of 269 performers appearing in 20 West End productions (12 dramas and eight musicals). RESULTS: In current productions, 46% of all performers sustained at least one injury for an average of 0.87 injuries per performer. Lower extremity injuries were the most common for dancers (52.2% of injuries) and actors (43.2%) with neck and back injuries the second most common. Sprains and strains were the most common diagnoses. 61% of performers thought that their injuries were preventable. Most performers consulted nonphysician healthcare providers. Factors significantly influencing the risk of injuries for performers include female sex, a history of previous injuries, missed performances due to previous injuries, more physically demanding roles, and performing on raked (angled) stages. CONCLUSION: West End performers commonly sustain injuries. Although primary prevention of most theatrical injuries is not possible, modification of raked stages may reduce the incidence. This study may be helpful to the growing number of healthcare providers who practice performing arts medicine and may stimulate additional concern and research in the medical and theatrical communities about the performance injuries of professionals, amateurs, and theatrical students worldwide.
 
PMCID: PMC1757638  PMID: 9861179
3.  Accident and emergency medicine--II. 
Postgraduate Medical Journal  1992;68(804):786-799.
PMCID: PMC2399520  PMID: 1461850
4.  Accident and emergency medicine--I. 
Postgraduate Medical Journal  1992;68(803):714-734.
PMCID: PMC2399445  PMID: 1480535
6.  Amplification of human platelet activation by surface pannexin-1 channels 
Background
Pannexin-1 (Panx1) forms an anion-selective channel with a permeability up to ∼1 kDa and represents a non-lytic, non-vesicular ATP release pathway in erythrocytes, leukocytes and neurons. Related connexin gap junction proteins have been reported in platelets; however, the expression and function of the pannexins remain unknown.
Objective
To determine the expression and function of pannexins in human plate-lets, using molecular, cellular and functional techniques.
Methods
Panx1 expression in human platelets was det-ermined using qPCR and antibody-based techniques. Contributions of Panx1 to agonist-evoked efflux of cytoplasmic calcein, Ca2+ influx, ATP release and aggregation were assessed in washed platelets under conditions where the P2X1 receptor response was preserved (0.32 U mL−1 apyrase). Thrombus formation in whole blood was assessed in vitro using a shear chamber assay. Two structurally unrelated and widely used Panx1 inhibitors, probenecid and carbenoxolone, were used throughout this study, at concentrations that do not affect connexin channels.
Results
PANX1, but not PANX2 or PANX3, mRNA was detected in human platelets. Furthermore, Panx1 protein is glycosylated and present on the plasma membrane of platelets, and displays weak physical association with P2X1 receptors. Panx1 inhibition blocked thrombin-evoked efflux of calcein, and reduced Ca2+ influx, ATP release, platelet aggregation and thrombus formation under arterial shear rates in vitro. The Panx1-dependent contribution was not additive to that of P2X1 receptors.
Conclusions
Panx1 is expressed on human platelets and amplifies Ca2+ influx, ATP release and aggregation through the secondary activation of P2X1 receptors. We propose that Panx1 represents a novel target for the management of arterial thrombosis.
doi:10.1111/jth.12566
PMCID: PMC4238786  PMID: 24655807
ATP; calcium; collagen; P2X1 receptor; pannexin 1, human
7.  Two algorithms for fitting constrained marginal models 
The two main algorithms that have been considered for fitting constrained marginal models to discrete data, one based on Lagrange multipliers and the other on a regression model, are studied in detail. It is shown that the updates produced by the two methods are identical, but that the Lagrangian method is more efficient in the case of identically distributed observations. A generalization is given of the regression algorithm for modelling the effect of exogenous individual-level covariates, a context in which the use of the Lagrangian algorithm would be infeasible for even moderate sample sizes. An extension of the method to likelihood-based estimation under L1-penalties is also considered.
doi:10.1016/j.csda.2013.02.001
PMCID: PMC3686142  PMID: 23794772
categorical data; L1-penalty; marginal log-linear model; maximum likelihood; non-linear constraint
8.  Complex Issues Affecting Student Pharmacist Debt 
It is time for colleges and schools of pharmacy to examine and confront the rising costs of pharmacy education and the increasing student loan debt borne by graduates. These phenomena likely result from a variety of complex factors. The academy should begin addressing these issues before pharmacy education becomes cost-prohibitive for future generations. This paper discusses some of the more salient drivers of cost and student debt load and offers suggestions that may help alleviate some of the financial pressures.
doi:10.5688/ajpe787131
PMCID: PMC4174373  PMID: 25258436
student loan; debt; tuition; higher education
9.  How do low back pain patients conceptualize their expectations regarding treatment? Content analysis of interviews 
European Spine Journal  2013;22(9):1986-1995.
Purpose
The purpose of this study was to gain insight into how low back pain (LBP) patients conceptualize the construct of expectations regarding treatment.
Methods
This study was nested within a mixed-method randomized clinical trial comparing three primary care interventions for LBP. A total of 77 participants with LBP lasting longer than 6 weeks were included; semi-structured interviews were conducted querying patients about their expectations for treatment. Also factors influencing their expectations were explored. Interviews were administered following enrollment into the study, but prior to study treatment. Two researchers independently conducted a content analysis using NVIVO 9 software.
Results
LBP patients’ expectations could be categorized in two main domains: outcome and process expectations, each with subdomains. Patients expressed expectations in all subdomains both as values (what they hoped) and probabilities (what they thought was likely). In multiple subdomains, there were differences in the nature (positive vs. negative) and frequency of value and probability expectations. Participants reported that multiple factors influenced their expectations of which past experience with treatment appeared to be of major influence on probability expectations.
Conclusion and recommendations
This study showed that LBP patients’ expectations for treatment are multifaceted. Current measurement instruments do not cover all domains and subdomains of expectations. Therefore, we recommend the development of new or improved measures that make a distinction between value and probability expectations and assess process and/or outcome expectations covering multiple subdomains. Some of the influencing factors found in this study may be useful targets for altering patients’ treatment expectations and improving health outcomes.
doi:10.1007/s00586-013-2803-8
PMCID: PMC3777054  PMID: 23661035
Patients’ expectations; Low back pain; Qualitative research; Psychological factors; Patient preference
10.  Plasma 8-hydroxy-2′-deoxyguanosine Levels in Huntington Disease and Healthy Controls Treated with Coenzyme Q10 
We analyzed plasma 8OHdG concentrations in 20 individuals enrolled in the Pre-2CARE study before and after treatment with CoQ. Treatment resulted in a mean reduction in 8OHdG of 2.9 ± 2.9 pg/ml for the cohort (p = 0.0003) and 3.0 ± 2.6 pg/ml, for the HD group (p = 0.002). Baseline 8OHdG levels were not different between individuals with HD and controls (19.3 ± 3.2 pg/ml vs. 19.5 ± 4.7 pg/ml, p = 0.87) though baseline CoQ levels were elevated in HD compared with controls (p < 0.001). CoQ treatment reduces plasma 8OHdG and this reduction may serve as a marker of pharmacologic activity of CoQ in HD.
doi:10.3233/JHD-2012-120007
PMCID: PMC4115297  PMID: 25063191
Huntington disease; coenzyme Q10; 8OHdG; oxidative injury
11.  Ventilator settings and outcome of respiratory failure in chronic interstitial lung disease 
Chest  2007;133(5):1113-1119.
Background
While patients with interstitial lung disease may be particularly susceptible to ventilator-induced lung injury, ventilator strategies have not been studied in this group of patients.
Purpose
To describe the clinical course and outcome of patients with interstitial lung disease and acute respiratory failure in relation to ventilatory parameters.
Methods
We retrospectively identified a cohort of ventilated patients with interstitial lung disease admitted to five ICUs at a single institution. We analyzed demographic data, pulmonary function tests, severity of illness, and initial 24 hours of continuous ventilator parameters. Primary outcomes were survival to hospital discharge and one-year survival.
Main results
Of 94 patients with interstitial lung disease, 44(47%) survived to hospital discharge and 39(41%) were alive at one-year. Non-survivors were less likely to be postoperative, had higher severity of illness and were ventilated at higher airway pressures and lower tidal volumes. Step changes in positive end-expiratory pressure >10 cmH2O were attempted in 20 patients and resulted in an increase in plateau pressure (median difference +16; IQR, 9 to 24 cm H2O) and a decrease in respiratory system compliance (median difference -0.28: IQR, -0.43 to -0.13 mL/kg/cm H2O). Cox model revealed high positive end-expiratory pressure (hazard ratio 4.72; 95% CI, 2.06, 11.15), APACHE III predicted mortality (hazard ratio 1.33; 95% CI, 1.18,1.50), age (hazard ratio 1.03; 95% CI, 1,1.05) and low PaO2/FiO2(hazard ratio 0.96;95% CI, 0.92,0.99) to be independent determinants of survival.
Conclusion
Both severity of illness and high PEEP predict the outcome of interstitial lung disease patients receiving mechanical ventilation.
doi:10.1378/chest.07-1481
PMCID: PMC4003484  PMID: 17989156
Interstitial lung disease; intensive care unit; respiration; artificial
12.  Mid-pregnancy maternal leptin levels, birthweight for gestational age and preterm delivery 
Clinical endocrinology  2013;78(4):607-613.
Summary
Objective
Maternal blood leptin levels are positively associated with adiposity. Recent studies suggest that leptin is also abundantly produced by the placenta and may function as a regulator of fetal growth. Our goal was to examine mid-pregnancy levels of leptin in maternal blood in relation to birthweight for gestational age (BW/GA) and timing of delivery after accounting for maternal pre-pregnancy body mass index (prepreg-BMI) and pregnancy complications.
Patients
Data were from 1,304 sub-cohort mother/infant pairs who participated in the Pregnancy Outcomes and Community Health (POUCH) Study (1998–2004).
Measurements
Leptin levels, measured at 16–27 weeks’ gestation, were log-transformed. Geometric mean (GMean) leptin levels were estimated by weighted linear regression with gestational age at blood draw as a covariate. GMean was re-transformed to the original scale for reporting.
Results
Using the GMeans leptin in mothers of term appropriate-for-gestational age (AGA) neonates as the referent (25.2 μg/L), we observed lower levels in mothers of preterm AGA (21.9 μg/L), term small-for-gestational age (SGA) (20.3 μg/L), and preterm SGA neonates (21.7 μg/L). Results were largely unchanged after adjustment for prepreg-BMI. Leptin levels were higher in mothers who delivered large-for-gestational age (LGA) neonates, both preterm (33.6 μg/L) and term (29.1 μg/L), but the GMeans were markedly attenuated after adjustment for prepreg-BMI.
Conclusion
The association between BW/GA and maternal leptin levels after adjustment for prepreg-BMI may represent: 1) a residual effect of maternal adiposity that is not fully captured by BMI; and/or 2) variation in placental leptin levels entering the maternal circulation. In conclusion, mid-pregnancy maternal blood leptin levels may be an early indicator of fetal growth status.
doi:10.1111/cen.12029
PMCID: PMC4004085  PMID: 22934578
13.  Derivation and diagnostic accuracy of the surgical lung injury prediction model 
Anesthesiology  2011;115(1):117-128.
Background
Acute lung injury (ALI) is a serious postoperative complication with limited treatment options. A preoperative risk prediction model would assist both clinicians and scientists interested in ALI. The objective of this investigation was to develop a surgical lung injury prediction (SLIP) model to predict risk of postoperative ALI based on readily available preoperative risk factors.
Methods
This is secondary analysis of a prospective cohort investigation including adult patients undergoing high-risk surgery. Preoperative risk factors for postoperative ALI were identified and evaluated for inclusion in the SLIP model. Multivariate logistic regression was used to develop the model. Model performance was assessed with the area under the Receiver Operating Characteristics Curve and the Hosmer and Lemeshow Goodness-of-fit test.
Results
Out of 4,366 patients, 113 (2.6%) developed early postoperative ALI. Predictors of postoperative ALI in multivariate analysis which were maintained in the final SLIP model included high-risk cardiac, vascular, and thoracic surgery, diabetes mellitus, chronic obstructive pulmonary disease, gastroesophageal reflux disease, and alcohol abuse. The SLIP score discriminated patients who developed early postoperative ALI from those who did not with an area under the Receiver Operating Characteristic Curve (95% CI) of 0.82 (0.78 – 0.86) and was well calibrated (Hosmer Lemeshow p = 0.55). Internal validation using 10-fold cross-validation noted minimal loss of diagnostic accuracy with a mean +/− standard deviation area under the Receiver Operating Characteristic Curve of 0.79 +/− 0.08.
Conclusions
Using readily available preoperative risk factors, we developed the SLIP scoring system to predict risk of developing early postoperative ALI.
doi:10.1097/ALN.0b013e31821b5839
PMCID: PMC3986041  PMID: 21694510
14.  Pharmacy Student Debt and Return on Investment of a Pharmacy Education 
Objective. To describe the current landscape within the profession of pharmacy regarding student tuition, indebtedness, salaries, and job potential.
Methods. Pharmacy tuition and student debt data were obtained through the American Association of Colleges of Pharmacy Institutional Research website. Tuition was defined as average first-year tuition and fees for accredited schools. Debt was defined as the total average amount borrowed. Median salaries and numbers of jobs were obtained from the United States Department of Labor.
Results. In-state tuition at public schools rose an average of $1,211 ± 31 (r2 = 0.996), whereas out-of-state tuition at public schools rose significantly faster at $1,838 ± 80 per year (r2 = 0.988). The average tuition cost for pharmacy school has increased 54% in the last 8 years. The average pharmacist salary has risen from $75,000 to over $112,000 since 2002. The increase in salary has been nearly linear (r2 = 0.988) rising $4,409 ± $170 dollars per year. However, average salary in 2011 was $3,064 below the predicted value based upon a linear regression of salaries over 10 years. The number of pharmacist jobs in the United States has risen from 215,000 jobs in 2003 to 275,000 in 2010. However, there were 3,000 fewer positions in 2012 than in 2011. In 2011, average indebtedness for pharmacy students ($114,422) was greater than average first-year salary ($112,160).
Conclusion. Rising tuition and student indebtedness is a multifaceted problem requiring attention from a number of parties including students, faculty members, universities, and accreditation and government entities.
doi:10.5688/ajpe7815
PMCID: PMC3930253  PMID: 24558273
15.  Nuclear Receptors and AMPK: Resetting Metabolism 
Cold Spring Harbor symposia on quantitative biology  2012;76:10.1101/sqb.2012.76.010470.
Obesity, and in particular central adiposity, is a key feature of metabolic syndrome, which includes trends toward increased triglycerides, insulin resistance, high blood pressure, hypercholesterolemia, and heart disease. It has a prevalence of 25% or more and is a dominant component of the health care budgets in Western societies. In addition to genetic causes, high-fat diets and disrupted sleep patterns have major influences on the development of metabolic syndrome. Recent studies have demonstrated active roles for the nuclear receptor superfamily and the energy-sensing kinase adenosine monophosphate (AMP)-activated protein kinase (AMPK) in regulating metabolism and circadian rhythm. In this chapter, we review these findings and attempt to develop a better understanding of the interplay between metabolism and circadian rhythm and their coordinated regulation by nuclear receptors and AMPK. This supraregulatory network may be considered a target for novel therapeutic applications against metabolic syndrome.
doi:10.1101/sqb.2012.76.010470
PMCID: PMC3870013  PMID: 22411605
17.  Lung disease with anti-CCP antibodies but not rheumatoid arthritis or connective tissue disease 
Respiratory medicine  2012;106(7):1040-1047.
Summary
Objective
We sought to characterize a novel cohort of patients with lung disease, anti-cyclic citrullinated peptide (CCP) antibody positivity, without rheumatoid arthritis (RA) or other connective tissue disease (CTD).
Methods
The study sample included 74 subjects with respiratory symptoms, evaluated January 2008–January 2010 and found to have a positive anti-CCP antibody but no evidence for RA or other CTD. Each underwent serologic testing, pulmonary physiology testing, and thoracic high-resolution computed tomography (HRCT) scan as part of routine clinical evaluation.
Results
The majority of subjects were women, and most were former cigarette smokers. Four distinct radiographic phenotypes were identified: isolated airways disease (54%), isolated interstitial lung disease (ILD) (14%), mixed airways disease and ILD (26%), and combined pulmonary fibrosis with emphysema (7%). This cohort had a predominance of airways disease, either in isolation or along with a usual interstitial pneumonia-pattern of ILD. Among subjects with high-titer anti-CCP positivity (n=33), three developed the articular manifestations of RA during a median follow-up of 449 days.
Conclusion
We have described a unique cohort of patients with anti-CCP antibody positivity and lung disease in the absence of existing RA or other CTD. The lung phenotypic characteristics of this cohort resemble those of established RA and a few of these patients have developed articular RA within a short period of follow-up. The implications of a positive anti-CCP antibody among patients with lung disease but not RA are not yet known, but we believe requires further investigation.
doi:10.1016/j.rmed.2012.03.006
PMCID: PMC3753791  PMID: 22503074
Anti-cyclic citrullinated peptide; Rheumatoid arthritis; Interstitial lung disease; Lung diseases
18.  Obstructive sleep apnea does not promote esophageal reflux in fibrosing interstitial lung disease 
Respiratory Medicine  2012;106(7):1033-1039.
Background
In patients with fibrosing interstitial lung disease (fILD), gastroesophageal reflux (GER) is highly prevalent, perhaps because of the effects of lung fibrosis on altering intrathoracic pressure, diaphragm morphology and lower esophageal sphincter (LES) function. For unclear reasons, obstructive sleep apnea (OSA) is also highly prevalent among patients with fILD. We conducted this study to test our hypothesis that, in patients with fILD, OSA would exacerbate diaphragm/LES dysfunction and increase the propensity for—and severity of—GER.
Methods
We identified patients with fILD who underwent screening polysomnogram and pH or pH/impedence probe at our center during the same week. We examined the association between OSA and GER and used logistic regression to determine independent predictors of OSA or GER.
Results
In 54 included subjects, neither OSA (dichotomous) nor apnea hypopnea index (continuous) predicted the presence of GER. Regardless of body position (upright, recumbent), GER was no more frequent or severe among subjects with OSA vs. those without OSA. Subjects with idiopathic pulmonary fibrosis (IPF) had an odds of GER nearly seven-fold greater than subjects with other forms of fILD (odds ratio=6.84, 95% confidence interval 1.36–34.43, p=0.02). For the entire cohort and the subgroup with IPF, there was no correlation between pulmonary physiology and GER.
Conclusions
In fILD, OSA does not appear to promote GER. Research is needed to determine if compensatory mechanisms emanating from the crural diaphragm prevent GER in fILD patients with OSA and to sort out whether GER has a role in the pathogenesis of certain forms of fILD.
doi:10.1016/j.rmed.2012.03.014
PMCID: PMC3362045  PMID: 22521226
19.  FEV1 over time in patients with connective tissue disease-related bronchiolitis 
Respiratory medicine  2013;107(6):883-889.
Summary
Background
Fibrosis or inflammation of the bronchioles is a well-known manifestation of connective tissue disease (CTD). However, the natural history of CTD-related bronchiolitis is largely unknown.
Methods
We analyzed consecutive patients evaluated at National Jewish Health (Denver, CO) from 1998 to 2008 with CTD and surgical lung biopsy-confirmed bronchiolitis. Linear mixed effects models were used to estimate the longitudinal postbronchodilator FEV1 %predicted (%pred) course and differences between subjects with or without constrictive bronchiolitis (CB).
Results
Of 28 subjects with a mean age of 53 ± 9 years, fourteen (50%) had CB. The most common CTD diagnosis was rheumatoid arthritis (n = 14; 50%). There were no significant differences in demographics, smoking status, underlying CTD diagnoses, 6-min walk distance, dyspnea score or drug therapy between subjects with CB and those with cellular bronchiolitis. Three subjects with CB (11%) and four with cellular bronchiolitis (14%) died. Compared with subjects with CB, those with cellular bronchiolitis had higher mean FEV1 %pred at all times. There were no significant differences in FEV1 %pred slope within- or between-groups (CB vs. cellular bronchiolitis) preceding surgical lung biopsy or afterward.
Conclusion
Subjects with CTD-related CB had lower FEV1 %pred values than those with CTD-related cellular bronchiolitis at all time points, but FEV1 %pred remained stable over time in both groups regardless of therapy received.
doi:10.1016/j.rmed.2013.02.019
PMCID: PMC3697096  PMID: 23582575
Pulmonary function testing; Autoimmune disease; Obliterative bronchiolitis
20.  Six-Month Dietary Changes in Ethnically Diverse, Obese Adolescents Participating in a Multidisciplinary Weight Management Program 
Clinical pediatrics  2011;50(5):408-416.
This study’s objective was to examine dietary and metabolic changes in obese adolescents who completed 6-months of participation in an outpatient multidisciplinary weight management program (N=67). Participants (75% African American, 66% female, M age=13.7) completed 24-hour dietary recalls and underwent measurement of anthropometrics and fasting blood lipid parameters at baseline and after 6 months of participation. General linear models suggested that participants significantly reduced total energy, total fat, saturated fat, carbohydrate, sodium, and sugar intakes, and increased fiber and fruit and vegetable intake (P<0.05). Gender stratified models showed differences in fruit/vegetable intake, % calories from fat, sodium and dietary cholesterol intakes by gender. Significant improvements in body mass index percentile and lipid profiles were also found, lending objective support to the dietary changes participants made. Findings suggest that participation in this multidisciplinary treatment helped participants make behaviorally based dietary changes, which were associated with improved dietary intakes and health status.
doi:10.1177/0009922810393497
PMCID: PMC3683394  PMID: 21224253
diet; weight management; adolescents; obesity
21.  A peroxisome proliferator-activated receptor-δ agonist provides neuroprotection in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson’s disease 
Neuroscience  2013;240(100):191-203.
Highlights
•We investigate the role of PPARδ in a model of Parkinson’s disease.•PPARδ is upregulated after the neurotoxin MPTP.•PPARδ antagonism enhances MPP+ toxicity which is reversible by PPARδ agonism.•PPARδ agonism protects against MPTP-toxicity.
Peroxisome proliferator-activated receptor (PPAR)-γ and PPARα have shown neuroprotective effects in models of Parkinson’s disease (PD). The role of the third, more ubiquitous isoform PPARδ has not been fully explored. This study investigated the role of PPARδ in PD using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to model the dopaminergic neurodegeneration of PD. In vitro administration of the PPARδ antagonist GSK0660 (1 μM) increased the detrimental effect of 1-methyl-4-phenylpyridinium iodide (MPP+) on cell viability, which was reversed by co-treatment with agonist GW0742 (1 μM). GW0742 alone did not affect MPP+ toxicity. PPARδ was expressed in the nucleus of dopaminergic neurons and in astrocytes. Striatal PPARδ levels were increased (over two-fold) immediately after MPTP treatment (30 mg/kg for 5 consecutive days) compared to saline-treated mice. PPARδ heterozygous mice were not protected against MPTP toxicity. Intra-striatal infusion of GW0742 (84 μg/day) reduced the MPTP-induced loss of dopaminergic neurons (5036 ± 195) when compared to vehicle-infused mice (3953 ± 460). These results indicate that agonism of PPARδ provides protection against MPTP toxicity, in agreement with the effects of other PPAR agonists.
doi:10.1016/j.neuroscience.2013.02.058
PMCID: PMC3661980  PMID: 23500098
DMEM, Dulbecco’s Modified Eagle Medium; DMSO, dimethyl sulfoxide; DPBS, Dulbecco’s phosphate-buffered saline; EDTA, ethylenediaminetetraacetic acid; FCS, foetal calf serum; GFAP, glial fibrillary acid protein; IL, interleukin; LDH, lactate dehydrogenase; MAC-1, macrophage antigen complex-1; MPP+, 1-methyl-4-phenylpyridinium iodide; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; MTT, 3-(4,5-dimethylthizol-2-yl)-2,5-diphenyltetrazolium bromide; PBS, phosphate-buffered saline; PD, Parkinson’s disease; PFA, paraformaldehyde; PPAR, peroxisome proliferator-activated receptor; TH, tyrosine hydroxylase; TNFα, tumour necrosis factor-α; MPP+; neurodegeneration; neuroinflammation; SH-SY5Y; MPTP; PPAR delta
22.  Deriving Measures of Intensive Care Unit Antimicrobial Use from Computerized Pharmacy Data: Methods, Validation and Overcoming Barriers 
Objective
To outline methods for deriving and validating intensive care unit (ICU) antimicrobial utilization (AU) measures from computerized data and to describe programming problems that emerged.
Design
Retrospective evaluation of computerized pharmacy and administrative data.
Setting
ICUs from four academic medical centers over 36 months.
Interventions
Investigators separately developed and validated programming code to report AU measures in selected ICUs. Antibacterial and antifungal drugs for systemic administration were categorized and expressed as antimicrobial days (each day that each antimicrobial drug was given to each patient) and patient-days on antimicrobials (each day that any antimicrobial drug was given to each patient). Monthly rates were compiled and analyzed centrally with ICU patient-days as the denominator. Results were validated against data collected from manual medical record review. Frequent discussion among investigators aided identification and correction of programming problems.
Results
AU data were successfully programmed though a reiterative process of computer code revision. After identifying and resolving major programming errors, comparison of computerized patient-level data with data collected by manual medical record review revealed discrepancies in antimicrobial days and patient-days on antimicrobials ranging from <1% to 17.7%. The hospital for which numerator data were derived from electronic medication administration records had the least discrepant results.
Conclusions
Computerized AU measures can be derived feasibly, but threats to validity must be sought and corrected. The magnitude of discrepancies between computerized AU data and a gold standard based on manual chart review varies, with electronic medication administration records providing maximal accuracy.
doi:10.1086/659760
PMCID: PMC3678980  PMID: 21515978
23.  Mycophenolate Mofetil Improves Lung Function in Connective Tissue Disease-associated Interstitial Lung Disease 
The Journal of rheumatology  2013;40(5):640-646.
Objective
Small series suggest mycophenolate mofetil (MMF) is well tolerated and may be an effective therapy for connective tissue disease-associated interstitial lung disease (CTD-ILD). We examined the tolerability and longitudinal changes in pulmonary physiology in a large and diverse cohort of patients with CTD-ILD treated with MMF.
Methods
We identified consecutive patients evaluated at our center between January 2008 and January 2011 and prescribed MMF for CTD-ILD. We assessed safety and tolerability of MMF and used longitudinal data analyses to examine changes in pulmonary physiology over time, before and after initiation of MMF.
Results
We identified 125 subjects treated with MMF for a median 897 days. MMF was discontinued in 13 subjects. MMF was associated with significant improvements in estimated percentage of predicted forced vital capacity (FVC%) from MMF initiation to 52, 104, and 156 weeks (4.9% ± 1.9%, p = 0.01; 6.1% ± 1.8%, p = 0.0008; and 7.3% ± 2.6%, p = 0.004, respectively); and in estimated percentage predicted diffusing capacity (DLCO%) from MMF initiation to 52 and 104 weeks (6.3% ± 2.8%, p = 0.02; 7.1% ± 2.8%, p = 0.01). In the subgroup without usual interstitial pneumonia (UIP)-pattern injury, MMF significantly improved FVC% and DLCO%, and in the subgroup with UIP-pattern injury, MMF was associated with stability in FVC% and DLCO%.
Conclusion
In a large diverse cohort of CTD-ILD, MMF was well tolerated and had a low rate of discontinuation. Treatment with MMF was associated with either stable or improved pulmonary physiology over a median 2.5 years of followup. MMF appears to be a promising therapy for the spectrum of CTD-ILD.
doi:10.3899/jrheum.121043
PMCID: PMC3676865  PMID: 23457378
INTERSTITIAL LUNG DISEASE; CONNECTIVE TISSUE DISEASE; MYCOPHENOLATE MOFETIL
24.  Ethnic and racial differences in the presence of idiopathic pulmonary fibrosis at death 
Respiratory Medicine  2012;106(4):588-593.
Background
In studies of idiopathic pulmonary fibrosis (IPF), whites make up the vast majority of subjects. Whether ethnic/racial differences in idiopathic pulmonary fibrosis occur in the general population is unknown.
Methods
To compare the presence of IPF between ethnic/racial groups of U.S. decedents from 1989-2007 by using the National Center for Health Statistics database.
Results
There were 251,058 U.S. decedents with IPF; 87.2% were non-Hispanic whites (White), 5.1% were non-Hispanic African-American (Black), 5.4% were Hispanic, and 2.2% were from other ethnic/racial groups (Other). Whites coded with IPF died older than those in the other groups (77.9 years vs. 72.1 years for Blacks, 75.3 years for Hispanics, and 75.6 years for Others; p<0.0001 for all pairwise comparisons). When controlling for age and for sex, compared with Whites, both Hispanics and Others were more likely to be coded with IPF (OR=1.47, 95% CI 1.44-1.49, p<0.0001 and OR=1.29, 95% CI 1.26-1.36, p<0.0001 respectively), while Blacks were significantly less likely to be coded with IPF (OR=0.48, 95% CI 0.47-0.49, p<0.0001). Among decedents with IPF, Hispanics were more likely, and Blacks were less likely, than Whites to die from IPF (OR=1.24, 95% CI 1.20-1.29, p<0.0001 and OR=0.91, 95% CI 0.87-0.94, p<0.0001).
Conclusion
From 1989-2007, Black decedents were less—and Hispanics were more— likely than Whites to die of/with IPF. Research is needed to determine if genetic differences between ethnic/racial groups explain these findings.
doi:10.1016/j.rmed.2012.01.002
PMCID: PMC3294009  PMID: 22296740
Idiopathic pulmonary fibrosis; mortality; race; epidemiology
25.  Exploiting inflammation for therapeutic gain in pancreatic cancer 
British Journal of Cancer  2013;108(5):997-1003.
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy associated with <5% 5-year survival, in which standard chemotherapeutics have limited benefit. The disease is associated with significant intra- and peritumoral inflammation and failure of protective immunosurveillance. Indeed, inflammatory signals are implicated in both tumour initiation and tumour progression. The major pathways regulating PDAC-associated inflammation are now being explored. Activation of leukocytes, and upregulation of cytokine and chemokine signalling pathways, both have been shown to modulate PDAC progression. Therefore, targeting inflammatory pathways may be of benefit as part of a multi-target approach to PDAC therapy. This review explores the pathways known to modulate inflammation at different stages of tumour development, drawing conclusions on their potential as therapeutic targets in PDAC.
doi:10.1038/bjc.2013.24
PMCID: PMC3619061  PMID: 23385734
pancreatic cancer; inflammation; therapy

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