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.
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).
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.
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.
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.
Anti-cyclic citrullinated peptide; Rheumatoid arthritis; Interstitial lung disease; Lung diseases
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.
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.
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.
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.
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.
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).
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.
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.
Pulmonary function testing; Autoimmune disease; Obliterative bronchiolitis
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.
diet; weight management; adolescents; obesity
•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.
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
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.
Retrospective evaluation of computerized pharmacy and administrative data.
ICUs from four academic medical centers over 36 months.
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.
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.
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.
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.
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.
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%.
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.
INTERSTITIAL LUNG DISEASE; CONNECTIVE TISSUE DISEASE; MYCOPHENOLATE MOFETIL
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.
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.
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).
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.
Idiopathic pulmonary fibrosis; mortality; race; epidemiology
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.
pancreatic cancer; inflammation; therapy
Salmonids are popular sport fishes, and as such have been subjected to widespread stocking throughout western North America. Historically, stocking was done with little regard for genetic variation among populations and has resulted in genetic mixing among species and subspecies in many areas, thus putting the genetic integrity of native salmonid populations at risk and creating a need to assess the genetic constitution of native salmonid populations. Cutthroat trout is a salmonid species with pronounced geographic structure (there are 10 extant subspecies) and a recent history of hybridization with introduced rainbow trout in many populations. Genetic admixture has also occurred among cutthroat trout subspecies in areas where introductions have brought two or more subspecies into contact. Consequently, management agencies have increased their efforts to evaluate the genetic composition of cutthroat trout populations to identify populations that remain uncompromised and manage them accordingly, but additional genetic markers are needed to do so effectively. Here we used genome reduction, MID-barcoding, and 454-pyrosequencing to discover single nucleotide polymorphisms that differentiate cutthroat trout subspecies and can be used as a rapid, cost-effective method to characterize the genetic composition of cutthroat trout populations.
Thirty cutthroat and six rainbow trout individuals were subjected to genome reduction and next-generation sequencing. A total of 1,499,670 reads averaging 379 base pairs in length were generated by 454-pyrosequencing, resulting in 569,060,077 total base pairs sequenced. A total of 43,558 putative SNPs were identified, and of those, 125 SNP primers were developed that successfully amplified 96 cutthroat trout and rainbow trout individuals. These SNP loci were able to differentiate most cutthroat trout subspecies using distance methods and Structure analyses.
Genomic and bioinformatic protocols were successfully implemented to identify 125 nuclear SNPs that are capable of differentiating most subspecies of cutthroat trout from one another. The ability to use this suite of SNPs to identify individuals of unknown genetic background to subspecies can be a valuable tool for management agencies in their efforts to evaluate the genetic structure of cutthroat trout populations prior to constructing and implementing conservation plans.
Conservation genetics; Genetic admixture; Hybridization; KASPar; Oncorhynchus clarkii; Oncorhynchus mykiss; Population genomics; SNP; Rainbow trout
Fluid and exocrine secretion of mucins by salivary mucous glands is regulated predominantly by parasympathetic activation of muscarinic receptors. A direct role for subsequent putative signaling steps, phospholipase C (PLC), increased intracellular calcium ([Ca2+]i), and isoforms of protein kinase C (PKC) in mediating muscarinic exocrine secretion has not been elucidated, and these are potential therapeutic targets to enhance mucin secretion in hyposalivary patients. We found that muscarinic-induced mucin secretion by rat sublingual tubulo-acini was dependent upon PLC activation and the subsequent increase in [Ca2+]i, and further identified a transient PKC-independent component of secretion dependent upon Ca2+ release from intracellular stores, whereas sustained secretion required entry of extracellular Ca2+. Interactions among carbachol, PKC inhibitors, phorbol 12-myristate 13-acetate, and thapsigargin to modulate [Ca2+]i implicated conventional PKC isoforms in mediating sustained secretion. With increasing times during carbachol perfusion of glands, in situ, PKC-α redistributed across glandular membrane compartments and underwent a rapid and persistent accumulation near the luminal borders of mucous cells. PKC-β1 displayed transient localization near luminal borders, whereas the novel PKCs, PKC-δ or PKC-ϵ, displayed little or no redistribution in mucous cells. Collective results implicate synergistic interactions between diacylglycerol (DAG) and increasing [Ca2+]i levels to activate cPKCs in mediating sustained muscarinic-induced secretion.
salivary glands; muscarinic cholinergic receptors; protein kinase C; mucous cells; exocrine secretion; stimulus-secretion coupling
The enormous amount of data being collected by electronic medical records (EMR) has found additional value when integrated and stored in data warehouses. The enterprise data warehouse (EDW) allows all data from an organization with numerous inpatient and outpatient facilities to be integrated and analyzed. We have found the EDW at Intermountain Healthcare to not only be an essential tool for management and strategic decision making, but also for patient specific clinical decision support. This paper presents the structure and two case studies of a framework that has provided us the ability to create a number of decision support applications that are dependent on the integration of previous enterprise-wide data in addition to a patient’s current information in the EMR.
Neisseria are obligate human pathogens causing bacterial meningitis, septicemia, and gonorrhea. Neisseria require iron for survival and can extract it directly from human transferrin for transport across the outer membrane. The transport system consists of TbpA, an integral outer membrane protein, and TbpB, a co-receptor attached to the cell surface; both proteins are potentially important vaccine and therapeutic targets. Two key questions driving Neisseria research are: 1) how human transferrin is specifically targeted, and 2) how the bacteria liberate iron from transferrin at neutral pH. To address them, we solved crystal structures of the TbpA-transferrin complex and of the corresponding co-receptor TbpB. We characterized the TbpB-transferrin complex by small angle X-ray scattering and the TbpA-TbpB-transferrin complex by electron microscopy. Collectively, our studies provide a rational basis for the specificity of TbpA for human transferrin, show how TbpA promotes iron release from transferrin, and elucidate how TbpB facilitates this process.
A common misperception of quantum gravity is that it requires accessing energies up to the Planck scale of 1019 GeV, which is unattainable from any conceivable particle collider. Thanks to the development of ultra-high intensity optical lasers, very large accelerations can be now the reached at their focal spot, thus mimicking, by virtue of the equivalence principle, a non Minkowski space-time. Here we derive a semiclassical extension of quantum mechanics that applies to different metrics, but under the assumption of weak gravity. We use our results to show that Thomson scattering of photons by uniformly accelerated electrons predicts an observable effect depending upon acceleration and local metric. In the laboratory frame, a broadening of the Thomson scattered x ray light from a fourth generation light source can be used to detect the modification of the metric associated to electrons accelerated in the field of a high power optical laser.
To understand how the source of information affects different adverse event (AE) surveillance methods.
Retrospective analysis of inpatient adverse drug events (ADEs) and hospital-associated infections (HAIs) detected by either a computerized surveillance system (CSS) or manual chart review (MCR).
Descriptive analysis of events detected using the two methods by type of AE, type of information about the AE, and sources of the information.
CSS detected more HAIs than MCR (92% vs 34%); however, a similar number of ADEs was detected by both systems (52% vs 51%). The agreement between systems was greater for HAIs than ADEs (26% vs 3%). The CSS missed events that did not have information in coded format or that were described only in physician narratives. The MCR detected events missed by CSS using information in physician narratives. Discharge summaries were more likely to contain information about AEs than any other type of physician narrative, followed by emergency department reports for HAIs and general consult notes for ADEs. Some ADEs found by MCR were detected by CSS but not verified by a clinician.
Inability to distinguish between CSS false positives and suspected AEs for cases in which the clinician did not document their assessment in the CSS.
The effect that information source has on different surveillance methods depends on the type of AE. Integrating information from physician narratives with CSS using natural language processing would improve the detection of ADEs more than HAIs.
Electronic surveillance; adverse drug event surveillance; hospital-associated infection surveillance; healthcare quality
Dentistry in Australia combines business and health care service, that is, the majority of patients pay money for tangible dental procedures such as fluoride applications, dental radiographs, dental fillings, crowns, and dentures among others. There is evidence that patients question dentists’ behaviours and attitudes during a dental visit when those highly technical procedures are performed. However, little is known about how patients’ experience dental care as a whole. This paper illustrates the findings from a qualitative study recently undertaken in general dental practice in Australia. It focuses on patients’ experiences of dental care, particularly on the relationship between patients and dentists during the provision of preventive care and advice in general dental practices.
Seventeen patients were interviewed. Data analysis consisted of transcript coding, detailed memo writing, and data interpretation.
Patients described their experiences when visiting dental practices with and without a structured preventive approach in place, together with the historical, biological, financial, psychosocial and habitual dimensions of their experience. Potential barriers that could hinder preventive activities as well as facilitators for prevention were also described. The offer of preventive dental care and advice was an amazing revelation for this group of patients as they realized that dentists could practice dentistry without having to “drill and fill” their teeth. All patients, regardless of the practice they came from or their level of clinical risk of developing dental caries, valued having a caring dentist who respected them and listened to their concerns without “blaming” them for their oral health status. These patients complied with and supported the preventive care options because they were being “treated as a person not as a patient” by their dentists. Patients valued dentists who made them aware of existing preventive options, educated them about how to maintain a healthy mouth and teeth, and supported and reassured them frequently during visits.
Patients valued having a supportive and caring dentist and a dedicated dental team. The experience of having a dedicated, supportive and caring dentist helped patients to take control of their own oral health. These dentists and dental teams produced profound changes in not just the oral health care routines of patients, but in the way patients thought about their own oral health and the role of dental professionals.
Qualitative research; Dentist-patient relationship; Prevention