Symptoms and patient factors associated with diagnostic intervals for pancreatic cancer (SYMPTOM pancreatic study): a prospective cohort study

This is the final version. Available on open access from Elsevier via the DOI in this recordBackground Pancreatic cancer is the tenth most common cancer in the UK; however, outcomes are poor, in part due to late diagnosis. We aimed to identify symptoms and other clinical and sociodemographic factors associated with pancreatic cancer diagnosis and diagnostic intervals. Methods We did this prospective cohort study at seven hospitals in two regions in England. We recruited participants aged 40 years or older who were referred for suspicion of pancreatic cancer. Data were collected by use of a patient questionnaire and primary care and hospital records. Descriptive and regression analyses were done to examine associations between symptoms and patient factors with the total diagnostic interval (time from onset of the first symptom to the date of diagnosis), comprising patient interval (time from first symptom to first presentation) and health system interval (time from first presentation to diagnosis). Findings We recruited 391 participants between Jan 1, 2011, and Dec 31, 2014 (24% response rate). 119 (30%) participants were diagnosed with pancreatic cancer (41 [34%] had metastatic disease), 47 (12%) with other cancers, and 225 (58%) with no cancer. 212 (54%) patients had multiple first symptoms whereas 161 (41%) patients had a solitary first symptom. In this referred population, no initial symptoms were reported more frequently by patients with cancer than by those with no cancer. Several subsequent symptoms predicted pancreatic cancer: jaundice (51 [49%] of 105 patients with pancreatic cancer vs 25 [12%] of 211 patients with no cancer; p<0·0001), fatigue (48/95 [51%] vs 40/155 [26%]; p=0·0001), change in bowel habit (36/87 [41%] vs 28/175 [16%]; p<0·0001), weight loss (55/100 [55%] vs 41/184 [22%]; p<0·0001), and decreased appetite (41/86 [48%] vs 41/156 [26%]; p=0·0011). There was no difference in any interval between patients with pancreatic cancer and those with no cancer (total diagnostic interval: median 117 days [IQR 57–234] vs 131 days [IQR 66–284]; p=0·32; patient interval 18 days [0–37] vs 15 days [1–62]; p=0·22; health system interval 76 days [28–161] vs 79 days [30–156]; p=0·68). Total diagnostic intervals were shorter when jaundice (hazard ratio [HR] 1·38, 95% CI 1·07–1·78; p=0·013) and decreased appetite (1·42, 1·11–1·82; p=0·0058) were reported as symptoms, and longer in patients presenting with indigestion (0·71, 0·56–0·89; p=0·0033), back pain (0·77, 0·59–0·99; p=0·040), diabetes (0·71, 0·52–0·97; p=0·029), and self-reported anxiety or depression, or both (0·67, 0·49–0·91; p=0·011). Health system intervals were likewise longer with indigestion (0·74, 0·58–0·95; p=0·0018), back pain (0·76, 0·58–0·99; p=0·044), diabetes (0·63, 0·45–0·89; p=0·0082), and self-reported anxiety or depression, or both (0·63, 0·46–0·88; p=0·0064), but were shorter with male sex (1·41, 1·1–1·81; p=0·0072) and decreased appetite (1·56, 1·19–2·06; p=0·0015). Weight loss was associated with longer patient intervals (HR 0·69, 95% CI 0·54–0·89; p=0·0047). Interpretation Although we identified no initial symptoms that differentiated people diagnosed with pancreatic cancer from those without pancreatic cancer, key additional symptoms might signal the disease. Health-care professionals should be vigilant to the possibility of pancreatic cancer in patients with evolving gastrointestinal and systemic symptoms, particularly in those with diabetes or mental health comorbidities. Funding National Institute for Health Research and Pancreatic Cancer Action.National Institute for Health Research (NIHR

Reassuring and managing patients with concerns about swine flu: Qualitative interviews with callers to NHS Direct

<p>Abstract</p> <p>Background</p> <p>During the early stages of the 2009 swine flu (influenza H1N1) outbreak, the large majority of patients who contacted the health services about the illness did not have it. In the UK, the NHS Direct telephone service was used by many of these patients. We used qualitative interviews to identify the main reasons why people approached NHS Direct with concerns about swine flu and to identify aspects of their contact which were reassuring, using a framework approach.</p> <p>Methods</p> <p>33 patients participated in semi-structured interviews. All patients had telephoned NHS Direct between 11 and 14 May with concerns about swine flu and had been assessed as being unlikely to have the illness.</p> <p>Results</p> <p>Reasons for seeking advice about swine flu included: the presence of unexpectedly severe flu-like symptoms; uncertainties about how one can catch swine flu; concern about giving it to others; pressure from friends or employers; and seeking 'peace of mind.' Most participants found speaking to NHS Direct reassuring or useful. Helpful aspects included: having swine flu ruled out; receiving an alternative explanation for symptoms; clarification on how swine flu is transmitted; and the perceived credibility of NHS Direct. No-one reported anything that had increased their anxiety and only one participant subsequently sought additional advice about swine flu from elsewhere.</p> <p>Conclusions</p> <p>Future major incidents involving other forms of chemical, biological or radiological hazards may also cause large numbers of unexposed people to seek health advice. Our data suggest that providing telephone triage and information is helpful in such instances, particularly where advice can be given via a trusted, pre-existing service.</p

Subaru FOCAS Spectroscopic Observations of High-Redshift Supernovae

We present spectra of high-redshift supernovae (SNe) that were taken with the Subaru low resolution optical spectrograph, FOCAS. These SNe were found in SN surveys with Suprime-Cam on Subaru, the CFH12k camera on the Canada-France-Hawaii Telescope (CFHT), and the Advanced Camera for Surveys (ACS) on the Hubble Space Telescope (HST). These SN surveys specifically targeted z>1 Type Ia supernovae (SNe Ia). From the spectra of 39 candidates, we obtain redshifts for 32 candidates and spectroscopically identify 7 active candidates as probable SNe Ia, including one at z=1.35, which is the most distant SN Ia to be spectroscopically confirmed with a ground-based telescope. An additional 4 candidates are identified as likely SNe Ia from the spectrophotometric properties of their host galaxies. Seven candidates are not SNe Ia, either being SNe of another type or active galactic nuclei. When SNe Ia are observed within a week of maximum light, we find that we can spectroscopically identify most of them up to z=1.1. Beyond this redshift, very few candidates were spectroscopically identified as SNe Ia. The current generation of super red-sensitive, fringe-free CCDs will push this redshift limit higher.Comment: 19 pages, 26 figures. PASJ in press. see http://www.supernova.lbl.gov/2009ClusterSurvey/ for additional information pertaining to the HST Cluster SN Surve

Neonatal-onset multisystem inflammatory disease responsive to interleukin-1 beta inhibition

BACKGROUND:Neonatal-onset multisystem inflammatory disease is characterized by fever, urticarial rash, aseptic meningitis, deforming arthropathy, hearing loss, and mental retardation. Many patients have mutations in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene, encoding cryopyrin, a protein that regulates inflammation.METHODS:We selected 18 patients with neonatal-onset multisystem inflammatory disease (12 with identifiable CIAS1 mutations) to receive anakinra, an interleukin-1-receptor antagonist (1 to 2 mg per kilogram of body weight per day subcutaneously). In 11 patients, anakinra was withdrawn at three months until a flare occurred. The primary end points included changes in scores in a daily diary of symptoms, serum levels of amyloid A and C-reactive protein, and the erythrocyte sedimentation rate from baseline to month 3 and from month 3 until a disease flare.RESULTS:All 18 patients had a rapid response to anakinra, with disappearance of rash. Diary scores improved (P<0.001) and serum amyloid A (from a median of 174 mg to 8 mg per liter), C-reactive protein (from a median of 5.29 mg to 0.34 mg per deciliter), and the erythrocyte sedimentation rate decreased at month 3 (all P<0.001), and remained low at month 6. Magnetic resonance imaging showed improvement in cochlear and leptomeningeal lesions as compared with baseline. Withdrawal of anakinra uniformly resulted in relapse within days; retreatment led to rapid improvement. There were no drug-related serious adverse events.CONCLUSIONS:Daily injections of anakinra markedly improved clinical and laboratory manifestations in patients with neonatal-onset multisystem inflammatory disease, with or without CIAS1 mutations

A global method for coupling transport with chemistry in heterogeneous porous media

Modeling reactive transport in porous media, using a local chemical equilibrium assumption, leads to a system of advection-diffusion PDE's coupled with algebraic equations. When solving this coupled system, the algebraic equations have to be solved at each grid point for each chemical species and at each time step. This leads to a coupled non-linear system. In this paper a global solution approach that enables to keep the software codes for transport and chemistry distinct is proposed. The method applies the Newton-Krylov framework to the formulation for reactive transport used in operator splitting. The method is formulated in terms of total mobile and total fixed concentrations and uses the chemical solver as a black box, as it only requires that on be able to solve chemical equilibrium problems (and compute derivatives), without having to know the solution method. An additional advantage of the Newton-Krylov method is that the Jacobian is only needed as an operator in a Jacobian matrix times vector product. The proposed method is tested on the MoMaS reactive transport benchmark.Comment: Computational Geosciences (2009) http://www.springerlink.com/content/933p55085742m203/?p=db14bb8c399b49979ba8389a3cae1b0f&pi=1

Complementary classifications of aeolian dunes based on morphology, dynamics, and fluid mechanics

Dunes form where winds blow over a bed of mobile sediment grains – conditions that are common in our solar system. On Earth, dunes abound in arid continental interiors and along sandy coastlines. Dune fields have also been recognized on Venus, Mars, Saturn's moon Titan, and Pluto. In response to the different boundary conditions and other environmental forcings, dunes adopt a rich diversity of shapes, sizes, and behaviors. Thus, people around the globe and over centuries have developed a rich vocabulary to describe dunes and their complexity. As a result, existing dune nomenclature often includes redundant terms with differing definitions across scientific communities. Previous studies have endeavored to link dune shape to environmental forcing, usually by means of correlation. Although instructive, correlation-based classifications can be misleading if not based on an underlying mechanics and if dune morphogenetic classes are not uniquely defined. Here, we synthesize existing dune terminology and use the last two decades of research on dune morphodynamics to propose three complementary dune classification schemes based on: (1) descriptive dune gemorphology, (2) morphodynamic processes, and (3) fluid mechanics and physics of sediment transport. The first classification relates dune types to geomorphic setting, presence or absence of vegetation or obstacles, and dune shape (including planform shape, and cross-sectional symmetry or asymmetry). Dune classes can be further subdivided where the direction of sand transport is known independently. The second classification relates dune types and shapes to bed properties (sand-covered vs partially starved bed) and wind forcing (directional variability or the relative strengths and directions of wind modes) that together influence dune dynamics (growth, migration, elongation) and select the dominant processes by which dunes are shaped and oriented relative to the resultant transport direction. The third classification relates, for different planetary environments, the range of possible dune sizes, from minimum to maximum wavelength, to flow regime (rough or smooth) and response of sediment transport, which influence the coupling between sand bed topography, fluid flow, and sediment transport. These characteristic lengths are useful scales for comparative geomorphology. The three classification schemes provide complementary information. Together, they form a unified framework for geomorphologists, sedimentologists, geographers, physicists, and others to describe windblown sand dunes on Earth and beyond through their shape, dynamics, and size as a response to winds and boundary conditions

Cellular responses of Candida albicans to phagocytosis and the extracellular activities of neutrophils are critical to counteract carbohydrate starvation, oxidative and nitrosative stress

Acknowledgments We thank Alexander Johnson (yhb1D/D), Karl Kuchler (sodD/D mutants), Janet Quinn (hog1D/D, hog1/cap1D/D, trx1D/D) and Peter Staib (ssu1D/D) for providing mutant strains. We acknowledge helpful discussions with our colleagues from the Microbial Pathogenicity Mechanisms Department, Fungal Septomics and the Microbial Biochemistry and Physiology Research Group at the Hans Kno¨ll Institute (HKI), specially Ilse D. Jacobsen, Duncan Wilson, Sascha Brunke, Lydia Kasper, Franziska Gerwien, Sea´na Duggan, Katrin Haupt, Kerstin Hu¨nniger, and Matthias Brock, as well as from our partners in the FINSysB Network. Author Contributions Conceived and designed the experiments: PM HW IMB AJPB OK BH. Performed the experiments: PM CD HW. Analyzed the data: PM HW IMB AJPB OK BH. Wrote the paper: PM HW OK AJPB BH.Peer reviewedPublisher PD

An examination of factors influencing the choice of therapy for patients with coronary artery disease

BACKGROUND: A diverse range of factors influence clinicians' decisions regarding the allocation of patients to different treatments for coronary artery disease in routine cardiology clinics. These include demographic measures, risk factors, co-morbidities, measures of objective cardiac disease, symptom reports and functional limitations. This study examined which of these factors differentiated patients receiving angioplasty from medication; bypass surgery from medication; and bypass surgery from angioplasty. METHODS: Univariate and multivariate logistic regression analyses were conducted on patient data from 214 coronary artery disease patients who at the time of recruitment had been received a clinical assessment and were reviewed by their cardiologist in order to determine the form of treatment they were to undergo: 70 would receive/continue medication, 71 were to undergo angioplasty and 73 were to undergo bypass surgery. RESULTS: Analyses differentiating patients receiving angioplasty from medication produced 9 significant univariate predictors, of which 5 were also multivariately significant (left anterior descending artery disease, previous coronary interventions, age, hypertension and frequency of angina). The analyses differentiating patients receiving surgery from angioplasty produced 12 significant univariate predictors, of which 4 were multivariately significant (limitations in mobility range, circumflex artery disease, previous coronary interventions and educational level). The analyses differentiating patients receiving surgery from medication produced 14 significant univariate predictors, of which 4 were multivariately significant (left anterior descending artery disease, previous cerebral events, limitations in mobility range and circumflex artery disease). CONCLUSION: Variables emphasised in clinical guidelines are clearly involved in coronary artery disease treatment decisions. However, variables beyond these may also be important factors when therapy decisions are undertaken thus their roles require further investigation

What do we know about emotional labour in nursing? A narrative review

Nurses have to manage their emotions and the expression of emotion to perform best care, and their behaviours pass through emotional labour (EL). However, EL seems to be an under-appreciated aspect of caring work and there is no synthetic portrait of literature about EL in the nursing profession. This review was conducted to synthesise and to critically analyse the literature in the nursing field related to EL. Twenty-seven papers were included and analysed with a narrative approach, where two main themes were found: EL strategies and EL antecedents and consequences. Hence, EL is a multidimensional, complex concept and it represents a nursing competence to provide the best care. Moreover, nurses have a high awareness of EL as a professional competence, which is a fundamental element to balance engagement with an appropriate degree of detachment to accomplish tasks for best practice, and to provide high-quality patient care