Digoxin treatment is associated with an increased incidence of breast cancer: a population-based case-control study

INTRODUCTION. Laboratory and epidemiologic studies have suggested a modifying effect of cardiac glycosides (for example, digoxin and digitoxin) on cancer risk. We explored the association between digoxin treatment and invasive breast cancer incidence among postmenopausal Danish women. METHODS. We used Danish registries to identify 5,565 postmenopausal women diagnosed with incident invasive breast carcinoma between 1 January 1991 and 31 December 2007, and 55,650 matched population controls. Cardiac glycoside prescriptions were ascertained from county prescription registries. All subjects had at least 2 years of recorded prescription drug and medical history data. We estimated the odds ratio associating digoxin use with breast cancer in conditional logistic regression models adjusted for age, county of residence, and use of anticoagulants, non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, and hormone replacement therapy. We also explored the impact of confounding by indication and detection bias. RESULTS. Digoxin was the sole cardiac glycoside prescribed to subjects during the study period. There were 324 breast cancer cases (5.8%) and 2,546 controls (4.6%) with a history of digoxin use at least 1 year before their index date (adjusted odds ratio (OR): 1.30; 95% confidence interval: 1.14 to 1.48). The breast cancer OR increased modestly with increasing duration of digoxin exposure (adjusted OR for 7 to 18 years of digoxin use: 1.39; 95% confidence interval: 1.10 to 1.74). The association was robust to adjustment for age, receipt of hormone replacement therapy, coprescribed drugs, and confounding by indication. A comparison of screening mammography rates between cases and controls showed no evidence of detection bias. CONCLUSIONS. Our results suggest that digoxin treatment increases the risk of invasive breast cancer among postmenopausal women.Congressionaly Directed Medical Research Programs (BC073012); Karen Elise Jensen Foundation; Western Danish Research Forum for Health Science

Microbiology and atmospheric processes: Biological, physical and chemical characterization of aerosol particles

The interest in bioaerosols has traditionally been linked to health hazards for humans, animals and plants. However, several components of bioaerosols exhibit physical properties of great significance for cloud processes, such as ice nucleation and cloud condensation. To gain a better understanding of their influence on climate, it is therefore important to determine the composition, concentration, seasonal fluctuation, regional diversity and evolution of bioaerosols. In this paper, we will review briefly the existing techniques for detection, quantification, physical and chemical analysis of biological particles, attempting to bridge physical, chemical and biological methods for analysis of biological particles and integrate them with aerosol sampling techniques. We will also explore some emerging spectroscopy techniques for bulk and single-particle analysis that have potential for in-situ physical and chemical analysis. Lastly, we will outline open questions and further desired capabilities (e. g., in-situ, sensitive, both broad and selective, on-line, time-resolved, rapid, versatile, cost-effective techniques) required prior to comprehensive understanding of chemical and physical characterization of bioaerosols

Evidence-based paramedic models of care to reduce unnecessary emergency department attendance – feasibility and safety

Background: As demand for Emergency Department (ED) services continues to exceed increases explained by population growth, strategies to reduce ED presentations are being explored. The concept of ambulance paramedics providing an alternative model of care to the current default ‘see and transport to ED’ has intuitive appeal and has been implemented in several locations around the world. The premise is that for certain noncritical ill patients, the Extended Care Paramedic (ECP) can either ‘see and treat’ or ‘see and refer’ to another primary or community care practitioner, rather than transport to hospital. However, there has been little rigorous investigation of which types of patients can be safely identified and managed in the community, or the impact of ECPs on ED attendance.Methods/Design: St John Ambulance Western Australia paramedics will indicate on the electronic patient care record (e-PCR) of patients attended in the Perth metropolitan area if they consider them to be suitable to be managed in the community. ‘Follow-up’ will examine these patients using ED data to determine the patient’s disposition from the ED. A clinical panel will then develop a protocol to identify those patients who can be safely managed in the community. Paramedics will then assess patients against the derived ECP protocols and identify those deemed suitable to ‘see and treat’ or ‘see and refer’. The ED disposition (and other clinical outcomes) of these ‘ECP protocol identified’ patients will enable us to assess whether it would have been appropriate to manage these patients in the community. We will also ‘track’ re-presentations to EDs within seven days of the initial presentation. This is a ‘virtual experiment’ with no direct involvement of patients or changes in clinical practice. A systems modelling approach will be used to assess the likely impact on ED crowding.Discussion: To date the efficacy, cost-effectiveness and safety of alternative community-based models of emergency care have not been rigorously investigated. This study will inform the development of ECP protocols through the identification of types of patient presentation that can be considered both safe and appropriate for paramedics to manage in the community

In vitro dissolution models for the prediction of in vivo performance of an oral mesoporous silica formulation

Drug release from mesoporous silica systems has been widely investigated in vitro using USP Type II (paddle) dissolution apparatus. However, it is not clear if the observed enhanced in vitro dissolution can forecast drug bioavailability in vivo. In this study, the ability of different in vitro dissolution models to predict in vivo oral bioavailability in a pig model was examined. The fenofibrate-loaded mesoporous silica formulation was compared directly to a commercial reference product, Lipantil Supra®. Three in vitro dissolution methods were considered; USP Type II (paddle) apparatus, USP Type IV (flow-through cell) apparatus and a USP IV Transfer model (incorporating a SGF to FaSSIF-V2 media transfer). In silico modelling, using a physiologically based pharmacokinetic modelling and simulation software package (Gastroplus™), to generate in vitro/in vivo relationships was also investigated. The study demonstrates that the in vitro dissolution performance of a mesoporous silica formulation varies depending on the dissolution apparatus utilised and experimental design. The findings show that the USP IV transfer model was the best predictor of in vivo bioavailability. The USP Type II (paddle) apparatus was not effective at forecasting in vivo behaviour. This observation is likely due to hydrodynamic differences between the two apparatus and the ability of the transfer model to better simulate gastrointestinal transit. The transfer model is advantageous in forecasting in vivo behaviour for formulations which promote drug supersaturation and as a result are prone to precipitation to a more energetically favourable, less soluble form. The USP IV transfer model could prove useful in future mesoporous silica formulation development. In silico modelling has the potential to assist in this process. However, further investigation is required to overcome the limitations of the model for solubility enhancing formulations

Which patients should be transported to the emergency department? A perpetual prehospital dilemma

Objective: To examine the ability of paramedics to identify patients who could be managed in the community and to identify predictors that could be used to accurately identify patients who should be transported to EDs. Methods: Lower acuity patients who were assessed by paramedics in the Perth metropolitan area in 2013 were studied. Paramedics prospectively indicated on the patient care record if they considered that the patient could be treated in the community. The paramedic decisions were compared with actual disposition from the ED (discharge and admission), and the occurrence of subsequent events (ambulance request, ED visit, admission and death) for discharged patients at the scene was investigated. Decision tree analysis was used to identify predictors that were associated with hospital admission. Results: In total, 57183 patients were transported to the ED, and 10204 patients were discharged at the scene by paramedics. Paramedics identified 2717 patients who could potentially be treated in the community among those who were transported to the ED. Of these, 1455 patients (53.6%) were admitted to hospital. For patients discharged at the scene, those who were indicated as suitable for community care were more likely to experience subsequent events than those who were not. The decision tree found that two predictors (age and aetiology) were associated with hospital admission. Overall discriminative power of the decision tree was poor; the area under the receiver operating characteristic curve was 0.686. Conclusion: Lower acuity patients who could be treated in the community were not accurately identified by paramedics. This process requires further evaluation. © 2016 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine

Transmission spectroscopy of the inflated exoplanet WASP-52b, and evidence for a bright region on the stellar surface

We have measured the transmission spectrum of the extremely inflated hot Jupiter WASP-52b using simultaneous photometric observations in Sloan Digital Sky Survey u΄, g΄ and a filter centred on the sodium doublet (Na i) with the ULTRACAM instrument mounted on the 4.2-m William Herschel Telescope. We find that Rayleigh scattering is not the dominant source of opacity within the planetary atmosphere and find a transmission spectrum more consistent with wavelength-independent opacity such as from clouds. We detect an in-transit anomaly that we attribute to the presence of stellar activity and find that this feature can be more simply modelled as a bright region on the stellar surface akin to solar faculae rather than spots. A spot model requires a significantly larger planet/star radius ratio than that found in previous studies. Our results highlight the precision that can be achieved by ground-based photometry with errors in the scaled planetary radii of less than one atmospheric scale height, comparable to Hubble Space Telescope observations

Boundedness, compactness and Schatten-class membership of weighted composition operators

The boundedness and compactness of weighted composition operators on the Hardy space ${\mathcal H}^2$ of the unit disc is analysed. Particular reference is made to the case when the self-map of the disc is an inner function. Schatten-class membership is also considered; as a result, stronger forms of the two main results of a recent paper of Gunatillake are derived. Finally, weighted composition operators on weighted Bergman spaces $\mathcal{A}^2 \alpha(\mathbb{D})$ are considered, and the results of Harper and Smith, linking their properties to those of Carleson embeddings, are extended to this situation.Comment: 12 page

Protracted venous infusion 5-fluorouracil in combination with subcutaneous interleukin-2 and alpha-interferon in patients with metastatic renal cell cancer: a phase II study

Our purpose was to assess the activity of alpha-interferon (IFN-α), interleukin-2 (IL-2) and 5 fluorouracil (5FU) administered by protracted venous infusion (PVI) as opposed to bolus injection. 55 patients with advanced renal cell cancer were treated as follows: IL-2 and IFN-α according to the schedule originally described by Atzpodien, with PVI 5FU 200 mg m–2 day–1 during weeks 5–9. 42 patients (76%) were of moderate or poor prognosis as defined by previous studies. The response rate by intention to treat was 31% (17 of 55, three complete response, 14 partial response; 95% CI = 19–45%) and in evaluable patients (completed one cycle, n = 42), it was 40% (95% CI = 26–57%). In addition, 24% (13 of 55) patients achieved disease stabilization. The overall median survival was 11 months with a 1-year survival of 45%. The median survival for evaluable patients was 18 months with 1- and 2-year survivals of 60% and 40% respectively. The median survival of responding patients was 31 months and the three patients achieving complete response remain progression-free at 14+, 18+ and 23+ months. Evaluable patients with poor prognostic features achieved a response rate of 54% and median survival of 18 months. Toxicity was significant yet manageable with 12 patients unable to complete one cycle due to side-effects and 36% experiencing grade 3–4 toxicities. The three on-treatment deaths were considered unlikely to be due to toxicity. The schedule of IFN-α, IL-2 and PVI 5FU has significant activity in advanced renal cell cancer with manageable toxicity. It is of particular interest that this regimen appears to have high activity in fit patients with poor prognostic features. © 2000 Cancer Research Campaig

Zeros of analytic functions, with or without multiplicities

The classical Mason-Stothers theorem deals with nontrivial polynomial solutions to the equation $a+b=c$. It provides a lower bound on the number of distinct zeros of the polynomial $abc$ in terms of the degrees of $a$, $b$ and $c$. We extend this to general analytic functions living on a reasonable bounded domain $\Omega\subset\mathbb C$, rather than on the whole of $\mathbb C$. The estimates obtained are sharp, for any $\Omega$, and a generalization of the original result on polynomials can be recovered from them by a limiting argument.Comment: This is a retitled and slightly revised version of my paper arXiv:1004.359