ACE inhibitor and angiotensin receptor-II antagonist prescribing and hospital admissions with acute kidney injury: A longitudinal ecological study

This is the final version. Available from the publisher via the DOI in this record.Background: ACE Inhibitors (ACE-I) and Angiotensin-Receptor Antagonists (ARAs) are commonly prescribed but can cause acute kidney injury (AKI) during intercurrent illness. Rates of hospitalization with AKI are increasing. We aimed to determine whether hospital AKI admission rates are associated with increased ACE-I/ARA prescribing. Methods and Findings: English NHS prescribing data for ACE-I/ARA prescriptions were matched at the level of the general practice to numbers of hospital admissions with a primary diagnosis of AKI. Numbers of prescriptions were weighted for the demographic characteristics of general practices by expressing prescribing as rates where the denominator is Age, Sex, and Temporary Resident Originated Prescribing Units (ASTRO-PUs). We performed a mixed-effect Poisson regression to model the number of admissions for AKI occurring in each practice for each of 4 years from 1/4/2007. From 2007/8-2010/11, crude AKI admission rates increased from 0.38 to 0.57 per 1000 patients (51.6% increase), and national annual ACE-I/ARA prescribing rates increased by 0.032 from 0.202 to 0.234 (15.8% increase). There was strong evidence (p<0.001) that increases in practice-level prescribing of ACE-I/ARA over the study period were associated with an increase in AKI admission rates. The increase in prescribing seen in a typical practice corresponded to an increase in admissions of approximately 5.1% (rate ratio = 1.051 for a 0.03 per ASTRO-PU increase in annual prescribing rate, 95%CI 1.047-1.055). Using the regression model we predict that 1,636 (95%CI 1,540-1,780) AKI admissions would have been avoided if prescribing rates were at the 2007/8 level, equivalent to 14.8% of the total increase in AKI admissions. Conclusion: In this ecological analysis, up to 15% of the increase in AKI admissions in England over a 4-year time period is potentially attributable to increased prescribing of ACE-I and ARAs. However, these findings are limited by the lack of patient level data such as indication for prescribing and patient characteristics. © 2013 Tomlinson et al.Cambridge Biomedical Research InstituteBritish Heart Foundatio

The accuracy of diagnostic coding for acute kidney injury in England - A single centre study

This is the final version. Available on open access from BMC via the DOI in this recordBackground: Acute kidney injury (AKI) is an independent risk factor for mortality and is responsible for a significant burden of healthcare expenditure, so accurate measurement of its incidence is important. Administrative coding data has been used for assessing AKI incidence, and shows an increasing proportion of hospital bed days attributable to AKI. However, the accuracy of coding for AKI and changes in coding over time have not been studied in England. Methods. We studied a random sample of admissions from 2005 and 2010 where ICD-10 code N17 (acute renal failure) was recorded in the administrative coding data at one acute NHS Foundation Trust in England. Using the medical notes and computerised records we examined the demographic and clinical details of these admissions. Results: Against a 6.3% (95% CI 4.8-7.9%) increase in all non-elective admissions, we found a 64% increase in acute renal failure admissions (95% CI 41%-92%, p<0.001) in 2010 compared to 2005. Median age was 78 years (IQR 72-87), 11-25% had a relevant pre-admission co-morbidity and 64% (55-73%) were taking drugs known to be associated with AKI. Over both years, 95% (91-99%) of cases examined met the Kidney Disease: Improving Global Outcomes criteria for AKI. Conclusions: Patients with hospital admissions where AKI has been coded are elderly with multiple co-morbidities. Our results demonstrate a high positive predictive value of coding data for a clinical diagnosis of AKI, with no suggestion of marked changes in coding of AKI between 2005 and 2010. © 2013 Tomlinson et al; licensee BioMed Central Ltd.Cambridge Biomedical Research InstituteBritish Heart Foundatio

Single dose oral dexamethasone versus multi-dose prednisolone in the treatment of acute exacerbations of asthma in children who attend the emergency department: study protocol for a randomized controlled trial.

BACKGROUND: Asthma is a major cause of pediatric morbidity and mortality. In acute exacerbations of asthma, corticosteroids reduce relapses, subsequent hospital admission and the need for ß2-agonist therapy. Prednisolone is relatively short-acting with a half-life of 12 to 36 hours, thereby requiring daily dosing. Prolonged treatment course, vomiting and a bitter taste may reduce patient compliance with prednisolone. Dexamethasone is a long-acting corticosteroid with a half-life of 36 to 72 hours. It is used frequently in children with croup and bacterial meningitis, and is well absorbed orally. The purpose of this trial is to examine whether a single dose of oral dexamethasone (0.3 mg/kg) is clinically non-inferior to prednisolone (1 mg/kg/day for three days) in the treatment of exacerbations of asthma in children who attend the Emergency Department. METHODS/DESIGN: This is a randomized, non-inferiority, open-label clinical trial. After informed consent with or without assent, patients will be randomized to either oral dexamethasone 0.3 mg/kg stat or prednisolone 1 mg/kg/day for three days. The primary outcome measure is the comparison between the Pediatric Respiratory Assessment Measure (PRAM) across both groups on Day 4. The PRAM score, a validated, responsive and reliable tool to determine asthma severity in children aged 2 to 16 years, will be performed by a clinician blinded to treatment allocation. Secondary outcomes include relapse, hospital admission and requirement for further steroid therapy. Data will be analyzed on an intention-to-treat and a per protocol basis. With a sample size of 232 subjects (105 in each group with an estimated 10% loss to follow-up), we will be able to reject the null hypothesis - that the population means of the experimental and control groups are equal with a probability (power) of 0.9. The Type I error probability associated with this test (of the null hypothesis) is 0.05. DISCUSSION: This clinical trial may provide evidence that a shorter steroid course using dexamethasone can be used in the treatment of acute pediatric asthma, thus eliminating the issue of compliance to treatment. REGISTRATION: ISRCTN26944158 and EudraCT Number 2010-022001-18

The Universal Plausibility Metric (UPM) & Principle (UPP)

<p>Abstract</p> <p>Background</p> <p>Mere possibility is not an adequate basis for asserting scientific plausibility. A precisely defined universal bound is needed beyond which the assertion of <it>plausibility</it>, particularly in life-origin models, can be considered operationally falsified. But can something so seemingly relative and subjective as plausibility ever be quantified? Amazingly, the answer is, "Yes." A method of objectively measuring the plausibility of any chance hypothesis (The Universal Plausibility Metric [UPM]) is presented. A numerical inequality is also provided whereby any chance hypothesis can be definitively falsified when its UPM metric of ξ is < 1 (The Universal Plausibility Principle [UPP]). Both UPM and UPP pre-exist and are independent of any experimental design and data set.</p> <p>Conclusion</p> <p>No low-probability hypothetical plausibility assertion should survive peer-review without subjection to the UPP inequality standard of formal falsification (ξ < 1).</p

Intranasal fentanyl versus intravenous morphine in the emergency department treatment of severe painful sickle cell crises in children: study protocol for a randomised controlled trial.

BACKGROUND: Children with sickle cell disease (SCD) frequently and unpredictably present to the emergency department (ED) with pain. The painful event is the hallmark acute clinical manifestation of SCD, characterised by sudden onset and is usually bony in origin. This study aims to establish if 1.5mcg/kg of intranasal fentanyl (INF; administered via a Mucosal Atomiser Device, MAD™) is non-inferior to intravenous morphine 0.1 mg/kg in severe SCD-associated pain. METHODS/DESIGN: This study is a randomised,double-blind, double-dummy active control trial of children (weighing more than 10 kg) between 1 year and 21 years of age with severe painful sickle cell crisis. Severe pain is defined as rated seven or greater on a 0 to 10 age-appropriate numeric pain scale or equivalent. The trial will be conducted in a single tertiary urban paediatric ED in Dublin, Ireland. Each patient will receive a single active agent and a single placebo via the intravenous and intranasal routes. All clinical and research staff, patients and parents will be blinded to the treatment allocation. The primary endpoint is severity of pain scored at 10 min from administration of the study medications. Secondary endpoints include pain severity measured at 0, 5, 15, 20, 30, 60 and 120 min after the administration of analgesia, proportion of patients requiring rescue analgesia and incidence of adverse events. The trial ends at 120 min after the administration of the study drugs. A clinically meaningful difference in validated pain scores has been defined as 13 mm. Setting the permitted threshold to 50% of this limit (6 mm) and assuming both treatments are on average equal, a sample size of 30 patients (15 per group) will provide at least 80% power to demonstrate that INF is non-inferior to IV morphine with a level of significance of 0.05. DISCUSSION: This clinical trial will inform of the role of INF 1.5mcg/kg via MAD in the acute treatment of severe painful sickle cell crisis in children in the ED setting. TRIAL REGISTRATION: Current Controlled Trials ISRCTN67469672 and EudraCT no. 2011-005161-20

Solutions of Several Coupled Discrete Models in terms of Lame Polynomials of Order One and Two

Coupled discrete models abound in several areas of physics. Here we provide an extensive set of exact quasiperiodic solutions of a number of coupled discrete models in terms of Lame polynomials of order one and two. Some of the models discussed are (i) coupled Salerno model, (ii) coupled Ablowitz-Ladik model, (iii) coupled saturated discrete nonlinear Schrodinger equation, (iv) coupled phi4 model, and (v) coupled phi6 model. Furthermore, we show that most of these coupled models in fact also possess an even broader class of exact solutions.Comment: 31 pages, to appear in Pramana (Journal of Physics) 201

Neutron Electric Dipole Moment Constraint on Scale of Minimal Left-Right Symmetric Model

Using an effective theory approach, we calculate the neutron electric dipole moment (nEDM) in the minimal left-right symmetric model with both explicit and spontaneous CP violations. We integrate out heavy particles to obtain flavor-neutral CP-violating effective Lagrangian. We run the Wilson coefficients from the electroweak scale to the hadronic scale using one-loop renormalization group equations. Using the state-of-the-art hadronic matrix elements, we obtain the nEDM as a function of right-handed W-boson mass and CP-violating parameters. We use the current limit on nEDM combined with the kaon-decay parameter $\epsilon$ to provide the most stringent constraint yet on the left-right symmetric scale $M_{W_R} > (10 \pm 3)$ TeV.Comment: 20 pages and 8 figure

P-odd and CP-odd Four-Quark Contributions to Neutron EDM

In a class of beyond-standard-model theories, CP-odd observables, such as the neutron electric dipole moment, receive significant contributions from flavor-neutral P-odd and CP-odd four-quark operators. However, considerable uncertainties exist in the hadronic matrix elements of these operators strongly affecting the experimental constraints on CP-violating parameters in the theories. Here we study their hadronic matrix elements in combined chiral perturbation theory and nucleon models. We first classify the operators in chiral representations and present the leading-order QCD evolutions. We then match the four-quark operators to the corresponding ones in chiral hadronic theory, finding symmetry relations among the matrix elements. Although this makes lattice QCD calculations feasible, we choose to estimate the non-perturbative matching coefficients in simple quark models. We finally compare the results for the neutron electric dipole moment and P-odd and CP-odd pion-nucleon couplings with the previous studies using naive factorization and QCD sum rules. Our study shall provide valuable insights on the present hadronic physics uncertainties in these observables.Comment: 40 pages, 7 figures. This is the final version. A discussion of the uncertainty of the calculation is adde