Sharp estimates for solutions to elliptic problems with mixed boundary conditions

We show, using symmetrization techniques, that it is possible to prove a comparison principle (we are mainly focused on $L^1$ comparison) between solutions to an elliptic partial differential equation on a smooth bounded set $\Omega$ with a rather general boundary condition, and solutions to a suitable related problem defined on a ball having the same volume as $\Omega$. This includes for instance mixed problems where Dirichlet boundary conditions are prescribed on part of the boundary, while Robin boundary conditions are prescribed on its complement

L-arginine: A unique amino acid for improving depressed wound immune function following hemorrhage

Objective: To determine whether L-arginine has any salutary effects on wound immune cell function following trauma-hemorrhage. Background. Depressed wound immune function contributes to an increased incidence of wound infections following hemorrhage. Although administration of L-arginine has been shown to restore depressed cell-mediated immune responses following hemorrhage potentially by maintaining organ blood flow, it remains unknown whether Larginine has any salutary effects on the depressed local immune response at the wound site. Methods: Male mice were subjected to a midline laparotomy and polyvinyl sponges were implanted subcutaneously in the abdominal wound prior to hemorrhage (35 +/- 5 mm Hg for 90 min and resuscitation) or sham operation. During resuscitation mice received 300 mg/kg body weight L-arginine or saline (vehicle). Sponges were harvested 24 h thereafter, wound fluid collected and wound immune cells cultured for 24 h in the presence of LPS. Pro- (IL-1beta, IL-6) and anti-inflammatory (IL-10) cytokines were determined in the supernatants and the wound fluid. In addition, wounds were stained for IL-6 immunohistochemically. In a separate set of animals, skin and muscle blood flow was determined by microspheres. Results: The capacity of wound immune cells to release IL-1beta and IL-6 in vitro was significantly depressed in hemorrhaged mice receiving vehicle. Administration of L-arginine, however, improved wound immune cell function. In contrast, in vivo the increased IL-6 release at the wound site was decreased in L-arginine-treated mice following hemorrhage. Moreover, IL-10 levels were significantly increased in the wound fluid in hemorrhaged animals receiving L-arginine compared to vehicle-treated mice. In addition, the depressed skin and muscle blood flow after hemorrhage was restored by L-arginine. Conclusions: Thus, L-arginine might improve local wound cell function by decreasing the inflammatory response at the wound site. Since L-arginine protected wound immune cell function this amino acid might represent a novel and useful adjunct to fluid resuscitation for decreasing wound complications following hemorrhage. Copyright beta 2002 S. Karger AG, Basel

Pharmacoepidemiology for nephrologists: do proton pump inhibitors cause chronic kidney disease?

Pharmacoepidemiology studies are increasingly used for research into safe prescribing in chronic kidney disease (CKD). Typically, patients prescribed a drug are compared with patients who are not on the drug and outcomes are compared to draw conclusions about the drug effects. This review article aims to provide the reader with a framework to critically appraise such research. A key concern in pharmacoepidemiology studies is confounding, in that patients who have worse health status are prescribed more drugs or different agents and their worse outcomes are attributed to the drugs not the health status. It may be challenging to adjust for this using statistical methods unless a comparison group with a similar health status but who are prescribed a different (comparison) drug(s) is identified. Another challenge in pharmacoepidemiology is outcome misclassification, as people who are more ill engage more often with the health service, leading to earlier diagnosis in people who are frequent attenders. Finally, using replication cohorts with the same methodology in the same type of health system does not ensure that findings are more robust. We use two recent papers that investigated the association of proton pump inhibitor drugs with CKD as a device to review the main pitfalls of pharmacoepidemiology studies and how to attempt to mitigate against potential biases that can occur

Chronic kidney disease and cause-specific hospitalisation: a matched cohort study using primary and secondary care patient data.

BACKGROUND: Although chronic kidney disease (CKD) is associated with various outcomes, the burden of each condition for hospital admission is unknown. AIM: To quantify the association between CKD and cause-specific hospitalisation. DESIGN AND SETTING: A matched cohort study in primary care using Clinical Practice Research Datalink linked to Hospital Episode Statistics in England. METHOD: Patients with CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2 for ≥3 months) and a comparison group of patients without known CKD (matched for age, sex, GP, and calendar time) were identified, 2004-2014. Outcomes were hospitalisations with 10 common conditions as the primary admission diagnosis: heart failure; urinary tract infection; pneumonia; acute kidney injury (AKI); myocardial infarction; cerebral infarction; gastrointestinal bleeding; hip fracture; venous thromboembolism; and intracranial bleeding. A difference in the incidence rate of first hospitalisation for each condition was estimated between matched patients with and without CKD. Multivariable Cox regression was used to estimate a relative risk for each outcome. RESULTS: In a cohort of 242 349 pairs of patients, with and without CKD, the rate difference was largest for heart failure at 6.6/1000 person-years (9.7/1000 versus 3.1/1000 person-years in patients with and without CKD, respectively), followed by urinary tract infection at 5.2, pneumonia at 4.4, and AKI at 4.1/1000 person-years. The relative risk was highest for AKI with a fully adjusted hazard ratio of 4.90, 95% confidence interval (CI) = 4.47 to 5.38, followed by heart failure with 1.66, 95% CI = 1.59 to 1.75. CONCLUSION: Hospitalisations for heart failure, infection, and AKI showed strong associations with CKD in absolute and(or) relative terms, suggesting targets for improved preventive care

Prescription of renin-angiotensin system blockers and risk of acute kidney injury: a population-based cohort study.

OBJECTIVE: To investigate whether there is an association between use of ACE inhibitors (ACEI) and angiotensin receptor blockers (ARB) and risk of acute kidney injury (AKI). STUDY DESIGN: We conducted a new-user cohort study of the rate of AKI among users of common antihypertensives. SETTING: UK primary care practices contributing to the Clinical Practice Research Datalink (CPRD) eligible for linkage to hospital records data from the Hospital Episode Statistics (HES) database between April 1997 and March 2014. PARTICIPANTS: New users of antihypertensives: ACEI/ARB, β-blockers, calcium channel blockers and thiazide diuretics. OUTCOMES: The outcome was first episode of AKI. We estimated incidence rate ratio (RR) for AKI during time exposed to ACEI/ARB compared to time unexposed, adjusting for age, sex, comorbidities, use of other antihypertensive drugs and calendar period using Poisson regression. Covariates were time updated. RESULTS: Among 570 445 participants, 303 761 were prescribed ACEI/ARB with a mean follow-up of 4.1 years. The adjusted RR of AKI during time exposed to ACEI/ARB compared to time unexposed was 1.12 (95% CI 1.07 to 1.17). This relative risk varied depending on absolute risk of AKI, with lower or no increased relative risk from the drugs among those at greatest absolute risk. For example, among people with stage 4 chronic kidney disease (who had 6.69 (95% CI 5.57 to 8.03) times higher rate of AKI compared to those without chronic kidney disease), the adjusted RR of AKI during time exposed to ACEI/ARB compared to time unexposed was 0.66 (95% CI 0.44 to 0.97) in contrast to 1.17 (95% CI 1.09 to 1.25) among people without chronic kidney disease. CONCLUSIONS: Treatment with ACEI/ARB is associated with only a small increase in AKI risk while individual patient characteristics are much more strongly associated with the rate of AKI. The degree of increased risk varies between patient groups

Car-to-cyclist accidents from the car driver's point of view

A promising approach to prevent road traffic accidents between passenger cars and cyclists is the development of driver assistance systems. To develop such systems with maximum ef-fectiveness in road traffic, car-to-cyclist accidents have to be analysed from the car driver’s point of view to gain insight into the situations with which the drivers were faced and espe-cially why they failed to manage these crash situations. The EU funded project PROSPECT (Proactive Safety for Pedestrians and Cyclists) considered this approach and made the pre-sented research possible. This paper reports findings from a case-by-case analysis of 3,550 car-to-cyclist accidents in Germany. The results of the accident analysis confirm findings of previous studies showing that crossing scenarios play a predominant role in car-to-cyclist ac-cidents. Moreover, the results show that both the orientation of the cyclist and the driver’s task (in terms of the driver’s maneuver intention, road layout, traffic regulations) have an in-fluence on the distribution of those scenarios in so far as certain combinations lead to a higher or lower distribution. The results contribute towards a better understanding of possi-ble reasons why the driver failed to manage certain situations. Regarding PROSPECT, the most relevant use cases will be used to specify and develop advanced measures that will be implemented in the next generation of active safety systems

Safety of Oral Paracetamol – Analysis of Data from a Spontaneous Reporting System in Poland

Purpose: To determine the safety of oral coated paracetamol tablets 500 mg and oral suspension 120 mg/5 mL produced by Hasco-Lek Poland.Methods: We analyzed sales volume and data obtained from the  monitoring of spontaneous reports on the adverse effects of paracetamol collected in the period between November 2000 and June 2012.Results: A total of 45,694 units of coated paracetamol tablets (500 mg) and 6,048,289 units of paracetamol oral suspension (120 mg/5 mL) were marketed during that period. There were 4 spontaneous reports of adverse effects.Conclusion: Oral paracetamol is a safe medication rarely causing adverse effects but it is possible that the existing spontaneous monitoring system for adverse effects in Poland is not sensitive enough to detect all adverse effects, and needs improvement.Keywords: Adverse reaction, NSAIDs, Pharmacovigillance,  Pharmoepidemiolog