Implementing an Endocarditis Interdisciplinary Pathway in a Large Academic Medical Center: A Quality Improvement Project

Infective endocarditis (IE) is an infection and or inflammation of the heart valves and endocardium and a potentially life threatening illness. Dependent on the infecting organism, the cardiac damage caused by IE can be indolent or very aggressive. Hospitalized patients with IE require management by an interdisciplinary team, including cardiologists, cardiac surgeons, infectious disease specialists, registered nurses, nurse practitioners, physician assistants, pharmacists, and social workers. Treatment is complex and patients often present with various comorbidities. Standardized interdisciplinary care protocols have been shown to reduce patient mortality and hospital length of stay. The development of the pathway guidelines was informed by stakeholder meetings and recommendations from the American Heart Association, American Association for Thoracic Surgery, and European Society of Cardiology. One IE-related pathway was published in the institution’s intranet with two subsections: IE Diagnosis and IE Management and Discharge Processes. Education sessions on pathway access were conducted for interdisciplinary staff across three cardiac care units. The frequency of pathway online views was measured over three months, accumulating a total of 191 views. The median number of daily views was 2.5 [IQR 2, 4]. Analysis of these initial measures will help guide future efforts to streamline and enhance interdisciplinary collaboration amongst staff that care for patients with IE

Making sense of risk. Donor risk communication in families considering living liverdonation to a child

This paper contributes to the growing line of thought in bioethics that respect for autonomy should not be equated to the facilitation of individualistic self determination through standard requirements of informed consent in all healthcare contexts. The paper describes how in the context of donation for living related liver transplantation (LRLT) meaningful, responsible decision making is often embedded within family processes and its negotiation. We suggest that good donor risk communication in families promote “conscientious autonomy” and “reflective trust”. From this, the paper offers the suggestion that transplant teams and other relevant professionals have to broaden their role and responsibility for risk communication beyond proper disclosure by addressing the impact of varied psychosocial conditions on risk interpretation and assessment for potential donors and family stakeholders. In conclusion, we suggest further research questions on how professional responsibility and role-taking in risk communication should be morally understood

Parents' alcohol use: gender differences in the impact of household and family chores.

BACKGROUND: Social roles influence alcohol use. Nevertheless, little is known about how specific aspects of a given role, here parenthood, may influence alcohol use. The research questions for this study were the following: (i) are family-related indicators (FRI) linked to the alcohol use of mothers and fathers? and (ii) does the level of employment, i.e. full-time, part-time employment or unemployment, moderate the relationship between FRI and parental alcohol use? METHODS: Survey data of 3217 parents aged 25-50 living in Switzerland. Mean comparisons and multiple regression models of annual frequency of drinking and risky single occasion drinking, quantity per day on FRI (age of the youngest child, number of children in the household, majority of child-care/household duties). RESULTS: Protective relationships between FRI and alcohol use were observed among mothers. In contrast, among fathers, detrimental associations between FRI and alcohol use were observed. Whereas maternal responsibilities in general had a protective effect on alcohol use, the number of children had a detrimental impact on the quantity of alcohol consumed per day when mothers were in paid employment. Among fathers, the correlations between age of the youngest child, number of children and frequency of drinking was moderated by the level of paid employment. CONCLUSION: The study showed that in Switzerland, a systematic negative relationship was more often found between FRI and women's drinking than men's. Evidence was found that maternal responsibilities per se may protect from alcohol use but can turn into a detrimental triangle if mothers are additionally in paid employment

Photometric Light Curves and Polarization of Close-in Extrasolar Giant Planets

The close-in extrasolar giant planets [CEGPs], \ltorder 0.05 AU from their parent stars, may have a large component of optically reflected light. We present theoretical optical photometric light curves and polarization curves for the CEGP systems, from reflected planetary light. Different particle sizes of three condensates are considered. In the most reflective case, the variability is $\approx 100$ micromagnitudes, which will be easily detectable by the upcoming satellite missions MOST, COROT, and MONS, and possibly from the ground in the near future. The least reflective case is caused by small, highly absorbing grains such as solid Fe, with variation of much less than one micromagnitude. Polarization for all cases is lower than current detectability limits. We also discuss the temperature-pressure profiles and resulting emergent spectra of the CEGP atmospheres. We discuss the observational results of Tau Boo b by Cameron et al. (1999) and Charbonneau et al. (1999) in context of our model results. The predictions - the shape and magnitude of the light curves and polarization curves - are highly dependent on the size and type of condensates present in the planetary atmosphere.Comment: 33 pages, accepted by Ap

Impact of bariatric surgery in the short and long term: a need for time-dependent dosing of drugs

Sparse information is available on pharmacokinetic changes of drugs over time after bariatric surgery. By reviewing the literature on the short- and long-term pharmacokinetic changes of drugs, several patterns were identified for 39 drugs. No relevant pharmacokinetic changes were identified for roughly a third of the drugs. Of the remaining drugs, levels were variable and partly unpredictable shortly after the surgery. In the long term, most of the drug levels remain altered, but in some cases they returned to preoperative values. Based on the changes and the efficacy-safety balance of each drug, clinicians may need to perform additional clinical monitoring for specific drugs, including measuring drug levels. This review provides suggestions for clinicians and pharmacists for specific time-dependent drug dosing advice.Pharmacolog

Commentary on the EMA Reflection Paper on the use of extrapolation in the development of medicines for paediatrics

Adopted guidelines reflect a harmonised European approach to a specific scientific issue and should reflect the most recent scientific knowledge. However, whilst EU regulations are mandatory for all member states and EU directives must be followed by national laws in line with the directive, EMA guidelines do not have legal force and alternative approaches may be taken, but these obviously require more justification. This new series of the BJCP, developed in collaboration with the EMA, aims to address this issue by providing an annotated version of some relevant EMA guidelines and regulatory documents by experts. Hopefully, this will help in promoting their diffusion and in opening a forum for discussion with our readers.Pharmacolog

The role of population PK-PD modelling in paediatric clinical research

Children differ from adults in their response to drugs. While this may be the result of changes in dose exposure (pharmacokinetics [PK]) and/or exposure response (pharmacodynamics [PD]) relationships, the magnitude of these changes may not be solely reflected by differences in body weight. As a consequence, dosing recommendations empirically derived from adults dosing regimens using linear extrapolations based on body weight, can result in therapeutic failure, occurrence of adverse effect or even fatalities. In order to define rational, patient-tailored dosing schemes, population PK-PD studies in children are needed. For the analysis of the data, population modelling using non-linear mixed effect modelling is the preferred tool since this approach allows for the analysis of sparse and unbalanced datasets. Additionally, it permits the exploration of the influence of different covariates such as body weight and age to explain the variability in drug response. Finally, using this approach, these PK-PD studies can be designed in the most efficient manner in order to obtain the maximum information on the PK-PD parameters with the highest precision. Once a population PK-PD model is developed, internal and external validations should be performed. If the model performs well in these validation procedures, model simulations can be used to define a dosing regimen, which in turn needs to be tested and challenged in a prospective clinical trial. This methodology will improve the efficacy/safety balance of dosing guidelines, which will be of benefit to the individual child

Population Pharmacokinetic Modeling of Acetaminophen and Metabolites in Children After Cardiac Surgery With Cardiopulmonary Bypass

Abstract Children undergoing cardiac surgery often receive acetaminophen (paracetamol) as part of their postoperative pain treatment. To date, there is no information on the pharmacokinetics (PK) of acetaminophen in this special population, even though differences, as a result of altered hemodynamics and/or use of cardiopulmonary bypass, may be anticipated. Therefore, the aim of this study was to investigate the PK of intravenous acetaminophen in children after cardiac surgery with cardiopulmonary bypass. In the study, both children with and without Down syndrome were included. A population PK analysis, using NONMEM 7.2, was performed based on 161 concentrations of acetaminophen, acetaminophen sulfate, acetaminophen glucuronide, and oxidative metabolites from 17 children with Down syndrome and 13 children without Down syndrome of a previously published study (median age, 177 days [range, 92–944], body weight, 6.1 kg [4.0–12.9]). All children received 3 intravenous acetaminophen doses of 7.5 mg/kg (<10 kg) or 15 mg/kg (10 kg) at 8–hour intervals after cardiac surgery. For acetaminophen and its metabolites, 1-compartment models were identified. Clearance of acetaminophen and metabolites increased linearly with body weight. Acetaminophen clearance in a typical child of 6.1 kg is 0.96 L/h and volume of distribution 7.96 L. Down syndrome did not statistically significantly impact any of the PK parameters for acetaminophen, nor did any other remaining covariate.When comparing the PK parameters of acetaminophen in children after cardiac surgery with cardiopulmonary bypass with those from children of the same age following noncardiac surgery reported in the literature, clearance of acetaminophen was lower and volume of distribution higher