Simulated drug administration: An emerging tool for teaching clinical pharmacology during anesthesiology training

A thorough understanding of the dose-response relationship is required for optimizing the efficacy of anesthetics while minimizing adverse drug effects.(1) Nowadays, except for the inhaled anesthetics (for which end-tidal concentrations can be measured online), most of the drugs used in clinical anesthesia are administered using standard dosing guidelines, without giving due consideration to their pharmacokinetics and dynamics in guiding their administration. Various studies have found that introducing pharmacokinetics and pharmacodynamics as part of the inputs in clinical anesthesiology could lead to better patient care.(2) With this in mind, it is extremely important that clinicians understand and apply the principles of clinical pharmacology that determine the time course of a drug's disposition and effect. Clinical pharmacology is one of the most challenging topics to teach in anesthesiology. The development of simulators to illustrate the time course of a drug's disposition and effect provides online visualization of pharmacokinetic pharmacodynamic information during the clinical use of anesthetics. The aim of this review is to discuss the importance of simulation as a clinical pharmacology teaching tool for trainees in anesthesiology

Influence of sow dietary polyunsaturated fatty acid source on the immunoglobulin profile of piglets

To examine the effect of different n-3 polyunsaturated fatty acid (PUFA) sources in sow diets on piglets’ immunoglobulin (Ig) profile, two groups of twelve sows each were fed different diets from day 45 of pregnancy and during lactation on two commercial farms. On farm I, a palm oil diet (25 g/kg; PALM) and a linseed oil containing diet (20 g/kg; LIN) were fed. On farm II, the same PALM diet and a fish oil containing diet (20 g/kg; FISH) were fed. All diets contained equal amounts of C18:2n-6 (13 g/kg). One day before parturition, blood (for serum) was taken and shortly after parturition, colostrum was taken from the sows (not from sows on farm I) for determination of Ig levels. On day 5 post partum and the day before weaning, blood (for serum) was taken from 4 piglets of six sows per group (24 piglets in total per group; for 5-d old piglets on farm II, only 6 piglets of the FISH group were sampled). In all samples total IgG, IgA, IgM concentration and specific F4-IgG, -IgA and -IgM titer (Log2 titer) against E. coli were determined. On farm I, the sows of the LIN group showed a trend towards lower IgG titers compared to the PALM group around farrowing (P<0.1). On farm II, the sows on the FISH diet showed a significantly (P<0.05) lower F4-IgG titer compared to the sows fed PALM. The colostrum samples on farm II showed no differences between both groups. On farm I, the 5-d old piglets from the LIN group had significantly higher IgA and IgM concentrations and higher F4-IgA and F4-IgM titers (P<0.05). F4-IgA and F4-IgG titers were also significantly higher at weaning in the LIN group compared to the PALM group. On farm II, the piglets of the FISH group had a significantly higher IgG concentration and F4-IgA titer (P<0.05) and a trend towards a higher IgM concentration (P<0.1) around weaning compared to the PALM group. It seems that fish oil in the maternal diet increases total IgG concentration, while linseed oil reduces total IgG and increases total IgA compared to a palm fat containing diet. Both fish and linseed oil seem to have a positive effect on total IgM concentration compared to the palm diet

Treatment and control: a qualitative study of older mentally ill offenders' perceptions on their detention and care trajectory

The life of older mentally ill offenders (OMIOs) is often characterized by successive periods of detention in correctional facilities, admissions to psychiatric services, and unsuccessful attempts to live independently. Through in-depth interviews, eight personal stories from OMIOs under supervision of the commission of social defence in Ghent (Belgium) were analyzed in the phenomenological research tradition. The results of the study reveal that OMIOs had more positive and less negative experiences in prison settings when compared with other institutional care settings. Independent living, unsurprisingly, is favored the most. This may be due to the fact that the latter option fosters personal competence, feelings of being useful, personal choices, and contact with the outside world. Even in later lifetime, a combined approach of risk assessment with improvement of well-being remains valuable to stimulate offender rehabilitation. Therefore, more research into concepts that could be used to support OMIOs needs further consideration

Failure of a dietary model to affect markers of inflammation in domestic cats

Background: Oxidative stress and inflammation can be altered by dietary factors in various species. However, little data are available in true carnivorous species such as domestic cats. As numerous anti-inflammatory and anti-oxidative additives become available and might be of use in cats with chronic low-grade inflammatory diseases, the current study aimed to develop a model of diet-induced inflammation by use of two opposite diets. It was hypothesized that a high fat diet enhanced in n-6 PUFA and with lower concentrations of antioxidants would evoke inflammation and oxidative stress in domestic cats. Results: Sixteen healthy adult cats were allocated to two groups. One group received a moderate fat diet, containing pork lard and salmon oil (AA:(EPA + DHA) ratio 0.19) (MFn-3), while the other group was fed a high fat diet, containing pork lard and chicken fat (AA:(EPA + DHA) ratio 2.06) (HFn-6) for 12 weeks. Prior to and 2, 4, 6, 8, 10 and 12 weeks after starting the testing period, blood samples were collected. Erythrocytic fatty acid profile showed clear alterations in accordance to the dietary fatty acid profile. Serum thiobarbituric acid reactive substances was higher when fed MFn-3 compared to the HFn-6, suggesting augmented oxidative stress. This was associated with a reduced serum vitamin E status, as serum a-tocopherol concentrations were lower with MFn-3, even with higher dietary levels of vitamin E. Serum cytokine and serum amyloid A concentrations were not influenced by diet. Conclusion: These results point towards a resistance of cats to develop dietary fat-induced inflammation, but also suggest a high susceptibility to oxidative stress when fed a fish oil-supplemented diet even with moderate fat level and additional vitamin E

Long-term outcome and health-related quality of life in difficult-to-wean patients with and without ventilator dependency at ICU discharge : a retrospective cohort study

Background: Long-term outcome and quality of life (QOL) in patients requiring prolonged mechanical ventilation after failure to wean in the ICU is scarcely documented. We aimed to evaluate long-term survival and QOL in patients discharged from the ICU with a tracheostomy for difficult weaning, and with or without ventilator dependency at ICU discharge. Methods: We retrospectively investigated post-ICU trajectories and survival in patients requiring tracheostomy for difficult weaning admitted to the medical ICU of a tertiary center between 1999 and 2013, discriminating between patients who were ventilator dependent or were weaned at ICU discharge. In 2014, a QOL assessment was done in survivors with the use of the Short Form Health Survey (SF-36) and the Severe Respiratory Insufficiency questionnaire. Results: A total of 114 patients was included, of whom 59 were ventilator dependent and 55 were weaned at ICU discharge. One-year survival rates were 73 % and 69 %, respectively. Overall QOL scores for physical functioning were low, and not significantly different between patients ventilated and those weaned at ICU discharge; scores for social functioning and mental health were less below norm and similar between both groups. Conclusions: Long-term survival in patients discharged from the ICU with tracheostomy and ventilator dependency after failure to wean was not significantly different from that of patients with tracheostomy and weaned at ICU discharge. Despite the physical QOL scores being low in both groups, mental QOL was acceptable. Given the intrinsic limitations of this retrospective study, prospective and preferentially multicenter studies are required to confirm these preliminary results

Prevention of severe infectious complications after colorectal surgery using oral non-absorbable antimicrobial prophylaxis:results of a multicenter randomized placebo-controlled clinical trial

BACKGROUND: Surgical site infections (SSIs) are common complications after colorectal surgery. Oral non-absorbable antibiotic prophylaxis (OAP) can be administered preoperatively to reduce the risk of SSIs. Its efficacy without simultaneous mechanical cleaning is unknown. METHODS: The Precaution trial was a double-blind, placebo-controlled randomized clinical trial conducted in six Dutch hospitals. Adult patients who underwent elective colorectal surgery were randomized to receive either a three-day course of preoperative OAP with tobramycin and colistin or placebo. The primary composite endpoint was the incidence of deep SSI or mortality within 30 days after surgery. Secondary endpoints included both infectious and non-infectious complications at 30 days and six months after surgery. RESULTS: The study was prematurely ended due to the loss of clinical equipoise. At that time, 39 patients had been randomized to active OAP and 39 to placebo, which reflected 8.1% of the initially pursued sample size. Nine (11.5%) patients developed the primary outcome, of whom four had been randomized to OAP (4/39; 10.3%) and five to placebo (5/39; 12.8%). This corresponds to a risk ratio in the intention-to-treat analysis of 0.80 (95% confidence interval (CI) 0.23-2.78). In the per-protocol analysis, the relative risk was 0.64 (95% CI 0.12-3.46). CONCLUSIONS: Observational data emerging during the study provided new evidence for the effectiveness of OAP that changed both the clinical and medical ethical landscape for infection prevention in colorectal surgery. We therefore consider it unethical to continue randomizing patients to placebo. We recommend the implementation of OAP in clinical practice and continuing monitoring of infection rates and antibiotic susceptibilities. TRIAL REGISTRATION: The PreCaution trial is registered in the Netherlands Trial Register under NL5932 (previously: NTR6113) as well as in the EudraCT register under 2015-005736-17

Neurofibromatosis type 1-related pseudarthrosis: Beyond the pseudarthrosis site.

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder affecting approximately 1 in 2,000 newborns. Up to 5% of NF1 patients suffer from pseudarthrosis of a long bone (NF1-PA). Current treatments are often unsatisfactory, potentially leading to amputation. To gain more insight into the pathogenesis we cultured cells from PA tissue and normal-appearing periosteum of the affected bone for NF1 mutation analysis. PA cells were available from 13 individuals with NF1. Biallelic NF1 inactivation was identified in all investigated PA cells obtained during the first surgery. Three of five cases sampled during a later intervention showed biallelic NF1 inactivation. Also, in three individuals, we examined periosteum-derived cells from normal-appearing periosteum proximal and distal to the PA. We identified the same biallelic NF1 inactivation in the periosteal cells outside the PA region. These results indicate that NF1 inactivation is required but not sufficient for the development of NF1-PA. We observed that late-onset NF1-PA occurs and is not always preceded by congenital bowing. Furthermore, the failure to identify biallelic inactivation in two of five later interventions and one reintervention with a known somatic mutation indicates that NF1-PA can persist after the removal of most NF1 negative cells

Sequential induction of auxin efflux and influx carriers regulates lateral root emergence

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