Multimodal prehabilitation to reduce the incidence of delirium and other adverse events in elderly patients undergoing elective major abdominal surgery: An uncontrolled before-and-after study.

BACKGROUND: Delirium is a common and serious complication in elderly patients undergoing major abdominal surgery, with significant adverse outcomes. Successful strategies or therapies to reduce the incidence of delirium are scarce. The objective of this study was to assess the role of prehabilitation in reducing the incidence of delirium in elderly patients. METHODS: A single-center uncontrolled before-and-after study was conducted, including patients aged 70 years or older who underwent elective abdominal surgery for colorectal carcinoma or an abdominal aortic aneurysm between January 2013 and October 2015 (control group) and between November 2015 and June 2018 (prehabilitation group). The prehabilitation group received interventions to improve patients' physical health, nutritional status, factors of frailty and preoperative anaemia prior to surgery. The primary outcome was incidence of delirium, diagnosed with the DSM-V criteria or the confusion assessment method. Secondary outcomes were additional complications, length of stay, unplanned ICU admission, length of ICU stay, readmission rate, institutionalization, and in-hospital or 30-day mortality. RESULT: A total of 360 control patients and 267 prehabilitation patients were included in the final analysis. The mean number of prehabilitation days was 39 days. The prehabilitation group had a higher burden of comorbidities and was more physically and visually impaired at baseline. At adjusted logistic regression analysis, delirium incidence was reduced significantly from 11.7 to 8.2% (OR 0.56; 95% CI 0.32-0.98; P = 0.043). No statistically significant effects were seen on secondary outcomes. CONCLUSION: Current prehabilitation program is feasible and safe, and can reduce delirium incidence in elderly patients undergoing elective major abdominal surgery. This program merits further evaluation. TRIAL REGISTRATION: Dutch Trial Registration, NTR5932.

The impact of skin decontamination on the time window for effective treatment of percutaneous VX exposure.

The main goal of the present study was to obtain insight into depot formation and penetration following percutaneous VX poisoning, in order to identify an appropriate decontamination window that can enhance or support medical countermeasures. The study was executed in two phases, using the hairless guinea pig as an animal model. In the first phase the effect of various decontamination regimens on levels of free VX in skin and plasma were studied as well as on blood cholinesterase levels. Animals were exposed to 0.5 mg/kg VX and were not decontaminated (control), decontaminated with RSDL once at 15 or 90 min after exposure or three times at 15, 25 and 35 (10-min interval) or 15, 45 and 75 min after exposure (30-min interval). There was no significant effect of any of the decontamination regimens on the 6-h survival rate of the animals. However, all animals that had been decontaminated 15 min after exposure, showed a survival rate of more than 90%, compared to 50-60% in animals that were not decontaminated or decontaminated at 90 min after exposure. In the second phase of the study, hairless guinea pigs were exposed to 1 mg/kg VX on the shoulder, followed either by decontamination with RSDL (10 min interval), conventional treatment on indication of clinical signs or a combination thereof. It appeared that a thorough, repeated decontamination alone could not save the majority of the animals. A 100% survival rate was observed in the group that received a combination of decontamination and treatment. In conclusion, the effects of VX exposure could be influenced by various RSDL decontamination regimens. The results in freely moving animals showed that skin decontamination, although not fully effective in removing all VX from the skin and skin depot is crucial to support pharmacological intervention.

Incomplete and incorrect epinephrine auto-injector training to food-allergic patients by pharmacists in the Netherlands.

BACKGROUND: Successful treatment of anaphylaxis in the community relies on early and correct use of epinephrine auto-injectors (EAI). In the Netherlands, pharmacists supply EAIs to patients and have a crucial role in instructing patients in how and when to use EAI. However, there are currently no data in Europe on the quality of such instruction provided by pharmacists. Therefore, the aims of this study were to investigate the knowledge, attitudes, and beliefs regarding food allergy among pharmacists in the Netherlands and to investigate the quality of EAI instructions and demonstrations to patients by pharmacists. METHODS: Pharmacists were asked to complete an online questionnaire. Quality of instructions and demonstration accuracy were assessed in mystery guest visits to randomly selected pharmacies. For the statistical analysis, descriptive methods were used. RESULTS: In total, 25 of 115 questionnaires were completed. Only two (8%) respondents gave correct answers concerning the proper EAI demonstration. Twenty-one (84%) respondents thought that the provision of instructions was the responsibility of pharmacists. In total, ten pharmacies were included in simulated patient visits. Five of them (50%) demonstrated the EAI. None of them demonstrated the EAI use correctly. CONCLUSION: Food-allergic patients at high risk for anaphylaxis who receive their EAI from a community pharmacy are often not instructed on how to use an EAI or receive incorrect instructions. Pharmacists show considerable gaps in knowledge about food allergy and its management. These data suggest that opportunities exist to improve the quality of care provided by pharmacies to high-risk food-allergic patients.

Evaluation of Staphylococcus aureus Eradication Therapy in Vascular Surgery.

INTRODUCTION: Surgical site infections (SSI) are a serious complication in vascular surgery which may lead to severe morbidity and mortality. Staphylococcus aureus nasal carriage is associated with increased risk for development of SSIs in central vascular surgery. The risk for SSI can be reduced by perioperative eradication of S. aureus carriage in cardiothoracic and orthopedic surgery. This study analyzes the relation between S. aureus eradication therapy and SSI in a vascular surgery population. METHODS: A prospective cohort study was performed, including all patients undergoing vascular surgery between February 2013 and April 2015. Patients were screened for S. aureus nasal carriage and, when tested positive, were subsequently treated with eradication therapy. The presence of SSI was recorded based on criteria of the CDC. The control group consisted of a cohort of vascular surgery patients in 2010, who were screened, but received no treatment. RESULTS: A total of 444 patients were screened. 104 nasal swabs were positive for S. aureus, these patients were included in the intervention group. 204 patients were screened in the 2010 cohort. 51 tested positive and were included in the control group. The incidence of S. aureus infection was 5 out of 51 (9.8%) in the control group versus 3 out of 104 in the eradication group (2.2%; 95% confidence interval 0.02-1.39; P = 0.13). A subgroup analysis showed that the incidence of S. aureus infection was 3 out of 23 (13.0%) in the control group in central reconstructive surgery versus 0 out of 44 in the intervention group (P = 0.074). The reduction of infection pressure by S. aureus was stronger than the reduction of infection pressure by other pathogens (exact maximum likelihood estimation; OR = 0.0724; 95% CI: 0.001-0.98; p = 0.0475). CONCLUSION: S. aureus eradication therapy reduces the infection pressure of S. aureus, resulting in a reduction of SSIs caused by S. aureus.

Late reactions in food-allergic children and adolescents after double-blind, placebo-controlled food challenges.

The time during which children are observed following a double-blind, placebo-controlled food challenge (DBPCFC) varies in clinical practice. There are little data on late reactions (LRs) following DBPCFCs. Therefore, we determined the prevalence, severity and clinical characteristics of late reactions in food-allergic children and adolescents after DBPCFC, and ascertained which factors are associated with, and may predict, LRs. Logistic regression analyses were performed to investigate which factors were associated with LRs and to develop the association and prediction models. A total of 1142 children underwent DBPCFCs (child-test combinations). Of these 1142 child-test combinations, 400 reported LRs following the DBPCFC. LRs in food-allergic children after DBPCFC are poorly predictable and are generally not severe. All LRs, including those on the placebo day, are more frequently reported in younger children. Children who do not experience severe immediate reactions may be safely discharged home 2 h after a DBPCFC.

The compliance and burden of treatment with the epinephrine auto-injector in food-allergic adolescents.

BACKGROUND: Food-allergic patients at high risk of potential fatal anaphylaxis should carry an epinephrine auto-injector (EAI) at all times. This treatment may be perceived as burdensome and this may affect compliance and health-related quality of life (HRQL). The aims of the study were (1) to determine the burden of treatment (BoT) of an EAI, (2) to examine the relationship between this burden and compliance, and (3) to analyze which factors contribute to the BoT of the EAI as perceived by food-allergic adolescents and their parents. METHODS: Dutch food-allergic adolescents prescribed an EAI, and their parents completed a questionnaire package (n = 55). Relationships between BoT and HRQL, illness severity and perception, and anxiety measures were investigated. RESULTS: Food-allergic adolescents and their parents were (extremely) positive about the EAI (54.5%; 72.7%, respectively) (=low BoT). The BoT measure showed a significantly greater burden in food-allergic adolescents prescribed an EAI who reported not carrying the EAI at all times than adolescents who reported they did. The BoT scores of both adolescents and their parents were not associated with HRQL, illness severity and perception, or trait anxiety. CONCLUSIONS: The majority of food-allergic adolescents and their parents were positive about the EAI (=low BoT). However, the BoT was significantly associated with self-reported compliance with carrying the EAI. The BoT was higher in food-allergic adolescents prescribed an EAI who reported not carrying the EAI at all times. The BoT measure seems to be a useful tool to study compliance with carrying an EAI. The BoT of an EAI is not associated with HRQL. The BoT measures a distinct concept related to compliance behavior.

Predictors of health-related quality of life of European food-allergic patients.

BACKGROUND: Although food allergy has universally been found to impair HRQL, studies have found significant differences in HRQL between countries, even when corrected for differences in perceived disease severity. However, little is known about factors other than disease severity which may contribute to HRQL in food-allergic patients. Therefore, the aim of this study was to identify factors which may predict HRQL of food-allergic patients and also to investigate the specific impact of having experienced anaphylaxis and being prescribed an EAI on HRQL. METHODS: A total of 648 European food-allergic patients (404 adults, 244 children) completed an age-specific questionnaire package including descriptive questions. Multivariable regression analyses were performed to develop models for predicting HRQL of these patients. RESULTS: For adults, the prediction model accounted for 62% of the variance in HRQL and included perceived disease severity, type of symptoms, having a fish or milk allergy, and gender. For children, the prediction model accounted for 28% of the variance in HRQL and included perceived disease severity, having a peanut or soy allergy, and country of origin. For both adults and children, neither experiencing anaphylaxis nor being prescribed an epinephrine auto-injector (EAI) contributed to impairment of HRQL. CONCLUSIONS: In this study, food allergy-related HRQL may be predicted to a greater extent in adults than in children. Allergy to certain foods may cause greater HRQL impairment than others. Country of origin may affect HRQL, at least in children. Experiencing anaphylaxis or being prescribed an EAI has no impact on HRQL in either adults or children.

Rapid detection of CWD PrP: comparison of tests designed for the detection of BSE or scrapie.

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) mainly affecting cervids in North America. The accumulation of an abnormal form of host-encoded prion protein (PrP(CWD) ) in the CNS and lymphoid tissues is characteristic of the disease and known to be caused by pathogenic prion proteins (PrP(res) ), which are thought to be transmitted mainly by contact with body fluids, such like saliva. Species known to be naturally infected by CWD include Rocky Mountain elk (Cervus elaphus nelsoni), white-tailed deer (Odocoileus virginianus) and mule deer (Odocoileus hemionus). Recently, large-scale disease eradication or control programs have been attempted to curtail the spread of disease. But reports of diseased free-ranging and farmed cervids in many locations in the USA and Canada are still continuing. The goal of this study was to find sensitive rapid test systems that are reliably able to detect CWD-associated PrP(CWD) in cervids, thereby reviewing an important control tool in case the disease spreads further and reaches Europe. Seven tests, originally developed for the detection of other TSE diseases such as Scrapie and bovine spongiform encephalopathy, including two Western blots, four enzyme-linked immunosorbent assays (ELISAs), and one lateral flow device, were included in this study. All seven tests evaluated were able to detect pathogenic prion proteins (PrP(CWD) ) in Northern American infected animals and distinguish physiologic prion protein (PrP(c) ) in brainstem (obex region) and lymph node samples from North American and European cervids, respectively. However, the specificity and sensitivity of the tests differed significantly. Highly sensitive tests for the detection of prion proteins are an important tool both for the design of effective disease surveillance and control strategies and the safety of the food chain. Thus, this study contributes to the emergency preparedness against CWD.

Imperfect Hopf bifurcation in spiral Poiseuille flow.

We present the results of an experimental study on the transition to spiral vortices in flow between concentric counter-rotating cylinders in the presence of an axial through-flow, i.e., in spiral Poiseuille flow. The experiments were performed in an apparatus having an aspect ratio Gamma=L/d=22.8 ( L axial length, d gap width between cylinders) and end plates enabling an in and outflow of mass. As a result of an applied axial through-flow the "classical" Hopf bifurcation to spiral vortices (SPI) splits up and a primary and secondary branch of down and upstream propagating SPI, respectively, as well as a transient quasiperiodic flow appear. Downstream propagating SPI resulting from the primary supercritical Hopf bifurcation are either convectively or absolutely unstable. The bifurcation structure observed in this open flow experiment is in qualitative agreement with predictions from theory of Hopf bifurcation with broken reflection symmetry [J. D. Crawford and E. Knobloch, Nonlinearity 1, 617 (1988)] and also in quantitative agreement with results from recent numerical calculations [A. Pinter, M. Lücke, and C. Hoffmann, Phys. Rev. E 67, 026318 (2003); C. Hoffmann, M. Lücke, and A. Pinter, Phys. Rev. E 69, 056309 (2004)].

Selective and sensitive trace analysis of sulfur mustard with thermal desorption and two-dimensional gas chromatography-mass spectrometry.

An improved method is presented for the trace analysis of sulfur mustard (HD) in biological samples, such as blood and tissue from laboratory animals. Using the internal standard method and liquid-liquid extraction with ethyl acetate, up to 400 microL of the extract was injected by thermal desorption from Tenax and analyzed by two-dimensional GC-MS/EI in SIM mode. The analysis was compared with a direct GC injection. Reversed thermal desorption was used as a tool for handling heavily contaminated (fat) samples, thus preventing contamination of the injection system and pre-column. A successful analytical configuration has been set up for the bioanalysis of HD at the low, toxicologically relevant pM level. A detection limit of 10 pg mL(-1) blood or pg g(-1) tissue of sulfur mustard (S/N=3) was established by using this configuration.

Lead contamination in American woodcock (Scolopax minor) from Wisconsin.

An initial survey of lead levels in American woodcock (Scolopax minor) from Wisconsin was conducted in 1998 using wing bones from hunter-donated woodcock. The results of this initial survey indicated that young-of-year woodcock were accumulating extremely high levels of lead in their bones. Similar collections were made (using steel shot) between 1999 and 2001. The combined results of this collection indicated that 43.4% of young-of-year woodcock (range 1.5-220.0 microg/g dry wt) and 70% of woodcock chicks (range 9.6-93.0 microg/g dry wt) had bone lead levels in the elevated range (>20 microg/g dry wt). Blood samples were collected from chicks at a site considered elevated based on bone lead results (Mead Wildlife Area) and a site considered background (Navarino Wildlife Area). These samples were analyzed for lead concentration and aminolevulinic acid dehydratase activity. The mean blood lead concentrations of woodcock chicks from both sites did not reach levels that are considered elevated in waterfowl (>0.200 microg/ml). However, blood lead concentrations of chicks from the Mead Wildlife Area were significantly higher than lead levels in chicks from Navarino Wildlife Area (p = 0.002). Although the ultimate sources of lead exposure for Wisconsin woodcock currently remain unidentified, anthropogenic sources cannot be ruled out. Our results indicate that elevated lead exposure in Wisconsin woodcock is common and begins shortly after hatch.

Chaos from Hopf bifurcation in a fluid flow experiment.

Results of an experimental study of a Hopf bifurcation with broken translation symmetry that organizes chaotic homoclinic dynamics from a T2 torus in a fluid flow as a direct consequence of physical boundaries are presented. It is shown that the central features of the theory of Hopf bifurcation in O(2)-symmetric systems where the translation symmetry is broken are robust and are appropriate to describe the appearance of modulated waves, homoclinic bifurcation, Takens-Bogdanov point, and chaotic dynamics in a fluid flow experiment.

Standing waves in flow between finite counterrotating cylinders.

Experimental evidence for standing waves resulting from a supercritical Hopf bifurcation that appears as the first pattern-forming instability in counterrotating Taylor-Couette flow is presented. Depending on the aspect ratio two different types of standing waves, denoted as SW0 and SW(pi), could be observed. Both modes have an azimuthal wave number m=1 but differ in symmetry. While for SW(pi), a spatiotemporal glide-reflection symmetry could be found, SW0 is purely spatial reflection symmetric. The transition between the two modes is found to be organized in a cusp bifurcation unfolded by variations of the aspect ratio. The "classical" spiral vortex flow appears in this control parameter regime only as a result of a secondary steady bifurcation from SW0. This transition is found to be either subcritical or supercritical. The experimentally observed bifurcation structure has been predicted by theory of Hopf bifurcation to spiral vortex flow in finite counterrotating Taylor-Couette systems.

Spinal epidural haematoma as a result of warfarin/fluconazole drug interaction.

This is the first reported case in the emergency medicine literature of a drug interaction between warfarin and fluconazole. We present a case of spinal epidural haematoma and summarize four other case reports reported elsewhere from 1988 to 1996. We admonish emergency physicians to be aware of this dangerous drug combination. Warfarin and fluconazole are frequently encountered drugs in the emergency department and thus any interaction between these drugs is of considerable importance.

Retrospective detection of exposure to organophosphorus anti-cholinesterases: mass spectrometric analysis of phosphylated human butyrylcholinesterase.

In this paper a novel and general procedure is presented for detection of organophosphate-inhibited human butyrylcholinesterase (HuBuChE), which is based on electrospray tandem mass spectrometric analysis of phosphylated nonapeptides obtained after pepsin digestion of the enzyme. The utility of this method is exemplified by the positive analysis of serum samples from Japanese victims of the terrorist attack with sarin in the Tokyo subway in 1995.

Fecal corticosterone reflects serum corticosterone in Florida sandhill cranes.

Florida sandhill cranes (Grus canadensis pratensis) were conditioned to confinement 6 hr/day for 7 days. On day 8, each bird's jugular vein was catheterized, blood samples were drawn, and each crane was confined for 6 hr. Using a randomized, restricted cross-over design, cranes were injected intravenously with either 0.9% NaCl solution or ACTH (cosyntropin; Cortrosyn; 0.25 mg). During the 6 hr of confinement, fecal samples (feces and urine) were collected from each of five cranes immediately after defecation. Individual fecal samples were collected approximately at hourly intervals and assayed for corticosterone. We showed previously that serum corticosterone did not vary significantly following saline injection, but peaked significantly 60 min after ACTH injection. Maximal fecal corticosterone concentrations (ng/g) were greater (P < 0.10; median 1087 ng/g) following ACTH stimulation compared to maximal fecal corticosterone concentrations at the end of acclimation (day 7; median 176) and following saline treatment (median 541). In cranes under controlled conditions, fecal corticosterone concentration reflects serum corticosterone levels, fecal corticosterone, Grus canadensis pratensis, sandhill cranes, serum corticosterone levels.

Bioanalysis of the enantiomers of (+/-)-sarin using automated thermal cold-trap injection combined with two-dimensional gas chromatography.

A fully automated multidimensional gas chromatographic system with thermal desorption injection and alkali flame detection was developed for analysis of the enantiomers of the nerve agent (+/-)-sarin. The chiral stationary phase was CP Cyclodex B on which the sarin enantiomers were completely resolved. The absolute detection limit was 2.5 pg per enantiomer. The method is intended to be used for the analysis of the sarin enantiomers in biological samples. For this purpose, sarin was isolated from guinea pig blood via solid-phase extraction. Deuterated sarin was used as internal standard. Stabilization of sarin in the blood sample by acidification and addition of an excess of a competitive organophosphorus compound (neopentyl sarin) appeared to be essential. The absolute recovery of the extraction procedure was 60%, whereas the recovery relative to the internal standard was 100%.

Intravenous and inhalation toxicokinetics of sarin stereoisomers in atropinized guinea pigs.

We report the first toxicokinetic studies of (+/-)-sarin. The toxicokinetics of the stereoisomers of this nerve agent were studied in anesthetized, atropinized, and restrained guinea pigs after intravenous bolus administration of a dose corresponding to 0.8 LD50 and after nose-only exposure to vapor concentrations yielding 0.4 and 0.8 LCt50 in an 8-min exposure time. During exposure the respiratory minute volume and frequency were monitored. Blood samples were taken for gas chromatographic analysis of the nerve agent stereoisomers and for measurement of the activity of blood acetylcholinesterase (AChE). In all experiments, the concentration of (+)-sarin was below the detection limit (<5 pg/ml). The concentration-time profile of the toxic isomer, i.e., (-)-sarin, after an intravenous bolus was adequately described with a two-exponential equation. (-)-Sarin is distributed ca. 10-fold faster than C(-)P(-)-soman, whereas its elimination proceeds almost 10-fold slower. During nose-only exposure to 0.4 and 0.8 LCt50 of (+/-)-sarin in 8 min, (-)-sarin appeared to be rapidly absorbed. The blood AChE activity decreased during the exposure period to ca. 15 and 70% of control activity, respectively. There were no effects on the respiratory parameters. A significant nonlinearity of the toxicokinetics with dose was observed for the respiratory experiments.