Fentanyl concentrations in ligated femoral blood in the presence and absence of NPS benzodiazepine drugs. A review of over 1250 benzo-dope / fentanyl toxicity cases in Alberta, Canada.

The drug combination referred to as 'benzo dope' has become prevalent in recent years, with an increasing number of fentanyl-related deaths reporting the concomitant presence of one or more benzodiazepine drug, such as etizolam, flualprazolam and flubromazepam. The central nervous system (CNS) depressant effects of these benzodiazepine drugs can exacerbate respiratory and CNS depressant effects resulting from the use/misuse of potent opioids such as fentanyl. This combined and enhanced drug-induced toxicity can pose a significant threat to life. Over a three-year period (2020-2022), the Office of the Chief Medical Examiner, Edmonton, Alberta, Canada issued 2812 case reports with fentanyl detected; of these cases, approximately 45% (1261) were positive for at least one benzodiazepine drug. This study presents concentrations of both fentanyl and benzodiazepine drugs in post mortem blood collected from a visualized, ligated femoral vein. The study demonstrates that the blood concentration of fentanyl in benzo-dope case reports is considerably higher than in cases where no benzodiazepine drug was detected.The median concentration of fentanyl in femoral blood for cases that also contained a benzodiazepine drug was 12.4 ng/mL (2020), 11.9 ng/mL (2021) and 14.0 ng/mL (2022). The median concentration of fentanyl in femoral blood for cases that did not contain a benzodiazepine drug was 8.5 ng/mL (2020), 7.0 ng/mL (2021) and 7.2 ng/mL (2022). The percent differences between the groups were similar with those observed from quantitative analysis of drug powders from unrelated police seizures in Alberta, Canada, suggesting the observed differences in blood fentanyl concentration may be due to the use of a drug substance with a higher concentration of fentanyl.Furthermore, the reported concentration of the benzodiazepine drug(s) is low, such that the role/contribution, if any, that this drug may have played in the decedents' death should be questioned and carefully considered by the certifying medical examiner/coroner.

The distribution and redistribution of carfentanil in post mortem samples.

This article compares 290 post mortem case reports that were positive for carfentanil. All the cases were submitted to, and analyzed by, the toxicology department of the Office of the Chief Medical Examiner, Edmonton, Alberta, Canada. This study highlights the varied distribution of carfentanil in the body after death as a result of misadventure, i.e., these are accidental drug overdose cases. Post mortem samples were collected from more than one anatomical site and analysed for carfentanil using a validated liquid chromatography-tandem mass spectrometry method. Ante-mortem samples were available in 15 of these cases and were also analysed. Post mortem mean blood carfentanil concentrations were found to be 0.362 µg/L (femoral), 0.442 µg/L (iliac), 0.484 µg/L (cardiac) and 0.692 µg/L (subclavian). The mean vitreous humor carfentanil concentration was 0.238 µg/L; the mean urine carfentanil concentration was found to be 0.697 µg/L. Little difference was found between ligated and 'blindstick' femoral blood carfentanil concentrations. Whilst carfentanil can readily be detected in both vitreous humor and urine samples neither were found to correlate with blood concentrations, limiting their use in interpretation. This study demonstrates the importance of multi-site sample collection and subsequent analysis for a thorough post mortem toxicological investigation. The study also highlights the risks and limitations associated with the interpretation of post mortem analytical results concerning carfentanil.

The distribution and redistribution of fentanyl & norfentanyl in post mortem samples.

This article compares 249 post mortem case reports that were positive for fentanyl/norfentanyl. All the cases were submitted to, and analyzed by, the toxicology department of the Office of the Chief Medical Examiner, Edmonton, Alberta, Canada. This study highlights the varied distribution of fentanyl in the body after death as a result of misadventure, i.e., these are accidental drug overdose cases as opposed to a study of analytical data resulting from fentanyl use/administration in a clinical environment and/or death as a result of suicide. Post mortem samples were collected from more than one anatomical site and analyzed for fentanyl and norfentanyl using liquid chromatography-tandem mass spectrometry. Ante-mortem samples were available in 4 of these cases and were also analyzed. Post mortem mean blood fentanyl concentrations were found to be 13.2ng/mL (femoral), 19.1ng/mL (iliac) and 42.0ng/mL (subclavian). For norfentanyl the mean concentrations were 4.6ng/mL (femoral), 4.6ng/mL (iliac) and 7.4ng/mL (subclavian). Mean vitreous fentanyl and norfentanyl concentrations were 10.8ng/mL and 3.5ng/mL respectively. Mean liver fentanyl and norfentanyl concentrations were found to be 185.5ng/g and 18.8ng/g respectively. This study demonstrates the importance of multi-site sample collection and subsequent analysis for a thorough post mortem toxicological investigation. The study also highlights the risks and limitations associated with the interpretation of post mortem analytical results concerning fentanyl.

'Caught in the middle'? Mental nurse training in England 1919-51.

The early history of mental health nurse training is one that has only been partially researched. While some writers have discussed the content and impact of training on the development of mental health nursing, little has been written on the professional and institutional factors that influenced this development. The medical profession, psychiatry, was to play an important role in the development of training and regulation of nursing staff in the large Victorian asylums and was an important influence on the knowledge base of mental health nursing. Their professional organization, the Medico-Psychological Association (the Royal Medico-Psychological Association after 1926 when they acquired a royal prefix) produced the first textbook for asylum nurses in 1885 and established a national training scheme for them 4 years later. However, in 1919 the Nurses Registration Act established the General Nursing Council for England and Wales and this body was given statutory responsibility for the training and registration of nurses, including 'mental' nurses. They were soon to be in conflict with the Medico-Psychological Association. The two organizations continued to run their own rival training schemes for mental health nurses for over 30 years, the Royal Medico-Psychological Association finally relinquishing their role in 1951. The Royal Medico-Psychological Association scheme proved far more popular than the General Nursing Councils, with significantly more nurses participating in it. This paper discusses these organizational influences on the development of 'mental nurse' training and discusses the possible impact that they have had on the knowledge base of mental health nursing.

An interaction between the IL-4Ralpha gene and infection is associated with atopic eczema in young children.

BACKGROUND: A gain of function mutation (Q551- > R) in the IL-4 receptor alpha-chain (IL-4Ralpha) has been found to be associated with atopy in some studies but not others. The different results may be explained by interactions between the IL-4Ralpha polymorphism and environmental factors. OBJECTIVES: To identify interactions between the R551 mutation and environmental factors that are associated with atopy. METHODS: DNA from the Children in Focus (CiF) cohort of the Avon Longitudinal Study of Parents and Children (ALSPAC) was genotyped by heteroduplex formation for the presence of the R551 polymorphism. The data were then analysed for associations with flexural eczema as an indicator of atopic eczema, skin prick tests to allergens and serum IgE levels, and for interactions with environmental factors. RESULTS: A significant (P = 0.02) positive association was seen between the R551 polymorphism and flexural eczema in children up to 6 months of age who had not been given antibiotics, but not in children who had been given antibiotics. This association was maintained as a trend until 30 to 42 months of age but was no longer statistically significant. There was no significant association between the R551 polymorphism and positive skin prick tests or levels of serum IgE at 61 months of age, consistent with the effect of the R551 polymorphism being restricted to early life. CONCLUSION: There is an association between the R551 polymorphism and flexural eczema in children at 6 months of age who have not had infection requiring treatment with antibiotics. Restriction of the R551 association with eczema to children who have not had antibiotics lends support to the 'hygiene hypothesis', which states that exposure to infection in childhood can protect against allergic disease.

Women in mental health nursing: angels or custodians?

Like other 'Cinderella' services mental health nursing has received much less attention from historians than general nursing. However a study of its history can illuminate such issues as the division of labour, gender, images of nursing, professionalisation and unionisation. Drawing on primary historical sources, including hospital archives and contemporaneous reports and journals, the author considers the role of women in mental health nursing, from its origins to the onset of the NHS in 1948. The development of mental health nursing differed substantially from general nursing. It could be argued that the tensions between the two were never more apparent than in the debate surrounding the registration of nursing in the early twentieth century. Female mental health nurses fighting with police in the Radcliff Strike in 1922 portrays a much less famous image in nursing's history than Florence Nightingale with her lamp. The dichotomy between the custodial nature of the Victorian asylum system and the caring ethos espoused by the advocates of 'moral management' created many tensions. Images of nurses as angels, responding to a calling or vocation, sat uneasily with the large numbers of men working in the asylums and the growth of trade unionism in this period, particularly after the foundation of the National Asylum Workers Union in 1910. The periods of industrial unrest in the mental hospitals of the inter-war years saw women members playing an important role; this has important ramifications for mental health nursing today.

Plasma chitotriosidase activity in Gaucher disease patients who have been treated either by bone marrow transplantation or by enzyme replacement therapy with alglucerase.

A marked elevation in plasma chitotriosidase (chitinase) activity has recently been observed in patients with Gaucher disease (Hollak et al 1994). It has been suggested that this phenomenon may serve as a useful marker for the efficacy of treatment with enzyme replacement therapy. We report our findings on the comparison of plasma chitotriosidase levels in 8 patients treated with the modified human placental enzyme alglucerase and 8 patients treated by allogeneic bone marrow transplantation (BMT). Two years after transplantation the activity in the BMT patients had fallen by over 93% and has continued to fall. Now, 5-12 years post-BMT, 6 patients have normal levels of plasma chitotriosidase and 2 patients have activities slightly above the reference range. Patients have been treated with alglucerase for a considerably shorter time than the BMT patients. The chitotriosidase activities have fallen and are continuing to fall in 7 patients but at a slower rate than in the BMT group. In one patient there has been no appreciable change in activity over the last 6 months, which would suggest that she may be on too low a dosage.

Counseling for physical activity: what primary-care physicians should know.

In Connecticut, 22.1% of the adult population report no physical activity other than activities of daily living. Primary care physicians can play a vital role in the flight against a sedentary lifestyle. As outlined in Healthy People 2000 and the Surgeon General's Report on Physical Activity and Health, the primary-care physician's role in the assessment and advising of physical activity is critical. The primary-care physicians that responded to the Connecticut survey appear to be doing an excellent job in delivering this important message. Recommendations made by the primary-care physician can be a great source of motivation for the patient. The primary-care physician's initial goal should be to get the patient active on a daily basis and than progress to more health-based fitness goals. The patient needs to receive instruction on goal setting, safe exercise tips, and adherence strategies. The primary-care physician's low-cost intervention of advising physical activity can help prevent medical problems in the future. The most current recommendation on physical activity states that, "All U.S. adults should accumulate 30 minutes or more of continuous or intermittent amounts of moderate-intensity physical activity on most, preferably all, days of the week." This latest recommendation offers primary-care physicians a broader range of activities to suggest to their patients. An overwhelming number of research studies indicate that physical activity is a powerful weapon in combating a host of lifestyle-related health problems.