A European cross-sectional survey to investigate how involved doctors training in clinical pharmacology are in drug concentration monitoring.

PURPOSE: Therapeutic drug monitoring (TDM) is widely recognised as a key attribute of clinical pharmacologists; yet, the extent to which physicians undertaking postgraduate training in clinical pharmacology (hereafter trainees) are involved in TDM is poorly characterised. Our own experience suggests wide variation in trainee exposure to TDM. METHOD: We performed a Europe-wide cross-sectional internet-based survey of trainees to determine the nature and extent of trainee involvement in TDM. RESULTS: There were 43 responses from eight countries analysed. Of the 21 respondents from the UK, all were also training in general internal medicine (GIM), while all of the respondents who were solely training in clinical pharmacology were from outside the UK. Overall, 86.0% of respondents reported access to drug monitoring for clinical care at their affiliated institution, of which 81.0% were personally involved in TDM in some capacity. On average, trainees reported that drug monitoring was available for 16 of the 33 (48%) of the drug/drug classes surveyed. UK-based respondents were involved in requesting drug-level investigations and interpreting the results for patients under their care in 76.2% and 85.7% of cases, respectively, while non-UK respondents supported other healthcare professionals to interpret results in 45.4% of cases. Trainees felt TDM training was generally either insufficient or very inadequate. CONCLUSION: While access to TDM is relatively available at institutions where trainees are based, the role of trainees is variable and affected by a variety of factors including country and training programme. Universally, trainees feel they need more education in TDM.

An investigation on the impact of substrate type, temperature, and iodine on moon jellyfish production.

Jellyfish are a popular public aquarium species, however, their collection from natural populations is undesirable due to impact on species abundance and bycatch. Thus, a sustainable supply of jellyfish bred in-house would be highly desirable. Here we describe an investigation into developing a sustainable moon jellyfish, Aurelia aurita, breeding program by determining the impact of substrate type on reattachment of polyps and the influence of iodine and temperature on strobilation and ephyra production. To test whether reattachment and growth of moon jellyfish polyps are influenced by substrate type polyps were provided with anthropogenic and natural substrates after being dislodged in experimental aquaria. Polyps selectively re-attached to plastics rather than natural materials. However, polyp growth was similar on all tested substrates. We tested whether cooling and addition of iodine affected strobilation. A period of cooling of around 10 °C while also introducing soluble iodine to the polyps enhanced strobilation rate. This method produced ephyra at a reliable rate in captivity negating the need for collection of wild individuals providing a supply of individuals for exhibit and for conservation research within a public aquarium. These results demonstrate that plastics should be adopted as an easier to colonize substrate and the use of cooling with iodine addition can enhance sustainable breeding protocols of moon jellyfish and may be relevant to the production of comparable jellyfish species.

Species-related variations in lipoprotein metabolism: the impact of FER(HDL) on susceptibility to atherogenesis.

Several animal models have been used to investigate the mechanisms of atherogenesis. Each animal species has advantages and disadvantages with regard to similarity with human lipoprotein metabolism. In humans, fractional esterification rate in apolipoprotein B-depleted plasma (FER(HDL)) has been shown to correlate with the quality of high density lipoprotein particles. Increased values of FER(HDL) indicate an atherogenic lipoprotein profile. Such an association has not been defined in animal models. Thus, we have characterized plasma lipoprotein profile and FER(HDL) values in four animal species namely, cats, pigs, guinea pigs and rabbits. These animal species have been used in experimental dyslipidemia and atherosclerosis. Our data indicate a wide rage of variations among various animal species. High-density lipoprotein (HDL) particles contain approximately 40% of total plasma cholesterol concentrations in rabbits, pigs and cats <10% in guinea pigs. A negative association between FER(HDL) values and plasma HDL-cholesterol levels was observed in pigs, rabbits and guinea pigs. On the other hand, FER(HDL) values showed a positive association with plasma triglyceride levels in all animal species tested. These findings are in agreement with data reported in humans. More research is needed to identify the better animal models which closely resemble human lipoprotein metabolism.

Profound metabolic acidosis from pyroglutamic acidemia: an underappreciated cause of high anion gap metabolic acidosis.

The workup of the emergency patient with a raised anion gap metabolic acidosis includes assessment of the components of "MUDPILES" (methanol; uremia; diabetic ketoacidosis; paraldehyde; isoniazid, iron or inborn errors of metabolism; lactic acid; ethylene glycol; salicylates). This approach is usually sufficient for the majority of cases in the emergency department; however, there are many other etiologies not addressed in this mnemonic. Organic acids including 5-oxoproline (pyroglutamic acid) are rare but important causes of anion gap metabolic acidosis. We present the case of a patient with profound metabolic acidosis with raised anion gap, due to pyroglutamic acid in the setting of malnutrition and chronic ingestion of acetaminophen.

Multiplying the serum aminotransferase by the acetaminophen concentration to predict toxicity following overdose.

CONTEXT: The first available predictors of hepatic injury following acetaminophen (APAP) overdose are the serum APAP and aminotransferases [AT, i.e., aspartate (AST) aminotransferase or alanine (ALT) aminotransferase]. OBJECTIVE: We describe the initial value, rate of change, and interrelationship between these biomarkers in patients who develop hepatotoxicity despite treatment following acute overdose. A new parameter, the APAP × AT multiplication product, is proposed for early risk stratification. METHODS: We conducted a descriptive study of individuals selected from a multicenter retrospective cohort of patients hospitalized for APAP poisoning. We selected those acute APAP overdose patients who subsequently developed AT > 1,000 IU/L. Rising serum AT values were compared to simultaneously measured (or estimated) falling serum APAP. The APAP × AT was expressed relative to initiation of acetylcysteine therapy and grouped by time to meeting hepatotoxicity criteria. RESULTS: In the 94 cases studied, serum APAP concentrations were still appreciable [median 570 (interquartile range (IQR) 314-983) µmol/L] at the time of the first measured AT [211 (77-511) IU/L at 15.3 (12.1-19.2) h post-ingestion], yielding an initial APAP × AT of 99,000 (52,000-240,000) µmol × IU/L(2). Because serum AT rose rapidly (doubling time 9.5 h ) and APAP fell slowly (half-life 4.8 h), the multiplication product remained elevated during the first 12-24 h of antidotal therapy, especially among patients who developed earlier hepatotoxicity (AT > 1,000 IU/L). DISCUSSION AND CONCLUSIONS: The APAP × AT multiplication product, calculated at the time of presentation and after several h of antidotal therapy, holds promise as a new risk predictor following APAP overdose. It requires neither graphical interpretation nor accurate time of ingestion, two limitations to current risk stratification.

When do the aminotransferases rise after acute acetaminophen overdose?

CONTEXT: Rising aminotransferases (ATs) [either aspartate aminotransferase (AST) or alanine aminotransferase (ALT) are one of the first signs of hepatotoxicity following acetaminophen (APAP)] overdose (OD). However, the timing and speed of such rises are not well characterized, hampering early risk prediction. OBJECTIVE: To describe the kinetics of AT release in acute APAP OD patients who develop hepatotoxicity despite treatment. METHODS: A descriptive study of acute APAP OD patients with peak AT > 1,000 IU/L taken from the derivation subset of the Canadian Acetaminophen Overdose Study (CAOS), a large, multicenter retrospective cohort of patients hospitalized for APAP poisoning. RESULTS: Of 2,488 hospital admissions for acute APAP OD, 94 met inclusion criteria. Treatment with acetylcysteine, mostly intravenously, was begun in all cases within 24 h of ingestion. The initial AT concentration was already elevated in most patients at presentation [median 211 (IQR 77-511) IU/L obtained at 15.3 (12.1-19.2) h postingestion], and exceeded 100 IU/L in almost all patients within 24 h of ingestion. Serum AT concentrations rose rapidly [doubling time 9.5 h (95% CI: 8.7-10.4 h)], especially in patients who developed AT > 1,000 IU/L within 48 h of ingestion. Coagulopathy was worse in these patients and in those with an AT > 250 IU/L during the first 12 h of treatment with acetylcysteine. DISCUSSION AND CONCLUSIONS: An abnormal and rapidly doubling AT at presentation is more typical in severely poisoned patients, as judged by the effects on clotting. These data suggest that risk prediction instruments may be improved by incorporating both the serum AT concentration at initiation of antidotal therapy and its rate of change. Further studies using such an approach are warranted.