Medication errors at hospital admission and discharge in Type 1 and 2 diabetes.

AIMS: To assess the prevalence and characteristics of medication errors at hospital admission and discharge in people with Type 1 and Type 2 diabetes, and identify potential risk factors for these errors. METHODS: This prospective observational study included all people with Type 1 (n = 163) and Type 2 diabetes (n = 508) admitted to the Diabetology-Department of the University Hospital of Montpellier, France, between 2013 and 2015. Pharmacists conducted medication reconciliation within 24 h of admission and at hospital discharge. Medication history collected from different sources (patient/family interviews, prescriptions/medical records, contact with community pharmacies/general practitioners/nurses) was compared with admission and discharge prescriptions to detect unintentional discrepancies in medication indicating involuntary medication changes. Medication errors were defined as unintentional medication discrepancies corrected by physicians. Risk factors for medication errors and serious errors (i.e. errors that may cause harm) were assessed using logistic regression. RESULTS: A total of 322 medication errors were identified and were mainly omissions. Prevalence of medication errors in Type 1 and Type 2 diabetes was 21.5% and 22.2% respectively at admission, and 9.0% and 12.2% at discharge. After adjusting for age and number of treatments, people with Type 1 diabetes had nearly a twofold higher odds of having medication errors (odds ratio (OR) 1.72, 95% confidence interval (CI) 1.02-2.94) and serious errors (OR 2.17, 95% CI 1.02-4.76) at admission compared with those with Type 2 diabetes. CONCLUSIONS: Medication reconciliation identified medication errors in one third of individuals. Clinical pharmacists should focus on poly-medicated individuals, but also on other high-risk people, for example, those with Type 1 diabetes.

Pharmacist intervention to detect drug adverse events on admission to the emergency department: Two case reports of neuroleptic malignant syndrome.

WHAT IS KNOWN AND OBJECTIVE: Neuroleptic malignant syndrome (NMS) is a rare but severe adverse effect of antipsychotic drugs. CASE DESCRIPTION: We report two cases of NMS highlighted by clinical pharmacists in an emergency unit during summer. One of them was fatal. Medication reconciliation processes performed at admission identified treatment with loxapine for one of them and with loxapine and clozapine for the other. Interview of the patients highlighted clinical symptoms suggesting NMS, allowing the pharmacists to alert the medical team. WHAT IS NEW AND CONCLUSION: Adverse drug events may be severe and clinical pharmacists in emergency departments can help to detect them.

Progastrin production transitions from Bmi1+/Prox1+ to Lgr5high cells during early intestinal tumorigenesis.

Progastrin is an unprocessed soluble peptide precursor with a well-described tumor-promoting role in colorectal cancer. It is expressed at small levels in the healthy intestinal mucosa, and its expression is enhanced at early stages of intestinal tumor development, with high levels of this peptide in hyperplastic intestinal polyps being associated with poor neoplasm-free survival in patients. Yet, the precise type of progastrin-producing cells in the healthy intestinal mucosa and in early adenomas remains unclear. Here, we used a combination of immunostaining, RNAscope labelling and retrospective analysis of single cell RNAseq results to demonstrate that progastrin is produced within intestinal crypts by a subset of Bmi1+/Prox1+/LGR5low endocrine cells, previously shown to act as replacement stem cells in case of mucosal injury. In contrast, our findings indicate that intestinal stem cells, specified by expression of the Wnt signaling target LGR5, become the main source of progastrin production in early mouse and human intestinal adenomas. Collectively our results suggest that the previously identified feed-forward mechanisms between progastrin and Wnt signaling is a hallmark of early neoplastic transformation in mouse and human colonic adenomas.

Effective population size, reproductive success and sperm precedence in the butterfly, Bicyclus anynana, in captivity.

A pedigree approach is used to estimate the effective population size yn two population cages of the butterfly, Bicyclus anynana. Each cage was founded with 54 individually marked adults of each sex. Matings were recorded over a 3-day period. Eggs were then collected from each female over a similar period before the numbers of hatching larvae were counted to assess progeny number. The males showed a higher variance in reproductive success than the females. Since about one-quarter of all females mated more than once, we also examined the pattern of sperm precedence using molecular markers or, in separate crossing experiments, wing pattern mutants. Both instances of complete first and last male sperm precedence, as well as of sperm mixing, were found. In some crosses a 'leakiness' was found in which some of the early eggs laid by a female were fertilized by a male partner which was subsequently completely unsuccessful. However, the estimates of effective population size were largely unaffected by the pattern of sperm precedence. Estimates for Ne : N in each cage were close to 0.60. The possibility of obtaining comparable estimates in selected natural populations of butterflies is discussed.

Defects in TLR3 expression and RNase L activation lead to decreased MnSOD expression and insulin resistance in muscle cells of obese people.

Obesity is associated with chronic low-grade inflammation and oxidative stress that blunt insulin response in its target tissues, leading to insulin resistance (IR). IR is a characteristic feature of type 2 diabetes. Skeletal muscle is responsible for 75% of total insulin-dependent glucose uptake; consequently, skeletal muscle IR is considered to be the primary defect of systemic IR development. Interestingly, some obese people stay insulin-sensitive and metabolically healthy. With the aim of understanding this difference and identifying the mechanisms responsible for insulin sensitivity maintenance/IR development during obesity, we explored the role of the latent endoribonuclease (RNase L) in skeletal muscle cells. RNase L is a regulator of innate immunity, of double-stranded RNA sensors and of toll-like receptor (TLR) 4 signaling. It is regulated during inflammation by interferons and its activity is dependent on its binding to 2-5A, an oligoadenylate synthesized by oligoadenylate synthetases (OAS). Increased expression of RNase L or downregulation of its inhibitor (RLI) improved insulin response in mouse myogenic C2C12 cells and in primary human myotubes from normal-weight subjects treated with palmitate, a saturated free fatty acid (FFA) known to induce inflammation and oxidative stress via TLR4 activation. While RNase L and RLI levels remained unchanged, OAS level was decreased in primary myotubes from insulin-resistant obese subjects (OB-IR) compared with myotubes from insulin-sensitive obese subjects (OB-IS). TLR3 and mitochondrial manganese superoxide dismutase (MnSOD) were also underexpressed in OB-IR myotubes. Activation of RNase L by 2-5A transfection allowed to restore insulin response, OAS, MnSOD and TLR3 expression in OB-IR myotubes. Due to low expression of OAS, OB-IR myotubes present a defect in RNase L activation and TLR3 regulation. Consequently, MnSOD level is low and insulin sensitivity is reduced. These results support that RNase L activity limits FFA/obesity-induced impairment of insulin response in muscle cells via TLR3 and MnSOD expression.

Lack of response to selection for lower fluctuating asymmetry of mutant eyespots in the butterfly Bicyclus anynana.

Fluctuating asymmetry (FA) is claimed both to provide a means of evaluating developmental stability, and to reflect an individual's quality or the stress experienced during development. FA refers to the nondirectional variation between left and right sides, whereas directional asymmetry (DA) refers to a significant directional variation between the sides. We studied four eyespots on the dorsal forewing of the tropical butterfly, Bicyclus anynana. Two of the eyespots were specified by a mutant allele, Spotty, that was fixed in the stock. These eyespots showed higher FA than the two flanking, wild-type eyespots, although they are all formed by the same developmental pathway. We applied artificial selection for lower FA of the novel eyespots in an attempt to increase their developmental stability. There was significant variation present in individual FA in our study. However, this did not change as a result of the artificial selection. Most of the variation in FA can be accounted for by individual differences in developmental stability rather than by the applied selection or by environmental variation. Thus, it was not possible to produce any increased developmental stability of the novel eyespots by selecting for low FA. The estimates of realized heritability for both FA and DA of each eyespot were not significantly different from zero. The results suggest that FA provides little, if any, potential for exploring the mechanistic basis of developmental stability.

Ribonucleic acid synthesis during the differentiation of sporangia in the water mold Achlya.

The role of ribonucleic acid (RNA) synthesis in the development of sporangia in the saprolegniaceous mold Achlya was studied. Methods were developed for growing and treating large populations of mycelia so that the hyphal tips would differentiate into sporangia with considerable synchrony. Under the starvation conditions imposed for the differentiation of sporangia, net RNA, deoxyribonucleic acid (DNA), and protein synthesis ceased. However, incorporation of radioactive precursors into RNA continued at a high rate throughout the period of differentiation, showing that the enzymatic mechanism for RNA synthesis was still in an active state. Actinomycin D inhibited the differentiation of sporangia and the incorporation of labeled precursors into RNA. The level of actinomycin used did not inhibit the normal outgrowth and branching of the mycelia that occurred during differentiation. Thus, DNA-dependent RNA synthesis was required for the differentiation of sporangia. Sucrose gradient analysis of newly synthesized RNA showed that only the ribosomal and soluble fractions of RNA were labeled during vegetative growth. During the differentiation of sporangia, ribosomal and soluble RNA fractions were also labeled, and, in addition, a heterodisperse fraction of labeled RNA which was heavier than ribosomal RNA appeared; this fraction was not evident in the newly synthesized RNA from vegetative mycelia.