Functionality of a novel follitropin alfa pen injector: results from human factor interactions by patients and nurses

Objective: The main objective of this user experience testing study was to evaluate the impact of human factors on the use of a disposable pen containing follitropin alfa by patients and nurses with special focus on the convenience, safety and ease of use, in different types of stimulation protocols.

Methods: Infertile women trying to conceive, and specialist nurses were recruited across 6 European countries. In total 18 patients and 19 nurses took part in the testing, which included both nurse-patient pairings and in-depth interviews. A standardized list of expected and pre-defined critical steps according to the Instructions for Use (IFU), was used to assess the correct handling of the pen.

Results: During the user experience testing, no critical errors, related to the use of the pen, which could affect the success of the injection process were identified. In general, both nurses and patients found the pen very easy to learn, use and would be confident using the pen for self-injection. Nurses also found the pen very easy to train the patients.

Conclusions: The study provides valuable information on the pen from both patient and nurse perspectives in different simulated scenarios reflecting standard practice.     

Presurgical selection of the ideal aneurysm clip by the use of a three-dimensional planning system

Aneurysm occlusion rate after clipping is higher than after endovascular treatment. However, a certain percentage of incompletely clipped aneurysms remains. Presurgical selection of the proper aneurysm clips could potentially reduce the rate of incomplete clippings caused by inadequate clip geometry. The aim of the present study was to assess whether preoperative 3D image-based simulation allows for preoperative selection of a proper aneurysm clip for complete occlusion in individual cases. Patients harboring ruptured or unruptured cerebral aneurysms prior to surgical clipping were analyzed. CT angiography images were transferred to a 3D surgical-planning station (Dextroscope®) with imported models of 58 aneurysm clips. Intracranial vessels and aneurysms were segmented and the virtual aneurysm clips were placed at the aneurysm neck. Operating surgeons had information about the selected aneurysm clip, and patients underwent clipping. Intraoperative clip selection was documented and aneurysm occlusion rate was assessed by postoperative digital subtraction angiography. Nineteen patients were available for final analysis. In all patients, the most proximal clip at the aneurysm neck was the preselected clip. All aneurysms except one were fully occluded, as assessed by catheter angiography. One aneurysm had a small neck remnant that did not require secondary surgery and was occluded 15 months after surgery. 3D image-based preselection of a proper aneurysm clip can be translated to the operating room and avoids intraoperative clip selection. The associated occlusion rate of aneurysms is high.

     

Pharmacological treatments prescribed to people with autism spectrum disorder (ASD) in primary health care

Rationale

Autism spectrum disorders (ASDs) affect 1 % of children, having significant impact on health and social outcomes. Psychotropic medication use by individuals with ASD in the USA increased over time, and polypharmacy occurred in >50 % of those prescribed. In the UK, no psychotropic drugs are approved in ASDs, and little is known about patterns of pharmacological treatment in the ASD population and associated co-morbidities.

Methods

We used The Health Improvement Network, a nationally representative primary care database, to assess the prevalence of ASD diagnoses, psychotropic drug prescribing and neuropsychiatric co-morbidities of 0–24 year olds between 1992 and 2008.

Results

ASD prevalence increased 65-fold from 0.01 % (1992) to 0.50 % (2008). Psychotropic drugs were prescribed to 29 % (1,619/5,651) of the ASD cohort; the most prescribed drugs were sleep medication (9.7 % of prescribed patients), psychostimulants (7.9 %) and antipsychotics (7.3 %). More patients were given psychostimulants and sleep medications over time from 1.5–6.3 % and 2.2–5.9 % respectively. Thirty-seven per cent of the cohort had ≥1 record of a neuropsychiatric co-morbidity, the most common being developmental difficulties and learning disabilities (12.6 %), behavioural, conduct and personality disorders (11.1 %) and attention deficit hyperactivity disorder (7.5 %).

Conclusions

British physicians are more conservative in prescribing practice than American colleagues. However, use of psychostimulants and antipsychotics is much higher in those with ASD than in the general population. Polypharmacy was seen in 34 % of prescribed patients in 2008. Additional studies examining use, efficacy, and long-term safety of antipsychotics and psychostimulants in autistic individuals are warranted.     

An effect of moderate hepatic impairment on the pharmacokinetics and safety of darapladib

Aim/MethodsThis was a phase 1, open label, non-randomized study designed to assess the pharmacokinetics and safety/tolerability of 10 consecutive once daily 40 mg oral doses of darapladib in subjects with moderate hepatic impairment (n = 12) compared with matched healthy volunteers (n = 12).ResultsFor total darapladib, a small increase in total and peak exposure was observed in the subjects with moderate hepatic impairment compared with the subjects with normal hepatic function. The area under the plasma concentration−time curve during a dosing interval of duration τ (AUC(0,τ), geometric mean 223 ng ml⁻¹ h [90% CI 158, 316 ng ml⁻¹h], in moderate hepatic impaired subjects, vs. geometric mean 186 ng ml⁻¹h [90% CI 159, 217 ng ml⁻¹h], in healthy subjects) and maximum concentration (C_max) were 20% and 7% higher, respectively, in the subjects with moderate hepatic impairment than in the healthy control subjects and there was no change in time to maximum concentration (t_max). Protein binding was performed to measure the amount of unbound drug vs. bound. Steady-state was achieved by day 10 for darapladib and its metabolites (M4, M3 and M10). Darapladib was generally well tolerated, with adverse events (AEs) reported by seven subjects in the hepatic impairment group and three subjects in the healthy matched group (five and one of which were drug-related AEs, respectively). The most common AEs were gastrointestinal. These AEs were mostly mild to moderate and there were no deaths, serious AEs or withdrawals due to AEs.ConclusionsThe results of this phase 1 study show that darapladib (40 mg) is well tolerated and its pharmacokinetics remain relatively unchanged in patients with moderate hepatic impairment.     

Is grandparental childcare socio-economically patterned? Evidence from the English longitudinal study of ageing

Grandparents play a vital role in providing childcare to families. Qualitative research and evidence from parents raise concerns that it is grandparents who are socio-economically disadvantaged who provide grandchild care more regularly, perform more intensive tasks, and care out of financial necessity. However, no European studies have investigated these issues at population level. This study is based on grandparents aged 50+ who looked after grandchildren. Data are from wave 8 of the nationally representative English Longitudinal Study of Ageing (2016/2017). We exploit newly collected information on frequency of grandchild care, activities, and reasons for care. Using multinomial regressions, we first examined the extent to which grandparents’ socio-economic characteristics (wealth and education) are associated with frequency of grandchild care. Second, using logistic regressions, we investigated whether wealth and education are associated with activities and reasons for grandchild care. Overall, grandparents from disadvantaged socio-economic backgrounds were more likely to provide more regular childcare. Similarly, grandparents in the lowest wealth quartile were more involved in hands-on activities (cooking, taking/collecting grandchildren to/from school), whereas highly educated grandparents were more likely to help grandchildren with homework. Finally, better-off grandparents were more likely to look after grandchildren to help parents and provide emotional support and less likely to report difficulty in refusing to provide care. Our findings show that grandparental childcare varies by socio-economic status with more intensive childcare activities falling disproportionately on those with fewer resources, and this may act to exacerbate existing socio-economic inequalities in later life.

     

Specific Recognition of Plasma Membranes by Embryonic Cells

Methods have been developed for preparation of plasma membrane fractions from embryonic neural retina and cerebellum. These membrane fractions are specifically bound by intact cells of the original tissue (homotypic binding) and not by cells from the other tissue (heterotypic binding). Aggregation of neural retina cells and cerebellar cells is prevented by addition of homotypic membranes but not by heterotypic membranes. We conclude that, under our assay conditions, these embryonic cells specifically recognize homotypic membranes, and that the specificity of recognition is the same as in the initial step in the process of cellular aggregation.     

Athymic nude mice: induction of tumors containing Epstein-Barr virus using Burkitt's-related cell lines.

We studied tumor induction in athymic nude mice by D98/HR-1 cells, an epithelial somatic cell hybrid containing the Epstein-Barr virus (EBV) genome, and by the parental D98 and HR-1 cells. Groups of animals were inoculated with cells grown in culture, with cells from tumors induced by the cell lines, or with cells from lines derived from tumors. The tumors induced by D98/HR-1 cells were undifferentiated carcinomas; those induced by D98 cells were carcinomas and those induced by HR-1 cells were poorly differentiated lymphomas. Preliminary data suggest that the number of EBV genome equivalents was sharply reduced in cells from both D98/HR-1 and HR-1 tumors. Subsequent passage of tumor cells in vitro resulted in a partial recovery in the number of EBV genome equivalents in HR-1 cells and a complete recovery in D98/HR-1 cells. The reduction in the number of EBV genomes in the tumor cells suggests that in vitro passage can influence the number of EBV genomes in these cells.     

Interleukin-3 treatment of rhesus monkeys leads to increased production of histamine-releasing cells that express interleukin-3 receptors at high levels

To understand the hematopoietic and nonhematopoietic responses to interleukin-3 (IL-3), expression of cell-surface IL-3 receptors (IL-3R) was examined on bone marrow (BM) cells and peripheral blood (PB) cells of rhesus monkeys during the course of in vivo IL-3 treatment. Whereas IL-3R expression is low in untreated monkeys, IL-3 administration led to a gradual increase in both low- and high-affinity binding sites for IL-3. This increase reflected the total number of cells expressing IL- 3Rs, as detected by flow cytometry using biotinylated IL-3. Most of these IL-3R+ cells in both BM and PB could be characterized as basophilic granulocytes that contained high levels of histamine. In contrast to the effect on these differentiated cells, IL-3 administration did not significantly alter the low level IL-3R expression on immature, CD34+ cells. Further flow cytometric analysis using biotinylated growth factors showed that the IL-3R+ basophils also expressed receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF), but not for IL-6 or Kit ligand. These findings indicated that the IL-3R+ cells included neither monocytes, which express GM-CSFRs and IL-6Rs abundantly, nor mast cells, which express c- kit. By combining flow cytometric and Scatchard data, it was calculated that the basophils contain as many as 1 to 2 x 10(3) high-affinity IL- 3Rs and 15 to 30 x 10(3) low-affinity sites. The finding that in vivo IL-3 treatment leads to the production of large numbers of cells that express high levels of IL-3R and are capable of producing histamine provides an explanation for the often severe allergic reactions that occur during prolonged IL-3 administration. It also indicates that IL- 3, in addition to its direct effects on hematopoietic cells, may also stimulate hematopoiesis through the release of secondary mediators such as histamine by IL-3-responsive mature cells.     

Malignant non-Hodgkin's lymphoma presenting with arrhythmia and conduction defects. Report of 2 cases

Primary cardiac lymphoma is very rare. Secondary localisations are more common, observed in 15 to 30% of autopsy series. Clinical symptoms of cardiac involvement are rare, explaining the usual post-mortem diagnosis. The presentation of cardiac involvement by arrhythmias and conduction defects is very uncommon. The authors report two cases, the first of a 35 year old man in whom primary cardiac lymphoma presented with ventricular tachycardia complicated secondarily by complete atrioventricular block (AVB) with pseudo-inferior wall infarction. The second case was a 37 year old man with a cutaneous T cell lymphoma in whom complete AVB was the first sign of a secondary cardiac localisation of his disease. The finding of cardiac lymphoma should lead to aggressive chemotherapy as soon as possible.     

Functional heterogeneity of cholangiocytes

The objective of this article is to summarize the findings related to the notion that cholangiocytes, within small and large intrahepatic ducts, are heterogeneous regarding (1) morphology; (2) secretion in response to hormones and peptides and to bile acids; and (3) proliferation in response to injury or toxins, including bile duct ligation (BDL), acute carbon tetrachloride (CCl 4 ) administration, chronic feeding of bile salts (i.e., taurocholate [TC] or taurolithocholate [TLC]) or alpha-naphthylisothiocyanate (ANIT). After an overview of the morphology of the biliary epithelium, we provide a summary of cholangiocyte function, the in vivo models, and the in vitro experimental tools (i.e., small and large cholangiocytes or small and large intrahepatic bile duct units [IBDU]), which allowed us to demonstrate cholangiocyte heterogeneity. After a discussion on the receptors, transporters, and channels that are heterogeneously expressed by cholangiocytes, we discuss the different-sized ducts that differentially respond to injury and toxins. Finally, we review the human diseases that selectively target specific-sized ducts.