Feasibility and initial efficacy of project-based treatment for people with ABI

Background: Communication impairments are common and pervasive for people a long time following acquired brain injury (ABI). These impairments have a significant impact on a person's quality of life (QOL) post‐injury. Project‐based treatment is a treatment approach that could have an impact on communication skills and QOL for people with ABI a long‐term post‐injury. This treatment is embedded in a context of meaningful activities chosen by people with ABI, whereby, as a group, they work collaboratively to achieve a tangible end product. Aims: To evaluate the feasibility and initial efficacy of project‐based treatment on improving the communication skills and QOL for people with ABI. Methods & Procedures: An exploratory controlled trial with alternate allocation of groups, and follow‐up at 6–8 weeks, was completed. Twenty‐one people with chronic ABI were recruited in groups of two to three from community settings, allocated to either a TREATMENT (n = 11) or WAITLIST group (n = 10). Participants attended a 20‐h group‐based treatment over 6 weeks where they worked towards achieving a project that helped others. To determine feasibility, four criteria were used: demand, implementation, practicality and acceptability. A range of communication and QOL outcomes was used to determine a fifth feasibility criterion, initial efficacy. Some of these criteria were additionally used to evaluate the feasibility of the outcomes. Outcomes & Results: All participants received the treatment as allocated with high attendance and no dropouts. The treatment was feasible to deliver as intended and was highly acceptable to participants. Medium and large effect sizes were found from pre‐ to post‐treatment, and from pre‐treatment to follow‐up for measures of conversation, perceived communicative ability and QOL. Conclusions & Implications: Project‐based treatment is feasible with indications of initial efficacy for both communication skills and QOL. The treatment provides a promising new approach for improving communication skills and QOL in people with chronic acquired brain injuries in the community setting

Future perspectives of PoseidOn stratification for clinical practice and research

A total of 50% of patients undergoing IVF treatment has previously been estimated to fulfill the POSEIDON classification criteria; importantly, although the reproductive prognosis differs between patients, POSEIDON patients share the same characteristic of a low ovarian response to exogenous gonadotropin stimulation\u2014independent of age. POSEIDON patients require focused attention as regards ovarian stimulation in order to increase the chances of having at least one euploid blastocyst for transfer\u2014the success criterion for stimulation set forth by the POSEIDON Group. The key to success seems to be individualization in all steps of treatment. In this perspective article we discuss the future impact of the POSEIDON stratification for daily clinical practice as well as for research

Simultaneous time-space resolved reflectivity and interferometric measurements of dielectrics excited with femtosecond laser pulses

13 pags., 7 figs., 1 tab.Simultaneous time-and-space resolved reflectivity and interferometric measurements over a temporal span of 300 ps have been performed in fused silica and sapphire samples excited with 800 nm, 120 fs laser pulses at energies slightly and well above the ablation threshold. The experimental results have been simulated in the frame of a multiple-rate equation model including light propagation. The comparison of the temporal evolution of the reflectivity and the interferometric measurements at 400 nm clearly shows that the two techniques interrogate different material volumes during the course of the process. While the former is sensitive to the evolution of the plasma density in a very thin ablating layer at the surface, the second yields an averaged plasma density over a larger volume. It is shown that self-trapped excitons do not appreciably contribute to carrier relaxation in fused silica at fluences above the ablation threshold, most likely due to Coulomb screening effects at large excited carrier densities. For both materials, at fluences well above the ablation threshold, the maximum measured plasma reflectivity shows a saturation behavior consistent with a scattering rate proportional to the plasma density in this fluence regime. Moreover, for both materials and for pulse energies above the ablation threshold and delays in the few tens of picoseconds range, a simultaneous >low reflectivity> and >low transmission> behavior is observed. Although this behavior has been identified in the past as a signature of femtosecond laser-induced ablation, its origin is alternatively discussed in terms of the optical properties of a material undergoing strong isochoric heating, before having time to substantially expand or exchange energy with the surrounding media.This work has been partly funded by Laserlab-Europe (Grant Agreement No. 284464, EU’s Seventh Framework Programme, Project No. SLIC002014), by the Spanish Ministry of Economy and Competiveness (Project No. TEC2014-52642- C2-1-R) as well as by the Danish Council for Independent Research | Natural Sciences. M.G.-L. acknowledges the FPU (Formación de Profesorado Universitario) Grant No. AP2012- 0217 awarded by the Spanish Ministry of Education.Peer Reviewe

Ultra-Long Pharmacokinetic Properties of Insulin Degludec are Comparable in Elderly Subjects and Younger Adults with Type 1 Diabetes Mellitus

BACKGROUND: Management of diabetes in elderly subjects is complex and careful management of glucose levels is of particular importance in this population because of an increased risk of diabetes-related complications and hypoglycaemia. OBJECTIVE: The aim of this study was to evaluate the pharmacokinetic and pharmacodynamic properties of insulin degludec (IDeg), a basal insulin with an ultra-long duration of action, in elderly subjects with type 1 diabetes compared with younger adults. METHODS: This trial was a randomised, double-blind, two-period, crossover trial conducted in a single centre and included both inpatient and outpatient periods. Subjects were men and women aged 18–35 years inclusive (younger adult group) or ≥65 years (elderly group) with type 1 diabetes who received IDeg (0.4 U/kg) via subcutaneous injection in the thigh once-daily for six days. Following 6-day dosing, a 26-hour euglycaemic glucose clamp procedure was conducted to evaluate the steady-state pharmacodynamic effects of IDeg. Blood samples were taken for pharmacokinetic analysis up to 120 h post-dose. Pharmacokinetic endpoints included the total exposure of IDeg, ie the area under the IDeg serum concentration curve during one dosing interval at steady state (AUC(IDeg,τ,SS)) (τ = 0–24 h, equal to one dosing interval) and the maximum IDeg serum concentration at steady state (C(max,IDeg,SS)). Pharmacodynamic endpoints included the total glucose-lowering effect of IDeg, ie the area under the glucose infusion rate (GIR) curve at steady state (AUC(GIR,τ,SS)), and the maximum GIR at steady state (GIR(max,IDeg,SS)). RESULTS: Total exposure (AUC(IDeg,τ,SS)) and maximum concentration (C(max,IDeg,SS)) of IDeg were comparable between elderly subjects and younger adults. Estimated mean age group ratios (elderly/younger adult) for AUC(IDeg,τ,SS) and C(max,IDeg,SS) and corresponding two-sided 95 % confidence intervals (CIs) were 1.04 (95 % CI 0.73–1.47) and 1.02 (95 % CI 0.74–1.39), respectively. Mean AUC(IDeg,0–12h,SS)/AUC(IDeg,τ,SS) was 53 % in both younger adult and elderly subjects, showing that in both age groups IDeg exposure was evenly distributed across the first and second 12 h of the 24-hour dosing interval. No statistically significant differences were observed between younger adult and elderly subjects with regard to AUC(GIR,τ,SS) (the primary endpoint of this study) and GIR(max,IDeg,SS). Estimated mean age group ratios (elderly/younger adult) for AUC(GIR,τ,SS) and GIR(max,IDeg,SS) and corresponding two-sided 95 % CIs were 0.78 (95 % CI 0.47–1.31) and 0.80 (95 % CI 0.54–1.17), respectively. Duration of action was beyond the clamp duration of 26 h in all subjects. CONCLUSIONS: The exposure of IDeg at steady state during once-daily dosing was similar in younger adult and elderly subjects. The glucose-lowering effect of IDeg was numerically lower in elderly subjects compared with younger adults, but no significant differences were observed between age groups. The ultra-long pharmacokinetic and pharmacodynamic properties of IDeg observed in younger adults were preserved in elderly subjects with type 1 diabetes. Clinical trials.gov number: NCT0096441

Personalized infection prevention and control: dentifying patients at risk of healthcare-associated infection

BackgroundFew healthcare-associated infection (HAI) studies focus on risk of HAI at the point of admission. Understanding this will enable planning and management of care with infection prevention at the heart of the patient journey from the point of admission.AimTo determine intrinsic characteristics of patients at hospital admission and extrinsic events, during the two years preceding admission, that increase risk of developing HAI.MethodsAn incidence survey of adults within two hospitals in NHS Scotland was undertaken for one year in 2018/19 as part of the Evaluation of Cost of Nosocomial Infection (ECONI) study. The primary outcome measure was developing any HAI using recognized case definitions. The cohort was derived from routine hospital episode data and linkage to community dispensed prescribing data.FindingsThe risk factors present on admission observed as being the most significant for the acquisition of HAI were: being treated in a teaching hospital, increasing age, comorbidities of cancer, cardiovascular disease, chronic renal failure and diabetes; and emergency admission. Relative risk of developing HAI increased with intensive care unit, high-dependency unit, and surgical specialties, and surgery 30 days in the two years to admission.ConclusionTargeting patients at risk of HAI from the point of admission maximizes the potential for prevention, especially when extrinsic risk factors are known and managed. This study proposes a new approach to infection prevention and control (IPC), identifying those patients at greatest risk of developing a particular type of HAI who might be potential candidates for personalized IPC interventions

FAM111 protease activity undermines cellular fitness and is amplified by gain-of-function mutations in human disease

Dominant missense mutations in the human serine protease FAM111A underlie perinatally lethal gracile bone dysplasia and Kenny-Caffey syndrome, yet how FAM111A mutations lead to disease is not known. We show that FAM111A proteolytic activity suppresses DNA replication and transcription by displacing key effectors of these processes from chromatin, triggering rapid programmed cell death by Caspase-dependent apoptosis to potently undermine cell viability. Patient-associated point mutations in FAM111A exacerbate these phenotypes by hyperactivating its intrinsic protease activity. Moreover, FAM111A forms a complex with the uncharacterized homologous serine protease FAM111B, point mutations in which cause a hereditary fibrosing poikiloderma syndrome, and we demonstrate that disease-associated FAM111B mutants display amplified proteolytic activity and phenocopy the cellular impact of deregulated FAM111A catalytic activity. Thus, patient-associated FAM111A and FAM111B mutations may drive multisystem disorders via a common gain-of-function mechanism that relieves inhibitory constraints on their protease activities to powerfully undermine cellular fitness

Epidemiology of healthcare-associated infection reported from a hospital-wide incidence study: considerations for infection prevention and control planning

BackgroundThe measure of disease frequency most widely used to report healthcare-associated infection (HAI) is the point-prevalence survey. Incidence studies are rarely performed due to time and cost constraints; they show which patients are affected by HAI, when and where, and inform planning and design of infection prevention and control (IPC) measures.AimTo determine the epidemiology of HAI within a general and a teaching hospital in Scotland.MethodsA prospective observational incidence study was undertaken for one year from April 2018 using data collected as part of the Evaluation of Cost of Nosocomial Infection (ECONI) study. A novel, robust approach was undertaken, using record linkage to national administrative data to provide full admission and discharge information. Cases were recorded if they met international HAI definitions.FindingsIncidence of HAI for the combined hospitals was 250 HAI cases per 100,000 acute occupied bed-days (AOBD). Highest frequency was in urinary tract (51.2 per 100,000 AOBD), bloodstream (44.7), and lower respiratory tract infection (42.2). The most frequently reported organisms were Escherichia coli, Staphylococcus aureus, and norovirus. Incidence of HAI was higher in older people and emergency cases. There was an increase in the rate of HAI in summer months (pneumonia, respiratory, surgical, and gastrointestinal infection) and in winter months norovirus gastrointestinal infection (P < 0.0001). The highest incidence specialties were intensive care, renal medicine, and cardiothoracic surgery. HAI occurred at a median of 9 days (interquartile range: 4–19) after admission. Incidence data were extrapolated to provide an annual national estimate of HAI in NHS Scotland of 7437 (95% confidence interval: 7021–7849) cases.ConclusionThis study provides a unique overview of incidence of HAI and identifies the burden of HAI at the national level for the first time. Understanding the incidence in different clinical settings, at different times, will allow targeting of IPC measures to those patients who would benefit the most