Assessment of an Innovative Medication Adherence Training Exercise in an Interprofessional Training Program

OBJECTIVE To assess the effect of an innovative training exercise on post-graduate healthcare trainees’ knowledge and perspectives of medication adherence and skills gained within an interprofessional training program. METHODS Postgraduate trainees (medicine, pharmacy, advanced practice nursing, and mental health) at the Michael E. DeBakey VA Medical Center’s Center of Excellence in Primary Care Education interprofessional training program participated in a medication adherence exercise and training session. The session included a formal PowerPoint presentation, an innovative medication adherence simulation exercise, clinical scenarios, and a journal club. Verbal feedback during the debriefing session occurred after the medication adherence simulation exercise and throughout the session. RESULTS Six trainees participated in the exercise and training session (2 medical residents, 2 nurse practitioner residents, 1 pharmacy resident, and 1 clinical psychology fellow). Trainees reported developing a greater understanding for barriers patients face with medication adherence, empathy, and strategies to manage patients’ medication adherence. CONCLUSIONS The medication adherence exercise and training session provided an opportunity for healthcare professionals from different professions to discuss medication adherence and share their educational training and previous clinical experiences within an interprofessional training program

Emergence of the GII-4 Norovirus Sydney2012 strain in England, winter 2012-2013.

Norovirus is the commonest cause of acute gastrointestinal disease and is the main aetiological agent of outbreaks of gastroenteritis, particularly in semi-closed environments. Norovirus infections in England typically peak between December and March each year. The most commonly detected norovirus strains belong to the genetically diverse genogroup-II genotype-4 (GII-4) genocluster and in the previous two norovirus winter seasons the majority of GII-4 strains in circulation worldwide have been genetically similar to the GII-4 strain New Orleans 1805/2009/USA. At the beginning of the 2012/13 season a genetically distinct GII-4 strain (Sydney 2012/NSW0514/2012/AU) was described which emerged worldwide during the winter of 2012/13. Here we describe the emergence of norovirus strains genetically related to Sydney2012 in England during the 2012/13 season to replace NewOrleans2009 strains as the most commonly detected variant of GII-4 norovirus in England. Furthermore, we demonstrate that whilst the emergence of Sydney2012 coincided with an early peak in the number of norovirus outbreaks, there was not an overall increase in norovirus activity compared to the previous season. Finally, we show that the Sydney2012 strain is associated with distinct genetic changes compared to the NewOrleans2009 strain, and these changes may have contributed to the emergence of the Sydney2012 strain

Generative modelling of the thalamo-cortical circuit mechanisms underlying the neurophysiological effects of ketamine

Cortical recordings of task-induced oscillations following subanaesthetic ketamine administration demonstrate alterations in amplitude, including increases at high-frequencies (gamma) and reductions at low frequencies (theta, alpha). To investigate the population-level interactions underlying these changes, we implemented a thalamo-cortical model (TCM) capable of recapitulating broadband spectral responses. Compared with an existing cortex-only 4-population model, Bayesian Model Selection preferred the TCM. The model was able to accurately and significantly recapitulate ketamine-induced reductions in alpha amplitude and increases in gamma amplitude. Parameter analysis revealed no change in receptor time-constants but significant increases in select synaptic connectivity with ketamine. Significantly increased connections included both AMPA and NMDA mediated connections from layer 2/3 superficial pyramidal cells to inhibitory interneurons and both GABAA and NMDA mediated within-population gain control of layer 5 pyramidal cells. These results support the use of extended generative models for explaining oscillatory data and provide in silico support for ketamine's ability to alter local coupling mediated by NMDA, AMPA and GABA-A

Neighbourhood unemployment and other socio-demographic predictors of emergency hospitalisation for infectious intestinal disease in England: A longitudinal ecological study

BACKGROUND:Previous studies have observed that infectious intestinal disease (IID) related hospital admissions are higher in more deprived neighbourhoods. These studies have mainly focused on paediatric populations and are cross-sectional in nature. This study examines recent trends in emergency IID admission rates, and uses longitudinal methods to investigate the effects of unemployment (as a time varying measure of neighbourhood deprivation) and other socio-demographic characteristics on IID admissions for adults and children in England. METHODS:A longitudinal ecological analysis was performed using Hospital Episode Statistics on emergency hospitalisations for IID, collected over the time period 2012-17 across England. Analysis was conducted at the neighbourhood (Lower-layer Super Output Area) level for three age groups (0-14; 15-64; 65+ years). Mixed-effect Poisson regression models were used to assess the relationship between trends in neighbourhood unemployment and emergency IID admission rates, whilst controlling for measures of primary and secondary care access, underlying morbidity and the ethnic composition of each neighbourhood. RESULTS:From 2012-17, declining trends in emergency IID admission rates were observed for children and older adults overall, while rates increased for some sub-groups in the population. Each 1 percentage point increase in unemployment was associated with a 6.3, 2.4 and 4% increase in the rate of IID admissions per year for children [IRR=1.06, 95%CI 1.06-1.07], adults [IRR=1.02, 95%CI 1.02-1.03] and older adults [IRR=1.04, 95%CI 1.036-1.043], respectively. Increases in poor primary care access, the percentage of people from a Pakistani ethnic background, and the prevalence of long-term health problems, in a neighbourhood, were also associated with increases in IID admission rates. CONCLUSIONS:Increasing trends in neighbourhood deprivation, as measured by unemployment, were associated with increases in emergency IID admission rates for children and adults in England, despite controlling for measures of healthcare access, underlying morbidity and ethnicity. Research is needed to improve understanding of the mechanisms that explain these inequalities, so that effective policies can be developed to reduce the higher emergency IID admission rates experienced by more disadvantaged communities

Effectiveness of successive booster vaccine doses against SARS-CoV-2 related mortality in residents of long-term care facilities in the VIVALDI study

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused severe disease in unvaccinated long-term care facility (LTCF) residents. Initial booster vaccination following primary vaccination is known to provide strong short-term protection, but data are limited on duration of protection and the protective effect of further booster vaccinations. OBJECTIVE: To evaluate the effectiveness of third, fourth and fifth dose booster vaccination against SARS-CoV-2 related mortality amongst older residents of LTCFs. DESIGN: Prospective cohort study. SETTING: LTCFs for older people in England participating in the VIVALDI study. METHODS: Residents aged >65 years at participating LTCFs were eligible for inclusion if they had at least one polymerase chain reaction or lateral flow device result within the analysis period 1 January 2022 to 31 December 2022. We excluded individuals who had not received at least two vaccine doses before the analysis period. Cox regression was used to estimate relative hazards of SARS-CoV-2 related mortality following 1-3 booster vaccinations compared with primary vaccination, stratified by previous SARS-CoV-2 infection and adjusting for age, sex and LTCF size (total beds). RESULTS: A total of 13,407 residents were included. Our results indicate that third, fourth and fifth dose booster vaccination provide additional short-term protection against SARS-CoV-2 related mortality relative to primary vaccination, with consistent stabilisation beyond 112 days to 45-75% reduction in risk relative to primary vaccination. CONCLUSIONS: Successive booster vaccination doses provide additional short-term protection against SARS-CoV-2 related mortality amongst older LTCF residents. However, we did not find evidence of a longer-term reduction in risk beyond that provided by initial booster vaccination

Effects of different segmentation methods on geometric morphometric data collection from primate skulls

1. An increasing number of studies are analysing the shapes of objects using geometric morphometrics with tomographic data, which are often segmented and transformed to three‐dimensional (3D) surface models before measurement. This study aimed to evaluate the effects of different image segmentation methods on geometric morphometric data collection using computed tomography data collected from non‐human primate skulls. 2. Three segmentation methods based on a visually selected threshold, a half‐maximum height protocol and a gradient and watershed algorithm were compared. For each method, the efficiency of surface reconstruction, the accuracy of landmark placement and the level of variation in shape and size compared with various levels of biological variation were evaluated. 3. The visual‐based method inflated the surface in high‐density anatomical regions, whereas the half‐maximum height protocol resulted in a large number of artificial holes and erosion. However, the gradient‐based method mitigated these issues and generated the most efficient surface model. The segmentation method used had a much smaller effect on shape and size variation than interspecific and inter‐individual differences. However, this effect was statistically significant and not negligible when compared with intra‐individual (fluctuating asymmetric) variation. 4. Although the gradient‐based method is not widely used in geometric morphometric analyses, it may be one of promising options for reconstructing 3D surfaces. When evaluating small variations, such as fluctuating asymmetry, care should be taken around combining 3D data that were obtained using different segmentation methods

Clinical effectiveness of SARS-CoV-2 booster vaccine against Omicron infection in residents and staff of Long-Term Care Facilities: a prospective cohort study (VIVALDI)

Background: Successive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have caused severe disease in long-term care facility (LTCF) residents. Primary vaccination provides strong short-term protection, but data are limited on duration of protection following booster vaccines, particularly against the Omicron variant. We investigated the effectiveness of booster vaccination against infections, hospitalizations, and deaths among LTCF residents and staff in England. Methods: We included residents and staff of LTCFs within the VIVALDI study (ISRCTN 14447421) who underwent routine, asymptomatic testing (December 12, 2021–March 31, 2022). Cox regression was used to estimate relative hazards of SARS-CoV-2 infection, and associated hospitalization and death at 0–13, 14–48, 49–83, 84–111, 112–139, and 140+ days after dose 3 of SARS-CoV-2 vaccination compared with 2 doses (after 84+ days), stratified by previous SARS-CoV-2 infection and adjusting for age, sex, LTCF capacity, and local SARS-CoV-2 incidence. Results: A total of 14 175 residents and 19 793 staff were included. In residents without prior SARS-CoV-2 infection, infection risk was reduced 0–111 days after the first booster, but no protection was apparent after 112 days. Additional protection following booster vaccination waned but was still present at 140+ days for COVID-associated hospitalization (adjusted hazard ratio [aHR], 0.20; 95% CI, 0.06–0.63) and death (aHR, 0.50; 95% CI, 0.20–1.27). Most residents (64.4%) had received primary course vaccine of AstraZeneca, but this did not impact pre- or postbooster risk. Staff showed a similar pattern of waning booster effectiveness against infection, with few hospitalizations and no deaths. Conclusions: Our findings suggest that booster vaccination provided sustained protection against severe outcomes following infection with the Omicron variant, but no protection against infection from 4 months onwards. Ongoing surveillance for SARS-CoV-2 in LTCFs is crucial

Cdc28/Cdk1 Regulates Spindle Pole Body Duplication through Phosphorylation of Spc42 and Mps1

AbstractDuplication of the Saccharomyces cerevisiae spindle pole body (SPB) once per cell cycle is essential for bipolar spindle formation and accurate chromosome segregation during mitosis. We have investigated the role that the major yeast cyclin-dependent kinase Cdc28/Cdk1 plays in assembly of a core SPB component, Spc42, to better understand how SPB duplication is coordinated with cell cycle progression. Cdc28 is required for SPB duplication and Spc42 assembly, and we found that Cdc28 directly phosphorylates Spc42 to promote its assembly into the SPB. The Mps1 kinase, previously shown to regulate Spc42 phosphorylation and assembly, is also a Cdc28 substrate, and Cdc28 phosphorylation of Mps1 is needed to maintain wild-type levels of Mps1 in cells. Analysis of nonphosphorylatable mutants in SPC42 and MPS1 indicates that direct Spc42 phosphorylation and indirect regulation of Spc42 through Mps1 are two overlapping pathways by which Cdc28 regulates Spc42 assembly and SPB duplication during the cell cycle