bluuebunny/crossref_metadata_2025 huggingface dataset:
2150 Understanding the COTE lingo: a quality improvement project
Authors: Havard M , Sarto R , Rowlands S , Long S
Published: August 2024

Introduction

The terminology surrounding manual-handling equipment and discharge planning is rarely taught in medical school. Yet, it is crucial for medical staff, particularly those working on Care of the Elderly (COTE) wards, to comprehend these terms to accurately assess a patient’s function and optimise discharge planning.

Methods

A 17-question survey was distributed to establish the baseline knowledge of medical staff in a district general hospital, with the aim of using PDSA (plan, do, study, act) cycles for improvement as needed. Following preliminary data analysis, a lunchtime hospital teaching session was designed to educate individuals on these key terms and equipment. Ten clinicians attended and took part in a mentimeter quiz reassessing knowledge post-teaching.

Results

Seventeen participants, ranging from physician associates and junior doctors to consultants, completed the initial survey anonymously. Knowledge varied widely, with scores ranging from 15% to 91%. All participants accurately identified a Zimmer frame, 15 (88%) correctly labelled a PAT slide and 13 (76%) a hoist. Reassuringly, all knew that the acronym ‘POC’ stood for Package of Care. Poorly recognised equipment included turn discs, standing hoists and hover jacks. Furthermore, the term ‘reablement’ and the healthboard-specific ‘complex needs booklet’ lacked clear definitions. While many participants could define fast track discharge, they could not distinguish between the two types. The average score per question increased from 53% in the pre-teaching survey to 59% post-teaching, however this was not statistically significant (P = 0.57).

Conclusions

Although medical staff were familiar with certain equipment, they lacked understanding of more specialist aspects of discharge planning and less commonly used equipment. Unfortunately, these results did not significantly change post-teaching, likely due to low attendance; however, we are hopeful that the survey distribution and teaching will spark discussion throughout the hospital. We have now adapted the teaching content into posters for the next PDSA cycle.
2275 Enhancing delirium awareness among patients’ relatives: a quality improvement project in elderly care
Authors: MohdDaud WNM , Bharathi D , Blazy L , McKeever C , Ford J
Published: August 2024

Aim

This Quality Improvement Project (QIP) addressed the pressing need for increased awareness of delirium among patients’ relatives. With a 26% rise in the elderly population in Cambridgeshire, surpassing the 18.6% national average, the project provides crucial information to enhance patients’ relatives access to information about delirium, a condition affecting up to 50% of older hospitalised patients.

Method

This prospective QIP was conducted across seven Cambridge University Hospital (CUH) geriatric wards. Qualitative surveys determined delirium awareness, understanding, interest and perception of information availability among patients’ relatives with delirium. Measurements included data on the views of online Trust delirium information. Interventions included designing a new eye-catching delirium information poster with a QR code linked to the Trust delirium information leaflet, strategically placing QR code-enabled posters in wards, awareness campaigns targeting healthcare professionals, liaison with the inpatient Dementia team, and targeted communication at Dementia and Delirium Champion training sessions for nursing and healthcare staff.

Results

Pre- and post-intervention questionnaires, involving 13 relatives visiting these wards, showed a 16%, 10% and 20% respective increase in respondents’ awareness, understanding, and interest in delirium. There was a 29% increase in awareness of location of delirium information post intervention. After the interventions, views of the Trust delirium website increased by 132%. Cycles of the QIP highlighted the importance of laminated posters to comply with infection control measures and the need liaison with ward teams about strategic poster placement.

Conclusion

this QIP successfully demonstrated the effectiveness of QR code enabled access to patient/relative information and that a multi-faceted approach is required to facilitate effective information provision. We also demonstrated these measures increased delirium awareness in relatives. Future recommendations include continuous monitoring of the availability of posters within clinical areas, content evaluation, and work with the Dementia team to roll this out to all wards with older people within Trust.
2342 A comprehensive profile of a retrospective care home cohort using linked health and social care data
Authors: Knight M , Clegg A , Todd O
Published: August 2024

Introduction

Many UK care home (CH) residents live with multiple long-term conditions, leading to high levels of healthcare utilisation. Previous studies have used routine data to describe their health and social care characteristics separately. Accurately identifying when an individual is admitted to a CH from routine data is challenging. This study aims to provide a combined health and social care profile of a cohort of long-stay CH residents, at the point of admission, using linked primary, secondary and social care data.

Methods

Individuals aged 65 and over registered to a GP practice contributing to the ‘Connected Bradford’ dataset who were admitted to a CH between January 2016 and December 2019 were included. Start and end dates for social care packages (nursing and residential) were identified from local authority social care data. Respite and reablement packages were excluded. Complete self-funders were not identified with this method. Linked secondary and primary care data were used to describe health characteristics. CH residents identified using primary care records and local authority data will be compared.

Results

2801 individuals were admitted to a CH during the study period of whom 2048 (73%) were long-stay residents (>6 weeks). Only 70% of participants identified using local authority data, had a primary care code indicating CH residency in their primary care records. Median length of stay was 272 days (IQR 63 to 480). Mean age at admission was 85 years (SD 8), median Index of Multiple Deprivation decile five. 59% of residents required nursing care from admission. 79% of individuals were taking 5 or more medications.

Conclusions

Using local authority data offers a novel way to identify and characterise CH residents. Linkage of primary care records to local authority data improves identification of CH residents using routine data. Additional linkage with address history would further improve accuracy.
2293 Targeted geriatric assessment in the emergency department: does it make a difference?
Authors: Barrera VC , Kee JXL , Tan-Patanao RT , Koh XY , Loi FC , Seah CYE , Mon HT , Rosario BH
Published: August 2024

Introduction

Older people represent between 21 to 40% of Emergency Department (ED) users and proportionally use more ED services than any other age group.

Method

Retrospective review was undertaken from 13th January 2022 until 23rd December 2022 in older patients discharged from the ED ambulatory area following a targeted geriatric assessment and recommended follow-up interventions at the geriatric clinic. Two groups were identified, those compliant to follow-up interventions (GpC) and those that defaulted (GpD). Demographic information, hospital utilisation and mortality (up to one year), and any post-visit fragility fractures were reviewed. Data collection included identification of osteoporosis or osteopenia and cognitive decline during or following the visit and findings were compared across the 2 groups.

Results

137 patients were reviewed, and 79 patients (58%) compliant to geriatric follow-up (GpC) and 58 patients (42%) non-compliant (GpD). Age and sex were similar, 80 vs 80 years, range 65–98 years and female s 58% vs 62%. ED 7-day re-attendances were similar, 9% vs 12%, but 30-day hospital admissions were lower 10% vs 16%, although 1 year ED attendances were higher in the compliant group, 56% vs 45%, which did not translate to more 1 year hospital admissions 35% vs 33%. Mortality was 11% vs 14%. More patients were identified as having osteoporosis 30% vs 21% or high-risk osteopenia 18% vs 9%, and a larger number of patients had unevaluated bone health in the non-compliant group 19% vs 47%. However, fragility fractures were similar, 9% vs 7%. AMT was 7.94 vs 5.02, range 0–10 and cognitive impairment identified in 43% vs 33%, with dementia in 24% vs 14%, Mild Cognitive Impairment in 15% vs 7% and suspected but not evaluated in 4% vs 12%.

Conclusion

Targeted geriatric assessment has shown earlier and improved identification of underlying frailty and geriatric syndromes.
2224 What are we teaching UK medical students about ageing? Results of the third BGS national curriculum survey
Authors: Watson A , Pearson GME , Fisher G , Redgrave M , Khoshnaghsh A , Winter R , Masud T , Blundell A , Gordon AL , Henderson EJ
Published: August 2024

Introduction

The ageing population means all doctors, regardless of specialty, will need knowledge, skills, and attitudes to care for older people with complex health conditions. An essential component of preparing the medical workforce to best care for older people is by including teaching on ageing and geriatric medicine in undergraduate medical curricula. Here we present results of the British Geriatrics Society (BGS) national curriculum survey 2021–22, highlighting progress made in undergraduate teaching in geriatric medicine.

Methods

All 35 UK GMC-registered medical schools at the time of data collection were invited to participate in an online survey on content, methodology, timing, and duration of teaching in ageing and geriatric medicine. The survey was structured around the 2013 BGS recommended undergraduate curriculum, for consistency with previous surveys.

Results

30/35 of UK medical schools responded (83% response rate). Most teaching occurred in the fourth year of study (21/30, 70%). The majority (15/30, 50%) reported a discrete module for geriatric medicine lasting 4–8 weeks, an increase on previous surveys. However, several programmes have reduced the amount of in-person teaching since the COVID-19 pandemic. Notably, three schools reported geriatric medicine exposure lasting >12 weeks. Of these, two were integrated clerkships and one a dedicated geriatric medicine module. There is increasing focus on multidisciplinary education, with emphasis on combining virtual or simulated teaching with other healthcare professions (n = 7). Every school (n = 30) taught at least one topic as small-group or case-based learning.

Conclusion

There is a trend towards increasing exposure to geriatric medicine compared to previous surveys in 2008 and 2013. However, several of the programmes reporting greater exposure incorporate geriatric medicine in an integrated clerkship rather than as a dedicated module. Programmes demonstrated a move from didactic teaching towards small-group and case-based learning, employing a wider variety of assessment methods than previous.
2165 Barriers perceived by medical students when considering a career in geriatric medicine.
Authors: Fisher G , True S
Published: August 2024

Introduction

Despite the UK’s increasing life expectancy, and increase in the elderly population, there is an overwhelming lack of Geriatricians in the UK; as of 2022, there is only 1 consultant Geriatrician per 8031 individuals over the age of 65 (BGS, 2023). To meet the complex care needs of this population, there must be a focus on increasing the interest that doctors have towards Geriatric Medicine, with the overall aim being to recruit more doctors into the speciality.

Method

The aim of this review was to investigate what factors medical students perceive as barriers to pursuing a career in Geriatric Medicine and then, from identifying these, generate a set of comprehensive suggestions as to how to tackle these barriers at a medical school level to increase the interest and ultimately uptake of Geriatric Medicine. The qualitative review contains literature published between 2003 and 2023 accessed using MedLine.

Results

Six themes were identified in answering our question: (a) high emotional burden, (b) caring for patients with complex needs, (c) negative preconceptions of non-clinical factors (prestige, salary, career progression), (d) negative influence of clinical educators, (e) lack of intellectual stimulation and (f) lack of exposure to the speciality and the elderly.

Conclusion

The barriers perceived by medical students when considering Geriatrics as a speciality are complex and multifaceted; these barriers must be tackled promptly in order to secure the next generation of Geriatricians. We suggest that this work can be used as a foundation for further qualitative studies with UK medical students to investigate barriers that are specific to UK students. From this, interventional courses designed to increase Geriatric Medicine uptake could be developed to strengthen the UK Geriatric Medicine workforce.
2253 Establishing a national network of trainee representatives in geriatric medicine higher specialty training
Authors: True S , O'Brien V
Published: August 2024

Introduction

This study demonstrates how a network of geriatric medicine trainee representatives was established across the UK. The intention of the network was threefold: accurately represent the interests of trainees by gathering national feedback, develop a job description of deanery trainee representatives and create a community of practice between representatives.

Method

Deanery trainee representatives were identified through TPDs then contacted to participate in an online questionnaire which also consented for whatsapp group invitation. Results: Deanery representatives were identified for 12 out of 13 deaneries, the final post was vacant. The survey response rate was 83% and all respondents gave permission to be added to the whatsapp group. We gathered information regarding eligibility, appointment and the role of deanery trainee representatives.

Results

Most deaneries (73%) do not require representatives to be a minimum grade whereas 27% required representatives to be ST4 or above. Over half (55%) were appointed following an expression of interest without an election, 27% required an election and 9% were approach and appointed directly either by the TPD or current representative. Once appointed 82% had no fixed term whilst 18% would have a term limited to two years. Once appointed the role entails an invitation to the local higher specialty training committee for 73% of respondents and 73% also reported a role in organising regional training.

Conclusions

The aim of this project to create a network between deanery representatives has been achieved and produced an engaged network of representatives facilitating accurate representation of trainees at a national level. Further applications include collaboration between trainees to share training practices. In a period of training recovery following the Covid-19 pandemic and a new geriatric medicine curriculum a community of practice between trainee representatives has enormous potential to improve training quality and experiences for geriatric medicine trainees in the UK.
2191 Physiotherapists’ perspectives of barriers and facilitators to effective community provision after hip fracture
Authors: Adams J , Jones G , Sadler E , Guerra S , Sobolev B , Sackley C , Sheehan K
Published: August 2024

Introduction

to investigate physiotherapists’ perspectives of effective community provision following hip fracture.

Methods

qualitative semi-structured interviews were conducted with 17 community physiotherapists across England. Thematic analysis drawing on the Theoretical Domains Framework identified barriers and facilitators to implementation of effective provision. Interviews were complemented by process mapping community provision in one London borough, to identify points of care where suggested interventions are in place and/or could be implemented.

Results

four themes were identified: ineffective coordination of care systems, ineffective patient stratification, insufficient staff recruitment and retention approaches and inhibitory fear avoidance behaviours. To enhance care coordination, participants suggested improving access to social services and occupational therapists, maximising multidisciplinary communication through online notation, extended physiotherapy roles, orthopaedic-specific roles and seven-day working. Participants advised the importance of stratifying patients on receipt of referrals, at assessment and into appropriately matched interventions. To mitigate insufficient staff recruitment and retention, participants proposed return-to-practice streams, apprenticeship schemes, university engagement, combined acute-community rotations and improving job description advertisements. To reduce effects of fear avoidance behaviour on rehabilitation, participants proposed the use of patient-specific goals, patient and carer education, staff education in psychological strategies or community psychologist access. Process mapping of one London borough identified points of care where suggested interventions to overcome barriers were in place and/or could be implemented.

Conclusion

physiotherapists propose that effective provision of community physiotherapy following hip fracture could be improved by refining care coordination, utilising stratification techniques, employing enhanced recruitment and retainment strategies and addressing fear avoidance behaviours.
2218 Experience of family caregivers for older patients with delirium: a qualitative study
Authors: Mahmoud A , Raghuraman S , Richards E , Allan L , Anderson R ,   on behalf of the RECOVERED Study team, Trimmer SM
Published: August 2024

Background

Delirium is associated with psychological and cognitive complications that have impacts beyond the patients. Although family members and carers can play a significant role in the management and recognition of delirium, there is limited research on the experience of family caregivers in the context of delirium. This study aims to explore the needs and experiences of family caregivers for a person with delirium and offer suggestions to support them.

Method

A qualitative interview study with family caregivers of persons with delirium. Data were analysed using an abductive analysis approach.

Results

Fourteen family caregivers were interviewed. Carers explained their feeling of responsibility to support their loved ones with delirium, however, they perceived their caregiving role negatively because of increasing demands and the lack of sufficient support. Carers attributed their emotional exhaustion and distress to the onset of delirium, change in the personality of the person with delirium, confusion and progression of delirium. Additionally, carers indicated the negative impact of caregiving on the quality of the relationship between them and person with delirium. This highlights the need to enhance the support provided to carers to mitigate the emotional and relationship impact of caregiving on the carer. We identified the needs of carers for people with delirium including: education on delirium, reassurance, information on care pathways and support from formal carers to take breaks.

Conclusions

Viable solutions to assist family caregivers include more support for the carer in formulating care plans for people with delirium, the development of support groups for family caregivers of people with delirium, and a case worker. These solutions may help to decrease re-hospitalisation and admission to care homes. Future research should focus on approaches to better support carers of people with delirium, and to shift the care plan from person-centred into person and family-centred approach.
2225 Geriatric patients in virtual wards; technology adoption style, ease of use, and adherence to remote monitoring technology
Authors: Pugmire J , Wilkes M , Kramer A , Zaniello B , Zahradka N
Published: August 2024

Introduction

NHS England is committed to the expansion of virtual wards, necessitating patient engagement with home care technology. Literature suggests there is a technology adoption lag among older populations. We investigated if this lag was evident in geriatric virtual ward patients.

Methods

Data from three NHS trusts using a virtual care platform (March 2021–August 2023) were aggregated to assess differences in perceived ease of use, technology adoption style, and measures of adherence. All patients received the Telehealth Usability Questionnaire Ease of Use (EOU) subsection (higher scores indicate higher EOU). Patients completed surveys via tablet, wore monitoring devices, and took blood pressure readings. We dichotomised age (<75 vs. 75+) and used Fisher’s exact and Wilcoxon-Mann–Whitney tests.

Results

Of 857 patients, 36.9% were geriatric (mean age 81.5 years). The younger group (mean age 59.1 years) had 541 patients. Gender was evenly split between age groups (p = 0.62). Median EOU scores were 5.5 (geriatric) and 6.2 (younger) (p < 0.001). Geriatric patients were more likely to avoid or delay technology adoption (82% vs. 56% in younger patients, p < 0.001). Geriatric patients had higher adherence to the wearable device (median 95.3%) compared to younger patients (93.3%, p < 0.001). Blood pressure (median 81.6%) and survey adherence (median 83.3%) did not significantly differ between groups (p = 0.076, p = 0.0501).

Conclusions

Despite perceptions and literature suggesting older patients are less comfortable with technology, our findings demonstrate high engagement in virtual ward technology. While differences exist in technology adoption and EOU scores, geriatric patients exhibit equal or higher adherence to remote monitoring tasks. These results challenge stereotypes and underscore the importance of incorporating technology in geriatric care.
2249 Exploring the experiences of sedentary behaviour in older adults aged ≥ 75 years
Authors: Tadrous R , Forster A , Farrin A , Coventry P , Clegg A
Published: August 2024

Introduction

Older adults are the fastest growing and most sedentary group in society. With sedentary behaviour associated with deleterious health outcomes, reducing sedentary time may improve overall well-being. Adults aged ≥75 years are underrepresented in sedentary behaviour research. This study aimed to qualitatively profile the sedentary behaviour of adults aged ≥75 years. This included ascertaining older adults’ understanding of sedentary behaviour; identifying the activities performed in sitting and standing and identifying the barriers and facilitators towards reducing sedentary time.

Methods

Four focus groups with community-dwelling older adults aged ≥75 years were held between October–December 2022. Audio recordings and workshop notes were transcribed verbatim and inductive and deductive thematic analyses were conducted.

Results

Six community-dwelling older adults with a mean age of 83 were recruited. Group members were largely unaware of their sedentary behaviour, and the risk associated with prolonged sedentary behaviour. The activities performed in sitting and standing, and barriers and facilitators to reducing sedentary time were charted to the Capability Opportunity Motivation-Behaviour (COM-B). Analytical themes explored sedentary behaviour throughout older adulthood, the influence of sedentary behaviour on sleep, and the importance of social connectedness to reduce sedentary time.

Conclusions

This study provided novel insights into older adults’ reports of sedentary behaviour progressing throughout older adulthood. Sedentary behaviour in adults aged ≥75 years present similarly to a younger subset of older adults with regards to the activities performed in sitting, and the barriers and facilitators to reducing their sedentary time. However, the activities performed in sitting may be performed for longer, and the barriers to reducing sedentary behaviour may present more frequently. Social support appears valuable when attempting to reduce sedentary time, however, further research is necessary to explore the views of older adults who are socially isolated.
2250 A mixed-method feasibility study of an intervention to reduce sedentary behaviour in community-dwelling older adults aged ≥ 75 years
Authors: Tadrous R , Forster A , Farrin A , Coventry P , Clegg A
Published: August 2024

Introduction

Older adults are the fastest growing and most sedentary group in society. With sedentary behaviour associated with negative health outcomes, reducing sedentary time may improve overall wellbeing. This single-arm mixed-method feasibility study explored the acceptability of an intervention to reduce sedentary behaviour in community-dwelling older adults aged ≥75 years.

Methods

Participants were recruited from the Community Ageing Research 75+ Study (CARE75+) cohort, with factors such as age, frailty status, living arrangements and levels of sedentariness being considered. The intervention consisted of an educational booklet including advice on how to reduce sedentary behaviour, a smartwatch with a sedentary reminder function, educational group sessions and follow up phone calls. The 9-week intervention was conducted from June–August 2023. Reach, uptake, adherence, and adverse events were recorded, and the acceptability of the intervention was explored through semi-structured exit interviews.

Results

Of the 39 eligible participants, 10 consented (5 M:5F) and had a mean age 84.3 years. The intervention had an uptake and reach of 25.6%, and retention of 100%. No falls, hospitalisations or deaths occurred, and three cases of mild irritation were reported which resolved during the study. 100% adherence was observed for the group sessions and follow-up phone calls, and 65% for self-monitoring. Qualitative data suggests that participants were receptive of the intervention according to the domains of the Theoretical Framework of Acceptability, and suggestions were provided on refining the intervention components.

Conclusion

Strategies to reduce sedentary behaviour were tested on a diverse sample of community-dwelling older adults in the oldest old age group, with varying levels of sedentary behaviour and frailty status. The presented strategies appear to be acceptable, appropriate, safe, and high levels of adherence were observed. Participant feedback will be used to refine the intervention.
2352 Disease burden of respiratory syncytial virus (RSV) in adults 60+ in the United Kingdom: targeted literature review (TLR)
Authors: Malmenas M , Bayerl B , Carroll S , Desai M , Balogh O , Ahmed T
Published: August 2024

Introduction

It is increasingly clear that RSV infections in older adults significantly impact the UKs already strained public health system. However, the true burden remains underestimated (Korsten K, Eur Respir J, 2021, 57, 2,002,688; Sharp A, Influenza Other Respir Viruses, 2022, 16, 125–131). We conducted a TLR to scrutinise the available data and reveal evidence gaps.

Methods

A TLR search was conducted in OVID Medline, Embase, and ECON Lit to identify existing literature from Jan 2011-Aug 2023 and grey literature. Eligibility criteria were defined based on population (intervention/comparator (no limit), outcomes (clinical, epidemiological, economic and QoL) and limited to UK-only results.

Results

Despite the broad criteria, only 14 out of 1013 studies were included. Nine studies reported on epidemiological outcomes, one on epidemiology and costs, and four on model outcomes. Due to the small number of studies and the heterogeneity in study design and outcomes, it was not possible to draw reliable conclusions on incidence, prevalence, and mortality. One model paper showed that a hypothetical RSV vaccine could be cost effective in the UK, depending on incidence, vaccine effectiveness and cost. All identified studies emphasise the challenges in estimating the true burden due to limitations in testing and a lack of standardised disease definition in older adults. There is a lack of evidence for risk groups, particularly clinical and economic consequences for RSV patients at a higher risk of infection and severe sequelae.

Conclusion

Only a limited number of studies meeting the criteria focused on RSV infection in older adults were found, with nearly no data on risk groups and related cost. It is imperative that surveillance and testing are improved to understand the true burden. This will serve as a basis for evaluating cost-effectiveness and decisions on the most effective measures to lower the burden, including vaccination programmes.
2146 Evaluation of pulmonary hypertension by echocardiogram in geriatrics patients with SARSCOV2 from a Latin American cohort
Authors: Gomez MC , Gomez JA , Gomez JA , Castillo SF , Blanco EC , Dulcey LA , Ciliberti MP , Lizcano AP , Medina MJ , Estevez MJ , Hernandez CJ , Martínez JC , Acevedo DA , Arias AF , Gutierrez EY , Amaya MC , Ramos GS
Published: August 2024

Introduction

Pulmonary hypertension evaluated by echocardiography and ROX index in older patients with COVID-19 could be linked to worse outcomes.

Methods

We conducted a retrospective cohort of adult patients with COVID-19. The main objective was to evaluate pulmonary hypertension as an echocardiographic finding and its association with hard outcomes in patients with COVID-19 infection. In the inferential statistical analysis, the OR with confidence intervals greater than 95% was used as a measure of association. Qualitative variables were evaluated using the Chi square test or Fisher’s exact test. In quantitative variables, the Student’s T test, or Mann–Whitney test, was used.

Results

306 individuals with COVID-19 infection were included; the majority of these were men (78% vs. 22% women). Patients who died had lower ROX values at 2 hours compared to survivors (4,5 with a SD of 3,6–5,6, vs. 5,8 with a SD of 4,7–6,1, respectively). This trend was maintained at 12 hours (4,9 with a SD of 3,8–6,0 for deceased patients vs. 7,8 with a SD of 5,2–8,7 for survivors). For the ROX index at 2 hours, an OR adjusted for age and gender of 8,5 with a CI of 2,0–91,4 was found, and at 12 hours, an OR of 17,6 with a CI of 2,8–93,6 was found. Low values of the ROX index were associated with pulmonary hypertension (p = 0.048) and higher mortality (p = 0.037).

Conclusions

In patients with COVID-19, the presence of pulmonary hypertension estimated by ecocardiography and the ROX index is associated with worse outcomes, including a higher rate of comorbidities and mortality in patients over 70 years of age. Prospective studies with a more representative population sample are required to validate the results found here.
Effect of different durations of treatment with antihypertensive drugs with anticholinergic effects on the risk of dementia: a target trial emulation study
Authors: Aguado Jaume , Gutierrez Lia , Forns Joan , Vila-Guilera Julia , Rothman Kenneth J , García-Albéniz Xabier
Published: August 2024

Studying the effect of duration of treatment on prognostic outcomes using real-world data is challenging because only people who survive for a long time can receive a treatment for a long time. Specifying a target trial helps overcome such challenge. We aimed to estimate the effect of different durations of treatment with antihypertensive drugs with anticholinergic properties (AC AHT) on the risk of vascular dementia and Alzheimer’s disease by emulating a target trial using the UK CPRD GOLD database (2001-2017). Comparing treatment for 3-6 years vs ≤3 years yielded null results for both types of dementia. Comparing a longer duration of treatment, >6 years vs ≤3 years, yielded a 10-year risk ratio of 0.69 (95% CI, 0.54-0.90) for vascular dementia and 0.91 (95% CI, 0.77-1.10) for Alzheimer’s disease. For illustration, we performed an analysis that failed to emulate a target trial by assigning exposure categories using postbaseline information, obtaining implausible beneficial estimates. Our findings indicate a modest benefit of longer duration of treatment with AC AHT on vascular dementia and highlight the value of the target trial emulation to avoid selection bias in the evaluation of the effect of different durations of treatment.

This article is part of a Special Collection on Pharmacoepidemiology.
Common Good Constitutionalism and the Individual—A Property Perspective
Authors: Walsh Rachael
Published: August 2024

This paper probes the position of the individual, and of their interests and rights, within a common good constitutionalism framework. To do so, it draws on long-running debates within property law and theory concerning the relative priority to be afforded to the individual and to the common good, with many of the concerns of Common Good Constitutionalism already in the mainstream of property law and theory. It compares debate about the existence, nature, and content of property’s “social function,” and its doctrinal manifestations, to Vermeule’s broad arguments about the common good dimensions of constitutionalism. Specifically, it analyzes the effectiveness and purpose of an “internal limitation” strategy, and the risk of excessive individual subordination to collective interests. Finally, it assesses how central a role coercive legal measures should play in encouraging virtuous conduct within a common good constitutionalism framework.
Confusing boundaries of the Labrador tea species: dispersal history explains the lack of clear species structure
Authors: Iunusova D R , Polezhaeva M A , Marchuk E A
Published: August 2024

Background and Aims

The Labrador teas (genus Rhododendron, subsection Ledum) are a complex of species widely distributed in the Northern Hemisphere. They occupy cold-resistant plant communities from highlands to forest understorey and wetland habitats almost circumboreally and they are especially abundant in Northeast Asia and northern North America, yet there are no clear species boundaries in this group. The genetic structure of species of subsect. Ledum from Eurasia and North America as well as the dispersal history of the group require clarification.

Methods

The phylogeny and biogeography of subsect. Ledum of the genus Rhododendron were assessed using phylogenetic trees constructed based on the analysis of variation in chloroplast petB-petD, trnV-ndhC, trnH-psbA, K2R-K707, atpB oligo2 – rbcL oligo5 and nuclear (ITS1) markers of four Eurasian and one American species (65 populations, 408 individuals). The data were evaluated with maximum parsimony and Bayesian analysis. Molecular dating and reconstruction of ancestral areas were performed.

Key Results

Dense sampling revealed widespread presence of shared haplotypes and ribotypes among Ledum populations and species. Two American, three mixed and one Eurasian lineage diversified during the Neogene climate cooling and then rapidly dispersed during the Pleistocene. The ability to accumulate high genetic diversity and to preserve it across distribution ranges and generations prevented Ledum from lineage sorting. As a result, a species complex with a reserve of genetic variability appeared.

Conclusions

Although no clear phylogenetic inference can be obtained at present, the plastid genealogy is consistent with the nuclear genealogy and demonstrates the processes involved in speciation in the Ledum species complex.
Cognitive Symptoms Are Not Associated with Cognitive Performance in Post-Acute mTBI
Authors: Levy Arielle M , Saling Michael M , Anderson Jacqueline F I
Published: August 2024

Objective

Subjective cognitive symptoms are commonly reported after mild traumatic brain injury (mTBI) but are often not associated with objective cognitive performance. This may be due to limitations in traditional cognitive performance measures, which may not be sensitive to subtle variations in cognition in post-acute mTBI. This study explored associations between objective and subjective cognition using computer-based tasks of increasing cognitive load, proposed to be more sensitive to subtle differences in performance.

Method

Individuals with mTBI (n = 68) and trauma controls (n = 40) were prospectively recruited and assessed approximately 8 weeks post-injury. Participants completed measures of subjective symptom reporting, objective cognitive performance (including two computer-based tasks of increasing cognitive load), and psychological distress.

Results

There were no significant associations between subjective and objective cognition reporting in the mTBI group, both in bivariate correlations (|r| = 0.01–0.20, p > .05) and when controlling for psychological distress (|r| = 0.00–0.17, p > .05). A similar pattern of results was observed in trauma controls, suggesting that the limited relationships between objective and subjective cognition in mTBI may not be specific to this population.

Conclusions

Despite employing measures of cognitive performance proposed to be more sensitive than traditional tasks, no significant relationships were observed between objective and subjective cognition in post-acute mTBI, and estimated effect sizes were small to negligible. This provides further evidence that at a group level 8 weeks after mTBI subjective cognitive symptoms primarily reflect factors aside from objective cognition.
Benchmarking of AlphaFold2 accuracy self-estimates as indicators of empirical model quality and ranking: a comparison with independent model quality assessment programmes
Authors: Edmunds Nicholas S , Genc Ahmet G , McGuffin Liam J
Published: August 2024

Motivation

Despite an increase in protein modelling accuracy following the development of AlphaFold2, there remains an accuracy gap between predicted and observed model quality assessment (MQA) scores. In CASP15, variations in AlphaFold2 model accuracy prediction were noticed for quaternary models of very similar observed quality. In this study, we compare plDDT and pTM to their observed counterparts the local distance difference test (lDDT) and TM-score for both tertiary and quaternary models to examine whether reliability is retained across the scoring range under normal modelling conditions and in situations where AlphaFold2 functionality is customized. We also explore plDDT and pTM ranking accuracy in comparison with the published independent MQA programmes ModFOLD9 and ModFOLDdock.

Results

plDDT was found to be an accurate descriptor of tertiary model quality compared to observed lDDT-Cα scores (Pearson r = 0.97), and achieved a ranking agreement true positive rate (TPR) of 0.34 with observed scores, which ModFOLD9 could not improve. However, quaternary structure accuracy was reduced (plDDT r = 0.67, pTM r = 0.70) and significant overprediction was seen with both scores for some lower quality models. Additionally, ModFOLDdock was able to improve upon AF2-Multimer model ranking compared to TM-score (TPR 0.34) and oligo-lDDT score (TPR 0.43). Finally, evidence is presented for increased variability in plDDT and pTM when using custom template recycling, which is more pronounced for quaternary structures.

Availability and implementation

The ModFOLD9 and ModFOLDdock quality assessment servers are available at https://www.reading.ac.uk/bioinf/ModFOLD/ and https://www.reading.ac.uk/bioinf/ModFOLDdock/, respectively. A docker image is available at https://hub.docker.com/r/mcguffin/multifold.
Attention-based approach to predict drug–target interactions across seven target superfamilies
Authors: Schulman Aron , Rousu Juho , Aittokallio Tero , Tanoli Ziaurrehman
Published: August 2024

Motivation

Drug–target interactions (DTIs) hold a pivotal role in drug repurposing and elucidation of drug mechanisms of action. While single-targeted drugs have demonstrated clinical success, they often exhibit limited efficacy against complex diseases, such as cancers, whose development and treatment is dependent on several biological processes. Therefore, a comprehensive understanding of primary, secondary and even inactive targets becomes essential in the quest for effective and safe treatments for cancer and other indications. The human proteome offers over a thousand druggable targets, yet most FDA-approved drugs bind to only a small fraction of these targets.

Results

This study introduces an attention-based method (called as MMAtt-DTA) to predict drug–target bioactivities across human proteins within seven superfamilies. We meticulously examined nine different descriptor sets to identify optimal signature descriptors for predicting novel DTIs. Our testing results demonstrated Spearman correlations exceeding 0.72 (P < 0.001) for six out of seven superfamilies. The proposed method outperformed fourteen state-of-the-art machine learning, deep learning and graph-based methods and maintained relatively high performance for most target superfamilies when tested with independent bioactivity data sources. We computationally validated 185 676 drug–target pairs from ChEMBL-V33 that were not available during model training, achieving a reasonable performance with Spearman correlation >0.57 (P < 0.001) for most superfamilies. This underscores the robustness of the proposed method for predicting novel DTIs. Finally, we applied our method to predict missing bioactivities among 3492 approved molecules in ChEMBL-V33, offering a valuable tool for advancing drug mechanism discovery and repurposing existing drugs for new indications.

Availability and implementation

https://github.com/AronSchulman/MMAtt-DTA.
Analysing the information content of the multimodal courtship display of a parasitoid wasp
Authors: Lang Sandra Regina , Conrad Taina , Steiger Sandra , Stökl Johannes
Published: August 2024

Courtship displays are generally composed of multiple signal components that are transmitted and perceived through different sensory modalities. However, previous studies on multimodal courtship displays have focused mainly on individual signals, thus failing to provide a full explanation of why these displays evolved despite the added costs involved. Therefore, it is essential to identify the purpose of each display component and link them to prevailing hypotheses on multimodal display function. Here, we study the multimodal courtship display of males of the parasitoid wasp Leptopilina heterotoma, which consists of wing fanning and a putative antennal pheromone, by determining the information conveyed about male quality through these two modalities. We found that a high wing-fanning frequency and a large body size led to a higher mating success, whereas we found no correlation of the pheromone composition with mating success. We conclude that the wing-fanning component conveys mate-assessment information, whereas the chemical display component, found to be species specific in a previous study, functions as a species-recognition mechanism but does not reflect the quality of a male. Altogether, our study suggests that the multimodal courtship display of L. heterotoma fits the multiple message hypothesis and might thus be a useful model for further studies.
Transcriptional profiling of mucus production in rhesus macaque endocervical cells under hormonal regulation
Authors: Rapp Katrina , Wei Shuhao , Roberts Mackenzie , Yao Shan , Fei Suzanne S , Gao Lina , Ray Karina , Wang Alexander , Godiah Rachelle , Han Leo
Published: August 2024

Objective

Endocervical mucus production is a key regulator of fertility throughout the menstrual cycle. With cycle-dependent variability in mucus quality and quantity, cervical mucus can either facilitate or block sperm ascension into the upper female reproductive tract. This study seeks to identify genes involved in the hormonal regulation of mucus production, modification, and regulation through profiling the transcriptome of endocervical cells from the non-human primate, the rhesus macaque (Macaca mulatta).

Intervention

We treated differentiated primary endocervical cultures with estradiol (E2) and progesterone (P4) to mimic peri-ovulatory and luteal-phase hormonal changes. Using RNA-sequencing, we identified differential expression of gene pathways and mucus-producing and mucus-modifying genes in cells treated with E2 compared to hormone-free conditions and E2 compared to E2-primed cells treated with P4.

Main Outcome Measures

We pursued differential gene expression analysis on RNA-sequenced cells. Sequence validation was done using quantitative PCR (qPCR).

Results

Our study identified 158 genes that show significant differential expression in E2-only conditions compared to hormone-free control and 250 genes that show significant differential expression in P4-treated conditions compared to E2-only conditions. From this list, we found hormone-induced changes in transcriptional profiles for genes across several classes of mucus production, including ion channels and enzymes involved in post-translational mucin modification that have not previously been described as hormonally regulated.

Conclusion

Our study is the first to use an in vitro culture system to create an epithelial cell–specific transcriptome of the endocervix. As a result, our study identifies new genes and pathways altered by sex steroids in cervical mucus production.

Summary Sentence

In vitro hormonal regulation of mucus production, modification, and secretion was profiled using primary epithelial endocervical cells.
578 - Cost per responder in Brazil (EASI-75, EASI90 and ΔNRS ≥4) of biologics and JAK inhibitors based on a network-meta-analysis of therapies for atopic dermatitis
Authors: Muzy Guilherme
Published: August 2024

Background

Atopic dermatitis (AD) poses a significant global health burden, affecting a substantial percentage of both pediatric and adult populations. Conventional systemic therapies exhibit limited efficacy and undesirable side effects, emphasizing the urgent need for more effective and economically viable treatment options.

Objective

This study aims to provide an updated analysis of the cost per response ratio for different systemic medications in monotherapy for moderate-to-severe AD, considering the unique Brazilian healthcare context. Additionally, it explores the number of successfully treated patients across various clinically meaningful endpoints.

Methods

The study includes biological therapies and JAK inhibitors approved by ANVISA up to January 2024. Efficacy was assessed using EASI and pruritus-NRS scores, aligning with HOME's Core Outcome Set for clinical trials. Costs were calculated based on each specific outcome, considering the factory price with an 18% increment for ICMS. Dosages and costs were derived from prescribing information and network meta-analyses.

Results

Upadacitinib 15 mg emerged as the most cost-effective therapy for achieving EASI-90, providing a substantial cost reduction compared to other medications. All JAK inhibitors demonstrated superior cost per response values for pruritus △NRS ≥ 4 compared to dupilumab.

Study limitations

This analysis was limited to the endpoints presented in the meta-analyses and other endpoints might offer different perspectives results.

Conclusion

This research contributes valuable insights into the cost-effectiveness of systemic therapies for AD in the Brazilian context. Despite not being obligatory, JAK inhibitors showcase notable cost-efficacy, providing an alternative to biological treatments. Decision-makers should leverage cost-effectiveness analyses for informed resource management and prioritize treatments that maximize clinical benefits and minimize costs.