Enhancing Medication Safety through Implementing the Qatar Tool for Reducing Inappropriate Medication (QTRIM) in Ambulatory Older Adults.

INTRODUCTION: To promote optimal healthcare delivery, safeguarding older adults from the risks associated with inappropriate medication use is paramount. OBJECTIVE: This study aims to evaluate the effectiveness of implementing the Qatar Tool for Reducing Inappropriate Medication (QTRIM) in ambulatory older adults to enhance medication safety. METHOD: The QTRIM was developed by an expert consensus panel using the Beers Criteria and contained a list of potentially inappropriate medications (PIMs) based on the local formulary. Using quality improvement methodology, it was piloted and implemented in two outpatient pharmacy settings serving geriatric medicine and dermatology clinics at Rumailah Hospital, Qatar. Key performance indicators (KPIs) using implementation documentation as a process measure and the percentage reduction in PIM prescriptions as an outcome measure were assessed before and after QTRIM implementation. This study was conducted between July 2022 and September 2023. RESULTS: In the outpatient department (OPD) geriatric pharmacy, the prescription rate of PIMs was reduced from an average of 1.2 ± 0.7 PIMs per 1000 orders in 2022 to an average of 0.8 ± 0.2 PIMs per 1000 orders in 2023. In the OPD geriatric pharmacy, the results showed a 66.6% reduction in tricyclic antidepressants (TCAs) (from 30 to 10), a reduction in first-generation antihistamines by 51.7% (29 to 14), and muscle relaxants by 33.3% (36 to 24). While in dermatology, the older adult prescription rate of PIMs was reduced from an average of 8 ± 3 PIMs per 1000 orders in 2022 to a rate of 5 ± 3 PIMs per 1000 orders in 2023; the most PIM reductions were (49.4%) in antihistamines (from 89 to 45), while muscle relaxants and TCAs showed a minimal reduction. CONCLUSIONS: Implementing QTRIM with pharmacy documentation monitoring markedly reduced the PIMs dispensed from two specialized outpatient pharmacies serving older adults. It may be a promising effective strategy to enhance medication safety in outpatient pharmacy settings.

An increasing proportion of the population is not covered by the current RDA for vitamin C - interrogation of EPIC-Norfolk and NHANES 2017/2018 cohorts.

With the rising prevalence of obesity globally, increasing proportions of the population may not be covered by current recommended daily allowances (RDAs) that are supposed to provide 97.5% of the population with a sufficient nutrient status but are typically based on a healthy young 70 kg male reference person. Using the EPIC-Norfolk (UK) and the NHANES (US) cohorts, we estimated the effect of body weight on the dose-concentration relationship to derive weight-based requirements to achieve an 'adequate' plasma concentration of vitamin C estimated to be 50 µmol/L. Inverse correlations between body weight and vitamin C were observed in both cohorts (p < 0.0001). Moreover, only about 2/3 of the cohorts achieved an adequate plasma vitamin C status by consuming the RDA or above, while only 1/3 to 1/2 of the cohorts achieved adequacy by an intake of the local RDA ± 10%. Using vitamin C as an example, the present data demonstrate that a considerable and expectedly increasing proportion of the world population is unable to achieve an adequate target plasma concentration with the current recommended daily intakes of vitamin C. This needs to be considered in future public health recommendations.

In this paper, we highlight the inverse association between body weight and vitamin C status. Our study strongly suggests that a large proportion of the population is not covered by the current recommended intakes of vitamin C.

Anticholinergic burden among in-patients: a cross-sectional study on prevalence, determinants, and impact on mortality in Ethiopia.

Background: Numerous studies report that anticholinergic burden (ACB) has been linked with several health consequences, including increased hospital admissions, prolonged hospitalization, and physical and cognitive impairment. However, low- and middle-income settings, as well as younger individuals, are underrepresented. Objectives: To assess the prevalence and determinants of ACB, and to assess the impact of ACB on in-hospital mortality among adult in-patients at University of Gondar Comprehensive Specialized Hospital (UOGCSH). Design: A cross-sectional study was conducted from June to August 2022 at UOGCSH among adult in-patients. Methods: A pre-tested questionnaire was utilized to collect data from patients and their corresponding medical charts. A consecutive sampling technique was used to select the participants. Descriptive statistics were used to summarize socio-demographic and clinical characteristics. Chi-squared, Fisher's exact, and Wilcoxon rank sum tests, as appropriate, were used to determine associations between independent variables and ACB. Kaplan-Meier survival curve and Cox proportional hazards regression test were used to assess the impact of ACB on in-hospital mortality. Results: A total of 420 adult in-patients, median (interquartile range) age of 38 (26, 55) years, participated in this study. Over half (58.3%) were exposed to anticholinergic medicines, with a high ACB (⩾3) seen in 11.2% of participants. High ACB was associated with higher median number of medicines per patient (p = 0.003) higher median hospital length of stay (p = 0.033), and having mental and behavioral disorders (p < 0.001). No significant association was found between ACB and in-hospital mortality (log-rank test p = 0.26, Cox regression adjusted hazard ratio: 1.47, 95% CI: 0.335-6.453, p = 0.61). Conclusion: Among adult in-patients, a significant majority (58.3%) were subjected to medications possessing anticholinergic properties, with a noteworthy 11.2% of the study subjects exhibiting a high ACB. Participants with higher median length of hospital stay were more likely to have high ACB even in this relatively younger adult patient population.

Background: Anticholinergics refers to substances that block the action of the neurotransmitter acetylcholine in the body. Previous studies have shown that medicines exhibiting anticholinergic effects could lead to increased hospital admissions, longer hospital stays, and both physical and cognitive impairments. Objective: In this study, we aimed to assess how medicines exhibiting anticholinergic effects might affect patients in Ethiopian in-patient settings. Methods: We conducted a cross-sectional study from June to August 2022, collecting data from adult in-patients through a questionnaire and medical charts. We used a widely recognized tool called Anticholinergic Cognitive Burden Score to measure anticholinergic burden. We used statistical analyses to identify associations between the use of anticholinergic medicines and various factors, including the number of medicines per patient and the length of hospital stay. Additionally, we explored the impact of anticholinergic burden on in-hospital mortality. Results: Out of the 420 participants, 245 were exposed to medicines with anticholinergic properties. High anticholinergic burden was observed in 47 patients. Patients with mental and behavioral disorders were more likely to have high anticholinergic burden, while those with diseases of the digestive system were less likely. Moreover, a high anticholinergic burden was linked to a greater median number of medicines per patient and an extended median hospital length of stay. However, the study found no significant difference in in-hospital mortality between patients with high and low anticholinergic burden. Conclusion: The study highlights that a significant proportion of the participants were exposed to medicines with anticholinergic properties, and a notable percentage experienced a high anticholinergic burden. This burden was particularly associated with mental and behavioral disorders, the use of higher number of medicines, and longer hospital stay. Importantly, the research did not find a clear link between anticholinergic burden and in-hospital mortality after accounting for other factors.

Understanding the impact of medicines with anticholinergic properties on patients at University of Gondar Hospital.

The Impact of Hospital Transfers on Surgical Delay and Associated Postoperative Outcomes for Hip Fracture Patients in Scotland: A Cohort Study.

Background/Objectives: Hip fractures exert a substantial burden on hospital systems. Within Scotland 20% of the population resides rurally, warranting investigation of how this impacts prompt access to surgical care. This study aims to determine whether indirect hospital admission via hospital transfer affects the likelihood of surgical management within 36 h for hip fracture patients. Methods: A retrospective cohort study was performed. This used Scottish Hip Fracture Audit data including patients aged ≥50 split into two propensity matched groups based on their transfer status. Descriptive analysis compared patient characteristics. Regression assessed achieving surgery within 36 h of admission in the unmatched and matched cohorts. Secondary outcomes included time to surgery, mortality, mobilization, returning to residence and length of stay. A sensitivity analysis was undertaken to assess for residual confounding effects. Results: The unmatched analysis included 20,132 patients. Transfer patients were younger (p = 0.007) and less-comorbid (p < 0.001). In the matched population, 711 (63.6%) transfer patients had surgery with 36 h of presentation to hospital, compared to 852 (75.3%) non-transfer patients. Transfer patients had 43% reduced odds of timely surgery (OR (95% CI) 0.57 (0.48 to 0.69); p < 0.001). No disparities emerged in mortality, mobilisation or returning to residence., Transfer patients experienced a significant increase in length of stay in hospital (median (IQR) 16 (8 to 33) vs. 13 (8 to 30); p = 0.024). Conclusions: Hospital transfer is associated with significantly reduced odds of timely surgery, a longer time to surgery and longer length of stay. Development of structured network pathways that minimize delay to transfer are required to potentially optimize outcomes and reduce associated cost.

Serum Albumin and Post-Stroke Outcomes: Analysis of UK Regional Registry Data, Systematic Review, and Meta-Analysis.

Hypoalbuminemia associates with poor acute ischemic stroke (AIS) outcomes. We hypothesised a non-linear relationship and aimed to systematically assess this association using prospective stroke data from the Norfolk and Norwich Stroke and TIA Register. Consecutive AIS patients aged ≥40 years admitted December 2003-December 2016 were included. Outcomes: In-hospital mortality, poor discharge, functional outcome (modified Rankin score 3-6), prolonged length of stay (PLoS) > 4 days, and long-term mortality. Restricted cubic spline regressions investigated the albumin-outcome relationship. We updated a systematic review (PubMed, Scopus, and Embase databases, January 2020-June 2023) and undertook a meta-analysis. A total of 9979 patients were included; mean age (standard deviation) = 78.3 (11.2) years; mean serum albumin 36.69 g/L (5.38). Compared to the cohort median, albumin < 37 g/L associated with up to two-fold higher long-term mortality (HRmax; 95% CI = 2.01; 1.61-2.49) and in-hospital mortality (RRmax; 95% CI = 1.48; 1.21-1.80). Albumin > 44 g/L associated with up to 12% higher long-term mortality (HRmax1.12; 1.06-1.19). Nine studies met our inclusion criteria totalling 23,597 patients. Low albumin associated with increased risk of long-term mortality (two studies; relative risk 1.57 (95% CI 1.11-2.22; I2 = 81.28)), as did low-normal albumin (RR 1.10 (95% CI 1.01-1.20; I2 = 0.00)). Strong evidence indicates increased long-term mortality in AIS patients with low or low-normal albumin on admission.

A randomised, double blind, placebo-controlled trial of a two-week course of dexamethasone for adult patients with a symptomatic Chronic Subdural Haematoma (Dex-CSDH trial).

Background: Chronic subdural haematoma is a collection of 'old blood' and its breakdown products in the subdural space and predominantly affects older people. Surgical evacuation remains the mainstay in the management of symptomatic cases. Objective: The Dex-CSDH (DEXamethasone in Chronic SubDural Haematoma) randomised trial investigated the clinical effectiveness and cost-effectiveness of dexamethasone in patients with a symptomatic chronic subdural haematoma. Design: This was a parallel, superiority, multicentre, pragmatic, randomised controlled trial. Assigned treatment was administered in a double-blind fashion. Outcome assessors were also blinded to treatment allocation. Setting: Neurosurgical units in the UK. Participants: Eligible participants included adults (aged ≥ 18 years) admitted to a neurosurgical unit with a symptomatic chronic subdural haematoma confirmed on cranial imaging. Interventions: Participants were randomly assigned in a 1 : 1 allocation to a 2-week tapering course of dexamethasone or placebo alongside standard care. Main outcome measures: The primary outcome was the Modified Rankin Scale score at 6 months dichotomised to a favourable (score of 0-3) or an unfavourable (score of 4-6) outcome. Secondary outcomes included the Modified Rankin Scale score at discharge and 3 months; number of chronic subdural haematoma-related surgical interventions undertaken during the index and subsequent admissions; Barthel Index and EuroQol 5-Dimension 5-Level utility index score reported at discharge, 3 months and 6 months; Glasgow Coma Scale score reported at discharge and 6 months; mortality at 30 days and 6 months; length of stay; discharge destination; and adverse events. An economic evaluation was also undertaken, during which the net monetary benefit was estimated at a willingness-to-pay threshold of £20,000 per quality-adjusted life-year. Results: A total of 748 patients were included after randomisation: 375 were assigned to dexamethasone and 373 were assigned to placebo. The mean age of the patients was 74 years and 94% underwent evacuation of their chronic subdural haematoma during the trial period. A total of 680 patients (91%) had 6-month primary outcome data available for analysis: 339 in the placebo arm and 341 in the dexamethasone arm. On a modified intention-to-treat analysis of the full study population, there was an absolute reduction in the proportion of favourable outcomes of 6.4% (95% confidence interval 11.4% to 1.4%; p = 0.01) in the dexamethasone arm compared with the control arm at 6 months. At 3 months, the between-group difference was also in favour of placebo (-8.2%, 95% confidence interval -13.3% to -3.1%). Serious adverse events occurred in 60 out of 375 (16.0%) in the dexamethasone arm and 24 out of 373 (6.4%) in the placebo arm. The net monetary benefit of dexamethasone compared with placebo was estimated to be -£97.19. Conclusions: This trial reports a higher rate of unfavourable outcomes at 6 months, and a higher rate of serious adverse events, in the dexamethasone arm than in the placebo arm. Dexamethasone was also not estimated to be cost-effective. Therefore, dexamethasone cannot be recommended for the treatment of chronic subdural haematoma in this population group. Future work and limitations: A total of 94% of individuals underwent surgery, meaning that this trial does not fully define the role of dexamethasone in conservatively managed haematomas, which is a potential area for future study. Trial registration: This trial is registered as ISRCTN80782810. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 13/15/02) and is published in full in Health Technology Assessment; Vol. 28, No. 12. See the NIHR Funding and Awards website for further award information.

Chronic subdural haematoma is one of the most common conditions managed in adult neurosurgery and mainly affects older people. It is an 'old' collection of blood and blood breakdown products found on the surface of the brain. Surgery to drain the liquid collection is effective, with most patients improving. Given that inflammation is involved in the disease process, a commonly used steroid, dexamethasone, has been used alongside surgery or instead of surgery since the 1970s. However, there is no consensus or high-quality studies confirming the effectiveness of dexamethasone for the treatment of chronic subdural haematoma. This study was designed to determine the effectiveness of adding dexamethasone to the normal treatment for patients with a symptomatic chronic subdural haematoma. The benefit of adding dexamethasone was measured using a disability score called the Modified Rankin Scale, which can be divided into favourable and unfavourable outcomes. This was assessed at 6 months after entry into the study. In total, 748 adults with a symptomatic chronic subdural haematoma treated in neurosurgical units in the UK participated. Each participant had an equal chance of receiving either dexamethasone or a placebo because they were assigned randomly. Neither the patients nor the investigators knew who received dexamethasone and who received placebo. Most patients in both groups had an operation to drain the haematoma and experienced significant functional improvement at 6 months compared with their initial admission to hospital. However, patients who received dexamethasone had a lower chance than patients who received placebo of favourable recovery at 6 months. Specifically, 84% of patients who received dexamethasone had recovered well at 6 months, compared with 90% of patients who received placebo. There were more complications in the group that received dexamethasone. This trial demonstrates that adding dexamethasone to standard treatment reduced the chance of a favourable outcome compared with standard treatment alone. Therefore, this study does not support the use of dexamethasone in treating patients with a symptomatic chronic subdural haematoma.

Impact of remoteness and rurality on the treatment and survival of patients with glioblastoma in the north of Scotland.

Background: The geographical catchment area served by the Neurosurgical Unit in Aberdeen, Scotland is the largest in the United Kingdom. We examined whether a distance-decay effect on survival exists for patients diagnosed with glioblastoma, who have to travel substantial distances for neurosurgical and oncological treatment in the north of Scotland. Methods: Electronic medical records of adult patients with glioblastoma, referred for treatment between 2007 and 2018, who underwent surgical resection were reviewed. Travel time by car (as a measure of distance travelled) was calculated from the patients' home to their general practice (GP) and to their main neuro-oncological centre. Results: There were 122 patients; 71 (58.2%) were male and the mean age was 57.8 years. The urban-rural split was 61.5% and 38.5%, respectively. Median driving time to the neuro-oncological centre was 36 min and to the GP this was 6 min. Most patients underwent either sub-total (49.6%) or gross total (46.3%) surgical resection. Post-operative treatments included: radiotherapy only (15.6%), chemotherapy only (6.6%), and chemotherapy with radiotherapy (63.1%). Temozolomide was used in 70.5% of patients. Seventeen patients did not receive any post-operative chemo-radiotherapy. The median survival time was 345 days. There was no statistically significant association between distance travelled and survival time in days. MGMT methylation status, extent of resection, Charlson co-morbidity index and treatment received significantly affected survival. Conclusions: There was no evidence of disadvantage on survival time for patients living further from their neuro-oncological centre compared to those who live nearer.

Impact of age on the prevalence of poor-quality dietary variety, associated lifestyle factors, and body composition profile (low body muscle mass and high body fat mass) in older people residing in Colombo district, Sri Lanka.

Aims: To assess the impact of age on the prevalence of poor-quality dietary variety, associated lifestyle factors, and body composition profile (low body muscle mass and high-fat mass) in older Sri Lankans. Methods: In this population-based cross-sectional study, older people of 60 years or above were selected using a multistage cluster sampling technique probability proportionate to the size. They were classified into 3 groups; 60-64, 65-69 and > 70-years. The poor-quality dietary variety was defined based on food variety, dietary diversity and dietary serving scores assessed using 24-h dietary recall. Body composition was measured using bio-electrical impedance. The impact of age on determinants of poor-quality dietary variety and being at risk of low muscle mass and high-fat mass were assessed by using multivariable logistic regression models. Results: Eight hundred older participants with a mean (SD) 68.1(5.8) years were included. There were 28.4%(n = 227), 36.2%(n = 290) and 35.4%(n = 283) in the 60-64, 65-69 and ≥ 70-year age groups, respectively. The prevalence of poor-quality dietary variety was similar across age groups. The urban living environment, and getting nutritional advice from the GP/hospital were found to have a significant negative association only in the 60-64 age group. A poor-quality dietary variety was significantly associated with no education or up to the primary level in the 65-69 age group and having diabetes or hypertension in the ≥70-year group. Odds of low muscle mass and high-fat mass were 2.43(1.46-4.03) and 2.17(1.30-3.63) respectively among the≥70-year age group compared to the 60-64-year group, after controlling for confounders. Conclusions: The prevalence of poor-quality dietary variety was similarly high in all age groups. Increasing age was associated with higher odds of low body muscle and high body fat mass despite similar dietary variety, indicating the need for special dietary attention.

Lower mental health related quality of life precedes dementia diagnosis: findings from the EPIC-Norfolk prospective population-based study.

Lower Health Related Quality of Life (HRQoL) precedes dementia in older adults in the USA. We explore prospective associations between HRQoL and dementia in British adults in mid and late-life, when interventions to optimise cognitive ageing may provide benefit. 7,452 community-dwelling participants (57% women; mean age 69.3 ± 8.3 years) attended the European Prospective Investigation of Cancer-Norfolk study's third health check (3HC) and reported their HRQoL using Short-Form 36 (SF-36). Cox Proportional Hazard regression models explored associations between standard deviation differences in baseline Physical Component (PCS) and Mental Component Summary (MCS) scores, as well as eight SF-36 sub-scales (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, mental health), and incident dementia over ten years. Logistic regression models explored cross-sectional relationships at the 3HC between HRQoL and objective global cognitive function (n = 4435; poor cognition = lowest performance decile). The cohort was examined as a whole and by age-group (50-69, ≥ 70), considering socio-demographics and co-morbidity. Higher MCS scores were associated with lower chance of incident dementia (Hazard Ratio [HR] = 0.74, 95% CI 0.68-0.81) and lower odds of poor cognition (Odds Ratio [OR] = 0.82, 0.76-0.89), with findings similar by age-group. Higher PCS scores were not associated with dementia in the whole cohort (HR = 0.93, 0.84-1.04) or considering age-groups; and were only associated with poor cognition in younger participants (OR = 0.81, 0.72-0.92). Similarly, associations between higher scores on subscales pertaining to mental, but not physical, HRQoL and lower dementia incidence were observed. Lower mental HRQoL precedes dementia diagnosis in middle-aged and older British adults.

Sex-specific lifetime risk of cardiovascular events: the European Prospective Investigation into Cancer-Norfolk prospective population cohort study.

AIMS: Better understanding of sex differences in cardiovascular disease (CVD) is essential in tailoring appropriate preventative strategies. Using a large population-based study with follow-up >25 years, we aimed to determine sex-specific lifetime risks of incident CVD and cardiovascular (CV) mortality amongst populations with and without prevalent CVD. METHODS AND RESULTS: Participants were drawn from the European Prospective Investigation into Cancer-Norfolk and followed up for a median of 26.2 years. Sex-specific lifetime risks were ascertained accounting for the competing risk of death. Models were adjusted for ethnicity and time-updated covariates: material deprivation, CV risk factors, lifestyle factors, comorbidities, and medication. A total of 23 859 participants [54.5% women; mean age (standard deviation) 59.2 (9.3) years at baseline] were included. Adjusted lifetime risks of incident CVD were higher in men than in women (69.1 vs. 57.7% at age 75): cause-specific hazard ratio (cHR) (99% confidence interval)-1.49 (1.41-1.57), while the risks of CV mortality at age 75 were 4.4% (men) and 3.1% (women): cHR-1.42 (1.31-1.54). Myocardial infarction was the predominant first presentation in men until the eighth decade. In women, the first CVD manifestations after their sixth decade were predominantly atrial fibrillation and stroke. The male-associated excess relative risks of incident CVD and CV mortality were halved in people with prevalent CVD. CONCLUSION: We characterized the sex-specific lifetime CV risks in a large cohort. Men had substantially higher risk of incident CVD and CV mortality than women, which was attenuated amongst people with prevalent CVD. Our findings provide an evidence base for sex-specific CV prevention.

In this population-based study, we aimed to understand the sex-specific lifetime trajectories of different heart and circulatory disorders and their relationship with death from heart disease. We included ∼24 000 participants in the analyses, who were followed up for >25 years. Men had a higher lifetime risk of heart and circulatory disorders compared with women. Heart attacks were the predominant first presentation in men until the eighth decade, while in women this was manifested as heart rhythm disorders and stroke after their sixth decade. The excess risk of death from heart disease observed in men with pre-existing heart disease was attenuated compared with those free of heart disease at baseline. In conclusion, men and women require tailored heart disease prevention efforts given the marked sex disparities in heart disease and death over the very long-term highlighted by our study.

Diabetes mellitus increases risk of adverse drug reactions and death in hospitalised older people: the SENATOR trial.

PURPOSE: Adverse drug reactions (ADRs) are a major cause of morbidity and mortality, especially in older people. Older people with diabetes mellitus may be at especially high risk of ADRs but this risk has not been well studied. This study aimed to compare severity and type of ADRs in hospitalised, multimorbid older people with and without diabetes and secondly to assess the impact of ADRs on mortality, rehospitalisation and length of stay. METHODS: Participants in the SENATOR (Software Engine for the Assessment and optimization of drug and non-drug Therapy in Older peRsons) trial were assessed for 12 common and 'other' prevalent and incident adverse drug reactions using a blinded end-point adjudication process. Descriptive analyses, logistic regression and mediation analyses were undertaken. RESULTS: Of 1537 people in the SENATOR trial, 540 (35.1%) had diabetes mellitus (mean age 77.4 ± 7.3 years, 58.5% male). In the total population, 773 prevalent and 828 incident ADRs were reported. Both prevalent and incident symptomatic hypoglycaemia and incident acute kidney injury (AKI) were significantly more common in people with diabetes (p < 0.05). Patients with diabetes had higher all-cause mortality at 12 weeks than those without (9.1% vs 6.3%, p = 0.04). Mediation analysis revealed that mortality was significantly higher (OR = 1.43, Sobel test p = 0.048) in people with diabetes and ADRs causing AKI. CONCLUSIONS: Older multimorbid people with diabetes presenting to hospital with acute illness have significantly more ADRs than those without, and a significantly higher mortality that is mediated by medication-associated AKI and poorer renal function.

Anticholinergic deprescribing interventions for reducing risk of cognitive decline or dementia in older adults with and without prior cognitive impairment.

BACKGROUND: Anticholinergics are medications that block the action of acetylcholine in the central or peripheral nervous system. Medications with anticholinergic properties are commonly prescribed to older adults. The cumulative anticholinergic effect of all the medications a person takes is referred to as the anticholinergic burden. A high anticholinergic burden may cause cognitive impairment in people who are otherwise cognitively healthy, or cause further cognitive decline in people with pre-existing cognitive problems. Reducing anticholinergic burden through deprescribing interventions may help to prevent onset of cognitive impairment or slow the rate of cognitive decline. OBJECTIVES: Primary objective • To assess the efficacy and safety of anticholinergic medication reduction interventions for improving cognitive outcomes in cognitively healthy older adults and older adults with pre-existing cognitive issues. Secondary Objectives • To compare the effectiveness of different types of reduction interventions (e.g. pharmacist-led versus general practitioner-led, educational versus audit and feedback) for reducing overall anticholinergic burden. • To establish optimal duration of anticholinergic reduction interventions, sustainability, and lessons learnt for upscaling • To compare results according to differing anticholinergic scales used in medication reduction intervention trials • To assess the efficacy of anticholinergic medication reduction interventions for improving other clinical outcomes, including mortality, quality of life, clinical global impression, physical function, institutionalisation, falls, cardiovascular diseases, and neurobehavioral outcomes. SEARCH METHODS: We searched CENTRAL on 22 December 2022, and we searched MEDLINE, Embase, and three other databases from inception to 1 November 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of interventions that aimed to reduce anticholinergic burden in older people and that investigated cognitive outcomes. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, extracted data, and assessed the risk of bias of included studies. The data were not suitable for meta-analysis, so we summarised them narratively. We used GRADE methods to rate our confidence in the review results. MAIN RESULTS: We included three trials with a total of 299 participants. All three trials were conducted in a cognitively mixed population (some cognitively healthy participants, some participants with dementia). Outcomes were assessed after one to three months. One trial reported significantly improved performance on the Digit Symbol Substitution Test (DSST) in the intervention group (treatment difference 0.70, 95% confidence interval (CI) 0.11 to 1.30), although there was no difference between the groups in the proportion of participants with reduced anticholinergic burden. Two trials successfully reduced anticholinergic burden in the intervention group. Of these, one reported no significant difference between the intervention versus control in terms of their effect on cognitive performance measured by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) immediate recall (mean between-group difference 0.54, 95% CI -0.91 to 2.05), CERAD delayed recall (mean between-group difference -0.23, 95% CI-0.85 to 0.38), CERAD recognition (mean between-group difference 0.77, 95% CI -0.39 to 1.94), and Mini-Mental State Examination (mean between-group difference 0.39, 95% CI -0.96 to 1.75). The other trial reported a significant correlation between anticholinergic burden and a test of working memory after the intervention (which suggested reducing the burden improved performance), but reported no effect on multiple other cognitive measures. In GRADE terms, the results were of very low certainty. There were no reported between-group differences for any other clinical outcome we investigated. It was not possible to investigate differences according to type of reduction intervention or type of anticholinergic scale, to measure the sustainability of interventions, or to establish lessons learnt for upscaling. No trials investigated safety outcomes. AUTHORS' CONCLUSIONS: There is insufficient evidence to reach any conclusions on the effects of anticholinergic burden reduction interventions on cognitive outcomes in older adults with or without prior cognitive impairment. The evidence from RCTs was of very low certainty so cannot support or refute the hypothesis that actively reducing or stopping prescription of medications with anticholinergic properties can improve cognitive outcomes in older people. There is no evidence from RCTs that anticholinergic burden reduction interventions improve other clinical outcomes such as mortality, quality of life, clinical global impression, physical function, institutionalisation, falls, cardiovascular diseases, or neurobehavioral outcomes. Larger RCTs investigating long-term outcomes are needed. Future RCTs should also investigate potential benefits of anticholinergic reduction interventions in cognitively healthy populations and cognitively impaired populations separately.

Engaging undergraduate medical and dental students with academic medicine: The Aberdeen INSPIRE summer school.

UK medical and dental school curricula limit opportunities for students to gain experience in research. This parallels a decline in the number of clinical academics. To address this at grass roots level, we organised and arranged a residential summer taster week; INSPIRE (Introducing New Skills to Promote Inspirational Research Experience)-Aberdeen). The purpose was to give first and second year medical and dental students who wished to explore a potential clinical academic career a taste of wet laboratory research and to gain experience in basic research skills. Seventeen students from eight different UK medical and dental schools attended this free residential course and were exposed to various laboratory techniques with clinical translation and application in diagnostic and therapeutic medicine. Students were given access to relevant online learning tools of the techniques being used beforehand and seminar style presentations were used to emphasise their clinical application. Students met daily with clinical academics from different specialities to give them a flavour of potential clinical academic career pathways and options. All students felt that the summer school helped them consider academic medicine as a career thus achieving our aim to inspire clinical academics of the future.

Estimating Vitamin C Intake Requirements in Diabetes Mellitus: Analysis of NHANES 2017-2018 and EPIC-Norfolk Cohorts.

Vitamin C is an essential enzyme cofactor and antioxidant with pleiotropic roles in human physiology. Circulating vitamin C concentrations are lower in people with diabetes mellitus, suggesting a higher dietary requirement for the vitamin. We interrogated the NHANES 2017-2018 and EPIC-Norfolk datasets to compare vitamin C requirements between those with and without diabetes mellitus using dose-concentration relationships fitted with sigmoidal (four-parameter logistic) curves. The NHANES cohort (n = 2828 non-supplementing adults) comprised 488 (17%) participants with diabetes (self-reported or HbA1c ≥ 6.5%). The participants with diabetes had a lower vitamin C status (median [IQR]) than those without (38 [17, 52] µmol/L vs. 44 [25, 61] µmol/L, p < 0.0001), despite comparable dietary intakes between the two groups (51 [26, 93] mg/d vs. 53 [24, 104] mg/d, p = 0.5). Dose-concentration relationships indicated that the group without diabetes reached adequate vitamin C concentrations (50 µmol/L) with an intake of 81 (72, 93) mg/d, whilst those with diabetes required an intake of 166 (126, NA) mg/d. In the EPIC-Norfolk cohort, comprising 20692 non-supplementing adults, 475 (2.3%) had self-reported diabetes at baseline. The EPIC cohort had a lower BMI than the NHANES cohort (26 [24, 28] kg/m2 vs. 29 [25, 34] kg/m2, p < 0.0001). Correspondingly, the EPIC participants without diabetes required a lower vitamin C intake of 64 (63, 65) mg/d while those with diabetes required 129 (104, NA) mg/d to reach adequate circulating vitamin C status. C-reactive protein concentrations were strongly correlated with body weight and BMI and provided a surrogate biomarker for vitamin C requirements. In conclusion, people with diabetes had 1.4 to 1.6 fold higher requirements for vitamin C than those without diabetes. This corresponds to additional daily vitamin C intake requirements of ~30-40 mg for people with diabetes, equating to a total daily intake of at least 125 mg/d.

Epidemiology of major trauma in older adults within Scotland: A national perspective from the Scottish Trauma Audit Group (STAG).

BACKGROUND: Major trauma in older adults (MTOA) poses distinctive health and social care challenges, further underlined by the unique socioeconomic and geographical environment of Scotland. This study provides epidemiological trends of MTOA, to provide insight into areas where further evaluation and research are required. MATERIALS AND METHODS: Pseudonymised aggregated demographic, injury and outcome data from 2011 to 2020 were obtained from the Scottish Trauma Audit Group (STAG) Database, covering 28 hospitals across Scotland. Only individuals age ≥ 70 with an Injury Severity Score (ISS) > 15 were included. RESULTS: There was an average of 216 annual cases of MTOA, with a 259 % rise in incidence from 2011 to 2020. This was predominantly driven by a rise in low velocity trauma (fall <2 m height; 287 % increase). The proportion of all major trauma attributable to those aged ≥70 rose from 18.5 % in 2011 to 34.6 % in 2020. Death censored median (IQR) acute hospital length of stay was 18 days (9-30). Overall, 30-day survival was 65.3 %, with no improvement seen between 2011 and 2020 (p = 0.50). Independent predictors of improved 30-day survival included Ages 70-79 & 80-89 [compared to reference ≥ 90] (OR 3.12; 95 %CI 2.24,4.31; p < 0.001 and OR 1.66; 95 %CI 1.21,2.29; p = 0.002 respectively), and Extremity injury (OR 1.89; 95 %CI 1.48,2.41; p < 0.001). Head injury (OR 0.72; 95 %CI 0.54,0.96; p = 0.027) and increasing ISS score (OR 0.88, 95 %CI 0.86,0.89; p < 0.001) were associated with lower likelihood of 30-day survival. A further model also including the admission ward (from eSTAG data November 2017 onwards) demonstrated an association with reduced 30-day survival with admission to General Surgery (OR 0.42; 95 %CI 0.19,0.93; p = 0.033), Intensive Care (OR 0.25; 95 %CI 0.10,0.60; p = 0.002) and Medical Specialities (OR 0.33; 95 %CI 0.15,0.73; p = 0.007) compared to the reference (Major Trauma). Exponential Smoothing predictions revealed a further potential 184 % rise in incidence of MTOA from 2021 to 2030 (3657 per 100,000 population at risk to 10,392 per 100,000 population at risk). CONCLUSION: MTOA is likely to be a rising health care burden, requiring larger quantities of health and social care resource. Urgent preventative strategies are required to reduce low velocity trauma (standing height falls), as well as the high mortality and morbidity of MTOA.

Glycated Haemoglobin (HbA1c) and Future Physical and Mental Functional Health in the European Prospective Investigation into Cancer (EPIC)-Norfolk Population-Based Study.

Little is understood about the relationship between glycated haemoglobin and future functional health in the general population. In this work, we aimed to assess if glycaemic control is associated with future physical and mental functional health at 18-month follow-up in a UK general population, in those with and without diabetes. This work was a cross-sectional study. Between 1995 and 1997, participants of the European Prospective Investigation into Cancer, Norfolk, attended a health check including blood testing for haemoglobin A1c (HbA1c) and completed a health and lifestyle questionnaire. Eighteen months later, self-reported physical and mental functional health were assessed using short form-36 (SF-36). Outcomes of interest included physical and mental component summary (PCS and MCS, respectively) scores of the SF-36. A total of 7343 participants (56% women, mean (SD) 58.1 ± 9.5 years) were eligible to be included, of whom 167 had prevalent diabetes. In our linear regression analysis, a higher HbA1c (mmol/mol) was found to be associated with a poorer PCS score (coefficient -0.15 (p < 0.0001)) at follow-up. After adjustment for comorbid conditions, including obesity, this association was no longer statistically significant. A higher HbA1c (mmol/mol) was associated with a better MCS score at follow-up; this finding was significant when adjusted for comorbid conditions (coefficient 0.029 (p < 0.05)). Our findings suggest that the association between a higher HbA1c and poorer physical functional health is explained by a higher BMI and comorbidity status in a general population. While higher HbA1c was found to be associated with higher mental functional health at follow-up, the magnitude of this association was small. Healthy responder bias and unmeasured confounding variables may have influenced this result; thus, it should be interpreted with caution.

National audit of pathways in epileptic seizure referrals (NAPIER): A national, multicentre audit of first seizure clinics throughout the UK and Ireland.

BACKGROUND: Current guidelines set clinical standards for the management of suspected first seizures and epilepsy. We aimed to assess if these standards are being met across first seizure clinics nationally, to describe variations in care and identify opportunities for service delivery improvement. METHODS: Multicentre audit assessing the care of adults (≥16 years) referred to first seizure clinics from 31st December 2019 going backwards (30 consecutive patients per centre). Patients with pre-existing diagnosis of epilepsy were excluded. Anonymised referral, clinic, and follow-up data are reported with descriptive statistics. RESULTS: Data provided for 727 patients from 25 hospitals in the UK and Ireland (median age 41 years [IQR 26-59], 52% males). Median time to review was 48 days (IQR 26-86), with 13.8% (IQR 3.3%-24.0%) of patients assessed within 2 weeks. Seizure recurrence was seen in 12.7% (IQR 6.6%-17.4%) of patients awaiting first appointment. Documentation for witness accounts and driving advice was evident in 85.0% (IQR 74.0%-100%) and 79.7% (IQR 71.2%-96.4%) of first seizure/epilepsy patients, respectively. At first appointment, discussion of sudden unexpected death in epilepsy was documented in 30.1% (IQR 0%-42.5%) of patients diagnosed with epilepsy. In epilepsy patients, median time to MRI neuroimaging was 37 days [IQR 22-56] and EEG was 30 days [IQR 19-47]. 30.4% ([IQR 0%-59.5%]) of epilepsy patients were referred to epilepsy nurse specialists. CONCLUSIONS: There is variability nationally in the documented care of patients referred to first seizure clinics. Many patients are facing delays to assessment with epilepsy specialists with likely subsequent impact on further management.

Poor outcomes in patients with sepsis undergoing emergency laparotomy and laparoscopy are attenuated by faster time to care measures.

AIM: Emergency laparotomy and laparoscopy (EmLap) are amongst the commonest surgical procedures, with high prevalence of sepsis and hence poorer outcomes. However, whether time taken to receive care influences outcomes in patients requiring antibiotics for suspected infection remains largely unexplored. The aim of this work was to determine whether (1) time to care contributes to outcome differences between patients with and without suspected infection and (2) its impact on outcomes only amongst those with suspected infection. METHOD: Clinical information was retrospectively obtained from the 2017-2018 Emergency Laparotomy and Laparoscopic Scottish Audit (ELLSA). Time to care referred to six temporal variables describing radiological investigation, anaesthetic triage and surgical management. Outcome measures [mortality, readmission, hospital death, postoperative destination and length of stay (LoS)] were compared using adjusted and unadjusted regression analyses to determine whether the outcome differences could be explained by faster or slower time to care. RESULTS: Amongst 2243 EmLap patients [median age 65 years (interquartile range 51-75 years), 51.1% female], 892 (39.77%) received antibiotics for suspected infection. Although patients with suspected infection had faster time to care (all p ≤ 0.001) and worse outcomes compared with those who did not, outcome differences were not statistically significant when accounted for time (all p > 0.050). Amongst those who received antibiotics, faster time to care was also associated with decreased risk of postoperative intensive care unit (ICU) stay and shorter LoS (all p < 0.050). CONCLUSION: Worse outcomes associated with infection in EmLap patients were attenuated by faster time to care, which additionally reduced the LoS and ICU stay risk amongst those with suspected infection.

In-hospital outcomes of acute ischaemic stroke patients with atrial septal defect. A national inpatient sample study.

BACKGROUND AND AIMS: Atrial septal defects (ASD) are a well-recognised risk factor for acute ischaemic stroke (AIS). We aimed to delineate the relationship between ASD and in-hospital AIS outcomes (mortality, severe stroke (National Institutes of Health Stroke Scale (NIHSS) > 15), prolonged hospitalisation > 4 days and routine home discharge) in contemporary practice using data from the United States National Inpatient Sample. METHODS: NIS admissions with a primary diagnosis of AIS between 2016-2018 were extracted. The NIHSS variable had 75% missing data, which were imputed using multiple imputations by chained equations. The relationship between ASD and the main outcomes was modelled using multivariable logistic regressions, adjusting for age, sex, comorbidities, stroke severity and revascularisation therapies. RESULTS: 245,859 records representative of 1,229,295 AIS admissions were included, 35,840 (2.91%) of whom had ASD. ASD patients were younger (median age 63 years versus 72 years) and less likely to have traditional cardiovascular risk factors than their counterparts without ASD. ASD was independently associated with 58% lower odds of in-hospital mortality (hazard ratio (95% confidence interval) = 0.42 (0.33-0.54)), 18% lower odds of severe stroke (0.82 (0.71-0.94)), 20% higher odds of routine home discharge (1.20 (1.14-1.28)) and 28% higher odds of prolonged hospitalisation (1.28 (1.21-1.35)). CONCLUSIONS: ASD was associated with better in-hospital outcomes, which were likely driven by younger age, lower prevalence of traditional cardiovascular risk factors, and lower stroke severity. Further research is warranted to clarify the ASD anatomical characteristics which are most strongly associated with these associations.