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BACKGROUND: While the effects of anticholinergic drug use have been increasingly highlighted, trends in anticholinergic use remain poorly understood. AIM: To determine the changes in frequency and pattern of anticholinergic drug use within a low- and middle-income country. METHOD: Comparisons were made between population-based datasets collected from Malaysian residents aged 55 years and older in 2013-15 and 2020-22. Anticholinergic exposure was determined using the anticholinergic cognitive burden (ACB) tool. Drugs with ACB were categorised according to the Anatomical Therapeutic Chemical (ATC) classification. RESULTS: A total number of 5707 medications were recorded from the 1616 participants included in the 2013-15 dataset. A total number of 6175 medications were recorded from 2733 participants in 2020-22. Two hundred and ninety-three (18.1%) and 280 (10.2%) participants consumed ≥ 1 medication with ACB ≥ 1 in 2013-15 and 2020-22 respectively. The use of nervous system drugs with ACB had increased (27 (0.47%) versus 39 (0.63%). The use of ACB drugs in the cardiovascular (224 (3.9%) versus 215 (3.4%)) and alimentary tract and metabolism (30 (0.52%) versus 4 (0.06%)) classes had reduced over time. Participants in 2020-22 were significantly less likely than those in 2013-15 to have total ACB = 1 - 2 (odds ratio [95% confidence interval] = 0.473[0.385-0.581]) and ACB ≥ 3 (0.251[0.137 - 0.460]) compared to ACB = 0 after adjustment for potential confounders (p < 0.001). CONCLUSION: Although anticholinergic exposure has decreased over time, the use of medications with anticholinergic effects in the nervous system class has risen. This increase is attributable to antipsychotic use, which is of concern due to potential cardiovascular complications, and deserves further evaluation.
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PURPOSE: To conduct a systematic review to assess drug exposure handling in diabetic retinopathy (DR) risk prediction models, a network-meta-analysis to identify drugs associated with DR and a meta-analysis to determine which drugs contributed to enhanced model performance. DESIGN: Systematic review and meta-analysis. METHODS: We included studies presenting DR models incorporating drug exposure as a predictor. We searched EMBASE, MEDLINE, and SCOPUS from inception to December 2023. We evaluated the quality of studies using the Prediction model Risk of Bias Assessment Tool and certainty using GRADE. We conducted network meta-analysis and meta-analysis to estimate the odds ratio (OR) and pooled C-statistic, respectively, and 95% confidence intervals (CI) (PROSPERO: CRD42022349764). RESULTS: Of 5,653 records identified, we included 28 studies of 678,837 type 1 or 2 diabetes participants, of which 38,579 (5.7%) had DR. A total of 19, 3, and 7 studies were at high, unclear, and low risk of bias, respectively. Drugs included in models as predictors were: insulin (n = 24), antihypertensives (n = 5), oral antidiabetics (n = 12), lipid-lowering drugs (n = 7), antiplatelets (n = 2). Drug exposure was modelled primarily as a categorical variable (n = 23 studies). Two studies handled drug exposure as time-varying covariates, and one as a time-dependent covariate. Insulin was associated with an increased risk of DR (OR = 2.50; 95% CI: 1.61-3.86). Models that included insulin (n = 9) had a higher pooled C-statistic (C-statistic = 0.84, CI: 0.80-0.88), compared to models (n = 9) that incorporated a combination of drugs alongside insulin (C-statistic = 0.79, CI: 0.74-0.84), as well as models (n = 3) not including insulin (C-statistic = 0.70, CI: 0.64-0.75). Limitations include the high risk of bias and significant heterogeneity in reviewed studies. CONCLUSION: This is the first review assessing drug exposure handling in DR prediction models. Drug exposure was primarily modelled as a categorical variable, with insulin associated with improved model performance. However, due to suboptimal drug handling, associations between other drugs and model performance may have been overlooked. This review proposes the following for future DR prediction models: (1) evaluation of drug exposure as a variable, (2) use of time-varying methodologies, and (3) consideration of drug regimen details. Improving drug exposure handling could potentially unveil novel variables capable of significantly enhancing the predictive capability of prediction models.
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BACKGROUND: Anticholinergic medications are now widely acknowledged for their unfavorable risk-to-benefit profile owing to their adverse effects. Health-related quality of life (HRQoL) is commonly regarded as a crucial person-centered outcome. AIM: This study aimed to investigate the association between anticholinergic burden and HRQoL in hospitalized and ambulatory patients seen in Ethiopia. METHOD: This cross-sectional study utilized a questionnaire and medical records to collect data from a convenience sample of adult patients attending both inpatient wards and ambulatory clinic of University of Gondar Comprehensive Specialized Hospital between April and September 2022. Anticholinergic burden was measured by anticholinergic cognitive burdens scale (ACBS), while HRQoL was measured using EQ5D-index (Euroqol-5 dimensions-5-Levels index) and EQ5D-VAS (visual analogue scale). Linear regression was used to assess the influence of high anticholinergic burden (ACBS score ≥ 3) on EQ5D-index and EQ5D-VAS, with adjustments made for sociodemographic and clinical confounders. RESULTS: A total of 828 patients participated in this study (median (IQR) age was 45.0 (30, 60) and 55.9% were female). On multiple linear regression analysis, high anticholinergic burden was associated with a statistically significant decline in HRQoL, as evidenced by reductions in both EQ5D index (- 0.174 (- 0.250, - 0.098)) and EQ5D-VAS scores (- 9.4 (- 13.3, - 5.2)). CONCLUSION: A significant association between high anticholinergic burden and diminished HRQoL was found among a relatively younger cohort in a resource-limited setting, even after adjustment for important confounding variables. Clinicians should be cognizant of the cumulative impact of anticholinergic burden on HRQoL outcomes and strive to minimize anticholinergic burden.
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BACKGROUND: Individually, diabetes mellitus and dementia are associated with poorer outcomes after stroke. However, the combined impact of these pre-existing factors on acute ischemic stroke (AIS) outcomes has not been examined. METHODS: All consecutive patients with AIS admitted to Norfolk and Norwich University Hospitals between 2003 and 2016 (catchment population ~ 900,000) were divided into four groups: those with neither diabetes nor dementia (reference), with diabetes without dementia, with dementia without diabetes, and with both co-morbidities. In-hospital mortality, length of hospital stay (LoS), and disability outcomes were analysed using logistic regressions. Post-discharge mortality and recurrence were assessed using Cox regressions. Additionally, interaction terms were added to the models for the short-term outcomes and long-term mortality to test for synergistic effects of diabetes and dementia. Models were adjusted for age, sex, Oxfordshire Community Stroke Project classification, comorbidities, hematological and biochemical measures, and antithrombotic medications. RESULTS: The cohort was 10,812 patients with 52% females and a median age of 80. The median follow-up was 3.8 years for stroke recurrence and 5.5 years for mortality. No significant differences between the four groups existed for in-hospital mortality and post-stroke disability. Patients with dementia had significantly longer LoS (OR 2.25 [95% CI: 1.34-3.77] and 1.31 [1.02-1.68] with and without diabetes, respectively). Patients with both comorbidities had the highest risk of stroke recurrence (HR 2.06 [1.12-3.77]), followed by those with only dementia (1.59 [1.15-2.20]) and only diabetes (1.25 [1.06-1.49]). Similarly, the patient group with both diabetes and dementia had the highest long-term mortality risk (1.76 [1.33-2.37]). The hazard ratios for patients with only dementia and only diabetes were 1.71 [1.46-2.01] and 1.19 [1.08-1.32], respectively. No significant interactions were seen between diabetes and dementia with regards to their effects on the outcomes. CONCLUSION: Individual and cumulative impacts of the two conditions on long-term mortality and stroke recurrence were notable. However, no synergistic impact of the two comorbidities were seen on the stroke outcomes tested in our study. Therefore, tailoring the management of stroke patients based on additional requirements associated with each pre-existing condition will be more impactful towards improving outcomes.
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Comorbilidad , Demencia , Diabetes Mellitus , Mortalidad Hospitalaria , Accidente Cerebrovascular Isquémico , Tiempo de Internación , Recurrencia , Sistema de Registros , Humanos , Femenino , Masculino , Anciano , Demencia/epidemiología , Demencia/mortalidad , Demencia/diagnóstico , Accidente Cerebrovascular Isquémico/mortalidad , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/epidemiología , Factores de Riesgo , Diabetes Mellitus/epidemiología , Diabetes Mellitus/mortalidad , Diabetes Mellitus/diagnóstico , Anciano de 80 o más Años , Factores de Tiempo , Medición de Riesgo , Inglaterra/epidemiología , Evaluación de la Discapacidad , Pronóstico , Persona de Mediana EdadRESUMEN
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.
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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.
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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.
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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.
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Mortalidad Hospitalaria , Sistema de Registros , Albúmina Sérica , Humanos , Anciano , Albúmina Sérica/análisis , Femenino , Masculino , Reino Unido/epidemiología , Accidente Cerebrovascular/mortalidad , Accidente Cerebrovascular/epidemiología , Anciano de 80 o más Años , Tiempo de Internación/estadística & datos numéricos , Hipoalbuminemia/epidemiología , Hipoalbuminemia/mortalidad , Accidente Cerebrovascular Isquémico/mortalidad , Accidente Cerebrovascular Isquémico/sangre , Accidente Cerebrovascular Isquémico/epidemiología , Persona de Mediana EdadRESUMEN
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.
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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.
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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.
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Hematoma Subdural Crónico , Adulto , Humanos , Anciano , Hematoma Subdural Crónico/tratamiento farmacológico , Hospitalización , Análisis Costo-Beneficio , Método Doble Ciego , Dexametasona/uso terapéuticoRESUMEN
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.
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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.
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Demencia , Calidad de Vida , Persona de Mediana Edad , Humanos , Femenino , Anciano , Masculino , Calidad de Vida/psicología , Salud Mental , Comorbilidad , Modelos Logísticos , Demencia/diagnóstico , Demencia/epidemiología , Encuestas y CuestionariosRESUMEN
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 â¼24 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.
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Enfermedades Cardiovasculares , Infarto del Miocardio , Neoplasias , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios de Cohortes , Estudios Prospectivos , Factores de Riesgo , Factores Sexuales , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Infarto del Miocardio/epidemiología , Neoplasias/diagnóstico , Neoplasias/epidemiología , Neoplasias/complicacionesRESUMEN
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.
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Lesión Renal Aguda , Diabetes Mellitus , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Hipoglucemia , Humanos , Masculino , Anciano , Anciano de 80 o más Años , Femenino , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/epidemiología , Hipoglucemia/inducido químicamente , Hipoglucemia/epidemiología , Multimorbilidad , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/epidemiologíaRESUMEN
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.
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Enfermedad de Alzheimer , Enfermedades Cardiovasculares , Disfunción Cognitiva , Deprescripciones , Anciano , Humanos , Antagonistas Colinérgicos/efectos adversos , Disfunción Cognitiva/prevención & controlRESUMEN
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.
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Educación de Pregrado en Medicina , Medicina , Estudiantes de Medicina , Humanos , Estudiantes de Odontología , Educación de Pregrado en Medicina/métodos , Curriculum , Instituciones Académicas , Selección de ProfesiónRESUMEN
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.
RESUMEN
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.