ObjectivesTo estimate the association between the duration and level of exposure to different classes of anticholinergic drugs and subsequent incident dementia.DesignCase-control study.SettingGeneral practices in the UK contributing to the Clinical Practice Research Datalink.Participants40 770 patients aged 65-99 with a diagnosis of dementia between April 2006 and July 2015, and 283 933 controls without dementia.InterventionsDaily defined doses of anticholinergic drugs coded using the Anticholinergic Cognitive Burden (ACB) scale, in total and grouped by subclass, prescribed 4-20 years before a diagnosis of dementia.Main outcome measuresOdds ratios for incident dementia, adjusted for a range of demographic and health related covariates.Results14 453 (35%) cases and 86 403 (30%) controls were prescribed at least one anticholinergic drug with an ACB score of 3 (definite anticholinergic activity) during the exposure period. The adjusted odds ratio for any anticholinergic drug with an ACB score of 3 was 1.11 (95% confidence interval 1.08 to 1.14). Dementia was associated with an increasing average ACB score. When considered by drug class, gastrointestinal drugs with an ACB score of 3 were not distinctively linked to dementia. The risk of dementia increased with greater exposure for antidepressant, urological, and antiparkinson drugs with an ACB score of 3. This result was also observed for exposure 15-20 years before a diagnosis.ConclusionsA robust association between some classes of anticholinergic drugs and future dementia incidence was observed. This could be caused by a class specific effect, or by drugs being used for very early symptoms of dementia. Future research should examine anticholinergic drug classes as opposed to anticholinergic effects intrinsically or summing scales for anticholinergic exposure.Trial registrationRegistered to the European Union electronic Register of Post-Authorisation Studies EUPAS8705.
Background: Evidence-based guidelines from the World Health Organization (WHO) have recommended a high (80%) fraction of inspired oxygen (FiO 2 ) to reduce surgical site infection in adult surgical patients undergoing general anaesthesia with tracheal intubation. However, there is ongoing debate over the safety of high FiO 2 . We performed a systematic review to define the relative risk of clinically relevant adverse events (AE) associated with high FiO 2 . Methods: We reviewed potentially relevant articles from the WHO review supporting the recommendation, including an updated (July 2018) search of EMBASE and PubMed for randomised and non-randomised controlled studies reporting AE in surgical patients receiving 80% FiO 2 compared with 30e35% FiO 2 . We assessed study quality and performed meta-analyses of risk ratios (RR) comparing 80% FiO 2 against 30e35% for major complications, mortality, and intensive care admission. Results: We included 17 moderateegood quality trials and two non-randomised studies with serious-critical risk of bias. No evidence of harm with high FiO 2 was found for major AE in the meta-analysis of randomised trials: atelectasis RR 0.91 [95% confidence interval (CI) 0.59e1.42); cardiovascular events RR 0.90 (95% CI 0.32e2.54); intensive care admission RR 0.93 (95% CI 0.7e1.12); and death during the trial RR 0.49 (95% CI 0.17e1.37). One non-randomised study reported that high FiO 2 was associated with major respiratory AE [RR 1.99 (95% CI 1.72e2.31)]. Conclusions: No definite signal of harm with 80% FiO 2 in adult surgical patients undergoing general anaesthesia was demonstrated and there is little evidence on safety-related issues to discourage its use in this population.
Aims: Recent research suggests the possibility of a bi-directional relationship whereby hypoglycaemia is a risk factor for dementia, and also where dementia increases risk of hypoglycaemia. We aimed to examine this relationship in older patients with diabetes mellitus treated with glucose lowering agents. Materials and Methods:We searched MEDLINE and EMBASE over a ten year span 2005 to 2015 (with automated PubMed updates to August 2015) for observational studies of the association between hypoglycaemia and cognitive impairment or dementia in participants aged >55 years. Assessment of study validity was based on ascertainment of hypoglycaemia, dementia and risk of confounding. We conducted random effects inverse variance meta-analyses, and assessed heterogeneity using the I 2 statistic. Results:We screened 1177 citations, and selected twelve studies, with nine suitable for meta-analysis. There were a total of 1,439,818 participants, mean age 75 years. Meta-analysis of five studies demonstrated a significantly increased risk of dementia in patients who had hypoglycaemic episodes, pooled odds ratio of 1.68 (95% Confidence Interval 1.45, 1.95). We also found a significantly increased risk of hypoglycaemia in patients with dementia, pooled odds ratio from five studies 1.61 (95% Confidence Interval 1.25, 2.06).Limitations are heterogeneity in the meta-analysis, and uncertain ascertainment of dementia and hypoglycaemic outcomes and temporal relationships. Publication bias may favour reporting of more significant findings. Conclusions:Our meta-analysis demonstrates a bi-directional relationship between cognitive impairment and hypoglycaemia in older patients. Glucose 3 lowering therapy should be carefully tailored and monitored in older patients who are susceptible to cognitive decline.4
Previous estimates of whether long-term exposure to benzodiazepines increases dementia risk are conflicting and are compromised by the difficulty of controlling for confounders and by reverse causation. We investigated how estimates for the association between benzodiazepine use and later dementia incidence varied based on study design choices, using a case-control study nested within the United Kingdom’s Clinical Practice Research Datalink. A total of 40,770 dementia cases diagnosed between April 2006 and July 2015 were matched on age, sex, available data history, and deprivation to 283,933 control subjects. Benzodiazepines and Z-drug prescriptions were ascertained in a drug-exposure period 4–20 years before dementia diagnosis. Estimates varied with the inclusion of new or prevalent users, with the timing of covariate ascertainment, and with varying time between exposure and outcome. There was no association between any new prescription of benzodiazepines and dementia (adjusted odds ratio (OR) = 1.03, 95% confidence interval (CI): 1.00, 1.07), whereas an inverse association was observed among prevalent users (adjusted OR = 0.91, 95% CI: 0.87, 0.95), although this was likely induced by unintentional adjustment for colliders. By considering the choice of confounders and timing of exposure and covariate measurement, our findings overall are consistent with no causal effect of benzodiazepines or Z-drugs on dementia incidence.
Aims:We aimed to conduct a meta-analysis of serious adverse events (macro-and micro-vascular events, falls and fractures, death) associated with hypoglycaemia in older patients. Methods:We searched MEDLINE and EMBASE spanning a ten-year period up to March 2015 (with automated PubMed updates to October 2015). We selected observational studies reporting on hypoglycaemia and associated serious adverse events, and conducted a meta-analysis. We assessed study validity based on ascertainment of hypoglycaemia, adverse events and adjustment for confounders. Conclusion:Our meta-analysis raises major concerns about a range of serious adverse events associated with hypoglycaemia. Clinicians should prioritize individualized therapy and closer monitoring strategies to avoid hypoglycaemia in susceptible older patients.
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