Hypoglycaemia in older people with dementia and diabetes

Objective To explore the effect of hypoglycaemia on adverse events in older people with diabetes and dementia and determine the feasibility of using continuous glucose monitoring in this patient group. Methods Systematic review on continuous glucose monitoring in older people with diabetes: Hypothesis-generating systematic review to inform my feasibility study and to identify gaps in the evidence. Feasibility study: I conducted a feasibility study of continuous blood glucose monitoring to explore continuous glucose monitoring in older people with diabetes and memory problems. Pharmacoepidemiological study: Retrospective cohort study using the Clinical Research Practice Datalink database to test the effect of exposure to hypoglycaemia in older patients with dementia. Systematic review and meta-analysis on the associations between hypoglycaemia and adverse events in older people treated with glucose-lowering agents: Updated systematic review and meta-analysis of serious adverse events associated with hypoglycaemia in older patients treated with glucose-lowering agents. Findings Systematic review on continuous glucose monitoring in older people with diabetes: 9 studies were included with a total of nearly 1000 patients. Hypoglycaemic episodes occurred in a sizeable proportion and most of these episodes were asymptomatic. Some patients spent nearly 2 hours per day in the hypoglycaemic range. CGM is acceptable to patients and improved health-related well-being. Feasibility study: 12 participants completed the study and found using CGM device acceptable. Data capture with this device varied considerably (3%-92%). The device captured hypoglycaemic episodes in 6 participants, two of which lasted for over 300 minutes. Pharmacoepidemiological study: Older people with dementia and diabetes who have had a hypoglycaemic event are at substantially higher risk of death, cardiovascular events, falls, fractures and emergency department attendances, than those who have not had a hypoglycaemic event. Systematic review and meta-analysis on the associations between hypoglycaemia and adverse events in older people treated with glucose-lowering agents: 42 included studies with over 2 million patients. Hypoglycaemia is associated with an 80% increased risk in vascular complications, a doubling in risk of all-cause mortality, a 55% increased risk in dementia, and a 78% and 68% increased risk in falls and fractures respectively. Conclusions My research has highlighted the complications associated with hypoglycaemia in older people with diabetes and dementia and set the ground work for future studies using continuous glucose monitoring in this patient group

Strengths and limitations of healthcare databases in the evaluation of hypoglycaemia

In this issue of DOM, Zaccardi et al. present an analysis of hypoglycaemia-related hospitalizations in the Hospital Episodes Statistics (HES) administrative database of the English National Health Service. [1] Notable strengths of the work include a large sample size involving more than 100 000 cases of hypoglycaemia, and nationwide capture spanning a duration of ten years. Key conclusions include the possibility of a U-shaped relationship between risk of hypoglycaemia and age, as well as possible associations between social deprivation and ethnicity with greater risk of hypoglycaemia

Meta-Analysis: Association Between Hypoglycemia and Serious Adverse Events in Older Patients Treated With Glucose-Lowering Agents

Aims: We conducted a meta-analysis of serious adverse events (dementia, macro- and micro-vascular events, falls and fractures, and death) associated with hypoglycemia in older patients treated with glucose lowering drugs. Materials and Methods: Meta-analysis of studies reporting on hypoglycemia and adverse events. The search included studies from two previously published systematic reviews, and an updated search of MEDLINE and EMBASE from April 2014 to November 2019. We assessed study validity based on ascertainment of hypoglycemia, adverse events and adjustment for confounders, and conducted a random effects meta-analyses, assessing heterogeneity using the I2 statistic. Results: We included 44 studies involving 2,507,434 participants. Most of the studies used adjusted analysis for confounders and hypoglycaemic events were typically identified based on healthcare databases (severe events). Hypoglycemia was associated with increased likelihood of death in a meta-analysis of eighteen studies, pooled OR 2.02 (95% Confidence Interval 1.75–2.32). Studies assessing mortality signal a time-response relationship with a higher risk of adverse events occurring within the first 90 days after hypoglycemia. Our meta-analysis of nine studies demonstrated that hypoglycaemic episodes were associated with dementia – pooled OR 1.50 (95% CI 1.29–1.74). Our meta-analysis of nineteen studies demonstrated associations between hypoglycaemia and macrovascular complications, pooled OR 1.81 (95% CI 1.70–1.94), and microvascular complications (two studies) pooled OR 1.77 (95% CI 1.49–2.10). There is also an association between hypoglycemia and cardiovascular death (six studies) – pooled OR 2.11 (95% CI 1.55 to 2.87). Similarly, our meta-analysis of six studies demonstrated an association between hypoglycemia and falls and fractures, pooled OR 1.78 (95% CI 1.44–2.21) and 1.68 (95% CI 1.37–2.07) respectively. Conclusion: This meta-analysis confirms previously reported concerns of serious harm following hypoglycemia, especially in the immediate time period after a hypoglycaemic event. Avoidance of hypoglycaemic episodes should be a priority in this vulnerable population

The effects of hypoglycemia and dementia on cardiovascular events, falls and fractures and all-cause mortality in older people:a retrospective cohort study

Aims: Older people with diabetes are susceptible to harm from hypoglycemia, however the consequences of hypoglycemia in older people with dementia are not known. We aimed to test association between hypoglycemia and serious adverse events in older patients with diabetes and dementia, and whether the consequences of hypoglycemia were affected by presence of dementia.  Materials and Methods: Cohort study using Clinical Practice Research Datalink in England (1997-2016). We selected participants, intervention (exposure) and follow-up to mirror two hypothetical target randomised controlled trials. Target trial 1’s exposure was hypoglycemia in patients with dementia. Target trial 2 examined adverse effects of hypoglycemia according to dementia status.We used Cox proportional hazard regression to estimate adjusted hazard ratios (aHR) for falls, fractures, cardiovascular events and mortality.  Results: In target trial 1, hypoglycemia was associated with an increased risk during 12 months follow-up of falls and fractures - aHR 1.94 (95% CI 1.67 to 2.24), cardiovascular events - aHR 2.00 (95% CI 1.61 to 2.48) and mortality - aHR 2.36 (95% CI 2.09 to 2.67).In target trial 2, presence of dementia was associated with increased risk of adverse events after hypoglycemia (12 months follow-up): falls & factures - aHR 1.72 (95% CI 1.51 to 1.96) and mortality - aHR 1.27 (95% CI 1.15 to 1.41), but had no effect on cardiovascular events - aHR 1.14 (95% CI 0.95 to 1.36).  Conclusions and Relevance: Hypoglycemia is associated with an early increased risk of serious adverse events in older people with diabetes and dementia

Continuous glucose monitoring in older people with diabetes and memory problems:a mixed-methods feasibility study in the UK

OBJECTIVES: Older people with diabetes are at increased risk of harm from hypoglycaemia, particularly where there are coexisting memory problems. Continuous glucose monitoring (CGM) offers important benefits in terms of detecting hypoglycaemia, but the feasibility of use and extent of data capture has not been tested in this patient group. Our objective was to investigate the feasibility of trialling a CGM intervention in the community setting in older people with diabetes and memory problems. DESIGN: Mixed-methods feasibility study. SETTING: Community dwellings in the UK. PARTICIPANTS: Patients aged ≥65 with diabetes and abbreviated mental test score ≤8 or known dementia. INTERVENTION: FreeStyle Libre CGM. PRIMARY AND SECONDARY OUTCOME MEASURES: Feasibility criteria were numbers of eligible patients, recruitment, attrition, extent of capture of glucose readings and adverse events. Qualitative interview. RESULTS: We identified 49 eligible participants; 17 consented, but 5 withdrew before recording of data because they or their carers felt unable to manage study procedures. 12 participants (mean age 85 years) completed the study without adverse events. Data capture across 14 days ranged between 3% and 92% (mean 55%); 6 participants had <60% capture. Hypoglycaemic events were recorded in six out of nine insulin users. Qualitative interviews found: the device does not interfere with daily activities, usability and comfort was positive, and it was helpful for carers in monitoring participants' glucose concentrations. CONCLUSIONS: The device was acceptable to participants, and carers reported greater ease in monitoring the participant's glucose concentrations. However, completeness of data capture varied considerably with this device due to the need for users to conduct ≥3 scans per day. Real-time devices with automated data transfer may be more suitable in older people with memory problems

Protocol for a feasibility randomised controlled trial of Screening and Enhanced Risk management for Vascular Event-related Decline in Memory (SERVED Memory)

INTRODUCTION: Stroke is a leading cause of death and disability. The development of dementia after stroke is common. Vascular risk factors (VRF) which contribute to stroke risk can also contribute to cognitive decline, especially in vascular dementia (VaD). There is no established treatment for VaD, therefore strategies for prevention could have major health resource implications. This study was designed to assess whether patients with early cognitive decline after stroke/transient ischaemic attack (TIA) can be easily identified and whether target-driven VRF management can prevent progression to dementia.  OBJECTIVES: The primary objective is to establish the feasibility of recruitment and retention of patients with early cognitive decline to a randomised controlled trial of enhanced VRF management. Secondary objectives include: (a) to determine the potential clinical benefit of the intervention; (b) to estimate the sample size for a future definitive multicentre randomised controlled trial; (c) to inform a future economic evaluation; (d) to explore the link between VRF control and the incidence of cognitive impairment on longitudinal follow-up in a UK population after stroke/TIA with current routine management.  METHODS: 100 patients with cognitive decline poststroke/TIA will be recruited from stroke services at the Norfolk and Norwich University Hospital. After collection of baseline data, they will be randomised to intervention (3 monthly follow-up with enhanced management) or control (treatment as usual by the general practitioner). At 12 months outcomes (repeat cognitive testing, VRF assessment) will be assessed. A further 100 patients without cognitive decline will be recruited to a parallel observational group from the same site. At 12 months they will have repeat cognitive testing.  ETHICS AND DISSEMINATION: Ethical approval has been granted in England. Dissemination is planned via publication in peer-reviewed medical journals and presentation at relevant conferences.  TRIAL REGISTRATION NUMBER: 42688361; Pre-results

Prognostic Tools for Early Mortality in Hemorrhagic Stroke: Systematic Review and Meta-Analysis

Background and Purpose: Several risk scores have been developed to predict mortality in intracerebral hemorrhage (ICH). We aimed to systematically determine the performance of published prognostic tools. Methods: We searched MEDLINE and EMBASE for prognostic models (published between 2004 and April 2014) used in predicting early mortality (<6 months) after ICH. We evaluated the discrimination performance of the tools through a random-effects meta-analysis of the area under the receiver operating characteristic curve (AUC) or c-statistic. We evaluated the following components of the study validity: study design, collection of prognostic variables, treatment pathways, and missing data. Results: We identified 11 articles (involving 41,555 patients) reporting on the accuracy of 12 different tools for predicting mortality in ICH. Most studies were either retrospective or post-hoc analyses of prospectively collected data; all but one produced validation data. The Hemphill-ICH score had the largest number of validation cohorts (9 studies involving 3,819 patients) within our systematic review and showed good performance in 4 countries, with a pooled AUC of 0.80 [95% confidence interval (CI)=0.77-0.85]. We identified several modified versions of the Hemphill-ICH score, with the ICH-Grading Scale (GS) score appearing to be the most promising variant, with a pooled AUC across four studies of 0.87 (95% CI=0.84-0.90). Subgroup testing found statistically significant differences between the AUCs obtained in studies involving Hemphill-ICH and ICH-GS scores (p=0.01). Conclusions: Our meta-analysis evaluated the performance of 12 ICH prognostic tools and found greater supporting evidence for 2 models (Hemphill-ICH and ICH-GS), with generally good performance overall

Safety of 80% vs 30–35% fraction of inspired oxygen in patients undergoing surgery: a systematic review and meta-analysis

Background: Evidence-based guidelines from the World Health Organization (WHO) have recommended a high (80%) fraction of inspired oxygen (FiO2) 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 FiO2. We performed a systematic review to define the relative risk of clinically relevant adverse events (AE) associated with high FiO2. 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% FiO2 compared with 30–35% FiO2. We assessed study quality and performed meta-analyses of risk ratios (RR) comparing 80% FiO2 against 30–35% for major complications, mortality, and intensive care admission. Results: We included 17 moderate–good quality trials and two non-randomised studies with serious-critical risk of bias. No evidence of harm with high FiO2 was found for major AE in the meta-analysis of randomised trials: atelectasis RR 0.91 [95% confidence interval (CI) 0.59–1.42); cardiovascular events RR 0.90 (95% CI 0.32–2.54); intensive care admission RR 0.93 (95% CI 0.7–1.12); and death during the trial RR 0.49 (95% CI 0.17–1.37). One non-randomised study reported that high FiO2 was associated with major respiratory AE [RR 1.99 (95% CI 1.72–2.31)]. Conclusions: No definite signal of harm with 80% FiO2 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