Katharina Mattishent

Meta-Review: Adverse Effects of Inhaled Corticosteroids Relevant to Older Patients

BackgroundIn recent years, clinical trials and observational studies have raised concerns about the potential adverse effects of inhaled corticosteroids (ICS) such as pneumonia, cataract, fractures and hyperglycaemia, which are of particular concern for older patients.MethodsWe conducted a meta-review by searching electronic databases (MEDLINE, EMBASE, PubMed) for systematic reviews and meta-analyses of ICS use and the adverse effects of interest. We also evaluated new primary studies that reported information beyond that available from previously published meta-analyses. Two reviewers independently extracted data on measures of associated harm with ICS use.ResultsWe identified five relevant meta-analyses for inclusion in this meta-review, and also three new studies of ICS and pneumonia. We found consistent evidence of a dose–response relationship between ICS use and serious adverse effects such as fractures and pneumonia. The estimated number needed to treat for harm due to fracture with ICS was 83 with 3-years use, and 60 per year for pneumonia. Both asthma and chronic obstructive pulmonary disease (COPD) users of ICS were at risk of pneumonia, with fluticasone appearing to confer higher risk than budesonide. There is also some suggestion that ICS use is associated with cataracts in a dose–response manner but the evidence is less robust here. Equally, the influence of ICS on diabetes mellitus remains uncertain.ConclusionsIn view of the dose–response relationship seen between ICS use and important adverse effects such as fractures and pneumonia, clinicians needs to carefully balance the benefits of ICS versus the harms in older patients receiving long-term high-dose ICS.

Bi-directional interaction between hypoglycaemia and cognitive impairment in elderly patients treated with glucose-lowering agents: a systematic review and meta-analysis

To examine the bi‐directional relationship, whereby hypoglycaemia is a risk factor for dementia, and where dementia increases risk of hypoglycaemia in older patients with diabetes mellitus treated with glucose‐lowering agents.

Anticholinergic drugs and risk of dementia: case-control study

Abstract Objectives To estimate the association between the duration and level of exposure to different classes of anticholinergic drugs and subsequent incident dementia. Design Case-control study. Setting General practices in the UK contributing to the Clinical Practice Research Datalink. Participants 40 770 patients aged 65-99 with a diagnosis of dementia between April 2006 and July 2015, and 283 933 controls without dementia. Interventions Daily 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 measures Odds ratios for incident dementia, adjusted for a range of demographic and health related covariates. Results 14 453 (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. Conclusions A 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 registration Registered to the European Union electronic Register of Post-Authorisation Studies EUPAS8705.

Meta-analysis: Association between hypoglycaemia and serious adverse events in older patients.

AIMS We aimed to conduct a meta-analysis of serious adverse events (macro- and microvascular 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. RESULTS We included 17 studies involving 1.86 million participants. Meta-analysis of eight studies demonstrated that hypoglycemic episodes were associated with macrovascular complications, odds ratio (OR) 1.83 (95% confidence interval [CI] 1.64, 2.05), and microvascular complications in two studies OR 1.77 (95% CI 1.49, 2.10). Meta-analysis of four studies demonstrated an association between hypoglycaemia and falls or fractures, OR 1.89 (95% CI 1.54, 2.32) and 1.92 (95% CI 1.56, 2.38) respectively. Hypoglycaemia was associated with increased likelihood of death in a meta-analysis of eight studies, OR 2.04 (95% Confidence Interval 1.68, 2.47). 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.

Prognostic indices for early mortality in ischaemic stroke – meta-analysis

Several models have been developed to predict mortality in ischaemic stroke. We aimed to evaluate systematically the performance of published stroke prognostic scores.

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.

Detection of asymptomatic drug-induced hypoglycemia using continuous glucose monitoring in older people – Systematic review

AIM We conducted a systematic review of the use of continuous glucose monitoring (CGM) in older patients, in order to consolidate the growing evidence base in this area. METHODS Our protocol was registered on PROSPERO (CRD42017068523). We searched SCI Web of Science, Ovid SP MEDLINE and EMBASE from January 2010 to June 2017 for observational studies and randomized controlled trial of CGM in older patients (mean age 65 or older) with diabetes. We excluded studies that involved only hospitalized patients. Two reviewers independently extracted data blood sugar values (in particular, hypoglycemic episodes) captured with the use of CGM. We also assessed adverse events and acceptability of CGM. RESULTS After screening 901 abstracts, we included nine studies with a total of 989 older patients with diabetes. The CGM studies reveal that hypoglycemic episodes were occurring in a sizeable proportion (28-65%) of participants. Most (80-100%) of these episodes were asymptomatic, with some patients spending nearly 2 h per day in the hypoglycemic range. Older people with diabetes found CGM acceptable and experienced improved health-related well-being. CONCLUSION CGM frequently picks up asymptomatic hypoglycemic episodes in older patients with diabetes. Users of CGM report improved well-being, and reduction of diabetes-related stress.

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.

Bladder cancer: Pioglitazone-when is a prescription drug safe?

In a recent issue of JAMA, Lewis et al. present long-term data on the likelihood of a link between pioglitazone and the risk of bladder cancer and ten other cancers. Their findings contradict previous concerns regarding the safety of pioglitazone, and add to the controversy surrounding interpretation of rare adverse events associated with prescription drugs.

Is gastroenterology research in decline? A comparison of abstract publication rates from The British Society of Gastroenterology meetings between 1995 and 2005.

Background: Reports have suggested that academic medicine may be in decline within the UK. Further evidence suggests that rates of subsequent full publication of abstracts presented at major scientific meetings are low and may be declining. We have compared the publication rates of abstracts presented at meetings of the British Society of Gastroenterology (BSG) between 1995 and 2005 and examined factors associated with full paper publication. Methods: Abstracts presented at BSG meetings in 1995 and 2005 were assessed by cross-referencing with multiple databases. Abstract characteristics associated with publication were analysed. Results: There were no differences in overall publication rates, impact factors or time to publication between 1995 and 2005. Overall, basic-science abstracts were twice as likely to achieve full publication than non-basic science. There was a significant fall in the publication rates for case series and audits, and significantly increased rates for fundamental/basic-science abstracts over the study period. There were non-significant increases in publication rates for controlled trials and systematic reviews. In general, publication rates for all predominantly clinically orientated abstracts reduced between the two periods with the most notable fall occurring in nutrition. Conclusions: There was no evidence of a decline in overall abstract publication rates between 1995 and 2005. There seemed to be trend for increased publication rates of abstracts using perceived high-quality study methodologies with a corresponding decrease in those with lower quality methods. The proportion of basic-science abstracts is likely to be a determinant of overall full publication rates following scientific meetings.