Effect of multiple episodes of Acute Kidney Injury on mortality:an observational study

Background Patients who survive an episode of acute kidney injury (AKI) are more likely to have further episodes of AKI. AKI is associated with increased mortality, with a further increase with recurrent episodes. It is not clear whether this is due to AKI or as a result of other patient characteristics. The aim of this study was to establish whether recurrence of AKI is an independent risk factor for mortality or if excess mortality is explained by other factors. Methods This observational cohort study included adult people from the Tayside region of Scotland, with an episode of AKI between 1 January 2009 and 31 December 2009. AKI was defined using the creatinine-based Kidney Disease: Improving Global Outcomes definition. Associations between recurrent AKI and mortality were examined using a Cox proportional hazards model. Results Survival was worse in the group identified to have recurrent AKI compared with those with a single episode of AKI [hazard ratio = 1.49, 95% confidence interval (CI) 1.37–1.63; P

Molecular epidemiology of lung cancer in the Liverpool lung project (LLP) cohort

The primary aim of the project was to evaluate the epidemiological and genetic susceptibility factors associated with lung cancer, in the Liverpool Lung Project (LLP) population. The associated datasets available for research with the LLP dataset (questionnaire) were: Office of National Statistics (ONS), Health Episode Statistics (HES) data with comorbidity data, single nucleotide polymorphism (SNP) data of 570 cases from Liverpool, 3000 controls from the 1958 Birth Cohort. The epidemiological (HES) data was used to study the effect of Charlson (CCI) and Elixhauser comorbidity index (ECI) on the incidence of lung cancer using the Cox proportional hazard regression and use the same HES data to design a 5-year sex specific incidence model for lung cancer with crucial covariates. The ECI and CCI were significant in both univariate and multivariate analyses adjusted for age at the start of the study, sex and smoking pack years. The developed models had a good discriminatory power (AUCmale = 0.73; AUCfemale = 0.77) when internally validated using a 10-fold cross validation. The genetic data for the LLP lung cancer cases was used in several contexts: i) to identify SNPS associated with lung cancer under a range of allelic models (additive, dominant, recessive and genotypic), using the Wellcome trust 1958 Birth Cohort as a control dataset; ii) to identify SNPs associated with cause specific and overall survival in lung cancer patients, utilising the Cox proportional hazard model with adjustment for various covariates; and iii) to identify gene pathways that are associated with lung cancer survival using the random forest survival method. SNPs within the genes PRDM11, ZNF382 and HMGA2 were identified in the genome wide case-control study when using the additive, dominant or genotypic models, whereas the recessive model identified the gene ITIH2. Significant SNPs (p≤10-6) associated with cause-specific survival in early stage cases were rs10230420 (WIPF3), rs3746619 and rs3827103 (both in MC3R). In advanced stage cases, significant SNPs were rs1868110 (NEK10) and rs2206779 (AF357533). For the overall survival analysis, significant SNPs were rs10230420 (WIPF3), rs2056533 (ZBTB20) and rs6708630 (CYS1) in early stage cases, whereas rs1868110 (NEK10) and rs2206779 (AF357533) were significantly associated with overall survival in advanced stage NSCLC cases. The pathway analysis using the random survival forest method was undertaken on 18 pathways for both cause-specific and overall survival of lung cancer cases. The results were consistent with apoptosis, base excision repair and mismatch repair being pathways influencing survival

Quinine exposure and the risk of acute kidney injury:a population based observational study of older people

Objectives to establish and quantify any observable association between the exposure to community prescriptions for quinine and acute kidney injury (AKI) events in a population of older adults. Design two observational studies using the same dataset, a retrospective longitudinal cohort study and a self-controlled case series (SCCS). Setting NHS health board in Scotland. Participants older adults (60+ years) who received quinine prescriptions in Tayside, Scotland, between January 2004 and December 2015. The first study included 12,744 individuals. The SCCS cohort included 5,907 people with quinine exposure and more than or equal to one AKI event. Main outcome measured in the first study, multivariable logistic regression was used to calculate odds ratios (ORs) for AKI comparing between episodes with and without recent quinine exposure after adjustment for demographics, comorbidities and concomitant medications. The SCCS study divided follow-up for each individual into periods ‘on’ and ‘off’ quinine, calculating incidence rate ratios (IRRs) for AKI adjusting for age. Results during the study period, 273,596 prescriptions for quinine were dispensed in Tayside. A total of 13,616 AKI events occurred during follow-up (crude incidence 12.5 per 100 person-years). In the first study, exposure to quinine before an episode of care was significantly associated with an increased probability of AKI (adjusted OR = 1.27, 95% confidence interval (CI) 1.21–1.33). In the SCCS study, exposure to quinine was associated with an increased relative incidence of AKI compared to unexposed periods (IRR = 1.20, 95% CI 1.15–1.26), with the greatest risk observed within 30 days following quinine initiation (IRR = 1.48, 95% CI 1.35–1.61). Conclusion community prescriptions for quinine in an older adult population are associated with an increased risk of AKI

The burden of psychotropic and anticholinergic medicines use in care homes:population-based analysis in 147 care homes

Background: older people living in care-homes are particularly vulnerable to adverse effects of psychotropic and anticholinergic drugs. Methods: anonymised dispensed prescription data from all 4,478 residents aged ≥ 60 years in 147 care-homes in two Scottish health boards were analysed. Psychotropic medicines examined were antipsychotics, antidepressants, hypnotic/anxiolytics, opioids and gabapentinoids. Anticholinergic burden was measured using the modified anticholinergic risk scale (mARS). Variation between care-homes and associations with individual and care-home characteristics were examined using multilevel logistic regression. Results: 63.5% of residents were prescribed at least one psychotropic drug, and 27.0% two or more, most commonly antidepressants (41.6%), opioids (20.3%), hypnotic/anxiolytics (16.9%) and antipsychotics (16.7%). 48.1% were prescribed an anticholinergic drug, and 12.1% had high anticholinergic burden (mARS ≥ 3). Variation between care-homes was high for antipsychotics (intra-cluster correlation coefficient [ICC] 8.2%) and hypnotics/anxiolytics (ICC = 7.3%), and moderate for antidepressants (ICC = 4.7%) and anticholinergics (ICC = 2.8%). Prescribing of all drugs was lower in the oldest old. People with dementia were more likely to be prescribed antipsychotics (adjusted OR = 1.45, 95%CI 1.23–1.71) but less likely to be prescribed anticholinergics (aOR = 0.61, 95%CI 0.51–0.74). Prescribing of antipsychotics was higher in Tayside (aOR = 1.52, 95%CI 1.20–1.92), whereas prescribing of antidepressants (particularly tricyclic-related) was lower (aOR = 0.66, 95%CI 0.56–0.79). There was no association with care-home regulator quality scores. Conclusion: care-home residents have high psychotropic and anticholinergic burden, with considerable variation between care-homes that is not related to existing measures of quality of care. Research to better understand variation between care-homes and the interaction with local prescribing cultures is needed

Development and external validation of an acute kidney injury risk score for use in the general population

Background: Improving recognition of patients at increased risk of acute kidney injury (AKI) in the community may facilitate earlier detection and implementation of proactive prevention measures that mitigate the impact of AKI. The aim of this study was to develop and externally validate a practical risk score to predict the risk of AKI in either hospital or community settings using routinely collected data. Methods: Routinely collected linked datasets from Tayside, Scotland, were used to develop the risk score and datasets from Kent in the UK and Alberta in Canada were used to externally validate it. AKI was defined using the Kidney Disease: Improving Global Outcomes serum creatinine–based criteria. Multivariable logistic regression analysis was performed with occurrence of AKI within 1 year as the dependent variable. Model performance was determined by assessing discrimination (C-statistic) and calibration. Results: The risk score was developed in 273 450 patients from the Tayside region of Scotland and externally validated into two populations: 218 091 individuals from Kent, UK and 1 173 607 individuals from Alberta, Canada. Four variables were independent predictors for AKI by logistic regression: older age, lower baseline estimated glomerular filtration rate, diabetes and heart failure. A risk score including these four variables had good predictive performance, with a C-statistic of 0.80 [95% confidence interval (CI) 0.80–0.81] in the development cohort and 0.71 (95% CI 0.70–0.72) in the Kent, UK external validation cohort and 0.76 (95% CI 0.75–0.76) in the Canadian validation cohort. Conclusion We have devised and externally validated a simple risk score from routinely collected data that can aid both primary and secondary care physicians in identifying patients at high risk of AKI

Risk of Acute Kidney Injury following community prescription of antibiotics:self-controlled case series

Abstract Background Development of acute kidney injury (AKI) following the use of antibiotics such as sulphonamides, trimethoprim and aminoglycosides is a frequently described phenomenon. More recently, an association between fluoroquinolone use and AKI has been suggested. The aim of this study was to evaluate the risk of AKI as an unintended consequence of commonly prescribed antibiotics in a large community cohort using a method that fully adjusts for underlying patient characteristics, including potential unmeasured confounders. Methods A self-controlled case study was conducted and included all individuals aged 18 years and over in the Tayside region of Scotland who had a serum creatinine measured between 1 January 2004 and 31 December 2012. AKI episodes were defined using the Kidney Disease: Improving Global Outcomes definition. Data on oral community-prescribed antibiotics (penicillins, cephalosporins, fluoroquinolones, sulphonamides and trimethoprim, macrolides and nitrofurantoin) were collected for all individuals. Incidence rate ratios (IRRs) for AKI associated with antibiotic exposure versus time periods without antibiotic exposure were calculated. Results Combined use of sulphonamides, trimethoprim and nitrofurantoin rose by 47% and incidence of community-acquired AKI rose by 16% between 2008 and 2012. During the study period 12 777 individuals developed 14 900 episodes of AKI in the community, of which 68% was AKI Stage 1, 16% Stage 2 and 16% Stage 3. The IRR of AKI during any antibiotic use was 1.16 [95% confidence interval (CI) 1.10—1.23], and this was highest during sulphonamides or trimethoprim use; IRR 3.07 (95% CI 2.81–3.35). Fluoroquinolone and nitrofurantoin use was not associated with a significantly increased rate of AKI; IRR 1.13 (95% CI 0.94–1.35) and 1.16 (95% CI 0.91–1.50), respectively. Conclusions Incidence of AKI rose by 16% between 2008 and 2012. In the same period the use of sulphonamides, trimethoprim and nitrofurantoin increased by 47%. A significant increased risk of AKI was seen with the use of sulphonamides and trimethoprim, but not with fluoroquinolones or nitrofurantoin. </jats:sec

Epidemiology and outcomes of people with dementia, delirium and unspecified cognitive impairment in the general hospital: prospective cohort study of 10,014 admissions

Background&nbsp; Cognitive impairment of various kinds is common in older people admitted to hospital, but previous research has usually focused on single conditions in highly-selected groups and has rarely examined associations with outcomes. This study examined prevalence and outcomes of cognitive impairment in a large unselected cohort of people aged 65+ with an emergency medical admission.&nbsp; Methods&nbsp; Between January 1, 2012, and June 30, 2013, admissions to a single general hospital acute medical unit aged 65+ underwent a structured specialist nurse assessment (n = 10,014). We defined &lsquo;cognitive spectrum disorder&rsquo; (CSD) as any combination of delirium, known dementia, or Abbreviated Mental Test (AMT) score &lt; 8/10. Routine data for length of stay (LOS), mortality, and readmission were linked to examine associations with outcomes.&nbsp; Results&nbsp; A CSD was present in 38.5% of all patients admitted aged over 65, and in more than half of those aged over 85. Overall, 16.7% of older people admitted had delirium alone, 7.9% delirium superimposed on known dementia, 9.4% known dementia alone, and 4.5% unspecified cognitive impairment (AMT score &lt; 8/10, no delirium, no known dementia). Of those with known dementia, 45.8% had delirium superimposed. Outcomes were worse in those with CSD compared to those without &ndash; LOS 25.0 vs. 11.8 days, 30-day mortality 13.6% vs. 9.0%, 1-year mortality 40.0% vs. 26.0%, 1-year death or readmission 62.4% vs. 51.5% (allP &lt; 0.01). There was relatively little difference by CSD type, although people with delirium superimposed on dementia had the longest LOS, and people with dementia the worst mortality at 1 year.&nbsp; Conclusions&nbsp; CSD is common in older inpatients and associated with considerably worse outcomes, with little variation between different types of CSD. Healthcare systems should systematically identify and develop care pathways for older people with CSD admitted as medical emergencies, and avoid only focusing on condition-specific pathways such as those for dementia or delirium alone