scholarly journals Relative toxicity of benzodiazepines and hypnotics commonly used for self-poisoning: An epidemiological study of fatal toxicity and case fatality

2018 ◽  
Vol 32 (6) ◽  
pp. 654-662 ◽  
Author(s):  
Galit Geulayov ◽  
Anne Ferrey ◽  
Deborah Casey ◽  
Claudia Wells ◽  
Alice Fuller ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Case Fatality ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Relative Toxicity ◽  
Reference Drug ◽  
Alcohol Involvement ◽  
Self Harm ◽  
Hypnotic Drugs ◽  
Using Data

The relative toxicity of anxiolytic and hypnotic drugs commonly used for self-poisoning was assessed using data on suicides, prescriptions and non-fatal self-poisonings in England, 2005–2012. Data on suicide by self-poisoning were obtained from the Office for National Statistics, information on intentional non-fatal self-poisoning was derived from the Multicentre Study of Self-harm in England and data on prescriptions in general practice from the Clinical Practice Research Datalink. We used two indices of relative toxicity: fatal toxicity (the number of fatal self-poisonings relative to the number of individuals prescribed each drug) and case fatality (the number of fatal relative to non-fatal self-poisonings). Diazepam was the reference drug in all analyses. Temazepam was 10 times (95% confidence interval 5.48–18.99) and zopiclone/zolpidem nine times (95% confidence interval 5.01–16.65) more toxic in overdose than diazepam (fatal-toxicity index). Temazepam and zopiclone/zolpidem were 13 (95% confidence interval 6.97–24.41) and 12 (95% confidence interval 6.62–22.17) times more toxic than diazepam, respectively (case-fatality index). Differences in alcohol involvement between the drugs were unlikely to account for the findings. Overdoses of temazepam and zopiclone/zolpidem are considerably more likely to result in death than overdoses of diazepam. Practitioners need to exercise caution when prescribing these drugs, especially for individuals who may be at risk of self-harm, and also consider non-pharmacological options.

scholarly journals Real-world presentation with heart failure in primary care: do patients selected to follow diagnostic and management guidelines have better outcomes?

Open Heart ◽  
2018 ◽  
Vol 5 (2) ◽  
pp. e000935
Author(s):  
Alex Bottle ◽  
Dani Kim ◽  
Paul P Aylin ◽  
F Azeem Majeed ◽  
Martin R Cowie ◽  
...  
Keyword(s):  
Heart Failure ◽  
Primary Care ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Initial Management ◽  
Risk Of Death ◽  
Specialist Referral ◽  
Partial Completion ◽  
General Practices ◽  
Using Data

ObjectiveTo describe associations between initial management of people presenting with heart failure (HF) symptoms in primary care, including compliance with the recommendations of the National Institute for Health and Care Excellence (NICE), and subsequent unplanned hospitalisation for HF and death.MethodsThis is a retrospective cohort study using data from general practices submitting records to the Clinical Practice Research Datalink. The cohort comprised patients diagnosed with HF during 2010–2013 and presenting to their general practitioners with breathlessness, fatigue or ankle swelling.Results13 897 patients were included in the study. Within the first 6 months, only 7% had completed the NICE-recommended pathway; another 18.6% had followed part of it (B-type natriuretic peptide testing and/or echocardiography, or specialist referral). Significant differences in hazards were seen in unadjusted analysis in favour of full or partial completion of the NICE-recommended pathway. Covariate adjustment attenuated the relations with death much more than those for HF admission. Compared with patients placed on the NICE pathway, treatment with HF medications had an HR of 1.16 (95% CI 1.05 to 1.28, p=0.003) for HF admission and 1.03 (95% CI 0.90 to 1.17, p= 0.674) for death. Patients who partially followed the NICE pathway had similar hazards to those who completed it. Patients on no pathway had the highest hazard for HF admission at 1.30 (95% 1.18 to 1.43, p<0.001) but similar hazard for death.ConclusionsPatients not put on at least some elements of the NICE-recommended pathway had significantly higher risk of HF admission but non-significant higher risk of death than other patients had.

scholarly journals Poisoning substances taken by young people: a population-based cohort study

2018 ◽  
Vol 68 (675) ◽  
pp. e703-e710 ◽  
Author(s):  
Edward G Tyrrell ◽  
Denise Kendrick ◽  
Kapil Sayal ◽  
Elizabeth Orton
Keyword(s):  
Cohort Study ◽  
Young People ◽  
Population Based ◽  
Incidence Rates ◽  
Practice Research ◽  
Mortality Data ◽  
Clinical Practice Research Datalink ◽  
Self Harm ◽  
Harm Prevention ◽  
Rate Ratios

BackgroundGlobally, poisonings account for most medically-attended self-harm. Recent data on poisoning substances are lacking, but are needed to inform self-harm prevention.AimTo assess poisoning substance patterns and trends among 10–24-year-olds across EnglandDesign and settingOpen cohort study of 1 736 527 young people, using linked Clinical Practice Research Datalink, Hospital Episode Statistics, and Office for National Statistics mortality data, from 1998 to 2014.MethodPoisoning substances were identified by ICD-10 or Read Codes. Incidence rates and adjusted incidence rate ratios (aIRR) were calculated for poisoning substances by age, sex, index of multiple deprivation, and calendar year.ResultsIn total, 40 333 poisoning episodes were identified, with 57.8% specifying the substances involved. The most common substances were paracetamol (39.8%), alcohol (32.7%), non-steroidal anti-inflammatory drugs (NSAIDs) (11.6%), antidepressants (10.2%), and opioids (7.6%). Poisoning rates were highest at ages 16–18 years for females and 19–24 years for males. Opioid poisonings increased fivefold from 1998–2014 (females: aIRR 5.30, 95% confidence interval (CI) = 4.08 to 6.89; males: aIRR 5.11, 95% CI = 3.37 to 7.76), antidepressant poisonings three-to fourfold (females: aIRR 3.91, 95% CI = 3.18 to 4.80, males: aIRR 2.70, 95% CI = 2.04 to 3.58), aspirin/NSAID poisonings threefold (females: aIRR 2.84, 95% CI = 2.40 to 3.36, males: aIRR 2.76, 95% CI = 2.05 to 3.72) and paracetamol poisonings threefold in females (aIRR 2.87, 95% CI = 2.58 to 3.20). Across all substances poisoning incidence was higher in more disadvantaged groups, with the strongest gradient for opioid poisonings among males (aIRR 3.46, 95% CI = 2.24 to 5.36).ConclusionIt is important that GPs raise awareness with families of the substances young people use to self-harm, especially the common use of over-the-counter medications. Quantities of medication prescribed to young people at risk of self-harm and their families should be limited, particularly analgesics and antidepressants.

scholarly journals Examining the risk of depression or self-harm associated with incretin-based therapies used to manage hyperglycaemia in patients with type 2 diabetes: a cohort study using the UK Clinical Practice Research Datalink

BMJ Open ◽  
2018 ◽  
Vol 8 (10) ◽  
pp. e023830 ◽  
Author(s):  
John-Michael Gamble ◽  
Eugene Chibrikov ◽  
William K Midodzi ◽  
Laurie K Twells ◽  
Sumit R Majumdar
Keyword(s):  
Cohort Study ◽  
Clinical Practice ◽  
Population Based ◽  
Practice Research ◽  
Primary Study ◽  
Clinical Practice Research Datalink ◽  
Glucose Lowering ◽  
Self Harm ◽  
The Uk ◽  
New Onset

ObjectivesTo compare population-based incidence rates of new-onset depression or self-harm in patients initiating incretin-based therapies with that of sulfonylureas (SU) and other glucose-lowering agents.DesignPopulation-based cohort study.SettingPatients attending primary care practices registered with the UK-based Clinical Practice Research Datalink (CPRD).ParticipantsUsing the UK-based CPRD, we identified two incretin-based therapies cohorts: (1) dipeptidyl peptidase-4 inhibitor (DPP-4i)-cohort, consisting of new users of DPP-4i and SU and (2) glucagon-like peptide-1 receptor agonists (GLP-1RA)-cohort, consisting of new users of GLP-1RA and SU, between January 2007 and January 2016. Patients with a prior history of depression, self-harm and other serious psychiatric conditions were excluded.Main outcome measuresThe primary study outcome comprised a composite of new-onset depression or self-harm. Unadjusted and adjusted Cox proportional hazards regression was used to quantify the association between incretin-based therapies and depression or self-harm. Deciles of High-Dimensional Propensity Scores and concurrent number of glucose-lowering agents were used to adjust for potential confounding.ResultsWe identified new users of 6206 DPP-4i and 22 128 SU in the DPP-4i-cohort, and 501 GLP-1RA and 16 409 SU new users in the GLP-1RA-cohort. The incidence of depression or self-harm was 8.2 vs 11.7 events/1000 person-years in the DPP-4i-cohort and 18.2 vs 13.6 events/1000 person-years in the GLP-1RA-cohort for incretin-based therapies versus SU, respectively. Incretin-based therapies were not associated with an increased or decreased incidence of depression or self-harm compared with SU (DPP-4i-cohort: unadjusted HR 0.70, 95% CI 0.51 to 0.96; adjusted HR 0.80, 95% CI 0.57 to 1.13; GLP-1RA-cohort: unadjusted HR 1.36, 95% CI 0.72 to 2.58; adjusted HR 1.25, 95% CI 0.63 to 2.50). Consistent results were observed for other glucose-lowering comparators including insulin and thiazolidinediones.ConclusionsOur findings suggest that the two incretin-based therapies are not associated with an increased or decreased risk of depression or self-harm.

scholarly journals Adverse effects of Z-drugs for sleep disturbance in people living with dementia: a population-based cohort study

BMC Medicine ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Kathryn Richardson ◽  
Yoon K. Loke ◽  
Chris Fox ◽  
Ian Maidment ◽  
Robert Howard ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Adverse Events ◽  
Confidence Interval ◽  
Ischaemic Stroke ◽  
Sleep Disturbance ◽  
Cox Regression ◽  
Population Based ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Health Related

Abstract Background Sleep disturbance is common in dementia and often treated with Z-drugs (zopiclone, zaleplon, and zolpidem). While some observational studies suggest that Z-drugs are associated with adverse events such as falls and fracture risks in older people, this has not been studied in dementia. Methods We used data from 27,090 patients diagnosed with dementia between January 2000 and March 2016 from the Clinical Practice Research Datalink linked to Hospital Episodes Statistics data in England. We compared adverse events for 3532 patients newly prescribed Z-drugs by time-varying dosage to (1) 1833 non-sedative-users with sleep disturbance; (2) 10,214 non-sedative-users with proximal GP consultation matched on age, sex, and antipsychotic use; and (3) 5172 patients newly prescribed benzodiazepines. We defined higher dose Z-drugs and benzodiazepines as prescriptions equivalent to ≥ 7.5 mg zopiclone or > 5 mg diazepam daily. Cox regression was used to estimate hazard ratios (HRs) for incident fracture, hip fracture, fall, mortality, acute bacterial infection, ischaemic stroke/transient ischaemic attack, and venous thromboembolism over a 2-year follow-up, adjusted for demographic- and health-related covariates. Results The mean (SD) age of patients was 83 (7.7) years, and 16,802 (62%) were women. Of 3532 patients prescribed Z-drugs, 584 (17%) were initiated at higher doses. For patients prescribed higher dose Z-drugs relative to non-users with sleep disturbance, the HRs (95% confidence interval) for fractures, hip fractures, falls, and ischaemic stroke were 1.67 (1.13–2.46), 1.96 (1.16–3.31), 1.33 (1.06–1.66), and 1.88 (1.14–3.10), respectively. We observed similar associations when compared to non-sedative-users with proximal GP consultation. Minimal or inconsistent excess risks were observed at ≤ 3.75 mg zopiclone or equivalent daily, and for mortality, infection, and venous thromboembolism. We observed no differences in adverse events for Z-drugs compared to benzodiazepines, except lower mortality rates with Z-drugs (HR [95% confidence interval] of 0.73 [0.64–0.83]). Conclusions Higher dose Z-drug use in dementia is associated with increased fracture and stroke risks, similar or greater to that for higher dose benzodiazepines. Higher dose Z-drugs should be avoided, if possible, in people living with dementia, and non-pharmacological alternatives preferentially considered. Prescriptions for higher dose Z-drugs in dementia should be regularly reviewed. Trial registration ENCePP e-register of studies, EUPAS18006

scholarly journals Assessment of Effectiveness of Seasonal Influenza Vaccination During Pregnancy in Preventing Influenza Infection in Infants in England, 2013–2014 and 2014–2015

2019 ◽  
Author(s):  
Jemma L Walker ◽  
Hongxin Zhao ◽  
Gavin Dabrera ◽  
Nick Andrews ◽  
Sarah L Thomas ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Confidence Interval ◽  
Influenza Vaccination ◽  
Seasonal Influenza ◽  
Influenza Infection ◽  
Screening Method ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Uptake Data ◽  
Maternal Influenza

AbstractMaternal influenza vaccination is increasingly recognized to protect infants from influenza infection in their first 6 months. We used the screening method to estimate vaccine effectiveness (VE) against laboratory-confirmed influenza in infants in England, using newly available uptake data from the Clinical Practice Research Datalink pregnancy register, matched on week of birth and region and adjusted for ethnicity. We found VE of 66% (95% confidence interval [CI], 18%–84%) in the 2013–2014 season and 50% (95% CI, 11%–72%) in 2014–2015, with similar VE against influenza-related hospitalization. VE against the dominant circulating influenza strain was higher, at 78% (95% CI, 16%–94%) against H1N1 in 2013–2014, and 60% (95% CI, 16%–81%) against H3N2 in 2014–2015.

Benefits of combining prevalent and incident cohorts: An application to myotonic dystrophy

2018 ◽  
Vol 28 (10-11) ◽  
pp. 3333-3345 ◽  
Author(s):  
David B Wolfson ◽  
Ana F Best ◽  
Vittorio Addona ◽  
Julian Wolfson ◽  
Shahinaz M Gadalla
Keyword(s):  
Myotonic Dystrophy ◽  
Survival Data ◽  
Disease Onset ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Survivor Function ◽  
Cohort Data ◽  
Prevalent Cohort ◽  
Using Data ◽  
Incident Cohort

It is frequently of interest to estimate the time that individuals survive with a disease, that is, to estimate the time between disease onset and occurrence of a clinical endpoint such as death. Epidemiologic survival data are commonly collected from either an incident cohort, whose members' disease onset occurs after the study baseline date, or from a cohort with prevalent disease that is followed forward in time. Incident cohort survival data are limited by study termination, while prevalent cohort data provide biased (left-truncated) survival data. In this article, we investigate the advantages of a study design featuring simultaneous follow-up of prevalent and incident cohorts to the estimation of the survivor function. Our analyses are supported by simulations and illustrated using data on survival after myotonic dystrophy diagnosis from the United Kingdom Clinical Practice Research Datalink (CPRD). We demonstrate that the NPMLE using combined incident and prevalent cohort data estimates the true survivor function very well, even for moderate sample sizes, and ameliorates the disadvantages of using a purely incident or prevalent cohort.

scholarly journals Prevalence of comorbid mental and physical illnesses and risks for self-harm and premature death among primary care patients diagnosed with fatigue syndromes

2019 ◽  
Vol 50 (7) ◽  
pp. 1156-1163
Author(s):  
Matthew J. Carr ◽  
Darren M. Ashcroft ◽  
Peter D. White ◽  
Nav Kapur ◽  
Roger T. Webb
Keyword(s):  
Cox Regression ◽  
Premature Mortality ◽  
Premature Death ◽  
Epidemiological Studies ◽  
Adverse Outcomes ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Hazard Ratios ◽  
History Of ◽  
Self Harm

AbstractBackgroundFatigue syndromes (FSs) affect large numbers of individuals, yet evidence from epidemiological studies on adverse outcomes, such as premature death, is limited.MethodsCohort study involving 385 general practices in England that contributed to the Clinical Practice Research Datalink (CPRD) with linked inpatient Hospital Episode Statistics (HES) and Office for National Statistics (ONS) cause of death information. A total of 10 477 patients aged 15 years and above, diagnosed with a FS during 2000–2014, were individually matched with up to 20 comparator patients without a history of having a FS. Prevalence ratios (PRs) were estimated to compare the FS and comparison cohorts on clinical characteristics. Adjusted hazard ratios (HRs) for subsequent adverse outcomes were estimated from stratified Cox regression models.ResultsAmong patients diagnosed with FSs, we found elevated baseline prevalence of: any psychiatric illness (PR 1.77; 95% CI 1.72–1.82), anxiety disorders (PR 1.92; 1.85–1.99), depression (PR 1.89; 1.83–1.96), psychotropic prescriptions (PR 1.68; 1.64–1.72) and comorbid physical illness (PR 1.28; 1.23–1.32). We found no significant differences in risks for: all-cause mortality (HR 0.99; 0.91–1.09), natural death (HR 0.99; 0.90–1.09), unnatural death (HR 1.00; 0.59–1.72) or suicide (HR 1.68; 0.78–3.63). We did, however, observe a significantly elevated non-fatal self-harm risk: HR 1.83; 1.56–2.15.ConclusionsThe absence of elevated premature mortality risk is reassuring. The raised prevalence of mental illness and increased non-fatal self-harm risk indicate a need for enhanced assessment and management of psychopathology associated with fatigue syndromes.

scholarly journals Previously diagnosed influenza infections and the risk of developing epilepsy

2014 ◽  
Vol 143 (11) ◽  
pp. 2408-2415 ◽  
Author(s):  
J. C. WILSON ◽  
S. TOOVEY ◽  
S. S. JICK ◽  
C. R. MEIER
Keyword(s):  
Viral Infections ◽  
Epidemiological Studies ◽  
Practice Research ◽  
Prior History ◽  
Clinical Practice Research Datalink ◽  
Control Analysis ◽  
Using Data ◽  
Simplex Virus

SUMMARYSeveral epidemiological studies suggest a possible involvement of viral infection in the development of epilepsy. While recent research from in vitro studies increasingly supports the role of herpes simplex virus type 1 (HSV-1) in the pathogenesis of epilepsy, little is known about the role of other viral infections such as influenza. Using data from the Clinical Practice Research Datalink (CPRD), we conducted a matched case-control analysis to assess the association between GP-diagnosed influenza infections and the risk of developing an incident diagnosis of epilepsy. During the study period 11 244 incident epilepsy cases and 44 976 matched control patients were identified. Prior exposure to influenza was reported in 7·5% of epilepsy cases and 6·7% of controls [adjusted odds ratio (aOR) 1·12, 95% confidence interval (CI) 1·03–1·22]. Prior history of ‘complicated influenza’, i.e. influenza associated with a possible super-infection, was associated with a slightly increased epilepsy risk (aOR 1·64, 95% CI 1·10–2·46), particularly if recorded within the 2 months preceding the epilepsy diagnosis (aOR 6·03, 95% CI 1·10–33·2). Our findings suggest that prior influenza exposure does not appear to materially alter the risk of developing epilepsy. By contrast, influenza episodes accompanied by complications were associated with a slightly increased epilepsy risk.

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