scholarly journals β 2-Agonists and the Incidence of Parkinson Disease

2020 ◽  
Vol 189 (8) ◽  
pp. 801-810 ◽  
Author(s):  
Francesco Giorgianni ◽  
Pierre Ernst ◽  
Sophie Dell’Aniello ◽  
Samy Suissa ◽  
Christel Renoux
Keyword(s):  
Confidence Interval ◽  
Parkinson Disease ◽  
Rate Ratio ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Reverse Causality ◽  
Β2 Agonist ◽  
Β2 Agonists ◽  
Apparent Association

Abstract A recent study found a decreased risk of Parkinson disease (PD) associated with the β2 adrenergic agonist (β2-agonist) salbutamol. However, other mechanisms might explain this apparent association. Using the UK Clinical Practice Research Datalink, we formed a cohort of 2,430,884 patients aged 50 years or older between 1995 and 2016. During follow-up, 8,604 cases of PD were identified and matched to 86,040 controls on sex, age, date of cohort entry, and duration of follow-up, after applying a 1-year latency time window. Incidence rate ratios of PD associated with use of β2-agonists were estimated using conditional logistic regression. Ever-use of β2-agonists was associated with a 17% decreased rate of PD (rate ratio = 0.83, 95% confidence interval: 0.75, 0.91) compared with no use. However, this association was limited to early short-term use and was no longer observed after more than 2 years of cumulative duration of use (rate ratio = 0.97, 95% confidence interval: 0.80, 1.17). A similar pattern was observed when stratifying by time since first β2-agonist prescription and by duration of follow-up. The apparent association of β2-agonists with a decreased risk of PD is likely the result of reverse causality rather than a biological effect of these drugs on the risk of PD.

scholarly journals Minocycline and the risk of acute psychiatric events in adolescence: A self-controlled case series

2019 ◽  
Vol 33 (4) ◽  
pp. 466-471 ◽  
Author(s):  
Ruth Brauer ◽  
Maria Herrero-Zazo ◽  
David J Barlow ◽  
Fiona Gaughran ◽  
David Taylor ◽  
...  
Keyword(s):  
United Kingdom ◽  
Confidence Interval ◽  
Incidence Rate ◽  
Rate Ratio ◽  
Incidence Rate Ratio ◽  
Psychiatric Symptoms ◽  
Case Series ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Psychiatric Referral

Background Minocycline has neurological anti-inflammatory properties and has been hypothesised to have antipsychotic effects. Aim The aim of this study was to investigate, using routinely collected United Kingdom primary health care data, whether adolescent men and women are more or less likely to receive an urgent psychiatric referral during treatment for acne with minocycline compared with periods of non-treatment. Method A self-controlled case series using United Kingdom Clinical Practice Research Datalink to calculate the incidence rate ratio of urgent psychiatric referrals for individuals, comparing periods during which minocycline was prescribed with unexposed periods, adjusted for age. Results We found 167 individuals who were at the time exposed to minocycline for a mean of 99 days and who received an urgent psychiatric referral. There was no difference in psychiatric referral risk during periods of exposure compared with periods of non-exposure: incidence rate ratio first 6 weeks of exposure 1.96, 95% confidence interval 0.82–4.71, p=0.132; incidence rate ratio remaining exposure period=1.97, 95% confidence interval 0.86–4.47, p=0.107. Conclusions We found no evidence in support of a protective effect of minocycline against severe psychiatric symptoms in adolescence.

scholarly journals Opioids and the Risk of Fracture: a Self-Controlled Case Series Study in the Clinical Practice Research Datalink

2021 ◽  
Author(s):  
Emily J Peach ◽  
Fiona A Pearce ◽  
Jack Gibson ◽  
Andrew J Cooper ◽  
Li-Chia Chen ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Incidence Rate ◽  
Rate Ratio ◽  
Incidence Rate Ratio ◽  
Case Series ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Risk Of Fracture ◽  
Adjusted Incidence Rate ◽  
Adjusted Incidence

Abstract Self-controlled study designs can be used to assess the association between exposures and acute outcomes while controlling for important confounders. Using routinely collected health data, a self-controlled case series design was used to investigate the association between opioid use and bone fractures in 2008–2017 among adults registered in the United Kingdom Clinical Practice Research Datalink. The relative incidence of fracture was estimated, comparing periods when exposed and unexposed to opioids, adjusted for time-varying confounders. Of 539,369 people prescribed opioids, 67,622 sustained fractures and were included. The risk of fracture was significantly increased when exposed to opioids, with an adjusted incidence rate ratio of 3.93 (95% confidence interval: 3.82, 4.04). Fracture-risk was greatest in the first week of starting opioids (adjusted incidence rate ratio: 7.81, 95% confidence interval: 7.40, 8.25) and declined with increasing duration of use. Re-starting opioids after a gap in exposure significantly increased fracture-risk (adjusted incidence rate ratio: 5.05, 95% confidence interval: 4.83, 5.29) when compared to non-use. These findings highlight the importance of raising awareness of fractures among patients at opioid initiation and demonstrate the utility of self-controlled methods for pharmacoepidemiologic research.

scholarly journals Epidemiology and current treatment patterns of treatment-resistant depression in Scotland: a CPRD study

BJPsych Open ◽  
2021 ◽  
Vol 7 (S1) ◽  
pp. S334-S334
Author(s):  
Timothy Ming ◽  
Tom Denee ◽  
Gemma Scott ◽  
Joachim Morrens ◽  
Christopher Weatherburn
Keyword(s):  
Clinical Practice ◽  
Incidence Rates ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Treatment Resistant Depression ◽  
Augmentation Therapy ◽  
Treatment Resistant ◽  
First Line ◽  
Resistant Depression

AimsTo assess the incidence and treatments currently used in clinical practice for the treatment of treatment-resistant depression (TRD) in Scotland.BackgroundPatients with major depressive disorder (MDD) who have not responded to at least two successive antidepressant (AD) treatments in a single episode are described as having Treatment-Resistant Depression (TRD). Epidemiological data on TRD in Scotland is lacking. Furthermore, there is no data to our knowledge on therapies prescribed in Scottish clinical practice to treat TRD.MethodA retrospective, longitudinal cohort study was conducted using Clinical Practice Research Datalink (CPRD) medical records. Adult patients were indexed on AD prescription, requiring MDD diagnosis within 90 days, from Jan 2011-May 2018 with 360-day baseline and 180-day minimum follow-up periods. Failure of ≥2 adequate oral AD regimens following indexing constituted TRD classification. Incidence rates of MDD and TRD (within the MDD cohort) and treatment lines following TRD classification were derived.ResultThe analysis included 20,059 patients with MDD (mean age 44 years, 63% female, median follow-up 59 months); 1,374 (6.8%) were classified as TRD. Median time-to-TRD classification was 25 months. The incidence rate of MDD was 15.9 per 1,000 patient-years and for TRD was 14.7 per 1,000 MDD-patient-years. For all first four post-TRD treatment lines, SSRI monotherapy was the most commonly prescribed therapy, followed by combination (dual/triple) therapy and augmentation therapy (at least one oral AD supplemented with lithium, an antipsychotic or an anticonvulsant therapy). At first-line of TRD treatment, 1,050 (76.4%) patients received monotherapy AD, 212 (15.4%) received combination AD therapy and 112 (8.2%) received augmentation therapy. The most common monotherapy treatments at first-line TRD were sertraline (15.6%), mirtazapine (13.8%), fluoxetine (12.2%) and venlafaxine (11.6%). Among combination therapies, mirtazapine, venlafaxine, sertraline and amitriptyline were frequently used. Among the TRD and MDD cohort, no somatic treatments were coded in CPRD, although the use of these treatments was likely underestimated.ConclusionMonotherapy AD treatment was the most common therapy type for all four post-TRD treatment lines. These data support the need for new treatments that can achieve and maintain therapeutic response, and avoid continuous cycling through similar AD therapies.This study was sponsored by Janssen Cilag Ltd.

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 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

Therapy persistence in newly diagnosed non-valvular atrial fibrillation treated with warfarin or NOAC

2016 ◽  
Vol 115 (01) ◽  
pp. 31-39 ◽  
Author(s):  
Anja Katholing ◽  
Christopher Wallenhorst ◽  
Saul Benedict Freedman ◽  
Carlos Martinez
Keyword(s):  
Atrial Fibrillation ◽  
Guideline Adherence ◽  
Practice Research ◽  
First Year ◽  
Clinical Practice Research Datalink ◽  
Supplementary Material ◽  
One Year ◽  
The Uk ◽  
Physician Adherence

SummaryEfforts to reduce stroke in atrial fibrillation (AF) have focused on increasing physician adherence to oral anticoagulant (OAC) guidelines, but high early vitamin K antagonist (VKA) discontinuation is a limitation. We compared persistence of non-VKA OAC (NOAC) with VKA treatment in the first year after OAC inception for incident AF in real-world practice. We studied 27,514 anticoagulant-naïve patients with incident non-valvular AF between January 2011 and May 2014 in the UK primary care Clinical Practice Research Datalink, with full medication use linkage: mean age 74.2 ± 12.4, 45.7 % female, mean follow-up 1.9 ± 1.1 years. After treatment initiation and follow-up until 1/2015, the proportion remaining on OAC at one year (persistence) was estimated using competing risk survival analyses. OAC was commenced ≤90 days after incident AF in 13,221 patients (48.1 %): 12,307 VKA and 914 NOAC (apixaban, dabigatran, rivaroxaban). Amongst those treated with OAC, the proportion commencing NOAC increased from zero in 1/2011 to 27.0 % in 5/2014, and OAC prescriptions for CHA2DS2VASc score ≥2 (guideline adherence) increased from 41.2 % to 65.5 %. Persistence with OAC declined over 12 months to 63.6 % for VKA and 79.2 % for NOAC (p< 0.0001). Persistence for those with CHA2DS2VASc ≥2 was significantly greater for NOAC (83.0 %) than VKA (65.3 %, p< 0.0001) at one year and all earlier time points. Comparison of VKA and NOAC cohorts matched on individual CHA2DS2VASc components showed consistent results. In conclusion, persistence was significantly higher with NOAC than VKA, and could alone lead to fewer cardioembolic strokes. Increased guideline adherence following NOAC introduction could further decrease AF stroke burden.Supplementary Material to this article is available online at www.thrombosis-online.com.

scholarly journals Evidence of disparities in the provision of the maternal postpartum 6-week check in primary care in England, 2015–2018: an observational study using the Clinical Practice Research Datalink (CPRD)

2021 ◽  
pp. jech-2021-216640
Author(s):  
Yangmei Li ◽  
Jennifer J Kurinczuk ◽  
Christopher Gale ◽  
Dimitrios Siassakos ◽  
Claire Carson
Keyword(s):  
Primary Care ◽  
Clinical Practice ◽  
Policy Change ◽  
Post Partum ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Younger Women ◽  
Preterm Babies ◽  
Deprived Areas

BackgroundA maternal postpartum 6-week check (SWC) with a general practitioner (GP) is now considered an essential service in England, a recent policy change intended to improve women’s health. We aimed to provide an up-to-date snapshot of the prevalence of SWC prior to the policy change as a baseline, and to explore factors associated with having a late or no check.MethodsWe conducted a cohort study using primary care records in England (Clinical Practice Research Datalink (CPRD)). 34 337 women who gave birth between 1 July 2015 and 30 June 2018 and had ≥12 weeks of follow-up post partum were identified in the CPRD Pregnancy Register. The proportion who had evidence of an SWC with a GP was calculated, and regression analysis was used to assess the association between women’s characteristics and risks of a late or no check.ResultsSixty-two per cent (95% CI 58% to 67%) of women had an SWC recorded at their GP practice within 12 weeks post partum, another 27% had other consultations. Forty per cent had an SWC at the recommended 6–8 weeks, 2% earlier and 20% later. A late or no check was more common among younger women, mothers of preterm babies or those registered in more deprived areas.ConclusionsNearly 40% of women did not have a postpartum SWC recorded. Provision or uptake was not equitable; younger women and those in more deprived areas were less likely to have a record of such check, suggesting postpartum care in general practice may be missing some women who need it most.

scholarly journals Sepsis Recording in Primary Care Electronic Health Records, Linked Hospital Episodes and Mortality Records: Population-based Cohort Study in England

2020 ◽  
Author(s):  
Emma Rezel-Potts ◽  
Martin C. Gulliford ◽  
Keyword(s):  
Primary Care ◽  
Cohort Study ◽  
Population Based ◽  
Incidence Rates ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Recent Period ◽  
General Practices ◽  
Different Sources

AbstractObjectivesSepsis is a growing concern for health systems, but the epidemiology of sepsis is poorly characterised. We evaluated sepsis recording across primary care electronic records, hospital episodes and mortality registrations.Methods and FindingsCohort study including 378 general practices in England from Clinical Practice Research Datalink (CPRD) GOLD database from 2002 to 2017 with 36,209,676 patient-years of follow-up with linked Hospital Episode Statistics (HES) and Office for National Statistics (ONS) mortality registrations. Incident sepsis episodes were identified for each source. Concurrent records from different sources were identified and age-standardised and age-specific incidence rates compared. Logistic regression analysis evaluated associations of gender, age-group, fifth of deprivation and period of diagnosis with concurrent sepsis recording.There were 20,206 first episodes of sepsis from primary care, 20,278 from HES and 13,972 from ONS. There were 4,117 (20%) first HES sepsis events and 2,438 (17%) mortality records concurrent with incident primary care sepsis records within 30 days. Concurrent HES and primary care records of sepsis within 30 days before or after first diagnosis were higher at younger or older ages and for patients with the most recent period of diagnosis with those diagnosed during 2007:2011 less likely to have a concurrent HES record given CPRD compared to those diagnosed during 2012 to 2017 (odd ratio 0.65, 95% confidence interval 0.60 to 0.70). At age 85 and older, primary care incidence was 5.22 per 1,000 patient years (95% CI 1.75 to 11.97) in men and 3.55 (0.87 to 9.58) in women which increased to 10.09 (4.86 to 18.51) for men and 7.22 (2.96 to 14.72) for women after inclusion of all three sources.ConclusionExplicit recording of sepsis is inconsistent across healthcare sectors with a high proportion of non-concurrent records. Incidence estimates are higher when linked data are analysed.

scholarly journals Sepsis recording in primary care electronic health records, linked hospital episodes and mortality records: Population-based cohort study in England

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0244764
Author(s):  
Emma Rezel-Potts ◽  
Martin C. Gulliford ◽  
Keyword(s):  
Primary Care ◽  
Cohort Study ◽  
Population Based ◽  
Incidence Rates ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Recent Period ◽  
General Practices ◽  
Different Sources

Background Sepsis is a growing concern for health systems, but the epidemiology of sepsis is poorly characterised. We evaluated sepsis recording across primary care electronic records, hospital episodes and mortality registrations. Methods and findings Cohort study including 378 general practices in England from Clinical Practice Research Datalink (CPRD) GOLD database from 2002–2017 with 36,209,676 patient-years of follow-up with linked Hospital Episode Statistics (HES) and Office for National Statistics (ONS) mortality registrations. Incident sepsis episodes were identified for each source. Concurrent records from different sources were identified and age-standardised and age-specific incidence rates compared. Logistic regression analysis evaluated associations of gender, age-group, fifth of deprivation and period of diagnosis with concurrent sepsis recording. There were 20,206 first episodes of sepsis from primary care, 20,278 from HES and 13,972 from ONS. There were 4,117 (20%) first HES sepsis events and 2,438 (17%) mortality records concurrent with incident primary care sepsis records within 30 days. Concurrent HES and primary care records of sepsis within 30 days before or after first diagnosis were higher at younger or older ages and for patients with the most recent period of diagnosis. Those diagnosed during 2007:2011 were less likely to have a concurrent HES record given CPRD compared to those diagnosed during 2012–2017 (odd ratio 0.65, 95% confidence interval 0.60–0.70). At age 85 and older, primary care incidence was 5.22 per 1,000 patient years (95% CI 1.75–11.97) in men and 3.55 (0.87–9.58) in women which increased to 10.09 (4.86–18.51) for men and 7.22 (2.96–14.72) for women after inclusion of all three sources. Conclusion Explicit recording of ‘sepsis’ is inconsistent across healthcare sectors with a high proportion of non-concurrent records. Incidence estimates are higher when linked data are analysed.

scholarly journals Impact of changes to national guidelines on hypertension related workload

2020 ◽  
pp. bjgp21X714281
Author(s):  
Sarah Lay-Flurrie ◽  
James Sheppard ◽  
Richard J Stevens ◽  
Christian Mallen ◽  
Carl Heneghan ◽  
...  
Keyword(s):  
Interrupted Time Series ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Interrupted Time Series Analysis ◽  
National Guidelines ◽  
Nice Guidelines ◽  
Face To Face ◽  
General Practices ◽  
The Impact

Background: In 2011, National Institute for Health and Care Excellence (NICE) guidelines recommended the routine use of out-of-office blood pressure (BP) monitoring for the diagnosis of hypertension. These changes were predicted to reduce unnecessary treatment costs and workload associated with misdiagnosis. Aim: To assess the impact of guideline change on rates of hypertension-related consultation in general practice. Design and Setting: Cohort study in adults registered with English general practices contributing to the Clinical Practice Research Datalink between 1/4/2006 and 31/3/2017. Method: The primary outcome was the rate of face-to-face, telephone and visit consultations related to hypertension with a GP or nurse. Age and sex standardized rates were analysed using interrupted time-series analysis. Results: In 3,937,191 adults (median follow-up = 4.2 years) there were 12,253,836 hypertension related consultations. The rate of hypertension related consultation was 71.0 per 100 person-years (95% CI 67.8 to 74.2) in April 2006, which remained flat prior to 2011. The introduction of the NICE hypertension guideline in 2011 was associated with a change in yearly trend (change in trend = -3.60 per 100 person-years, 95% CI -5.12 to -2.09). The rate of consultation subsequently decreased to 59.2 per 100 person-years (95% CI 56.5 to 61.8) in March 2017. These changes occurred around the time of diagnosis and persisted when accounting for wider trends in all consultations. Conclusion: Hypertension-related workload has declined in the last decade, in association with guideline changes. This is due to changes in workload at the time of diagnosis, rather than reductions in misdiagnosis.

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