scholarly journals PROTOCOL: A cohort study examining the association between mirtazapine and mortality risk in adults with a diagnosis of depression

Author(s):  
Rebecca M Joseph ◽  
Ruth H Jack ◽  
Richard Morriss ◽  
Roger David Knaggs ◽  
Chris Hollis ◽  
...  

ABSTRACTThis protocol describes a cohort study comparing the risks of mortality and serious self-harm (suicide or near-fatal deliberate self-harm) between adults with depression prescribed mirtazapine, a selective serotonin reuptake inhibitor (SSRI), amitriptyline, or venlafaxine. The study is set within English primary care electronic health records from the Clinical Practice Research Datalink (CPRD) and covers the period 01 January 2005 – 30 November 2018. The study described uses an active comparator new user design: patients are included if they are first prescribed an SSRI before being prescribed mirtazapine, a different SSRI, amitriptyline, or venlafaxine as their second antidepressant. Patients are followed from the initial prescription for the second antidepressant until an outcome (mortality, serious self-harm), end of CPRD follow-up, or study end. Inverse probability of treatment weighting is used to account for confounding variables. The protocol was submitted to the CPRD Independent Scientific Advisory Committee for review and was approved in November 2019 (protocol number 19_241).

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lisa M. Lix ◽  
Shamsia Sobhan ◽  
Audray St-Jean ◽  
Jean-Marc Daigle ◽  
Anat Fisher ◽  
...  

Abstract Background Cardiovascular death is a common outcome in population-based studies about new healthcare interventions or treatments, such as new prescription medications. Vital statistics registration systems are often the preferred source of information about cause-specific mortality because they capture verified information about the deceased, but they may not always be accessible for linkage with other sources of population-based data. We assessed the validity of an algorithm applied to administrative health records for identifying cardiovascular deaths in population-based data. Methods Administrative health records were from an existing multi-database cohort study about sodium-glucose cotransporter-2 (SGLT2) inhibitors, a new class of antidiabetic medications. Data were from 2013 to 2018 for five Canadian provinces (Alberta, British Columbia, Manitoba, Ontario, Quebec) and the United Kingdom (UK) Clinical Practice Research Datalink (CPRD). The cardiovascular mortality algorithm was based on in-hospital cardiovascular deaths identified from diagnosis codes and select out-of-hospital deaths. Sensitivity, specificity, and positive and negative predictive values (PPV, NPV) were calculated for the cardiovascular mortality algorithm using vital statistics registrations as the reference standard. Overall and stratified estimates and 95% confidence intervals (CIs) were computed; the latter were produced by site, location of death, sex, and age. Results The cohort included 20,607 individuals (58.3% male; 77.2% ≥70 years). When compared to vital statistics registrations, the cardiovascular mortality algorithm had overall sensitivity of 64.8% (95% CI 63.6, 66.0); site-specific estimates ranged from 54.8 to 87.3%. Overall specificity was 74.9% (95% CI 74.1, 75.6) and overall PPV was 54.5% (95% CI 53.7, 55.3), while site-specific PPV ranged from 33.9 to 72.8%. The cardiovascular mortality algorithm had sensitivity of 57.1% (95% CI 55.4, 58.8) for in-hospital deaths and 72.3% (95% CI 70.8, 73.9) for out-of-hospital deaths; specificity was 88.8% (95% CI 88.1, 89.5) for in-hospital deaths and 58.5% (95% CI 57.3, 59.7) for out-of-hospital deaths. Conclusions A cardiovascular mortality algorithm applied to administrative health records had moderate validity when compared to vital statistics data. Substantial variation existed across study sites representing different geographic locations and two healthcare systems. These variations may reflect different diagnostic coding practices and healthcare utilization patterns.


2018 ◽  
Vol 68 (675) ◽  
pp. e703-e710 ◽  
Author(s):  
Edward G Tyrrell ◽  
Denise Kendrick ◽  
Kapil Sayal ◽  
Elizabeth Orton

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.


BMJ Open ◽  
2018 ◽  
Vol 8 (10) ◽  
pp. e023830 ◽  
Author(s):  
John-Michael Gamble ◽  
Eugene Chibrikov ◽  
William K Midodzi ◽  
Laurie K Twells ◽  
Sumit R Majumdar

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.


2015 ◽  
Vol 100 (3) ◽  
pp. 214-219 ◽  
Author(s):  
Cornelia H M van Jaarsveld ◽  
Martin C Gulliford

ObjectiveThis study aimed to use primary care electronic health records to evaluate the prevalence of overweight and obesity in 2–15-year-old children in England and compare trends over the last two decades.DesignCohort study of primary care electronic health records.Setting375 general practices in England that contribute to the UK Clinical Practice Research Datalink.PatientsIndividual participants were sampled if they were aged between 2 and 15 years during the period 1994–2013 and had one or more records of body mass index (BMI).Main outcome measurePrevalence of overweight (including obesity) was defined as a BMI equal to or greater than the 85th centile of the 1990 UK reference population.ResultsData were analysed for 370 544 children with 507 483 BMI records. From 1994 to 2003, the odds of overweight and obesity increased by 8.1% per year (95% CI 7.2% to 8.9%) compared with 0.4% (−0.2% to 1.1%) from 2004 to 2013. Trends were similar for boys and girls, but differed by age groups, with prevalence stabilising in 2004 to 2013 in the younger (2–10 year) but not older (11–15 year) age group, where rates continued to increase.ConclusionsPrimary care electronic health records in England may provide a valuable resource for monitoring obesity trends. More than a third of UK children are overweight or obese, but the prevalence of overweight and obesity may have stabilised between 2004 and 2013.


2020 ◽  
Author(s):  
Emma Rezel-Potts ◽  
Martin C. Gulliford ◽  

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.


PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0244764
Author(s):  
Emma Rezel-Potts ◽  
Martin C. Gulliford ◽  

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.


BMJ Open ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. e042652
Author(s):  
Kimberley J Smith ◽  
Mark D Peterson ◽  
Christina Victor ◽  
Jennifer M Ryan

ObjectivesDetermine the risk of incident dementia in adults with cerebral palsy (CP) compared with age, sex and general practice (GP) matched controls.DesignRetrospective cohort study.SettingUK GPs linked into the Clinical Practice Research Datalink (CPRD).ParticipantsCPRD data were used to identify adults aged 18 or older with a diagnosis of CP. Each adult with CP was matched to three controls who were matched for age, sex and GP. In total, 1703 adults with CP and 5109 matched controls were included in the analysis. The mean baseline age of participants was 33.30 years (SD: 15.48 years) and 46.8% of the sample were female.Primary outcomeNew diagnosis of dementia during the follow-up period (earliest date of 1987 to latest date of 2015).ResultsDuring the follow-up, 72 people were identified with a new diagnosis of dementia. The overall proportion of people with and without CP who developed dementia was similar (CP: n=19, 1.1%; matched controls n=54, 10.0%). The unadjusted HR suggested that people with CP had an increased hazard of being diagnosed with dementia when compared with matched controls (HR 2.69, 95% CI 1.44 to 5.00). This association was attenuated when CP comorbidities (sensory impairment, intellectual disability and epilepsy) were accounted for (HR 1.92, 95% CI 0.92 to 4.02).ConclusionsThere was no difference in the proportion of people with CP and matched controls who were diagnosed with dementia during the follow-up. Furthermore, while there was evidence for an increased hazard of dementia among people with CP, the fact that this association was attenuated after controlling for comorbidities indicates that this association may be explained by comorbidities rather than being a direct result of CP. Findings should be interpreted with caution due to the low number of incident cases of dementia.


2018 ◽  
Vol 68 (suppl 1) ◽  
pp. bjgp18X696749 ◽  
Author(s):  
Maimoona Hashmi ◽  
Mark Wright ◽  
Kirin Sultana ◽  
Benjamin Barratt ◽  
Lia Chatzidiakou ◽  
...  

BackgroundChronic Obstructive Airway Disease (COPD) is marked by often severely debilitating exacerbations. Efficient patient-centric research approaches are needed to better inform health management primary-care.AimThe ‘COPE study’ aims to develop a method of predicting COPD exacerbations utilising personal air quality sensors, environmental exposure modelling and electronic health records through the recruitment of patients from consenting GPs contributing to the Clinical Practice Research Datalink (CPRD).MethodThe study made use of Electronic Healthcare Records (EHR) from CPRD, an anonymised GP records database to screen and locate patients within GP practices in Central London. Personal air monitors were used to capture data on individual activities and environmental exposures. Output from the monitors were then linked with the EHR data to obtain information on COPD management, severity, comorbidities and exacerbations. Symptom changes not equating to full exacerbations were captured on diary cards. Linear regression was used to investigate the relationship between subject peak flow, symptoms, exacerbation events and exposure data.ResultsPreliminary results on the first 80 patients who have completed the study indicate variable susceptibility to environmental stressors in COPD patients. Some individuals appear highly susceptible to environmental stress and others appear to have unrelated triggers.ConclusionRecruiting patients through EHR for a study is feasible and allows easy collection of data for long term follow up. Portable environmental sensors could now be used to develop personalised models to predict risk of COPD exacerbations in susceptible individuals. Identification of direct links between participant health and activities would allow improved health management thus cost savings.


BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Thomas Inns ◽  
Kate M. Fleming ◽  
Miren Iturriza-Gomara ◽  
Daniel Hungerford

Abstract Background Rotavirus infection has been proposed as a risk factor for coeliac disease (CD) and type 1 diabetes (T1D). The UK introduced infant rotavirus vaccination in 2013. We have previously shown that rotavirus vaccination can have beneficial off-target effects on syndromes, such as hospitalised seizures. We therefore investigated whether rotavirus vaccination prevents CD and T1D in the UK. Methods A cohort study of children born between 2010 and 2015 was conducted using primary care records from the Clinical Practice Research Datalink. Children were followed up from 6 months to 7 years old, with censoring for outcome, death or leaving the practice. CD was defined as diagnosis of CD or the prescription of gluten-free goods. T1D was defined as a T1D diagnosis. The exposure was rotavirus vaccination, defined as one or more doses. Mixed-effects Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CIs). Models were adjusted for potential confounders and included random intercepts for general practices. Results There were 880,629 children in the cohort (48.8% female). A total of 343,113 (39.0%) participants received rotavirus vaccine; among those born after the introduction of rotavirus vaccination, 93.4% were vaccinated. Study participants contributed 4,388,355 person-years, with median follow-up 5.66 person-years. There were 1657 CD cases, an incidence of 38.0 cases per 100,000 person-years. Compared with unvaccinated children, the adjusted HR for a CD was 1.05 (95% CI 0.86–1.28) for vaccinated children. Females had a 40% higher hazard than males. T1D was recorded for 733 participants, an incidence of 17.1 cases per 100,000 person-years. In adjusted analysis, rotavirus vaccination was not associated with risk of T1D (HR = 0.89, 95% CI 0.68–1.19). Conclusions Rotavirus vaccination has reduced diarrhoeal disease morbidity and mortality substantial since licencing in 2006. Our finding from this large cohort study did not provide evidence that rotavirus vaccination prevents CD or T1D, nor is it associated with increased risk, delivering further evidence of rotavirus vaccine safety.


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