An analysis of antidepressant prescribing trends in England 2015-2019

Background Growing concerns about the impact of coronavirus disease 2019 (COVID-19) will likely lead to increased mental health diagnoses and treatment. To provide a pre-COVID-19 baseline, we have examined antidepressant prescribing trends for 5 years preceding COVID-19.Methods A retrospective analysis of anonymised data on medicines prescribed by GPs in England from the Open-Prescribing Database (January 2015 to December 2019) identified the 10 most prescribed antidepressant and, for comparison, cardiovascular medicines.Results Prescription items for the 10 most prescribed antidepressants rose 25% from 58 million (2015) to 72 million (2019). Citalopram was the most prescribed antidepressant; prescriptions for sertraline rose fastest at 2 million items year on year. Over the same period, costs for antidepressant prescribing fell 27.8%. Across all Clinical Commissioning Groups (CCGs) in England, antidepressant prescribing levels, adjusted for population were positively correlated with the index of multiple deprivation (IMD) score. In comparison, prescribing for the top 10 most prescribed cardiovascular medicines increased by 2.75% from 207 million (2015) to 213 million (2019) items.Limitations Anonymised data in the Open-Prescribing Database means no patient diagnoses or treatment plans are linked to this data.Conclusion Antidepressant prescribing, particularly sertraline, is increasing. Prescribing is higher in more deprived regions, but costs are falling to < 2% of all items prescribed. Absolute numbers of prescriptions for cardiovascular medicines are higher, likely reflecting the greater prevalence of cardiovascular disease, and are rising more slowly. This study will enable future work to look at the impact of COVID-19 on prescribing for mental health

A systematic review of observational studies comparing direct oral anticoagulants with vitamin K antagonists for stroke prevention in older people with atrial fibrillation

Direct oral anticoagulants (DOACs) were introduced in 2009 as an alternative to warfarin. Randomised controlled trials found direct oral anticoagulants to be as safe and effective as warfarin for stroke prevention in atrial fibrillation (AF). However, older people were underrepresented in these studies and there is uncertainty as to which treatment offers the best risk/benefit ratio1,2. The aim of this systematic review was to compare the effectiveness and safety of DOACs to vitamin K antagonists (VKAs) in people ≥75 years with AF when treated in routine clinical practice. Studies were included in the systematic review if they used an observational study design, compared a DOAC to a VKA and presented data for an outcome of interest in participants ≥75 years old with AF. An exhaustive search was undertaken: Medline, EMBASE, Scopus, and Web of Science were searched from 01.01.09 to 03.01.18. Pharmaceutical companies were contacted to request unpublished data; reference lists were screened; foreign language articles were translated. Abstracts, editorials and letters were excluded as they did not include sufficient methodology information. The Newcastle‐Ottawa scale was used to assess studies for risk of bias. The study protocol was registered with PROSPERO (CRD42018081696). Ethical approval is not required for reviews.Database searches returned 12,330 original articles. Articles were screened for inclusion and 23 studies were included in the review. The majority (n = 11) of studies were conducted in the USA and Canada, Asia (n = 6), Europe (n = 5), and New Zealand (n = 1). No studies were identified from the UK. The most studied DOAC was dabigatran (n = 21), followed by rivaroxaban (n = 12) and apixaban (n = 7). Generally, the included studies were rated highly with over half scoring 7 or above. Seven studies scored 6, one study scored 5 and three studies scored 4 or below.Effectiveness and safety outcomes: Ischaemic stroke: The majority of studies (6/9) found no significant difference between DOACs and VKAs, two found a decreased risk and one an increased risk with DOACs.Major bleeding: Most studies (8/12) found no significant difference between the groups, three found a decreased risk and one an increased risk with DOACs.Intracranial haemorrhage: Six studies reported that DOACs significantly decreased the risk, whereas five studies reported no significant difference.Gastrointestinal bleeding: Seven studies reported an increased risk with DOACs and two found no significant difference.This review found no difference in effectiveness between DOACs and VKAs but variable safety outcomes in those aged ≥75. However, the findings were limited by the low numbers of older people in the included studies and the low quality scores of those involving only the over 75s. The strength of this study was the broad search strategy; the main limitation was the reliance on published results as access to individual participant data was not available. The majority of studies did not report event rates so effect sizes could not be recalculated. This review has highlighted the need for high quality research investigating the comparative safety and effectiveness of DOACs in older people. It supports further work to examine this question

Use of oral anticoagulants in older people with atrial fibrillation in UK general practice : protocol for a cohort study using the Clinical Practice Research Datalink (CPRD) database

Introduction Warfarin has frequently been underused in older people for stroke prevention in atrial fibrillation (AF). Direct oral anticoagulants (DOACs) entered the UK market from 2008 and have been recommended as an alternative to warfarin. This study aimed to describe any changes in the prescribing of oral anticoagulants (OACs) to people aged ≥75 years in UK general practice before and after the introduction of DOACs, to examine differences in patient characteristics which may influence prescribers' decisions regarding anticoagulation, to evaluate the time people stay on OACs and switching between OACs. Methods and analysis A retrospective cohort study design will be used. Patients with a diagnosis of AF will be identified from the Clinical Practice Research Datalink (CPRD). The study period will run from 1 January 2003 to 27 December 2017. Patients enter the cohort at the latest date of the start of the study period, first AF diagnosis, 75th birthday or a year from when they started to contribute research standard data. Follow-up continues until they leave the practice, death, the date the practice stops contributing research standard data or the end of the study period (27 December 2017). Exposure to OACs will be defined as ≥1 prescription issued for an OAC of interest during the study period. Patients issued an OAC in the year preceding study entry will be defined as a 'prevalent users'. Patients starting on an OAC during the study period will be defined as a 'incident users'. Incidence and prevalence of OAC prescribing, patient demographics and characteristics will be described during three time periods: 2003-2007, 2008-2012 and 2013-2017. Persistence (defined as the time from initiation to discontinuation of medication) with and switching between different OACs will be described. Ethics and dissemination The protocol for this study was approved by the CPRD Independent Scientific Advisory Committee. The results will be disseminated in a peer-reviewed journal and at conferences. Trial registration number EUPAS29923

Prescribing of direct oral anticoagulants and warfarin to older people with atrial fibrillation in UK general practice:a cohort study

BackgroundAnticoagulation for stroke prevention in atrial fibrillation (AF) has, historically, been under-used in older people. The aim of this study was to investigate prescribing of oral anticoagulants (OACs) for people aged ≥ 75 years in the UK before and after direct oral anticoagulants (DOACs) became available.MethodsA cohort of patients aged ≥ 75 years with a diagnosis of AF was derived from the Clinical Practice Research Datalink (CPRD) between January 1, 2003, and December 27, 2017. Patients were grouped as no OAC, incident OAC (OAC newly prescribed) or prevalent OAC (entered study on OAC). Incidence and point prevalence of OAC prescribing were calculated yearly. The risk of being prescribed an OAC if a co-morbidity was present was calculated; the risk difference (RD) was reported. Kaplan-Meier curves were used to explore persistence with anticoagulation. A Cox regression was used to model persistence with warfarin and DOACs over time.ResultsThe cohort comprised 165,596 patients (66,859 no OAC; 47,916 incident OAC; 50,821 prevalent OAC). Incidence of OAC prescribing increased from 111 per 1000 person-years in 2003 to 587 per 1000 person-years in 2017. Older patients (≥ 90 years) were 40% less likely to receive an OAC (RD -0.40, 95% CI -0.41 to -0.39) than younger individuals (75-84 years). The likelihood of being prescribed an OAC was lower with a history of dementia (RD -0.34, 95% CI -0.35 to -0.33), falls (RD -0.17, 95% CI -0.18 to -0.16), major bleeds (RD -0.17, 95% CI -0.19 to -0.15) and fractures (RD -0.13, 95% CI -0.14 to -0.12). Persistence with warfarin was higher than DOACs in the first year (0-1 year: HR 1.25, 95% CI 1.17-1.33), but this trend reversed by the third year of therapy (HR 0.75, 95% CI 0.63-0.89).ConclusionsOAC prescribing for older people with AF has increased; however, substantial disparities persist with age and co-morbidities. Whilst OACs should not be withheld solely due to the risk of falls, these results do not reflect this national guidance. Furthermore, the under-prescribing of OACs for patients with dementia or advancing age may be due to decisions around risk-benefit management.Trial registrationEUPAS29923 . First registered on: 27/06/2019

Effectiveness and safety of direct oral anticoagulants versus vitamin K antagonists for people aged 75 years and over with atrial fibrillation : a systematic review and meta-analysis of observational studies

Older people, are underrepresented in randomised controlled trials of direct oral anticoagulants (DOACs) for stroke prevention in atrial fibrillation (AF). The aim of this study was to combine data from observational studies to provide evidence for the treatment of people aged ≥75 years. Medline, Embase, Scopus and Web of Science were searched. The primary effectiveness outcome was ischaemic stroke. Safety outcomes were major bleeding, intracranial haemorrhage, gastrointestinal bleeding, myocardial infarction, and mortality. Twenty-two studies were eligible for inclusion. Two studies related specifically to people ≥75 years but were excluded from meta-analysis due to low quality; all data in the meta-analyses were from subgroups. The pooled risk estimate of ischaemic stroke was slightly lower for DOACs. There was no significant difference in major bleeding, mortality, or myocardial infarction. Risk of intracranial haemorrhage was 44% lower with DOACs, but risk of GI bleeding was 46% higher. Our results suggest that DOACs may be preferable for the majority of older patients with AF, provided they are not at significant risk of a GI bleed. However, these results are based entirely on data from subgroup analyses so should be interpreted cautiously. There is a need for adequately powered research in this patient group

The incidence of primary glomerulonephritis worldwide:a systematic review of the literature

Background. Little is known about the worldwide variation in incidence of primary glomerulonephritis (GN). The objective of this review was to critically appraise studies of incidence published in 1980-2010 so that an overall view of trends of these diseases can be found. This would provide important information for determining changes in rates and understanding variations between countries. Methods. All relevant papers found through searches of Medline, Embase and ScienceDirect were critically appraised and an assessment was made of the reliability of the reported incidence data. Results. This review includes 40 studies of incidence of primary GN from Europe, North and South America, Canada, Australasia and the Middle East. Rates for the individual types of disease were found to be in adults, 0.2/100 000/year for membrano-proliferative GN, 0.2/100 000/year for mesangio-proliferative GN, 0.6/100 000/year for minimal change disease, 0.8/100 000/year for focal segmental glomerulosclerosis, 1.2/100 000/year for membranous nephropathy and 2.5/100 000/year for IgA nephropathy. Rates were lower in children at around 0.1/100 000/year with the exception of minimal change disease where incidence was reported to be 2.0/100 000/year in Caucasian children with higher rates in Arabian children (9.2/100 000/year) and Asian children (6.2-15.6/100 000/year). Conclusions. This study found that incidence rates of primary GN vary between 0.2/100 000/year and 2.5/100 000/ year. The incidence of IgA nephropathy is at least 2.5/100 000/year in adults; this disease can exist subclinically and is therefore only detected by chance in some patients. In addition, referral policies for diagnostic biopsy vary between countries. This will affect the incidence rates found

Use of laser speckle contrast imaging to assess digital microvascular function in primary Raynaud phenomenon and systemic sclerosis:a comparison using the Raynaud condition score diary

Objective.Evaluate objective assessment of digital microvascular function using laser speckle contrast imaging (LSCI) in a cross-sectional study of patients with primary Raynaud phenomenon (RP) and systemic sclerosis (SSc), comparing LSCI with both infrared thermography (IRT) and subjective assessment using the Raynaud Condition Score (RCS) diary.Methods.Patients with SSc (n = 25) and primary RP (n = 18) underwent simultaneous assessment of digital perfusion using LSCI and IRT with a cold challenge on 2 occasions, 2 weeks apart. The RCS diary was completed between assessments. The relationship between objective and subjective assessments of RP was evaluated. Reproducibility of LSCI/IRT was assessed, along with differences between primary RP and SSc, and the effect of sex.Results.There was moderate-to-good correlation between LSCI and IRT (Spearman rho 0.58–0.84, p &lt; 0.01), but poor correlation between objective assessments and the RCS diary (p &gt; 0.05 for all analyses). Reproducibility of IRT and LSCI was moderate at baseline (ICC 0.51–0.63) and immediately following cold challenge (ICC 0.56–0.86), but lower during reperfusion (ICC 0.3–0.7). Neither subjective nor objective assessments differentiated between primary RP and SSc. Men reported lower median daily frequency of RP attacks (0.82 vs 1.93, p = 0.03). Perfusion using LSCI/IRT was higher in men for the majority of assessments.Conclusion.Objective and subjective methods provide differing information on microvascular function in RP. There is good convergent validity of LSCI with IRT and acceptable reproducibility of both modalities. Neither subjective nor objective assessments could differentiate between primary RP and SSc. Influence of sex on subjective and objective assessment of RP warrants further evaluation.</jats:sec