OpenSAFELY NHS Service Restoration Observatory 2: changes in primary care clinical activity in England during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has disrupted healthcare activity across a broad range of clinical services. The NHS stopped non-urgent work in March 2020, later recommending services be restored to near-normal levels before winter where possible. AIM: To describe changes in the volume and variation of coded clinical activity in general practice across six clinical areas: cardiovascular disease, diabetes, mental health, female and reproductive health, screening and related procedures, and processes related to medication. DESIGN AND SETTING: With the approval of NHS England, a cohort study was conducted of 23.8 million patient records in general practice, in situ using OpenSAFELY. METHOD: Common primary care activities were analysed using Clinical Terms Version 3 codes and keyword searches from January 2019 to December 2020, presenting median and deciles of code usage across practices per month. RESULTS: Substantial and widespread changes in clinical activity in primary care were identified since the onset of the COVID-19 pandemic, with generally good recovery by December 2020. A few exceptions showed poor recovery and warrant further investigation, such as mental health (for example, for 'Depression interim review' the median occurrences across practices in December 2020 was down by 41.6% compared with December 2019). CONCLUSION: Granular NHS general practice data at population-scale can be used to monitor disruptions to healthcare services and guide the development of mitigation strategies. The authors are now developing real-time monitoring dashboards for the key measures identified in this study, as well as further studies using primary care data to monitor and mitigate the indirect health impacts of COVID-19 on the NHS.

A scoping review of non-professional medication practices and medication safety outcomes during public health emergencies.

OBJECTIVES: Public health emergencies (PHE) can disrupt personal medication practices and increase the risk of medication-related harm and other negative medication-related outcomes. Our aim was to examine the extent and nature of published research on this topic to guide future research and practice. STUDY DESIGN: Scoping review. METHODS: Standard electronic databases were searched. PRISMA-ScR guidelines were followed. Extracted data were organised in response to review questions and narrative accounts developed. RESULTS: A total of 129 studies were included, conducted across 32 countries, mostly in the USA (n = 42). Sixty-eight (53%) reported on infectious events, 49 (39%) climatological or ecological events and the remainder a mixture of terrorism, war or other disasters. The studies described several medication safety outcomes (medication-related harm, adherence, supply) and adaptive medication practices (self-altering prescribed medications, sharing medications and changing healthcare providers). Challenges to maintaining routine medication practices during a PHE included transport, finance, quarantine and knowledge-related issues. Twenty-eight studies (22%) examined health inequalities pertaining to adverse medication-related outcomes, with findings suggesting that gender, age, ethnicity, educational and socio-economic status may be related to inequalities. Research gaps identified included carers', children's and minority communities' experiences and intervention studies. CONCLUSIONS: There is considerable evidence of disruptions to routine personal medication practices during PHEs and of medication-related harm and other negative outcomes. Maintaining medication supply for the management of chronic conditions is a universal problem across all emergency types. Research is needed to address these disruptions, particularly amongst people who experience health inequalities who may need additional support.

Using primary care data to assess comparative effectiveness and safety of apixaban and rivaroxaban in patients with nonvalvular atrial fibrillation in the UK: an observational cohort study.

OBJECTIVE: To compare real-world effectiveness and safety of direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation (AFib) for prevention of stroke. STUDY DESIGN AND SETTING: A comparative cohort study in UK general practice data from The Health Improvement Network database. PARTICIPANTS AND INTERVENTIONS: Before matching, 5655 patients ≥18 years with nonvalvular AFib who initiated at least one DOAC between 1 July 2014 and 31 December 2020 were included. DOACs of interest included apixaban, rivaroxaban, edoxaban and dabigatran, with the primary comparison between apixaban and rivaroxaban. Initiators of DOACs were defined as new users with no record of prescription for any DOAC during 12 months before index date. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was stroke (ischaemic or haemorrhagic). Secondary outcomes included the occurrence of all-cause mortality, myocardial infarction (MI), transient ischaemic attacks (TIA), major bleeding events and a composite angina/MI/stroke (AMS) endpoint. RESULTS: Compared with rivaroxaban, patients initiating apixaban showed similar rates of stroke (HR: 0.93; 95% CI 0.64 to 1.34), all-cause mortality (HR: 1.03; 95% CI 0.87 to 1.22), MI (HR: 0.95; 95% CI 0.54 to 1.68), TIA (HR: 1.03; 95% CI 0.61 to 1.72) and AMS (HR: 0.96; 95% CI 0.72 to 1.27). Apixaban initiators showed lower rates of major bleeding events (HR: 0.60; 95% CI 0.47 to 0.75). CONCLUSIONS: Among patients with nonvalvular AFib, apixaban was as effective as rivaroxaban in reducing rate of stroke and safer in terms of major bleeding episodes. This head-to-head comparison supports conclusions drawn from indirect comparisons of DOAC trials against warfarin and demonstrates the potential for real-world evidence to fill evidence gaps and reduce uncertainty in both health technology assessment decision-making and clinical guideline development.

Professional workforce training needs for Health Impact Assessment in spatial planning: A cross sectional survey.

Objectives: Heath Impact Assessment (HIA) in spatial planning can influence wider determinants and prevent ill-health, promote good health and reduce inequalities. They remain underutilised in England, partly due to inadequate workforce training. This study sought to identify the training needs of Public Health Professionals, Planners and Impact Assessment Practitioners in England in 2021. Study design: Cross-sectional survey. Methods: A survey was undertaken of Public Health Professionals, Planners and Impact Assessment Practitioners to ascertain their training needs. Descriptive statistics, frequency tables and charts summarised feedback. Results: 76% (68) of 90 total respondents, never received any training in HIAs. Quantifying impact of planning on health, especially in monetary terms and monitoring success of HIA recommendations, were common challenges for all professions. Musculoskeletal health and infectious disease were among specific health impacts where professionals welcomed further training. Public Health professionals requested support to identify high-impact interventions and work more collaboratively with Planners and a need to justify budgets for undertaking HIAs. Planners expressed training needs around justifying requirement for HIAs, data collection; and identifying local public health priorities. Impact Assessment Practitioners expressed uncertainty about policy triggers needed to undertake HIAs citing that the scale of HIAs must be proportional to project scope, the challenge of identifying planning interventions and a need to apply consistent methodological approaches in HIAs. Conclusion: There is need for baseline training to upskill all professionals, alongside tailored-training on key topic areas to address profession- and locality-specific needs to ensure spatial planning decisions better influence wider determinants and address local health priorities.

Spotlight environmental sustainability: a strategic priority for NICE.

This article provides the context for the ambition outlined in the the National Institute for Health and Care Excellence (NICE) 2021-2026 strategy to 'lead globally on the potential to include environmental impact data in its guidance to reduce the carbon footprint of health and care'. Anthropogenic environmental changes pose a catastrophic risk to human health, with potential to widen national and global health inequalities. Recognising the fact that NICE guidance influences the way health and care is delivered and its consequent environmental impact, NICE has included environmental sustainability among its strategic priorities. This article outlines the work underway to meet this sustainability agenda at NICE.

Initiation of antidepressant medication in people with type 2 diabetes living in the United Kingdom-A retrospective cohort study.

INTRODUCTION: Depression is a common comorbidity in people with type 2 diabetes and it is associated with poorer outcomes. There is limited data on the treatments used for depression in this population. The aim of this study was to explore the rates of initiation of antidepressant prescriptions in people with type 2 diabetes in the UK and identify those most at risk of needing such treatment. RESEARCH DESIGN AND METHODS: This was a retrospective cohort study using data from IQVIA Medical Research Data (IMRD)-UK data. Data from general practices in IMRD-UK between January 2008 and December 2017 were used for this study. RESULTS: The overall rates of antidepressant prescribing were stable over the study period. The rate of initiation of antidepressant medication in people with type 2 diabetes was 22.93 per 1000 person years at risk (PYAR) with a 95%CI 22.48 to 23.39 compared to 16.89 per 1000 PYAR (95%CI 16.77 to 17.01) in an age and gender matched cohort. The risk of being prescribed antidepressant medication with age had a U-shaped distribution with the lowest risk in the 65-69 age group. The peak age for antidepressant initiation in men and women was 40-44, with a rate in men of 32.78 per 1000 PYAR (95% CI 29.57 to 36.34) and a rate in women of 46.80 per 1000 PYAR (95% CI 41.90 to 52.26). People with type 2 diabetes with in the least deprived quintile had an initiation rate of 19.66 per 1000 PYAR (95%CI 18.67 to 20.70) compared to 27.19 per 1000 PYAR (95%CI 25.50 to 28.93) in the most deprived quintile, with a 32% increase in the risk of starting antidepressant medication (95%CI 1.22 to 1.43). CONCLUSIONS: People with type 2 diabetes were 30% more likely to be started on antidepressant medication than people without type 2 diabetes. Women with type 2 diabetes were 35% more likely than men to be prescribed antidepressants and the risks increased with deprivation and in younger or older adults, with the lowest rates in the 65-69 year age band. The rates of antidepressant prescribing were broadly stable over the 10-year period in this study. The antidepressant medications prescribed changed slightly over time with sertraline becoming more widely used and fewer prescriptions of citalopram.

Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) randomized controlled trial: a systematic review of published responses.

OBJECTIVES: The objective of this review was to assess the nature and tone of the published responses to the Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) randomized controlled trial. METHODS: Published articles that cited the PulMiCC trial were identified from Clarivate Web of Science (©. Duplicates and self-citations were excluded and relevant text was extracted. Four independent researchers rated the extracts independently using agreed scales for the representativeness of trial data and the textual tone. The ratings were aggregated and summarized. Two PulMiCC authors carried out a thematic analysis of the extracts. RESULTS: Sixty-four citations were identified and relevant text was extracted and examined. The consensus rating for data inclusion was a median of 0.25 out of 6 (range 0-5.25, interquartile range 0-1.5) and, for textual tone, the median rating was 1.87 out of 6 (range 0-5.75, interquartile range 1-3.5). The majority of citations did not provide adequate representation of the PulMiCC data and the overall textual tone was dismissive. Although some were supportive, many discounted the findings because the trial closed early and was underpowered to show non-inferiority. Two misinterpreted the authors' conclusions but there was an acceptance that 5-year survival was much higher than widely assumed. CONCLUSIONS: Published comments reveal a widespread reluctance to consider seriously the results of a carefully conducted randomized trial. This may be because the results challenge accepted practice because of 'motivated reasoning', but there is a widespread misunderstanding of the fact that though PulMiCC with 93 patients was underpowered to test non-inferiority, it still provides reliable evidence to undermine the widespread belief in a major survival benefit from metastasectomy.

Cardiovascular outcomes of type 2 diabetic patients treated with DPP­4 inhibitors versus sulphonylureas as add-on to metformin in clinical practice.

DPP-4 inhibitors (DPP-4i) and sulphonylureas remain the most widely prescribed add-on treatments after metformin. However, there is limited evidence from clinical practice comparing major adverse cardiovascular events (MACE) in patients prescribed these treatments, particularly among those without prior history of MACE and from vulnerable population groups. Using electronic health records from UK primary care, we undertook a retrospective cohort study with people diagnosed type-2 diabetes mellitus, comparing incidence of MACE (myocardial infarction, stroke, major cardiovascular surgery, unstable angina) and all-cause mortality among those prescribed DPP-4i versus sulphonylureas as add-on to metformin. We stratified analysis by history of MACE, age, social deprivation and comorbidities and adjusted for HbA1c, weight, smoking-status, comorbidities and medications. We identified 17,570 patients prescribed sulphonylureas and 6,267 prescribed DPP-4i between 2008-2017. Of these, 16.3% had pre-existing MACE. Primary incidence of MACE was similar in patients prescribed DPP-4i and sulphonylureas (10.3 vs 8.5 events per 1000 person-years; adjusted Hazard Ratio (adjHR): 0.94; 95%CI 0.80-1.14). For those with pre-existing MACE, rates for recurrence were higher overall, but similar between the two groups (21.8 vs 17.2 events per 1000 person-years; adjHR: 0.93; 95%CI 0.69-1.24). For those aged over 75 and with BMI less than 25 kg/m2 there was a protective effect for DPP-I, warranting further investigation. Patients initiating a DPP-4i had similar risk of cardiovascular outcomes to those initiating a sulphonylurea. This indicates the choice should be based on safety and cost, not cardiovascular prognosis, when deciding between a DPP-4i or sulphonylurea as add-on to metformin.

Time trends in the incidence of clinically diagnosed type 2 diabetes and pre-diabetes in the UK 2009-2018: a retrospective cohort study.

INTRODUCTION: To describe recent trends in the incidence of clinically diagnosed type 2 diabetes and pre-diabetes in people seen in UK general practice. RESEARCH DESIGN AND METHODS: A retrospective cohort study using IQVIA Medical Research Data looking at people newly diagnosed with type 2 diabetes and pre-diabetes through primary care registers in the UK between 1 January 2009 and 31 December 2018. RESULTS: A cohort of 426 717 people were clinically diagnosed with type 2 diabetes and 418 656 people met the criteria for a diagnosis of pre-diabetes in that time period. The incidence of clinically diagnosed type 2 diabetes per 1000 person years at risk (PYAR) in men decreased from a peak of 5.06 per 1000 PYAR (95% CI 4.97 to 5.15) in 2013 to 3.56 per 1000 PYAR (95% CI 3.46 to 3.66) by 2018. For women, the incidence of clinically diagnosed type 2 diabetes per 1000 PYAR decreased from 4.45 (95% CI 4.37 to 4.54) in 2013 to 2.85 (2.76 to 2.93) in 2018. The incidence rate of pre-diabetes tripled by the end of the same study period in men and women. CONCLUSIONS: Between 2009 and 2018, the incidence rate of new clinical diagnoses of type 2 diabetes recorded in a UK primary care database decreased by a third from its peak in 2013-2014, while the incidence of pre-diabetes has tripled. The implications of this on timely treatment, complication rates and mortality need further longer term exploration.

Impact of Being Eligible for Type 2 Diabetes Treatment on All-Cause Mortality and Cardiovascular Events: Regression Discontinuity Design Study.

BACKGROUND: Individuals with type 2 diabetes (T2D) have a twofold increased risk for cardiovascular events (CVE), and CVE is responsible for nearly 80% of the mortality. Current treatment guidelines state that individuals should immediately initiate antidiabetic treatment and cardiovascular risk-factor management from T2D diagnosis. However, the evidence base is sparse, and randomized trials are unlikely to be conducted. We examined the impact of being eligible for T2D treatment, as determined by the threshold of HbA1c ≥6.5% (≥48 mmol/mol), on all-cause mortality and CVE. We hypothesised that individuals who were just above this threshold had a lower risk of CVE and all-cause mortality than individuals just below. METHODS AND FINDINGS: We used the regression discontinuity design (RDD), a quasi-experimental design, comparing rates of all-cause mortality and CVE in people just below and just above the eligibility for treatment threshold. We included Danish healthcare records from 43,070 individuals aged 40-80 years with no previous T2D record and the first record of HbA1c in the range of 6.0-7.0% (42-53 mmol/mol) between 2006 and 2014. In total, 36,360 individuals had the first record of HbA1c between 6.0% and 6.4% (42-47 mmol/mol), and 6710 individuals had a first record between 6.5% and 7.0% (48-53 mmol/mol). Individuals with a measurement just above 6.5% (48 mmol/mol) had a 21% lower rate of death or CVE, compared to those just below (hazard ratio: 0.79 (95% CI 0.69-0.90)). Few individuals received early metformin treatment. However, the chance of metformin treatment initiation within 3 months was substantially higher for individuals with an HbA1c measurement above (14%) than below (1%) the threshold. CONCLUSION: Individuals with first record of HbA1c measure just above treatment threshold experienced a 21% lower rate of death or CVE than those just below. Lifestyle modifications and cardiovascular risk-factor management may contribute to this reduced rate.

Comparative effectiveness of sitagliptin vs sulphonylureas in older people.

BACKGROUND: two common anti-diabetic treatments used are sitagliptin and sulphonylureas however evidence examining their comparative effectiveness in older people is limited. OBJECTIVE: to evaluate effectiveness of sitagliptin vs sulphonylureas when added to metformin in older (aged ≥75) vs younger people (18-75). DESIGN: retrospective cohort study. SETTING: UK Primary Care. SUBJECTS: 2,904 individuals prescribed sitagliptin (223 aged≥75) and 13,683 prescribed sulphonylureas (1,725 aged ≥75). METHODS: multivariable regression to analyse difference in HbA1c and weight, 12 months after add-on initiation and proportion achieving different glycaemic targets. RESULTS: after multivariate adjustment to remove baseline differences, the HbA1c after 12 months of treatment was on average 1 mmol/mol (95%CI -0.7 to 2.8) higher with sitagliptin vs sulphonylureas in older people though this was not statistically significant. The weight however, was significantly lower -1.4 kg (95%CI -2.1 to -0.7) with sitagliptin vs sulphonylureas. A lower proportion prescribed sitagliptin vs sulphonylureas recorded HbA1c < 48 mmol/mol by study end: Odds Ratio 0.63 (95%CI 0.42-0.95). In younger people, similar HbA1c reductions were also observed with both treatments, however weight after 12 months was even lower with sitagliptin vs sulphonylureas: -2.3 kg (95%CI -2.5 to -2.0). CONCLUSIONS: similar HbA1c reduction was observed when sitagliptin or sulphonylureas were added to metformin in older and younger age-groups. Sitagliptin use led to modest comparative weight loss. There may be greater risk of over-treatment with sulphonylureas evidenced by greater proportion recording HbA1c < 48 mmol/mol by study end. This evidence supporting use of sitagliptin when add-on therapy is selected in older adults should be considered alongside the wider evidence-base and patient-preference.

Ethnic Differences in the Prevalence of Type 2 Diabetes Diagnoses in the UK: Cross-Sectional Analysis of the Health Improvement Network Primary Care Database.

AIMS/HYPOTHESIS: Type 2 diabetes mellitus is associated with high levels of disease burden, including increased mortality risk and significant long-term morbidity. The prevalence of diabetes differs substantially among ethnic groups. We examined the prevalence of type 2 diabetes diagnoses in the UK primary care setting. METHODS: We analysed data from 404,318 individuals in The Health Improvement Network database, aged 0-99 years and permanently registered with general practices in London. The association between ethnicity and the prevalence of type 2 diabetes diagnoses in 2013 was estimated using a logistic regression model, adjusting for effect of age group, sex, and social deprivation. A multiple imputation approach utilising population-level information about ethnicity from the UK census was used for imputing missing data. RESULTS: Compared with those of White ethnicity (5.04%, 95% CI 4.95 to 5.13), the crude percentage prevalence of type 2 diabetes was higher in the Asian (7.69%, 95% CI 7.46 to 7.92) and Black (5.58%, 95% CI 5.35 to 5.81) ethnic groups, while lower in the Mixed/Other group (3.42%, 95% CI 3.19 to 3.66). After adjusting for differences in age group, sex, and social deprivation, all minority ethnic groups were more likely to have a diagnosis of type 2 diabetes compared with the White group (OR Asian versus White 2.36, 95% CI 2.26 to 2.47; OR Black versus White 1.65, 95% CI 1.56 to 1.73; OR Mixed/Other versus White 1.17, 95% CI 1.08 to 1.27). CONCLUSION: The prevalence of type 2 diabetes was higher in the Asian and Black ethnic groups, compared with the White group. Accurate estimates of ethnic prevalence of type 2 diabetes based on large datasets are important for facilitating appropriate allocation of public health resources, and for allowing population-level research to be undertaken examining disease trajectories among minority ethnic groups, that might help reduce inequalities.

Observational studies of treatment effectiveness: worthwhile or worthless?

Observational studies which evaluate effectiveness are often viewed with skepticism owing to the fact that patients are not randomized to treatment, meaning that results are more prone to bias. Therefore, randomized controlled trials remain the gold standard for evaluating treatment effectiveness. However, it is not always possible to conduct randomized trials. This may be due to financial constraints, for example, in identifying funding for a randomized trial for medicines that have already gained market authorization. There can also be challenges with recruitment, for example, of people with rare conditions or in hard-to-reach population subgroups. This is why observational studies are still needed. In this manuscript, we discuss how researchers can mitigate the risk of bias in the most common type of observational study design for evaluation of treatment effectiveness, the cohort study. We outline some key issues that warrant careful consideration at the outset when the question is being developed and the cohort study is being designed. We focus our discussion on the importance of deciding when to start follow-up in a study, choosing a comparator, managing confounding and measuring outcomes. We also illustrate the application of these considerations in a more detailed case study based on an examination of comparative effectiveness of two antidiabetic treatments using data collected during routine clinical practice.

Effectiveness of sitagliptin compared to sulfonylureas for type 2 diabetes mellitus inadequately controlled on metformin: a systematic review and meta-analysis.

OBJECTIVE: To assess the effectiveness of sitagliptin compared to sulfonylureas as add-on to metformin in adults with type 2 diabetes mellitus from both randomised controlled trials (RCTs) and 'real-world' non-randomised studies. METHODS AND ANALYSES: We conducted a systematic review of EMBASE, MEDLINE, CENTRAL and grey literature for RCTs and non-randomised studies. We reported outcomes relating to change in HbA1c, fasting glucose, weight, blood pressure and lipids from baseline and need for treatment change. No study investigating macrovascular and microvascular diabetes complications was found. Meta-analysis was used where studies were sufficiently homogenous. RESULTS: Seven RCTs and five non-randomised studies were eligible for inclusion from 1335 articles retrieved. Meta-analysis of three homogenous RCTs revealed a statistically significant decrease in weight with sitagliptin when compared to sulfonylureas (weighted mean difference (WMD) -2.05 kg; 95% CI -2.38 to -1.71); however, a similar change from baseline in HbA1c (WMD 0.05; 95% CI -0.03 to 0.12), fasting glucose (WMD 0.11; 95% CI -0.08 to -0.29), blood pressure, lipids and the proportion achieving HbA1c <7% by study end (OR 0.98; 95% CI 0.85 to 1.13) was observed.Non-randomised studies identified consisted of four prospective and one retrospective cohort study. Three of these five studies were of moderate/high quality, and results though less precise suggested similar real-world comparative glycaemic and weight effectiveness for both treatments. Data from two cohort studies suggested that treatment change (HR 0.65; 95% CI 0.57 to 0.73) and insulin initiation (HR 0.76; 95% CI 0.65 to 0.90) were less likely among those prescribed sitagliptin; however, inadequate reporting of HbA1c at time of treatment change made interpreting results challenging. CONCLUSION: Sitagliptin users experienced modest weight loss compared to gain with sulfonylureas; however, this difference was around 2 kg, which may not be of major clinical significance for most individuals. Similar change was observed across most other effectiveness outcomes reported. Further studies are needed to address longer-term effectiveness outcomes for sitagliptin compared to sulfonylureas as add-on to metformin. PROSPERO REGISTRATION NUMBER: CRD42016033983.

An algorithm for identification and classification of individuals with type 1 and type 2 diabetes mellitus in a large primary care database.

BACKGROUND: Research into diabetes mellitus (DM) often requires a reproducible method for identifying and distinguishing individuals with type 1 DM (T1DM) and type 2 DM (T2DM). OBJECTIVES: To develop a method to identify individuals with T1DM and T2DM using UK primary care electronic health records. METHODS: Using data from The Health Improvement Network primary care database, we developed a two-step algorithm. The first algorithm step identified individuals with potential T1DM or T2DM based on diagnostic records, treatment, and clinical test results. We excluded individuals with records for rarer DM subtypes only. For individuals to be considered diabetic, they needed to have at least two records indicative of DM; one of which was required to be a diagnostic record. We then classified individuals with T1DM and T2DM using the second algorithm step. A combination of diagnostic codes, medication prescribed, age at diagnosis, and whether the case was incident or prevalent were used in this process. We internally validated this classification algorithm through comparison against an independent clinical examination of The Health Improvement Network electronic health records for a random sample of 500 DM individuals. RESULTS: Out of 9,161,866 individuals aged 0-99 years from 2000 to 2014, we classified 37,693 individuals with T1DM and 418,433 with T2DM, while 1,792 individuals remained unclassified. A small proportion were classified with some uncertainty (1,155 [3.1%] of all individuals with T1DM and 6,139 [1.5%] with T2DM) due to unclear health records. During validation, manual assignment of DM type based on clinical assessment of the entire electronic record and algorithmic assignment led to equivalent classification in all instances. CONCLUSION: The majority of individuals with T1DM and T2DM can be readily identified from UK primary care electronic health records. Our approach can be adapted for use in other health care settings.

Trends in incidence, prevalence and prescribing in type 2 diabetes mellitus between 2000 and 2013 in primary care: a retrospective cohort study.

OBJECTIVE: To investigate trends in incident and prevalent diagnoses of type 2 diabetes mellitus (T2DM) and its pharmacological treatment between 2000 and 2013. DESIGN: Analysis of longitudinal electronic health records in The Health Improvement Network (THIN) primary care database. SETTING: UK primary care. PARTICIPANTS: In total, we examined 8,838,031 individuals aged 0-99 years. OUTCOME MEASURES: The incidence and prevalence of T2DM between 2000 and 2013, and the effect of age, sex and social deprivation on these measures were examined. Changes in prescribing patterns of antidiabetic therapy between 2000 and 2013 were also investigated. RESULTS: Overall, 406,344 individuals had a diagnosis of T2DM, of which 203,639 were newly diagnosed between 2000 and 2013. The incidence of T2DM rose from 3.69 per 1000 person-years at risk (PYAR) (95% CI 3.58 to 3.81) in 2000 to 3.99 per 1000 PYAR (95% CI 3.90 to 4.08) in 2013 among men; and from 3.06 per 1000 PYAR (95% CI 2.95 to 3.17) to 3.73 per 1000 PYAR (95% CI 3.65 to 3.82) among women. Prevalence of T2DM more than doubled from 2.39% (95% CI 2.37 to 2.41) in 2000 to 5.32% (95% CI 5.30 to 5.34) in 2013. Being male, older, and from a more socially deprived area was strongly associated with having T2DM, (p<0.001). Prescribing changes over time reflected emerging clinical guidance and novel treatments. In 2013, metformin prescribing peaked at 83.6% (95% CI 83.4% to 83.8%), while sulfonylureas prescribing reached a low of 41.4% (95% CI 41.1% to 41.7%). Both remained, however, the most commonly used pharmacological treatments as first-line agents and add-on therapy. Thiazolidinediones and incretin based therapies (gliptins and GLP-1 analogues) were also prescribed as alternate add-on therapy options, however were rarely used for first-line treatment in T2DM. CONCLUSIONS: Prevalent cases of T2DM more than doubled between 2000 and 2013, while the number of incident cases increased more steadily. Changes in prescribing patterns observed may reflect the impact of national policies and prescribing guidelines on UK primary care.

Efficacy and Harms of Direct Oral Anticoagulants in the Elderly for Stroke Prevention in Atrial Fibrillation and Secondary Prevention of Venous Thromboembolism: Systematic Review and Meta-Analysis.

BACKGROUND: Evidence regarding the use of direct oral anticoagulants (DOACs) in the elderly, particularly bleeding risks, is unclear despite the presence of greater comorbidities, polypharmacy, and altered pharmacokinetics in this age group. METHODS AND RESULTS: We performed a systematic review and meta-analysis of randomized trials of DOACs (dabigatran, apixaban, rivaroxaban, and edoxaban) for efficacy and bleeding outcomes in comparison with vitamin K antagonists (VKA) in elderly participants (aged ≥75 years) treated for acute venous thromboembolism or stroke prevention in atrial fibrillation. Nineteen studies were eligible for inclusion, but only 11 reported data specifically for elderly participants. The efficacy in managing thrombotic risks for each DOAC was similar or superior to VKA in elderly patients. A nonsignificantly higher risk of major bleeding than with VKA was observed with dabigatran 150 mg (odds ratio, 1.18; 95% confidence interval, 0.97-1.44) but not with the 110-mg dose. Significantly higher gastrointestinal bleeding risks with dabigatran 150 mg (1.78, 1.35-2.35) and dabigatran 110 mg (1.40, 1.04-1.90) and lower intracranial bleeding risks than VKA for dabigatran 150 mg (0.43, 0.26-0.72) and dabigatran 110 mg (0.36, 0.22-0.61) were also observed. A significantly lower major bleeding risk in comparison with VKA was observed for apixaban (0.63, 0.51-0.77), edoxaban 60 mg (0.81, 0.67-0.98), and 30 mg (0.46, 0.38-0.57), whereas rivaroxaban showed similar risks. CONCLUSIONS: DOACs demonstrated at least equal efficacy to VKA in managing thrombotic risks in the elderly, but bleeding patterns were distinct. In particular, dabigatran was associated with a higher risk of gastrointestinal bleeding than VKA. Insufficient published data for apixaban, edoxaban, and rivaroxaban indicate that further work is needed to clarify the bleeding risks of these DOACs in the elderly. SYSTEMATIC REVIEW REGISTRATION: http://www.crd.york.ac.uk/PROSPERO. Unique identifier: PROSPERO CRD42014007171/.