Atrial fibrillation (AF) causes a third of all strokes, but often goes undetected before stroke. Identification of unknown AF in the community and subsequent anti-thrombotic treatment could reduce stroke burden. We investigated community screening for unknown AF using an iPhone electrocardiogram (iECG) in pharmacies, and determined the cost-effectiveness of this strategy.Pharmacists performedpulse palpation and iECG recordings, with cardiologist iECG over-reading. General practitioner review/12-lead ECG was facilitated for suspected new AF. An automated AF algorithm was retrospectively applied to collected iECGs. Cost-effectiveness analysis incorporated costs of iECG screening, and treatment/outcome data from a United Kingdom cohort of 5,555 patients with incidentally detected asymptomatic AF. A total of 1,000 pharmacy customers aged ≥65 years (mean 76 ± 7 years; 44% male) were screened. Newly identified AF was found in 1.5% (95% CI, 0.8-2.5%); mean age 79 ± 6 years; all had CHA2DS2-VASc score ≥2. AF prevalence was 6.7% (67/1,000). The automated iECG algorithm showed 98.5% (CI, 92-100%) sensitivity for AF detection and 91.4% (CI, 89-93%) specificity. The incremental cost-effectiveness ratio of extending iECG screening into the community, based on 55% warfarin prescription adherence, would be $AUD5,988 (€3,142; $USD4,066) per Quality Adjusted Life Year gained and $AUD30,481 (€15,993; $USD20,695) for preventing one stroke. Sensitivity analysis indicated cost-effectiveness improved with increased treatment adherence.Screening with iECG in pharmacies with an automated algorithm is both feasible and cost-effective. The high and largely preventable stroke/thromboembolism risk of those with newly identified AF highlights the likely benefits of community AF screening. Guideline recommendation of community iECG AF screening should be considered.

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.

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Chronic thromboembolic pulmonary hypertension (CTEPH) is a complication of unresolved organised pulmonary emboli/thrombi obstructing the major pulmonary arteries. The aim of this study was to estimate the incidence and risk factors of CTEPH in a cohort with first venous thromboembolism (VTE). This was a population-based cohort study of patients with first VTE and no active cancer in England between 2001 and 2012. CTEPH was assessed using a rigorous case-ascertainment algorithm. Risk factors for CTEPH were studied using a nested case-control approach by matching CTEPH cases to VTE patients without CTEPH. Adjusted odds ratios (OR) of comorbidities were estimated from conditional logistic regression. During 81,413 person-years of follow-up among 23,329 patients with first VTE (mean follow-up 3.5 years; maximum 11.0 years) 283 patients were diagnosed with CTEPH (incidence rate 3.5 per 1000 person-years); cumulative incidence was 1.3% and 3.3% at 2 and 10 years after pulmonary embolism, and 0.3% and 1.3% following deep vein thrombosis (DVT), respectively. Risk factors for CTEPH included age over 70, OR 2.04 (95% CI 1.23 to 3.38), female gender, 1.44 (1.06 to 1.94), pulmonary embolism at first VTE, 3.11 (2.23 to 4.35), subsequent pulmonary embolism and DVT, 3.17 (2.02 to 4.96) and 2.46 (1.34 to 4.51) respectively, chronic obstructive pulmonary disease 3.17 (2.13 to 4.73), heart failure 2.52 (1.76 to 3.63) and atrial fibrillation, 2.42 (1.71 to 3.42). CTEPH develops most commonly after pulmonary embolism and less frequently after DVT. Awareness of risk factors may increase referrals to specialised centres for confirmation of CTEPH and initiation of specific treatment.

Introduction Atrial fibrillation (AF) is associated with dementia. Anticoagulation may modify this relationship, but it is unclear if this is due to stroke reduction alone. Methods Age- and sex-matched individuals from the U.K. Clinical Practice Research Datalink (2008–2016) with and without an incident diagnosis of AF were followed for a new dementia diagnosis. We estimated adjusted hazard ratios (aHRs) for incident dementia diagnosis in the AF cohort, overall and stratified by anticoagulation status, using the matched non-AF cohorts as reference. We performed a sensitivity analysis excluding individuals with stroke/transient ischaemic attack (TIA) before the observation period. Results Over 193,082 person-years (mean follow-up 25.7 ± 0.1 months), 347/15,276 AF (2.3%) and 1,085/76,096 non-AF (1.4%) were newly diagnosed with dementia (aHR, 1.31, 95% confidence interval, 1.15–1.49). The AF group had more co-morbidity and higher rates of dementia, both with and without anticoagulation, than non-AF. When those with history of stroke/ TIA before the observation period were excluded and those with incident stroke/TIA during the observation period were censored, AF individuals not on anticoagulation had significantly higher rates of dementia compared with non-AF, aHR 1.30 (1.06–1.58). Conclusion Our findings support the hypothesis that AF is a distinct risk factor for dementia, independent of stroke/TIA and other vascular risk factors. In those without stroke/TIA, risk of dementia is increased only in those who are not on anticoagulation, suggesting anticoagulation is protective presumably through reduction of sub-clinical embolic events. Further prospective research is needed to better ascertain the role of anticoagulation amongst targeted therapeutic strategies to reduce cognitive decline in AF.

Objective:To investigate the incidence of tinnitus that burdens the health service in England.Design:This was an observational study of 4.7 million residents of England under 85 years of age who were at risk for developing clinically significant tinnitus (sigT). SigT was defined by a discharge from hospital with a primary diagnosis of tinnitus, or a primary care recording of tinnitus with subsequent related medical follow-up within 28 days. The database used was the Clinical Practice Research Datalink and individual records were linked to additional data from the Hospital Episode Statistics. The observational period was from January 1, 2002 to December 31, 2011. Age-, gender-, and calendar year-specific incidence rates for and cumulative incidences of sigT were estimated and a projection of new cases of sigT between 2012 and 2021 was performed.Results:There were 14,303 incident cases of sigT identified among 26.5 million person-years of observation. The incidence rate was 5.4 new cases of sigT per 10,000 person-years (95% confidence interval: 5.3 to 5.5). The incidence rate did not depend on gender but increased with age, peaking at 11.4 per 10,000 in the age group 60 to 69 years. The annual incidence rate of sigT increased from 4.5 per 10,000 person-years in 2002 to 6.6 per 10,000 person-years in 2011. The 10-year cumulative incidence of sigT was 58.4 cases (95% confidence interval: 57.4 to 59.4) per 10,000 residents. Nearly 324,000 new cases of sigT are expected to occur in England between 2012 and 2021.Conclusions:Tinnitus presents a burden to the health care system that has been rising in recent years. Population-based studies provide crucial underpinning evidence; highlighting the need for further research to address issues around effective diagnosis and clinical management of this heterogeneous condition.

ObjectivesThe purpose of this study was to estimate the annual incidence of Lyme disease (LD) in the UK.DesignThis was a retrospective descriptive cohort study.SettingStudy data were extracted from the Clinical Practice Research Datalink (CPRD), a primary care database covering about 8% of the population in the UK in 658 primary care practices.ParticipantsCohort of 8.4 million individuals registered with general practitioners with 52.4 million person-years of observation between 1 January 2001 and 31 December 2012.Primary and secondary outcome measuresLD was identified from recorded medical codes, notes indicating LD, laboratory tests and use of specific antibiotics. Annual incidence rates and the estimated total number of LD cases were calculated separately for each UK region.ResultsThe number of cases of LD increased rapidly over the years 2001 to 2012, leading to an estimated incidence rate of 12.1 (95% CI 11.1 to 13.2) per 100 000 individuals per year and a UK total of 7738 LD cases in 2012. LD was detected in every UK region with highest incidence rates and largest number of cases in Scotland followed by South West and South England. If the number of cases has continued to rise since the end of the study period, then the number in the UK in 2019 could be over 8000.ConclusionsThe incidence of LD is about threefold higher than previously estimated, and people are at risk throughout the UK. These results should lead to increased awareness of the need for preventive measures.Trial registration numberThis study was approved by the Independent Scientific Advisory Committee for CPRD research (Protocol number 13_210R).

Background: It is uncertain whether stroke risk of asymptomatic ambulatory atrial fibrillation (AA-AF) incidentally-detected in primary care is comparable with other clinical AF presentations in primary care or hospital. Methods: The stoke risk of 22,035 patients with incident non-valvular AF from the UK primary care Clinical Practice Research Datalink with linkage to hospitalization and mortality data, was compared to 23,605 controls without AF (age and sex-matched 5:1 to 5,409 AA-AF patients). Incident AF included 5,913 with symptomatic ambulatory AF (SA-AF); 4,989 with Primary and 5,724 with non-Primary Hospital AF discharge diagnosis (PH-AF and Non-PH-AF); and 5,409 with AA-AF. Ischemic stroke adjusted subhazard ratios (aSHR) within 3 years of AA-AF were compared with SA-AF, PH-AF, Non-PH-AF and controls, accounting for mortality as competing risk and adjusted for ischemic stroke risk factors. Results: There were 1026 ischemic strokes in 49,544 person-years in patients with incident AF (crude incidence rate 2.1 ischemic strokes/100 person-years). Ischemic stroke aSHR over 3 years showed no differences between AA-AF, and SA-AF, PH-AF and nonPH-AF groups (aSHR 0.87-1.01 vs AA-AF). All AF groups showed a significantly higher aSHR compared to controls. (subhazard rate ratio 0.40 [0.34 - 0.47]. Conclusion: Ischemic stroke risk in patients with AA-AF incidentally-detected in primary care is far from benign, and not less than incident AF presenting clinically in general practice or hospital. This provides justification for identification of previously undetected AF, e.g. by opportunistic screening, and subsequent stroke prevention with thromboprophylaxis, to reduce the approximately 10% of ischemic strokes related to unrecognized AF.