Background In nonvalvular atrial fibrillation (AF), oral anticoagulants prevent ischemic strokes and transient ischemic attacks (TIAs), but nonpersistence with vitamin K antagonist (VKA) oral ...anticoagulant therapy (20-50% at 1 year) is problematic. The precise risk of stroke/TIA after VKA cessation and its time course during extended follow-up is unknown. Methods and Results The study cohort of incident AF in patients receiving initial VKA between 2001 and 2013 was identified from the UK Clinical Practice Research Datalink (linked hospitalizations and causes of death). Using a nested case-control analysis, patients with incident stroke/TIA were matched to patients without stroke/TIA (controls). Relative risk with time since VKA cessation compared with current VKA use was approximated from conditional logistic regression. We studied 16 696 patients with incident AF and initial VKA treatment. There were 489 stroke/TIA cases matched to 2137 controls (mean CHA
DS
-VASc score 4.3). Compared with current VKA use, the excess incidence rate of stroke/TIA following VKA cessation in the first year after AF diagnosis was 2.29 (95% CI, 0.98-3.90) per 100 person-years of VKA cessation or 1 additional stroke/TIA per 43 patients per year discontinuing VKA, compared with 1.43 (95% CI, 0.97-1.88) per 100 person-years corresponding to 1 additional stroke/TIA per 70 patients per year, when VKA was discontinued more than 1 year after AF diagnosis. Conclusions VKA cessation is associated with a continuous excess thromboembolic stroke/TIA risk. Increasing oral anticoagulant persistence, especially in the year after AF diagnosis, should be a therapeutic target to reduce stroke/TIA in AF.
To determine whether the incidence of atrial fibrillation (AF) is static or rising in the UK.
Among the cohort of all individuals aged ≥45 years in the UK Clinical Practice Research Datalink (CPRD) ...(linked to hospital discharges) we identified incident non-valvular AF cases between 2001 and 2013. Overall and annual AF incidence rates were calculated and standardised to the UK population.
The cohort of 2.23 million individuals included 91,707 patients with incident AF. The overall standardised AF incidence rate was 6.7 (95% CI 6.7 to 6.8) per 1000 person-years, increasing exponentially with age and higher in men of all ages. There was a small increase in the standardised incidence of AF in the last decade from 5.9 (5.8 to 6.1)/1000 person-years in 2001 to 6.9 (6.8 to 7.1)/1000 person-years in 2013, mostly attributable to subjects aged >80 years with a non-primary hospital discharge diagnosis of AF. Standardised incidence rates of AF among white patients was 8.1 (8.1 to 8.2)/1000 person-years, compared with 5.4 (4.6 to 6.3) for Asians and 4.6 (4.0 to 5.3) for black patients. AF diagnosis was first made in general practice in 39% of incident AF.
The incidence of AF in the UK has increased gradually in the last decade, with more than 200 000 first-ever non-valvular AF cases expected in 2015. This increase is only partly due to population ageing, though the principal increase has been in the elderly hospitalised for a reason other than AF.
The value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in the detection of prostate cancer is controversial. There are currently insufficient peer reviewed published data or ...expert consensus to support routine adoption of DCE-MRI for clinical use. Thus, the objective of this study was to explore the optimal temporal resolution and measurement length for DCE-MRI to differentiate cancerous from normal prostate tissue of the peripheral zone of the prostate by non-parametric MRI analysis and to compare with a quantitative MRI analysis. Predictors of interest were onset time, relative signal intensity (RSI), wash-in slope, peak enhancement, wash-out and wash-out slope determined from non-parametric characterisation of DCE-MRI intensity-time profiles. The discriminatory power was estimated from C-statistics based on cross validation. We analyzed 54 patients with 97 prostate tissue specimens (47 prostate cancer, 50 normal prostate tissue) of the peripheral zone, mean age 63.8 years, mean prostate-specific antigen 18.9 ng/mL and mean of 10.5 days between MRI and total prostatectomy. When comparing prostate cancer tissue with normal prostate tissue, median RSI was 422% vs 330%, and wash-in slope 0.870 vs 0.539. The peak enhancement of 67 vs 42 was higher with prostate cancer tissue, while wash-out (-30% vs -23%) and wash-out slope (-0.037 vs -0.029) were lower, and the onset time (32 seconds) was comparable. The optimal C-statistics was 0.743 for temporal resolution of 8.0 seconds and measurement length of 2.5 minutes compared with 0.656 derived from a quantitative MRI analysis. This study provides evidence that the use of a non-parametric approach instead of a more established parametric approach resulted in greater precision to differentiate cancerous from normal prostate tissue of the peripheral zone of the prostate.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
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 nonvalvular AF from the United Kingdom primary care Clinical Practice Research Datalink with linkage to hospitalization and mortality data was compared with 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 nonprimary hospital AF discharge diagnosis (PH-AF and non-PH-AF); and 5,409 with AA-AF. Ischemic stroke adjusted subhazard ratios (aSHRs) within 3 years of AA-AF were compared with SA-AF, PH-AF, non-PH-AF, and no AF, accounting for mortality as competing risk and adjusted for ischemic stroke risk factors.
Results
There were 1,026 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 non-PH-AF groups (aSHR: 0.87–1.01 vs. AA-AF). All AF groups showed a significantly higher aSHR compared with no AF.
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.
Efforts 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.
Abstract
Objective
We evaluated stroke risk in patients with single time-point screen-detected atrial fibrillation (AF) and the effect of oral anticoagulants (OACs).
Methods
Consecutive patients ...aged ≥65 years attending medical outpatient clinics were prospectively enrolled for AF screening using handheld single-lead electrocardiogram (ECG; AliveCor) from December 2014 to December 2017 (NCT02409654). Repeated screening was performed in patients with >1 visit during this period. Three cohorts were formed: screen-detected AF, clinically diagnosed AF, and no AF. Ischemic stroke risk was estimated using adjusted subdistribution hazard ratios (aSHRs) from multivariate regression and no AF as reference, and stratified according to OAC use.
Results
Of 11,972 subjects enrolled, 2,238 (18.7%) had clinically diagnosed AF at study enrollment. The yield of screen-detected AF on initial screening was 2.3% (
n
= 223/9,734). AF was clinically diagnosed during follow-up in 2.3% (
n
= 216/9,440) and during subsequent screening in 71 initially screen-negative patients. Compared with no AF, patients with screen-detected AF without OAC treatment had the highest stroke risk (aSHR: 2.63; 95% confidence interval: 1.46–4.72), while aSHR for clinically diagnosed AF without OAC use was 2.01 (1.54–2.62). Among screen-detected AF, the risk of stroke was significantly less with OAC (no strokes in 196 person-years) compared with those not given OAC (12 strokes in 429 person-years),
p
= 0.01.
Conclusion
The prognosis of single time-point ECG screen-detected AF is not benign. The risk of stroke is high enough to warrant OAC use, and reduced by OAC.
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. Conclusions The 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).
Summary
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 performed pulse 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 CHA
2
DS
2
-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.
Previous Presentation: This study was presented in part as an oral presentation at the Cardiac Society of Australia and New Zealand Conference; 9 August 2013; Sydney, Australia, abstract published in Heart Lung Circulation 2013;22:S223.
Trial registration: Australian New Zealand clinical trials registry: ACTRN12612000406808.
Cancer-associated venous thromboembolism (Ca-VTE) treatment with anticoagulation is associated with bleeding complications and there are limited data on risk factors. Current models do not provide ...accurate bleeding risk prediction.
UK Clinical Practice Research Datalink data (2008-2020) were used to generate a cohort of patients with anticoagulant initiation for first Ca-VTE. Patients were observed up to 180 days for significant bleeding including major bleeding and clinically relevant nonmajor bleeding requiring hospitalization (CRNMB-H). A scoring scheme was developed from sub-distribution hazard ratios, and its discrimination (expressed by the C-statistic) estimated from cross-validation.
A total of 15,749 patients with Ca-VTE and anticoagulant treatment were included. In total, 537 significant bleeding events, 161 major bleeds, and 376 CRNMB-H were identified after adjudicated review in 4,914 person-years of observation. Incidence rates of 3.3 and 7.7 per 100 person-years were noted for major bleeding and CRNMB-H. Independent predictors of significant bleeding included cancer of the bladder, central nervous system, cervix, kidney, melanoma, prostate and upper gastrointestinal tract, metastases, minor surgery, minor trauma, and history of major bleeding or CRNMB (before or after the Ca-VTE diagnosis). Patients recognized as low, medium, and high risk (30.4, 56.8, and 1.7% of the population, respectively) had a 6-month significant bleeding incidence rate of 5.1, 19.0, and 56.5 per 100 person-years, respectively. Overall C-statistic for significant bleeding was 0.70 (95% confidence interval: 0.65-0.75), and 0.76 (0.68-0.84) and 0.67 (0.61-0.73) for major bleeding and for CRNMB-H, respectively.
This risk score may identify patients at risk of significant bleeding, while also helping to determine treatment duration.
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 interval5.3 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 interval57.4 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.
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