[Role of red blood cell (RBC) transfusions in patients with prolonged mechanical ventilation during weaning process]. / Einfluss von Erythrozytenkonzentrat-Transfusionen auf den Weaning-Prozess bei prolongiert beatmeten Patienten.

AIM: Patients undergoing long-term ventilation often show anemia. The aim of the study was to investigate the duration and success of weaning from mechanical ventilation in patients with RBC transfusion. METHODS: A retrospective analysis of patient data from a weaning unit was performed. Transfused and non-transfused patients were matched using a propensity score. Of the 249 patients in the database, 31 transfused and the same number of non-transfused cases with similar disease severity as measured by the Simplified Acute Physiology Score (SAPS) could be analyzed. Additional sensitivity analyses were performed. RESULTS: In the group of transfused patients, the difference in weaning duration was longer than in non-transfused patients (1.35 days and 3.26 days, respectively). Weaning success also varied. The risk of weaning failure was twice as high in the group of transfused patients. The groups also differed in terms of mortality, 25.8% of the transfused patients died, while in the non-transfused patients the mortality rate was 6.5%. The risk of death was increased in patients who received RBC transfusion. The differences were not statistically significant. CONCLUSION: A high proportion of patients with prolonged mechanical ventilation have anemia. RBC transfusion does not improve their prognosis. The need for transfusion is associated with higher mortality and longer duration of weaning in this population. The indication for RBC transfusion should therefore be restrictive.

The budget impact of implementing atrial fibrillation-screening in European countries.

A budget impact analysis estimates the short-term difference between the cost of the current treatment strategy and a new treatment strategy, in this case to implement population screening for atrial fibrillation (AF). The aim of this study is to estimate the financial impact of implementing population-based AF-screening of 75-year-olds compared with the current setting of no screening from a healthcare payer perspective in eight European countries. The net budget impact of AF-screening was estimated in country-specific settings for Denmark, Germany, Ireland, Italy, Netherlands, Serbia, Spain, and Sweden. Country-specific parameters were used to allow for variations in healthcare systems and to reflect the healthcare sector in the country of interest. Similar results can be seen in all countries AF-screening incurs savings of stroke-related costs since AF treatment reduces the number of strokes. However, the increased number of detected AF and higher drug acquisition will increase the drug costs as well as the costs of physician- and control visits. The net budget impact per invited varied from €10 in Ireland to €122 in the Netherlands. The results showed the increased costs of implementing AF-screening were mainly driven by increased drug costs and screening costs. In conclusion, across Europe, though the initial cost of screening and more frequent use of oral anti-coagulants will increase the healthcare payers' costs, introducing population screening for AF will result in savings of stroke-related costs.

Comparison of Clinical Outcomes in Patients with Active Cancer Receiving Rivaroxaban or Low-Molecular-Weight Heparin: The OSCAR-UK Study.

BACKGROUND: In most patients with cancer-associated venous thromboembolism (CT), essentially those not at high risk of bleeding, guidelines recommend treatment with direct oral anticoagulants as an alternative to low-molecular-weight heparins (LMWHs). Population-based studies comparing these therapies are scarce. OBJECTIVES: To compare the risk of venous thromboembolism (VTE) recurrences, significant bleeding, and all-cause mortality in patients with CT receiving rivaroxaban or LMWHs. PATIENTS/METHODS: Using UK Clinical Practice Research Datalink data from 2013 to 2020, we generated a cohort of patients with first CT treated initially with either rivaroxaban or LMWH. Patients were observed 12 months for VTE recurrences, significant bleeds (major bleeds or clinically relevant nonmajor bleeding requiring hospitalization), and all-cause mortality. Overlap weighted sub-distribution hazard ratios (SHRs) compared rivaroxaban with LMWH in an intention-to-treat analysis. RESULTS: The cohort consisted of 2,259 patients with first CT, 314 receiving rivaroxaban, and 1,945 LMWH, mean age 72.4 and 66.9 years, respectively. In the 12-month observational period, 184 person-years following rivaroxaban and 1,057 following LMWH, 10 and 66 incident recurrent VTE events, 20 and 102 significant bleeds, and 10 and 133 deaths were observed in rivaroxaban and LMWH users, respectively. The weighted SHR at 12 months for VTE recurrences in rivaroxaban compared with LMWH were 0.80 (0.37-1.73); for significant bleeds 1.01 (0.57-1.81); and for all-cause mortality 0.49 (0.23-1.06). CONCLUSION: Patients with CT, not at high risk of bleeding, treated with either rivaroxaban or LMWH have comparable effectiveness and safety outcomes. This supports the recommendation that rivaroxaban is a reasonable alternative to LMWH for the treatment of CT.

A Novel Risk Prediction Score for Clinically Significant Bleeding in Patients Anticoagulated for Venous Thromboembolism with Active Cancer.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: This risk score may identify patients at risk of significant bleeding, while also helping to determine treatment duration.

Optimal length and temporal resolution of dynamic contrast-enhanced MR imaging for the differentiation between prostate cancer and normal peripheral zone tissue.

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.

Atrial Fibrillation Detected by Single Time-Point Handheld Electrocardiogram Screening and the Risk of Ischemic Stroke.

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.

Risk of Ischemic Stroke in Asymptomatic Atrial Fibrillation Incidentally Detected in Primary Care Compared with Other Clinical Presentations.

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.

Refined atrial fibrillation screening and cost-effectiveness in the German population.

OBJECTIVE: Little is known on optimal screening population for detecting new atrial fibrillation (AF) in the community. We describe characteristics and estimate cost-effectiveness for a single timepoint electrocardiographic screening. METHODS: We performed a 12-lead ECG in the German population-based Gutenberg Health Study between 2007 and 2012 (n=15 010), mean age 55±11 years, 51% men and collected more than 120 clinical and biomarker variables, including N-terminal pro B-type natriuretic peptide (Nt-proBNP), risk factors, disease symptoms and echocardiographic variables. RESULTS: Of 15 010 individuals, 466 (3.1%) had AF. New AF was found in 32 individuals, 0.2% of the total sample, 0.5% of individuals aged 65-74 years and predominantly men (86%). The classical risk factor burden was high in individuals with new AF. The median estimated stroke risk was 2.2%/year, while risk of developing heart failure was 21% over 10 years. In the 65-74 year age group, the cost per quality-adjusted life-year gained resulting from a single timepoint screening was €30 361. In simulations, the costs were highly sensitive to AF detection rates, proportion of treatment and type of oral anticoagulant. Prescreening by Nt-proBNP measurements was not cost-effective in the current setting. CONCLUSIONS: In our middle-aged population cohort, we identified 0.2% new AF by single timepoint screening. There was a significant estimated risk of stroke and heart failure in these individuals. Cost-effectiveness for screening may be reached in individuals aged 65 years and older. The simple age cut-off is not improved by using Nt-proBNP as a biomarker to guide a screening programme.

Intravenous immunoglobulin and the current risk of moderate and severe anaphylactic events, a cohort study.

This large cohort study from the US Premier Healthcare Database evaluated the risk and predictors of anaphylaxis in association with intravenous immunoglobulin (IvIg) therapy in the inpatient and outpatient setting. Data were collected retrospectively (January 2009-December 2018) from 24 919 patients administered IgPro10 IvIg, median age 54 years. Immunoglobulins of interest were IgPro10 and other IvIg given before or after IgPro10. Moderate and severe anaphylaxis was identified from same-day parenteral epinephrine and IvIg use and reviews of patient record summaries. Predictors for first anaphylactic reactions associated with IvIg administration were derived from adjusted incidence rate ratios (IRR) using Poisson regression. Moderate anaphylaxis in IvIg use was rare and severe anaphylaxis very rare based on a total of 124 moderate and four non-fatal severe first anaphylactic events, incidence rate of 7.11 and 0.23/10 000 IvIg administrations, respectively. Age under 18 years was an independent predictor of moderate or severe anaphylactic events [adjusted incidence rate ratio = 2.94, 0.95 confidence interval  = 1.91-4.52] compared with those aged 18 years and older. First IvIg administration was a strong predictor of anaphylaxis. The IRR in those with a subsequent IvIg administration in the preceding 42 days decreased to 0.27 (0.17-0.42) and in those effectively IvIg-naive (no IvIg for > 42 days) to 0.76 (0.44-1.32) compared with first IvIg use. The key conclusions from this study are that the risk of anaphylaxis has progressively reduced over the last decade, from 14.87 of 10 000 in 2009-10 to 4.39 of 10 000 IvIg administrations in 2017-18 and is rare overall, and that the risk of anaphylaxis is increased in those aged under 18 years.

Anti-A/B isoagglutinin reduction in an intravenous immunoglobulin product and risk of hemolytic anemia: a hospital-based cohort study.

BACKGROUND: Intravenous immunoglobulins (IVIG) are derived from large human plasma pools. IVIG-associated hemolytic anemia (HA) is a known class effect, likely attributed to dose-dependent passive transfer of anti-A/B isoagglutinins. Two isoagglutinin reduction steps were implemented in the manufacturing process of Privigen (human 10% liquid IVIG): exclusion of high-anti-A-titer donors in 2013, replaced by specific immunoaffinity chromatography in 2015. We aim to estimate the clinical effectiveness of both measures. STUDY DESIGN AND METHODS: Using the US hospital-based Premier Healthcare Database, three Privigen cohorts were generated based on calendar periods indicative of manufacturing changes: Period 1 (baseline) January 2008 to December 2012, Period 2 (high-anti-A-titer donor exclusion) October 2013 to December 2015, and Period 3 (immunoaffinity chromatography) October 2016 to April 2019. HA within a 10-day at-risk period after Privigen administrations was identified from review of patient record summaries. Incidence rate ratios (IRRs) were estimated from Poisson regression (Period 1 reference) adjusting for hospital setting, sex, age, Privigen indication, dose, and first use. RESULTS: Crude incidence rates of HA were 1.49 per 10,000 person-days in Period 1 (38 HA, 9439 patients), 1.01 in Period 2 (20 HA, 7710 patients), and 0.14 in Period 3 (3 HA, 7759 patients). Adjusted IRR for HA in Period 2 was 0.71 (95% confidence interval [CI], 0.41-1.23), and in Period 3 was 0.10 (0.03-0.33) compared with Period 1. The IRR for HA in Period 3 compared with Period 2 was 0.14 (95% CI, 0.04-0.47). CONCLUSION: Implementation of immunoaffinity chromatography in Privigen manufacturing resulted in a significant 90% reduction of HA risk. HA has become a rare event in association with Privigen use.

Variation in the Association between Antineoplastic Therapies and Venous Thromboembolism in Patients with Active Cancer.

BACKGROUND: Venous thromboembolism (VTE) is a major cause of death in cancer patients. Although patients with cancer have numerous risk factors for VTE, the relative contribution of cancer treatments is unclear. OBJECTIVE: The objective of this study is to evaluate the association between cancer therapies and the risk of VTE. METHODS: From UK Clinical Practice Research Datalink, data on patients with first cancer diagnosis between 2008 and 2016 were extracted along with information on hospitalization, treatments, and cause of death. Primary outcome was active cancer-associated VTE. To establish the independent effects of risk factors, adjusted subhazard ratios (adj-SHR) were calculated using Fine and Gray regression analysis accounting for death as competing risk. RESULTS: Among 67,801 patients with a first cancer diagnosis, active cancer-associated VTE occurred in 1,473 (2.2%). During a median observation time of 1.2 years, chemotherapy, surgery, hormonal therapy, radiation therapy, and immunotherapy were given to 71.1, 37.2, 17.2, 17.5, and 1.4% of patients with VTE, respectively. The active cancers associated with the highest risk of VTE-as assessed by incidence rates-included pancreatic cancer, brain cancer, and metastatic cancer. Chemotherapy was associated with an increased risk of VTE (adj-SHR: 3.17, 95% confidence interval [CI]: 2.76-3.65) while immunotherapy with a not significant reduced risk (adj-SHR: 0.67, 95% CI: 0.30-1.52). There was no association between VTE and radiation therapy (adj-SHR: 0.91, 95% CI: 0.65-1.27) and hormonal therapies. CONCLUSION: VTE risk varies with cancer type. Chemotherapy was associated with an increased VTE risk, whereas with radiation and immunotherapy therapy, an association was not confirmed.

Ischemic Stroke and Transient Ischemic Attack Risk Following Vitamin K Antagonist Cessation in Newly Diagnosed Atrial Fibrillation: A Cohort Study.

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 CHA2DS2-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.

Prediction of significant bleeding during vitamin K antagonist treatment for venous thromboembolism in outpatients.

Bleeding is the most concerning complication associated with anticoagulant therapy but poorly characterized and important for risk/benefit assessment. We developed a risk stratification score to predict vitamin K antagonist (VKA)-associated bleeding in venous thromboembolism (VTE) using the UK Clinical Practice Research Datalink. Significant bleeding events in outpatients consisted of major bleeding and clinically relevant non-major bleeding requiring hospitalisation (CRNMB-H) within 90 days of VKA initiation. A scoring scheme for predicting bleeding was developed from subhazard ratios, validated using cross-validation and expressed by the C-statistic. The study cohort consisted of 10,010 patients with first VTE receiving initial VKA treatment, mean age 62·2 years. Between 2008 and 2016, 167 significant bleeding events were recorded (1·7%), i.e. incidence rate was 7·4/100 person-years. Independent predictors for community-acquired significant bleeding included active cancer, trauma/surgical procedure, male gender, dementia, liver disease, anaemia, history of bleeding, cerebrovascular, renal and chronic pulmonary disease, VTE presenting as pulmonary embolism and age over 75. The overall C-statistic was 0·68 (95% CI, 0·60-0·76), 0·75 (0·60-0·88) for major bleeding and 0·65 (0·55-0·75) for CRNMB-H, and higher than in other risk schemes applied to our study population. The developed risk score may identify patients having a significant bleeding risk, in particular major bleeding events, in outpatients.

Incidence of Lyme disease in the UK: a population-based cohort study.

OBJECTIVES: The purpose of this study was to estimate the annual incidence of Lyme disease (LD) in the UK. DESIGN: This was a retrospective descriptive cohort study. SETTING: Study 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. PARTICIPANTS: Cohort 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 MEASURES: LD 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. RESULTS: The 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 NUMBER: This study was approved by the Independent Scientific Advisory Committee for CPRD research (Protocol number 13_210R).

Incident Atrial Fibrillation, Dementia and the Role of Anticoagulation: A Population-Based Cohort Study.

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.

Therapy persistence in newly diagnosed non-valvular atrial fibrillation treated with warfarin or NOAC. A cohort study.

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.

Increasing incidence of non-valvular atrial fibrillation in the UK from 2001 to 2013.

OBJECTIVE: To determine whether the incidence of atrial fibrillation (AF) is static or rising in the UK. DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.

Incidence rates of clinically significant tinnitus: 10-year trend from a cohort study in England.

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.

Feasibility and cost-effectiveness of stroke prevention through community screening for atrial fibrillation using iPhone ECG in pharmacies. The SEARCH-AF study.

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.