Safety of Switching From a Vitamin K Antagonist to a Non-Vitamin K Antagonist Oral Anticoagulant in Frail Older Patients With Atrial Fibrillation: Results of the FRAIL-AF Randomized Controlled Trial.

BACKGROUND: There is ambiguity whether frail patients with atrial fibrillation managed with vitamin K antagonists (VKAs) should be switched to a non-vitamin K oral anticoagulant (NOAC). METHODS: We conducted a pragmatic, multicenter, open-label, randomized controlled superiority trial. Older patients with atrial fibrillation living with frailty (≥75 years of age plus a Groningen Frailty Indicator score ≥3) were randomly assigned to switch from international normalized ratio-guided VKA treatment to an NOAC or to continued VKA treatment. Patients with a glomerular filtration rate <30 mL·min-1·1.73 m-2 or with valvular atrial fibrillation were excluded. Follow-up was 12 months. The cause-specific hazard ratio was calculated for occurrence of the primary outcome that was a major or clinically relevant nonmajor bleeding complication, whichever came first, accounting for death as a competing risk. Analyses followed the intention-to-treat principle. Secondary outcomes included thromboembolic events. RESULTS: Between January 2018 and June 2022, a total of 2621 patients were screened for eligibility and 1330 patients were randomly assigned (mean age 83 years, median Groningen Frailty Indicator score 4). After randomization, 6 patients in the switch-to-NOAC arm and 1 patient in the continue-with-VKA arm were excluded due to the presence of exclusion criteria, leaving 662 patients switched from a VKA to an NOAC and 661 patients continued VKAs in the intention-to-treat population. After 163 primary outcome events (101 in the switch arm, 62 in the continue arm), the trial was stopped for futility according to a prespecified futility analysis. The hazard ratio for our primary outcome was 1.69 (95% CI, 1.23-2.32). The hazard ratio for thromboembolic events was 1.26 (95% CI, 0.60-2.61). CONCLUSIONS: Switching international normalized ratio-guided VKA treatment to an NOAC in frail older patients with atrial fibrillation was associated with more bleeding complications compared with continuing VKA treatment, without an associated reduction in thromboembolic complications. REGISTRATION: URL: https://eudract.ema.europa.eu; Unique identifier: 2017-000393-11. URL: https://eudract.ema.europa.eu; Unique identifier: 6721 (FRAIL-AF study).

Heart failure with preserved ejection fraction: everything the clinician needs to know.

Heart failure with preserved ejection fraction (HFpEF) is increasingly recognised and diagnosed in clinical practice, a trend driven by an ageing population and a rise in contributing comorbidities, such as obesity and diabetes. Representing at least half of all heart failure cases, HFpEF is recognised as a complex clinical syndrome. Its diagnosis and management are challenging due to its diverse pathophysiology, varied epidemiological patterns, and evolving diagnostic and treatment approaches. This Seminar synthesises the latest insights on HFpEF, integrating findings from recent clinical trials, epidemiological research, and the latest guideline recommendations. We delve into the definition, pathogenesis, epidemiology, diagnostic criteria, and management strategies (non-pharmacological and pharmacological) for HFpEF. We highlight ongoing clinical trials and future developments in the field. Specifically, this Seminar offers practical guidance tailored for primary care practitioners, generalists, and cardiologists who do not specialise in heart failure, simplifying the complexities in the diagnosis and management of HFpEF. We provide practical, evidence-based recommendations, emphasising the importance of addressing comorbidities and integrating the latest pharmacological treatments, such as SGLT2 inhibitors.

Long-term cardiovascular health status and physical functioning of nonhospitalized patients with COVID-19 compared with non-COVID-19 controls.

Coronavirus disease 2019 (COVID-19) is reported to have long-term effects on cardiovascular health and physical functioning, even in the nonhospitalized population. The physiological mechanisms underlying these long-term consequences are however less well described. We compared cardiovascular risk factors, arterial stiffness, and physical functioning in nonhospitalized patients with COVID-19, at a median of 6 mo postinfection, versus age- and sex-matched controls. Cardiovascular risk was assessed using blood pressure and biomarker concentrations (amino-terminal pro-B-type-natriuretic-peptide, high-sensitive cardiac troponin I, C-reactive protein), and arterial stiffness was assessed using carotid-femoral pulse wave velocity. Physical functioning was evaluated using accelerometry, handgrip strength, gait speed and questionnaires on fatigue, perceived general health status, and health-related quality of life (hrQoL). We included 101 former patients with COVID-19 (aged 59 [interquartile range, 55-65] yr, 58% male) and 101 controls. At 175 [126-235] days postinfection, 32% of the COVID-19 group reported residual symptoms, notably fatigue, and 7% required post-COVID-19 care. We found no differences in blood pressure, biomarker concentrations, or arterial stiffness between both groups. Former patients with COVID-19 showed a higher handgrip strength (43 [33-52] vs. 38 [30-48] kg, P = 0.004) and less sleeping time (8.8 [7.7-9.4] vs. 9.8 [8.9-10.3] h/day, P < 0.001) and reported fatigue more often than controls. Accelerometry-based habitual physical activity levels, gait speed, perception of general health status, and hrQoL were not different between groups. In conclusion, one in three nonhospitalized patients with COVID-19 reports residual symptoms at a median of 6 mo postinfection, but we were unable to relate these symptoms to increases in cardiovascular risk factors, arterial stiffness, or physical dysfunction.NEW & NOTEWORTHY We examined cardiovascular and physical functioning outcomes in nonhospitalized patients with COVID-19, at a median of 6 mo postinfection. When compared with matched controls, minor differences in physical functioning were found, but objective measures of cardiovascular risk and arterial stiffness did not differ between groups. However, one in three former patients with COVID-19 reported residual symptoms, notably fatigue. Follow-up studies should investigate the origins of residual symptoms and their long-term consequences in former, nonhospitalized patients with COVID-19.

Relative fat mass and prediction of incident atrial fibrillation, heart failure and coronary artery disease in the general population.

BACKGROUND: Relative fat mass (RFM) is an emerging marker of obesity that estimates body fat percentage using a sex-specific formula containing height and waist circumference (WC). We studied the association of RFM with incident atrial fibrillation (AF), heart failure (HF), and coronary artery disease (CAD) and explored RFM cutoffs for cardiovascular disease (CVD) prediction. METHODS: We studied 95,003 participants (age 45 ± 13 years, 59% women) without prevalent AF, HF or CAD from the population-based Lifelines study. Outcomes were ascertained using electrocardiography and self-reported questionnaire data. We used logistic regression to study the association of RFM with individual outcomes and a composite outcome (incident AF, HF, and/or CAD). Multivariable models were adjusted for components of the SCORE risk model (age, sex, systolic blood pressure, cholesterol, and smoking). Optimal cutoffs were determined using the Youden index. RESULTS: During a median follow-up of 3.8 (3.0-4.6) years, 224 (0.2%) participants developed AF, 1003 (1.1%) HF and 657 (0.7%) CAD. After multivariable adjustment, RFM was significantly associated with all outcomes (standardised OR 1.26, 95% CI 1.18-1.34 for the composite outcome). Optimal RFM cutoffs ( ≥26 for men, ≥38 for women) were lower than previously proposed RFM cutoffs ( ≥30 for men, ≥40 for women). In general, overall discriminative ability of RFM and its cutoffs was at least similar (in women) or better (in men) compared to BMI and WC. Since RFM was substantially correlated with age, we additionally determined age-specific cutoffs, which ranged from 23 to 27 in men and 33 to 43 in women. CONCLUSIONS: RFM is associated with incident AF, HF, and CAD and may be used as a simple and intuitive marker of obesity and cardiovascular risk in the general population. This study provides potential RFM cutoffs for CVD prediction that may be used by future studies or preventive strategies targeting obesity and cardiovascular risk.

Home-based initiatives for acute management of COVID-19 patients needing oxygen: differences across The Netherlands.

OBJECTIVE: During the COVID-19 pandemic new collaborative-care initiatives were developed for treating and monitoring COVID-19 patients with oxygen at home. Aim was to provide a structured overview focused on differences and similarities of initiatives of acute home-based management in the Netherlands. METHODS: Initiatives were eligible for evaluation if (i) COVID-19 patients received oxygen treatment at home; (ii) patients received structured remote monitoring; (iii) it was not an 'early hospital discharge' program; (iv) at least one patient was included. Protocols were screened, and additional information was obtained from involved physicians. Design choices were categorised into: eligible patient group, organization medical care, remote monitoring, nursing care, and devices used. RESULTS: Nine initiatives were screened for eligibility; five were included. Three initiatives included low-risk patients and two were designed specifically for frail patients. Emergency department (ED) visit for an initial diagnostic work-up and evaluation was mandatory in three initiatives before starting home management. Medical responsibility was either assigned to the general practitioner or hospital specialist, most often pulmonologist or internist. Pulse-oximetry was used in all initiatives, with additional monitoring of heart rate and respiratory rate in three initiatives. Remote monitoring staff's qualification and authority varied, and organization and logistics were covered by persons with various backgrounds. All initiatives offered remote monitoring via an application, two also offered a paper diary option. CONCLUSIONS: We observed differences in the organization of interprofessional collaboration for acute home management of hypoxemic COVID-19 patients. All initiatives used pulse-oximetry and an app for remote monitoring. Our overview may be of help to healthcare providers and organizations to set up and implement similar acute home management initiatives for critical episodes of COVID-19 (or other acute disorders) that would otherwise require hospital care.

Incidence of atrial fibrillation, ischaemic heart disease and heart failure in patients with diabetes.

BACKGROUND: Diabetes has strongly been linked to atrial fibrillation, ischaemic heart disease and heart failure. The epidemiology of these cardiovascular diseases is changing, however, due to changes in prevalence of obesity-related conditions and preventive measures. Recent population studies on incidence of atrial fibrillation, ischaemic heart disease and heart failure in patients with diabetes are needed. METHODS: A dynamic longitudinal cohort study was performed using primary care databases of the Julius General Practitioners' Network. Diabetes status was determined at baseline (1 January 2014 or upon entering the cohort) and participants were followed-up for atrial fibrillation, ischaemic heart disease and heart failure until 1 February 2019. Age and sex-specific incidence and incidence rate ratios were calculated. RESULTS: Mean follow-up was 4.2 years, 12,168 patients were included in the diabetes group, and 130,143 individuals in the background group. Incidence rate ratios, adjusted for age and sex, were 1.17 (95% confidence interval 1.06-1.30) for atrial fibrillation, 1.66 (1.55-1.83) for ischaemic heart disease, and 2.36 (2.10-2.64) for heart failure. Overall, incidence rate ratios were highest in the younger age categories, converging thereafter. CONCLUSION: There is a clear association between diabetes and incidence of the major chronic progressive heart diseases, notably with heart failure with a more than twice increased risk.

Integrated management of atrial fibrillation in primary care: results of the ALL-IN cluster randomized trial.

AIMS: To evaluate whether integrated care for atrial fibrillation (AF) can be safely orchestrated in primary care. METHODS AND RESULTS: The ALL-IN trial was a cluster randomized, open-label, pragmatic non-inferiority trial performed in primary care practices in the Netherlands. We randomized 26 practices: 15 to the integrated care intervention and 11 to usual care. The integrated care intervention consisted of (i) quarterly AF check-ups by trained nurses in primary care, also focusing on possibly interfering comorbidities, (ii) monitoring of anticoagulation therapy in primary care, and finally (iii) easy-access availability of consultations from cardiologists and anticoagulation clinics. The primary endpoint was all-cause mortality during 2 years of follow-up. In the intervention arm, 527 out of 941 eligible AF patients aged ≥65 years provided informed consent to undergo the intervention. These 527 patients were compared with 713 AF patients in the control arm receiving usual care. Median age was 77 (interquartile range 72-83) years. The all-cause mortality rate was 3.5 per 100 patient-years in the intervention arm vs. 6.7 per 100 patient-years in the control arm [adjusted hazard ratio (HR) 0.55; 95% confidence interval (CI) 0.37-0.82]. For non-cardiovascular mortality, the adjusted HR was 0.47 (95% CI 0.27-0.82). For other adverse events, no statistically significant differences were observed. CONCLUSION: In this cluster randomized trial, integrated care for elderly AF patients in primary care showed a 45% reduction in all-cause mortality when compared with usual care.

Clinical research study implementation of case-finding strategies for heart failure and chronic obstructive pulmonary disease in the elderly with reduced exercise tolerance or dyspnea: A cluster randomized trial.

BACKGROUND: Heart failure (HF) and chronic obstructive pulmonary disease (COPD) often remain undiagnosed in older individuals, although both disorders inhibit functionality and impair health. The aim of the study was to assess the effectiveness of a case-finding strategy of these disorders. METHODS: This is a clustered randomized trial; 18 general practices from the vicinity of Utrecht, the Netherlands, were randomly allocated to a case-finding strategy or usual care. Multimorbid community subjects (≥65 years) with dyspnea or reduced exercise tolerance were eligible for inclusion. The case-finding strategy consisted of history taking, physical examination, blood tests, electrocardiography, spirometry, and echocardiography. Subsequent treatment decisions were at the discretion of the general practitioner. Questionnaires regarding health status and functionality were filled out at baseline and after 6 months of follow-up. Information regarding changes in medication and health care use during the 6 months follow-up was extracted. RESULTS: A total of 829 participants were randomized: 389 in the case-finding strategy group and 440 in the usual care group. More patients in the case-finding group received a new diagnosis of HF or COPD than the usual care group (cumulative incidence 34% vs 2% and 17% vs. 2%, respectively). Scores for health status, functionality, and health care use were similar between the 2 strategies after 6 months of follow-up. CONCLUSIONS: A case-finding strategy applied in primary care to multimorbid older people with dyspnea or reduced exercise tolerance resulted in a number of new diagnoses of HF and COPD but did not result in short-term improvement of health status compared to usual care.

Proactive screening for symptoms: A simple method to improve early detection of unrecognized cardiovascular disease in primary care. Results from the Lifelines Cohort Study.

Cardiovascular disease (CVD) often goes unrecognized, despite symptoms frequently being present. Proactive screening for symptoms might improve early recognition and prevent disease progression or acute cardiovascular events. We studied the diagnostic value of symptoms for the detection of unrecognized atrial fibrillation (AF), heart failure (HF), and coronary artery disease (CAD) and developed a corresponding screening questionnaire. We included 100,311 participants (mean age 52 ± 9 years, 58% women) from the population-based Lifelines Cohort Study. For each outcome (unrecognized AF/HF/CAD), we built a multivariable model containing demographics and symptoms. These models were combined into one 'three-disease' diagnostic model and questionnaire for all three outcomes. Results were validated in Lifelines participants with chronic obstructive pulmonary disease (COPD) and diabetes mellitus (DM). Unrecognized CVD was identified in 1325 participants (1.3%): AF in 131 (0.1%), HF in 599 (0.6%), and CAD in 687 (0.7%). Added to age, sex, and body mass index, palpitations were independent predictors for unrecognized AF; palpitations, chest pain, dyspnea, exercise intolerance, health-related stress, and self-expected health worsening for unrecognized HF; smoking, chest pain, exercise intolerance, and claudication for unrecognized CAD. Area under the curve for the combined diagnostic model was 0.752 (95% CI 0.737-0.766) in the total population and 0.757 (95% CI 0.734-0.781) in participants with COPD and DM. At the chosen threshold, the questionnaire had low specificity, but high sensitivity. In conclusion, a short questionnaire about demographics and symptoms can improve early detection of CVD and help pre-select people who should or should not undergo further screening for CVD.

Chest discomfort at night and risk of acute coronary syndrome: cross-sectional study of telephone conversations.

BACKGROUND: During telephone triage, it is difficult to assign adequate urgency to patients with chest discomfort. Considering the time of calling could be helpful. OBJECTIVE: To assess the risk of acute coronary syndrome (ACS) in certain time periods and whether sex influences this risk. METHODS: Cross-sectional study of 1655 recordings of telephone conversations of patients who called the out-of-hours services primary care (OHS-PC) for chest discomfort. Call time, patient characteristics, symptoms, medical history and urgency allocation of the triage conversations were collected. The final diagnosis of each call was retrieved at the patient's general practice. Absolute numbers of patients with and without ACS were plotted and risks per hour were calculated. The risk ratio of ACS at night (0 to 9 am) was calculated by comparing to the risk at other hours and was adjusted for gender and age. RESULTS: The mean age of callers was 58.9 (standard deviation ±19.5) years, 55.5% were women and, in total, 199 (12.0%) had an ACS. The crude risk ratio for an ACS at night was 1.80 (confidence interval 1.39-2.34, P < 0.001): 2.33 (1.68-3.22, P < 0.001) for men and 1.29 (0.83-1.99, P = 0.256) for women. The adjusted risk ratio for ACS of all people at night was 1.82 (1.07-3.10, P = 0.039). CONCLUSIONS: Patients calling the OHS-PC for chest discomfort between 0 and 9 am have almost twice a higher risk of ACS than those calling other hours, a phenomenon more evident in men than in women. At night, dispatching ambulances more 'straightaway' could be considered for these patients with chest discomfort. TRIAL NUMBER: NTR7331.

Accuracy of telephone triage in patients suspected of transient ischaemic attack or stroke: a cross-sectional study.

BACKGROUND: The Netherlands Triage Standard (NTS) is a widely used decision support tool for telephone triage at Dutch out-of-hours primary care services (OHS-PC), which, however, has never been validated against clinical outcomes. We aimed to determine the accuracy of the NTS urgency allocation for patients with neurological symptoms suggestive of a transient ischaemic attack (TIA) or stroke, with the clinical outcomes TIA, stroke, and other (neurologic) life-threatening events (LTEs) as the reference. METHOD: A cross-sectional study of telephone triage recordings of patients with neurological symptoms calling the OHS-PC between 2014 and 2016.The allocated NTS urgencies were derived from the electronic medical records of the OHS-PC. The clinical outcomes were retrieved from the electronic medical records of the patients' own general practitioners. The accuracy of a high NTS urgency allocation (medical help within 3 h) was calculated in terms of sensitivity, specificity, positive and negative predictive values (PPV and NPV) with the clinical outcomes TIA/stroke/other LTEs as the reference. RESULTS: Of 1269 patients, 635 (50.0%) received the diagnosis TIA/stroke (34.2% TIA/minor stroke, 15.8% major ischaemic or haemorrhagic stroke), and 4.8% other LTEs. For TIA/stroke/other LTEs, the sensitivity and specificity of the NTS urgency allocation were 0.72 (95%CI 0.68-0.75) and 0.48 (95%CI 0.43-0.52), and the PPV and NPV were 0.62 (95%CI 0.60-0.64) and 0.58 (95%CI 0.54-0.62). CONCLUSIONS: The NTS decision support tool used in Dutch OHS-PC performed poor to moderately regarding safety (sensitivity) and efficiency (specificity) in allocating adequate urgencies to patients with and without TIA/stroke/other LTEs. TRIAL REGISTRATION: The Netherlands National Trial Register, identification number NTR7331 /Trial NL7134 .

How to diagnose heart failure with preserved ejection fraction: the HFA-PEFF diagnostic algorithm: a consensus recommendation from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC).

Making a firm diagnosis of chronic heart failure with preserved ejection fraction (HFpEF) remains a challenge. We recommend a new stepwise diagnostic process, the 'HFA-PEFF diagnostic algorithm'. Step 1 (P=Pre-test assessment) is typically performed in the ambulatory setting and includes assessment for HF symptoms and signs, typical clinical demographics (obesity, hypertension, diabetes mellitus, elderly, atrial fibrillation), and diagnostic laboratory tests, electrocardiogram, and echocardiography. In the absence of overt non-cardiac causes of breathlessness, HFpEF can be suspected if there is a normal left ventricular ejection fraction, no significant heart valve disease or cardiac ischaemia, and at least one typical risk factor. Elevated natriuretic peptides support, but normal levels do not exclude a diagnosis of HFpEF. The second step (E: Echocardiography and Natriuretic Peptide Score) requires comprehensive echocardiography and is typically performed by a cardiologist. Measures include mitral annular early diastolic velocity (e'), left ventricular (LV) filling pressure estimated using E/e', left atrial volume index, LV mass index, LV relative wall thickness, tricuspid regurgitation velocity, LV global longitudinal systolic strain, and serum natriuretic peptide levels. Major (2 points) and Minor (1 point) criteria were defined from these measures. A score ≥5 points implies definite HFpEF; ≤1 point makes HFpEF unlikely. An intermediate score (2-4 points) implies diagnostic uncertainty, in which case Step 3 (F1: Functional testing) is recommended with echocardiographic or invasive haemodynamic exercise stress tests. Step 4 (F2: Final aetiology) is recommended to establish a possible specific cause of HFpEF or alternative explanations. Further research is needed for a better classification of HFpEF.

Tinkering and overruling the computer decision support system: Working strategies of telephone triage nurses who assess the urgency of callers suspected of having an acute cardiac event.

AIMS AND OBJECTIVES: To understand clinical reasoning and decision-making of triage nurses during telephone conversations with callers suspected of having acute cardiac events, and support from a computer decision support system (CDSS) herewith. BACKGROUND: In telephone triage, nurses assess the urgency of callers' conditions with clinical reasoning, often supported by CDSS. The use of CDSS may trigger interactional workability dilemmas. DESIGN: Qualitative study using principles of a grounded theory approach following COREQ criteria for qualitative research. METHODS: Audio-stimulated recall interviews were conducted amongst twenty-four telephone triage nurses at nine out-of-hours primary care centres (OHS-PC). RESULTS: Telephone triage nurses use clinical reasoning elements for urgency assessment. Typically in telephone triage, they interpret the vocal-but not worded-elements in communication (paralanguage) such as tone of voice and shortness of breath and create a mental image to compensate for lack of visual information. We confirmed that interactional workability dilemmas occur. Congruence, established when the CDSS supports the triage nurses' decision-making, is essential for the CDSS' value. If congruence is absent, triage nurses may apply four working strategies: (a) tinker to make CDSS final recommendation align with their own assessment, (b) overrule the CDSS recommendation, (c) comply with the CDSS recommendation or (d) transfer responsibility to the GP. CONCLUSION: Triage nurses who assess urgency may experience absence of congruence between the CDSS and their decision-making. Awareness of how triage nurses reason and make decisions about urgency and what aspects influence their working strategies can help in achieving optimal triage of callers suspected of acute cardiac events at OHS-PC. RELEVANCE TO CLINICAL PRACTICE: Triage nurses' reasoning and their working strategies are vital for outcome of triage decisions. Understanding these processes is essential for CDSS developers and OHS-PC managers, who should value how triage nurses interact with the CDSS, while they have the benefit of callers in mind.

Diagnostic Accuracy of the Explicit Diagnostic Criteria for Transient Ischemic Attack: A Validation Study.

Background and Purpose- The clinical diagnosis of a transient ischemic attack (TIA) can be difficult. Evidence-based criteria hardly exist. We evaluated if the recently proposed Explicit Diagnostic Criteria for TIA (EDCT), an easy to perform clinical tool focusing on type, duration, and mode of onset of clinical features, would facilitate the clinical diagnosis of TIA. Methods- We used data from patients suspected of a TIA by a general practitioner and referred to a TIA service in the region of Utrecht, the Netherlands, who participated in the MIND-TIA (Markers in the Diagnosis of TIA) study. Information about the clinical features was collected with a standardized questionnaire within 72 hours after onset. A panel of 3 experienced neurologists ultimately determined the definite diagnosis based on all available diagnostic information including a 6-month follow-up period. Two researchers scored the EDCT. Sensitivity, specificity, and predictive values of the EDCT were assessed using the panel diagnosis as reference. A secondary analysis was performed with modified subcriteria of the EDCT. Results- Of the 206 patients, 126 (61%) had a TIA (n=104) or minor stroke (n=22), and 80 (39%) an alternative diagnosis. Most common alternative diagnoses were migraine with aura (n=24; 30.0%), stress related or somatoform symptoms (n=16; 20.0%), and syncope (n=9; 11.3%). The original EDCT had a sensitivity of 98.4% (95% CI, 94.4-99.8) and a specificity of 61.3% (49.7-71.9). Negative and positive predictive values were 96.1% (86.0-99.0) and 80.0% (75.2-84.1), respectively. The modified EDCT showed a higher specificity of 73.8% (62.7-83.0) with the same sensitivity and a similar negative predictive value of 96.7%, but a higher positive predictive value of 85.5% (80.3-89.5). Conclusions- The EDCT has excellent sensitivity and negative predictive value and could be a valuable diagnostic tool for the diagnosis of TIA.

Candidate Biomarkers for the Diagnosis of Transient Ischemic Attack: A Systematic Review.

BACKGROUND AND PURPOSE: A rapid serum biomarker that confirms or rules out a transient ischemic attack (TIA) would be of great value in clinical practice. We aimed to systematically review current evidence for the diagnostic accuracy of blood biomarkers in the early diagnosis of TIA. METHODS: This is a systematic review with quality appraisal of individual studies using the QUADAS-2 tool. MEDLINE and EMBASE databases were searched up to May 1, 2017, to select primary diagnostic accuracy studies evaluating potential biomarkers in blood for the diagnosis of TIA or ischemic stroke. RESULTS: Of 4,215 studies retrieved, 78 met our eligibility criteria. Forty-five studies restricted their population to ischemic stroke patients, 32 included both TIA and ischemic stroke patients, and only one study was restricted to TIA patients. In total 62/78 (79.5%) studies had a case-control design comparing TIA or stroke patients with healthy subjects. Overall, 125 single biomarkers and 5 biomarker panels were studied, with a median number of participants per study of 92.0 (interquartile range 44.8-144.5), varying from 8 to 915. Sufficient information to extract 2 × 2 tables was available for 35 (44.9%) articles, and for 60 (48.0 %) biomarkers. Several markers, such as NR2A/B (antibodies), Parkinson 7, nucleoside diphosphate kinase A, ubiquitin fusion degradation protein-1, and heart-type fatty acid binding protein, have shown moderate to high diagnostic accuracy in multiple studies. CONCLUSIONS: Although the methodological quality of studies evaluating biomarkers of brain ischemia was poor, several biomarkers have shown the potential to detect transient brain ischemia in an early phase. Diagnostic accuracy studies in suspected cases of TIA are needed to determine their true clinical value.

Determinants of Patient Delay in Transient Ischemic Attack.

INTRODUCTION: Early diagnosis and stroke preventive treatment in patients with transient ischemic attack (TIA) are crucial, but hampered by delayed reporting of symptoms. Previous studies on causes of patient delay provided inconsistent results. We aimed to assess determinants of patient delay among patients with symptoms suggestive of TIA. METHODS: We interviewed participants referred by their general practitioner to an outpatient TIA clinic within 72 h from symptom onset. We determined (i) the exact time from symptom onset to the first contact with a medical service (patient delay); (ii) demographic and clinical characteristics; (iii) patient's initial perception, and reaction to symptoms; and (iv) patient's knowledge about TIA. We used multivariable linear regression to identify determinants of patient delay. RESULTS: We interviewed 202 suspected TIA patients (mean age 67.7 (SD 13.7) years, 111 (55.0%) male), of whom 123 (60.9%) received a definite diagnosis of TIA or minor stroke. Median patient delay was 1.5 (interquartile range 0.4-14.6) hours. Of all patients, 119 (58.9%) considered a TIA (or stroke) as the cause of their symptoms. Among them, 30 (25.2%) thought it was a medical emergency, while of the 83 not considering TIA as the cause of symptoms 38 (45.8%) thought of a medical emergency. Independently related to increased delay were (i) symptom onset out of hours, (ii) absence of dysarthria, (iii) being unaware that TIA requires urgent treatment, (iv) not considering the event an emergency, and (v) knowledge of TIA symptoms. Results for patients with a definite diagnosis of TIA/minor stroke were similar to those with alternative diagnoses. CONCLUSION: Patients still tend to wait till office hours to report TIA symptoms. Speech difficulties, and specifically dysarthria, are related to shorter delay. To reduce patient delay, awareness of TIA symptoms should increase and more importantly lay people should be educated to consider a TIA an emergency.

Prevalence of left ventricular systolic dysfunction and heart failure with reduced ejection fraction in men and women with type 2 diabetes mellitus: a systematic review and meta-analysis.

BACKGROUND: Type 2 diabetes mellitus (T2D) is associated with the development of left ventricular systolic dysfunction (LVSD) and heart failure with reduced ejection fraction (HFrEF). T2D patients with LVSD are at higher risk of mortality and morbidity than patients without LVSD, while progression of LVSD can be delayed or halted by the use of proven therapies. As estimates of the prevalence are scarce and vary considerably, the aim of this study was to retrieve summary estimates of the prevalence of LVSD/HFrEF in T2D and to see if there were any sex differences. METHODS: A systematic search of Medline and Embase was performed to extract the prevalence of LVSD/HFrEF in T2D (17 studies, mean age 50.1 ± 6.3 to 71.5 ± 7.5), which were pooled using random-effects meta-analysis. RESULTS: The pooled prevalence of LVSD was higher in hospital populations (13 studies, n = 5835, 18% [95% CI 17-19%]), than in the general population (4 studies, n = 1707, 2% [95% CI 2-3%]). Seven studies in total reported sex-stratified prevalence estimates (men: 7% [95% CI 5-8%] vs. women: 1.3% [95% CI 0.0.2.2%]). The prevalence of HFrEF was available in one general population study (5.8% [95% CI 3.7.6%], men: 6.8% vs. women: 3.0%). CONCLUSIONS: The summary prevalence of LVSD is higher among T2D patients from a hospital setting compared with from the general population, with a higher prevalence in men than in women in both settings. The prevalence of HFrEF among T2D in the population was only assessed in a single study and again was higher among men than women.

Routine primary care data for scientific research, quality of care programs and educational purposes: the Julius General Practitioners' Network (JGPN).

BACKGROUND: General Practitioners (GPs) in the Netherlands routinely register all patient contacts electronically. These records include longitudinally gathered clinical information of the patient contacts in coded data and free text. METHODS: Diagnoses are coded according to the International Coding of Primary Care (ICPC). Drug prescriptions are labelled with the Anatomical Therapeutic Chemical Classification (ATC), and letters of hospital specialists and paramedic health care professionals are linked or directly incorporated in the electronic medical files. A network of a large group of GPs collecting routine care data on an ongoing basis can be used for answering various research questions. RESULTS: The Julius General Practitioners' Network (JGPN) database consists of routine care data from over ten years of a dynamic cohort of around 370,000 individuals registered with the participating GPs from the city of Utrecht and its vicinity. Health care data are extracted anonymously every quartile of a year and these data are used by researchers. CONCLUSION: We describe the content and usability of our JGPN database, and how a wide variety of research questions could be answered, as illustrated with examples of published articles.