Biomarkers predictive of atrial fibrillation in patients with cryptogenic stroke. Insights from the Nordic Atrial Fibrillation and Stroke (NOR-FIB) study.

BACKGROUND AND PURPOSE: There are currently no biomarkers to select cryptogenic stroke (CS) patients for monitoring with insertable cardiac monitors (ICMs), the most effective tool for diagnosing atrial fibrillation (AF) in CS. The purpose of this study was to assess clinically available biomarkers as predictors of AF. METHODS: Eligible CS and cryptogenic transient ischaemic attack patients underwent 12-month monitoring with ICMs, clinical follow-up and biomarker sampling. Levels of cardiac and thromboembolic biomarkers, taken within 14 days from symptom onset, were compared between patients diagnosed with AF (n = 74) during monitoring and those without AF (n = 185). Receiver operating characteristic curves were created. Biomarkers reaching area under the receiver operating characteristic curve ≥ 0.7 were dichotomized by finding optimal cut-off values and were used in logistic regression establishing their predictive value for increased risk of AF in unadjusted and adjusted models. RESULTS: B-type natriuretic peptide (BNP), N-terminal pro-brain natriuretic peptide (NT-proBNP), creatine kinase, D-dimer and high-sensitivity cardiac troponin I and T were significantly higher in the AF than non-AF group. BNP and NT-proBNP reached the predefined area under the curve level, 0.755 and 0.725 respectively. Optimal cut-off values were 33.5 ng/l for BNP and 87 ng/l for NT-proBNP. Regression analysis showed that NT-proBNP was a predictor of AF in both unadjusted (odds ratio 7.72, 95% confidence interval 3.16-18.87) and age- and sex-adjusted models (odds ratio 4.82, 95% confidence interval 1.79-12.96). CONCLUSION: Several clinically established biomarkers were associated with AF. NT-proBNP performed best as AF predictor and could be used for selecting patients for long-term monitoring with ICMs.

Frequency of 'warning signs of cancer' in Norwegian general practice, with prospective recording of subsequent cancer.

BACKGROUND: Early diagnosis of cancer is an important challenge in general practice. Symptoms are the most common starting points. OBJECTIVE: To assess the association between symptoms presented and subsequent cancer. DESIGN: A cohort study of all patients seen consecutively by GPs. Prospective recording of cancer diagnosis, new cancer or new recurrence. SETTING: Two hundred and eighty-three general practice surgeries and 10 working days. METHOD: During patient consultations, GPs registered seven focal symptoms and three general symptoms, commonly considered as warning signs of cancer (WSC). Follow-up 6-11 months later with registration of any subsequent diagnosis of cancer was done. RESULTS: Of 51 073 patients, 6321 (12.4%) had recordings of 7704 WSC. During a median follow-up period of 8 months, 263 patients were diagnosed with cancer and 59 of them with recurrence of a previously diagnosed cancer. Of the cancer patients, 106 (40%) had presented one or more WSC during a preceding consultation. Examined symptoms had likelihood ratios for cancer from 1.5 to 8.2 and positive predictive values (PPVs) from 0.8% to 3.8%. Limited to older age groups, PPVs were a little higher. General symptoms were rarely associated with cancer unless a focal symptom had been recorded as well. Multiple symptoms increased the probability of cancer. CONCLUSION: 12.4% of GP patients presented with WSC. A general symptom may have cancer diagnostic value, but usually, only when it occurs along with a focal symptom. PPV of any single symptom is low, and decisions about referral require additional information.

Atrial fibrillation in cryptogenic stroke and transient ischaemic attack - The Nordic Atrial Fibrillation and Stroke (NOR-FIB) Study: Rationale and design.

PURPOSE: Paroxysmal atrial fibrillation is often suspected as a probable cause of cryptogenic stroke. Continuous long-term ECG monitoring using insertable cardiac monitors is a clinically effective technique to screen for atrial fibrillation and superior to conventional follow-up in cryptogenic stroke. However, more studies are needed to identify factors which can help selecting patients with the highest possibility of detecting atrial fibrillation with prolonged rhythm monitoring. The clinical relevance of short-term atrial fibrillation, the need for medical intervention and the evaluation as to whether intervention results in improved clinical outcomes should be assessed. METHOD: The Nordic Atrial Fibrillation and Stroke Study is an international, multicentre, prospective, observational trial evaluating the occurrence of occult atrial fibrillation in cryptogenic stroke and transient ischaemic attack. Patients with cryptogenic stroke or transient ischaemic attack from the Nordic countries are included and will have the Reveal LINQ® Insertable cardiac monitor system implanted for 12 months for atrial fibrillation detection. Biomarkers which can be used as predictors for atrial fibrillation and may identify patients, who could derive the most clinical benefit from the detection of atrial fibrillation by prolonged monitoring, are being studied. CONCLUSION: The primary endpoint is atrial fibrillation burden within 12 months of continuous rhythm monitoring. Secondary endpoints are atrial fibrillation burden within six months, levels of biomarkers predicting atrial fibrillation, CHA2DS2-VASc score, incidence of recurrent stroke or transient ischaemic attack, use of anticoagulation and antiarrhythmic drugs, and quality of life measurements. The clinical follow-up period is 12 months. The study started in 2017 and the completion is expected at the end of 2020.

Cancer suspicion in general practice: the role of symptoms and patient characteristics, and their association with subsequent cancer.

BACKGROUND: Awareness of detail in ambiguous complaints may help GPs suspect cancer when a malignancy is present. AIM: To study the contribution of symptoms and patient characteristics to GPs' suspicions of cancer being present, and to what degree these suspicions were confirmed. DESIGN AND SETTING: Prospective cohort study of patients in 283 rural and urban general practices throughout Norway. METHOD: During patient consultations (over a period of 10 days) GPs registered whether there was a suspicion of cancer when a patient presented with at least one of seven focal symptoms and three general symptoms commonly considered to be warning signs of cancer. Follow-up questionnaires were sent to GPs 6-7 months later, requesting information on any subsequent diagnosis of cancer in these patients. RESULTS: Out of 51 073 patients, 6321 presented with warning signs of cancer; of these, 106 had a subsequent cancer diagnosis. Of the patients presenting with warning signs, 1515 (24%) patients were suspected of having cancer; this was correct for 3.8% of suspected cases. Of the 106 patients diagnosed with cancer who presented with warning signs, cancer was suspected in 58 (54.7%). GPs' correct cancer suspicions were six times more frequent than their erroneous lack of suspicion. Multiple symptoms, previous cancer, comorbidity, and multiple consultations increased the probability of cancer, but only multiple symptoms and previous cancer increased suspicion. Suspicion led to an increase in the number of diagnostic procedures undertaken. The proportion of cancer cases where GPs recorded a lack of suspicion was relatively small, but important. CONCLUSION: Selected symptoms appropriately resulted in GPs suspecting cancer. Comorbidity and multiple consultations were underestimated by GPs as factors associated with cancer. Cancer suspicion should rely on symptoms in combination with other relevant information.