Net Clinical Benefit of Oral Anticoagulation Among Frail Patients With Atrial Fibrillation: Nationwide Cohort Study.

BACKGROUND: Frail people with atrial fibrillation are often undertreated with oral anticoagulants (OACs), and evidence for the net clinical benefit (NCB) of OAC is sparse. We, therefore, examined the risk of thromboembolic events, major bleeding, and NCB of anticoagulation treatment. METHODS: This was a nationwide cohort study including frail patients aged with incident atrial fibrillation between 2013 and 2018. Patients were categorized according to OAC treatment exposure. One-year risks of thromboembolic events and major bleeding were ascertained where death was treated as a competing risk. The NCB of anticoagulation was assessed by a bivariate trade-off between thromboembolism and bleeding. RESULTS: We identified 36 223 frail patients with atrial fibrillation (median age, 79 years; 50.5% female), of whom 61.8% started OAC therapy, while 38.2% were untreated despite indication for stroke prevention. At 1 year, the risk of thromboembolic events was 2.1% (95% CI, 1.8%-2.3%) among patients not receiving OAC versus 1.5% (95% CI, 1.4%-1.7%) in patients with OAC. The bleeding risk was 3.2% (95% CI, 2.9%-3.5%) among patients without OAC versus 3.5% (95% CI, 3.2%-3.8%) among anticoagulated patients. The NCB was 0.70% (95% CI, 0.32%-1.08%), suggesting a benefit of OAC treatment; however, the NCB declined with age and increasing frailty and was lowest among patients >75 years of age or with high frailty level. CONCLUSIONS: Frail patients with atrial fibrillation are often untreated with OAC in routine clinical care despite an indication for stroke prevention. The NCB balancing thromboembolic events and major bleeding was in favor of anticoagulation but decreased with advancing age and increasing frailty.

External Validation of the OAC3-PAD Bleeding Score in a Nationwide Population of Patients Undergoing Invasive Treatment for Peripheral Arterial Disease.

OBJECTIVE: The OAC3-PAD score was developed to predict bleeding risk in patients with lower extremity peripheral arterial disease (PAD), but its performance in concomitant international cohorts is largely unknown. This study aimed to validate the OAC3-PAD score in an unselected nationwide population of patients undergoing invasive treatment for symptomatic PAD. METHODS: This was a nationwide cohort study including all patients who underwent a first revascularisation procedure or major amputation for symptomatic PAD in Denmark from 2000 - 2021. The study population was stratified based on OAC3-PAD score, and the one year risk of major bleeding was assessed, accounting for the competing risk of death. The score performance was evaluated using calibration plots, C statistic, Brier score, and the index of prediction accuracy (IPA). RESULTS: A total of 52 016 patients were included (mean age 71 years, 43.8% female). The one year risk of major bleeding increased with higher OAC3-PAD score, ranging from 1.6% (95% confidence interval [CI] 1.4 - 1.8%) to 2.3% (95% CI 2.0 - 2.5%), 3.5% (95% CI 3.2 - 3.8%), and 5.2% (95% CI 4.8 - 5.6%) for patients with low, low moderate, moderate high, and high score, respectively. Using patients with low risk as reference, the OAC3-PAD score effectively categorised patients, demonstrating statistically significant differences in bleeding risk across strata. However, the score showed modest discriminative performance, with a C statistic of 65% (95% CI 63 - 66%) and a Brier score of 2.6% (95% CI 2.5 - 2.7%). Nevertheless, it performed significantly better than the null model, as indicated by an IPA of 3.1%. CONCLUSION: Among patients who underwent invasive treatment for symptomatic PAD in routine care, the OAC3-PAD score was associated with greater risk of major bleeding with increasing score level. However, its discriminatory ability was modest, and the clinical utility remains to be determined.

Adherence and Persistence to Antiplatelet Therapy in Lower Extremity Peripheral Arterial Disease: A Danish Population Based Cohort Study.

OBJECTIVE: Adherence to antiplatelet therapy is recommended but unexplored in patients with symptomatic lower extremity peripheral arterial disease (PAD). Therefore, this study aimed to determine adherence and persistence to antiplatelet therapy in patients with PAD, defined as intermittent claudication and chronic limb threatening ischaemia. DESIGN: Population based nationwide cohort study. METHODS: This study included all Danish citizens aged ≥ 40 years with a first inpatient or outpatient diagnosis of symptomatic PAD between 2010 - 2017, and who had at least one prescription claim for aspirin and/or clopidogrel within 90 days after diagnosis. Adherence was determined by the proportion of days covered (PDC) during the first year after diagnosis. Persistence was defined as no treatment gap ≥ 30 days between prescription renewals over three year follow up. RESULTS: A total of 39 687 patients were eligible for inclusion, of whom 23 279 (58.7%) claimed a prescription for aspirin and/or clopidogrel within 90 days of diagnosis. Among these, 12 898 (55.4%) were prevalent users, while the remainder comprised new users who initiated the therapy after the index PAD diagnosis. The mean PDC was 74.5% (SD 35.0%) for prevalent users and 60.5% (SD 30.5%) for new users. Adherence increased with age and number of concomitant drugs. The overall one year cumulative incidence treatment discontinuation was 13.0% (95% CI 12.5 - 13.4%) overall, 17.2% (CI 16.6 - 17.9%) for prevalent users, and 7.9% (CI 7.4 - 8.4%) for new users. At three year follow up, the cumulative incidence of discontinuation was 31.5% (CI 30.9 - 32.2%) overall, 44.6% (CI 43.7 - 45.4%) for prevalent users, and 14.6% (CI 13.9 - 15.3) for new users. CONCLUSION: Less than 60% of patients with newly diagnosed symptomatic PAD claimed a prescription for antiplatelet therapy within 90 days of diagnosis, and both adherence and persistence were moderate during the first year after diagnosis. These findings underscore the importance of efforts to improve the initiation and continuation of antiplatelet therapy in patients with PAD.

Continuous Glucose Monitoring Reveals Perioperative Hypoglycemia in Most Patients With Diabetes Undergoing Major Surgery: A Prospective Cohort Study.

OBJECTIVE: To investigate the frequency and duration of hypo- and hyperglycemia, assessed by continuous glucose monitoring (CGM) during and after major surgery, in departments with implemented diabetes care protocols. SUMMARY BACKGROUND DATA: Inadequate glycemic control in the perioperative period is associated with serious adverse events, but monitoring currently relies on point blood glucose measurements, which may underreport glucose excursions. METHODS: Adult patients without (A) or with diabetes [non-insulin-treated type 2 (B), insulin-treated type 2 (C) or type 1 (D)] undergoing major surgery were monitored using CGM (Dexcom G6), with an electrochemical sensor in the interstitial fluid, during surgery and for up to 10 days postoperatively. Patients and health care staff were blinded to CGM values, and glucose management adhered to the standard diabetes care protocol. Thirty-day postoperative serious adverse events were recorded. The primary outcome was duration of hypoglycemia (glucose <70 mg/dL). Clinicaltrials.gov: NCT04473001. RESULTS: Seventy patients were included, with a median observation time of 4.0 days. CGM was recorded in median 96% of the observation time. The median daily duration of hypoglycemia was 2.5 minutes without significant difference between the 4 groups (A-D). Hypoglycemic events lasting ≥15 minutes occurred in 43% of all patients and 70% of patients with type 1 diabetes. Patients with type 1 diabetes spent a median of 40% of the monitoring time in the normoglycemic range 70 to 180 mg/dL and 27% in the hyperglycemic range >250 mg/dL. Duration of preceding hypo- and hyperglycemia tended to be longer in patients with serious adverse events, compared with patients without events, but these were exploratory analyses. CONCLUSIONS: Significant duration of both hypo- and hyperglycemia was detected in high proportions of patients, particularly in patients with diabetes, despite protocolized perioperative diabetes management.

Editor's Choice - Long Term Outcomes After Invasive Treatment of Carotid Artery Stenosis: a Longitudinal Study of German Health Insurance Claims.

OBJECTIVE: There is a paucity of observational data including long term outcomes after invasive treatment for carotid artery stenosis. METHODS: This retrospective study used nationwide insurance claims from the third largest provider in Germany, DAK-Gesundheit. Patients who underwent inpatient carotid endarterectomy (CEA) or carotid artery stenting (CAS) between 1 January 2008 and 31 May 2017 were included. The Elixhauser comorbidity scores from longitudinally linked hospital episodes were used. Kaplan-Meier analysis and the log rank test were used to determine long term stroke free survival. Multivariable regression models were developed to adjust for confounding. RESULTS: A total of 22 637 individual patients (41.6% female, median age 72.5 years) were included, of whom 15 005 (66.3%) were asymptomatic and 17 955 (79.3%) underwent CEA. After a median of 48 months, 5 504 any stroke or death events were registered. The mortality rate varied between 0.4% (CEA for asymptomatic stenosis) and 2.1% (urgent CAS for acute stroke patients) at 30 days, and between 4.1% and 8.4% at one year, respectively. The rate for any stroke varied between 0.6% (CEA for asymptomatic stenosis) and 2.5% (CAS for symptomatic patients) at 30 days, and between 2.5% and 6.4% at one year, respectively. The combined rate for any stroke and mortality at one year was 6.3% (CEA for asymptomatic stenosis), 8.7% (CAS for asymptomatic stenosis), and 12.5% (urgent CAS for acute stroke patients). After five years, the overall stroke rate was 7.4% after CEA and 9.0% after CAS. In adjusted analyses, both older age and van Walraven comorbidity score were associated with events, while treatment of asymptomatic stenosis was associated with lower event rates. CONCLUSION: The current study revealed striking differences between previous landmark trials and real world practice. It further suggested excess deaths among invasively treated asymptomatic patients.

Epidemiological Trends and Projections of Incidence, Prevalence, and Disease Related Mortality Associated With Peripheral Arterial Disease: Observations Using Nationwide Danish Data.

OBJECTIVE: Peripheral arterial disease (PAD) trends remain unclear because contemporary data are sparse and conflicting. This nationwide cohort study quantified changes in PAD incidence, prevalence, and all cause mortality, and projected prevalence development through to 2040. METHODS: Population based registries covering the entire Danish population aged ≥ 40 years from 2000 to 2018 were linked to assess trends in PAD incidence, prevalence, and all cause mortality, overall and by sex and age groups. Based on observed trends in incidence and mortality, and estimated future annual age distribution and population mortality, the PAD prevalence through to 2040 was projected. RESULTS: The Danish population aged 40 - 99 years in 2000 - 2018 included 4 811 281 individuals, among whom 145 870 incident PAD diagnoses were identified. The age and sex standardised PAD incidence decreased from 2.26 per 1 000 person years in 2000 to 1.65 in 2018 (incidence RR 0.74, 95% CI 0.72 - 0.77). The incidence was approximately 20% higher in men than women but declined similarly over time. Concurrently, PAD prevalence in the Danish adult population increased from 1.3% to 1.6% (prevalence ratio 1.28, 95% CI 1.26 - 1.30). Among patients aged ≥ 80 years, the prevalence reached 5.7% in women and 7.9% in men. The age and sex standardised annual mortality among patients with PAD decreased from 9.8% in 2000 to 7.2% in 2018 (mortality ratio 0.75, 95% CI 0.72 - 0.78). Projections of PAD prevalence demonstrated that the rising PAD prevalence will continue until around 2030, followed by a decline towards 2040. Among individuals aged ≥ 80 years, the prevalence was projected to plateau at 8.9% for men and 6.2% for women before declining. CONCLUSION: Within an unselected nationwide population, the incidence and all cause mortality of PAD have declined over the last two decades. Concurrently, prevalence increased and is projected to increase further over the coming decade, emphasising the growing burden of this common atherosclerotic disease in ageing populations.

Temporal Changes in Secondary Prevention and Cardiovascular Outcomes After Revascularization for Peripheral Arterial Disease in Denmark: A Nationwide Cohort Study.

BACKGROUND: Patients with peripheral arterial disease (PAD) are at increased risk of cardiovascular morbidity and mortality. Medical prevention with antithrombotic and statin therapies is a mainstay of treatment to prevent adverse outcomes; nevertheless, patients with PAD are often undertreated. This study describes the temporal changes in medical prevention and adverse outcomes in a national cohort of patients with symptomatic PAD after revascularization. METHODS: We identified all patients with a first open surgical or endovascular revascularization procedure in the lower extremities or abdomen in Denmark, from 2000 to 2016. We examined temporal changes in the use of aspirin, clopidogrel, and statins and 1-year cause-specific hazard ratios for adverse clinical outcomes, after adjusting for procedure type, treatment indication, age, sex, and cardiovascular risk factors. The analyses were performed overall and within strata of index procedure (endovascular versus surgical), treatment indication, age, sex, and high-risk comorbidities. RESULTS: Between 2000 and 2016, we identified 32 911 patients who underwent revascularization for symptomatic PAD. The mean age was 69 years and increased over time, as did the burden of comorbidity. The cumulative incidence of medication use increased between 2000 to 2004 and 2013 to 2016, respectively, from 57.3% to 64.3% for aspirin, 3.6% to 24.8% for clopidogrel, and 36.2% to 77.1% for statins. Concurrently, the 1-year outcome rates declined. Compared with 2000 to 2004, the adjusted hazard ratios in 2013 to 2016 were 0.73 (95% CI, 0.62-0.84) for major adverse cardiovascular events, 0.92 (95% CI, 0.85-1.00) for major adverse limb events, 0.60 (95% CI, 0.48-0.74) for myocardial infarction, 0.94 (95% CI, 0.75-1.18) for ischemic stroke, 0.92 (95% CI, 0.75-1.12) for major bleeding, 0.54 (95% CI, 0.39-0.76) for cardiovascular death, and 0.80 (95% CI, 0.72-0.88) for all-cause death. These improvements in prognosis were most prominent from 2000 to 2004 to 2005 to 2008 and occurred in all strata of index procedure, treatment indication, sex, age, and comorbidity. In contrast, the adjusted hazard ratio for major amputations was 1.00 (95% CI, 0.90-1.11) when comparing 2013 to 2016 to 2000 to 2004. CONCLUSIONS: Medical prevention of adverse events has increased considerably over time in patients who underwent revascularization for symptomatic PAD. This increase was accompanied by reductions in all adverse outcomes, except major amputations.

Oral anti-coagulant treatment patterns in atrial fibrillation patients diagnosed with cancer: A Danish nationwide cohort study.

Data on the use of oral anti-coagulants (OAC) for stroke prevention in cancer patients with atrial fibrillation (AF) are sparse. Nationwide cohort study of patients with AF (2012-2018) and an indication for OAC who were diagnosed with cancer at least one year later (N = 12 756). We identified treatment with OAC at cancer diagnosis and the following year and described the incidence of discontinuing or switching between warfarin and direct oral anti-coagulants (DOACs). We also described baseline characteristics associated with OAC non-persistence. One third of the cancer patients received no OAC therapy, whereas 42% received warfarin and 24% received DOAC treatment. Switching incidence between OACs was higher for those receiving warfarin treatment (8.6%) than DOAC treatment (1.7%) within one year. Treatment discontinuation was 61% for warfarin and 26% for DOAC. Females were less likely to discontinue DOAC than males (ratio 0.77, 95% confidence interval: 0.66, 0.90). Increasing cancer stage was associated with discontinuation of DOAC, but not warfarin. OAC for stroke prevention in AF was used by two thirds of patients with newly diagnosed cancer. Switching between OACs and discontinuation was more common for warfarin than DOAC, and females had higher persistence with DOACs.

Disparities in oral anticoagulation initiation in patients with schizophrenia and atrial fibrillation: A nationwide cohort study.

AIMS: Schizophrenia is associated with poor anticoagulation control and clinical prognosis in patients with atrial fibrillation (AF). Little is known about initiation of oral anticoagulation therapy (OAC) in this patient population. METHODS: In the nationwide Danish health registries, we identified all patients with incident AF and schizophrenia with indication for OAC treatment. Patients with schizophrenia (n = 673) were matched 1:5 on sex, age, stroke risk score, and calendar-period to incident AF patients without schizophrenia. We calculated absolute risk and risk difference (RD) of OAC initiation, adjusting for stroke and bleeding risk factors. Analyses were stratified by calendar period (2000-2011 and 2012-2018) to account for changes after the introduction of non-vitamin K OACs (NOAC). RESULTS: Among patients with schizophrenia (mean age 69.5 years, 50.3% females), 33.7% initiated OAC within the first year after AF diagnosis, compared with 54.4% of patients without schizophrenia, corresponding to an adjusted RD of -20.7 (95% confidence interval [CI]: -24.7 to -16.7). OAC initiation increased over time regardless of schizophrenia status. During 2000-2011, 18.3% of patients with schizophrenia and 42.9% without schizophrenia initiated OAC (adjusted RD -23.6%, 95% CI -28.8 to -18.6). During 2012-2018, this was 48.5% and 65.7%, respectively (adjusted RD -14.4%, 95% CI -20.4 to -8.4). CONCLUSION: Initiation of OAC was substantially lower among patients with AF and schizophrenia compared with matched AF peers. These findings accentuate the importance of close attention to disparities in initiation of OAC treatment, and potential missed opportunities for prevention of disabling strokes in AF patients with schizophrenia.

Revascularisation for Symptomatic Peripheral Artery Disease: External Applicability of the VOYAGER PAD Trial.

OBJECTIVE: In the VOYAGER PAD trial, rivaroxaban 2.5 mg plus aspirin significantly reduced the primary composite efficacy outcome of acute limb ischaemia, major amputation, myocardial infarction, ischaemic stroke, or cardiovascular death compared with aspirin alone. However, patients enrolled in the trial may not reflect patients encountered in daily clinical practice. This study described the proportion of patients eligible for VOYAGER PAD within the nationwide Danish Vascular Registry (DVR), reasons for ineligibility, and outcomes according to eligibility. METHODS: In total, 32 911 patients who underwent lower extremity revascularisation for symptomatic peripheral arterial disease (PAD) in the DVR (2000-2016) were identified. Trial inclusion and exclusion criteria were applied, and the three year cumulative incidence of primary and secondary trial outcomes was estimated. RESULTS: Altogether, 27.1% of patients with PAD in the DVR were "VOYAGER eligible". Of those not included, 30.7% had at least one exclusion criterion ("VOYAGER excluded"), and an additional 42.3% did not fulfil the inclusion criteria ("VOYAGER not included"). The main reasons for exclusion were atrial fibrillation (32.3%), poorly regulated hypertension (20.6%), requirement for long term dual antiplatelet therapy (10.9%), cytochrome P450 inhibitors or inducers (9.7%), and renal failure (9.3%). The three year rate of the primary efficacy outcome was 10.08 per 100 person years among the "VOYAGER eligible", 16.32 among "VOYAGER excluded", and 6.98 among the "VOYAGER not included". For the primary safety outcome of thrombolysis in myocardial infarction (TIMI) major bleeding, rates were 2.24, 3.76, and 1.17, respectively. Rates of secondary endpoints were also consistently lower for patients who did not meet the inclusion criteria (predominantly due to central aorto-iliac procedures) and highest for "VOYAGER excluded" patients. "VOYAGER eligible" patients experienced a higher cumulative incidence of most endpoints than patients enrolled in the control arm of the VOYAGER PAD trial. CONCLUSION: Among patients in routine clinical practice, 27.1% were eligible for the VOYAGER PAD trial. These patients were older, had more severe vascular symptoms, higher bleeding risk, and worse prognosis than trial participants.

Continuous monitoring of vital sign abnormalities; association to clinical complications in 500 postoperative patients.

BACKGROUND: Patients undergoing major surgery are at risk of complications, so-called serious adverse events (SAE). Continuous monitoring may detect deteriorating patients by recording abnormal vital signs. We aimed to assess the association between abnormal vital signs inspired by Early Warning Score thresholds and subsequent SAEs in patients undergoing major abdominal surgery. METHODS: Prospective observational cohort study continuously monitoring heart rate, respiratory rate, peripheral oxygen saturation, and blood pressure for up to 96 h in 500 postoperative patients admitted to the general ward. Exposure variables were vital sign abnormalities, primary outcome was any serious adverse event occurring within 30 postoperative days. The primary analysis investigated the association between exposure variables per 24 h and subsequent serious adverse events. RESULTS: Serious adverse events occurred in 37% of patients, with 38% occurring during monitoring. Among patients with SAE during monitoring, the median duration of vital sign abnormalities was 272 min (IQR 110-447), compared to 259 min (IQR 153-394) in patients with SAE after monitoring and 261 min (IQR 132-468) in the patients without any SAE (p = .62 for all three group comparisons). Episodes of heart rate ≥110 bpm occurred in 16%, 7.1%, and 3.9% of patients in the time before SAE during monitoring, after monitoring, and without SAE, respectively (p < .002). Patients with SAE after monitoring experienced more episodes of hypotension ≤90 mm Hg/24 h (p = .001). CONCLUSION: Overall duration of vital sign abnormalities at current thresholds were not significantly associated with subsequent serious adverse events, but more patients with tachycardia and hypotension had subsequent serious adverse events. TRIAL REGISTRATION: Clinicaltrials.gov, identifier NCT03491137.

Abdominal Aortic Aneurysm - Disease or a Defect - Patients' Perceptions of Aortic Aneurysm in the Presence of Multimorbidity.

OBJECTIVES: Abdominal aortic aneurysm is associated with substantial comorbidity and significant long-term mortality. Reduction of cardiovascular risk factors and smoking cessation improves prognosis, but implementation of recommendations is suboptimal. Patient's disease-awareness and level of multimorbidity are important factors affecting treatment- adherence. This study explored the perception of disease in patients with abdominal aortic aneurysms and multimorbidity. METHODS: In a qualitative design we assessed patients' perception of aortic aneurysms in the presence of multimorbidity and cardiovascular risk factors. We conducted a workshop including patients from the aneurysm ultrasound-surveillance-program at a tertiary vascular department. Data from the workshop were analyzed using a qualitative exploratory design with an inductive approach. RESULTS: A total of 10 patients with abdominal aortic aneurysm and multimorbidity participated in the workshop. Three categories describing the patient's perception of disease emerged from the analysis. (1) Abdominal aortic aneurysm is not a disease; it is a defect, (2) Someone else is in control, (3) Abdominal aortic aneurysm is an isolated condition. CONCLUSION: Patients with abdominal aortic aneurysms and multimorbidity did not perceive their aneurysm as a disease, but merely as a bodily defect. Growth and rupture of the aneurysm were the main concerns related to the condition, and the participants relied solely on the health professionals to control this by regular ultrasound-surveillance. Consequently, the participants did not perceive abdominal aortic aneurysm as a motivation for cardiovascular risk factor modification by optimization in medication or smoking-cessation.

Non-Vitamin K Antagonist Oral Anticoagulants Versus Warfarin in Atrial Fibrillation Patients With Intracerebral Hemorrhage.

Background and Purpose- Recurrent bleeding associated with oral anticoagulants (OACs) causes a dilemma in patients with atrial fibrillation (AF) sustaining an intracerebral hemorrhage. Treatment recommendations guiding clinical practice on optimal OAC agent selection in this population are lacking. This study aimed to investigate the comparative effectiveness and safety of non-vitamin K antagonist OAC (NOAC) versus warfarin in patients with AF sustaining an intracerebral hemorrhage. Methods- We conducted a nationwide observational cohort study including patients with AF sustaining an intracerebral hemorrhage and who subsequently claimed an OAC prescription. Contrasts of 1-year risks for ischemic stroke and intracerebral hemorrhage risks were obtained and evaluated by inverse probability treatment weighted absolute risk reduction and risk ratios. Results- Among 622 AF patients with intracerebral hemorrhage, 274 claimed a warfarin prescription and 348 a NOAC prescription. Mean age was 76 years (39% females); 72% had an index nonsevere event and 28% moderate to severe index event according to the Scandinavian Stroke Severity scale. The 1-year ischemic stroke risk was 7.85% for warfarin and 4.01% for NOACs, with a weighted absolute risk reduction of 3.78% (95% CI, -0.15% to 7.71%); the weighted risk ratio was 0.52 (0.27-1.00). For recurrent intracerebral hemorrhage, the risk was 7.00% for warfarin and 5.07% for NOACs. The absolute risk reduction was 1.93% (-2.02% to 5.87%), with an a weighted risk ratio of 0.72 (0.38-1.38). Conclusions- NOACs were associated with a nonsignificant lower risk of ischemic stroke and recurrent intracerebral hemorrhage compared with warfarin. The results add to current recommendations of selecting a NOAC agent for stroke prophylaxis treatment in patients with AF, including those with sustaining an intracerebral hemorrhage.

Risk Stratification for Ischemic Cerebrovascular Events and Mortality among Intracerebral Hemorrhage Patients with and without Atrial Fibrillation: A Nationwide Cohort Study.

BACKGROUND: Intracerebral hemorrhage is a devastating clinical event, and secondary prevention is pivotal to avoid further cerebral complications, but no clear guidance exist for selecting high-risk patients. The CHA2DS2-VASc score is a widespread tool to assess the risk of stroke among patients with atrial fibrillation (AF). OBJECTIVES: We investigated the ability of the CHA2DS2-VASc score for estimating cerebrovascular ischemic events in patients with recent intracerebral hemorrhage with or without comorbid AF. METHODS: Patients with a diagnosis of intracerebral hemorrhage between 2003 and 2018 were considered for inclusion. Four registries were linked to obtain individual-level information, and included patients were followed for the occurrence of cerebrovascular ischemic events and all-cause mortality. We report absolute risks at 5 years stratified by baseline CHA2DS2-VASc score and AF prevalence. RESULTS: The study included 12,245 patients (46.4% females) of whom 19% had prevalent AF. Patients without AF were younger (mean age: 70 vs. 78 years) and had a lower CHA2DS2-VASc score (2.5 vs. 3.6). The overall 5-year risk of cerebrovascular ischemic events was 5.2% (95% CI 4.7-5.6) for patients without AF and 7.3% (95% CI 6.0-8.5) for AF patients; all-cause mortality was higher than 30 and 50% in patients without or with AF, respectively. The predictive performance of the CHA2DS2-VASc score was poor with c-statistics around 0.56 regardless of AF status. Among patients without AF, a score ≥6 was associated with a 7.0% risk of cerebrovascular ischemic events. In patients with AF, the associated risk was lowest for patients with a CHA2DS2-VASc score of 1 (4.1%) and highest among those with a score of 5 (11.9%). CONCLUSION: In this nationwide cohort of intracerebral hemorrhage patients with or without AF, the risk of cerebrovascular ischemic events and mortality was substantial. The CHA2DS2-VASc score may be used for the estimation of stroke risk in patients sustaining an intracerebral hemorrhage, although its discriminative performance was poor.

Human papillomavirus infection and lymphoma incidence using cervical conization as a surrogate marker: a Danish nationwide cohort study.

Persistent human papillomavirus (HPV) infection may promote carcinogenesis by hyperactivation of the immune system. We, therefore, explored the associations between HPV infection and risk of Hodgkin and non-Hodgkin lymphoma in a nationwide cohort study using conization as a surrogate marker. We identified all Danish women who underwent conization between 1978 and 2011. We computed standardized incidence ratios and 95% confidence intervals for Hodgkin and non-Hodgkin lymphoma based on national cancer incidence rates. Among 87 435 women who underwent conization, we noted an increased incidence of Hodgkin (standardized incidence ratio 1.48, 95% confidence interval 1.05-2.02) but only a slight increase for non-Hodgkin lymphoma (standardized incidence ratio 1.10, 95% confidence interval 0.97-1.25). As measured by conization, HPV infection is associated with an increased risk of lymphoma. This association may be attributable to a chronic immune activation induced by persistent HPV infection and/or failure of the immune system both to clear HPV infection and to control lymphoma development. Copyright © 2015 John Wiley & Sons, Ltd.

Impact of appropriate empirical antibiotic treatment on recurrence and mortality in patients with bacteraemia: a population-based cohort study.

BACKGROUND: Data on the impact of empirical antibiotic treatment (EAT) on patient outcome in a population-based setting are sparse. We assessed the association between EAT and the risk of recurrence within one year, short-term- (2-30 days) and long-term (31-365 days) mortality in a Danish cohort of bacteraemia patients. METHODS: A cohort study including all patients hospitalized with incident bacteraemia during 2007-2008 in the Copenhagen City and County areas and the North Denmark Region. EAT was defined as the antibiotic treatment given at the 1st notification of a positive blood culture. The definition of recurrence took account of pathogen species, site of infection, and time frame and was not restricted to homologous pathogens. The vital status was determined through the civil registration system. Association estimates between EAT and the outcomes were estimated by Cox and logistic regression models. RESULTS: In 6483 eligible patients, 712 (11%) had a recurrent episode. A total of 3778 (58%) patients received appropriate EAT, 1290 (20%) received inappropriate EAT, while EAT status was unrecorded for 1415 (22%) patients. The 2-30 day mortality was 15.1%, 17.4% and 19.2% in patients receiving appropriate EAT, inappropriate EAT, and unknown EAT, respectively. Among patients alive on day 30, the 31-365 day mortality was 22.3% in patients given appropriate EAT compared to 30.7% in those given inappropriate EAT. Inappropriate EAT was independently associated with recurrence (HR 1.25; 95% CI = 1.03-1.52) and long-term mortality (OR 1.35; 95% CI = 1.10-1.60), but not with short-term mortality (OR 0.85; 95% CI = 0.70-1.02) after bacteraemia. CONCLUSIONS: Our data indicate that appropriate EAT is associated with reduced incidence of recurrence and lower long-term mortality following bacteraemia.

Microbiological point of care testing before antibiotic prescribing in primary care: considerable variations between practices.

BACKGROUND: Point-of-care testing (POCT) in primary care may improve rational antibiotic prescribing. We examined use of POCT in Denmark, including patient- and general practitioner (GP)-related predictors. METHODS: We linked nationwide health care databases to assess POCT use (C-reactive protein (CRP), group A streptococcal (GAS) antigen swabs, bacteriological cultures, and urine test strips) per 1,000 overall GP consultations, 2004-2013. We computed odds ratios (OR) of POCT in patients prescribed antibiotics according to patient and GP age and sex, GP practice type, location, and workload. RESULTS: The overall use of POCT in Denmark increased by 45.8% during 2004-2013, from 147.2 per 1,000 overall consultations to 214.8. CRP tests increased by 132%, bacteriological cultures by 101.7% while GAS swabs decreased by 8.6%. POCT preceded 28% of antibiotic prescriptions in 2004 increasing to 44% in 2013. The use of POCT varied more than 5-fold among individual practices, from 54.9 to 394.7 per 1,000 consultations in 2013. POCT use varied substantially with patient age, and males were less likely to receive POCT than females (adjusted OR = 0.75, 95% CI 0.74-0.75) driven by usage of urine test strips among females (18% vs. 7%). Odds of POCT were higher among female GPs and decreased with higher GP age, with lowest usage among male GPs >60 years. GP urban/rural location and workload had little impact. CONCLUSION: GPs use POCT increasingly with the highest use among young female GPs. In 2013, 44% of all antibiotic prescriptions were preceded by POCT but testing rates vary greatly across individual GPs.