High Incidence of Cardiovascular Disease in Patients With Oesophageal Cancer-A Registry-Based Cohort Study.

BACKGROUND: The cardiovascular disease (CVD) burden among patients with oesophageal cancer (EC) treated with curative intent is unclear. AIM: To determine CVD incidence and all-cause mortality in patients with EC. METHOD: Danish national health registries were used to identify patients diagnosed with primary EC between 2008 and 2018. Each EC patient was matched with 10 individuals from the general population. The primary endpoint was a CVD hospital contact (CVD-HC), either admission or outpatient contact. Cox proportional hazard regression models were used to compare the risk of incident CVD-HCs between the cohorts. RESULTS: The study included 1,525 patients with EC and 15,250 individuals from the general population. Patients with EC had a post-diagnosis one-year adjusted hazard ratio (HR) of CVD-HC of 6.1 (95% confidence intervals [CIs] 5.6-6.8) compared with the general population. During the next nine years, the risk of CVD-HC was comparable between the two cohorts, with an adjusted HR of 1.0 (95% CI 0.9-1.3). Patients with EC, and particularly those with prevalent CVD, had a high risk of atrial fibrillation, ischaemic heart disease, and venous thromboembolism within the first year after EC diagnosis. Prevalent CVD among patients with EC was not associated with higher mortality. CONCLUSIONS: CVD morbidity was transiently increased in the first year following EC diagnosis compared with the general population. All-cause mortality risks were high but did not appear to be affected by prevalent CVD. The very high risk of CVD in patients with primary EC to be treated with curative intent calls for healthcare initiatives to advance preventive and post-treatment strategies.

Transport Strategy in Patients With Suspected Acute Large Vessel Occlusion Stroke: TRIAGE-STROKE, a Randomized Clinical Trial.

BACKGROUND: When patients with acute ischemic stroke present with suspected large vessel occlusion in the catchment area of a primary stroke center (PSC), the benefit of direct transport to a comprehensive stroke center (CSC) has been suggested. Equipoise remains between transport strategies and the best transport strategy is not well established. METHODS: We conducted a national investigator-driven, multicenter, randomized, assessor-blinded clinical trial. Patients eligible for intravenous thrombolysis (IVT) who were suspected for large vessel occlusion were randomized 1:1 to admission to the nearest PSC (prioritizing IVT) or direct CSC admission (prioritizing endovascular therapy). The primary outcome was functional improvement at day 90 for all patients with acute ischemic stroke, measured as shift towards a lower score on the modified Rankin Scale score. RESULTS: From September 2018 to May 2022, we enrolled 171 patients of whom 104 had acute ischemic stroke. The trial was halted before full recruitment. Baseline characteristics were well balanced. Primary analysis of shift in modified Rankin Scale (ordinal logistic regression) revealed an odds ratio for functional improvement at day 90 of 1.42 (95% CI, 0.72-2.82, P=0.31). Onset to groin time for patients with large vessel occlusion was 35 minutes (P=0.007) shorter when patients were transported to a CSC first, whereas onset to needle (IVT) was 30 minutes (P=0.012) shorter when patients were transported to PSC first. IVT was administered in 67% of patients in the PSC group versus 78% in the CSC group and EVT was performed in 53% versus 63% of the patients, respectively. CONCLUSIONS: This trial investigated the benefit of bypassing PSC. We included only IVT-eligible patients presenting <4 hours from onset and with suspected large vessel occlusion. Lack of power prevented the results from showing effect on functional outcome for patients going directly to CSC. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03542188.

Time trends in income-related disparity in incidence of acute coronary syndrome.

BACKGROUND: Higher incidence of acute coronary syndrome (ACS), among those with lower income, has been recognized in the most recent decades. Still, there is a paucity of data on temporal changes. This study aims to investigate 20-year time trends in income-related disparity in the incidence of ACS in Denmark. METHODS: This Population-based repeated cross-sectional study included all patients with first-time ACS, aged ≥20 years, registered in the Danish National Patient Registry 1998-2017. Aggregated sociodemographic data for the Danish population was accessed from Statistics Denmark. Yearly incidence rates (IR) and incidence rate ratios (IRR), with the highest-income quartile as a reference, were standardized using cell-specific personal equivalent income according to year, sex and age group with 95% confidence intervals. Interaction analysis was executed for differences in IR of ACS between the lowest- and highest-income quartile over time. RESULTS: A total of 220 070 patients hospitalized with ACS from 1998 to 2017 were identified. The yearly standardized ACS IRs decreased in all income quartiles. However, the IR remained higher in the lowest-income quartile compared to the highest for both men [1998: IRR 1.45 (95% confidence interval, CI 1.39-1.52) and 2017: 1.47 (1.40-1.54)] and women [1998: IRR 1.73 (1.64-1.82) and 2017: 1.76 (1.65-1.88)]. Interaction analysis showed that over the period the difference in IR between the lower- and the highest-income quartile decreased with 1-5 ACS cases per 100 000 person-year. CONCLUSION: Income-related disparity in the incidence of ACS was present in Denmark between 1998 and 2017. Despite a marked overall decrease in the yearly ACS incidence, the extent of income-related disparity remained unchanged.

Longitudinal outcomes in pediatric- and adult-onset bipolar patients compared to healthy and schizophrenia controls.

OBJECTIVES: Comparing outcomes of bipolar disorder (BD) with schizophrenia (SCZ) and psychiatrically healthy controls (PHC), contrasting pediatric-onset with adult-onset disorders. METHODS: A nationwide cohort study, including patients with an incident diagnosis of BD or SCZ registered in the Danish National Patient Registry and corresponding PHCs. Outcomes were (a) duration of hospitalization, (b) psychiatric admissions, (c) psychiatric outpatient contacts, (d) bone-fracture-related healthcare contacts, (e) self-harm-related healthcare contacts (including suicide and non-suicidal self-injuries), and (f) criminal charges. Incidence rate ratios (IRRs), adjusted for age at first psychiatric contact, substance abuse and parental psychiatric illness, were calculated, comparing pediatric-onset BD (5-17 years) and adult-onset BD (18-39 years) with age- and sex-matched SCZ patients and PHC. RESULTS: Pediatric-onset BD (n = 349) performed better than 1:1-matched pediatric-onset SCZ (n = 349) on all six outcomes (IRR = 0.30 for self-harm-related contacts (P < 0.001) to IRR = 0.86 for criminal charges (P = 0.05). Similar, but less pronounced results were observed comparing 1:1-matched adult-onset BD (n = 5515) with adult-onset SCZ (n = 5515) IRR = 0.58 for psychiatric outpatient contact (P < 0.001) to IRR = 0.93 for criminal charges (P < 0.001), except for more bone-fracture-related contacts in adult-onset BD (IRR = 1.13, P < 0.01). Comparing pediatric-onset BD (n = 365) to 1:3-matched PHC (n = 1095), only self-harm-related contacts differed significantly (IRR = 2.80, P < 0.001). Conversely, comparing adult-onset BD (n = 6005) with 1:3-matched PHC (n = 18 015), self-harm-related contacts (IRR = 16.68, P < 0.001), bone fractures (IRR = 1.74, P < 0.001), and criminal charges (IRR = 2.03, P < 0.001) were more common in BD. CONCLUSION: BD was associated with poorer outcomes than PHC, but better outcomes than SCZ. Furthermore, outcomes were more favorable in pediatric-onset BD when indirectly contrasted to adult-onset BD.

An outreach collaborative model for early identification and treatment of mental disorder in Danish workplaces.

BACKGROUND: Depression and anxiety are prevalent mental disorders among the working population with potentially high personal and financial cost. The overall aim of this study was to test the applicability of an outreach collaborative model for early identification and treatment of clinical and sub-clinical mental disorders among Danish employees. This applicability was examined by I) investigating the fractions of identified and treated clinical and subclinical cases, II) describing the distribution and characteristics of cases identified and III) investigating the effect of allocated treatment. METHODS: A longitudinal study design with four assessments (T0-T3) over 16 months was applied. Self-reporting questionnaires probing for psychopathology were distributed to all employees in six consecutively enrolled companies at the four time points. Employees meeting the screening criteria at T1 were assessed diagnostically. Subjects diagnosed with a clinical mental disorder were allocated to outpatient psychiatric treatment, and subjects with subclinical conditions were allocated to preventive cognitive behavioural therapy. Follow-up was conducted 6 and 12 months after initiation of treatment. We used chi-squared test and F-test to compare the different groups on baseline characteristics and mixed effects linear regression to analyse the treatment effects. RESULTS: Forty (6.8%) of the 586 responders at T1 were diagnosed with a clinical mental disorder and referred to outpatient psychiatric treatment. Thirty-three (5.6%) were affected by a subclinical condition and referred to preventive treatment. Nearly two-thirds (63%) of the employees diagnosed with a clinical condition had never received treatment before. Symptom severity decreased significantly for both treated groups until follow-up. When compared to a composed control group, subclinical cases displayed a more rapid initial significant symptomatic decrease on the global symptom scale (coefs = - 0.914, 95% CI [- 1.754, - 0,075]) and anxiety sub-scale (coefs = - 1.043, 95% CI [- 2.021, - 0.066]). This did not apply to the clinical cases as no significant difference in change were identified. CONCLUSIONS: The outreach collaborative model demonstrated an applicability to identify both clinical and subclinical cases, among these a high number of employees with an unmet need for treatment. We found evidence of a positive initial effect on symptomatology from the allocated preventive treatment among the subclinical cases, but not for clinical cases. TRIAL REGISTRATION: Retrospectively registered at December 18, 2018 at clinicaltrials.gov, identifier: NCT03786328 .

Formulation of probabilistic models of protein structure in atomic detail using the reference ratio method.

We propose a method to formulate probabilistic models of protein structure in atomic detail, for a given amino acid sequence, based on Bayesian principles, while retaining a close link to physics. We start from two previously developed probabilistic models of protein structure on a local length scale, which concern the dihedral angles in main chain and side chains, respectively. Conceptually, this constitutes a probabilistic and continuous alternative to the use of discrete fragment and rotamer libraries. The local model is combined with a nonlocal model that involves a small number of energy terms according to a physical force field, and some information on the overall secondary structure content. In this initial study we focus on the formulation of the joint model and the evaluation of the use of an energy vector as a descriptor of a protein's nonlocal structure; hence, we derive the parameters of the nonlocal model from the native structure without loss of generality. The local and nonlocal models are combined using the reference ratio method, which is a well-justified probabilistic construction. For evaluation, we use the resulting joint models to predict the structure of four proteins. The results indicate that the proposed method and the probabilistic models show considerable promise for probabilistic protein structure prediction and related applications.

PHAISTOS: a framework for Markov chain Monte Carlo simulation and inference of protein structure.

We present a new software framework for Markov chain Monte Carlo sampling for simulation, prediction, and inference of protein structure. The software package contains implementations of recent advances in Monte Carlo methodology, such as efficient local updates and sampling from probabilistic models of local protein structure. These models form a probabilistic alternative to the widely used fragment and rotamer libraries. Combined with an easily extendible software architecture, this makes PHAISTOS well suited for Bayesian inference of protein structure from sequence and/or experimental data. Currently, two force-fields are available within the framework: PROFASI and OPLS-AA/L, the latter including the generalized Born surface area solvent model. A flexible command-line and configuration-file interface allows users quickly to set up simulations with the desired configuration. PHAISTOS is released under the GNU General Public License v3.0. Source code and documentation are freely available from http://phaistos.sourceforge.net. The software is implemented in C++ and has been tested on Linux and OSX platforms.

An AI-based patient-specific clinical decision support system for OA patients choosing surgery or not: study protocol for a single-centre, parallel-group, non-inferiority randomised controlled trial.

BACKGROUND: Osteoarthritis (OA) affects 20% of the adult Danish population, and the financial burden to society amounts to DKK 4.6 billion annually. Research suggests that up to 75% of surgical patients could have postponed an operation and managed with physical training. ERVIN.2 is an artificial intelligence (AI)-based clinical support system that addresses this problem by enhancing patient involvement in decisions concerning surgical knee and hip replacement. However, the clinical outcomes and cost-effectiveness of using such a system are scantily documented. OBJECTIVE: The primary objective is to investigate whether the usual care is non-inferior to ERVIN.2 supported care. The second objective is to determine if ERVIN.2 enhances clinical decision support and whether ERVIN.2 supported care is cost-effective. METHODS: This study used a single-centre, non-inferiority, randomised controlled in a two-arm parallel-group design. The study will be reported in compliance with CONSORT guidelines. The control group receives the usual care. As an add-on, the intervention group have access to baseline scores and predicted Oxford hip/knee scores and HRQoL for both the surgical and the non-surgical trajectory. A cost-utility analysis will be conducted alongside the trial using a hospital perspective, a 1-year time horizon and effects estimated using EQ-5D-3L. Results will be presented as cost per QALY gain. DISCUSSION: This study will bring knowledge about whether ERVIN.2 enhances clinical decision support, clinical effects, and cost-effectiveness of the AI system. The study design will not allow for the blinding of surgeons. TRIAL REGISTRATION: ClinicalTrials.gov NCT04332055 . Registered on 2 April 2020.

Diagnostic performance of Glial Fibrillary Acidic Protein and Prehospital Stroke Scale for identification of stroke and stroke subtypes in an unselected patient cohort with symptom onset < 4.5 h.

INTRODUCTION: Rapid identification and treatment of stroke is crucial for the outcome of the patient. We aimed to determine the performance of glial fibrillary acidic protein (GFAP) independently and in combination with the Prehospital Stroke Score (PreSS) for identification and differentiation of acute stroke within 4.5 h after symptom onset. PATIENTS AND METHODS: Clinical data and serum samples were collected from the Treat-Norwegian Acute Stroke Prehospital Project (Treat-NASPP). Patients with suspected stroke and symptoms lasting ≤ 4.5 h had blood samples collected and were evaluated with the National Institutes of Health Stroke Scale prospectively. In this sub study, NIHSS was retrospectively translated into PreSS and GFAP was measured using the sensitive single molecule array (SIMOA). RESULTS: A total of 299 patients with suspected stroke were recruited from Treat-NASPP and included in this study (44% acute ischemic stroke (AIS), 10% intracranial hemorrhage (ICrH), 7% transient ischemic attack (TIA), and 38% stroke mimics). ICrH was identified with a cross-fold validated area under the receiver-operating characteristic curve (AUC) of 0.73 (95% CI 0.62-0.84). A decision tree with PreSS and GFAP combined, first identified patients with a low probability of stroke. Subsequently, GFAP detected patients with ICrH with a 25.0% sensitivity (95% CI 11.5-43.4) and 100.0% specificity (95% CI 98.6-100.0). Lastly, patients with large-vessel occlusion (LVO) were detected with a 55.6% sensitivity (95% CI 35.3-74.5) and 82.4% specificity (95% CI 77.3-86.7). CONCLUSION: In unselected patients with suspected stroke, GFAP alone identified ICrH. Combined in a decision tree, GFAP and PreSS identified subgroups with high proportions of stroke mimics, ICrH, LVO, and AIS (non-LVO strokes).

Temporal trends in socioeconomic disparity in clinical outcomes for patients with acute coronary syndrome.

AIMS: Socioeconomic factors are well-established determinants of clinical outcomes among patients with acute coronary syndrome (ACS) although quality of care has improved the last decades. This study aims to investigate 20-years temporal trends of socioeconomic disparity in 1-year incidence of major adverse cardiac events (MACE) among ACS patients in Denmark. METHODS: This population-based cohort study included all incident ACS patients in the Danish National Patient Registry during 1998-2017. Socioeconomic disparity was assessed by income and educational level. Patients were followed 1-year for MACE; defined as all-cause mortality, recurrent ACS, revascularization, stroke, or cardiac arrest. Adjusted MACE incidence rates (aIR) and hazard rate ratios (aHR) were computed with 95 % confidence intervals (CI) for five-year-periods. Changes in trends were examined from interaction analyses between the HR for five-year-periods and income and education, respectively. RESULTS: The study included 220,887 patients with first-time ACS. The incidence of MACE decreased within all income and education levels. In 1998-2002 the MACE aIR among patients with low income was 885[95%CI:863-907] versus 733[711-756]/1000-person-year among those with high income (aHR: 1.19[95%CI:1.15-1.23]). The aIRs decreased to 506[489-522] and 405[388-423]/1000-person-year, respectively, in 2013-2017 (aHR: 1.23[1.17-1.29]). The aIRs of MACE decreased correspondingly within all educational levels from 1998 to 2002 to 2013-2017. However, the socioeconomic disparity according to the interaction analyses persisted both according to income and educational level. CONCLUSION: Although 1-year clinical outcomes following ACS has improved substantially over the last decades, socioeconomic disparity persisted both according to income and education level.

Associations between emergency call stroke triage and pre-hospital delay, primary hospital admission, and acute reperfusion treatment among early comers with acute ischemic stroke.

To investigate the association between the Emergency Medical Service dispatcher's initial stroke triage and prehospital stroke management, primary admission to hospitals offering revascularization treatment, prehospital time delay, and rate of acute revascularization. In an observational cohort study, patients with acute ischemic stroke (AIS) in Denmark (2017-2018) were included if the emergency call to the Emergency Medical Dispatch Center (EMDC) was made within three hours after symptom onset. Among 3546 included AIS patients, the EMS dispatcher identified 74.6% (95% confidence interval (CI) 73.1-76.0) correctly as stroke. EMS dispatcher stroke recognition was associated with a higher rate of primary admission to a hospital offering revascularization treatment (85.8 versus 74.5%); producing an adjusted risk difference (RD) of 11.1% (95% CI 7.8; 14.3) and a higher rate of revascularization treatment (49.6 versus 41.6%) with an adjusted RD of 8.4% (95% CI 4.6; 12.2). We adjusted for sex, age, previous stroke or transient ischemic attack, and stroke severity. EMDC stroke recognition was associated with shorter prehospital delay. For all AIS patients, the adjusted difference was - 33.2 min (95% CI - 44.4; - 22.0). Among patients receiving acute revascularization treatment (n = 1687), the adjusted difference was -12.6 min (95% CI - 18.9; - 6.3). Stroke recognition by the EMS dispatcher was associated with a higher probability of primary admission to a hospital offering acute stroke treatment, and subsequently with a higher rate of acute revascularization treatment, and with an overall reduction in prehospital delay.

Evidence-Based Process Performance Measures and Clinical Outcomes in Patients With Incident Heart Failure With Reduced Ejection Fraction: A Danish Nationwide Cohort Study.

BACKGROUND: Data on the association between quality of heart failure (HF) care and outcomes among patients with incident HF are sparse. We examined the association between process performance measures and clinical outcomes in patients with incident HF with reduced ejection fraction. METHODS: Patients with incident HF with reduced ejection fraction (n=10 966) between January 2008 and October 2015 were identified from the Danish HF Registry. Data from public registries were linked. Multivariable regression analyses were used to assess the association between 6 guideline-recommended HF care processes (New York Heart Association assessment, use of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, beta-blockers, and mineralocorticoid receptor antagonists, exercise training, and patient education) and all-cause and HF readmission, all-cause and HF hospital days, and mortality within 3 to 12 months after HF diagnosis. The associations were analyzed according to the percentages of all relevant performance measures fulfilled for the individual patient (0%-50% [reference group], >50%-75%, and >75%-100%) and for the individual performance measures. RESULTS: Fulfilling >75% to 100% of the performance measures (n=5341 [48.7%]) was associated with lower risk of all-cause readmission (adjusted hazard ratio, 0.78 [95% CI, 0.68-0.89]) and HF readmission (adjusted hazard ratio, 0.71 [95% CI, 0.54-0.92]), lower use of all-cause hospital days (adjusted mean ratio, 0.73 [95% CI, 0.70-0.76]) and HF hospital days (adjusted mean ratio, 0.79 [95% CI, 0.70-0.89]), and lower mortality (adjusted hazard ratio, 0.42 [95% CI, 0.32-0.53]). A dose-response relationship was observed between fulfilling more performance measures and mortality (adjusted hazard ratio, 0.62 [95% CI, 0.49-0.77] fulfilling >50%-75% of the measures). Fulfilling individual performance measures, except mineralocorticoid receptor antagonist therapy, was associated with lower adjusted all-cause readmission, lower adjusted use of all-cause and HF hospital days, and lower adjusted mortality. CONCLUSIONS: Fulfilling more process performance measures was associated with better clinical outcomes in patients with incident HF with reduced ejection fraction.

Real-world effects of anti-dementia treatment on mortality in patients with Alzheimer´s dementia.

To examine the real-world effects of the cholinesterase inhibitors (AChEI) on all-cause mortality. A nationwide, retrospective cohort study. Participants were diagnosed with incident AD in Denmark from January 1, 2000 to December 31, 2011 with follow-up until December 31, 2012. A total of 36,513 participants were included in the current study with 22,063 deaths during 132,426 person-years of follow-up. At baseline, patients not treated with AChEI (n = 28,755 [9961 males (35%)]) had a mean age ±â€…standard deviation (SD) of 80.33 ±â€…7.98 years (78.97 ±â€…8.26 for males and 81.04 ±â€…7.98 for females), as compared to 79.95 ±â€…7.67 (78.87 ±â€…7.61 for males and 80.61 ±â€…7.63 for females) in the group exposed at baseline. Patients treated with AChEI had a beneficial hazard ratio (HR) of 0.69, 95% confidence interval (CI) (0.67-0.71) for all-cause mortality as compared to patients not treated, with donepezil (HR 0.80, 95% CI [0.77-0.82]) and galantamine (HR 0.93,95% CI [0.89-0.97]) having beneficial effects on mortality rate as compared to non-treatment, whereas rivastigmine (HR 0.99, 95% CI [0.95-1.03]) was associated with a mortality rate comparable to non-treatment with AChEI. Patients were primarily exposed to donepezil (65.8%) with rivastigmine (19.8%) and galantamine (14.4%) being used less often. These findings underscore the effect of AChEI on not only reducing speed of cognitive decline but also directly prolonging life, which could result in changes in treatment recommendation for when to stop treatment.

Survival after aortic root replacement with a stentless xenograft is determined by patient characteristics.

OBJECTIVES: Our objective was to examine intermediate-term survival and reinterventions in unselected patients, stratified according to indication, who received a Freestyle (Medtronic Inc, Minneapolis, Minn) bioprosthesis as a full aortic root replacement. METHODS: Data from medical records were retrospectively collected for patients who had aortic root replacement using Freestyle bioprostheses between 1999 and 2018 at 6 North-Atlantic centers. Survival status was extracted from national registries and results stratified according to indication for surgery. RESULTS: We included 1030 implantations in 1008 patients with elective indications for surgery: aneurysm (39.8%), small root (8.3%), and other (13.8%), and urgent/emergent indications: endocarditis (26.7%) and Stanford type A aortic dissection (11.4%). Across indications, 46.3% were nonelective cases and 34.0% were reoperations. Median age was 66.0 (interquartile range, 58.0-71.8) years and median follow-up was 5.0 (interquartile range, 2.6-7.9) years. Thirty-day mortality varied from 2.9% to 27.4% depending on indication. Intermediate survival for 90-day survivors with elective indications were not different from the general population standardized for age and sex (P = .95, .83, and .16 for aneurysms, small roots, and other, respectively). In contrast, patients with endocarditis and type A dissection had excess mortality (P < .001). Freedom from valve reinterventions was 95.0% and 94.4% at 5 and 8 years, respectively. In all, 52 patients (5.2%) underwent reinterventions, most because of endocarditis. CONCLUSIONS: At intermediate term follow-up this retrospective study provides further support for the use of the Freestyle bioprosthesis in the real-world setting of diverse, complex, and often high-risk aortic root replacement and suggests that outcome is determined by patient and disease, rather than by prosthesis, characteristics.

Inequalities in heart failure care in a tax-financed universal healthcare system: a nationwide population-based cohort study.

AIMS: Data on socioeconomic-related differences in heart failure (HF) care are sparse. Inequality in care may potentially contribute to a poor clinical outcome. We examined socioeconomic-related differences in quality of HF care among patients with incident HF with reduced ejection fraction (EF) (HFrEF). METHODS AND RESULTS: We conducted a nationwide population-based cohort study among patients with HFrEF (EF ≤40%) registered from January 2008 to October 2015 in the Danish Heart Failure Registry, a nationwide registry of patients with a first-time primary HF diagnosis. Associations between individual-level socioeconomic factors (cohabitation status, education, and family income) and the quality of HF care defined by six guideline-recommended process performance measures [New York Heart Association (NYHA) classification, treatment with angiotensin-converting-enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB), beta-blockers and mineralocorticoid receptor antagonists, exercise training, and patient education] were assessed using multiple imputation and multivariable logistic regression controlling for potential confounders. Among 17 122 HFrEF patients included, 15 290 patients had data on all six process performance measures. Living alone was associated with lower odds of NYHA classification [adjusted OR (aOR) 0.81; 95% confidence interval (CI): 0.72-0.90], prescription of ACEI/ARB (aOR 0.76; 95% CI: 0.68-0.88) and beta-blockers (aOR 0.84; 95% CI: 0.76-0.93), referral to exercise training (aOR 0.75; 95% CI: 0.69-0.81), and patient education (aOR 0.73; 95% CI: 0.67-0.80). Compared with high-level education, low-level education was associated with lower odds of NYHA classification (aOR 0.93; 95% CI: 0.79-1.11), treatment with ACEI/ARB (aOR 0.99; 95% CI: 0.81-1.20) and beta-blockers (aOR 0.93; 95% CI: 0.79-1.09), referral to exercise training (aOR 0.73; 95% CI: 0.65-0.82), and patient education (aOR 0.86, 95% CI: 0.75-0.98). An income in the lowest tertile was associated with lower odds of NYHA classification (aOR 0.67; 95% CI: 0.58-0.79), prescription of ACEI/ARB (aOR 0.80, 95% CI: 0.67-0.95) and beta-blockers (aOR 0.88, 95% CI: 0.86-1.01), referral to exercise training (aOR 0.59, 95% CI: 0.53-0.64), and patient education (aOR 0.66; 95% CI: 0.59-0.74) compared with an income in the highest tertile. Overall, no systematic differences were seen when the analyses were stratified by sex and age groups. CONCLUSIONS: Living alone, low-level education, and income in the lowest tertile were associated with reduced use of recommended processes of HF care among Danish HFrEF patients with a first-time primary HF diagnosis. Efforts are warranted to ensure guideline-recommended HF care to all HFrEF patients, irrespective of socioeconomic background.

A multicentre, randomised, sham-controlled trial on REmote iSchemic conditioning In patients with acute STroke (RESIST) - Rationale and study design.

RATIONALE: Remote ischaemic conditioning, applied in the prehospital setting and continued in-hospital, may improve functional outcome in patients with acute ischaemic stroke and intracerebral haemorrhage. AIMS: To evaluate whether combined remote ischaemic per- and postconditioning can improve long-term functional outcome in acute ischaemic stroke and intracerebral haemorrhage patients. METHODS AND DESIGN: Danish multicentre, prospective, randomised, patient-assessor blinded, sham-controlled study. Adult patients with a putative stroke identified prehospital with symptom duration <4 h, who are independent in daily activities will be randomised 1:1 to remote ischaemic conditioning or Sham-remote ischaemic conditioning. The treatment protocol will be five cycles, each consisting of 5 min with a blood pressure cuff inflation and 5 min with a deflated cuff placed on the upper extremity. The cuff pressure for remote ischaemic conditioning will be 200 mmHg-285 mmHg according to the individual systolic blood pressure and 20 mmHg sham-remote ischaemic conditioning during inflation. The study is approved as an acute study and consent is waived in the acute phase.Sample size estimation: For a 7% increased odds for a beneficial shift on the modified Rankin Scale at a significance level of 5% and power of 90%, 1000 patients with a target diagnosis of acute ischaemic stroke and intracerebral haemorrhage and a total of 1500 patients with a prehospital presumed stroke will be included.Study outcomes: The primary outcome will be the modified Rankin Scale score measured at three-month follow-up (analysed using ordinal logistic regression). ClinicalTrials.gov Identifier: NCT03481777.

TRIAGE-STROKE: Treatment strategy In Acute larGE vessel occlusion: Prioritize IV or endovascular treatment-A randomized trial.

RATIONALE: For patients with acute ischemic stroke and large vessel occlusions, intravenous thrombolysis and endovascular therapy are standard of care, but the effect of endovascular therapy is superior to intravenous thrombolysis. If a severe stroke with symptoms indicating large vessel occlusions occurs in the catchment area of a primary stroke center, there is equipoise regarding optimal transport strategy. AIM: For patients presenting with suspected large vessel occlusions (PASS ≥ 2) and a final diagnosis of acute ischemic stroke, we hypothesize that bypassing the primary stroke center will result in an improved 90-day functional outcome. SAMPLE SIZE: We aim to randomize 600 patients, 1:1. DESIGN: A national investigator-driven, multi-center, randomized assessor-blinded clinical trial. The Prehospital Acute Stroke Severity Scale has been developed. It identifies most patients with large vessel occlusions in the pre-hospital setting. Patients without a contraindication for intravenous thrombolysis are randomized to either transport directly to a comprehensive stroke centers for intravenous thrombolysis and of endovascular therapy or to a primary stroke center for intravenous thrombolysis and subsequent transport to a comprehensive stroke centers for of endovascular therapy, if needed. OUTCOMES: The primary outcome will be the 90-day modified Rankin Scale score (mRS) for all patients with acute ischemic stroke. Secondary outcomes include 90-day mRS for all randomized patients, all patients with ischemic stroke but without large vessel occlusions, and patients with hemorrhagic stroke. The safety outcomes include severe dependency or death and time to intravenous thrombolysis for ischemic stroke patients. DISCUSSION: Study results will influence decision making regarding transport strategy for patients with suspected large vessel occlusions.

Blood Pressure Thresholds and Neurologic Outcomes After Endovascular Therapy for Acute Ischemic Stroke: An Analysis of Individual Patient Data From 3 Randomized Clinical Trials.

Importance: The optimal blood pressure targets during endovascular therapy (EVT) for acute ischemic stroke (AIS) are unknown. Objective: To study whether procedural blood pressure parameters, including specific blood pressure thresholds, are associated with neurologic outcomes after EVT. Design, Setting, and Participants: This retrospective cohort study included adults with anterior-circulation AIS who were enrolled in randomized clinical trials assessing anesthetic strategy for EVT between February 2014 and February 2017. The trials had comparable blood pressure protocols, and patients were followed up for 90 days. A total of 3630 patients were initially approached, and 3265 patients were excluded. Exposure: Endovascular therapy. Main Outcomes and Measures: The primary efficacy variable was functional outcome as defined by the modified Rankin Scale (mRS) score at 90 days. Associations of blood pressure parameters and time less than and greater than mean arterial blood pressure (MABP) thresholds with outcome were analyzed. Results: Of the 365 patients included in the analysis, the mean (SD) age was 71.4 (13.0) years, 163 were women (44.6%), and the median National Institutes of Health Stroke Scale score was 17 (interquartile range [IQR], 14-21). For the entire cohort, 182 (49.9%) received general anesthesia and 183 (50.1%) received procedural sedation. A cumulated period of minimum 10 minutes with less than 70 mm Hg MABP (adjusted OR, 1.51; 95% CI, 1.02-2.22) and a continuous episode of minimum 20 minutes with less than 70 mm Hg MABP (adjusted OR, 2.30; 95% CI, 1.11-4.75) were associated with a shift toward higher 90-day mRS scores, corresponding to a number needed to harm of 10 and 4, respectively. A cumulated period of minimum 45 minutes with greater than 90 mm Hg MABP (adjusted OR, 1.49; 95% CI, 1.11-2.02) and a continuous episode of minimum 115 minutes with greater than 90 mm Hg MABP (adjusted OR, 1.89; 95% CI, 1.01-3.54) were associated with a shift toward higher 90-day mRS scores, corresponding to a number needed to harm of 10 and 6, respectively. Conclusions and Relevance: Critical MABP thresholds and durations for poor outcome were found to be MABP less than 70 mm Hg for more than 10 minutes and MABP greater than 90 mm Hg for more than 45 minutes, both durations with a number needed to harm of 10 patients. Mean arterial blood pressure may be a modifiable therapeutic target to prevent or reduce poor functional outcome after EVT.

Outcomes Following Adherence to a Randomized Stroke Trial Protocol.

This secondary analysis of a randomized clinical trial assesses whether compliance with the study protocol is associated with a better functional outcome even among participants in the sham-control group.

Effects of Antipsychotics on Secular Mortality Trends in Patients With Alzheimer's Disease.

OBJECTIVE: To investigate secular changes in mortality rates between patients with Alzheimer's disease (AD) and the general population as well as changes in antipsychotic drug treatment and the association between drug treatment and mortality in patients with AD in Denmark during a 12-year study period. METHODS: This nationwide, retrospective cohort study identified all-cause mortality in all Danish patients with incident ICD-10-defined AD from 2000 through 2011. The cumulative antipsychotic dosages from dementia diagnosis until end of study for each participant were calculated and categorized in 1 of 5 groups per the World Health Organization Defined Daily Doses (DDDs). Data were obtained from relevant Danish national registers. RESULTS: The study included 32,001 patients (11,194 male and 20,807 female). During the study period, an increasing trend was found in median survival time, but no decline was seen in standardized mortality ratios, which spanned from 1.19 (95% CI, 0.98-1.46) in 2001 to 1.52 (95% CI, 1.38-1.68) in 2011. The findings showed a decline in proportion of patients with incident AD exposed to antipsychotic drugs as well as decline in mean annual cumulative DDDs. Adjusted Cox regression analyses revealed that current exposure to antipsychotic drugs was associated with increased mortality, although hazard ratios declined during the study period from 2.24 (95% CI, 2.07-2.43) in 2000-2002 to 1.24 (95% CI, 1.09-1.41) in 2009-2011, with P values < .001. CONCLUSIONS: These findings appear to underscore the current guideline recommendations for using antipsychotic drugs at only the lowest effective dose and only in patients for whom all non-pharmacologic options have been exhausted. Furthermore, these results seem to indicate that the reduced use of antipsychotic drugs has no impact on relative mortality, suggesting that the AD population has gained less from improvements in care of other diseases that impact mortality rates in patients with AD as well as in the general population.