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BACKGROUND: It has previously been described that fall-associated injuries including fractures are commonly observed among patients with bradyarrhythmia. However, knowledge on the risk of pacemaker implantation after admission due to femur fracture from large population-based epidemiologic data is lacking. Therefore, we investigated the risk of pacemaker implantation following femur fracture in patients with and without a history of previous syncope. METHODS All patients with femur fracture between 2005-2017 were identified using the Danish Nationwide Patient Registry. Among these, patients already having a pacemaker were excluded. Primary outcome was one-year risk of pacemaker implantation and secondary outcome was one-year all-cause mortality. Multivariable logistic regression was used to obtain absolute and relative risks of the study endpoint in relation to patients with versus without history of syncope and standardized to the age, sex, selected comorbidity and pharmacotherapy distribution of all patients. RESULTS Of 93,093 patients with femur fracture, 5508 (5.9%) had a history of syncope within five years. Patients with prior syncope were slightly older (84 vs. 83 years), more often male (33.6% vs. 29.4%), and had more often comorbidities relative to those without history of syncope. All-cause mortality was significantly higher among those with previous history of syncope compared to those without previous syncope (29.9% vs. 28.6%, P = 0.021). The relative mortality risk was 1.05 (95% CI: 1.01-1.09, P = 0.021). A total of 695 (0.8%) patients underwent pacemaker implantation within 5 years following femur fracture, and a significantly higher proportion of patients with syncope had a pacemaker implanted within one year (1.6% vs. 0.7%, P < 0.001; relative risk, 2.01 [95% CI: 1.55-2.46]). CONCLUSIONS In patients with femur fracture, a history of syncope was significantly associated with a higher one-year risk of pacemaker implantation. [ABSTRACT FROM AUTHOR]

Background: It is well established that the different antipsychotics used for schizophrenia symptoms differ substantially in their side effects. However, relatively little is known about the impact of these side effects on functioning from the patient's perspective. We aimed to understand how key side effects of second-generation antipsychotics impact the functioning and quality of life (QoL) of patients with schizophrenia. Methods: This is a cross-sectional, web-based survey of patient-reported side effect burden of antipsychotic drugs in adults with schizophrenia. The survey was deployed in the United States, Canada, Australia, Spain, Italy, Norway, and Denmark. It included sociodemographic and clinical questions, the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF), and the Glasgow Antipsychotic Side-Effect Scale (GASS). Eight pre-defined key side effects classified as activating ("Shaky hands or arms," "Restlessness," and "Difficulty sleeping"), sedating ("Sleepy during the day", "Feeling drugged or like a zombie," and "Feeling dizzy/Fainted") or other side effects ("Problems enjoying sex" and "Gaining weight"), and additional questions related to impacts on function and quality of life were asked. Results: In total, 435 participants (mean age: 38 years, 53.8% female) were included. The total Q-LES-Q-SF score indicated overall medium satisfaction with their quality of life (score of 44.3; possible range 14–70). The most prevalent side effects were "Sleepy during the day" (83.2%), "Difficulty sleeping" (74.7%), "Dry mouth" (63.9%), "Problems enjoying sex" (53.4%) and "Gaining weight" (52.4%). Women reported the side effects of "Sleepy during the day", "Problems enjoying sex" and "Gaining weight" more frequently than men. Key side effects impacted physical, social, occupational and psychological aspects of functioning. Patients with key side effects often felt frustrated by their experiences. Total Q-LES-Q-SF score showed a significant inverse correlation with the score of pre-defined groups of side effects indicating worse QoL in association with more severe key side effects in these patients. Conclusion: Stable patients with schizophrenia taking second-generation antipsychotics live with many side effects, including activating and sedating side effects, sexual side effects, and weight gain. Presence of these side effects is associated with substantial impacts across all aspects of daily functioning and lower quality of life and satisfaction. [ABSTRACT FROM AUTHOR]

Background: Many studies have been conducted to investigate risk factors of falls in older people, but little is known about falls among centenarians. We analyzed the cross-sectional data from the Five-Country Oldest Old Project (5-COOP) to investigate the prevalence and correlates of falls among centenarians.Methods: Data collection was carried out in 2011-2014 in Japan, France, Switzerland, Sweden, and Denmark. The sample consisted of 1,165 centenarians who were at least 100 years old in 2011. The outcome variable was falls in the past 6 months. Demographics, chronic conditions, pain, visual impairment, global cognitive function, dizziness and syncope, number of medications, functional limitation (ie, dressing, bathing, toileting, transferring, incontinence, and feeding), mobility difficulty, poor strength, and assistive device usage were included in the analysis.Results: The prevalence of falls within the last 6 months was 33.7%, ranging from 21.6% (Japan) to 40.9% (France). Being male, experiencing dizziness, syncope, incontinence, and using assistive devices indoors were associated with an increased risk of falls among centenarians. Significant cross-country differences in the relationships between some risk factors (ie, gender, difficulty with bathing, toileting, transferring, and feeding, and using assistive devices for walking indoors and outdoors) and falls were observed. Subsample analysis using data from each country also showed that factors related to falls were different.Conclusions: The prevalence of falls among centenarians is high and fall-related factors may be different than those for their younger counterparts. Given that centenarians is an emerging population, more studies investigating risk factors are needed to better understand falls among centenarians. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) vaccination has been associated with subsequent diffuse symptoms in girls, reducing public confidence in the vaccine. We examined whether girls have nonspecific outcomes of HPV vaccination, using triangulation from cohort, self-controlled case series (SCCS), and population time trend analyses carried out in Denmark between 2000 and 2014. The study population consisted of 314,017 HPV-vaccinated girls and 314,017 age-matched HPV-unvaccinated girls (cohort analyses); 11,817 girls with hospital records (SCCS analyses); and 1,465,049 girls and boys (population time trend analyses). The main outcome measures were hospital records of pain, fatigue, or circulatory symptoms. The cohort study revealed no increased risk among HPV vaccine-exposed girls, with incidence rate ratios close to 1.0 for abdominal pain, nonspecific pain, headache, hypotension/syncope, tachycardia (including postural orthostatic tachycardia syndrome), and malaise/fatigue (including chronic fatigue syndrome). In the SCCS analyses, we observed no association between HPV vaccination and subsequent symptoms. In time trend analyses, we observed a steady increase in these hospital records in both girls and (HPV-unvaccinated) boys, with no relationship to the 2009 introduction of HPV vaccine to Denmark's vaccination program. This study, which had nationwide coverage, showed no evidence of a causal link between HPV vaccination and diffuse autonomic symptoms leading to hospital contact. [ABSTRACT FROM AUTHOR]

Background: We examined if syncope was a marker of an occult cancer by comparing the risk in patients with a syncope episode with that of the general population.Methods: Using Danish population-based medical registries, we identified all patients diagnosed with syncope during 1994-2013 and followed them until a cancer diagnosis, emigration, death or end of follow-up, whichever came first. We computed cumulative risks and standardised incidence ratios (SIR) with 95% confidence intervals (CI).Results: Among 208,361 patients with syncope, 20,278 subsequent cancers were observed. The 6-month cumulative risk of any cancer was 1.2%, increasing to 17.9 % for 1-20 years of follow-up. The highest cumulative risks after 6 months of follow-up were lung cancer (0.2%), colorectal cancer (0.2%), prostate cancer (0.1%) and brain cancer (0.1%). The 6-month SIR were 2.7 (95% CI: 2.4-3.0) for lung cancer, 2.0 (95% CI: 1.8-2.2) for colorectal cancer, 1.7 (95% CI: 1.5-1.9) for prostate cancer and 10.0 (95% CI: 8.6-11.4) for brain cancer.Conclusions: Syncope was a weak marker of an occult cancer. In short-term the highest cumulative risks were observed for lung, colorectal, prostate and brain cancers. An aggressive search for occult cancer in a patient with syncope is probably not warranted. [ABSTRACT FROM AUTHOR]

Background: First-time syncopal episodes usually occur in adults of working age, but their impact on occupational safety and employment remains unknown. We examined the associations of syncope with occupational accidents and termination of employment.Methods and Results: Through linkage of Danish population-based registers, we included all residents 18 to 64 years from 2008 to 2012. Among 3 410 148 eligible individuals, 21 729 with a first-time diagnosis of syncope were identified, with a median age 48.4 years (first to third quartiles, 33.0-59.5), and 10 757 (49.5%) employed at time of the syncope event. Over a median follow-up of 3.2 years (first to third quartiles, 2.0-4.5), 622 people with syncope had an occupational accident requiring hospitalization (2.1/100 person-years). In multiple Poisson regression analysis, the incidence rate ratio in the employed syncope population was higher than in the employed general population (1.44; 95% confidence interval [CI], 1.33-1.55) and more pronounced in people with recurrences (2.02; 95% CI, 1.47-2.78). The 2-year risk of termination of employment was 31.3% (95% CI, 30.4%-32.3%), which was twice the risk of the reference population (15.2%; 95% CI, 14.7%-15.7%), using the Aalen-Johansen estimator. Factors associated with termination of employment were age <40 years (incidence rate ratio, 1.48; 95% CI, 1.37-1.59), cardiovascular disease (1.20; 95% CI, 1.06-1.36), depression (1.72; 95% CI, 1.55-1.90), and low educational level (2.61; 95% CI, 2.34-2.91).Conclusions: In this nationwide cohort, syncope was associated with a 1.4-fold higher risk of occupational accidents and a 2-fold higher risk of termination of employment compared with the employed general population. [ABSTRACT FROM AUTHOR]

Aims: Guidelines recommend evaluation of family members of sudden cardiac death victims. However, initiation of cascade screening in families with uncertain diagnoses is not cost-effective and may cause unnecessary concern. For these reasons, we set out to assess to what extent cardiac magnetic resonance imaging (CMR) would increase the diagnostic precision and thereby possibly change the indication for family screening in patients with ventricular tachyarrhythmias.Methods and Results: We retrospectively collected data from 79 patients hospitalized with aborted cardiac arrest (resuscitated from a cardiac arrest), ventricular tachycardia (VT), or syncope who underwent a CMR at the Copenhagen University Hospital, Rigshospitalet, Denmark. Besides CMR, the patients were evaluated with an electrocardiogram, echocardiogram (both 100%), coronary angiogram (CAG)/coronary computed tomography scan (CT-CAG) (81%), exercise stress test (47%), late potentials (54%), electrophysiological study (44%), pharmacological provocation (44%), and/or myocardial biopsy (16%). Family screening was indicated for 53 probands (67%) prior to CMR. After full workup, only 43 cases (54%) warranted evaluation of relatives (19% decrease, P = 0.034). The full evaluation changed whether family screening was indicated in 18 probands (14/18 moved to no indication for family screening). In the 18 where recommendations on family screening changed, CMR findings were the major driver for re-classification in 17 cases.Conclusion: Cardiac magnetic resonance imaging re-defines the cardiac diagnoses in a significant proportion of cases and reduces the number of patients in whom family screening is warranted. Cardiac magnetic resonance imaging is highly relevant for optimal care and resource allocation when an inherited heart disease is the presumed cause of life-threatening arrhythmias. [ABSTRACT FROM AUTHOR]

Aims: Hypertrophic cardiomyopathy (HCM) is a frequent cause of sudden cardiac death (SCD) among the young (SCDY). The aim of this study was to characterize symptoms before SCDY due to HCM.Methods and Results: Through review of all death certificates, we identified all SCDs in Danes aged 1-35 years in 2000-2009. Nationwide we included all deaths (n = 8756) and identified 431 autopsied SCDYs. All available records from hospitals and general practitioners were retrieved. To compare symptoms, we included a control groups consisting of traffic accident victims (n = 74). In the 10-year study period, 431 autopsied SCDY cases were reviewed and 38 cases (9%) were included, of which 22 (58%) had morphologic findings diagnostic of HCM and 16 (42%) had findings suggestive, but not diagnostic, of HCM ('possible HCM'). Cardiac symptoms >1 h prior to death were reported in 21 (55%) of cases, and 16 (42%) sought medical attention. One (1%) control had cardiac symptoms before death. Consequently, a significantly higher proportion of cases had cardiac symptoms before death and cases more often sought medical attention than controls (P < 0.001).Conclusion: In conclusion, this nationwide study demonstrates a high frequency of cardiac symptoms prior to death in SCDY cases who died of HCM, as 55% had cardiac symptoms and nearly half of the cases sought medical attention. [ABSTRACT FROM AUTHOR]

Novel implantable cardioverter defibrillator (ICD) discrimination algorithms and programming strategies have significantly reduced the incidence of inappropriate shocks, but there are still gains to be made with respect to reducing appropriate but unnecessary antitachycardia pacing (ATP) and shocks. We examined whether programming a number of intervals to detect (NID) of 60/80 for ventricular tachyarrhythmia (VT)/ventricular fibrillation (VF) detection was safe and the impact of this strategy on (1) adverse events related to ICD shocks and syncopal events; (2) ATPs/shocks; and (3) patient-reported outcomes. The "ENHANCED Implantable Cardioverter Defibrillator programming to reduce therapies and improve quality of life" study (ENHANCED-ICD study) was a prospective, safety-monitoring study enrolling 60 primary and secondary prevention patients at the University Medical Center Utrecht. Patients implanted with any type of ICD with SmartShock technology and aged 18 to 80 years were eligible to participate. In all patients, a prolonged NID 60/80 was programmed. The cycle length for VT/fast VT/VF was 360/330/240 ms, respectively. Programming a NID 60/80 proved safe for ICD patients. Because of the new programming strategy, unnecessary ICD therapy was prevented in 10% of ENHANCED-ICD patients during a median follow-up period of 1.3 years. With respect to patient-reported outcomes, levels of distress were highest and perceived health status lowest at the time of implantation, which both gradually improved during follow-up. In conclusion, the ENHANCED-ICD study demonstrates that programming a NID 60/80 for VT/VF detection is safe for ICD patients and does not negatively impact their quality of life. [ABSTRACT FROM AUTHOR]

Symptoms Before SADS Introduction No studies in an unselected and nationwide setting have characterized the symptoms and medical history of patients with sudden arrhythmic death syndrome (SADS). The aim of this study was to identify and describe the symptoms and medical history of patients before the presentation of SADS. Methods and Results We have previously identified all of the autopsied sudden cardiac deaths (SCD; n = 314) in Danes aged 1-35 years between 2000 and 2006. After comprehensive pathological and toxicological investigation did not reveal a cause of SCD, 136 of the patients were identified as SADS. The National Patient Registry was utilized to obtain information on all in- and outpatient activity in Danish hospitals. All medical records from hospitals and general practitioners, including death certificates and autopsy reports were reviewed. Before death, 48 (35%) SADS patients had cardiac symptoms; among these, 30 (22%) had contacted the healthcare system. Antecedent symptoms (symptoms >24 hours before death) were present in 34 (25%) patients. Prodromal symptoms (symptoms ≤24 hours before death) were present in 23 (17%) patients. Cardiac symptoms included chest pain (n = 16, 12%), dyspnea (n = 18, 13%), palpitations (n = 2, 1%), presyncope/syncope (n = 23, 17%), and aborted SCD (n = 2, 1%). In addition, seizures (n = 25, 18%) were prevalent. In 61 (45%) SADS cases, no previous medical history were recorded. Conclusion In this unselected, nationwide study of 136 young SADS patients, 35% had experienced cardiac symptoms before death, most commonly presyncope/syncope, but only one out of five had contacted a healthcare provider with cardiac symptoms. [ABSTRACT FROM AUTHOR]

Objective: To examine workforce attachment among patients with congenital long QT syndrome (cLQTS) following diagnosis and identify factors associated with workforce attachment., Methods and Results: In this nationwide cohort study, all patients diagnosed with cLQTS in Denmark between 1996 and 2016 aged 18-60 years at diagnosis were identified using nationwide registries. Patients attached to the workforce at diagnosis were included. Attachment to the workforce 1 year after cLQTS diagnosis was examined and compared with a background population matched 1:4 on age, sex and employment status. Multiple logistic regression was performed to identify factors associated with 1-year workforce detachment among patients with cLQTS. 298 patients fulfilled the inclusion criteria. Six months after cLQTS diagnosis, 90.9% of patients with cLQTS were attached to the workforce compared with 95.0% in the background population (p=0.006 for difference). One year after diagnosis, 93.3% of patients with cLQTS were attached to the workforce compared with 93.8% in the background population (p=0.26). Among patients with cLQTS, a severe cLQTS disease manifestation was associated with workforce detachment 1 year after diagnosis (compared with asymptomatic patients; aborted cardiac arrest OR 20.4 (95% CI, 1.7 to 249.9); ventricular tachycardia/syncope OR 10.9 (95% CI, 1.1 to 110.5)). No other associated factors were identified., Conclusions: More than 90% of patients with cLQTS remained attached to the workforce 1 year after diagnosis, which was similar to a matched background population. Patients with a severe cLQTS disease manifestation were less likely to be attached to the workforce 1 year after diagnosis., Competing Interests: Competing interests: CT-P reports grant from Bayer for randomised trials and from Novo Nordisk for epidemiological study, all unrelated to the present work. GG reports grants from Boehringer Ingelheim, Bristol-Myers Squibb and Pfizer, unrelated to the present work. HKJ is supported by grants from Novo Nordisk Foundation, Denmark (NNF18OC0031258 and NNF20OC0065151) and received lecture fees from Abbott, Denmark and Biosense Webster, Europe, all unrelated to the present work. JHB reports advisory honoraria from Bayer, outside the present work. LK reports honorarium form Novo, Novartis, AstraZeneca and Boehringer, unrelated to this manuscript. All remaining authors have declared no conflicts of interest., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To identify risk factors and to develop a predictive risk score for pacemaker implantation in patients with atrial fibrillation (AF)., Methods: Using Danish nationwide registries, patients with newly diagnosed AF from 2000 to 2014 were identified. Cox proportional-hazards regression computed HRs for risk factors of pacemaker implantation. A logistic regression was used to fit a prediction model for 3-month risk of pacemaker implantation and derived a risk score using 80% of the data and its predictive accuracy estimated using the remaining 20%., Results: Among 155 934 AF patients included, the median age (IQR) was 75 (65-83) and 51.3% were men. During a median follow-up time of 3.4 (1.2-5.0) years, 8348 (5.4%) patients received a pacemaker implantation. Risk factors of pacemaker implantation were (in order of highest risk first) age above 60 years, congenital heart disease, heart failure at age under 60 years, prior syncope, valvular AF, hypertension, ischaemic heart disease, male sex and diabetes mellitus. The derived risk score assigns points ranging from 1 to 14 to each of these risk factors. The 3-month risk of pacemaker implantation increased from 0.4% (95% CI: 0.2 to 0.8) at 1 point to 2.6% (95% CI: 1.9 to 3.6) at 18 points. Area under the receiver operator characteristics curve was 62.9 (95% CI: 60.3 to 65.5)., Conclusion: We highlighted risk factors of pacemaker implantation in newly diagnosed AF patients and created a risk score. The clinical utility of the risk score needs further investigation., Competing Interests: Competing interests: The authors declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: Gunnar Gislason has ownership of stocks in Novo Nordisk Pharmaceuticals and reports research grants from AstraZeneca, Pfizer, Bristol Myers Squibb, Boerhringer Ingelheim and Bayer. Christian Torp-Pedersen declares grants for studies from Bayer. Other authors have no conflict of interest to declare., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Syncope is a common condition associated with frequent hospitalization or visits to the emergency department. Family aggregation and twin studies have shown that syncope has a heritable component. We investigated whether common genetic variants predispose to syncope and collapse., Methods and Results: We used genome-wide association data on syncope on 408 961 individuals with European ancestry from the UK Biobank study. In a replication study, we used the Integrative Psychiatric Research Consortium (iPSYCH) cohort (n = 86 189), to investigate the risk of incident syncope stratified by genotype carrier status. We report on a genome-wide significant locus located on chromosome 2q32.1 [odds ratio = 1.13, 95% confidence interval (CI) 1.10-1.17, P = 5.8 × 10-15], with lead single nucleotide polymorphism rs12465214 in proximity to the gene zinc finger protein 804a (ZNF804A). This association was also shown in the iPSYCH cohort, where homozygous carriers of the C allele conferred an increased hazard ratio (1.30, 95% CI 1.15-1.46, P = 1.68 × 10-5) of incident syncope. Quantitative polymerase chain reaction analysis showed ZNF804A to be expressed most abundantly in brain tissue., Conclusion: We identified a genome-wide significant locus (rs12465214) associated with syncope and collapse. The association was replicated in an independent cohort. This is the first genome-wide association study to associate a locus with syncope and collapse., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: Management of atrial fibrillation (AF) with rate and/or rhythm control could lead to fall-related injuries and syncope, especially in the older AF population. We aimed to determine the association of rate and/or rhythm control with fall-related injuries and syncope in a real-world older AF cohort., Design: A retrospective cohort study., Setting: Danish nationwide administrative registries from 2000 to 2015., Participants: A total of 100 935 patients with AF aged 65 years or older claiming prescription of rate-lowering drugs (RLDs) and/or anti-arrhythmic drugs (AADs) were included. We compared the use of rate-lowering monotherapy with rate-lowering dual therapy, AAD monotherapy, and AAD combined with rate-lowering therapy., Measurements: Outcomes were fall-related injuries and syncope as a composite end point (primary) or separate end point (secondary)., Results: In this population, the median age was 78 years (interquartile range [IQR] = 72-84 y), and 53 481 (53.0%) were women. During a median follow-up of 2.1 years (IQR = 1.0-5.1), 17 132 (17.0%) experienced a fall-related injury, 5745 (5.7%) had a syncope, and 21 093 (20.9%) experienced either. Compared with rate-lowering monotherapy, AADs were associated with a higher risk of fall-related injuries and syncope. The incidence rate ratio (IRR) for the composite end point was 1.29 (95% confidence interval [CI]: 1.17-1.43) for AAD monotherapy and 1.46 [95% CI = 1.34-1.58] for AAD combined with rate-lowering therapy. When stratifying by individual drugs, amiodarone significantly increased the risk of fall-related injuries and syncope (IRR = 1.40 [1.26-1.55]). Compared with more than 180 days of rate-lowering monotherapy, a higher risk of all outcomes was seen in the first 90 days of any treatment; however, the greatest risk was in the first 14 days for those treated with AADs., Conclusion: In AF patients aged 65 years and older, AAD use was associated with a higher risk of fall-related injuries and syncope, and the risk was highest within the first 14 days for those treated with AADs. Only amiodarone use was associated with a higher risk. J Am Geriatr Soc 67:2023-2030, 2019., (© 2019 The American Geriatrics Society.)