Kidney function, future health costs, and quality-adjusted life-years in kidney transplant recipients transplanted during the SARS-Cov-2 lockdown in Denmark - An observational study.

BACKGROUND: It is unknown whether lockdown due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may affect both clinical outcome in kidney transplant recipients and health care economics in Denmark. METHODS: We compared kidney transplant data at a tertiary university hospital before and during the lockdown period from March 13, 2020 until March 31, 2021, as well as kidney transplant data from Scandiatransplant for entire Denmark. Outcome variables included fall of plasma creatinine during the first postoperative day, and graft function three months posttransplant. We calculated the quality-adjusted life-years (QALYs) and costs which were caused by the lockdown recommendations. FINDINGS: The portion of living donation kidney transplantation was largely reduced during the lockdown period compared to before the lockdown: AB0-incompatible living donation declined from 14% to 7% (P < 0.01), and AB0-compatible living donation declined from 34% to 20% (p < 0.01).In entire Denmark during the lockdown period 78 living donor kidney transplants out of 268 kidney transplants (29%) were performed, whereas there were 878 living donor kidney transplants out of 2218 kidney transplants (39%) before the lockdown (P = 0.01).The observed reduction of living donor kidney transplants and consecutive reduction of graft survival will cause a loss of 5.04 QALYs.The additional costs in kidney transplant recipients who received a kidney transplant during the lockdown period will be 277,298 EUR. INTERPRETATION: SARS-CoV-2 lockdown period largely reduced living donation kidney transplants which will lead to reduced QALY as well as higher costs in kidney transplant recipients.

The Cost-Effectiveness of a COVID-19 Vaccine in a Danish Context.

BACKGROUND AND OBJECTIVES: Covid-19 vaccines approved by the EU, UK and USA have been found to be safe and effective. The cost effectiveness of these vaccines depends upon a number of factors. The aim of this paper is to explore the cost effectiveness of a COVID-19 vaccine and to analyse how the price of the vaccine and the cost of administrating it influence its cost effectiveness. METHODS: We considered an epidemiological model developed by an expert group within 'Statens Serum Institut', which is a unit under the auspices of the Danish Ministry of Health. The model allowed us to differentiate between two population groups, those aged ≥60 years and those aged <60 years. We used the model to consider four scenarios: (i) vaccination of 25% of the total population (corresponding to approximately 1.5 million persons) but targeting vaccines towards the population aged ≥60 years, (ii) vaccination of 25% of the total population, targeting vaccines only towards the population aged <60 years, (iii) vaccination of 40% of the total population where 15% are aged <60 years and 25% are aged ≥60 years (corresponding approximately to the full Danish population aged >60 years), and (iv) 40% of the total population is vaccinated but vaccines are targeted solely towards those aged <60 years. The time horizon of the analysis was six months, and the perspective was that of the Danish healthcare sector. RESULTS: The results show that inclusion of the elderly population aged ≥60 years was more cost effective than a vaccination strategy that targeted a population aged <60 years old only, when productivity losses were not included. Furthermore, the results show that an extension of the target group from the elderly population only, to also include the younger population comes with an increasing cost per life-year gained. The incremental cost-effectiveness ratio depends on the price of the vaccine, hereunder also the administration costs, and the discount rate used for the estimation of life-years or quality-adjusted life-years gained from a vaccine. Furthermore, inclusion of productivity losses in the analyses influenced the cost effectiveness of vaccination of the population aged <60 years of age. CONCLUSION: The cost effectiveness of a COVID-19 vaccine is sensitive to whether or not productivity losses are included in the analyses. Without productivity losses, the elderly population should always be part of the target group for a COVID-19 vaccination programme. Taking productivity losses into account, at least in the case of low vaccine prices, vaccinating the younger population first can actually be cost effective.

Day-to-day measurement of physical activity and risk of atrial fibrillation.

AIMS: The aim of this study was to investigate the association between within-individual changes in physical activity and onset of atrial fibrillation (AF). METHODS AND RESULTS: A total of 1410 participants from the general population (46.2% women, mean age 74.7 ± 4.1 years) with risk factors but with no prior AF diagnosis underwent continuous monitoring for AF episodes along with daily accelerometric assessment of physical activity using an implantable loop recorder during ≈3.5 years. The combined duration of monitoring was ≈1.6 million days, where 10 851 AF episodes lasting ≥60 min were detected in 361 participants (25.6%) with a median of 5 episodes (2, 25) each. The median daily physical activity was 112 (66, 168) min/day. A dynamic parameter describing within-individual changes in daily physical activity, i.e. average daily activity in the last week compared to the previous 100 days, was computed and used to model the onset of AF. A 1-h decrease in average daily physical activity was associated with AF onset the next day [odds ratio 1.24 (1.18-1.31)]. This effect was modified by overall level of activity (P < 0.001 for interaction), and the signal was strongest in the tertile of participants with lowest activity overall [low: 1.62 (1.41-1.86), mid: 1.27 (1.16-1.39), and high: 1.10 (1.01-1.19)]. CONCLUSIONS: Within-individual changes in physical activity are associated with the onset of AF episodes as detected by continuous monitoring in a high-risk population. For each person, a 1-h decrease in daily physical activity during the last week increased the odds of AF onset the next day by ≈25%, while the strongest association was seen in the group with the lowest activity overall. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02036450.

Implantable loop recorder detection of atrial fibrillation to prevent stroke (The LOOP Study): a randomised controlled trial.

BACKGROUND: It is unknown whether screening for atrial fibrillation and subsequent treatment with anticoagulants if atrial fibrillation is detected can prevent stroke. Continuous electrocardiographic monitoring using an implantable loop recorder (ILR) can facilitate detection of asymptomatic atrial fibrillation episodes. We aimed to investigate whether atrial fibrillation screening and use of anticoagulants can prevent stroke in individuals at high risk. METHODS: We did a randomised controlled trial in four centres in Denmark. We included individuals without atrial fibrillation, aged 70-90 years, with at least one additional stroke risk factor (ie, hypertension, diabetes, previous stroke, or heart failure). Participants were randomly assigned in a 1:3 ratio to ILR monitoring or usual care (control) via an online system in permuted blocks with block sizes of four or eight participants stratified according to centre. In the ILR group, anticoagulation was recommended if atrial fibrillation episodes lasted 6 min or longer. The primary outcome was time to first stroke or systemic arterial embolism. This study is registered with ClinicalTrials.gov, NCT02036450. FINDINGS: From Jan 31, 2014, to May 17, 2016, 6205 individuals were screened for inclusion, of whom 6004 were included and randomly assigned: 1501 (25·0%) to ILR monitoring and 4503 (75·0%) to usual care. Mean age was 74·7 years (SD 4·1), 2837 (47·3%) were women, and 5444 (90·7%) had hypertension. No participants were lost to follow-up. During a median follow-up of 64·5 months (IQR 59·3-69·8), atrial fibrillation was diagnosed in 1027 participants: 477 (31·8%) of 1501 in the ILR group versus 550 (12·2%) of 4503 in the control group (hazard ratio [HR] 3·17 [95% CI 2·81-3·59]; p<0·0001). Oral anticoagulation was initiated in 1036 participants: 445 (29·7%) in the ILR group versus 591 (13·1%) in the control group (HR 2·72 [95% CI 2·41-3·08]; p<0·0001), and the primary outcome occurred in 318 participants (315 stroke, three systemic arterial embolism): 67 (4·5%) in the ILR group versus 251 (5·6%) in the control group (HR 0·80 [95% CI 0·61-1·05]; p=0·11). Major bleeding occurred in 221 participants: 65 (4·3%) in the ILR group versus 156 (3·5%) in the control group (HR 1·26 [95% CI 0·95-1·69]; p=0·11). INTERPRETATION: In individuals with stroke risk factors, ILR screening resulted in a three-times increase in atrial fibrillation detection and anticoagulation initiation but no significant reduction in the risk of stroke or systemic arterial embolism. These findings might imply that not all atrial fibrillation is worth screening for, and not all screen-detected atrial fibrillation merits anticoagulation. FUNDING: Innovation Fund Denmark, The Research Foundation for the Capital Region of Denmark, The Danish Heart Foundation, Aalborg University Talent Management Program, Arvid Nilssons Fond, Skibsreder Per Henriksen, R og Hustrus Fond, The AFFECT-EU Consortium (EU Horizon 2020), Læge Sophus Carl Emil Friis og hustru Olga Doris Friis' Legat, and Medtronic.

Atrial fibrillation burden and cognitive decline in elderly patients undergoing continuous monitoring.

AIMS: To study the relationship between subclinical atrial fibrillation (AF) and changes in cognitive function in a large cohort of individuals with stroke risk factors. METHODS: Individuals with no prior AF diagnosis but with risk factors for stroke were recruited to undergo annual cognitive assessment with the Montreal Cognitive Assessment (MoCA) along with implantable loop recorder (ILR) monitoring for AF for 3 years. If AF episodes lasting ≥6 minutes were detected, oral anticoagulation (OAC) treatment was initiated. RESULTS: A total of 1194 participants (55.2 % men, mean age 74.5 (±3.9)) had a combined duration of heart rhythm monitoring of ≈1.3 million days. Among these, 339 participants (28.3%) had adjudicated AF, with a median AF burden of 0.072% (0.02, 0.39), and 324 (96%) initiated OAC. When stratifying the participants into AF burden groups (No AF, AFlow (AF burden <0.25%), and AFhigh, (AF burden >0.25%)), only participants in the AFlow group had a decrease in MoCA score over time (P = .03), although this was not significant after adjustment for stroke risk factors. A subgroup analysis of 175 participants (14.6%) with a MoCA <26 at 3 years found no association to AF diagnosis or burden. CONCLUSIONS: In a high-risk population, subclinical AF detected by continuous monitoring and subsequently treated with OAC was not associated with a significant change in MoCA score over a 3-year period.

Comparison of the three-level and the five-level versions of the EQ-5D.

EQ-5D is a generic instrument to measure health-related quality of life. In 2009, a new version, EQ-5D-5L, was introduced as an attempt to reduce ceiling effects and improve sensitivity to small changes over time. The objective of this study was to assess the measurement properties of the EQ-5D-5L instrument compared to the EQ-5D-3L instrument in an elderly general population with a moderate to a high degree of comorbidity. A subgroup of participants in a large clinical trial completed the EQ-5D-3L and the EQ-5D-5L questionnaires. Based on the collected data, we tested for feasibility and ceiling and floor effects. Furthermore, we assessed the redistribution properties of the responses and examined the level of inconsistency, informativity, and convergent validity. A total of 1002 persons diagnosed with hypertension, diabetes, heart failure, and/or previous stroke completed both the EQ-5D-3L and the EQ-5D-5L questionnaires. The overall ceiling effect decreased from 46% with the EQ-5D-3L to 30% with the EQ-5D-5L and absolute and relative informativity were higher for EQ-5D-5L, and there was a stronger correlation between EQ-5D-5L and EQ VAS. The EQ-5D-5L seemed to perform better than the EQ-5D-3L in terms of feasibility, ceiling effect, discriminatory power, and convergent validity. The overall ceiling effect was higher than that found in patient samples in previous studies but lower than the one found in population studies.

Left Atrial Late Gadolinium Enhancement is Associated With Incident Atrial Fibrillation as Detected by Continuous Monitoring With Implantable Loop Recorders.

OBJECTIVES: The authors hypothesized that left atrial (LA) fibrosis was associated with incident atrial fibrillation (AF) as detected by continuous long-term monitoring in an at-risk population. BACKGROUND: LA late gadolinium enhancement (LGE) measured with cardiac magnetic resonance is emerging as a marker of atrial fibrosis and has been associated with worse outcomes in AF ablation procedures; however, the prognostic value of LA LGE for incident AF remains unknown. METHODS: Cardiac magnetic resonance, including measurement of left ventricular and LA volumes and function, as well as left ventricular extracellular volume fraction and LA LGE, was acquired in 68 patients aged at least 70 years with risk factors for stroke. All included patients received an implantable loop recorder and were continuously monitored for previously unknown AF. Incident AF was adjudicated by senior cardiologists. RESULTS: Patients were monitored for AF with an implantable loop recorder during a median of 41 (interquartile range: 7) months. AF episodes lasting ≥6 min were detected in 32 patients (47%), and 16 patients (24%) experienced AF episodes lasting ≥5.5 h. In Cox regression analyses adjusted for sex, age, and comorbidities, we found that LA volumes and function and LA LGE were independently associated with incident AF. For LA LGE, the hazard ratios for time to AF episodes lasting ≥6 min and ≥5.5 h were 1.40 (95% CI: 1.03 to 1.89) per 10 cm2 increase (p = 0.03) and 1.63 (95% CI: 1.11 to 2.40) per 10 cm2 increase (p = 0.01), respectively. LA LGE was significantly associated with high burden of AF. The addition of LA LGE to a multivariable risk prediction model for incident AF significantly increased the predictive value. CONCLUSIONS: Extent of LA fibrosis measured by LA LGE was significantly associated with incident AF detected by implantable loop recorder. (Atrial Fibrillation Detected by Continuous ECG Monitoring [LOOP]; NCT02036450).

Comprehensive Evaluation of Rhythm Monitoring Strategies in Screening for Atrial Fibrillation: Insights From Patients at Risk Monitored Long Term With an Implantable Loop Recorder.

BACKGROUND: Stroke is an increasing health problem worldwide. Atrial fibrillation (AF) is a major risk factor for stroke, and the attention given to AF screening is rising, as new monitoring technologies emerge. We aimed to evaluate the performance of a large panel of screening strategies and to assess population characteristics associated with diagnostic yield. METHODS: Individuals with stroke risk factors but without AF were recruited from the general population to undergo screening with an implantable loop recorder. New-onset AF lasting ≥6 minutes was adjudicated by senior cardiologists. After continuous monitoring for >3 years, complete day-to-day heart rhythm data sets were reconstructed for every participant, including exact time of onset and termination of all AF episodes. Random sampling was applied to assess the sensitivity and negative predictive value of screening with various simulated screening strategies compared with the implantable loop recorder. The diagnostic yield across strategies and population subgroups was compared by use of nonparametric tests. RESULTS: The rhythm data sets comprised 590 participants enduring a total of 659 758 days of continuous monitoring and 20 110 AF episodes. In these data, a single 10-second ECG yielded a sensitivity (and negative predictive value) of 1.5% (66%) for AF detection, increasing to 8.3% (67%) for twice-daily 30-second ECGs during 14 days and to 11% (68%), 13% (68%), 15% (69%), 21% (70%), and 34% (74%) for a single 24-hour, 48-hour, 72-hour, 7-day, or 30-day continuous monitoring, respectively. AF detection further improved when subsequent screenings were performed or when the same monitoring duration was spread over several periods compared with a single period (eg, three 24-hour monitorings versus one 72-hour monitoring; P<0.0001 for all comparisons). The sensitivity was consistently higher among participants with age ≥75 years, male sex, CHADS2 score >2, or NT-proBNP (N-terminal pro-B-type natriuretic peptide) ≥40 pmol/L and among participants with underlying ≥24-hour AF episodes compared with shorter AF (P<0.0001 for all screening strategies). CONCLUSIONS: In screening for AF among participants with stroke risk factors, the diagnostic yield increased with duration, dispersion, and number of screenings, although all strategies had low yield compared with the implantable loop recorder. The sensitivity was higher among participants who were older, were male, or had higher NT-proBNP. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02036450.

Left atrial volume and function assessed by cardiac magnetic resonance imaging are markers of subclinical atrial fibrillation as detected by continuous monitoring.

AIMS: We aimed to investigate whether left atrial (LA) markers from cardiovascular magnetic resonance (CMR) were able to predict atrial fibrillation (AF) in elderly patients with risk factors for stroke. METHODS AND RESULTS: At baseline, 203 participants with stroke risk factors but without history of AF underwent advanced CMR and received an implantable loop recorder. During a median of 40 (37-42) months of continuous monitoring, incident AF was detected in 79 patients (39%). With regards to CMR markers, a steep increase in incidence rate of AF was seen with LA maximum volume (LAmax) above 55 mL/m2, LA minimum volume (LAmin) above 30 mL/m2, LA total emptying fraction (LA TEF) below 45%, LA active emptying fraction (LA AEF) below 37%, LA strain S below 25%, LA strain A below 17%, and LA strain rate A above -1.7 s-1. After multivariate adjustment, the above-mentioned CMR markers remained associated with AF incidence: hazard ratio (95% confidence interval) 1.25 (1.06-1.48) and 1.51 (1.22-1.87) per 10 mL/m2 increase of LAmax and LAmin, respectively, 1.49 (1.26-1.76) and 1.46 CI (1.25-1.71) per 5% decrease in LA TEF and LA AEF, respectively, 1.23 (1.05-1.44) and 1.56 (1.18-2.06) per 5% decrease in LA strain S and A, respectively, and 2.06 (1.31-3.23) per s-1 increase in LA strain rate A. In prediction analyses, LA functional indices increased area under the receiver operating characteristic curve significantly. CONCLUSION: The risk of AF, including asymptomatic AF, increases significantly with increasing LA volumes and worsening LA function.

Incidence and predictors of atrial fibrillation episodes as detected by implantable loop recorder in patients at risk: From the LOOP study.

BACKGROUND: Recent studies have suggested a high prevalence of subclinical atrial fibrillation (AF) in various patient populations, and interest in AF screening has increased. However, knowledge about episode duration is scarce, and risk factors for short or long subclinical AF episodes have yet to be recognized. The aim of the study was to assess AF by long-term continuous screening and to investigate predictors of episodes lasting ≥6 minutes, ≥5.5 hours, or ≥24 hours, respectively. METHODS: A total of 597 patients aged ≥70 years and diagnosed with ≥1 of hypertension, diabetes, previous stroke, or heart failure were recruited from the general population to receive implantable loop recorder with remote monitoring. Exclusion criteria included history of AF or cardiac implantable electronic device. AF episodes were adjudicated by senior cardiologists. RESULTS: During 40 (37; 42) months of continuous monitoring, AF was detected in 209 (35%) of the patients. The cumulative incidences at 3 years were 33.8% (30.2%-37.8%), 16.1% (13.4%-19.4%), and 5.7% (4.1%-7.9%) for AF episodes lasting ≥6 minutes, ≥5.5 hours, and ≥24 hours, respectively. Slower resting sinus rate and higher body mass index, N-terminal prohormone of brain natriuretic peptide, and troponin T at baseline were independently associated with AF detection. Addition of these markers to a model of sex, age, and comorbidities improved prediction of AF episodes ≥24 hours (time-dependent area under the receiver operating characteristic curve 79% vs 65%, P = .037). CONCLUSIONS: A considerable burden of previously unknown AF was detected when long-term monitoring was applied in at-risk patients. Biomarkers were associated with AF incidence and improved prediction of long AF episodes.

Natural History of Subclinical Atrial Fibrillation Detected by Implanted Loop Recorders.

BACKGROUND: As new heart rhythm monitoring technologies emerge, subclinical atrial fibrillation (AF) signifies a future challenge to health care systems. The pathological characteristics of this condition are largely unknown. OBJECTIVES: This study sought to characterize the natural history of subclinical AF in at-risk patients from the general population. METHODS: The authors studied 590 individuals ≥70 years of age with ≥1 of hypertension, diabetes, previous stroke, or heart failure, without history of AF, undergoing long-term implantable loop recorder monitoring as part of the LOOP (Atrial Fibrillation Detected by Continuous ECG Monitoring Using Implantable Loop Recorder to Prevent Stroke in High-risk Individuals) study. Baseline assessments included N-terminal pro-B-type natriuretic peptide (NT-proBNP). All day-to-day heart rhythm and symptom data were extracted from the device. Endpoints included AF burden, AF progression, symptom reports, and heart rate during AF. RESULTS: A total of 685,445 monitoring days were available for analysis. Adjudicated AF episodes lasting ≥6 min were detected in 205 participants (35%). The AF burden was median 0.13% (interquartile range: 0.03% to 1.05%) of the monitoring time and changed by a factor of 1.31 (95% CI: 1.02 to 1.68) per doubling of NT-proBNP. AF episodes were present 2.7% (interquartile range: 1.0% to 15.7%) of monitoring days after debut. Progression to 24-h episodes was seen in 33 of the AF patients (16%), whereas 46 (22%) had no AF episodes in the last 6 months of monitoring or longer. Symptoms were absent in 185 (90%) at debut, and 178 (87%) never reported AF-related symptoms during follow-up. The averaged heart rate during AF was 96 (interquartile range: 83 to 114) beats/min, 24 (interquartile range: 9 to 41) beats/min faster than daytime sinus rates. CONCLUSIONS: Although previously unknown AF was highly prevalent, the burden was low, and progression was limited. In addition, symptoms were scarce, and the heart rate was only modestly elevated. (Atrial Fibrillation Detected by Continuous ECG Monitoring Using Implantable Loop Recorder to Prevent Stroke in High-risk Individuals [LOOP]; NCT02036450).

Cost-utility analysis of minimally invasive surgery for lung cancer: a randomized controlled trial.

OBJECTIVES: Minimally invasive video-assisted thoracic surgery (VATS) was first introduced in the early 1990s. For decades, numerous non-randomized studies demonstrated advantages of VATS over thoracotomy with lower morbidity and shorter hospital stay, but only recently did a randomized trial document that VATS results in lower pain scores and better quality of life. Opposing arguments for VATS have always been increased costs and concerns about oncological adequacy. In this paper, we aim to investigate the cost-effectiveness of VATS. METHODS: The study was designed as a cost-utility analysis of the first 12 months following surgery and was performed together with a clinical randomized controlled trial of VATS versus thoracotomy for lobectomy of stage 1 lung cancer during a 6-year period (2008-2014). All health-related expenses were retrieved from a national database (Statistics Denmark) including hospital readmissions, outpatient clinic visits, prescription medication costs, consultations with general practitioners, specialists, physiotherapists, psychologists and chiropractors. RESULTS: One hundred and three VATS patients and 103 thoracotomy patients were randomized. Mean costs per patient operated by VATS were 103 108 Danish Kroner (Dkr) (€13 818) and 134 945 Dkr (€18 085) by thoracotomy, making the costs for VATS 31 837 Dkr (€4267) lower than thoracotomy (P < 0.001). The difference in quality-adjusted life years gained over 52 weeks of follow-up was 0.021 (P = 0.048, 95% confidence interval -0.04 to -0.00015) in favour of VATS. The median duration of the surgical procedure was shorter after thoracotomy (79 vs 100 min; P < 0.001). The mean length of hospitalization was shorter following VATS (4.8 vs 6.7 days; P = 0.027). The use of other resources was not significantly different between groups. The costs of resources were lower in the VATS group. This difference was primarily due to reduced costs of readmissions (VATS 29 247 Dkr vs thoracotomy 51 734 Dkr; P < 0.001) and costs of outpatient visits (VATS 51 412 Dkr vs thoracotomy 61 575 Dkr; P = 0.012). CONCLUSIONS: VATS is a cost-effective alternative to thoracotomy following lobectomy for stage 1 lung cancer. Economical outcomes as measured by quality-adjusted life years were significantly better and overall costs were lower for VATS. CLINICAL TRIAL REGISTRATION NUMBER: NCT01278888.

The cost effectiveness of Helicobacter pylori population screening-economic evaluation alongside a randomised controlled trial with 13-year follow-up.

BACKGROUND: Helicobacter pylori eradication improves dyspeptic symptoms in 8%-10%, prevents peptic ulcer and may reduce the risk of gastric cancer. Availability of a high quality diagnostic test and an effective treatment makes population screening and eradication of Helicobacter pylori an attractive option. AIM: To evaluate the cost effectiveness of Helicobacter pylori population screening and eradication. METHODS: Cost effectiveness analysis and cost utility analysis alongside randomised controlled trial with 13 years follow-up. The evaluation has a societal perspective. A random general population sample of 20 011 individuals aged 40-65 were randomised and invited in 1998-1999; 12 530 were enrolled and, of these, 8658 have been successfully followed up at 1, 5, and 13 years after intervention. Questionnaires included the quality of life instrument SF-36. From SF-36 responses an SF-6D score was derived and used for calculation of quality-adjusted life years. Register data on costs, use of health care resources and medication were obtained for all randomised individuals. The intervention was an invitation to Helicobacter pylori screening by in-office blood test; positive tests were validated by 13 C-urea breath test. Those who tested positive were offered eradication therapy. Main outcome measures were Incremental cost per quality-adjusted life year and life-years gained. RESULTS: Helicobacter pylori population screening and eradication with 13 years follow-up was not effective in regards to quality of life and the cost per screened person was higher than not screening (mean difference 11 269 DKK [95% CI: 3175-19 362]). The probability of being cost-effective was 80% at a threshold of 400 000 DKK (approximately 53,800 Euros) of willingness-to-pay per life-year gained. CONCLUSIONS: Helicobacter pylori population screening and eradication with 13 years follow-up was not effective in regards to quality of life and the cost of screening was higher than not screening.

Atrial fibrillation detected by continuous electrocardiographic monitoring using implantable loop recorder to prevent stroke in individuals at risk (the LOOP study): Rationale and design of a large randomized controlled trial.

Atrial fibrillation (AF) increases the rate of stroke 5-fold, and AF-related strokes have a poorer prognosis compared with non-AF-related strokes. Atrial fibrillation and stroke constitute an intensifying challenge, and health care organizations are calling for awareness on the topic. Previous studies have demonstrated that AF is often asymptomatic and consequently undiagnosed. The implantable loop recorder (ILR) allows for continuous, long-term electrocardiographic monitoring with daily transmission of arrhythmia information, potentially leading to improvement in AF detection and stroke prevention. METHODS: The LOOP study is an investigator-initiated, randomized controlled trial with 6,000 participants randomized 3:1 to a control group or to receive an ILR with continuous electrocardiographic monitoring. Participants are identified from Danish registries and are eligible for inclusion if 70years or older and previously diagnosed as having at least one of the following conditions: hypertension, diabetes mellitus, heart failure, or previous stroke. Exclusion criteria include history of AF and current oral anticoagulation treatment. When an AF episode lasting ≥6minutes is detected, oral anticoagulation will be initiated according to guidelines. Expected follow-up is 4years. The primary end point is time to stroke or systemic embolism, whereas secondary end points include time to AF diagnosis and death. CONCLUSION: The LOOP study will evaluate health benefits and cost-effectiveness of ILR as a screening tool for AF to prevent stroke in patients at risk. Secondary objectives include identification of risk factors for the development of AF and characterization of arrhythmias in the population. The trial holds the potential to influence the future of stroke prevention.

User Fees in General Practice: Willingness to Pay and Potential Substitution Patterns-Results from a Danish GP Patient Survey.

BACKGROUND: Increases in public expenditures to general practitioner (GP) services and specialist care have spurred debate over whether to implement user fees for healthcare services such as GP consultations in Denmark. OBJECTIVE: The objective of this study was to examine Danish patients' attitudes towards user fees and their willingness to pay (WTP) for a consultation, and to investigate how user charges may impact patients' behaviour. METHODS: A questionnaire survey was conducted in a GP clinic. RESULTS: A total of 343 individual persons answered the questionnaire. One hundred and seventy (50%) persons were not willing to pay for a consultation. Among patients reporting positive WTP values, the mean WTP was 137 (standard deviation 140) Danish kroner (DKK). Patients who were 65 years old or older were more likely to be willing to pay for a GP consultation than patients under the age of 65 years. Furthermore, patients with a personal annual income of more than 200,000 DKK were more likely to be willing to pay for a consultation than other income groups. With respect to patients with a positive WTP value, their own assessment of the seriousness of the consultation and their self-assessed health influenced the amount they would be willing to pay. Finally, we observed a stated willingness to substitute GP consultations with alternatives that are free of charge. CONCLUSION: About half of the patients with an appointment for a GP consultation are willing to pay for the consultation. User charges may potentially influence the patients' behaviour. ClinicalTrials.gov NCT01784731.

Postoperative pain and quality of life after lobectomy via video-assisted thoracoscopic surgery or anterolateral thoracotomy for early stage lung cancer: a randomised controlled trial.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) is used increasingly as an alternative to thoracotomy for lobectomy in the treatment of early-stage non-small-cell lung cancer, but remains controversial and worldwide adoption rates are low. Non-randomised studies have suggested that VATS reduces postoperative morbidity, but there is little high-quality evidence to show its superiority over open surgery. We aimed to investigate postoperative pain and quality of life in a randomised trial of patients with early-stage non-small-cell lung cancer undergoing VATS versus open surgery. METHODS: We did a randomised controlled patient and observer blinded trial at a public university-based cardiothoracic surgery department in Denmark. We enrolled patients who were scheduled for lobectomy for stage I non-small-cell lung cancer. By use of a web-based randomisation system, we assigned patients (1:1) to lobectomy via four-port VATS or anterolateral thoracotomy. After surgery, we applied identical surgical dressings to ensure masking of patients and staff. Postoperative pain was measured with a numeric rating scale (NRS) six times per day during hospital stay and once at 2, 4, 8, 12, 26, and 52 weeks, and self-reported quality of life was assessed with the EuroQol 5 Dimensions (EQ5D) and the European Organisation for Research and Treatment of Cancer (EORTC) 30 item Quality of Life Questionnaire (QLQ-C30) during hospital stay and 2, 4, 8, 12, 26, and 52 weeks after discharge. The primary outcomes were the proportion of patients with clinically relevant moderate-to-severe pain (NRS ≥3) and mean quality of life scores. These outcomes were assessed longitudinally by logistic regression across all timepoints. Data for the primary analysis were analysed by modified intention to treat (ie, all randomised patients with pathologically confirmed non-small-cell lung cancer). This trial is registered with ClinicalTrials.gov, number NCT01278888. FINDINGS: Between Oct 1, 2008, and Aug 20, 2014, we screened 772 patients, of whom 361 were eligible for inclusion and 206 were enrolled. We randomly assigned 103 patients to VATS and 103 to anterolateral thoracotomy. 102 patients in the VATS group and 99 in the thoracotomy group were included in the final analysis. The proportion of patients with clinically relevant pain (NRS ≥3) was significantly lower during the first 24 h after VATS than after anterolateral thoracotomy (VATS 38%, 95% CI 0·28-0·48 vs thoracotomy 63%, 95% CI 0·52-0·72, p=0·0012). During 52 weeks of follow-up, episodes of moderate-to-severe pain were significantly less frequent after VATS than after anterolateral thoracotomy (p<0·0001) and self-reported quality of life according to EQ5D was significantly better after VATS (p=0·014). By contrast, for the whole study period, quality of life according to QLQ-C30 was not significantly different between groups (p=0·13). Postoperative surgical complications (grade 3-4 adverse events) were similar between the two groups, consisting of prolonged air leakage over 4 days (14 patients in the VATS group vs nine patients in the thoracotomy group), re-operation for bleeding (two vs none), twisted middle lobe (one vs three) or prolonged air leakage over 7 days (five vs six), arrhythmia (one vs one), or neurological events (one vs two). Nine (4%) patients died during the follow-up period (three in the VATS group and six in the thoracotomy group). INTERPRETATION: VATS is associated with less postoperative pain and better quality of life than is anterolateral thoracotomy for the first year after surgery, suggesting that VATS should be the preferred surgical approach for lobectomy in stage I non-small-cell lung cancer. FUNDING: Simon Fougner Hartmanns Familiefond, Guldsmed AL & D Rasmussens Mindefond, Karen S Jensens legat, The University of Southern Denmark, The Research Council at Odense University Hospital, and Department of Cardiothoracic Surgery, Odense University Hospital.

Cost-effectiveness estimate of prehospital thrombolysis: results of the PHANTOM-S study.

OBJECTIVE: To analyze the cost-effectiveness of shorter delays to treatment and increased thrombolysis rate as shown in the PHANTOM-S (Prehospital Acute Neurological Treatment and Optimization of Medical Care in Stroke) Study. METHODS: In addition to intermediate outcomes (time to thrombolysis) and treatment rates, we registered all resource consequences of the intervention. The analyzed treatment effects of the intervention were restricted to distribution of IV thrombolysis (IVT) administrations according to time intervals. Intermediate outcomes were extrapolated to final outcomes according to numbers needed to treat derived from pooled IVT trials and translated to gains in quality-adjusted life-years (QALYs). RESULTS: The net annual cost of the Stroke Emergency Mobile (STEMO) prehospital stroke concept was €963,954. The higher frequency of IVT administrations per year (310 vs 225) and higher proportions of patients treated in the early time interval (within 90 minutes: 48.1% vs 37.4%; 91-180 minutes: 37.4% vs 50%; 181-270 minutes: 14.5% vs 12.8%) resulted in an annual expected health gain of avoidance of 18 cases of disability equaling 29.7 QALYs. This produced an incremental cost-effectiveness ratio of €32,456 per QALY. CONCLUSIONS: Depending on willingness-to-pay thresholds in societal perspectives, the STEMO prehospital stroke concept has the potential of providing a reasonable innovation even in health-economic dimensions.

Evaluation of a controlled, national collaboration study on a clinical pharmacy service of screening for risk medications.

BACKGROUND: Risk medications are frequently associated with adverse events and hospitalisations. OBJECTIVE: To evaluate a risk medication screening service for in-patients at Danish hospitals. SETTING: Danish hospitals. METHODS: The study was designed as a controlled, prospective intervention study. Inpatients were screened for the use of five risk medications; anticoagulants, digoxin, methotrexate, NSAIDs and opioids, and during the intervention period recommendations were made by clinical pharmacists according to a standardized intervention scheme. The recommendations were discussed with the physician face-to-face. MAIN OUTCOME MEASURE: Readmissions within 6 months after discharge. RESULTS: In total, 1,007 control and 775 intervention patients were included in the study. The study found that half of the patients (50 % during the control and 48 % during the intervention period) admitted to Danish hospitals were treated with at least one of the five selected risk medications, significantly more drug related problems (DRPs) were identified during the control period (1.7/patient during the control and 1.4/patient during the intervention period (p < 0.001)), and the acceptance rate of recommendations (62 %) was similar to medication management service studies in the literature (39-100 %). However, no impact on outcome measures was found. The majority (69 %) of the clinical pharmacists reported that they had increased their professional competences by participating in the study, and that a national clinical pharmacy study may be used in promoting and implementing a unique clinical pharmacy service throughout the country (67 %). CONCLUSION: The study showed that a national screening service for risk medications could help identify and address DRPs. Despite no impact on the selected outcome measures, it is likely that the screening service could be included in a medication management review with further focus on the individual patient to ensure positive outcomes, or that the screening service should be delivered to selected patients groups, who might have maximum benefit of the service.