Real-World Cost-Effectiveness of Pulmonary Vein Isolation for Atrial Fibrillation: A Target Trial Approach.

OBJECTIVES: Randomized controlled trials of pulmonary vein isolation (PVI) for treating atrial fibrillation (AF) have proven the procedure's efficacy. Studies assessing its empirical cost-effectiveness outside randomized trial settings are lacking. We aimed to evaluate the effectiveness and cost-effectiveness of PVI versus medical therapy for AF. METHODS: We followed a target trial approach using the Swiss-AF cohort, a prospective observational cohort study that enrolled patients with AF between 2014 and 2017. Resource utilization and cost information were collected through claims data. Quality of life was measured with EQ-5D-3L utilities. We estimated incremental cost-effectiveness ratios (ICERs) from the perspective of the Swiss statutory health insurance system. RESULTS: Patients undergoing PVI compared with medical therapy had a 5-year overall survival advantage with a hazard ratio of 0.75 (95% CI 0.46-1.21; P = .69) and a 19.8% SD improvement in quality of life (95% CI 15.5-22.9; P < .001), at an incremental cost of 29 604 Swiss francs (CHF) (95% CI 16 354-42 855; P < .001). The estimated ICER was CHF 158 612 per quality-adjusted life-year (QALY) gained within a 5-year time horizon. Assuming similar health effects and costs over 5 additional years changed the ICER to CHF 82 195 per QALY gained. Results were robust to the sensitivity analyses performed. CONCLUSIONS: Our results show that PVI might be a cost-effective intervention within the Swiss healthcare context in a 10-year time horizon, but unlikely to be so at 5 years, if a willingness-to-pay threshold of CHF 100 000 per QALY gained is assumed. Given data availability, we find target trial designs are a valuable tool for assessing the cost-effectiveness of healthcare interventions outside of randomized controlled trial settings.

Do Medicine Shortages Reduce Access and Increase Pharmaceutical Expenditure? A Retrospective Analysis of Switzerland 2015-2020.

OBJECTIVES: We analyze how shortages led to changes in access to and expenditure for pharmaceutical care in the Swiss health system between 2015 and 2020. METHODS: We combined cross-sectional and longitudinal data to study medicine shortages by incidence, duration, intensity, and pharmaceutical expenditure. We assessed 4119 markets defined by active ingredient, dosage form, and strength. We classified markets by essential medicine status and other characteristics. We differentiated shortages by the degree to which alternative options are still available. We investigated the first lockdown period of the pandemic, considering also the shortage of COVID-19-specific medicines. RESULTS: A total of 1964 markets never reported shortages, and 1336 markets reported some shortages; 819 markets reported shortages lasting at least 14 days. Markets with a higher number of manufacturers, a lower co-payment share, and lower prices more frequently reported shortages. We did not find differences by essential medicine status. In 50% of instances, the average price of substitutes available was lower than the price of the product on shortage. The total pharmaceutical expenditure attributed to shortages increased by CHF 17.00 million (€15.63 million) in 2018. CONCLUSIONS: Medicine shortages have substantially reduced access to pharmaceuticals. Switzerland has experienced shortages on a scale similar to that in other countries. Prices of substitutes available at the time of shortages can be higher or lower, indicating an unelastic demand for medicines.

Patients on vitamin K treatment: is switching to direct-acting oral anticoagulation cost-effective? A target trial on a prospective cohort.

AIMS: Direct-acting oral anticoagulants (DOACs) have, to a substantial degree, replaced vitamin K antagonists (VKA) as treatments for stroke prevention in atrial fibrillation (AF) patients. However, evidence on the real-world causal effects of switching patients from VKA to DOAC is lacking. We aimed to assess the empirical incremental cost-effectiveness of switching patients to DOAC compared with maintaining VKA treatment. METHODS: The target trial approach was applied to the prospective observational Swiss-AF cohort, which enrolled 2415 AF patients from 2014 to 2017. Clinical data, healthcare resource utilisation and EQ-5D-based utilities representing quality of life were collected in yearly follow-ups. Health insurance claims were available for 1024 patients (42.4%). Overall survival, quality-of-life, costs from the Swiss statutory health insurance perspective and cost-effectiveness were estimated by emulating a target trial in which patients were randomly assigned to switch to DOAC or maintain VKA treatment. RESULTS: 228 patients switching from VKA to DOAC compared with 563 patients maintaining VKA treatment had no overall survival advantage over a 5-year observation period (HR 0.99, 95% CI 0.45, 1.55). The estimated gain in quality-adjusted life years (QALYs) was 0.003 over the 5-year period at an incremental costs of CHF 23 033 (€ 20 940). The estimated incremental cost-effectiveness ratio was CHF 425 852 (€ 387 138) per QALY gained. CONCLUSIONS: Applying a causal inference method to real-world data, we could not demonstrate switching to DOACs to be cost-effective for AF patients with at least 1 year of VKA treatment. Our estimates align with results from a previous randomised trial.

Restoring estuarine ecosystems using nature-based solutions: Towards an integrated eco-engineering design guideline.

Traditional solutions to estuarine flood risk management have typically involved the implementation of static 'hard' shoreline protection structures, often at the expense of the natural landscape and the societal and ecosystem benefits they provide. In a changing climate, there is an increasing need to restore these estuarine ecosystems, and alternative measures in the form of Nature-based Solutions (NbS) are being considered. Guidance that balances ecology and engineering is required for NbS to establish as self-sustaining ecosystems. In this study, a review of NbS guidelines was undertaken, revealing an absence of technical content bridging ecological and engineering values. Instead, most guidelines focus on NbS project implementation, identifying engineering aspects, and providing frameworks for investors and project managers. Integration of technical engineering and ecological outcomes within NbS guidelines is needed. A conceptual approach for integrating eco-engineering aspects for estuarine ecosystems is proposed. This conceptual approach focuses on the critical thresholds and parameter relationships associated with establishment, growth, recovery and mortality, and functionality of estuarine NbS, in efforts to quantify changes in ecological development and flood risk mitigation services. The conceptual approach documents how the suggested relationships between parameters can be adopted by practitioners in the short-term, medium-term, and long-term. The application of this conceptual approach to multi-habitat restoration is explored, including lifecycle timing and ecosystem/design functionality. The findings of this study demonstrate the need for an integrated NbS design guideline that balances ecology and engineering research for the long-term success of estuarine ecosystems.

Subjective burden of government-imposed Covid-19 restrictions in Switzerland: Evidence from the 2022 LINK Covid-19 survey.

BACKGROUND: While a large literature has quantified the health and economic impact of COVID-19, estimates on the subjective losses in quality of life due to government imposed restrictions remain scarce. METHODS: We conducted a nationally representative online survey in Switzerland in February 2022 to measure average self-reported quality of life with government restrictions. We used a discrete choice experiment to compute average willingness to pay for avoiding specific restrictions and time-trade-off questions to quantify the relative quality of life under restrictions. RESULTS: A total of 1299 Swiss residents completed the online survey between February 9th and 15th, 2022. On average, respondents valued life under severe restrictions at 39% of their usual life (estimated relative utility 0.39 [0.37, 0.42]). Willingness to pay for avoiding restrictions was lowest for masks (CHF 663 [319, 1007]), and highest for schools and daycares (CHF 4123 [3443, 4803]) as well as private parties (CHF 4520 [3811, 5229]). We estimate that between March 2020 and February 2022 a total of 5.7 Million QALYs were lost due to light, moderate and severe restrictions imposed by the governments. CONCLUSIONS: The quality of life losses due to government restrictions are substantial, particularly when it comes to the closure of schools and daycares, as well as the prohibition of private gatherings. Future policies should weigh these costs against the health benefits achievable with specific measures.

A global assessment of estuarine tidal response to sea level rise.

Climate change induced sea level rise (SLR) is one of the greatest challenges threatening the sustainable management of estuaries worldwide. Current knowledge regarding SLR and estuarine hydrodynamics is primarily focused on individual case studies, which provides limited guidance on how different estuary typologies will respond to SLR. To expand the current knowledge, this research used an idealised hydrodynamic approach to analyse the tidal range dynamics of 25 real-world estuaries with diverse shapes and boundary conditions, providing insights into estuarine response to SLR-induced tidal variations. Under present-day conditions, short length estuaries with wide entrances, deep waters, strong convergence, macro-tidal conditions, low values of roughness, and low upland river inflows are likely to experience amplified tidal range patterns; whereas lengthy estuaries with narrow entrances, shallow water depths, micro/meso-tidal conditions, high values of roughness, and high upland river inflows often exhibit a mix of dampened-amplified or fully dampened tidal range patterns. Under the effects of SLR, estuarine tidal range dynamics change depending on their present-day tidal range patterns. Where the present-day tidal range pattern is either dampening, a mix of dampening/amplification, or amplification, SLR increases (up to 61 %), moderately increases (up to 26 %), and slightly decreases/increases (up to 5 %) the tidal range of estuaries, respectively. Considering the relationship between an estuary's present-day tidal range pattern and its response to SLR, the presented approach may be useful in providing an initial assessment of SLR effects in estuaries worldwide. This approach may also help to identify sites most impacted by future SLR, and to direct decision-making towards evidence-based management approaches.

Patient clusters and cost trajectories in the Swiss Atrial Fibrillation cohort.

OBJECTIVE: Evidence on long-term costs of atrial fibrillation (AF) and associated factors is scarce. As part of the Swiss-AF prospective cohort study, we aimed to characterise AF costs and their development over time, and to assess specific patient clusters and their cost trajectories. METHODS: Swiss-AF enrolled 2415 patients with variable duration of AF between 2014 and 2017. Patient clusters were identified using hierarchical cluster analysis of baseline characteristics. Ongoing yearly follow-ups include health insurance clinical and claims data. An algorithm was developed to adjudicate costs to AF and related complications. RESULTS: A subpopulation of 1024 Swiss-AF patients with available claims data was followed up for a median (IQR) of 3.24 (1.09) years. Average yearly AF-adjudicated costs amounted to SFr5679 (€5163), remaining stable across the observation period. AF-adjudicated costs consisted mainly of inpatient and outpatient AF treatment costs (SFr4078; €3707), followed by costs of bleeding (SFr696; €633) and heart failure (SFr494; €449). Hierarchical analysis identified three patient clusters: cardiovascular (CV; N=253 with claims), isolated-symptomatic (IS; N=586) and severely morbid without cardiovascular disease (SM; N=185). The CV cluster and SM cluster depicted similarly high costs across all cost outcomes; IS patients accrued the lowest costs. CONCLUSION: Our results highlight three well-defined patient clusters with specific costs that could be used for stratification in both clinical and economic studies. Patient characteristics associated with adjudicated costs as well as cost trajectories may enable an early understanding of the magnitude of upcoming AF-related healthcare costs.

Estimating the cost impact of atrial fibrillation using a prospective cohort study and population-based controls.

AIMS: Atrial fibrillation (AF) costs are expected to be substantial, but cost comparisons with the general population are scarce. Using data from the prospective Swiss-AF cohort study and population-based controls, we estimated the impact of AF on direct healthcare costs from the Swiss statutory health insurance perspective. METHODS: Swiss-AF patients, enrolled from 2014 to 2017, had documented, prevalent AF. We analysed 5 years of follow-up, where clinical data, and health insurance claims in 42% of the patients were collected on a yearly basis. Controls from a health insurance claims database were matched for demographics and region. The cost impact of AF was estimated using five different methods: (1) ordinary least square regression (OLS), (2) OLS-based two-part modelling, (3) generalised linear model-based two-part modelling, (4) 1:1 nearest neighbour propensity score matching and (5) a cost adjudication algorithm using Swiss-AF data non-comparatively and considering clinical data. Cost of illness at the Swiss national level was modelled using obtained cost estimates, prevalence from the Global Burden of Disease Project, and Swiss population data. RESULTS: The 1024 Swiss-AF patients with available claims data were compared with 16 556 controls without known AF. AF patients accrued CHF5600 (EUR5091) of AF-related direct healthcare costs per year, in addition to non-AF-related healthcare costs of CHF11100 (EUR10 091) per year accrued by AF patients and controls. All five methods yielded comparable results. AF-related costs at the national level were estimated to amount to 1% of Swiss healthcare expenditure. CONCLUSIONS: We robustly found direct medical costs of AF patients were 50% higher than those of population-based controls. Such information on the incremental cost burden of AF may support healthcare capacity planning.

Longitudinal Changes in Health-Related Quality of Life in Patients With Atrial Fibrillation.

Background Optimizing health-related quality of life (HRQoL) is an important aim of atrial fibrillation (AF) treatment. Little is known about patients' long-term HRQoL trajectories and the impact of patient and disease characteristics. The aim of this study was to describe HRQoL trajectories in an observational AF study population and in clusters of patients with similar patient and disease characteristics. Methods and Results We used 5-year follow-up data from the Swiss-Atrial Fibrillation prospective cohort, which enrolled 2415 patients with prevalent AF from 2014 to 2017. HRQoL data, collected yearly, comprised EuroQoL-5 dimension utilities and EuroQoL visual analog scale scores. Patient clusters with similar characteristics at enrollment were identified using hierarchical clustering. HRQoL trajectories were analyzed descriptively and with inverse probability-weighted regressions. Effects of postbaseline clinical events were additionally assessed using time-shifted event variables. Among 2412 (99.9%) patients with available baseline HRQoL, 3 clusters of patients with AF were identified, which we characterized as follows: "cardiovascular dominated," "isolated symptomatic," and "severely morbid without cardiovascular disease." Utilities and EuroQoL visual analog scale scores remained stable over time for the full population and the clusters; isolated symptomatic patients showed higher levels of HRQoL. Utilities were reduced after occurrences of stroke, hospitalization for heart failure, and bleeding, by -0.12 (95% CI, -0.18 to -0.06), -0.10 (95% CI, -0.13 to -0.08), and -0.06 (95% CI, -0.08 to -0.04), respectively, on a 0 to 1 utility scale. Utility of surviving patients returned to preevent levels 4 years after heart failure hospitalization; 3 years after bleeding; and 1 year after stroke. Conclusions In patients with prevalent AF, HRQoL was stable over time, irrespective of baseline patient characteristics. Clinical events of hospitalization for heart failure, stroke, and bleeding had only a temporary effect on HRQoL.

Decision thresholds with genetic testing.

A genetic test is a test for the presence or absence of a genetic mutation. A positive test outcome that reveals a mutation associated with increased risk for a disease may lead a patient to seek preventive treatment provided that the penetrance (probability of developing the disease given the mutation) is sufficiently high. We derive the test threshold and the test-treatment threshold, which confine the mutation probability interval for the use of the genetic test. Test and treatment costs as well as a low penetrance rate of the mutation narrow this interval. We illustrate the model with parameters of the test for BRCA1 and BRCA2 genes as well as of preventive treatment options for breast cancer.

Decision Thresholds for Medical Tests Under Ambiguity Aversion.

We consider medical decision-making under diagnostic and therapeutic uncertainty and analyze how ambiguity aversion affects the decisions to test and treat, thereby contributing to the understanding of the observed heterogeneity of such decisions. We show that under diagnostic ambiguity (i.e., the probability of disease is ambiguous), prior testing becomes more attractive if the default option is no treatment and less so if the default option is treatment. Conversely, with therapeutic ambiguity (i.e., the probability of a successful treatment is ambiguous), ambiguity aversion reduces the tolerance toward treatment failure so that the test option is chosen at a lower probability of failure. We differentiate between conditional and unconditional ambiguity aversion and show that this differentiation has implications for the propensity to test. We conclude by discussing the normative scope of ambiguity aversion for the recommendations and decisions of regulatory bodies.

Burden of Covid-19 restrictions: National, regional and global estimates.

BACKGROUND: A growing literature has documented the high global morbidity, mortality and mental health burden associated with the current Covid-19 pandemic. In this paper, we aimed to quantify the total utility and quality of life loss resulting from Covid-19-related government restrictions imposed at the national, regional and global levels. METHODS: We conducted quality of life online surveys in France, India, Italy, UK and the United States of America between June 21st and September 13th 2021, and used regression models to estimate the average quality of life loss due to light and severe restrictions in these countries. We then combined estimated disutility weights from the pooled sample with the latest data on Covid-19 restrictions exposure in each country to estimate the total disutility generated by restrictions at the national, regional and global level. We also embedded a discrete choice experiment (DCE) into the online survey to estimate average willingness to pay to avoid specific restrictions. FINDINGS: A total of 947 surveys were completed. Thirty-five percent of respondents were female, and 69.5% were between 18 and 39 years old. The weighted average utility weight was 0.71 (95% CIs 0.69-0.74) for light restrictions, and 0.65 (0.63-0.68) for severe restrictions. At the global scale, this implies a total loss of 3259 million QALYs (95% 3021, 3496) as of September 6th, 2021, with the highest burden in lower and upper middle-income countries. Utility losses appear to be particularly large for closures of schools and daycares as well as restaurants and bars, and seem relatively small for wearing masks and travel restrictions. INTERPRETATION: The results presented here suggest that the QALY losses due to restrictions are substantial. Future mitigation strategies should try to balance potential reductions in disease transmission achievable through specific measures against their respective impact on quality of life. Additional research is needed to determine differences in restriction-specific disutilities across countries, and to determine optimal policy responses to similar future disease threats. FUNDING: No funding was received for this project.

Sea level rise impacts on estuarine dynamics: A review.

Sea level rise (SLR) poses a hazard to ecosystems and economies in low-lying coastal and estuarine areas. To better understand the potential impacts of SLR in estuaries, a comprehensive review of existing theory, literature, and assessment tools is undertaken. In addition, several conceptual models are introduced to assist in understanding interlinked estuarine processes and their complex responses to SLR. This review indicates that SLR impacts in estuaries should not be assessed via static (bathtub) approaches as they fail to consider important hydrodynamic effects such as tidal wave amplification, dampening, and reflection. Where hydrodynamic models are used, the existing literature provides a relatively detailed understanding of how SLR will affect estuarine hydrodynamics (e.g., tides and inundation regimes). With regards to the current understanding of, and ability to model, the connections between altered hydrodynamics (under SLR) and dependent geomorphic, ecological, and bio-geochemical processes, significant knowledge gaps remain. This is of particular concern as there is currently a paradigm shift towards more integrated and holistic management of estuaries. Estuarine management under accelerating SLR is likely to become increasingly complex, as decision-making will be undertaken with uncertainty. As such, this review highlights that there is a fundamental requirement for more sophisticated and interdisciplinary studies that integrate physical, ecological, bio-geochemical, and geomorphic responses of estuaries to SLR.

Estuarine tidal range dynamics under rising sea levels.

How an estuary responds to sea level rise (SLR) is complex and depends on energy drivers (e.g., tides and river inflows), estuarine geometry (e.g., length and depth), intrinsic fluid properties (e.g., density), and bed/bank roughness. While changes to the tidal range under SLR can impact estuarine sediment transport, water quality, and vegetation communities, studies on the altered tidal range under SLR are often based on case studies with outcomes applicable to a specific site. As such, this study produced a large ensemble of estuarine hydrodynamic models (>1800) to provide a systematic understanding of how tidal range dynamics within different estuary types may change under various SLR and river inflow scenarios. The results indicated that SLR often amplifies the tidal range of different estuary types, except for short estuaries with a low tidal range at the mouth where SLR attenuates the tides. SLR alters the location of the points with minimum tidal range and overall tidal range patterns in an estuary. Variations in tidal range were more evident in converging estuaries, shallower systems, or in estuaries with strong river inflows. These findings provide an indication of how different estuary types may respond to estuaries and may assist estuarine managers and decision makers.

The treatment decision under uncertainty: The effects of health, wealth and the probability of death.

Medical treatment reduces diagnostic risk, increases therapeutic risk and lowers the probability of death. This paper analyzes the effects of initial health, wealth and the probability of death on the propensity to treat under diagnostic and therapeutic risk. It shows that treatment propensity increases with the probability of death, but can decrease with the severity of illness. The effect of wealth depends on the cross-derivative of the utility function with respect to health and wealth. These results have implications for treatment decisions at the end of life.

The variance of length of stay and the optimal DRG outlier payments.

Prospective payment schemes in health care often include supply-side insurance for cost outliers. In hospital reimbursement, prospective payments for patient discharges, based on their classification into diagnosis related group (DRGs), are complemented by outlier payments for long stay patients. The outlier scheme fixes the length of stay (LOS) threshold, constraining the profit risk of the hospitals. In most DRG systems, this threshold increases with the standard deviation of the LOS distribution. The present paper addresses the adequacy of this DRG outlier threshold rule for risk-averse hospitals with preferences depending on the expected value and the variance of profits. It first shows that the optimal threshold solves the hospital's tradeoff between higher profit risk and lower premium loading payments. It then demonstrates for normally distributed truncated LOS that the optimal outlier threshold indeed decreases with an increase in the standard deviation.

Use of cardiac magnetic resonance imaging and single photon emission computed tomography for the diagnosis of stable coronary artery disease in Switzerland.

BACKGROUND: Direct invasive testing in the diagnosis of stable coronary artery disease (CAD) involves high costs and relevant risks. By comparison, single-photon emission computed tomography (SPECT) and cardiac magnetic resonance imaging (CMR) are noninvasive diagnostic tests. SPECT is currently the most widely used diagnostic technique, but new medical and economic evidence favours CMR. Guidelines do not recommend one technique in preference to the other, and their use in Switzerland is poorly documented, as a scoping study by the Swiss Medical Board reported. We aimed at a quantitative and qualitative analysis of the use of these diagnostic techniques in Swiss hospitals. METHODS: We contacted nine Swiss hospitals to obtain the number of SPECT/CMR investigations used to diagnose stable CAD in 2014–2016 and submitted a questionnaire to investigate the advantages and limitations of the two imaging techniques. In addition, two experts in SPECT and CMR, respectively, at two university hospitals were interviewed, using open questions. RESULTS: Data were obtained from 8 hospitals, and 22 questionnaires were returned. In Switzerland, both techniques have been implemented very differently in different hospitals, but the overall number of diagnostic procedures has increased. The questionnaires reported lower scores for CMR regarding the availability of the scans, contraindications and the suitability of the technique for the diagnosis of CAD. The experts described potential conflicts of interest in some institutions, depending on how the cardiology and radiology departments collaborated, and highlighted the debated results of studies comparing CMR with SPECT for the diagnosis of CAD. The main conclusion drawn from the interviews was the recommendation of a patient-centred evaluation. CONCLUSION: The use of SPECT versus CMR in Switzerland for the diagnosis of stable CAD is heterogeneous, but reflects the guidelines, which do not distinguish between the two diagnostic techniques. Expert opinions underlined that discussion should not be so much about the choice of the diagnostic modality but about how a clinical question in a patient can best be answered.

To wait or to pay for medical treatment? Restraining ex-post moral hazard in health insurance.

We explore the hierarchy of two instruments, waiting time and coinsurance for medical treatment, for optimally solving the tradeoff between the economic gains from risk sharing and the losses from moral hazard. We show that the optimal waiting time is zero, given that the coinsurance rate is optimally set.

Threshold analysis in the presence of both the diagnostic and the therapeutic risk.

The well-established a priori probability of illness threshold in medical decision making, introduced by Pauker and Kassirer (N Engl J Med 293:229-234, 1975; N Engl J Med 302:1109-1117, 1980), involves the diagnostic risk only. We generalize the threshold analysis by adding the therapeutic risk, i.e., in accounting for the risk that a treatment might sometimes fail. We derive a priori probability of illness threshold as a function of the probability of successful treatment, as well as the inverted function, where the successful treatment probability threshold is a function of the a priori probability of illness. The thresholds in the general model are higher than those in the special cases where one of the two risks is absent. Applications show that the changes in the thresholds can be substantial. Our general model might explain empirical findings of much higher thresholds than the Pauker-Kassirer model suggests.

Evaluating the consequences of rheumatoid arthritis.

Patients and non-patients tend to attach different utility values to the state of suffering from specific illnesses. This observation naturally leads to the question whose utility values should be used as the basis in cost-effectiveness analysis (CEA). Intuitively, one would presume that patients are better informed about the consequences of their illness, and public authorities should, therefore, use the patients' utility values in CEA. Contrary to this presumption, it has been argued that society at large should determine which values are to be used and not the patients because, in the end, it is societal resources that are to be allocated. Against this background, we use data from a discrete choice experiment (DCE) that was completed by patients of rheumatoid arthritis (RA) and non-patients to explore the discrepancies between the two groups' utility estimates for typical consequences of RA. Our results indicate that both groups attach remarkably similar part-worth utilities to the symptoms pain, fatigue, and functional limitations. However, non-patients significantly undervalue the ability to work when compared to patients.