UNASSIGNED: Approximately one-half of all heart failure (HF) consists of heart failure with preserved ejection fraction (HFpEF) or heart failure with mid-range ejection fraction (HFmrEF). Although several recent trials have investigated treatments for HFpEF/HFmrEF, there is limited insight on the long-term clinical trajectory of this population.
UNASSIGNED: The purpose of this study was to model clinical outcomes in patients with symptomatic (NYHA functional class II-IV) HFpEF/HFmrEF over 10 years.
UNASSIGNED: We developed a Markov model with stable HF, HF hospitalization, and death states to follow a cohort of patients with HFpEF/HFmrEF treated with standard of care (SoC) recommended by the American Heart Association/American College of Cardiology/Heart Failure Society of America. Population characteristics and clinical event probabilities were derived from recent phase 3 HFpEF/HFmrEF trials. We used weighted averages for control and sodium-glucose cotransporter-2 inhibitor outcomes. SoC was informed by baseline treatments reported in clinical trials.
UNASSIGNED: In a cohort of U.S. patients with HFpEF/HFmrEF treated with SoC, our model estimated 0.53 cumulative HF hospitalizations per patient over 10 years. Overall, 37% had at least 1 HF hospitalization, and 26% experienced cardiovascular death. The model estimated 6.1 years of life expectancy from age 72 and total cost of care over this time of $123,900.
UNASSIGNED: HFpEF/HFmrEF is associated with high rates of HF hospitalization and cardiovascular mortality based on contemporary clinical trials in this population. Furthermore, clinical trial results are likely to be more optimistic than real-world outcomes. Continuing to optimize care and treatment may reduce clinical burden and improve population health.

Background: Creutzfeldt-Jakob disease (CJD) and fatal familial insomnia (FFI) are prion diseases characterized by severe neurodegenerative conditions and a short duration of illness. Methods: This study explores the characteristics of hospitalizations for CJD and FFI in Spain from 2016 to 2022 using the Spanish National Hospital Discharge Database (SNHDD). Results: We identified a total of 1063 hospital discharges, including 1020 for CJD and 43 for FFI. Notably, the number of hospitalized patients with FFI showed a significant peak in 2017. The average length of hospital stay (LOHS) was 13 days for CJD and 6 days for FFI, with in-hospital mortality rates (IHM) of 36.37% for CJD and 32.56% for FFI. Among CJD patients, the average LOHS was 14 days, with a significantly longer duration for those who experienced IHM. Conclusions: The presence of sepsis or pneumonia and older age were associated with a higher IHM rate among CJD patients. The total estimated cost for managing CJD and FFI patients over the study period was EUR 6,346,868. This study offers new insights into the epidemiology and healthcare resource utilization of CJD and FFI patients, which may inform future research directions and public health strategies.

Plasticity is found in all domains of life and is particularly relevant when populations experience variable environmental conditions. Traditionally, evolutionary models of plasticity are non-mechanistic: they typically view reactions norms as the target of selection, without considering the underlying genetics explicitly. Consequently, there have been difficulties in understanding the emergence of plasticity, and in explaining its limits and costs. In this paper, we offer a novel mechanistic approximation for the emergence and evolution of plasticity. We simulate random \"epigenetic mutations\" in the genotype-phenotype mapping, of the kind enabled by DNA-methylations/demethylations. The frequency of epigenetic mutations at loci affecting the phenotype is sensitive to organism stress (trait-environment mismatch), but is also genetically determined and evolvable. Thus, the \"random motion\" of epigenetic markers enables developmental learning-like behaviors that can improve adaptation within the limits imposed by the genotypes. However, with random motion being \"goal-less,\" this mechanism is also vulnerable to developmental noise leading to maladaptation. Our individual-based simulations show that epigenetic mutations can hide alleles that are temporarily unfavorable, thus enabling cryptic genetic variation. These alleles can be advantageous at later times, under regimes of environmental change, in spite of the accumulation of genetic loads. Simulations also demonstrate that plasticity is favored by natural selection in constant environments, but more under periodic environmental change. Plasticity also evolves under directional environmental change as long as the pace of change is not too fast and costs are low.

UNASSIGNED: The rising popularity of reverse total shoulder arthroplasties (RTSA) demands attention to its growing costs on the healthcare system, especially with the implementation of bundled payments. Charges associated with patients\' inpatient stays can be mitigated with a better understanding of the drivers of cost following RTSA. In this study, we evaluate potential pre-operative and post-operative factors associated with higher inpatient costs following RTSA.
UNASSIGNED: We identified 59,925 patients who underwent RTSA using the National Inpatient Sample between 2016 and 2019. Total inpatient hospital charges were collected, and patients were divided into \"normal cost\" or \"high cost\" groups. The high cost group was defined as patients with total costs greater than the 75th percentile. Univariate and multivariate analyses were performed on pre-operative demographic and comorbidity variables as well as post-operative surgical and medical complications to predict factors associated with higher costs. T-tests and Chi-squared tests were performed, and odds ratios were calculated.
UNASSIGNED: The mean total charges were $141.213.93 in the high cost group and $59,181.94 in the normal cost group. Following multivariate analysis, non-white patients were associated with higher costs by 1.31-fold (P<0.001), but sex and age were not. Cirrhosis and non-elective admission had higher odds of higher costs by 1.56-fold (P<0.001) and 3.13-fold (P<0.001), respectively. Among surgical complications, there were higher odds of high costs for periprosthetic infection by 2.43-fold (P<0.001), periprosthetic mechanical complication by 1.28-fold (P<0.001), and periprosthetic fracture by 1.56-fold (P<0.001). Medical complications generally had higher odds of high costs than surgical complications, with deep vein thrombosis having nearly five times (P<0.001) and myocardial infarction almost four times (P<0.001) higher odds of high inpatient costs.
UNASSIGNED: Post-operative medical complications were the most predictive factors of higher cost following RTSA. Pre-operative optimization to prevent infection and medical complications is imperative to mitigate the economic burden of RTSA\'s.

BACKGROUND: Varicella is a highly infectious disease, particularly affecting children, that can lead to complications requiring antibiotics or hospitalization. Antibiotic use for varicella management is poorly documented. This study assessed antibiotic use for varicella and its complications in a pediatric population in England.
METHODS: Data were drawn from medical records in the Clinical Practice Research Datalink and Hospital Episode Statistics data sets. The study included patients <18 years old with varicella diagnosed during 2014-2018 and 3-month follow-up available. We determined varicella-related complications, medication use, healthcare resource utilization, and costs from diagnosis until 3 months after diagnosis.
RESULTS: We identified 114 578 children with a primary varicella diagnosis. Of these, 7.7% (n = 8814) had a varicella-related complication, the most common being ear, nose, and throat related (37.1% [n = 3271]). In all, 25.9% (n = 29 706 of 114 578) were prescribed antibiotics. A higher proportion of patients with complications than without complications were prescribed antibiotics (64.3% [n = 5668 of 8814] vs 22.7% [n = 24 038 of 105 764]). Mean annualized varicella-related costs were £2 231 481 for the study cohort. Overall, antibiotic prescriptions cost approximately £262 007.
CONCLUSIONS: This study highlights high antibiotic use and healthcare resource utilization associated with varicella management, particularly in patients with complications. A national varicella vaccination program in England may reduce varicella burden and related complications, medication use, and costs.

BACKGROUND: Mobile Link is a mobile phone-based intervention to increase access to, and use of, health care services among female entertainment workers in Cambodia who face higher risks for specific diseases and gender-based violence. A multisite randomized controlled trial showed that Mobile Link connected female entertainment workers with outreach workers for information and escorted referrals after 6 months but did not lead to statistically significant improvements in HIV and sexually transmitted infection testing, contraceptive use, and condom use.
OBJECTIVE: This study aims to conduct a 3-part economic evaluation of Mobile Link to understand its costs, value, and affordability.
METHODS: We conducted cost, cost-effectiveness, and budget impact analyses of Mobile Link using cost and outcomes data from the Mobile Link trial and other sources. For the cost analysis, we estimated the total, per-person, and incremental costs of Mobile Link compared with usual care. Using probabilistic decision-analytic models, we estimated the 1-year cost-effectiveness of Mobile Link from payer and combined payer and patient perspectives by converting selected primary and secondary outcomes from the trial to disability-adjusted life years (DALYs) averted. Finally, we estimated the financial costs of scaling up Mobile Link\'s messaging and outreach services to 70% of female entertainment workers in 5 years.
RESULTS: The incremental costs of Mobile Link were US $199 from a payer perspective and US $195 per person from a combined payer and patient perspective. With an average of 0.018 (95% predicted interval -0.088 to 0.126) DALYs averted, Mobile Link\'s cost-effectiveness was US $10,955 per DALY from a payer perspective (US $10,755 per DALY averted from a payer and patient perspective). The costs of Mobile Link would have to decrease by 85%, or its effectiveness would have to be 5.56 times higher, for the intervention to meet the upper limit of recommended cost-effectiveness thresholds in Cambodia (US $1671 per DALY averted). The 5-year cost of scaling Mobile Link to 34,790 female entertainment workers was estimated at US $1.64 million or US $46 per person per year.
CONCLUSIONS: This study provided a comprehensive economic evaluation of Mobile Link. We found that Mobile Link is not likely to be cost-effective unless its costs decrease or its effectiveness increases. Scaling up Mobile Link to more female entertainment workers is estimated to cost less than the costs of the trial. Given the importance of linking female entertainment workers to essential services, future research should focus on enhancing the effectiveness of Mobile Link or developing new mobile health interventions for this population.
BACKGROUND: ClinicalTrials.gov NCT03117842; https://clinicaltrials.gov/study/NCT03117842.

This cost analysis of a community-based viral hepatitis screening program in Cameroon found an investment of $3.52 per person screened, $50.63 per new diagnosis of hepatitis B, $159.45 per new diagnosis of hepatitis C, and $47.97 per new diagnosis of either hepatitis B or C.

Combination COVID-19/influenza rapid tests provide a way to quickly and accurately differentiate between the two infections. The goal of this economic evaluation was to assess the cost and health benefits of a combination COVID-19/influenza Rapid Diagnostic Test (RDT) vs. current standard-of-care in the Brazilian private healthcare setting. A dual decision tree model was developed to estimate the impact of rapid differentiation of COVID-19 and influenza in a hypothetical cohort of 1,000 adults with influenza-like illness in an ambulatory healthcare setting. The model compared the use of a combination COVID-19/influenza RDT to Brazil standard diagnostic practice of a COVID-19 RDT and presumptive influenza diagnosis. Different levels of influenza prevalence were modeled with co-infection estimated as a function of the COVID-19 prevalence. Outcomes included accuracy of diagnosis, antiviral prescriptions and healthcare resource use (hospital bed days and ICU occupancy). Depending on influenza prevalence, considering 1,000 patients with influenza-like illness, a combination RDT compared to standard practice was estimated to result in between 88 and 149 fewer missed diagnoses of influenza (including co-infection), 161 to 185 fewer cases of over-diagnosis of influenza; a 24 to 34% reduction in hospital bed days and a 16 to 26% reduction in ICU days. In the base case scenario (20% influenza, 5% COVID-19), the combination RDT was estimated to result in cohort cost savings of $99. Based upon a de novo economic model, this analysis indicates that use of a combination RDT could positively impact influenza antiviral prescriptions and lower healthcare resource use.

UNASSIGNED: Risk assessment is essential in the prevention of cardiovascular disease. In patients with recent acute coronary syndrome (ACS) or coronary revascularization, risk prediction tools, like the European Society of Cardiology guideline recommended SMART-REACH risk score, are increasingly used to predict the risk of recurrent cardiovascular events enabling risk-based personalized prevention. However, little is known about the association between risk stratification and the social and healthcare costs at a population level. This study evaluated the associations between baseline SMART-REACH risk scores, long-term recurrent clinical events, cumulative costs, and post-index event LDL-C goal attainment in patients with recent ACS and/or revascularization.
UNASSIGNED: This retrospective study used electronic health records and was conducted in the North Karelia region of Finland. The study cohort included all patients aged 45-85 admitted to a hospital for ACS or who underwent percutaneous coronary intervention or coronary artery bypass surgery between 1 January 2017 and 31 December 2021. Patients were divided into quintiles based on their baseline SMART-REACH risk scores to examine the associations between predicted 5-year scores and selected clinical and economic outcomes. In addition, simple age-based stratification was conducted as a sensitivity analysis. The observed 5-year cumulative incidence of recurrent events ranged from 20% in the lowest to 41% in the highest risk quintile, whereas the corresponding predicted risks ranged from 13% to 51%, and cumulative 5-year mean total costs per patient ranged from 15 827 to 46 182€, respectively. Both monitoring and attainment of low LDL-C values were suboptimal.
UNASSIGNED: The use of the SMART-REACH quintiles as a population-level risk stratification tool successfully stratified patients into subgroups with different cumulative numbers of recurrent events and cumulative total costs. However, more research is needed to define clinically and economically optimal threshold values for a population-level stratification.

BACKGROUND: The burden of chronic kidney disease (CKD) is high in the Northern Territory (NT), Australia. This study aims to describe the healthcare use and associated costs of people at risk of CKD (e.g. acute kidney injury, diabetes, hypertension, and cardiovascular disease) or living with CKD in the NT, from a healthcare funder perspective.
METHODS: We included a retrospective cohort of patients at risk of, or living with CKD, on 1 January 2017. Patients on kidney replacement therapy were excluded from the study. Data from the Territory Kidney Care database, encompassing patients from public hospitals and primary health care services across the NT was used to conduct costing. Annual healthcare costs, including hospital, primary health care, medication, and investigation costs were described over a one-year follow-up period. Factors associated with high total annual healthcare costs were identified with a cost prediction model.
RESULTS: Among 37,398 patients included in this study, 23,419 had a risk factor for CKD while 13,979 had CKD (stages 1 to 5, not on kidney replacement therapy). The overall mean (± SD) age was 45 years (± 17), and a large proportion of the study cohort were First Nations people (68%). Common comorbidities in the overall cohort included diabetes (36%), hypertension (32%), and coronary artery disease (11%). Annual healthcare cost was lowest in those at risk of CKD (AUD$7,958 per person) and highest in those with CKD stage 5 (AUD$67,117 per person). Inpatient care contributed to the majority (76%) of all healthcare costs. Predictors of increased total annual healthcare cost included more advanced stages of CKD, and the presence of comorbidities. In CKD stage 5, the additional cost per person per year was + $53,634 (95%CI 32,769 to 89,482, p < 0.001) compared to people in the at risk group without CKD.
CONCLUSIONS: The total healthcare costs in advanced stages of CKD is high, even when patients are not on dialysis. There remains a need for effective primary prevention and early intervention strategies targeting CKD and related chronic conditions.