Additional Life Years Research Articles

The competence in health issues of population of circumpolar region of the Russian Federation

The health literacy of citizen is determined by a set of demographic and social factors. The deficiency of health literacy of population in the Russian Arctic Zone conditions delay in indicators characterizing population health from their all-Russian values and menaces ability to achieve the targets of the National Strategy of Development of Russian Arctic Zone and Ensuring National Security up to 2035.The purpose of the study is to assess level of health literacy of patients and healthy population residing in circumpolar territories of Russia (Arkhangelsk Oblast).The level of general health literacy in the subgroups of respondents varied in narrow range of 26.9-36.3 points. The most significant difference was established between scores of interactive health literacy (Δ = 4.1 points) and critical health literacy (Δ = 3.4 points), which were higher in group of healthy respondents. The predictors of level of general health literacy are clinical status (value of dependent variables in healthy respondents was on average higher on 0.75-1.73 points), self-assessment of one's positioning in society (every additional point increases average level of general health literacy by 0.47-0.79 points) and age (every additional year of life reduces level of general health literacy by 0.08 - 0.09 points). The results of the study indicate on dependency between clinical status and the level of health literacy, determine social characteristics of risk group with low health literacy as object of additional preventive measures directed at citizen residing in in circumpolar terrotories of The Russian Federation.

Population, Clinical, and Scientific Impact of National Cancer Institute's National Clinical Trials Network Treatment Studies.

In the United States, the National Cancer Institute National Cancer Clinical Trials Network (NCTN) groups have conducted publicly funded oncology research for 50 years. The combined impact of all adult network group trials has never been systematically examined. We identified randomized, phase III trials from the adult NCTN groups, reported from 1980 onward, with statistically significant findings for ≥ 1 clinical, time-dependent outcomes. In the subset of trials in which the experimental arm improved overall survival, gains in population life-years were estimated by deriving trial-specific hazard functions and hazard ratios to estimate the experimental treatment benefit and then mapping this trial-level benefit onto the US cancer population using registry and life-table data. Scientific impact was based on citation data from Google Scholar. Federal investment costs per life-year gained were estimated. The results were derived through December 31, 2020. One hundred sixty-two trials comprised of 108,334 patients were analyzed, representing 29.8% (162/544) of trials conducted. The most common cancers included breast (34), gynecologic (28), and lung (14). The trials were cited 165,336 times (mean, 62.2 citations/trial/year); 87.7% of trials were cited in cancer care guidelines in favor of the recommended treatment. These studies were estimated to have generated 14.2 million (95% CI, 11.5 to 16.5 million) additional life-years to patients with cancer, with projected gains of 24.1 million (95% CI, 19.7 to 28.2 million) life-years by 2030. The federal investment cost per life-year gained through 2020 was $326 in US dollars. NCTN randomized trials have been widely cited and are routinely included in clinical guidelines. Moreover, their conduct has predicted substantial improvements in overall survival in the United States for patients with oncologic disease, suggesting they have contributed meaningfully to this nation's health. These findings demonstrate the critical role of government-sponsored research in extending the lives of patients with cancer.

Decomposition of caste differential in life satisfaction among older adults in India

BackgroundBeing a multi-cultured country, India has varied social groups which largely shape the lives of individuals. Literature has shown that life satisfaction is highly associated with the social status of individuals. However, changing age dynamics (growing older) and definition of life among people presses the need to understand whether the additional years of life in older adults are manifested with the disparity in life satisfaction among the Scheduled Caste (SC)/ Scheduled Tribes (ST) and non-SC/ST social groups in recent years. The present study explored the factors contributing to such differences in life satisfaction across social groups.MethodsThis study used data from the Longitudinal Aging Study in India conducted during 2017-18. The analytical sample of the study was 30,370 older adults. Life satisfaction was the outcome variable with a score ranging from 5 to 35. Descriptive statistics and bivariate analysis were conducted. Simple linear regression analysis was used to establish the association between the outcome and explanatory variables. Further, the Blinder-Oaxaca decomposition model was used to analyse the role of explanatory factors in the caste difference in life satisfaction among older people.ResultsOverall, the life satisfaction score among older adults in the study was 23.9 (SD- 7.3). Older adults from non-SC/ST group had significantly higher likelihood of having life satisfaction in comparison to older adults from SC/ST group [Coef: 0.31; CI: 0.14, 0.49]. The decomposition results showed that the model explained 74.3% of the caste gap (between SC/ST and non-SC/ST) in life satisfaction among older adults in India. Subjective social status (39.0%) was widening the gap for life satisfaction among older adults from SC/ST and non-SC/ST group. Similarly, level of education (15.2%) followed by satisfaction with living arrangement (13.2%) and place of residence (5.3%) contributed for widening the gap for life satisfaction among older adults from SC/ST and non-SC/ST group. Region of country (− 11.5%) followed by self-rated health (− 3.0%) and major depression (− 2.7%) contributed for narrowing down the gap for life satisfaction among older adults from SC/ST and non-SC/ST group.ConclusionOlder adults belonging to non-SC/ST groups were more likely to have a higher level of life satisfaction than those from the SC/ST group. Factors like subjective social status, educational level, living arrangement satisfaction, and place of residence explained the caste differential in life satisfaction among older adults. In addition, factors such as psychological health and perceived health status should be the area of concern and special focus for policy makers and researchers in terms of reducing social inequalities in wellbeing among older population.

GSOR15 Presentation Time: 11:40 AM: Underutilization of Brachytherapy: A Retrospective State Level Analysis of Brachytherapy Delivery in Locally Advanced Cervical Cancer

<h3>Purpose</h3> The standard of care for locally advanced cervical cancer is concurrent chemotherapy and external beam radiation therapy (EBRT) followed by a brachytherapy boost. Decreased rate of brachytherapy in cervical cancer patients has shown a declining survival for these patients. This study aims to characterize the utilization of brachytherapy in Oregon in order to better understand how care delivery can be improved. <h3>Materials and Methods</h3> The Oregon State Cancer Registry database was used to identify patients diagnosed with FIGO 2008 Stage IB2-IVB cervical cancer between 2007 and 2016. Patients who received initial EBRT were categorized by whether they received brachytherapy boost or not. Age at diagnosis, county, rural/urban status of the county, race/ethnicity, and insurance payer were studied using multivariable logistic regression to identify possible underserved populations. Survival data was compared using a Cox proportional hazard survival model. Changes in brachytherapy use over time were also examined by grouping patients by year of diagnosis and comparing the rates of brachytherapy utilization over the duration of the study. <h3>Results</h3> 401 patients who received primary EBRT for FIGO stage IB2-IVB cervical cancer were identified in the 10-year span. Breakdown by stage is: 16% stage IB2, 23.9% stage II, 37.4% stage III, and 22.7% stage IV. Of those, 154 (38.4%) received brachytherapy boost treatment, 75 (18.7%) received a different boost modality, and 172 (42.9%) received no boost. Stage IV (p=0.001) and uninsured patients (p=0.04) were significantly less likely to receive brachytherapy. Older age was also associated with decreased brachytherapy usage, as each additional year of life correlated with a decreased likelihood of brachytherapy receipt of 1.8% (p=0.04). Native American and Pacific Islander patients were the only group significantly more likely to receive brachytherapy (p=0.003). There was no significant difference in the rate of brachytherapy boost based on urban/rural status of the county (p=0.63 to 0.69), other racial/ethnic categories (p=0.66 to 0.80), or among the other stages (p=0.45 to 0.63). In Cox proportional hazard survival analysis, patients that received brachytherapy showed a 42% reduction in risk of cancer specific mortality, though this did not reach the level of statistical significance (p=0.057). In terms of brachytherapy utilization by year, no definitive trend was shown. Yearly rates varied from 25% to 52%, with a dip in utilization in 2013 and 2014 at around 30% before a jump in utilization in 2015 and 2016 to around 50%. <h3>Conclusions</h3> The brachytherapy boost rates among locally advanced cervical cancer patients were 38.4%. Though not statistically significant, a reduction in cancer specific mortality in patients receiving brachytherapy by 42% was seen. Older patients, stage IV patients, and uninsured patients were less likely to receive brachytherapy. Given the low overall brachytherapy usage, these data may indicate barriers to access and delivery of brachytherapy care. The increased brachytherapy use in the American Indian and Pacific Islander patient population should be further studied to identify facilitators to treatment completion and potentially extrapolate to other groups.

The psychedelic renaissance: can psilocybin possibly combat depression?

The psychedelic renaissance: can psilocybin possibly combat depression?

현대인의 건강증진을 위한 국내 도시공원 액티브디자인 분석 - 뉴욕시 액티브 디자인 적용을 중심으로 -

Due to the development of medical and scientific technology, people are living longer than ever before. With these additional years of life, people are showing a renewed interest in health-promoting physical activities but are seeking to do so in a time efficient manner, as they go about their daily lives. Therefore, this study analyzed environments in which people can naturally and sustainably improve their health. Previous studies were used to examine the importance of modern people’s health activities and the use of urban parks. We used the New York Active Design Guidelines and Seoul Urban Design Guidelines to create an active design checklist for domestic urban parks, and based on the checklist, we analyzed the active design of the six domestic urban parks: Seoullo7017, Son Kee-chung Sports Park, Training Center Park, Munjeong Neighborhood Park, Asia Neighborhood Park, and Ogeum Neighborhood Park. Our analysis revealed a need for significant design improvements. Firstly, various internal facilities and guidance facilities should be provided in order to increase the openness and publicity of the park. Secondly, all pedestrians, including the disabled, should be able to engage in safe and enjoyable activities which promote the continued use of physical exercise. In the future, further research will be needed to promote the ‘Seoul Active Design Guidelines’ to ensure parks match the needs and characteristics of the citizens of Seoul.

Identifying Disparities in Cervical Cancer Brachytherapy Delivery

<h3>Purpose/Objective(s)</h3> The standard of care for locally advanced cervical cancer is concurrent chemotherapy and external beam radiation therapy (EBRT) followed by a brachytherapy boost. Some studies show a decreased usage of brachytherapy in cervical cancer patients despite the standard of care and known survival advantage. This study aims to characterize the utilization of brachytherapy in Oregon and identify where disparities in treatment may exist. <h3>Materials/Methods</h3> The Oregon State Cancer Registry database was used to identify patients diagnosed with FIGO Stage IB2-IVB cervical cancer between 2007 and 2016. Patients who received initial EBRT were categorized by whether they received brachytherapy boost or not. Age at diagnosis, county, rural/urban status of the county, race/ethnicity, and insurance payer were studied using multivariable logistic regression to identify possible underserved populations. Survival data was compared using a Cox proportional hazard survival model. <h3>Results</h3> 401 patients who received primary EBRT for FIGO stage IB2-IVB cervical cancer were identified in the 10-year span. Breakdown by stage is: 16% Stage IB2, 23.9% stage II, 37.4% stage III, and 22.7% stage IV. Of those, 154 (38.4%) received brachytherapy boost treatment, 75 (18.7%) received a different boost modality, and 42.9% received no boost. Stage IV (p=0.001) and uninsured patients (p=0.04) were significantly less likely to receive brachytherapy. Older age was also associated with decreased brachytherapy usage, as each additional year of life decreased brachytherapy receipt by 1.8% (p=0.04). Native American and Pacific Islander patients were the only group significantly more likely to receive brachytherapy (p=0.003). There was no significant difference in the rate of brachytherapy boost identified based on urban/rural status of the county (p=0.63 to 0.69), other racial/ethnic categories (p=0.66 to 0.80), or among the other stages (p=0.45 to 0.63). In Cox proportional hazard survival analysis, patients that received brachytherapy showed a 42% reduction in risk of cancer specific mortality, though this did not reach the level of statistical significance (p=0.057). <h3>Conclusion</h3> The brachytherapy boost rates among locally advanced cervical cancer patients were 38.4%, similar to national averages. Though not statistically significant, data also showed a reduction in cancer specific mortality in patients receiving brachytherapy. Older patients, stage IV patients, and uninsured patients were less likely to receive brachytherapy. Given the low overall brachytherapy usage, these data indicate access and delivery of brachytherapy care needs to be improved across the state. The increased brachytherapy use in the American Indian and Pacific Islander patient population should be further studied to identify facilitators to treatment completion and potentially extrapolate to other groups.

Cost-Utility and Budget Impact Analysis of Implementing Anticoagulation Clinics and Point-of-Care Monitoring Devices in Anticoagulated Patients in Argentina.

BackgroundWorldwide, 1 % of the population receives anticoagulation therapy, with prevalence higher in older adults. Difficulties in the adequate management of these patients have led to the development of strategies focused on achieving therapeutic control and reducing adverse events with efficient use of resources.ObjectiveTo estimate the cost utility and budget impact on the Argentinean health system of implementation of anticoagulation clinics (ACs) (with and without use of point-of-care [POC] CoaguChek® devices [Roche Diagnostics International Ltd]) compared with the traditional laboratory method (non-AC settings) for the management of anticoagulated patients.MethodsFor the cost-utility analysis, a cohort-based state transition model was designed to compare costs and health outcomes of implementing ACs for outpatient management of anticoagulated patients. The budget impact analysis used an analytical model to estimate the differential costs of implementing an AC and the expected adverse events avoided, and the differential costs of an international normalized ratio (INR) determination using a POC device rather than a conventional laboratory.ResultsWe calculated the study outcomes for a cohort of 1000 patients. Considering a 5 % discount rate, the use of ACs generated 13.9 additional quality-adjusted life-years (0.014 per patient) and 12.5 additional life-years (0.013 per patient). Incremental cost-effectiveness ratios of AC implementation with and without the use of POC devices compared with the scenario without ACs were dominant in both cases. In the probabilistic sensitivity analysis, nearly all simulated results were cost effective (i.e., below the 1 or 3 gross domestic product per capita thresholds). Budget impact analysis results showed AC implementation generated savings from the first year of implementation, with savings of AR $265,325 by year 5. The addition of POC devices in the ACs also generated savings as early as the first year of implementation, with savings of AR $488,072 by year 5 (AR $488 per patient).ConclusionsAnticoagulation clinics are estimated to be cost effective and generate notable savings in the treatment of patients on long-term oral anticoagulant therapy when compared with non-AC settings. These savings are considerably higher when POC devices are added as part of the patient management, due to lower laboratory technician costs per INR determination.Supplementary InformationThe online version contains supplementary material available at 10.1007/s41669-022-00352-4.

Headspace early intervention for psychosis in Australia: Is it still a 'best buy'?

Australia is piloting a stand-alone early intervention programme for psychosis, based on the Early Psychosis Prevention and Intervention Centre (EPPIC) model that was developed within mainstream Victorian State Government psychiatric services. The Australian early intervention programme is located in primary care, and badged as 'headspace Early Psychosis Youth Services'. There are currently six metropolitan early intervention services with two further services planned for the 2023 Financial Year. We discuss key findings from an external evaluation of the first six services, released by the Australian Government Department of Health under a Freedom of Information request. headspace Early Psychosis Youth Services received high ratings for patient satisfaction and engagement, which was associated with symptomatic improvement and functional recovery. However, governance was complicated, costs were relatively high, and caseload targets were not met. The cost for an additional year of good quality life was estimated at AUD 318,954, which exceeds the usual thresholds for defining a 'good buy'. Integrated models should be investigated, as they seem in principle to offer efficiencies and improved continuity of care.

Cost-effectiveness analysis of nivolumab plus ipilimumab versus platinum-doublet chemotherapy for first-line treatment of stage IV or recurrent non-small cell lung cancer in the United States

Aim We evaluated the cost-effectiveness of nivolumab in combination with ipilimumab (NIVO + IPI) versus platinum-doublet chemotherapy (PDC) for the first-line treatment of stage IV or recurrent non-small cell lung cancer (NSCLC) from a third-party payer perspective in the United States (US). Methods A partitioned survival model was developed using efficacy, safety, and utility inputs derived from Part 1 of the phase 3 CheckMate 227 trial (NCT02477826) with 37.7-month minimum follow-up for overall survival (OS). OS and progression-free (PF) survival were extrapolated over a 20-year time-horizon using parametric spline-based models selected based on goodness of fit and validated with data from external sources. Duration of treatment Kaplan–Meier curves were used for treatment cost calculations. US-specific costs (2021 dollars) for drug acquisition, administration, and monitoring; disease management (PF and progressed disease health states); end-of-life care; adverse events; and subsequent treatments were derived from publicly available sources. Time-to-death utilities were applied in the base case, whereas treatment-specific progression-based utilities were tested in a scenario analysis. Main outcomes included incremental cost per life-year gained (LYG) and quality-adjusted life-year (QALY). Model uncertainty was assessed through deterministic and probabilistic sensitivity analyses. Results NIVO + IPI resulted in 1.53 additional life-years, 1.33 additional QALYs, and $142 088 in additional costs compared with PDC. The incremental cost per LYG was $92 651, whereas incremental cost per QALY gained was $106 553. The application of treatment-specific progression-based utilities yielded an incremental cost per QALY gained of $117 076. Probabilistic sensitivity analysis revealed a 98% probability that NIVO + IPI was cost-effective versus PDC at a willingness-to-pay threshold of $150 000 per QALY. Conclusions NIVO + IPI was estimated to be cost-effective as a first-line treatment for stage IV or recurrent NSCLC in the US, with increased survival and higher cost compared with PDC.

Health outcomes modelling of RNA-based versus DNA-based detection of driver gene rearrangements in non-small cell lung cancer.

e18837 Background: There are several FDA-approved targeted therapies for NSCLC with driver gene rearrangements (DGRs) involving ALK, ROS1, RET, NTRK1-3, and MET exon 14. DNA-based sequencing panels miss 15-20% of DGRs compared to RNA-based methods (Benayed et al., 2019; Solomon et al., 2020). We modelled the years of life gained by using RNA- instead of DNA-based methods for DGR detection. Methods: We used the IVI-NSCLC open-source model to analyze the relationship between stable disease, progression, and death as previously described in a multi-state model. Previously reported PFS hazard ratios for targeted therapies (versus chemotherapy) treating DGRs range from 0.17 to 0.52 (Hoang et al., 2020). Therefore, we assumed that the HRs corresponding to the parameter estimates for the targeted therapy option built into the model would approximate treatment-specific relative effects of targeted therapies for DGRs (PFS = 0.3; OS = 0.8). We simulated life-years and quality-adjusted life years (QALYs) for a cohort of 1,000 patients with DGRs matched to appropriate targeted therapies over a 5-year time horizon. We used population-level prevalence data to estimate the number of patients with metastatic NSCLC and DGRs. We then estimated the number of false negatives generated by DNA-only sequencing and calculated the additional life-years gained if RNA-based methods were used instead. Results: In a simulated cohort of 1,000 patients with DGRs detected through RNA sequencing and receiving targeted therapy, median PFS and OS were 1.8 and 3.7 years, respectively. The use of targeted therapy (instead of chemotherapy) in these patients increased life-years by 3.46 years (95% CI, 3.04-3.90) and QALYs by 2.27 years (95% CI 1.91-2.71) on average per patient. There were approximately 235,768 new lung cancers in the US in 2021, 56% of which were metastatic at diagnosis (SEER). Approximately 50% of lung cancers are adenocarcinomas, and approximately 12% of adenocarcinomas have DGRs: ALK (5%) , MET (4%) , ROS1 (2%) , RET (1%) , and NTRK1-3 (&lt; 1%). Thus, there were approximately 7,922 new metastatic NSCLC cases with DGRs in 2021. Prior studies have shown that DNA-only methods have a sensitivity of 80-85% for DGRs compared to RNA-based methods. At the level of the US population, this implies 1,188-1,584 false negative cases in 2021. The clinical impact of eliminating these false negatives by using RNA- instead of DNA-based methods to identify DGRs amounts to 4,110–5,480 life-years or 2,696–3,595 QALYs gained by appropriately matching patients with DGRs to targeted therapy over chemotherapy. Conclusions: DNA-only sequencing methods have limited sensitivity for DGRs in lung cancer, leading to false negatives and missed opportunities for targeted therapy. This modeling study suggests that the elimination of such false negatives using RNA-based detection methods would lead to meaningful gains in patient outcomes.

Cancer surveillance for patients with Li-Fraumeni Syndrome in Brazil: A cost-effectiveness analysis

In Brazil, there is a higher prevalence of Li-Fraumeni Syndrome (LFS) compared to worldwide, due to the founder mutation in the TP53 gene p.R337H. However, a large portion of the population, that depends on National Health Care System, does not have access to effective screening through the Toronto Protocol guidelines that enables early diagnosis and improves overall survival. Population strategies for early cancer detection recommended in Brazil are limited and additional screening is not offered to patients at a high risk, leading to late diagnoses and higher cancer mortality. This study aims to assess the cost-effectiveness of introducing annual screening that follows the Toronto Protocol for patients diagnosed with LFS in Brazil. A Markov decision analytic model was developed to estimate cost-effectiveness of 1,000 LFS carriers under surveillance and non-surveillance strategies over a patient's lifetime. The main outcome was the incremental cost-effectiveness ratio (ICER), expressed as cost per additional life year gained, comparing surveillance and non-surveillance strategies in p.R337H TP53 carriers. For females, the model showed a mean cost of $2,222 and $14,640 and yielded 22 and 26·2 life years for non-surveillance and surveillance strategies, respectively. The ICER for early cancer surveillance versus no surveillance was $2,982 per additional life year gained. For males, the model predicts mean lifetime costs of $1,165 and $12,883 and average life years of 23·5 and 26·3 for non-surveillance and surveillance strategies, respectively. This amounts to an ICER of $ 4,185 per additional life year. Surveillance had 64% and 45% probabilities of being the most cost-effective strategy for early cancer detection in female and male carriers, respectively. The adoption of surveillance for patients diagnosed with LFS by the Brazilian National Health Care System is cost-beneficial for both males and females. This research received no specific grant from any funding agency.

Optimising colorectal cancer screening in Shanghai, China: a modelling study

IntroductionTo reduce the burden of colorectal cancer (CRC) in Shanghai, China, a CRC screening programme was commenced in 2013 inviting those aged 50–74 years to triennial screening with a faecal...

Potential Gains in Life Expectancy Associated With Achieving Treatment Goals in US Adults With Type 2 Diabetes

Improvements in control of factors associated with diabetes risk in the US have stalled and remain suboptimal. The benefit of continually improving goal achievement has not been evaluated to date. To quantify potential gains in life expectancy (LE) among people with type 2 diabetes (T2D) associated with lowering glycated hemoglobin (HbA1c), systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), and body mass index (BMI) toward optimal levels. In this decision analytical model, the Building, Relating, Assessing, and Validating Outcomes (BRAVO) diabetes microsimulation model was calibrated to a nationally representative sample of adults with T2D from the National Health and Nutrition Examination Survey (2015-2016) using their linked short-term mortality data from the National Death Index. The model was then used to conduct the simulation experiment on the study population over a lifetime. Data were analyzed from January to October 2021. The study population was grouped into quartiles on the basis of levels of HbA1c, SBP, LDL-C, and BMI. LE gains associated with achieving better control were estimated by moving people with T2D from the current quartile of each biomarker to the lower quartiles. Life expectancy. Among 421 individuals, 194 (46%) were women, and the mean (SD) age was 65.6 (8.9) years. Compared with a BMI of 41.4 (mean of the fourth quartile), lower BMIs of 24.3 (first), 28.6 (second), and 33.0 (third) were associated with 3.9, 2.9, and 2.0 additional life-years, respectively, in people with T2D. Compared with an SBP of 160.4 mm Hg (fourth), lower SBP levels of 114.1 mm Hg (first), 128.2 mm Hg (second), and 139.1 mm Hg (third) were associated with 1.9, 1.5, and 1.1 years gained in LE in people with T2D, respectively. A lower LDL-C level of 59 mg/dL (first), 84.0 mg/dL (second), and 107.0 mg/dL (third) were associated with 0.9, 0.7, and 0.5 years gain in LE, compared with LDL-C of 146.2 mg/dL (fourth). Reducing HbA1c from 9.9% (fourth) to 7.7% (third) was associated with 3.4 years gain in LE. However, a further reduction to 6.8% (second) was associated with only a mean of 0.5 years gain in LE, and from 6.8% to 5.9% (first) was not associated with LE benefit. Overall, reducing HbA1c from the fourth quartile to the first is associated with an LE gain of 3.8 years. These findings can be used by clinicians to motivate patients in achieving the recommended treatment goals and to help prioritize interventions and programs to improve diabetes care in the US.

The potential long-term comparative effectiveness of larotrectinib vs standard of care for treatment of metastatic TRK fusion thyroid cancer, colorectal cancer, and soft tissue sarcoma

BACKGROUND: Larotrectinib is approved for patients with metastatic TRK fusion cancers, including differentiated thyroid (DTC), colorectal cancer (CRC), and soft tissue sarcoma (STS). Given the basket clinical trial design of larotrectinib, direct comparisons against standard of care in each of the mentioned cancers have not been assessed. Also, owing to the limited duration of follow-up in clinical trials, long-term outcomes for treatments are generally not known or estimated. OBJECTIVE: To compare expected life-years (LYs) and quality-adjusted life-years (QALYs) for patients with metastatic DTC, CRC, and STS who are eligible to receive larotrectinib against patients with unknown NTRK gene fusion status receiving standard-of-care therapy. METHODS: We developed a partitioned survival model to estimate the long-term comparative effectiveness of larotrectinib and standard of care for 3 tumor types. Larotrectinib survival data, assessed by independent review committee, were derived from an updated July 2020 analysis of 19, 8, and 23 adult patients (aged ≥ 18 years) with metastatic TRK fusion DTC, CRC, and STS, respectively. The DTC survival data also included 2 patients aged less than 18 years for a total of 21 patients. Survival estimates for standard of care were derived from published clinical trials. Progressionfree and overall survival for all treatments were estimated using survival distributions (Exponential, Weibull, Log-logistic, and Lognormal) fit to the available data. The final exponential form was selected based on goodness-of-fit and clinical plausibility. QALYs were estimated by adjusting the time spent in the preprogression and postprogression health states by utility weights derived from publicly available literature. RESULTS: Patients receiving larotrectinib experienced more LYs and QALYs compared with those receiving standard-of-care treatments across all 3 assessed cancer types. In DTC, patients receiving larotrectinib had 7.15-8.26 additional LYs (5.87-6.12 QALYs); in CRC, patients receiving larotrectinib had 1.26-1.27 additional LYs (1.00 QALYs); and in STS, patients receiving larotrectinib had 5.56 additional LYs (1.99 QALYs). CONCLUSIONS: Compared with standard of care in metastatic TRK wild-type cancers, larotrectinib is estimated to result in improved LY and QALY outcomes based on parametric extrapolations of intrial survival data. Because patient-level data were unavailable for adjusted analyses, a cross-trial comparison was performed. Given the limitations of this analytic approach and the small sample size for larotrectinib in trials, future studies should reassess the comparative effectiveness of larotrectinib vs standard of care as treated patients accrue and long-term survival data mature. DISCLOSURES: K. Suh, J. Carlson, and S. Sullivan report consulting fees from Bayer US LLC. F. Xia and T. Williamson are employees of Bayer US LLC. This study was funded by Bayer US LLC. The sponsor had no role in the design of the study and did not have any role in the execution, analyses, interpretation of the data, or decision to submit results.

Cardiovascular health and healthy longevity in people with and without cardiometabolic disease: A prospective cohort study.

SummaryBackgroundExisting evidence suggest an association of cardiovascular health (CVH) level with cardiometabolic disease (CMD) and mortality, but the effect of CVH on life expectancy, particularly survival years in CMD patients, has not been well-established. This study aimed to investigate the association of CVH defined using the 7-item tool from the American Heart Association (AHA) with life expectancy in people with and without CMD.MethodsBetween 2006 and 2010, a total of 341,331 participants (age 37–73 years) in the UK Biobank were examined and thereafter followed up to 2020. The CVH raised by the AHA included 4 behavioral (smoking, diet, physical activity, body mass index) and 3 biological (fasting glucose, blood cholesterol, blood pressure) metrics, coded on a three-point scale (0, 1, 2). The CVH score was the sum of 7 metrics (score range 0–14) and was then categorized into poor (scores 0–6), intermediate (7–11), and ideal (12–14) CVH. The flexible parametric survival models were applied to estimate life expectancy.FindingsDuring a median follow-up of 11.4 years, 18,420 (5.4%) deaths occurred. The multivariable-adjusted hazard ratio (HRs) of all-cause mortality were 2.21 (95% CI: 1.77 to 2.75) for male and 2.63 (95% CI: 2.22 to 3.12) for female with prevalent CMD and a poor CVH compared with CMD-free and ideal CVH group, an ideal CVH attenuated the CMD-related risk of mortality by approximately 62% for male and 53% for female. In CMD patients, an ideal CVH compared to poor CVH was associated with additional life years gain of 5.50 (95% CI: 3.94–7.05) for male 4.20 (95% CI: 2.77–5.62) for female at the age of 45 years. Corresponding estimates in those without CMD were 4.55 (95% CI: 3.62–5.48) and 4.89 (95% CI: 3.99–5.79), respectively. Ideal smoking status, fasting glucose and physical activity for male and ideal smoking status, cholesterol level and physical activity for female contributed to the greatest survival benefit.InterpretationAn ideal CVH is associated with a lower risk of premature mortality and longer life expectancy whether in general population or CMD patients. Our study highlights the benefits of maintaining better CVH across the life course and calls attention to the need for comprehensive strategies (healthy behavioral lifestyle and biological phenotypes) to preserve and restore a higher CVH level.FundingScientific Research Foundation for Scholars of HZNU (Grant No. 4265C50221204119)

Impact of the COVID-19 pandemic\u2019s first wave on the care and treatment situation of intravitreal injections in a German metropolitan region

PurposeThis study aims to evaluate the impact of the first coronavirus 2019 (COVID-19) wave in 2020 on patients scheduled for intravitreal injections (IVI) in a German metropolitan region.MethodsWe performed a multicentre prospective survey and retrospective analysis of the records of patients treated with intravitreal injections during the 20-week period from March to July 2020 in all four hospital eye departments in the city of Hamburg using a questionnaire (on treatment adherence, SarsCoV2-related personal, familial and social data) and treatment data.ResultsA total of 1038 patients (2472 IVI, 1231 eyes) and 818 questionnaires were evaluated. Longer duration of therapy, lower visual acuity (VA) of the treated and higher VA of the fellow untreated eye was were associated with a higher probability of visit cancellation. Every additional year of life posed a 2.6% lower risk of noncompliance. A COVID-19 infection in the family environment displayed a 5.5-fold chance of visit cancellation. Patients treated for neovascular age-related macular degeneration (nAMD) had a 36% reduced risk of visit cancellation compared to patients with diabetic macular oedema (DME).ConclusionA long preceding treatment period, low VA of the treated eye, high VA of the untreated eye, COVID-19 in the family and DME were identified as risk factors for IVI visit cancellations during the COVID-19 pandemic. Compliance to treatment might be improved in the future by taking these risk factors into account when scheduling patients for IVI during the exceptional circumstances of a pandemic.

Optimal Sequencing of Deceased Donor and Live Donor Kidney Transplant Among Pediatric Patients With Kidney Failure

In the US, live donor (LD) kidney transplant rates have decreased in pediatric recipients. Pediatric patients with kidney failure will likely need more than 1 kidney transplant during their lifetime, but the optimal sequence of transplant (ie, deceased donor [DD] followed by LD or vice versa) is not known. To determine whether pediatric recipients should first receive a DD allograft followed by an LD allograft (DD-LD sequence) or an LD allograft followed by a DD allograft (LD-DD sequence). This decision analytical model examined US pediatric patients with kidney failure included in the US Renal Data System 2019 Report who were waiting for a kidney transplant, received a transplant, or experienced graft failure. Kidney transplant sequences of LD-DD vs DD-LD. Difference in projected life-years between the 2 sequence options. Among patients included in the analysis, the LD-DD sequence provided more net life-years in those 5 years of age (1.82 [95% CI, 0.87-2.77]) and 20 years of age (2.23 [95% CI, 1.31-3.15]) compared with the DD-LD sequence. The net outcomes in patients 10 years of age (0.36 [95% CI, -0.51 to 1.23] additional life-years) and 15 years of age (0.64 [95% CI, -0.15 to 1.39] additional life-years) were not significantly different. However, for those aged 10 years, an LD-DD sequence was favored if eligibility for a second transplant was low (2.09 [95% CI, 1.20-2.98] additional life-years) or if the LD was no longer available (2.32 [95% CI, 1.52-3.12] additional life-years). For those aged 15 years, the LD-DD sequence was favored if the eligibility for a second transplant was low (1.84 [95% CI, 0.96-2.72] additional life-years) or if the LD was no longer available (2.49 [95% CI, 1.77-3.27] additional life-years). Access to multiple DD transplants did not compensate for missing the LD opportunity. These findings suggest that the decreased use of LD kidney transplants in pediatric recipients during the past 2 decades should be scrutinized. Given the uncertainty of future recipient eligibility for retransplant and future availability of an LD transplant, the LD-DD sequence is likely the better option. This strategy of an LD transplant first would not only benefit pediatric recipients but allow DD kidneys to be used by others who do not have an LD option.

Cost-Effectiveness Threshold for Healthcare: Justification and Quantification.

Every public health expenditure, including the one that saves lives or extends life expectancy of particular persons (target population), bears a cost. Although cost-effectiveness analysis (CEA) is routinely performed in health policy, ethical justification of CEA is rarely discussed. Also, there is neither consensus value nor even consensus method for determining cost-effectiveness threshold (CET) for life-extending measures. In this study, we performed ethical analysis of CEA by policy impact assessment based on connection of health and wealth (poorer people have statistically shorter life expectancies) and concluded that CEA is not only a practical but also an ethical necessity. To quantify CET, we used three independent methods: (1) literature survey of analyzing salaries in risky occupations, (2) utilizing Prospect Theory suggesting that people value their lives in monetary terms twice more than their lifetime earnings, and (3) literature survey of the U.S. current legal practice. To the best of our knowledge, nobody applied method (2) to determine CET. The three methods yielded rather similar results with CET about 1.0 ± 0.4 gross domestic product per capita (GDPpc) per quality-adjusted life-year. Therefore, a sum of not higher than 140% GDPpc is statistically sufficient to “purchase” an additional year of life—or, alternatively, to “rob” one year of life if taken away. Therefore, 140% GDP per capita per quality-adjusted life-year should be considered as the upper limit of prudent and ethically justified expenditure on life extension programs.

Promising measures to reduce the mortality in Russia: an analytical review

The purpose of the study was to identify promising measures to reduce mortality in Russia. Methods used included analysis of systematic reviews from PubMed, Web of Science, Scopus, and Google Scholar. Results. Many reasonable measures for reducing mortality in Russia include promoting healthy behaviour (tobacco control, alcohol control, support for healthy diet, physical activity) and preventing death due to external causes. It is necessary to increase the effectiveness of disease management, including arterial hypertension, hypercholesterolemia, diabetes mellitus, cardiovascular accidents, hepatitis C, HIV. This could require intensifying digital transformation of health care, implementing modern teamwork approaches to the patient’s treatment and follow-up with greater involvement of nurses and other personnel. In terms of screening, it is essential to expand coverage and introduce modern, effective screening methods for colorectal cancer, cervical cancer, and neonatal screening. It is necessary to expand vaccination against Covid-19, vaccination of the elderly from Pneumococcus, and adolescents from HPV. Prevention of mortality from external causes should include sets of measures targeted at the prevention of suicides, traffic accidents, fires, drownings, etc., in addition to alcohol control measures. Finally, increasing health care financing, including medication provision, can bring additional years of life. Conclusions. Russia has significant potential to implement new measures to reduce the mortality rate.