The socioeconomic distribution of life expectancy and healthy life expectancy in Chile.

BACKGROUND: Life expectancy (LE) has usually been used as a metric to monitor population health. In the last few years, metrics such as Quality-Adjusted-Life-Expectancy (QALE) and Health-Adjusted-Life- Expectancy (HALE) have gained popularity in health research, given their capacity to capture health related quality of life, providing a more comprehensive approach to the health concept. We aimed to estimate the distribution of the LE, QALEs and HALEs across Socioeconomic Status in the Chilean population. METHODS: Based on life tables constructed using Chiang II´s method, we estimated the LE of the population in Chile by age strata. Probabilities of dying were estimated from mortality data obtained from national registries. Then, life tables were stratified into five socioeconomic quintiles, based on age-adjusted years of education (pre-school, early years to year 1, primary level, secondary level, technical or university). Quality weights (utilities) were estimated for age strata and SES, using the National Health Survey (ENS 2017). Utilities were calculated using the EQ-5D data of the ENS 2017 and the validated value set for Chile. We applied Sullivan´s method to adjust years lived and convert them into QALEs and HALEs. RESULTS: LE at birth for Chile was estimated in 80.4 years, which is consistent with demographic national data. QALE and HALE at birth were 69.8 and 62.4 respectively. Men are expected to live 6.1% less than women. However, this trend is reversed when looking at QALEs and HALEs, indicating the concentration of higher morbidity in women compared to men. The distribution of all these metrics across SES showed a clear gradient in favour of a better-off population-based on education quintiles. The absolute and relative gaps between the lowest and highest quintile were 15.24 years and 1.21 for LE; 18.57 HALYs and 1.38 for HALEs; and 21.92 QALYs and 1.41 for QALEs. More pronounced gradients and higher gaps were observed at younger age intervals. CONCLUSION: The distribution of LE, QALE and HALEs in Chile shows a clear gradient favouring better-off populations that decreases over people´s lives. Differences in LE favouring women contrast with differences in HALEs and QALEs which favour men, suggesting the need of implementing gender-focused policies to address the case-mix complexity. The magnitude of inequalities is greater than in other high-income countries and can be explained by structural social inequalities and inequalities in access to healthcare.

Cost-Effectiveness of Mepolizumab Add-On in the Treatment of Severe Eosinophilic Asthma in Chile.

OBJECTIVE: Asthma is one of the 4 leading causes of death worldwide. Severe asthma is associated with poor quality of life, decreased life expectancy, and higher health resources consumption such as the use of oral corticosteroids (OCSs). This study aimed to assess the cost-effectiveness of mepolizumab as an add-on compared with the standard care of the Chilean public health system (combined inhaled corticosteroid therapy and a long-acting beta-agonist, short-acting beta-agonist, and OCS). MATERIALS AND METHODS: A Markov model was adapted to represent the day-to-day of patients with severe asthma over a lifetime horizon. Deterministic and probabilistic sensitivity analyses were performed to account for the second-order uncertainty of the model. In addition, a risk subgroup analysis was conducted to evaluate the cost-effectiveness of mepolizumab across different risk populations. RESULTS: Mepolizumab produces more benefits than standard of care alone (1 additional quality-adjusted life-year, a decrease of OCS usage, an approximated 11 avoided exacerbations) but it cannot be considered cost-effective in the light of the Chilean threshold (incremental cost-effectiveness ratio: US dollars [USD] 105 967/quality-adjusted life-year vs USD 14 896). Despite this, cost-effectiveness increases in specific subgroups, with an incremental cost-effectiveness ratio of USD 44 819 in patients with eosinophil count ≥ 300 cell/mcL and exacerbation history of at least 4 exacerbations in the past year. CONCLUSION: Mepolizumab cannot be considered a cost-effective strategy for the Chilean health system. Nevertheless, price discount in specific subgroups improves its cost-effectiveness profile significantly and may offer opportunities for access to specific subgroups.

Impact of Adjuvant FOLFOX on Quality of Life and Peripheral Neuropathy Incidence in Patients With Gastric Cancer: A Prospective Cohort Study.

OBJECTIVES: Perioperative and adjuvant chemotherapy have demonstrated clinical benefits in localized gastric cancer. Nevertheless, the reports on their effects on patient's health-related quality of life (HRQoL) are scarce. Here, we prospectively assessed quality of life and the incidence of chemotherapy-induced peripheral neuropathy (CIPN) in a cohort of patients treated with adjuvant FOLFOX. METHODS: Localized stomach or gastroesophageal junction adenocarcinoma patients who underwent curative resection were recruited at a single center. All patients received adjuvant FOLFOX6, and HRQoL and CIPN were assessed using the European organization for research and treatment of cancer quality life (EORTC) C30 and the EORTC CIPN20 questionnaires, respectively. Clinically significant deterioration of HRQoL was also assessed as a coprimary outcome in a longitudinal analysis. RESULTS: We recruited a total of 63 patients. Median age was 62.5 years, and 75% had stomach tumors. Twenty-four weeks after the start of treatment, the probability of being free from HRQoL deterioration and CIPN was 29% (95% confidence interval [CI] 18%-42%) and 6% (95% CI 2%-17%), respectively. Five-year disease-free survival was 45% (95% CI 24%-64%) and 5-year overall survival was 63% (95% CI 48%-76%). CONCLUSIONS: Adjuvant FOLFOX is associated with a high rate of long-term survival in localized gastric cancer; nevertheless, it has detrimental effects on patients' quality of life.

Budget impact analysis of the freestyle libre flash continuous glucose monitoring system® in patients with diabetes mellitus type 1 in Chile.

OBJECTIVE: To estimate the budget impact of covering the FreeStyle Libre Flash Continuous Glucose Monitoring System (FSL) for type 1 Diabetes Mellitus patients (T1DM), compared to self-monitoring of blood glucose (SMBG), from the perspective of public and private third-party payers in Chile. METHODS: A budget impact model was developed to estimate the cost difference between SMBG and FSL over five years. Two FSL coverage schemes were assessed. Input parameters were retrieved from the literature review and complemented by expert opinion. Healthcare costs were estimated by a micro-costing approach and reported in USD. RESULTS: For a public sector third-party payer, incorporating FSL implied a cost increase up to USD 0.013 per member per month (PMPM) for the fifth year under the broad coverage scheme and a net saving of 0.0001 PMPM (all years) under the restricted coverage scheme. From a private sector third-party payer, incorporating FSL implied savings up to USD 0.028 PMPM (fifth year) for the broad coverage scheme and up to USD 0.012 PMPM (fifth year) for the restricted scheme. CONCLUSION: Incorporating the FSL for T1DM patients was associated with a marginal incremental cost for the public sector third-party payer and cost savings in Chile's private healthcare sector.

Estimation of the demand for palliative care in non-oncologic patients in Chile.

BACKGROUND: Access to palliative care is an emerging global public health challenge. In Chile, a palliative care law was recently enacted to extend palliative care coverage to the non-oncologic population. Thus, a reliable and legitimate estimate of the demand for palliative care is needed for proper health policy planning. OBJECTIVE: To estimate the demand for Palliative Care in Chile. METHODOLOGY: Diseases likely to require palliative care were identified according to literature and expert judgement. Annual deaths of diseases identified were estimated for the periods 2018-2020. Demand estimation corresponds to the identification of the proportion of deceased patients requiring palliative care based on the burden of severe health-related suffering. Finally, patient-years were estimated based on the expected survival adjustment. RESULTS: The estimated demand for palliative care varies between 25,650 and 21,679 patients depending on the approximation used. In terms of annual demand, this varies between 1,442 and 10,964 patient-years. The estimated need has a minor variation between 2018 and 2019 of 0.85% on average, while 2020 shows a slightly higher decrease (7.26%). CONCLUSION: This is a replicable method for estimating the demand of palliative care in other jurisdictions. Future studies could approach the demand based on the decedent population and living one for a more precise estimation and better-informed health planning. It is hoped that our methodological approach will serve as an input for implementing the palliative care law in Chile, and as an example of estimating the demand for palliative care in other jurisdictions.

Health State Utility Values of Type 2 Diabetes Mellitus and Related Complications: A Systematic Review and Meta-Analysis.

OBJECTIVES: This study aims to synthesize health state utility values (HSUVs) of type 2 diabetes mellitus (T2DM) and its related complications published in the literature, conducting a meta-analysis of the data when possible. METHODS: We conducted a systematic search in MEDLINE and School of Health and Related Research Health Utilities Database repository. Studies focused on T2DM and its complications reporting utility values elicited using direct and indirect methods were selected. We categorized the results according to the instrument to describe health and meta-analyzed them accordingly. Data included in the analysis were pooled in a fixed-effect model by the inverse of variance mean and random-effects DerSimonian-Laird method. Two approaches on sensitivity analysis were performed: leave-one-out method and including data of HSUVs obtained by foreign population value sets. RESULTS: We identified 70 studies for the meta-analysis from a total of 467 studies. Sufficient data to pool T2DM HSUVs from EQ-5D instrument, hypoglycemia, and stroke were obtained. HSUVs varied from 0.7 to 0.92 in direct valuations, and the pooled mean of 3-level version of EQ-5D studies was 0.772 (95% confidence interval 0.763-0.78) and of 5-level version of EQ-5D 0.815 (95% confidence interval 0.808-0.823). HSUVs of complications varied from 0.739 to 0.843, or reductions of HSUVs between -0.014 and -0.094. In general, HSUVs obtained from 3-level version of EQ-5D and Health Utility Index 3 instruments were lower than those directly elicited. A considerable amount of heterogeneity was observed. Some complications remained unable to be pooled due to scarce of original articles. CONCLUSIONS: T2DM and its complications have a considerable impact on health-related quality of life. 5-level version of EQ-5D estimates seems comparable with direct elicited HSUVs.

El costo esperado de cáncer en Chile / The expected cost of cancer in Chile

BACKGROUND: Cancer is a public health priority in Chile. AIM: To estimate the expected annual cost of cancer in Chile, due to direct costs of health services, working allowances and indirect costs for productivity losses. MATERIAL AND METHODS: We undertook an ascendent costing methodology to calculate direct costs. We built diagnostic, treatment and follow-up cost baskets for each cancer type. Further, we estimated the expenditure due to sick leave subsidies. Both estimates were performed either for the public or private sector. Costs related to productivity loss were estimated using the human capital approach, incorporating disease related absenteeism premature deaths. The time frame for all estimates was one year. RESULTS: The annual expected costs attributed to cancer was $1,557 billion of Chilean pesos. The health services expected annual costs were $1,436 billion, 67% of which are spent on five cancer groups (digestive, hematologic, respiratory, breast and urinary tract). The expected costs of sick leave subsidies and productivity loss were $48 and $71 billion, respectively. CONCLUSIONS: Cancer generates costs to the health system, which obliges health planners to allocate a significant proportion of the health budget to this disease. The expected costs estimated in this study are equivalent to 8.9% of all health expenditures and 0.69% of the Gross Domestic Product. This study provides an updated reference for future research, such as those aimed at evaluating the current health policies in cancer.

Health and economic effects on patients with type 2 diabetes mellitus in the long run: predictions for the Chilean population.

BACKGROUND: Diabetes is associated to a high financial and disease burden, explaining a large proportion of expenditure of the health system in one year. The purpose of this study was to estimate long-term costs and health outcomes of recently diagnosed patients with type 2 diabetes in Chile. METHODS: Cost and consequence study based on mathematical discrete event simulation (DES) model. We modelled expected costs (USD) and quality-adjusted life-years (QALYs) from diagnosis to death (or the age of 95) of a hypothetical cohort of 100,000 incident cases, simulated based on the Chilean National Health Survey 2018. The incidence of twelve complications was estimated assuming the hazard functions provided by the United Kingdom Prospective Diabetes Study. We explore heterogeneity across patients based on their baseline risk covariates and their impact on costs and QALYs. RESULTS: The expected cost and QALY of a recently diagnosed type 2 diabetes patient in Chile were USD 8660 and 12.44 QALYs. Both costs and QALYs were independently determined by baseline risk and the patient's life expectancy from the diagnosis. Length of life since diagnosis showed the major impact on costs (5.2% increase for every additional year). Myocardial infarction was the most frequent complication (47.4%) and the most frequent cause of death. CONCLUSION: Diabetes type 2 determines a significant expenditure of the health system and substantial health losses. Although the control of cardiovascular risk factors and the metabolic control of the disease, both have an important impact on costs and outcomes, the main impact is achieved by postponing the age of onset of the disease.

Cost analysis of chronic pain due to musculoskeletal disorders in Chile.

The magnitude of the cost of chronic pain has been a matter of concern in many countries worldwide. The high prevalence, the cost it implies for the health system, productivity, and absenteeism need to be addressed urgently. Studies have begun describing this problem in Chile, but there is still a debt in highlighting its importance and urgency on contributing to chronic pain financial coverage. This study objective is to estimate the expected cost of chronic pain and its related musculoskeletal diseases in the Chilean adult population. We conducted a mathematical decision model exercise, Markov Model, to estimate costs and consequences. Patients were classified into severe, moderate, and mild pain groups, restricted to five diseases: knee osteoarthritis, hip osteoarthritis, lower back pain, shoulder pain, and fibromyalgia. Data analysis considered a set of transition probabilities to estimate the total cost, sick leave payment, and productivity losses. Results show that the total annual cost for chronic pain in Chile is USD 943,413,490, corresponding an 80% to the five diseases studied. The highest costs are related to therapeutic management, followed by productivity losses and sick leave days. Low back pain and fibromyalgia are both the costlier chronic pain-related musculoskeletal diseases. We can conclude that the magnitude of the cost in our country's approach to chronic pain is related to increased productivity losses and sick leave payments. Incorporating actions to ensure access and financial coverage and new care strategies that reorganize care delivery to more integrated and comprehensive care could potentially impact costs in both patients and the health system. Finally, the impact of the COVID-19 pandemic will probably deepen even more this problem.

Analisis del proceso de Evaluación de Tecnologías Sanitarias del Sistema de Protección Financiera Para Diagnósticos y Tratamientos de Alto Costo en Chile (Ley Ricarte Soto).

OBJECTIVES: In Chile, Ricarte Soto Law defines a financial protection system for high-cost health technologies through a process of prioritization and evaluation of health technologies (ETESA). This study aims to evaluate the ETESA process in terms of its technical content and its coherence with the Chilean regulatory framework. METHODS: This is a documentary review of 34 reports prepared by the Ministry of Health. A data extraction matrix was applied to evaluate the elements in content and process. The analysis evaluated technical errors, process inconsistencies, and disagreements in interpreting results. RESULTS: From 98 technologies, 59 were considered favorable, and 25 received coverage. A total of 20 inconsistencies were identified in the evaluation process, and 39 disagreements were documented on interpreting the results and technical errors. In the prioritization stage, we identified controversies in 44 technologies. CONCLUSION: The ETESA process of the Ricarte Soto Law is generally consistent with the regulations. Nevertheless, weaknesses persist in both technical and procedural terms. It is expected that the regulatory entity can use these results to implement the necessary improvements.

Cost-effectiveness analysis: fluticasone furoate/umeclidinium/vilanterol for the treatment of moderate to severe chronic obstructive pulmonary disease from the perspective of the Chilean public health system.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease characterized by long-term breathing problems and airflow limitations. International guidelines recommend using bronchodilators like long-acting beta- and muscarinic antagonists, and inhalational corticosteroids. OBJECTIVES: The cost-effectiveness of single-inhaler triple therapy containing fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) was compared to the treatments Fluticasone Furoate/Vilanterol (FF/VI), Umeclidinio/Vilanterol (UMEC/VI) and Fluticasone Propionate 250 mcg/Salmeterol 25mcg + Tiotropio 18 mcg (FP/SAL/TIO) for patients with COPD from the Chilean public health system perspective. METHODS: A cost-effectiveness analysis was performed, including a deterministic and probabilistic sensitivity analysis over a 25-year time horizon. Two scenarios were assessed to study the effect of a 3%-discount for costs and outcomes on FF/UMEC/VI. RESULTS: The incremental cost-effectiveness (ICER) of FF/UMEC/VI versus FF/VI was $10,076/QALY, being a cost-effective alternative to a threshold of one Gross Domestic Product per capita (GDPpc), while versus FP/SAL/TIO the ICER increased to $50,288/QALY, showing to be a non-cost effective alternative to 1 GDPpc, but at a threshold of 3 GDPpc. CONCLUSION: FF/UMEC/VI appears to be a cost-effective intervention for treating COPD compared to FF/VI. However, FF/UMEC/VI compared to FP/SAL/TIO showed an ICER above the threshold of 1 GDPpc, but, in comparison with lower price, the ICER was below 3 GDPpc.

[The expected cost of cancer in Chile]. / El costo esperado de cáncer en Chile.

BACKGROUND: Cancer is a public health priority in Chile. AIM: To estimate the expected annual cost of cancer in Chile, due to direct costs of health services, working allowances and indirect costs for productivity losses. MATERIAL AND METHODS: We undertook an ascendent costing methodology to calculate direct costs. We built diagnostic, treatment and follow-up cost baskets for each cancer type. Further, we estimated the expenditure due to sick leave subsidies. Both estimates were performed either for the public or private sector. Costs related to productivity loss were estimated using the human capital approach, incorporating disease related absenteeism premature deaths. The time frame for all estimates was one year. RESULTS: The annual expected costs attributed to cancer was $1,557 billion of Chilean pesos. The health services expected annual costs were $1,436 billion, 67% of which are spent on five cancer groups (digestive, hematologic, respiratory, breast and urinary tract). The expected costs of sick leave subsidies and productivity loss were $48 and $71 billion, respectively. CONCLUSIONS: Cancer generates costs to the health system, which obliges health planners to allocate a significant proportion of the health budget to this disease. The expected costs estimated in this study are equivalent to 8.9% of all health expenditures and 0.69% of the Gross Domestic Product. This study provides an updated reference for future research, such as those aimed at evaluating the current health policies in cancer.

The impact of hypoglycemia on healthcare costs: a modeling study from Chile.

BACKGROUND: This study aimed to estimate the expected cost of hypoglycemia in Diabetes Mellitus type-2 patients receiving hypoglycemic treatment in Chile and to explore the effect of the potential reduction of hypoglycemia over the total cost incurred by its public health system. RESEARCH DESIGN AND METHODS: A cost analysis was carried out based on a state transition mathematical model. The model used microsimulation with data from the National Health Survey 2016-2017 in Chile. Costs included follow-up, in-hospital and ambulatory care. Separate analysis was conducted for patients treated with insulin, or sulfonylurea. RESULTS: The annual expected total cost of hypoglycemia estimated for the Chilean public system was USD 288,922,523 (USD 273 per patient). The subgroup treated with insulin reached USD 353 per patient whereas the sulfonylurea subgroup was USD 217 per patient. The analysis revealed that for every 1% reduction of the incidence rate of severe hypoglycemia the cost is reduced 0.79% in total, 0.59% for the insulin subgroup, and 0.95% for the sulfonylurea subgroup. CONCLUSIONS: The cost of hypoglycemia represents a high proportion of the public health budget in Chile, being similar to those resources allocated to provide coverage of diabetic treatments through its universal health benefit plan. ABBREVIATIONS: DM2: type 2 diabetes mellitus; RR: relative risk; ENS: national health survey in Chile.

A Model-Based Economic Evaluation of Cladribine Versus Alemtuzumab, Ocrelizumab and Natalizumab for the Treatment of Relapsing-Remitting Multiple Sclerosis with High Disease Activity in Chile.

PURPOSE: The aim of this study was to evaluate the cost effectiveness of cladribine compared with alemtuzumab, natalizumab, and ocrelizumab for the treatment of highly active multiple sclerosis (HAD-MS) from the perspective of the Chilean health care public sector. MATERIALS AND METHODS: A Markov model was used to compare costs and quality-adjusted life-years (QALYs) over a 45-year time horizon using a 3% discount rate for costs and outcomes. Natural history of the disease was modeled in terms of progression of disability according to the Expanded Disability Status Scale (EDSS). A network meta-analysis was used as a source of comparative effectiveness for disability progression and annual relapse rates. Differences in costs and outcomes were modeled for only 10 years due to high temporal uncertainty. Ocrelizumab was assumed to have the same efficacy as cladribine due to lack of data. Direct costs were taken from national tariffs and expressed in 2019 US dollars. Utilities for EDSS health states were obtained from the literature. Second-order uncertainty was characterized through deterministic and probabilistic sensitivity analysis. FINDINGS: Compared with natalizumab (the current strategy covered in Chile), cladribine is associated with incremental costs and QALYs of US$70,989 and 1.875, respectively (incremental cost-effectiveness ratio [ICER] $37,861). Ocrelizumab was extendedly dominated by cladribine and natalizumab, and alemtuzumab was dominated by cladribine. A scenario analysis of a 10% discount did not modify the results substantially, but showed a decrease in the ICER of cladribine versus natalizumab (ICER $29,833/QALY). IMPLICATIONS: Cladribine is a new oral alternative to treat patients with HAD-MS that is expected to produce higher QALYs than all evaluated alternatives. In the context of a conservative analysis, cladribine cannot be considered cost effective for the Chilean health care public sector using a 1 GDP per capita threshold. However, under reasonable discount scenarios, cladribine becomes an attractive alternative for the health system.

Prevalence, burden of disease, and lost in health state utilities attributable to chronic musculoskeletal disorders and pain in Chile.

BACKGROUND: Musculoskeletal disorders are a leading cause of disability adjusted life years (DALY) in the world. We aim to describe the prevalence and to compare the DALYs and loss of health state utilities (LHSU) attributable to common musculoskeletal disorders in Chile. METHODS: We used data from the Chilean National Health Survey carried out in 2016-2017. Six musculoskeletal disorders were detected through the COPCOPRD questionnaire: chronic musculoskeletal pain, chronic low back pain, chronic shoulder pain, osteoarthritis of hip and knee, and fibromyalgia. We calculated the DALY for each disorder for 18 sex and age strata, and LHSU following an individual and population level approaches. We also calculated the fraction of LHSU attributable to pain. RESULTS: Chronic musculoskeletal pain disorder affects a fifth of the adult population, with a significant difference between sexes. Among specific musculoskeletal disorders highlights chronic low back pain with the highest prevalence. Musculoskeletal disorders are a significant cause of LHSU at the individual level, especially in the case of fibromyalgia. Chronic musculoskeletal pain caused 503,919 [283,940 - 815,132] DALYs in 2017, and roughly two hundred thousand LSHU at population level, which represents 9.7% [8.8-10.6] of the total LSHU occurred in that year. Discrepancy in the burden of musculoskeletal disorders was observed according to DALY or LSHU estimation. The pain and discomfort domain of LHSU accounted for around half of total LHSU in people with musculoskeletal disorders. CONCLUSION: Chronic musculoskeletal pain is a major source of burden and LHSU. Fibromyalgia should deserve more attention in future studies. Using the attributable fraction offers a straightforward and flexible way to explore the burden of musculoskeletal disorders.

Different Alternatives to Assess the Burden of Disease Using Attributable Fraction on a Disability Variable: The Case of Pain and Chronic Musculoskeletal Disorders in Chile.

OBJECTIVES: To estimate the burden of disease through 4 complementary procedures to years lived with disability (YLDs) using the concept of attributable fraction and including analysis of subdomains of disability. METHODS: We explored the burden on disability for 7 common musculoskeletal disorders (CMD) using the 2009 to 2010 Chilean National Health Survey, which included the Community Oriented Programme for the Control of Rheumatic Disease Core Questionnaire to identify cases with CMD, and an 8-domain questionnaire for health state descriptions. We calculated the proportion of disability attributable to pain in the general population and people with CMD. We also estimated the burden of CMD expressed as YLD and as the proportion of the disability in the general population attributable to people with CMD, with a particular focus in the pain domain of disability. Second order of uncertainty around point estimations was also characterized. RESULTS: Pain domain of disability accounted for 23.4% of the total disability in the general population, and between 20% (fibromyalgia) to 27.1% (osteoarthritis of the hip) in people with some of the selected CMD. People with chronic musculoskeletal pain accounted for 21.2% of total disability from general population, which generated 1.2 million of YLD (6679 YLD/100 000 inhabitants). Chronic low back pain and osteoarthritis of the knee were in the top position of specific CMDs, explaining the highest national burden. CONCLUSION: Pain is an essential component of disability in people with CMD and also in the general population. The approach used can be easily applied to other health conditions and other domains of disability.

Early versus deferred anti-SARS-CoV-2 convalescent plasma in patients admitted for COVID-19: A randomized phase II clinical trial.

BACKGROUND: Convalescent plasma (CP), despite limited evidence on its efficacy, is being widely used as a compassionate therapy for hospitalized patients with COVID-19. We aimed to evaluate the efficacy and safety of early CP therapy in COVID-19 progression. METHODS AND FINDINGS: The study was an open-label, single-center randomized clinical trial performed in an academic medical center in Santiago, Chile, from May 10, 2020, to July 18, 2020, with final follow-up until August 17, 2020. The trial included patients hospitalized within the first 7 days of COVID-19 symptom onset, presenting risk factors for illness progression and not on mechanical ventilation. The intervention consisted of immediate CP (early plasma group) versus no CP unless developing prespecified criteria of deterioration (deferred plasma group). Additional standard treatment was allowed in both arms. The primary outcome was a composite of mechanical ventilation, hospitalization for >14 days, or death. The key secondary outcomes included time to respiratory failure, days of mechanical ventilation, hospital length of stay, mortality at 30 days, and SARS-CoV-2 real-time PCR clearance rate. Of 58 randomized patients (mean age, 65.8 years; 50% male), 57 (98.3%) completed the trial. A total of 13 (43.3%) participants from the deferred group received plasma based on clinical aggravation. We failed to find benefit in the primary outcome (32.1% versus 33.3%, odds ratio [OR] 0.95, 95% CI 0.32-2.84, p > 0.999) in the early versus deferred CP group. The in-hospital mortality rate was 17.9% versus 6.7% (OR 3.04, 95% CI 0.54-17.17 p = 0.246), mechanical ventilation 17.9% versus 6.7% (OR 3.04, 95% CI 0.54-17.17, p = 0.246), and prolonged hospitalization 21.4% versus 30.0% (OR 0.64, 95% CI, 0.19-2.10, p = 0.554) in the early versus deferred CP group, respectively. The viral clearance rate on day 3 (26% versus 8%, p = 0.204) and day 7 (38% versus 19%, p = 0.374) did not differ between groups. Two patients experienced serious adverse events within 6 hours after plasma transfusion. The main limitation of this study is the lack of statistical power to detect a smaller but clinically relevant therapeutic effect of CP, as well as not having confirmed neutralizing antibodies in donor before plasma infusion. CONCLUSIONS: In the present study, we failed to find evidence of benefit in mortality, length of hospitalization, or mechanical ventilation requirement by immediate addition of CP therapy in the early stages of COVID-19 compared to its use only in case of patient deterioration. TRIAL REGISTRATION: NCT04375098.

Medication review with follow-up for cardiovascular outcomes: a trial based cost-utility analysis.

Aim: To assess the trial-based cost-effectiveness of medication review with follow-up compared with usual care in primary care. Materials & methods: A cluster randomized controlled trial included patients if they were independent older adults, receiving five or more prescriptions, with moderate or high cardiovascular risk. Costs were estimated from the public healthcare sector perspective, and health benefits were measured as quality-adjusted life years. Both of which were used to calculate the incremental cost-effectiveness ratio. Results: Twelve centers completed the study, six (146 patients) in the intervention group and six (145 patients) in the control group. The base-case analysis showed an incremental cost-effectiveness ratio of US$ (2019) 434.4/quality-adjusted life year (95% CI 64.20-996.03). Conclusion: The intervention was cost-effective in the public primary care setting.

High Proportion of Potential Candidates for Immunotherapy in a Chilean Cohort of Gastric Cancer Patients: Results of the FORCE1 Study.

Gastric cancer (GC) is a heterogeneous disease. This heterogeneity applies not only to morphological and phenotypic features but also to geographical variations in incidence and mortality rates. As Chile has one of the highest mortality rates within South America, we sought to define a molecular profile of Chilean GCs (ClinicalTrials.gov identifier: NCT03158571/(FORCE1)). Solid tumor samples and clinical data were obtained from 224 patients, with subsets analyzed by tissue microarray (TMA; n = 90) and next generation sequencing (NGS; n = 101). Most demographic and clinical data were in line with previous reports. TMA data indicated that 60% of patients displayed potentially actionable alterations. Furthermore, 20.5% were categorized as having a high tumor mutational burden, and 13% possessed micro-satellite instability (MSI). Results also confirmed previous studies reporting high Epstein-Barr virus (EBV) positivity (13%) in Chilean-derived GC samples suggesting a high proportion of patients could benefit from immunotherapy. As expected, TP53 and PIK3CA were the most frequently altered genes. However, NGS demonstrated the presence of TP53, NRAS, and BRAF variants previously unreported in current GC databases. Finally, using the Kendall method, we report a significant correlation between EBV+ status and programmed death ligand-1 (PDL1)+ and an inverse correlation between p53 mutational status and MSI. Our results suggest that in this Chilean cohort, a high proportion of patients are potential candidates for immunotherapy treatment. To the best of our knowledge, this study is the first in South America to assess the prevalence of actionable targets and to examine a molecular profile of GC patients.

Chilean Registry for Neuroendocrine Tumors: A Latin American Perspective.

Neuroendocrine tumors (NETs) are relatively rare and highly heterogeneous neoplasms. Despite this, recent studies from North America and Central Europe have suggested an increase in incidence. In Latin America, NET data are scarce and scattered with only a few studies reporting registries. Our goal was to establish a NET registry in Chile. Here, we report the establishment and our first 166 NET patients. We observed a slight preponderance of males, a median age at diagnosis of 53 years and a median overall survival of 110 months. As anticipated, most tumors were gastroenteropancreatic (GEP). Survival analyses demonstrated that non-GEP or stage IV tumors presented significantly lower overall survival (OS). Similarly, patients with surgery classified as R0 had better OS compared to R1, R2, or no surgery. Furthermore, patients with elevated chromogranin A (CgA) or high Ki67 showed a trend to poorer OS; however, these differences did not reach statistical significance (log-rank test p = 0.07). To the best of our knowledge, this is the first report of a NET registry in Chile. Median OS in our registry (110 months) is in line with other registries from Argentina and Spain. Other variables including age at diagnosis and gender were similar to previous studies; however, our data indicate a high proportion of small-bowel NETs compared to other cohorts, reflecting the need for NET regional registries. Indeed, these registries may explain regional discrepancies in incidence and distribution, adding to our knowledge on this seemingly rare, highly heterogeneous disease.