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.

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.

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.

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.

[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.

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.

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.

Patient inflammatory status and CD4+/CD8+ intraepithelial tumor lymphocyte infiltration are predictors of outcomes in high-grade serous ovarian cancer.

BACKGROUND: High-grade serous ovarian cancer (HGSOC) is the most prevalent and aggressive histologic type of ovarian cancer. To date, there are no reliable biomarkers to effectively predict patient prognosis. Studies have demonstrated inflammation and tumor infiltrating lymphocytes (TILs) correlate with a bad and good prognosis, respectively. Here, we sought to evaluate systemic inflammation and TILs as early prognostic markers of survival. METHODS: Neutrophil-to-lymphocyte ratio (NLR) and serum Lactate Dehydrogenase (LDH) were used as indicators of systemic inflammation. NLR, serum LDH, tumor infiltrating lymphocytes (TILs), PDL1 and quality of debulking surgery were evaluated as determinants of progression-free survival (PFS) and overall survival (OS) in a cohort of 128 HGSOC patients. RESULTS: Initial univariate analysis showed that systemic inflammation measures (NLR and serum LDH), debulking surgery, and intra-epithelial TILs have a significant impact on both PFS and OS. After adjustment for several variables, multivariate analyses confirmed intraepithelial CD4+ T-cells, systemic inflammation measures, PDL1 and debulking surgery as determinants of better OS and PFS. CONCLUSIONS: Systemic inflammation and TILs are early determinants of OS in HGSOC. Other variables such as the quality of debulking surgery and PDL1 also improve survival of patients. Regarding TIL sub-populations, intraepithelial CD4+ cells are associated to an increase in both PFS and OS. We also confirmed previous reports that demonstrate intraepithelial CD8+ cells correlate with an increase on PFS in ovarian cancer. A combined score using systemic inflammation and TILs may be of prognostic value for HGSOC patients.

Chilean Gastric Cancer Task Force: A study protocol to obtain a clinical and molecular classification of a cohort of gastric cancer patients.

Gastric cancer (GC) is the world's second-leading cause of neoplastic mortality. Genetic alterations, response to treatments, and mortality rates are highly heterogeneous across different regions. Within Latin America, GC is the leading cause of cancer death in Chile, affecting 17.6 per 100,000 people and causing >3000 deaths/y. Clinical outcomes and response to "one size fits all" therapies are highly heterogeneous and thus a better stratification of patients may aid cancer treatment and response.The Gastric Cancer Task Force is a Chilean collaborative, noninterventional study that seeks to stratify gastric adenocarcinomas using clinical outcomes and genomic, epigenomic, and protein alterations in a cohort of 200 patients. Tumor samples from the Pathology Department and the Cancer Center at UC-Christus healthcare network, Pontificia Universidad Católica de Chile will be analyzed using a panel of 143 known cancer genes (Oncomine Comprehensive Assay) at the Center of Excellence in Precision Medicine in Santiago, Chile. In addition, promoter methylation for selected genes will be performed along with tissue microarray for clinically relevant proteins (e.g., PD-L1, Erb-2, VEGFR2, among others) and Helicobacter pylori and Epstein-Barr virus status. Obtained data will be correlated to 120 clinical parameters retrieve from medical records, including general patient information, cancer history, laboratory studies, comorbidity index, chemotherapy, targeted therapies, efficacy, and follow-up.The development of a clinically meaningful classification that encompasses comprehensive clinical and molecular parameters may improve patient treatment, predict clinical outcomes, aid patient selection/stratification for clinical trials and may offer insights into future preventive and/or therapeutic strategies in patients from Latin America region. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03158571, Registered on May 18, 2017.

Eficacia del manejo conservador de las fracturas de calles en los pacientes en el Hospital Escuela Dr. Roberto Calderón G

Se realizó un estudio descriptivo y prospectivo con el objetivo de determinar algunos factores que puedan intervenir y provocar la inadecuada evolución de las fracturas de calles que deja secuela de orden inmediata y mediata. El estudio se realizó a los pacientes que asistieron a sala de Emergencia del Hospital Escuela Dr. Roberto Calderón, durante el período de junio a septiembre de 1999 y que fueron transferido a consulta externa con diagnóstico de fractura de calles. Los pacientes estudiados fueron 52 que asistieron a consulta externa del servicio de Ortopedía y Traumatología con diagnóstico de Fractura de Calles, y a los que se les dió seguimiento durante 7 meses desde su primera evaluación en consulta externa hasta su alta con un mes de fisioterapía