Economic Implications of Endometriosis: A Review.

Endometriosis is a chronic inflammatory disease that can have serious physical and emotional consequences for patients in terms of pain, quality of life, and infertility. Despite affecting about 10% of women, the pathophysiology and economic impact of the disease are not fully understood. This study aimed to review and summarize research articles quantifying the direct and indirect costs of endometriosis in the context of current national and international treatment guidelines. A search including the terms 'endometriosis' AND 'costs' OR 'cost of illness' OR 'cost analysis' OR 'economic burden' was performed, focusing on studies published between January 2000 and May 2022. Total costs, costs of primary and secondary care, productivity losses, and indirect costs were reported. The medical costs of endometriosis were principally registered in secondary care settings, where surgery was the main cost driver. There was considerable variability of populations and study settings, with the overall direct medical cost range of endometriosis from US$1459 to US$20,239 (2022) per patient per year. An increasing trend has been reported in secondary care costs over time; however, not enough data were available at this time to evaluate inpatient and outpatient costs versus treatment strategies. Similarly, further research is required to evaluate the costs and potential savings associated with new therapies. Numerous studies have evaluated the indirect costs of endometriosis in recent years, finding costs between US$4572 and US$14,079 (2022). Currently, limited data are available on the economic burden of the disease at the patient level.

Hospital incidence and medical costs of polycythemia vera in Spain: a retrospective database analysis.

BACKGROUND: Polycythemia vera (PV) is one of the most common chronic myeloproliferative neoplasms, yet, little data is available on the epidemiology of PV in Spain and the costs of its management. This study aimed to evaluate the hospital incidence and mortality rate of PV in Spain, and to estimate hospital medical costs. METHODS: Hospital admission records of patients with PV registered between 2005 and 2019 were obtained from a Spanish hospital discharge database and analyzed in a retrospective multicenter study. RESULTS: Admission files of 490 patients were reviewed. Median age was 74 years; patients presented numerous conditions associated to age, namely hypertension, diabetes or anemia. Hospital mortality rate was associated to pulmonary heart disease, respiratory conditions and kidney disease. Most of the files analyzed corresponded to inpatient admissions; hospital incidence decreased over the study period in patients over 60 years. Median admission cost was €5580, increasing in patients deceased during the hospitalization. Admission cost increased significantly between 2006 and 2011. CONCLUSIONS: This study provides an evaluation of hospital management and costs of PV in Spain. Future studies should focus on the revision of disease management in the country and measuring total medical costs, which could be higher than global estimations.

Hospital care of endometriosis in Spain: a retrospective multicenter analysis of patient characteristics and costs.

BACKGROUND: Despite the potential serious outcomes associated with endometriosis, few data is available describing the real clinical practice and costs. The aim of this study was to evaluate the characteristics of patients diagnosed with endometriosis in Spain, to measure incidences within the hospital setting and the associated medical costs.Methods: Admission records of patients with endometriosis registered between 2009 and 2018 were obtained from a Spanish hospital discharge database and analyzed in a retrospective multicenter study. RESULTS: Data corresponded primarily to inpatient admissions, with a median length of stay of 3 days. Length of stay correlated with patients' age. Admissions were mainly associated with surgical procedures, namely local excision or destruction of lesions. The majority of secondary diagnoses registered corresponded to inflammatory disease of female pelvic organs; 9.2% of patients presented neoplasms of uterus and only 0.9% registered ovarian neoplasms. Mean admission cost was €3566 over the study period. CONCLUSIONS: The majority of admissions reviewed in this study corresponded to the removal of ovarian lesions, although data suggested a decrease in the number of cases that were treated as hospital inpatient admissions over the study period. Older patients, surgical procedures, and lengthier admissions were associated with higher medical costs.

Incidence, mortality and medical costs of patients hospitalized with melanoma in Spain: a retrospective multicentre observational study.

OBJECTIVE: This study aimed to update and analyze the in-hospital incidence and in-hospital mortality of melanoma in Spain, to evaluate any temporal trends in both measures and to quantify the direct medical costs of specialized care that are associated to this malignancy. METHODS: Anonymized specialized care admission records registered between 1 Jan 2011 and 31 Dec 2017 were extracted from a Spanish nationwide hospital discharge database. RESULTS: Records included corresponded to 16,657 patients, of which 50.62% were male. In nearly 38% of all admissions secondary malignant tumors were registered, principally tumors in the lymph nodes. In-hospital incidence of melanoma was 67.5 and 58.2 per 100,000 males and females, respectively, in the study period (2011-2017), with a decreasing tendency measured after the year 2014. Mortality increased with patients' age and over time in patients over 75 years of age. In-hospital mortality was 7.73% for males and 5.29% for female patients, and was principally associated to metastatic tumors, principally in the lungs, liver and brain. Mean length of hospital stay was 4.36 days, with a readmission rate of 6.93% and a 15.70% of urgent admissions. The mean annual direct medical cost per patient was €4175, increasing between 2014 and 2017. CONCLUSIONS: The increasing in-hospital incidence of melanoma appeared to reverse in 2014, as did the increasing mortality rate measured in older males. The shift in melanoma in-hospital incidence could respond to the increasing trend to treat patients in primary care settings. Further studies will be required to confirm these trends in order to adapt the healthcare system.

Burden of Hodgkin and non-Hodgkin lymphoma in Spain over a 10-year period: productivity losses due to premature mortality.

Background: Cancer is annually responsible for millions of deaths in Europe and billions of euros in productivity losses; the estimated mortality rate of lymphoma was of 7.07 per 100,000 individuals in Spain in 2018. This study aimed to evaluate the burden that lymphoma mortality represents for the Spanish society. Methods: The human capital approach was used to estimate the costs derived from premature mortality due to lymphoma between 2008 and 2017. Results: The number of deaths attributable to lymphoma increased steadily over the study period; the major number of deaths occurred among males aged 80 to 84 years. During the study period, 97,069 years of productive life were lost, a parameter that decreased noticeably over time due to the reduction in the number of deaths at working age. Productivity losses decreased accordingly. Lymphoma represented the 45.36% of losses due to hematological malignancies, generating €121 million in losses the year 2017. Hodgkin lymphoma was, among hematological malignancies, the malignancy accounting for the highest portion of losses per individual. Conclusions: Lymphoma represents a significant burden that can be reduced with the implementation of improved diagnosis and treatment methods, which must be taken into account in resource allocation and management policies.

Analysis of hospital incidence and direct medical costs of intrahepatic cholangiocarcinoma in Spain (2000-2018).

INTRODUCTION: Intrahepatic cholangiocarcinomas (iCCA) are aggressive tumors, often diagnosed in advanced stages and with limited curative treatment options. Their incidence has raised in the past years, increasing their associated economic burden. This study aimed to measure hospital incidence and mortality of iCCA and to evaluate direct medical costs. METHODS: Records of admissions due to iCCA between 1 January 2000 and 31 December 2018 were obtained from a Spanish National discharge database. Hospital incidence and mortality were measured within the hospitalized population and medical costs were assessed for specialized healthcare. RESULTS: Admission files corresponded to 23,315 patients, with a median age of 73 years (IQR = 17) and 55.9% of males. Cholangiocarcinoma presented a hospital incidence of 6.9 per 10,000 persons in 2018, increasing significantly over the study period. In-hospital mortality was 31.5% in the year 2018 and remained stable over the study period. The mean annual direct medical cost of secondary care was €9417 per patient in the year 2017, and increased significantly between 2000 and 2008, stabilizing after 2009. CONCLUSION: The incidence of iCCA in Spain increased over the past years. The medical costs of iCCA per patient stabilized after 2008 but total costs are expected to increase if incidence continues to raise.

Evaluation of productivity losses due to premature mortality from colorectal cancer.

Cancer is responsible annually for around 27% of all deaths in Spain, 15% of which are caused by colorectal cancer. This malignancy has increased its incidence considerably over the past years, which surely impacts global productivity losses. The evaluation of lost productivity due to premature mortality provides valuable information that guides healthcare policies into the establishment of prevention and screening programs. The purpose of this study was to assess the productivity losses from premature deaths due to colorectal cancer over a ten year period (2008-2017). The costs derived from premature mortality due to this highly prevalent cancer were estimated using data on mortality, age- and sex-specific reference salaries and unemployment rates in Spain via the human capital approach. Between 2008 and 2017, 15,103 persons died per year from colorectal cancer, representing almost 15% of all cancer-related deaths. Annually, 25,333 years of potential productive life were estimated to be lost on average, 14,992 in males and 10,341 in females. Productivity losses summed €510.8 million in in 2017, and the cancers of the colon and rectum accounted for 9.6% of cancer-related productivity losses in 2017 in Spain. Colorectal cancer has an important weight in terms of productivity losses within the Spanish population, consequently, prevention and early detection programmes should be promoted and implemented to achieve significant reductions in mortality and productivity losses.

Epidemiology, management, and economic impact of acute myeloid leukemia and myelodysplastic syndrome in Spain at the hospital level: a claims database analysis.

OBJECTIVES: This study reviewed patient characteristics, management, and medical costs of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDSs) in Spanish hospitals. METHODS: Data were extracted from the Spanish Ministry of Health records via a claims database containing patient records from 192 private and 313 public hospitals between 1997 and 2015 for AML, and 2008 and 2015 for MDS. Direct medical costs at the hospital level were calculated based on mean medical procedure costs determined per the Spanish Ministry of Health. RESULTS: Records for 39,568 patients with AML and 33,091 with MDS were analyzed. The median age of AML patients was 65 years (interquartile range (IQR) = 27) and of MDS patients was 81 years (IQR = 12). In terms of disease management, 58% and 83% of admissions were due to emergencies for patients with AML and MDS, respectively; median length of hospital stay was 14 days (IQR = 25) for AML and seven days (IQR = 9) for MDS. There was an increase in allogeneic hematopoietic stem cell transplantations over time for patients with AML or MDS. Mean annual direct medical costs of AML and MDS, respectively, were €66,422,245 and €42,635,313 for total costs, and €30,775 and €10,312 per patient. Of the total costs, transplantations contributed total annual costs of €15,843,982 and €2,705,791 for patients with AML and MDS, respectively. CONCLUSIONS: This study provides novel data to assist decision makers in allocating resources. AML and MDS represent a significant burden for the National Spanish Healthcare System, with substantial costs incurred in secondary care, principally associated with the increasing number of transplantations.

Current status of lung cancer in Spain: a retrospective analysis of patient characteristics, use of healthcare resources and in-hospital mortality.

Objective: This study aimed to describe the current status of lung cancer in Spain, including patient characteristics and in-hospital mortality, and to revise disease management and the direct medical costs of secondary care.Methods: A retrospective observational study was set to analyse anonymized primary and secondary care records of patients admitted with lung cancer in Spain between 2011 and 2016. Data were obtained from the Primary Care Dataset and the Centralised Hospital Discharge Database.Results: Admissions files from 12,119 primary care and 113,574 secondary care patients were analyzed. Only 21% of all patients were females, yet the number of female patients presented an increasing trend over the study period. Non-small-cell lung carcinoma represented 85.29% of all lung malignant neoplasms; metastatic or secondary malignant neoplasms were diagnosed in 76.66% of admissions. Other relevant comorbid conditions registered at the hospital level were hypertension, disorders of lipoid metabolism, diabetes mellitus and a history of tobacco use. In-hospital mortality was 22% over the study period and was associated with respiratory failure. Mean hospitalization time was 9.57 days and most admissions were due to emergencies. The mean cost of secondary care per patient was €8475, increasing significantly over the study period. Cost per patient was higher in those diagnosed with a squamous cell carcinoma.Conclusions: Preventive and early detection measures are recommended, continuing to focus on females. In parallel, a multidisciplinary approach could optimize patient journey considering the presence of disease comorbidities, although its role in lung cancer mortality should be further explored.

Results after 10 years of colorectal cancer screenings in Spain: Hospital incidence and in-hospital mortality (2011-2016).

BACKGROUND: Colorectal cancer incidence in Spain increased considerably between the early nineties and 2010. To reverse this tendency, screenings were progressively implemented starting the year 2001, targeting the population aged 50 to 69 years. OBJECTIVES: This study aimed to update colorectal cancer incidence and mortality trends in Spain and provide a detailed analysis of disease management and risk factors involved in in-hospital mortality. METHODS: To this aim, anonymised primary and specialised care admission records from 2011 to 2016 were extracted from a Spanish claims database representative of all Spanish regions. RESULTS: Primary care files from 37,317 patients and specialised care files from 192,048 patients were obtained, in which males represented the 56.17% and 60.70% of patients respectively. In-hospital mortality rate was 10.07% and remained stable during the study period, similarly to colorectal cancer incidence within the hospitalised population, which was 106 per 10,000 patients. Patients deceased during the hospitalisation presented an increased presence of metastatic tumours. Mean length of hospital stay decreased significantly over the study period from 13.43 days to 11.67 days (p<0.001), similarly to patients' 30-day readmission rate, which registered a decrease from the 15.29% to 13.58% (p<0.001). In consequence, the direct medical cost measured per patient, of €10,992, decreased over time. The implementation of colorectal cancer screening programmes caused a significant decrease in the number of new diagnoses in patients aged 75 to 79 years that may be attributable to the implementation of colorectal cancer screening programmes; however, in-hospital mortality was not reduced. Metastatic tumours and other conditions as anaemia are associated with higher in-hospital mortality rates.

Exploring the current status of neuroendocrine tumours: a population-based analysis of epidemiology, management and use of resources.

BACKGROUND: Neuroendocrine tumours (NETs) are rare malignancies characterised by its capacity to synthesise and secrete monoamines, due to its neuroendocrine origin. Its varied locations and symptoms have traditionally been responsible for extended delays in their diagnosis. The interest of this study was to characterise the patient population diagnosed with NETs in Spain and to revise how the disease is managed, together with the hospitalisation costs of these patients. METHODS: The database included records of all patients diagnosed with a NET between 2010 and 2015. Admission records were used to evaluate hospitalisation, disease management data and costs, and single-patient files were used to characterise the population. RESULTS: Nine Thousand One Hundred Twenty patients were diagnosed with a neuroendocrine tumour between 2010 and 2015, with a 2 fold increase in the diagnosis rate over the study period. 42.25% of the patients were females, while 57.75% were males, and mean diagnosis age was 62.58 years (SD = 14.65). Considering all the registered neuroendocrine neoplasms, 46.86% of the patients had malignant well-differentiated NETs, 32.02% had a malignant poorly differentiated neuroendocrine carcinoma and 42.93% of patients developed metastatic NETs. In addition, 18.59% of patients were diagnosed with benign well-differentiated NETs. The most common tumour sites were the bronchus, lung and other sites, including pancreatic tumours; metastasis was found in the liver and distant lymph nodes. Pancreatic resection was the most common surgical procedure utilised in these patients, summing 19% of total expenses, the injection of an unspecified therapeutic substance (including targeted therapies) was registered in 11.40% of admissions, while chemotherapy was registered in only 6.85% of admissions. The annual healthcare cost of NETs was €15,373,961, corresponding to €9092 per patient. CONCLUSIONS: The implementation of standard diagnosis procedures should be prioritised, with a focus on the pancreas and lung, and taking into account that 42.93% of the patients develop a metastatic tumour. The presence of comorbidities and multimorbidities should be considered in order to develop more efficient disease management protocols.

The cost of lost productivity due to premature lung cancer-related mortality: results from Spain over a 10-year period.

BACKGROUND: Cancer mortality is one of the major causes of productivity loss; and within all cancer sites, malignant neoplasms of the lung continue to be the principal cancer-related cause of death in Spain, with a survival rate of only 10.7%. Thus its effects in labour productivity are a major concern and represent a great social impact. The objective of this study was to evaluate the productivity losses that occur as a result of premature deaths due to lung cancer in Spain. METHODS: The human capital approach was used to calculate the costs derived from the premature mortality due to lung cancer, via the extraction of data on mortality, reference salaries and unemployment rates. RESULTS: Deaths due to lung cancer represented the 28.90% and the 10.83% of all cancer-related deaths in 2017 in males and females respectively, with an increasing tendency in this last group. In addition, the YPPLL count increased in the study period among females. Lung cancer was responsible annually for 60,846 YPPLL, and productivity losses summed €13.1 billion over the 10 year period. CONCLUSIONS: The assessment of productivity losses due to lung cancer provides new information that may assist decision makers in the allocation of resources, reducing the burden it supposes in working-age individuals.

Hazard assessment of three haloacetic acids, as byproducts of water disinfection, in human urothelial cells.

Disinfection by-products (DBPs) are compounds produced in the raw water disinfection processes. Although increased cancer incidence has been associated with exposure to this complex mixture, the carcinogenic potential of individual DBPs remains not well known; thus, further studies are required. Haloacetic acids (HAAs) constitute an important group among DBPs. In this study, we have assessed the in vitro carcinogenic potential of three HAAs namely chloro-, bromo-, and iodoacetic acids. Using a long-term (8 weeks) and sub-toxic doses exposure scenario, different in vitro transformation markers were evaluated using a human urothelial cell line (T24). Our results indicate that long-term exposure to low doses of HAAs did not reproduce the genotoxic effects observed in acute treatments, where oxidative DNA damage was induced. No changes in the transformation endpoints analyzed were observed, as implied by the absence of significant morphological, cell growth rate and anchorage-independent cell growth pattern modifications. Interestingly, HAA-long-term exposed cells developed resistance to oxidative stress damage, what would explain the observed differences between acute and long-term exposure conditions. Accordingly, data obtained under long-term exposure to sub-toxic doses of HAAs could be more accurate, in terms of risk assessment, than under acute exposure scenarios.

In vitro studies on the tumorigenic potential of the halonitromethanes trichloronitromethane and bromonitromethane.

Epidemiological data indicate that chronic exposure to water disinfection by-products (DBPs) may result in increased risk of cancer. However, the real carcinogenic potential of individual DBPs is not well known. In this study, we assessed the in vitro carcinogenic potential of trichloronitromethane (TCNM) and bromonitromethane (BNM), two halonitromethanes (HNMs) commonly found in DBPs' mixtures at comparably high concentrations. Human lung BEAS-2B cells were exposed for 8weeks to TCNM and BNM, and the acquisition of different in vitro cancer-like features was evaluated. The results indicate that long-term exposure to non-cytotoxic doses of TCNM and BNM did not cause carcinogenic transformation as indicated by the absence of morphological changes, no effects on cell growth, no changes in the level of matrix metalloproteinases (MMPs) secretion, and no increased anchorage-independent cell growth capacity. Furthermore, TCNM- and BNM-exposed BEAS-2B cells were unable to enhance tumour growth directly or by indirect influence of the surrounding stroma. Our results indicate that the carcinogenic effects of DBP mixtures cannot be attributed to the evaluated HNMs. This is the first study evaluating the cell transformation effects of TCNM and BNM under a long-term exposure scenario using suitable hallmarks of the cancer process.