Treatment patterns and outcomes in light chain amyloidosis: An institutional registry of amyloidosis report in Argentina.

Light chain (AL) amyloidosis is a form of systemic amyloidosis, causing organ dysfunction, mainly affecting the heart and kidney. Patient-tailored and risk-adapted decision making is critical in AL amyloidosis management. There is limited real-world evidence data from Argentina and Latin America regarding the treatment approaches for AL amyloidosis. This retrospective cohort study aimed to describe the treatment patterns and outcomes in adult patients (>18 years) diagnosed with AL amyloidosis at the Hospital Italiano in Buenos Aires, Argentina, using a 10-yearfollow-up data (June 1, 2010 to May 31, 2019) from the institutional registry of amyloidosis (IRA). The study population had a mean age of 63 years and 54.4% weremale. Heart and kidney were the most frequently affected organs. Of the 90 eligible patients included in the study, 70underwent treatment. Bortezomib-based regimen was the preferred first-line treatment (75.7% patients). Overall,54.4% of the patients presented a deep response (complete or very good partial response). Median overall survival (OS) was 5years, the 1-year OS and progression free survival rates were 80% (95% confidence interval [CI]: 68-87) and 80% (95%CI 68-87)), respectively. This study provides vital real-world evidence for the long-term treatment patterns and survival in a large cohort of AL amyloidosis patients in Argentina.

Clinical Outcomes of Patients With B-Cell Non-Hodgkin Lymphoma in Real-World Settings: Findings From the Hemato-Oncology Latin America Observational Registry Study.

PURPOSE: Real-world evidence on non-Hodgkin lymphoma (NHL) management in Latin America is currently lacking. The objective of this study was to describe treatment characteristics and outcomes of NHL in Latin America. METHODS: A total of 2,967 patients with NHL with aggressive and indolent subtypes, including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle-cell lymphoma (MCL), and mucosa-associated lymphoid tissue (MALT) lymphoma, with incident or prevalent diagnosis between 2006 and 2015, were retrospectively identified using clinical charts registered in the Hemato-Oncology Latin America Observational Registry. Associations between treatment regimen and age at diagnosis with clinical outcomes within each subtype were estimated using Cox proportional hazard regression. RESULTS: Most patients with NHL received 1L chemoimmunotherapy, most commonly cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with/without rituximab. Five-year survival rates were higher for MALT lymphoma (90.8%) and FL (87.6%) versus DLBCL (69.0%) and MCL (57.1%), with variations between countries. The median overall survival from first relapse for patients with DLBCL was 6.6 years, with lower risk of death for those diagnosed at age < 65 years (hazard ratio = 0.732; P = .0161). Patients achieved a longer median progression-free survival with 1L rituximab-CHOP (R-CHOP) versus CHOP or rituximab, cyclophosphamide, vincristine, and prednisone (RCVP) (7.7 v 3.0 or 1.8 years, respectively). Use of regimens other than R-CHOP was associated with a higher risk of death/progression for patients with DLBCL (rituximab, ifosfamide, carboplatin, and etoposide/ifosfamide, carboplatin, and etoposide) and FL (CHOP). There was no relationship between treatment prescribed and age at diagnosis with outcomes from first/second relapse in DLBCL and FL. CONCLUSION: Differences in treatment outcomes between NHL subtypes were observed, reflecting variations in NHL management and barriers to treatment access in Latin America. These data provide necessary evidence to understand NHL management in this region and highlight the need to improve treatment outcomes for these patients.

Seek COVER: using a disease proxy to rapidly develop and validate a personalized risk calculator for COVID-19 outcomes in an international network.

BACKGROUND: We investigated whether we could use influenza data to develop prediction models for COVID-19 to increase the speed at which prediction models can reliably be developed and validated early in a pandemic. We developed COVID-19 Estimated Risk (COVER) scores that quantify a patient's risk of hospital admission with pneumonia (COVER-H), hospitalization with pneumonia requiring intensive services or death (COVER-I), or fatality (COVER-F) in the 30-days following COVID-19 diagnosis using historical data from patients with influenza or flu-like symptoms and tested this in COVID-19 patients. METHODS: We analyzed a federated network of electronic medical records and administrative claims data from 14 data sources and 6 countries containing data collected on or before 4/27/2020. We used a 2-step process to develop 3 scores using historical data from patients with influenza or flu-like symptoms any time prior to 2020. The first step was to create a data-driven model using LASSO regularized logistic regression, the covariates of which were used to develop aggregate covariates for the second step where the COVER scores were developed using a smaller set of features. These 3 COVER scores were then externally validated on patients with 1) influenza or flu-like symptoms and 2) confirmed or suspected COVID-19 diagnosis across 5 databases from South Korea, Spain, and the United States. Outcomes included i) hospitalization with pneumonia, ii) hospitalization with pneumonia requiring intensive services or death, and iii) death in the 30 days after index date. RESULTS: Overall, 44,507 COVID-19 patients were included for model validation. We identified 7 predictors (history of cancer, chronic obstructive pulmonary disease, diabetes, heart disease, hypertension, hyperlipidemia, kidney disease) which combined with age and sex discriminated which patients would experience any of our three outcomes. The models achieved good performance in influenza and COVID-19 cohorts. For COVID-19 the AUC ranges were, COVER-H: 0.69-0.81, COVER-I: 0.73-0.91, and COVER-F: 0.72-0.90. Calibration varied across the validations with some of the COVID-19 validations being less well calibrated than the influenza validations. CONCLUSIONS: This research demonstrated the utility of using a proxy disease to develop a prediction model. The 3 COVER models with 9-predictors that were developed using influenza data perform well for COVID-19 patients for predicting hospitalization, intensive services, and fatality. The scores showed good discriminatory performance which transferred well to the COVID-19 population. There was some miscalibration in the COVID-19 validations, which is potentially due to the difference in symptom severity between the two diseases. A possible solution for this is to recalibrate the models in each location before use.

Daratumumab Plus Bortezomib, Melphalan, and Prednisone Versus Standard of Care in Latin America for Transplant-Ineligible Newly Diagnosed Multiple Myeloma: Propensity Score Matching Analysis.

INTRODUCTION: The phase 3 ALCYONE study demonstrated significantly longer progression-free and overall survival (PFS/OS) and higher overall response rates (ORR) with daratumumab plus bortezomib, melphalan, and prednisone (D-VMP) versus VMP alone in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). In Latin America, bortezomib- or thalidomide-based regimens remain standard of care (SoC) for this population. No head-to-head trials have compared D-VMP with SoC regimens used in Latin America. METHODS: Propensity score matching (PSM) was used to control for baseline differences between patient populations and compare outcomes for D-VMP versus SoC regimens used in Latin America. Data for the D-VMP cohort were from the D-VMP arm of the ALCYONE trial (n = 350). Data for the SoC cohort were from the retrospective, observational Hemato-Oncology Latin America (HOLA) study, which included patients with NDMM who did not receive a transplant (n = 729). Propensity scores were estimated using logistic regression. Exact, optimal, and nearest-neighbor PSM were applied to pick the best-performing method. Doubly robust estimation was the base case, since some baseline imbalances persisted. RESULTS: All 350 patients from the D-VMP arm of ALCYONE were included in OS/PFS analyses and 338 in ORR analysis; 478 and 324 patients, respectively, from HOLA were included in these analyses. Naïve comparison revealed important differences in baseline characteristics (age, chronic kidney disease, hypercalcemia, and International Staging System [ISS] stage). After nearest-neighbor matching, baseline characteristics, except ISS stage, were well balanced; comparisons favored D-VMP over SoC for OS (hazard ratio = 0.41; 95% confidence interval [CI] 0.25-0.66; P = 0.002) and PFS (hazard ratio = 0.48; 95% CI 0.35-0.67; P < 0.001). After exact matching, imbalances remained in age and ISS stage; comparisons favored D-VMP over SoC for ORR (odds ratio = 5.44; 95% CI 2.65-11.82; P < 0.001). CONCLUSION: In transplant-ineligible patients with NDMM, D-VMP showed superior effectiveness versus bortezomib- and thalidomide-based regimens, supporting adoption of daratumumab-containing regimens in Latin America.

Real-world analysis of treatment patterns and clinical outcomes in patients with newly diagnosed chronic lymphocytic leukemia from seven Latin American countries.

OBJECTIVE: To describe chronic lymphocytic leukemia (CLL) treatment patterns and patient outcomes in Latin America. METHODS: This chart review study (NCT02559583; 2008-2015)evaluated time to progression (TTP) and overall survival (OS) outcomes among patients with CLL who initiate done (n = 261) to two (n = 96) lines of therapy (LOT) since diagnosis. Differences in TTP and OS were assessed by Kaplan-Meier analysis, with a log-rank test for statistical significance. Association between therapeutic regimen and risk for disease progression or death was estimated using Cox proportional hazard regression. RESULTS: The most commonly prescribed therapies in both LOTs were chlorambucil-, followed by fludarabine- and cyclophosphamide (C)/CHOP-based therapies. Chlorambucil- and C/CHOP-based therapies were largely prescribed to elderly patients (≥65 years) while fludarabine-based therapy was predominantly used by younger patients (≤65 years). In LOT1, relative to chlorambucil-administered patients, those prescribed fludarabine-based therapies had lower risk of disease progression (hazard ratio [HR] and 95% confidence interval [CI] 0.32 [0.19-0.54]), whereas C/CHOP-prescribed patients had higher risk (HR 95%CI 1.88 [1.17-3.04]). Similar results were observed in LOT2. There was no difference in OS between treatments in both LOTs. DISCUSSION: Novel therapies such as kinase inhibitors were rarely prescribed in LOT1 or LOT2in Latin America. The greater TTP observed forfludarabine-based therapies could be attributed to the fact that fludarabine-based therapies are predominantly administered to young and healthy patients. CONCLUSION: Chlorambucil-based therapy, which has limited benefits, is frequently prescribed in Latin America. Prescribing novel agents for fludarabine-based therapy-ineligible patients with CLL is the need of the hour. Trial registration: ClinicalTrials.gov identifier: NCT02559583.

Epidemiology of inflammatory bowel disease in Mexico and Colombia: Analysis of health databases, mathematical modelling and a case-series study.

BACKGROUND AND AIMS: Ulcerative Colitis (UC) and Crohn's Disease (CD) have a major impact on quality of life and medical costs. The aim of the study was to estimate the prevalence, incidence and clinical phenotypes of Inflammatory Bowel Disease (IBD) cases in Mexico and Colombia. METHODS: We analyzed official administrative and health databases, used mathematical modelling to estimate the incidence and complete prevalence, and performed a case-series of IBD patients at a referral center both in Mexico and Colombia. RESULTS: The age-adjusted complete prevalence of UC per 100,000 inhabitants for 2015/2016 ranged from 15.65 to 71.19 in Mexico and from 27.40 to 69.97 in Colombia depending on the model considered. The prevalence of CD per 100,000 inhabitants in Mexico ranged from 15.45 to 18.08 and from 16.75 to 18.43 in Colombia. In Mexico, the age-adjusted incidence of UC per 100,000 inhabitants per year ranged from 0.90 to 2.30, and from 0.55 to 2.33 in Colombia. The incidence for CD in Mexico ranged from 0.35 to 0.66 whereas in Colombia, the age-adjusted incidence of CD ranged from 0.30 to 0.57. The case-series included 200 IBD patients from Mexico and 204 patients from Colombia. The UC/CD prevalence ratio in Mexico and Colombia was 1.50:1 and 4.5:1 respectively. In Mexico, the female/male prevalence ratio for UC was 1.50:1 and 1.28:1 for CD, while in Colombia this ratio was 0.68:1 for UC and 0.8:1 for CD. In Mexico the relapse rate for UC was 63.3% and 72.5% for CD, while those rates in Colombia were 58.2% for UC and 58.3% for CD. CONCLUSIONS: The estimated burden of disease of IBD in Mexico and Colombia is not negligible. Although these findings need to be confirmed by population-based studies, they are useful for decision-makers, practitioners and patients with this condition.

Multiple myeloma treatment patterns and clinical outcomes in the Latin America Haemato-Oncology (HOLA) Observational Study, 2008-2016.

Limited data are available regarding contemporary multiple myeloma (MM) treatment practices in Latin America. In this retrospective cohort study, medical records were reviewed for a multinational cohort of 1103 Latin American MM patients (median age, 61 years) diagnosed in 2008-2015 who initiated first-line therapy (LOT1). Of these patients, 33·9% underwent autologous stem cell transplantation (ASCT). During follow-up, 501 (45·4%) and 129 (11·7%) patients initiated second- (LOT2) and third-line therapy (LOT3), respectively. In the LOT1 setting, from 2008 to 2015, there was a decrease in the use of thalidomide-based therapy, from 66·7% to 42·6%, and chemotherapy from, 20·2% to 5·9%, whereas use of bortezomib-based therapy or bortezomib + thalidomide increased from 10·7% to 45·5%. Bortezomib-based therapy and bortezomib + thalidomide were more commonly used in ASCT patients and in private clinics. In non-ASCT and ASCT patients, median progression-free survival (PFS) was 15·0 and 31·1 months following LOT1 and 10·9 and 9·5 months following LOT2, respectively. PFS was generally longer in patients treated with bortezomib-based or thalidomide-based therapy versus chemotherapy. These data shed light on recent trends in the management of MM in Latin America. Slower uptake of newer therapies in public clinics and poor PFS among patients with relapsed MM point to areas of unmet therapeutic need in Latin America.

Epidemiology of Hematologic Malignancies in Real-World Settings: Findings From the Hemato-Oncology Latin America Observational Registry Study.

PURPOSE: Limited information is available on multiple myeloma (MM), chronic lymphocytic leukemia (CLL), and non-Hodgkin lymphoma (NHL) management in Latin America. The primary objective of the Hemato-Oncology Latin America (HOLA) study was to describe patient characteristics and treatment patterns of Latin American patients with MM, CLL, and NHL. METHODS: This study was a multicenter, retrospective, medical chart review of patients with MM, CLL, and NHL in Latin America identified between January 1, 2006, and December 31, 2015. Included were adults with at least 1 year of follow-up (except in cases of death within 1 year of diagnosis) treated at 30 oncology hospitals (Argentina, 5; Brazil, 9; Chile, 1; Colombia, 5; Mexico, 6; Panama/Guatemala, 4). RESULTS: Of 5,140 patients, 2,967 (57.7%) had NHL, 1,518 (29.5%) MM, and 655 (12.7%) CLL. Median follow-up was 2.2 years for MM, 3.0 years for CLL, and 2.2 years for NHL, and approximately 26% died during the study observation period. Most patients had at least one comorbidity at diagnosis. The most frequent induction regimen was thalidomide-based chemotherapy for MM and chlorambucil with or without prednisone for CLL. Most patients with NHL had diffuse large B-cell lymphoma (DLBCL; 49.1%) or follicular lymphoma (FL; 19.5%). The majority of patients with DLBCL or FL received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. CONCLUSION: The HOLA study generated an unprecedented level of high-quality, real-world evidence on characteristics and treatment patterns of patients with hematologic malignancies. Regional disparities in patient characteristics may reflect differences in ethnoracial identity and level of access to care. These data provide needed real-world evidence to understand the disease landscape in Latin America and may be used to inform clinical and health policy decision making.

There is much to be learnt about the costs of multiple sclerosis in Latin America / Hay mucho a ser aprendido sobre los costos de la esclerosis multiple en America Latina

METHOD: A systematic review of the literature from 1990 to 2011 was conducted. Outcome measures included: mean cost of disease modifying therapies (DMTs), mean cost of treatment of relapses and mean cost of disease by stage stratification measured by the expanded disability status scale (EDSS). RESULTS: Seven studies from three countries (Brazil, Argentina and Colombia) were included. In 2004, in Argentina, the mean cost of DMT treatment was reported to be USD 35,000 per patient treated. In Brazil, the total MS expenditure of DMTs rose from USD 14,011,700 in 2006 to USD 122,575,000 in 2009. Patient costs ranged between USD 10,543 (EDSS 8-9.5) and USD 25,713 (EDSS 3-5.5). Indirect costs markedly increased for the EDSS 8-9.5 patients. CONCLUSION: Further research assessing the economic burden of MS in LA is warranted. .

MÉTODOS: Revisión sistemática de la literatura desde 1990 hasta 2011. Los resultados evaluados fueron: coste medio de los tratamientos modificadores de la enfermedad (DMTs), coste medio del tratamiento de las recaídas y la media de coste de la enfermedad estratificado por la Expanded Disability Status Scale (EDSS). RESULTADOS: Siete estudios de tres países (Brasil, Argentina y Colombia) fueron incluidos. El costo promedio del tratamiento de DMTs fue de USD 35.000 por paciente para el año 2004 en Argentina y el total del costo de los DMTs aumentó de USD 14.011,700 en 2006 a USD 122.575,000 en Brasil en 2009. Los costos de pacientes oscilaron entre USD 10.543 (EDSS 8-9.5) y USD 25.713 (EDSS 3.5 a 5). Los costes indirectos aumentaron para la EDSS mayor discapacidad (EDSS 8-9.5). CONCLUSIÓN: Estudios adicionales del costo de la EM en AL son necesarios.. .

Three-year post-transplant Medicare payments in kidney transplant recipients: associations with pre-transplant comorbidities.

Little is known about the influence of pre-transplant comorbidities on post-transplant expenditures. We estimated the associations between pre-transplant comorbidities and post-transplant Medicare costs, using several comorbidity classification systems. We included recipients of first-kidney deceased donor transplants from 1995 through 2002 for whom Medicare was the primary payer for at least one year pre-transplant (N = 25,175). We examined pre-transplant comorbidities as classified by International Classification of Diseases (ICD-9-CM) codes from Medicare claims with the Clinical Classifications Software (CCS) and Charlson and Elixhauser algorithms. Post-transplant costs were calculated from payments on Medicare claims. We developed models considering Organ Procurement and Transplantation Network (OPTN) variables plus: 1) CCS categories, 2) Charlson, 3) Elixhauser, 4) number of Charlson and 5) number of Elixhauser comorbidities, independently. We applied a novel regression methodology to account for censoring. Costs were estimated at individual and population levels. The comorbidities with the largest impact on mean Medicare payments included cardiovascular disease, malignancies, cerebrovascular disease, mental conditions and functional limitations. Skin ulcers and infections, rheumatic and other connective tissue disease and liver disease also contributed to payments and have not been considered or described previously. A positive graded relationship was found between costs and the number of pre-transplant comorbidities. In conclusion, we showed that expansion beyond the usually considered pre-transplant comorbidities with inclusion of CCS and Charlson or Elixhauser comorbidities increased the knowledge about comorbidities related to augmented Medicare payments. Our expanded methodology can be used by others to assess more accurately the financial implications of renal transplantation to Medicare and individual transplant centers.

Kidney transplant Medicare payments and length of stay: associations with comorbidities and organ quality.

INTRODUCTION: We investigated associations between pre-transplant comorbidities, length of stay (LOS) and Medicare payments for transplant hospitalization. MATERIAL AND METHODS: We examined United States Renal Data System for 24,963 recipients of first deceased-donor kidney transplants in 1995-2002 for whom Medicare was the primary payer for at least a year pre-transplant. Pre-transplant ICD-9-CM codes from claims were classified with the Charlson and Elixhauser algorithms. Regression models for payments and LOS included: 1) baseline recipient, donor and transplant factors from the Organ Procurement and Transplant Network (OPTN), 2) OPTN variables and individual comorbidities and 3) OPTN variables and counts of Charlson or Elixhauser comorbidities. RESULTS: Factors most strongly associated with LOS were type I diabetes, cold ischemia time > 36 h, expanded criteria donor (ECD) and donation after cardiac death (DCD). Except for ECD, each was associated with increased payments. Upper respiratory disease, liver disease, peptic ulcer disease, diabetes, cancer and other diseases were also associated with increased LOS and payments. Each additional Charlson comorbidity increased LOS by 2.94% and payments by $471 (Elixhauser results: 1.71% for LOS, $277 for payments). Use of ECD or DCD organs were associated with 10-15% higher LOS and 5% increased Medicare payments for DCD. CONCLUSIONS: This methodology could be used to explore if Medicare reimbursement for transplantation of higher-risk recipients and using non-standard organs is financially adequate and to analyze related questions in other healthcare systems.

O custo econômico da doença de Alzheimer: sobrecarga familiar ou da saúde pública? / The economic cost of Alzheimers disease: family or public-health burden?

Alzheimers disease (AD) patients suffer progressive cognitive, behavioral and functional impairment which result in a heavy burden to patients, families, and the public-health system. AD entails both direct and indirect costs. Indirect costs (such as loss or reduction of income by the patient or family members) are the most important costs in early and community-dwelling AD patients. Direct costs (such as medical treatment or social services) increase when the disorder progresses, and the patient is institutionalized or a formal caregiver is required. Drug therapies represent an increase in direct cost but can reduce some other direct or indirect costs involved. Several studies have projected overall savings to society when using drug therapies and all relevant cost are considered, where results depend on specific patient and care setting characteristics. Dementia should be the focus of analysis when public health policies are being devised. South American countries should strengthen their policy and planning capabilities by gathering more local evidence about the burden of AD and how it can be shaped by treatment options.

O paciente com doença de Alzheimer (DA) sofre comprometimento progressivo cognitivo, comportamental e funcional, que resulta numa grande sobrecarga aos pacientes, familiares e à saúde pública. A DA inclui custos diretos e indiretos. Os custos indiretos (como perda ou redução dos ganhos pelo paciente ou membros da família) são os mais importantes custos dos pacientes leves e na comunidade. Os custos diretos (tais como tratamento médico ou serviços sociais) aumentam com a progressão da doença, quando o paciente é institucionalizado ou quando um cuidador formal é requerido. A terapia com drogas representam um aumento nos custos diretos, mas podem reduzir alguns outros custos diretos ou indiretos envolvidos. Vários estudos projetam uma economia global da sociedade quando é usada terapia com drogas e todos os custos relevantes são considerados; e os resultados dependerão de um paciente específico e características do meio envolvido no cuidado. A demência pode ser um assunto de análise quando as políticas de saúde são desenhadas. Os países da América do Sul deveriam fortalecer suas políticas e capacidades de planejamento, pela geração de maiores evidências locais sobre a sobrecarga da DA e como poderia ser norteada pelas opções de tratamento.

Probabilistic modeling of cytomegalovirus infection under consensus clinical management guidelines.

BACKGROUND: Cytomegalovirus (CMV) is the most common viral pathogen after renal transplantation and remains a major therapeutic challenge with important clinical and economic implications from both direct and indirect consequences of infection. METHODS: This 5-year study modeled the relationship between CMV infection and biopsy-proven graft rejection, graft loss, or death after renal transplantation in an inception cohort using Canadian consensus guidelines for CMV management as a component of a detailed cost-analysis of viral infection. RESULTS: Probabilities of CMV viremia and syndrome/disease among 270 sequential graft recipients were 0.27 and 0.09, respectively; 91% of cases occurred in the first 6 months. Probability of CMV infection as the first event was 0.29, with a probability of subsequent biopsy-proven acute rejection (BPAR) of 0.05 (mean: 62+/-26 days, range: 32-85 days), whereas the probability of BPAR as the first event was 0.18, with a probability of subsequent CMV infection of 0.38 (mean: 63+/-31, range: 27-119 days). Probability of freedom from both CMV infection and BPAR throughout the period of observation was 0.53. Time-dependent Cox analysis showed that neither donor/recipient CMV risk stratum nor CMV infection influenced the risks of BPAR (P=0.24; P=0.74) or of graft loss or death (P=0.26; P=0.34). In contrast, BPAR significantly increased the risk of both subsequent CMV infection (hazard ratio=1.77, P=0.03) and of graft loss or death (hazard ratio=8.31, P<0.0001). CONCLUSIONS: Although current antiviral therapy seems to mitigate the reported deleterious effects of CMV infection on BPAR or graft survival, BPAR remains a significantly risk factor for both CMV infection and functional graft survival.