Burden of lupus activity on health care resources utilization in Buenos Aires, Argentina.

OBJECTIVE: The aim is to analyze health care resource utilization (HCRU) of patients with lupus (SLE) from a health management organization (HMO) in Buenos Aires, Argentina, compared with matched controls and comparing periods of flare, low disease activity, and remission. METHODS: This is a retrospective observational study including all SLE incident cases (ACR 1997/SLICC 2012 criteria) between 2000 and 2020 and 5 matched controls. Clinical data and HCRU (medical and nonmedical consultations, lab and imaging tests performed, emergency room visits, hospitalizations, and drugs prescribed) were obtained from administrative databases and electronic medical records. For each patient with SLE, an activity state was determined in every month of follow-up: flare (BILAG A or 2 BILAG B); low disease activity (LLDAS); remission (DORIS definition); or intermediate activity (not fulfilling any of previous). Incidence rates for each HCRU item and incidence rate ratios between SLE and control patients were and between remission and flare periods were calculated. Multivariate negative binomial logistic regression analyses were performed for identification of variables associated with major resource use. RESULTS: A total of 62 SLE and 310 control patients were included, 88.7% were women, the median age at diagnosis was 46 years, and were followed for more than 8 years. Patients with SLE contributed with 537.2 patient-years (CI 95% 461.1-613.3) and controls with 2761.9 patient-years (CI 95% 2600.9-2922.8). HCRU in patients with SLE was significantly higher than in controls in all items, even in remission periods. Patients with SLE remained 74.4% of the time in remission, 12.1% in LLDAS, 12.2% in intermediate activity, and 1.3% in flare (there were 64 flares in 36 patients). HCRU was significantly higher during flare periods compared with remission periods. Number of flares was independently associated with emergency department consultations, lab tests and X-ray performed, number of drugs prescribed, and hospitalizations. CONCLUSION: Significantly more HCRU was observed in patients with SLE in flare compared to remission periods.

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.

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.

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.

Insurance status and demographic and clinical factors associated with pharmacologic treatment of depression: associations in a cohort in Buenos Aires.

OBJECTIVE: There is a paucity of evidence about insurance status and the likelihood of receiving medical services in Latin America. The objective of this analysis was to examine the association between insurance status and pharmacologic treatment for depression. METHODS: Patients referred to a memory clinic of a public hospital in Buenos Aires, Argentina, and identified with any of four types of depression (subsyndromal, dysthymia, major, and due to dementia) were included. Age, years of education, insurance status, Beck Depression Inventory score, and number of comorbidities were considered. Associations between these factors and not receiving pharmacologic treatment for depression were examined with logistic regression. Use of prescription neuroleptics, hypnotics, and anticholinesterase inhibitors was also explored. RESULTS: Out of 100 patients, 92 with insurance status data were used. Sixty-one patients (66%) had formal insurance and 31 patients (34%) lacked insurance. Twenty-seven (44%) insured patients and 23 (74%) uninsured patients did not receive antidepressants (P = 0.001). Controlling for other factors, uninsured patients had 7.12 higher odds of not receiving treatment compared to insured patients (95% confidence interval 1.88-28.86). Older patients and those with more comorbidities had higher odds of not receiving treatment. More educated patients, those with higher Beck Depression Inventory score, and those without subsyndromal depression had lower odds of not receiving treatment. None of those associations were statistically significant. CONCLUSIONS: These results suggest a potential negative effect of the lack of formal insurance regarding pharmacologic treatment for depression. These findings should be confirmed with larger samples, and for other diseases.

The long-term outcomes and costs of diabetes mellitus among renal transplant recipients: tacrolimus versus cyclosporine.

Anti-rejection regimens for renal transplants have changed dramatically during the past 20 years, but there are few long-term studies relating cost, mortality, or graft failure simultaneously to disease-pharmacotherapy couplets. We analyzed US Renal Data System data on a matched-pair cohort of first, single organ kidney transplants from 1998 through 2002 over up to 5 years following transplantation for patients on tacrolimus or low-dose cyclosporine, stratifying by whether the recipient had pre-existing or new onset diabetes. Kaplan-Meier survival curves show mortality and survival differences associated with diabetes, but no additional incremental effects of immune suppression regimen. Significant cost increases are reported for patients receiving tacrolimus above and beyond the extra costs associated with diabetes.

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.

Validity and reliability of the SF-36 administered to caregivers of patients with alzheimer's disease: evidence from a south american sample.

BACKGROUND: Being a caregiver of a patient with Alzheimer's disease is associated with impaired health status and declines in health-related quality of life (HRQoL). This paper evaluates the reliability and validity of the Argentinean version of the Medical Outcomes Study Short-Form Health Survey (SF-36) among caregivers of patients with Alzheimer's disease. METHODS: Forty-eight caregivers of Alzheimer's disease patients completed the SF-36, the Zarit Burden Interview (ZBI) and the Neuropsychiatric Inventory (NPI). Patients were evaluated for dementia severity using the Clinical Dementia Rating (CDR) and for cognitive status using the Mini Mental State Examination (MMSE). RESULTS: The SF-36 scales demonstrated adequate-to-strong internal consistency (Cronbach's alpha range: 0.72 to 0.92). Correlations between the SF-36 scales and the ZBI were moderate to strong (range: -0.19 to -0.79, all p < 0.01 expect for physical function). Significant correlations between the SF-36 scales and the CDR, MMSE and NPI were lower (range: -0.30 to -0.40, p < 0.001) and strongest in mental health-related scales of the SF-36. The SF-36 demonstrated good factorial validity. CONCLUSIONS: The Argentinean translation of the SF-36 is reliable and valid for use to measure the HRQoL of caregivers of patients with Alzheimer's disease.

Cognitive, functional and behavioral factors associated with the burden of caring for geriatric patients with cognitive impairment or depression: evidence from a South American sample.

OBJECTIVE: To examine behavioral, cognitive and functional factors associated with psychosocial burden in caregivers of geriatric patients. METHODS: Primary caregivers assessed were included if the geriatric patient cared for had a cognitive impairment or dementia (degenerative, vascular or mixed) (Group 1) or depression and cerebrovascular disease (CVD) (Group 2). Caregivers completed the Zarit questionnaire, the Neuropsychiatric Inventory (NPI) and Instrumental Activities of Daily Living (IADL). Patients were evaluated for dementia severity using the Clinical Dementia Rating (CDR), Mini Mental State Examination (MMSE) and Beck Depression Inventory (BDI). Structural equation modelling (SEM) was used to assess measurement models and the factors associated with burden. RESULTS: Two hundred and fifty-eight caregiver-patient pairs were included. The best model fit was obtained with a model with two constructs: function-cognition (CDR, MMSE, and IADL) and behavior (neuropsychiatric symptoms from the NPI). In Group 1, both function (B = 0.32. T = 2.79) and behavior (B = 0.72, T = 7.84) were significantly correlated with caregiver burden, although the strength of association was more than two times higher for behavior. In Group 2, behavior was related to caregiver burden (B = 0.68, T = 6) but not function-cognition (B = 0.16, T = 1.36). CONCLUSION: These findings suggest that behavioral symptoms are an important factor associated with caregiver burden in patients with cognitive impairment, dementia, or depression, while functional and cognitive factors seem to also have an influence in patients with cognitive impairment.

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.

Increased risk of graft failure in kidney transplant recipients after a diagnosis of dyspepsia or gastroesophageal reflux disease.

BACKGROUND: Gastrointestinal complications are common in patients who undergo kidney transplantation and may affect posttransplant outcomes. We examined the incidence and predictors of gastroesophageal reflux disease (GERD) and dyspepsia and their associations with graft survival and mortality after transplant. METHODS: We examined United States Renal Data System data and Medicare billing claims to identify diagnoses of dyspepsia and GERD among Medicare beneficiaries transplanted in 1995-2002 (n=42,257). Among GERD cases, we identified patients with reflux esophagitis (RE). We determined independent predictors of upper gastrointestinal complications and modeled these conditions as time-dependent outcomes predictors with Cox regression. RESULTS: The 3-year cumulative incidences of GERD, RE, and dyspepsia were 20%, 5%, and 6%, respectively. Overall, 23% of transplant recipients received a diagnosis of at least one of these complications by 3 years after transplant. Female gender and a pretransplant upper gastrointestinal disease diagnosis predicted posttransplant gastrointestinal complications. Older age, obesity, Caucasian, and African-American race were associated to increased risk of developing GERD. Patients diagnosed with any of the examined upper gastrointestinal complications experienced an increased risk of graft-failure (hazard ratio 1.58; 95% confidence interval 1.48-1.69) and death (hazard ratio 1.61; 95% confidence interval 1.46-1.77). CONCLUSIONS: Upper gastrointestinal complications are relatively common after kidney transplantation and are associated with a significantly increased risk of graft loss and death. Further research is needed to elucidate mechanisms underlying the observed adverse prognoses conferred by diagnosis of upper gastrointestinal complications after kidney transplant.

Economic impact and long-term graft outcomes of mycophenolate mofetil dosage modifications following gastrointestinal complications in renal transplant recipients.

INTRODUCTION: Gastrointestinal (GI) complications are common following renal transplantation. Discontinuing or reducing the dosage of mycophenolate mofetil can improve GI tolerability but adversely affect graft outcomes. This analysis was undertaken to assess the 3-year economic and clinical impact of mycophenolate mofetil dosage modifications or discontinuation following post-transplant GI events compared with no dosage modification. METHODS: Adult renal transplant recipients with a Medicare-covered mycophenolate mofetil prescription at the time of GI complication between 1995 and 2000 were drawn from the US Renal Data System (USRDS). The 3-year graft survival rates after first diagnosis of a GI complication were obtained in four cohorts of patients according to mycophenolate mofetil administration within 6 months of initial GI diagnosis: (i) no dosage change in mycophenolate mofetil (NC); (ii) one or more episodes of mycophenolate mofetil dosage reduction <50% of the initial dosage, lasting >30 days (DR <50%); (iii) one or more episodes of mycophenolate mofetil dosage reduction >or=50% of the initial dosage, lasting >30 days (DR >or=50%); and (iv) one or more episodes of mycophenolate mofetil discontinuation >30 days (DC).Two multivariate models were used to estimate the association between DR and DC and graft survival <6 months after GI diagnosis and 6-36 months after diagnosis. In each cohort, Medicare costs for maintaining a patient with stable function were calculated using regression and were augmented with cost of graft failure, resumed maintenance dialysis and death post-graft loss using Medicare data supplied by the USRDS. Survival and cost outcomes were integrated in a 3-year Markov model with 6-month cycles. The perspective was that of Medicare, and costs and outcomes were discounted by 3% per annum. RESULTS: Adult patients (n = 3589) with a mycophenolate mofetil prescription at time of diagnosis of GI event were identified: NC = 2230 (62.1%); DR <50% = 247 (6.9%); DR >or=50% = 348 (9.7%); and DC = 764 (21.3%). In the first 6 months after GI diagnosis, DC was associated with increased risk of graft failure (hazard ratio [HR] 3.20; 95% CI 1.71, 5.99; p < 0.0001). During the period 6-36 months after GI diagnosis, the HR for graft loss was higher for the DR >or=50% group (HR 1.32; 95% CI 1.02, 1.70; p < 0.05) and DC group (HR 1.35; 95% CI 1.09, 1.69; p < 0.01) relative to the NC group.Expected 3-year cumulative Medicare costs per patient were USD 68,495 for the NC and DR <50% groups, USD 70,886 for the DR >or=50% group, USD 79,015 for the DC group and USD 70,967 overall. Respective QALYs were 2.32, 2.30, 2.27 and 2.31. In sensitivity analysis, reducing the rate of DR and DC by 25% would have lowered expected costs by USD 2.2 million in the study population and increased QALYs by 11.2. Monte Carlo simulation indicated a 93% probability that such reduction in the relative risk of mycophenolate mofetil DR/DC was cost saving or cost neutral. CONCLUSION: Dosage reduction or discontinuation of mycophenolate mofetil in the first 6 months after diagnosis of GI complications is associated with significantly increased risk of graft failure and increased healthcare costs in adult renal transplant recipients.

Gastrointestinal (GI)-Specific patient reported outcomes instruments differentiate between renal transplant patients with or without GI symptoms: results from a South American cohort.

BACKGROUND: Immunosuppressive therapies have burdensome side effects which may lead to sub-therapeutic dosing and non-compliance. Patients on different immunosuppressant regimens may feel less bothered by Gastrointestinal (GI) side effects or report better health-related quality of life (HRQL). We evaluated the reliability and validity of two GI-specific outcome instruments (Gastrointestinal Symptom Rating Scale (GSRS; higher scores = increased severity) and Gastrointestinal Quality of Life Index (GIQLI; higher scores = better GI-specific HRQL)) in renal transplant patients in South America. METHODS: Data from 5 South American centers participating in an international, longitudinal, observational study were analyzed. Patients were > or = 1 month post transplant and on mycophenolate mofetil (MMF) and a calcineurin inhibitor. Patients completed the GSRS, GIQLI, and Psychological General Well-Being (PGWB; higher scores = better HRQL) Index at baseline and at 4-6 weeks. Internal consistency, test-retest reliability and construct and discriminant validity were assessed. RESULTS: Sixty-two participants were enrolled. Mean age was 42 years; mean time since transplant was 3.3 years; 57% were male; 65% received a deceased organ transplant and 68%had GI events. The GSRS and GIQLI demonstrated high internal consistency (Cronbach's alphas 0.72-0.96). Test-retest reliability was adequate (intraclass correlation coefficient > 0.6) for all GIQLI subscales and all GSRS subscales except Diarrhea and Reflux syndrome. Correlations between the GSRS and PGWB were moderate (range: -0.21 to -0.53, all p < 0.001 except 6 correlations with p < 0.05); correlations between the GIQLI and PGWB were higher (range: 0.36 to 0.71 p < 0.001), indicating good construct validity. The GSRS and GIQLI demonstrated good discriminant validity, as they clinically and statistically distinguished between patients with and without GI complaints and among patients with varying GI complication severity. Patients with GI complaints reported higher GSRS scores than patients without complaints (all p < 0.001). GIQLI scores were lower in patients with GI complaints than patients without complaints (all p < 0.001). The GSRS and GIQLI differentiated among patients with four GI severity levels (overall Kruskall-Wallis test p < 0.001, except for one scale). The GSRS and GIQLI are acceptable for use in South American renal transplant patients. These two instruments demonstrate adequate reliability and validity. Patients with GI complaints reported poor HRQL and strategies are needed to improve patients' HRQL.

Diabetic complications associated with new-onset diabetes mellitus in renal transplant recipients.

BACKGROUND: Data are scarce regarding the incidence and risk factors for complications of new-onset diabetes mellitus (NODM) in renal transplant patients. METHODS: United States Renal Data System (USRDS) data from primary renal transplant recipients during 1995-2001 who developed NODM was used to examine diabetic complications over the first three years posttransplant. Prognostic models were used to evaluate patient characteristics and treatment choices associated with risk of each class of complications. Propensity scores for choice of calcineurin inhibitor were included in multivariate analyses. RESULTS: The analysis included 21,489 patients, of whom 4,105 developed NODM by 3 years posttransplant. One or more NODM complications developed in 2,393 patients (58.3% of all patients with NODM), comprising ketoacidosis (334, 8.1%), hyperosmolarity (131, 3.2%), renal complications (1,286, 31.3%), ophthalmic complications (340, 8.3%), neurological complications (665, 16.2%), peripheral circulatory disorders (170, 4.1%) and hypoglycemia/shock (301, 7.3%). Complications developed within a mean of 500 to 600 days from diagnosis of NODM. Multivariate analysis showed that increased recipient age, higher body mass index, African-American race, hepatitis C infection, hypertension as cause of end-stage renal disease, cold ischemia >or=30 hours, and use of tacrolimus each increased risk of complications. CONCLUSION: NODM is associated with similar complications to those seen in the general population, but these appear to develop at an accelerated rate. Obesity and use of tacrolimus are the only modifiable factors that appear to affect risk of NODM or its complications.

Patient-Reported Outcomes in Latin America: Implementation in Research and Role in Emerging HTA Systems.

BACKGROUND: Patient-reported outcomes (PROs) are increasingly used to demonstrate the value of interventions and support health technology assessment (HTA). OBJECTIVE: The objective of this work was to analyze trends regarding PROs in Latin America (LatAm), highlight challenges in the application of PROs in this region, and suggest solutions. METHODS: A team of researchers with expertise in PROs conducted a nonsystematic PubMed literature search pertaining to the use of PROs in LatAm. The experts also drew on their experience working with PROs to assess the application of PROs in LatAm. RESULTS: The literature search yielded more than 4000 publications, with an increasing publication rate in recent years. PROs are being used in LatAm in various study types: instrument validation, phase III international clinical trials, health service research. A large Inter-American Development Bank study demonstrates the growing importance of PROs in the region. The growth in local value sets for the EuroQol five-dimensional questionnaire in LatAm reflects the regional emergence of HTA systems. Operational challenges relate to ensuring the use of good-quality questionnaires that, at a minimum, have undergone appropriate cultural adaptation and ideally have established psychometric properties. CONCLUSIONS: PROs are increasingly important in LatAm. Future efforts should aim to strengthen the operational and research infrastructure around PROs in the region. Innovation should be encouraged, including studying alternative methods of eliciting health utilities for economic evaluation. A wider scope around PRO uses for decision making by HTA bodies is an international trend with potential positive prospects in LatAm.

Pulse pressure and stroke risk: development and validation of a new stroke risk model.

OBJECTIVE: This study aims to develop and validate a stroke risk model incorporating pulse pressure (PP) as a potential risk factor. Recent evidence suggests that PP, defined as the difference between systolic blood pressure (SBP) and diastolic blood pressure (DBP), could be an incremental risk factor beyond SBP. METHODS: Electronic health records (EHRs) of hypertensive patients from a US integrated health delivery system were analyzed (January 2004 to May 2012). Patients with ≥ 1 PP reading and ≥ 6 months of observation prior to the first diagnosis of hypertension were randomly split into development (two-thirds of sample) and validation (one-third of sample) datasets. Stroke events were identified using ICD-9-CM 433.xx-436.xx. Cox proportional hazards models assessed time to first stroke event within 3 years of first hypertension diagnosis based on baseline risk factors, including PP, age, gender, diabetes, and cardiac comorbidities. The optimal model was selected using the least absolute shrinkage and selection operator (LASSO); performance was evaluated by the c-statistic. RESULTS: Among 34,797 patients selected (mean age 59.3 years, 48% male), 4272 patients (12.3%) had a stroke. PP was higher among patients who developed stroke (mean [SD] PP, stroke: 02.0 [15.3] mmHg; non-stroke: 58.1 [14.0] mmHg, p < 0.001). The best performing risk model (c-statistic, development: 0.730; validation: 0.729) included PP (hazard ratio per mmHg increase: 1.0037, p < 0.001) as a significant risk factor. LIMITATIONS: This study was subject to limitations similar to other studies using EHRs. Only patient encounters occurring within the single healthcare network were captured in the data source. Though the model was tested internally, external validation (using a separate data source) would help assess the model's generalizability and calibration. CONCLUSIONS: This stroke risk model shows that greater PP is a significant predictive factor for increased stroke risk, even in the presence of known risk factors. PP should be considered by practitioners along with established risk factors in stroke treatment strategies.

There is much to be learnt about the costs of multiple sclerosis in Latin America.

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.