Direct costs associated with lupus nephritis management in the Private Healthcare System in Brazil: an expert panel perspective / Custos diretos associados ao manejo da nefrite lúpica no Sistema de Saúde Privado no Brasil: uma perspectiva segundo painel de especialistas

Objective: To estimate direct medical costs of lupus nephritis (LN) in the Brazilian private healthcare system. Methods: An expert panel of five specialists were convened to discuss health resource usage in LN patient management. The discussion included diagnosis, treatment, and disease monitoring, including dialysis and kidney transplantation. Unit costs (in BRL) were obtained from public sources, and an estimation of 1-year costs was conducted. Results: Approximately 76.0% of patients with LN undergo kidney biopsy, of which 48.1% present with LN classes III­IV and 21.4% have class V. Around 67.5% of patients with LN classes III­IV experience an average of four renal flares annually. Overall, 20.3% of patients present refractory LN, and 10.3% have end-stage kidney disease (ESKD), requiring dialysis and kidney transplantation. Estimated total weighted annual costs per patient were BRL 115,824.81 for LN classes III­IV, BRL 85,684.79 for LN class V, BRL 115,594.98 for refractory LN; and BRL 325,712.88 for ESKD. The main annual cost driver for LN classes III­IV was renal flares (BRL 60,240.41; 52.0%) and dialysis for LN class V (BRL 31,128.38; 36.3%). Conclusions: Total direct costs increase when LN progresses to ESKD. Although it is challenging to improve the diagnosis, identification of the disease at an early stage, together with rapid initiation of treatment, are fundamental elements to optimize results, potentially reducing costs to the system and the impact of disease burden and quality of life on patients.

Objetivo: Estimar os custos médicos diretos da nefrite lúpica (NL) no sistema suplementar de saúde brasileiro. Métodos: Um painel de cinco especialistas foi estruturado para discutir o uso de recursos em saúde no manejo de pacientes com NL. Nesta discussão, incluíram-se o diagnóstico, o tratamento e o monitoramento da doença, contemplando também diálise e transplante renal. Os custos unitários foram obtidos de fontes públicas e os resultados expressos em custo anual. Resultados: Aproximadamente 76,0% dos pacientes com NL são submetidos à biópsia renal, sendo 48,1% com NL de classes III-IV e 21,4% de classe V. Cerca de 67,5% dos pacientes com classes III-IV apresentam, aproximadamente, quatro flares renais anuais. No geral, 20,3% dos pacientes apresentam NL refratária e 10,3% desenvolvem doença renal terminal (DRT), necessitando de diálise e transplante renal. O custo ponderado anual estimado por paciente foi de R$ 115.824,81 para NL de classes III-IV, R$ 85.684,79 para classe V, R$ 115.594,98 para NL refratária e R$ 325.712,88 para DRT. O principal fator para incremento dos custos anuais para NL de classes III-IV foram os flares renais (R$ 60.240,41; 52,0%) e, na classe V, a diálise (R$ 31.128,38; 36,3%). Conclusões: Há um incremento dos custos diretos da NL na progressão para DRT. Embora seja desafiador melhorar o diagnóstico, a identificação da doença em uma fase precoce, aliada ao tratamento iniciado de forma célere, são elementos fundamentais para otimizar os resultados, potencialmente reduzindo os custos ao sistema e o impacto da carga da doença e qualidade de vida dos pacientes.

A comprehensive assessment of lymphocyte subsets, their prognostic significance, and changes after first-line therapy administration in patients with chronic lymphocytic leukemia.

BACKGROUND: In chronic lymphocytic leukemia (CLL), changes in the peripheral blood lymphocyte subsets play an important role in disease progression and infectious complications. The impact of chemoimmunotherapy (CIT) on these changes has not been extensively studied METHODS: We used multi-color flow cytometry, to prospectively measure absolute and relative numbers of CD4+ and CD8+ T-cells and their subsets in 45 patients with indolent untreated CLL, 86 patients indicated for first-line treatment, and 34 healthy controls. In 55 patients, we analyzed the impact of CIT RESULTS: CLL patients had a significant increase in most cell populations in comparison to controls. Progression of CLL was characterized by significantly elevated counts with the exception of a lower percentage of naïve T-cells. After treatment, the percentage of naïve T-cells further decreased at the expense of effector memory T-cells (TEM). In patients with indolent CLL, higher percentages of naïve CD4+ (p = 0.0026) and naïve CD8+ (p = 0.023) T-cells were associated with a longer time to first treatment (TTFT). The elevation of CD4+ central memory T-cells (TCM) (p = 0.27) and TEM (p = 0.003) counts and a higher percentage of CD4+ TEM (p = 0.0047), were linked with shorter TTFT. In treated patients, increased regulatory T-cells count was associated with shorter time to next treatment (TTNT) (p = 0.042), while higher CD4+ TCM count with shorter TTNT (p = 0.035) and shorter overall survival (p = 0.041). CONCLUSION: Our results indicate that naïve cell depletion and CD4+ TCM and TEM increases are detrimental to CLL patients' prognosis.

Chronic Community Exposure to Environmental Metal Mixtures Is Associated with Selected Cytokines in the Navajo Birth Cohort Study (NBCS).

Many tribal populations are characterized by health disparities, including higher rates of infection, metabolic syndrome, and cancer-all of which are mediated by the immune system. Members of the Navajo Nation have suffered chronic low-level exposure to metal mixtures from uranium mine wastes for decades. We suspect that such metal and metalloid exposures lead to adverse health effects via their modulation of immune system function. We examined the relationships between nine key metal and metalloid exposures (in blood and urine) with 11 circulating biomarkers (cytokines and CRP in serum) in 231 pregnant Navajo women participating in the Navajo Birth Cohort Study. Biomonitored levels of uranium and arsenic species were considerably higher in participants than NHANES averages. Each biomarker was associated with a unique set of exposures, and arsenic species were generally immunosuppressive (decreased cellular and humoral stimulating cytokines). Overall, our results suggest that environmental metal and metalloid exposures modulate immune status in pregnant Navajo women, which may impact long-term health outcomes in mothers and their children.

Assessment of the Immune Response to Tumor Cell Apoptosis and Efferocytosis.

Apoptotic cells are cleared from the body principally through recognition and engulfment by neighboring phagocytes, a process known as efferocytosis. During efferocytosis, phagocytes are recruited to the site/activated by "find me" signals released from apoptotic cells, precisely identify apoptotic cells by the recognition of "eat me" signals on the apoptotic cell surface, and engulf the apoptotic cells to prevent secondary necrosis and inflammation. Thus, efferocytosis is critical for tissue homeostasis in normal physiology. However, efferocytosis of apoptotic tumor cells-performed by tumor-associated macrophages-suppresses immunity within the tumor microenvironment and limits the antitumor response. This phenomenon is further exacerbated in tumor residual disease because of the high apoptotic cell burden generated by cytotoxic therapies. Blocking efferocytosis could be a powerful approach to boost tumor immunogenicity, particularly as a combination approach with cytotoxic therapies that produce many apoptotic cells, but little is currently known about the immune response to efferocytosis. Moreover, there is a dearth of in vivo models available to study the immunologic and therapeutic consequences of blocking efferocytosis in tumor residual disease.Here, we describe a model that enables in vivo studies of tumor immunology in the aftermath of cytotoxic therapy with an emphasis on the impact of efferocytosis. Orthotopic HER2+ mammary tumors are established in immune-competent mice, followed by a single administration of lapatinib, a receptor tyrosine kinase inhibitor of HER2, to the mice that induces widespread, transient apoptosis in the tumor microenvironment. In the days following lapatinib treatment, agents that block efferocytosis such as BMS-777607 are administered. Tissue is collected from cohorts of mice at day 2 (after lapatinib treatment only) to assess apoptosis, day 8 (after lapatinib treatment followed by blockade of efferocytosis) to assess the immune response to apoptosis and efferocytosis, and day 28 (after 4 consecutive weeks of treatment) to assess therapeutic efficacy. This model enables mechanistic studies of tumor immunology in residual disease as well as therapeutic efficacy studies of targeted agents that disrupt efferocytosis.

Prevalence and management of chronic hepatitis B in pemphigus and pemphigoid patients: New evidence for the safety of rituximab.

Although the treatments of pemphigus and pemphigoid patients have tended toward safer options, patients with chronic infections seem to be still at the risk of infection reactivation when they are exposed to any of immunosuppressive treatments. A retrospective study on 1646 registered pemphigus and pemphigoid patients was conducted between January 2017 and February 2019 and the prevalence of HBV, the association between the treatments, mainly prednisolone and rituximab with HBV reactivation as well as outcomes of patients after management with antiviral therapies were evaluated. From 1646 reviewed patients, 10 (0.60%) patients with chronic HBV were identified. We found a negative correlation between the ALT (p-value<0.001), AST (p-value = 0.090), and Pemphigus Disease Area Index (PDAI) (p-value = 0.034) and age of patients. At the time points that prednisolone dosage was higher, higher levels of ALT, but no difference in AST levels was noted. The portion of patients with normal ALT was significantly higher (p-value = 0.036; OR = 2.22) in those who had received rituximab within the previous 6 months (38 of 49; 77.6%) as compared to those who did not (81 of 133; 60.9%). We concluded that avoidance (high dose) systemic corticosteroids in patients with chronic HBV, and using rituximab instead in severe cases benefit this group of patients.

Kidney Transplantation, Immunosuppression and the Risk of Fracture: Clinical and Economic Implications.

Rationale & Objective: Disorders of bone and mineral metabolism frequently develop with advanced kidney disease, may be exacerbated by immunosuppression after kidney transplantation, and increase the risk of fractures. Study Design: Retrospective database study. Setting & Participants: Kidney-only transplant recipients aged ≥18 years from 2005 to 2016 in the United States captured in US Renal Data System records, which integrate Organ Procurement and Transplantation Network/United Network for Organ Sharing records with Medicare billing claims. Exposures: Various immunosuppression regimens in the first 3 months after kidney transplantation. Outcomes: The development of fractures, as ascertained using diagnostic codes on Medicare billing claims. Analytical Approach: We used multivariable Cox regression with inverse propensity weighting to compare the incidence of fractures >3 months-to-3 years after kidney transplantation associated with various immunosuppression regimens compared to a reference regimen of antithymocyte globulin (TMG) or alemtuzumab (ALEM) with tacrolimus + mycophenolic acid + prednisone using inverse probability treatment weighting. Results: Overall, fractures were identified in 7.5% of kidney transplant recipients (women, 8.8%; men, 6.7%; age < 55 years, 5.9%; age ≥ 55 years, 9.3%). In time-varying regression, experiencing a fracture was associated with a substantially increased risk of subsequent death within 3 months (adjusted hazard ratio [aHR], 3.06; 95% confidence interval [CI], 2.45-3.81). Fractures were also associated with increased Medicare spending (first year: $5,122; second year: $10,890; third year: $11,083; [P < 0.001]). Induction with TMG or ALEM and the avoidance or early withdrawal of steroids significantly reduced the risk of fractures in younger (aHR, 0.63; 95% CI, 0.54-0.73) and older (aHR, 0.83; 95% CI, 0.74-0.94) patients. The avoidance or early withdrawal of steroids with any induction was associated with a reduced risk of fractures in women. Limitations: This was a retrospective study which lacked data on immunosuppression levels. Conclusions: Fractures after kidney transplantation are associated with significantly increased mortality risk and costs. The early avoidance or early withdrawal of steroids after induction with TMG or ALEM reduces the risk of fractures after kidney transplantation and should be considered for patients at high-risk of this complication, including older adults and women.

Biomarker-Based Assessment for Infectious Risk Before and After Heart Transplantation.

PURPOSE OF REVIEW: Survival outcomes for heart transplant recipients have improved in recent decades, but infection remains a significant cause of morbidity and mortality. In this review, we discuss several biological markers, or biomarkers, that may be used to monitor immunologic status in this patient population. RECENT FINDINGS: While modest, data on the utility of immune biomarkers in heart transplant recipients suggest correlation between low level of immune response and increased infection risk. More novel assays, such as the detection of circulating levels of pathogen cell-free DNA in plasma and the use of Torque teno virus load as a surrogate for net state of immunosuppression, have potential to be additional important biomarkers. Biomarker approaches to individualize immunosuppression therapy among heart transplant recipients is a promising area of medicine. However, additional studies are needed to inform the optimal protocol in which to incorporate these biomarkers into clinical practice.

A Cost-effectiveness Analysis of Adherence Promotion Strategies to Improve Rejection Rates in Adolescent Kidney Transplant Recipients.

RATIONALE & OBJECTIVE: Nonadherence to medical regimens increases the risk of graft loss among adolescent and young adult recipients of kidney transplants. Interventions that improve adherence may decrease rejection rates, but their perceived costs are a barrier to clinical implementation. We developed a model to assess the cost-effectiveness of an adherence promotion strategy, the Medication Adherence Promotion System (MAPS). STUDY DESIGN: Simulation-based. Data sources included published articles indexed in Medline or referenced in bibliographies of relevant English-language articles. Data on costs and outcomes were taken from a single clinical center. SETTING & POPULATION: US adolescent patients after their first kidney transplant. INTERVENTION: Usual posttransplant care versus usual care plus MAPS. OUTCOME: Effectiveness measured in quality-adjusted life years (QALYs) and costs measured in 2020 US dollars. MODEL, PERSPECTIVE, & TIMEFRAME: Markov state transition decision model. We used a health care system perspective with a lifelong time horizon. RESULTS: In the base-case analysis, MAPS was more effective and less costly than usual care. MAPS cost $9,106 per patient less than usual care and resulted in a gain of 0.32 QALYs. In probabilistic sensitivity analyses, MAPS was cost saving 100% of the time. Extending results to a program level with 100 patients, any adherence promotion intervention similar in effectiveness to MAPS would cost less than $50,000/QALY if the start-up costs were <$2.5 million and annual costs <$188,000. Strategies with costs similar to MAPS that reduce the risk of rejection by as little as 3% would also have similar cost-effectiveness. LIMITATIONS: Estimates of components and costs for MAPS were based on a single center. CONCLUSIONS: Adherence promotion strategies with costs similar to MAPS can be cost-effective as long as they reduce rejection rates by at least 3%. This model can be applied to study the cost-effectiveness of adherence promotion strategies with varying costs and outcomes.

Telemedicine in monitoring pediatric LT patients before and during COVID-19 pandemic.

BACKGROUND: The delivery of healthcare services by telemedicine decreases costs of traveling for patients, is less time-consuming, and most importantly permits the connection between highly skilled specialists and patients. However, whether the use of telemedicine (text messaging) for LT patients was affected by the COVID-19 pandemic is unknown. METHODS: We collected data (following consent from patients and parents) from 57 patients (33 male/24 female) with a median age of 47 (IQR: 9-91) months, whom we followed up with text messaging between September 2019 and September 2020, spanning the 6 months prior to COVID-19 and during this period. RESULTS: In total, 723 text message mediated consultations occurred during this period, henceforth simply referred to as "messages." Three hundred and twenty-eight (45%) messages occurred during the 6 months up to the start of the pandemic. Following the COVID-19 outbreak, the number of messages increased to 395 (55%). The three most common reasons of messaging were post-liver-LT follow-up messages (n = 215/723, 29.7%), consultations for drug use (n = 157/723, 21.7%), and medication prescriptions (n = 113/723, 15.6%). Protocol biopsy discussions (n = 33/723, 4.6%) and fever (n = 27/723, 3.7%) were among others (vaccination, rash, diarrhea, cough, fatigue, acne). During the COVID-19 outbreak, only post-LT follow-up messages increased significantly to 132/395 (33%) from 83/328 (25%) (p-value: .02). CONCLUSIONS: We found that the pandemic resulted in an increase in the total number of text message mediated consultations and specifically for the use of post-LT follow-up. Messaging was effective for post-LT follow-ups and all patients were at least satisfied.

Assessment of Immunological Potential of Glial Restricted Progenitor Graft In Vivo-Is Immunosuppression Mandatory?

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease, causing motor neuron and skeletal muscle loss and death. One of the promising therapeutic approaches is stem cell graft application into the brain; however, an immune reaction against it creates serious limitations. This study aimed to research the efficiency of glial restricted progenitors (GRPs) grafted into murine CNS (central nervous system) in healthy models and the SOD1G93A ALS disease model. The cellular grafts were administered in semiallogenic and allogeneic settings. To investigate the models of immune reaction against grafted GRPs, we applied three immunosuppressive/immunomodulatory regimens: preimplantation factor (PiF); Tacrolimus; and CTLA-4, MR1 co-stimulatory blockade. We tracked the cells with bioluminescence imaging (BLI) in vivo to study their survival. The immune response character was evaluated with brain tissue assays and multiplex ELISA in serum and cerebrospinal fluid (CSF). The application of immunosuppressive drugs is disputable when considering cellular transplants into the immune-privileged site/brain. However, our data revealed that semiallogenic GRP graft might survive inside murine CNS without the necessity to apply any immunomodulation or immunosuppression, whereas, in the situation of allogeneic mouse setting, the combination of CTLA-4, MR1 blockade can be considered as the best immunosuppressive option.

Quantifying spillover benefits in value assessment: a case study of increased graft survival on the US kidney transplant waitlist.

AIM: To quantify the wider impacts of increased graft survival on the size of the kidney transplant waitlist and health and economic outcomes. MATERIALS AND METHODS: The analysis employed known steady-state solutions to a double-queueing system as well as simulations of this system. Baseline input parameters were sourced from the Organ Procurement and Transplant Network and the United States Renal Data System. Three increased graft survival scenarios were modeled: decreases in repeat transplant candidates joining the waitlist of 25%, 50%, and 100%. RESULTS: Under the three scenarios, we estimated that the US waitlist size would decrease from 91,822 to 85,461 (6.9% decrease), 80,073 (12.8% decrease), and 69,340 (24.4% decrease), respectively. Patient outcomes improved, with lifetime quality-adjusted life years (QALYs) for a 1-year cohort of transplant recipients increasing by 10,010, 16,888, and 43,345 over the three scenarios. Discounted lifetime costs for the cohort in the new steady state were lower by $1.6 billion, $2.3 billion, and $9.0 billion for each scenario, respectively. Spillover impacts (i.e. benefits that accrued beyond the patients who directly experienced increased graft survival) accounted for 41-48% of the QALY gains and ranged from cost increases of 3.3% to decreases of 5.5%. LIMITATIONS: The model is a simplification of reality and does not account for the full degree of patient heterogeneity occurring in the real world. Health economic outcomes are extrapolated based on the assumption that the median patient is representative of the overall population. CONCLUSIONS: Increasing graft survival reduces demand from repeat transplants candidates, allowing additional candidates to receive transplants. These spillover impacts decrease waitlist size and shorten wait times, leading to improvements in graft and patient survival as well as quality-of-life. Cost-effectiveness analyses of treatments that increase kidney graft survival should incorporate spillover benefits that accrue beyond the direct recipient of an intervention.

Experimental Assessment of Possible Factors Associated with Tick-Borne Encephalitis Vaccine Failure.

Currently the only effective measure against tick-borne encephalitis (TBE) is vaccination. Despite the high efficacy of approved vaccines against TBE, rare cases of vaccine failures are well documented. Both host- and virus-related factors can account for such failures. In this work, we studied the influence of mouse strain and sex and the effects of cyclophosphamide-induced immunosuppression on the efficacy of an inactivated TBE vaccine. We also investigated how an increased proportion of non-infectious particles in the challenge TBE virus would affect the protectivity of the vaccine. The vaccine efficacy was assessed by mortality, morbidity, levels of viral RNA in the brain of surviving mice, and neutralizing antibody (NAb) titers against the vaccine strain and the challenge virus. Two-dose vaccination protected most animals against TBE symptoms and death, and protectivity depended on strain and sex of mice. Immunosuppression decreased the vaccine efficacy in a dose-dependent manner and changed the vaccine-induced NAb spectrum. The vaccination protected mice against TBE virus neuroinvasion and persistence. However, viral RNA was detected in the brain of some asymptomatic animals at 21 and 42 dpi. Challenge with TBE virus enriched with non-infectious particles led to lower NAb titers in vaccinated mice after the challenge but did not affect the protective efficacy.

Longitudinal assessment of IFN-I activity and immune profile in critically ill COVID-19 patients with acute respiratory distress syndrome.

BACKGROUND: Since the onset of the pandemic, only few studies focused on longitudinal immune monitoring in critically ill COVID-19 patients with acute respiratory distress syndrome (ARDS) whereas their hospital stay may last for several weeks. Consequently, the question of whether immune parameters may drive or associate with delayed unfavorable outcome in these critically ill patients remains unsolved. METHODS: We present a dynamic description of immuno-inflammatory derangements in 64 critically ill COVID-19 patients including plasma IFNα2 levels and IFN-stimulated genes (ISG) score measurements. RESULTS: ARDS patients presented with persistently decreased lymphocyte count and mHLA-DR expression and increased cytokine levels. Type-I IFN response was initially induced with elevation of IFNα2 levels and ISG score followed by a rapid decrease over time. Survivors and non-survivors presented with apparent common immune responses over the first 3 weeks after ICU admission mixing gradual return to normal values of cellular markers and progressive decrease of cytokines levels including IFNα2. Only plasma TNF-α presented with a slow increase over time and higher values in non-survivors compared with survivors. This paralleled with an extremely high occurrence of secondary infections in COVID-19 patients with ARDS. CONCLUSIONS: Occurrence of ARDS in response to SARS-CoV2 infection appears to be strongly associated with the intensity of immune alterations upon ICU admission of COVID-19 patients. In these critically ill patients, immune profile presents with similarities with the delayed step of immunosuppression described in bacterial sepsis.

Ideal Body Weight-Based Dosing of Rabbit Antithymocyte Globulin for Cost Minimization in Kidney Transplantation.

INTRODUCTION: Contemporary dosing strategies for rabbit anti-thymocyte globulin (rATG) in kidney transplantation aim to reduce cumulative exposure, minimizing long-term adverse events. The use of ideal body weight-based dosing has been trialed, however concern for increased rejection post-transplant exists due to lower doses of rATG. Research Questions: The primary aim of this study was to compare rejection rates between rATG dosing protocols using actual body weight and ideal body weight and secondarily to evaluate cost savings following protocol implementation. DESIGN: This was a retrospective study surrounding implementation of an ideal body weight-based dosing protocol for rATG. We compared 75 kidney transplant recipients in whom rATG was dosed based on actual body weight (pre-protocol group) to 64 in whom dosing was based on ideal body weight (post-protocol group), following a nine-month washout. RESULTS: The mean cumulative rATG dose in the pre-protocol group was 6.3 mg/kg of actual body weight. When ideal body weight was used in the post-protocol group, the mean dose was 4.5 mg/kg of actual body weight. The rejection rate was 18.7% pre-protocol and 23.4% postprotocol, which did not represent a statistically significant difference (p = 0.491). The actual annual cost savings after protocol implementation exceeded $162,000, approximately $2,500 per patient. CONCLUSION: Results suggest ideal body weight-based dosing of rATG may reduce exposure and cost, without significantly impacting the risk of rejection in kidney transplant recipients. More studies are needed to confirm these findings.

Impact of the COVID-19 pandemic on liver donation and transplantation: A review of the literature.

The coronavirus disease 2019 (COVID-19) pandemic has upended healthcare systems worldwide and led to an inevitable decrease in liver transplantation (LT) activity. During the first pandemic wave, administrators and clinicians were obliged to make the difficult decision of whether to suspend or continue a life-saving procedure based on the scarce available evidence regarding the risk of transmission and mortality in immunosuppressed patients. Those centers where the activity continued or was heavily restricted were obliged to screen donors and recipients, design COVID-safe clinical pathways, and promote telehealth to prevent nosocomial transmission. Despite the ever-growing literature on COVID-19, the amount of high-quality literature on LT remains limited. This review will provide an updated view of the impact of the pandemic on LT programs worldwide. Donor and recipient screening, strategies for waitlist prioritization, and posttransplant risk of infection and mortality are discussed. Moreover, a particular focus is given to the possibility of donor-to-recipient transmission and immunosuppression management in COVID-positive recipients.

Thromboelastometry assessment of mycophenolate mofetil effect on thrombotic risk in dogs with primary and secondary immune-mediated hemolytic anemia and by Erhlichia canis infection / [Avaliação por tromboelastometria do efeito do micofenolato de mofetila no risco trombótico em cães com anemia hemolítica imunomediada primária e secundária à infecção por Erhlichia canis]

This study aimed to identify, by means of thromboelastometry assessment, altered thrombotic risk in dogs with primary and secondary IMHA by E. canis infection after initiating the immunosuppressive therapy with mycophenolate mofetil. The animals' screening was based on complete blood count (CBC), biochemical and urine tests. Dogs with moderate to severe anemia (hematocrit ≤ 25%) which showed symptoms of immune-mediated hemolysis, such as spherocytosis, positive saline agglutination, bilirubinuria and/or hemoglobinuria, were included. Blood and urine samples were collected at two different moments. The first sample (M1) was collected at the time of diagnosis, when hematocrit was lower or equal to 25% before treatment with mycophenolate mofetil (Accord ®); the second sample (M2) was collected after treatment with mycophenolate mofetil, when hematocrit was greater or equal to 30%. Five out of the twelve animals selected died before the end of the study. No reduction in thrombotic risk was observed in the animals treated with mycophenolate mofetil. The animals that presented hypocoagulation at the time of diagnosis showed the worst prognosis, and their reticulocyte count displayed a better prognostic value than their erythrocytes count at the time of diagnosis.(AU)

O objetivo deste estudo foi esclarecer se há alteração do risco trombótico em cães com anemia hemolítica imunomediada primária e secundária a E.canis, avaliado por meio da tromboelastometria, após início de tratamento com micofenolato de mofetila. A seleção dos animais foi baseada na avaliação de hemograma, exame bioquímico e urinálise. Cães com anemia moderada a severa (hematócrito ≤ 25%), com sinais de hemólise imunomediada, como esferocitose, aglutinação em salina positivo, bilirrubinúria e/ ou hemoglobinúria, foram incluídos. As amostras de sangue e urina foram coletadas em dois momentos diferentes. A primeira amostra (M1) foi coletada no momento do diagnóstico, quando o hematócrito era igual ou inferior a 25%, sem fazer uso do micofenolato de mofetila (Accord®), e o segundo momento (M2), após tratamento com micofenolato de mofetila, quando o hematócrito era igual ou maior que 30%. Doze animais foram selecionados, cinco morreram antes do término do estudo. Não houve diminuição do risco trombótico entre os animais tratados com micofenolato de mofetila; os animais que apresentaram menor coagulabilidade apresentaram pior prognóstico, e a contagem de reticulócitos apresentou melhor valor prognóstico do que a contagem de hemácias no momento do diagnóstico.(AU)

Assessment of chitosan nanoparticles in improving the efficacy of nitazoxanide on cryptosporidiosis in immunosuppressed and immunocompetent murine models.

Cryptosporidiosis is one of the major causes of diarrhea in immunocompetent and immunocompromised patients. It is self-limited in immunocompetent individuals. However, in the immunocompromised it can cause life-threatening diarrhea and results in chronic malabsorption of fluids, vitamins and electrolytes resulting in wasting. Our study is concerned with assessing and comparing the efficacy of nitazoxanide (NTZ) alone and NTZ loaded chitosan nanoparticles (NTZ loaded CS NPs) in the treatment of experimental cryptosporidiosis using parasitological and histopathological parameters. One hundred mice were divided into 5 groups (20 mice each). Each group was divided into 2 subgroups according to the immune status [a-immunocompetent, b-immunosuppressed]. group 1: control (healthy), group 2: control infected by Cryptosporidium oocysts, group 3: infected treated by NTZ, group 4: infected then treated by NTZ loaded CS NPs and group 5: infected then treated by chitosan nanoparticles (CS NPs) alone. Treatment of Cryptosporidium infected mice with NTZ loaded on CS NPs resulted in the highest significant reduction in oocysts shedding in both immunocompetent and immunosuppressed groups followed by treatment with NTZ form then by treatment with CS NPs alone. The treatment with NTZ loaded CS NPs displayed a remarkable improvement of the histopathological changes of the intestine, liver and lung while NTZ treated group showed some improvement. Treatment with NTZ loaded CS NPs in murine cryptosporidiosis gave the best results as it caused marked reduction in fecal oocysts counts and improvement of histopathological changes in immunocompetent and immunosuppressed groups.

A multicenter case series documenting Medicare Part D plan denials of immunosuppressant drug coverage for organ transplant recipients.

Medicare Part D plans make coverage decisions according to FDA-labeled indications and off-label uses endorsed by two CMS-recognized compendia. Patients who rely on Medicare Part D for immunosuppressive drug coverage are at risk for denied coverage when these medications are prescribed off-label. The purpose of this multicenter collaboration was to assemble a case series documenting situations where immunosuppressive therapies prescribed for transplant patients were denied by Medicare Part D prescription drug plans. This case series documents 66 instances in 39 patients where immunosuppressive drug claims were denied coverage due to off-label use not endorsed by the compendia. Patients were recipients of lung (n = 28, 72%), heart (n = 7, 18%), or liver (n = 4, 10%) transplants. Denied claims were for mycophenolate mofetil (n = 22, 33%), azathioprine (n = 18, 27%), sirolimus (n = 15, 23%), mycophenolate sodium (n = 5, 8%), everolimus (n = 5, 8%), and belatacept (n = 1, 1%). Most denials were upheld across all the levels of attempted appeal, including those escalated to a Medicare Administrative Law Judge. This case series demonstrates a critical flaw in the construct of the Medicare Prescription Drug Benefit. The currently referenced compendia are not up to date and do not reflect best practices in organ transplantation.

Assessment of the Readability, Availability, and Quality of Online Patient Education Materials Regarding Uveitis Medications.

Purpose: To assess the availability, quality, and readability of online patient education materials regarding uveitis medications.Methods: The top 10 Google search results for 10 commonly prescribed uveitis medications (prednisone, azathioprine, methotrexate, mycophenolate mofetil, cyclosporine, tacrolimus, chlorambucil, cyclophosphamide, adalimumab, and infliximab) were analyzed for readability and accountability. Readability was assessed with the Flesch reading ease score, Flesch-Kincaid grade level, Gunning Fog Index, Simple Measure of Gobbledygook Index, and Coleman Liau Index. JAMA benchmarks were used to assign websites accountability scores. Statistical analysis was performed with two-tailed t-tests.Results: Of 100 search results, none complied with the recommended sixth-grade reading level across all readability formulas. Only one website satisfied all 4 JAMA benchmarks, two websites were able to satisfy three benchmarks, and the remainder achieved two or less.Conclusions: Online information regarding uveitis medications lacks accountability and is not written at an appropriate level for the average patient.