Hematologic Complications,Healthcare Utilization,and Costs in Commercially Insured Patients with Myelodysplastic Syndrome Receiving Supportive Care

Background

Myelodysplastic syndrome (MDS) is rare in people aged <50 years. Most patients with this disorder experience progressive worsening of blood cytopenias, with an increasing need for transfusion. The more advanced and severe the disorder, the greater the risk that it will progress to acute myeloid leukemia. Therapy is typically based on the patient''s risk category, age, and performance status. Supportive care alone is a major option for lower-risk, older patients with MDS or those with comorbidities. The only potentially curative treatment option is hematopoietic stem-cell transplantation, which is typically used to treat high-risk, younger patients.

Objective

To describe and compare the hematologic complications, healthcare utilization, and costs of supportive care in patients with MDS aged <50 years and in older patients aged ≥50 years.

Methods

Using the i3/Ingenix LabRx claims database, this retrospective study included patients who were continuously enrolled (ie, 6 months preindex through 1 year postindex) in the study and who had an initial claim of MDS (index date) between February 1, 2007, and July 31, 2008. Patients treated with hypomethylating agents or thalidomide analogues were excluded. Claims included information on office visits, medical procedures, hospitalizations, drug use, and tests performed. The hematologic complications, costs, and utilization analyses were stratified by age into 2 age-groups—patients aged <50 years and those aged ≥50 years. The MDS-related diagnoses, utilization, and costs were analyzed postindex. The data used in this study spanned the period from August 1, 2006, to July 31, 2009.

Results

We identified 1133 newly diagnosed patients with MDS who received supportive care only during the study period; of these, 19.5% were younger than age 50 years. These younger patients included more females (62.0% vs 52.5%; P = .011) and had fewer comorbidities (mean Charlson comorbidy index, 1.2 vs 2.4; P <.001) and physician office visits than those aged ≥50 years. Postindex, compared with the older patients, the younger patients had less use of erythropoietin therapy and fewer transfusions, anemia diagnoses, and potential complications of neutropenia and pneumonia diagnoses; however, more diagnoses of neutropenia and of decreased white blood cell counts were seen in the younger patients than in the older patients (P ≤.034 for all comparisons). Furthermore, younger patients had fewer mean office visits in the postindex period than older patients (17.5 vs 24.2, respectively; P <.001) and fewer hospitalizations (32.1% vs 44.6%, respectively; P = .004), but they had a longer (although not statistically significant) mean length of hospital stay (21 vs 14 days, respectively; P = .131). Mean total healthcare charges were $96,277 (median, $21,287) in younger patients compared with $84,102 (median, $39,402) in older patients, although this difference, too, was not significant.

Conclusions

MDS is associated with frequent and prolonged hospitalizations, frequent outpatient visits, and high costs in younger and in older patients who are receiving supportive care. Although this study shows that younger patients aged <50 years do not have significantly higher costs overall, a small proportion may have a higher healthcare utilization and cost-related burden of MDS than patients aged ≥50 years.Myelodysplastic syndrome (MDS) encompasses a heterogeneous group of clonal disorders of hematopoiesis and is characterized by dysplastic morphology of marrow and blood cells, ineffective hematopoiesis, and peripheral blood cytopenias.1,2 Most patients with MDS experience progressive worsening of blood cytopenias, with an increasing need for transfusion.2 These patients also have an increasing number of potentially fatal infections and hemorrhagic complications.2 The more advanced and severe the MDS is, the greater the risk that the disease will progress to acute myeloid leukemia (AML).3 The disease may be classified into 1 of 5 subtypes—refractory anemia, refractory anemia with ringed sideroblasts (RARS), refractory anemia with excess of blasts (RAEB), RAEB in transformation (RAEB-T), or chronic myelomonocytic leukemia.3 Approximately 5% to 15% of the relatively lower-risk patients with refractory anemia/RARS transform to AML; by contrast, 40% to 50% of the high-risk patients with RAEB/RAEB-T transform to AML.3The therapeutic options that are tailored for specific MDS subgroups are typically based on factors such as the patient''s risk category, age, and performance status.3,4 The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology recommend that all patients with MDS receive supportive care,3 which includes blood transfusions, erythropoietin with or without granulocyte colony-stimulating factor, iron chelation therapy, and prophylactic antibiotics.4,5 Other therapies indicated for the treatment of patients with MDS include the thalidomide analogue lenalidomide and the hypomethylating agents decitabine and 5-azacytidine.3,4 The only potentially curative treatment option is hematopoietic stem-cell transplantation, which is typically used to treat younger, high-risk patients.3,4 Supportive care alone remains a leading option for the treatment of lower-risk, older patients with MDS or those with comorbidities.3,4Data on the distribution of MDS in the general population are inconsistent, possibly because of misdiagnoses and/or underreporting of the disease.6,7 The most recent estimates of the annual incidence of MDS in the United States range from 3.3 to 5.0 per 100,000 persons.3,7,8 Some studies indicate that the median age of patients with MDS is approximately 65 years, whereas others note that more than 70% of cases occur in patients aged ≥70 years in the United States.3,6,9 The incidence of MDS in individuals aged ≥70 years is between 22 and 45 per 100,000 persons and increases with age.3,6,9–11Less than 10% of patients with MDS are aged <50 years; therefore, little is known about this disease in this younger age-group, particularly among patients who receive supportive care only.6,11,12 Some data suggest that younger patients with MDS have less aggressive disease.12,13 We compared hematologic complications, healthcare utilization, and costs in patients aged <50 years and in those aged ≥50 years who were newly diagnosed with MDS and received supportive care only.

KEY POINTS

• ▸ The more advanced and severe the myelodysplastic syndrome (MDS) is, the greater the risk of progression to acute myeloid leukemia. Therapy is currently based on risk category, age, and performance status.
• ▸ In the United States, the majority of newly diagnosed patients with MDS receive only supportive care, although for younger patients at high-risk, hematopoietic stem-cell transplantation is potentially the only curative option.
• ▸ This analysis compares the hematologic complications, healthcare utilization, and cost of care between patients with MDS aged <50 years and those aged ≥50 years who receive supportive care only.
• ▸ Although the younger patients had fewer office visits, they had longer mean length of hospital stay than the older group (21 vs 14 days, respectively).
• ▸ Mean total healthcare charges were $96,277 in younger patients compared with $84,102 in older patients.
• ▸ Based on this study, approximately 20% of patients with MDS are under age 50 years.
• ▸ The results of this study suggest that a small proportion of younger patients with MDS who receive supportive care only may have a higher healthcare utilization and cost-related burden of MDS than older patients with this condition.

     

Endovideosurgical antireflux operations in combination with cholecystectomy

In the city center of endovideosurgery during 1999-2005 there were 205 patients examined and treated for cholelithiasis combined with gastro-esophageal-reflux disease (GERD) and hiatal hernias. Simultaneous interventions, antireflux operation and cholecystectomy were performed in 150 patients. Cholecystectomy followed by conservative treatment of GERD was performed in 55 patients. The results of treatment were followed up during 1 and 6 months.     

Race and gender associations between obesity and nine health-related quality-of-life measures

Purpose  

To assess how health-related quality of life (HRQoL) varies by body mass index (BMI) category among gender and racial subgroups using nine HRQoL measures.     

Follow-up intervals in patients with Cushing’s disease: recommendations from a panel of experienced pituitary clinicians

Purpose

Follow-up guidelines are needed to assess quality of care and to ensure best long-term outcomes for patients with Cushing’s disease (CD). The purpose of this study was to assess agreement by experts on recommended follow-up intervals for CD patients at different phases in their treatment course.

Methods

The RAND/UCLA modified Delphi process was used to assess expert consensus. Eleven clinicians who regularly manage CD patients rated 79 hypothetical patient scenarios before and after (“second round”) an in-person panel discussion to clarify definitions. Scenarios described CD patients at various time points after treatment. For each scenario, panelists recommended follow-up intervals in weeks. Panel consensus was assigned as follows: “agreement” if no more than two responses were outside a 2 week window around the median response; “disagreement” if more than two responses were outside a 2 week window around the median response. Recommendations were developed based on second round results.

Results

Panel agreement was 65.9% before and 88.6% after the in-person discussion. The panel recommended follow-up within 8 weeks for patients in remission on glucocorticoid replacement and within 1 year of surgery; within 4 weeks for patients with uncontrolled persistent or recurrent disease; within 8–24 weeks in post-radiotherapy patients controlled on medical therapy; and within 24 weeks in asymptomatic patients with stable plasma ACTH concentrations after bilateral adrenalectomy.

Conclusions

With a high level of consensus using the Delphi process, panelists recommended regular follow-up in most patient scenarios for this chronic condition. These recommendations may be useful for assessment of CD care both in research and clinical practice.

     

Inducing Hepatitis C Virus Resistance After Pig Liver Transplantation—A Proof of Concept of Liver Graft Modification Using Warm Ex Vivo Perfusion

Normothermic ex vivo liver perfusion (NEVLP) offers the potential to optimize graft function prior to liver transplantation (LT). Hepatitis C virus (HCV) is dependent on the presence of miRNA(microRNA)‐122. Miravirsen, a locked‐nucleic acid oligonucleotide, sequesters miR‐122 and inhibits HCV replication. The aim of this study was to assess the efficacy of delivering miravirsen during NEVLP to inhibit miR‐122 function in a pig LT model. Pig livers were treated with miravirsen during NEVLP or cold storage (CS). Miravirsen absorption, miR‐122 sequestration, and miR‐122 target gene derepression were determined before and after LT. The effect of miravirsen treatment on HCV infection of hepatoma cells was also assessed. NEVLP improved miravirsen uptake versus CS. Significant miR‐122 sequestration and miR‐122 target gene derepression were seen with NEVLP but not with CS. In vitro data confirmed miravirsen suppression of HCV replication after established infection and prevented HCV infection with pretreatment of cells, analogous to the pretreatment of grafts in the transplant setting. In conclusion, miravirsen delivery during NEVLP is a potential strategy to prevent HCV reinfection after LT. This is the first large‐animal study to provide “proof of concept” for using NEVLP to modify and optimize liver grafts for transplantation.     

The emotional face of anorexia nervosa: The neural correlates of emotional processing

Social–emotional processing difficulties have been reported in Anorexia Nervosa (AN), yet the neural correlates remain unclear. Previous neuroimaging work is sparse and has not used functional connectivity paradigms to more fully explore the neural correlates of emotional difficulties. Fifty‐seven acutely unwell AN (AAN) women, 60 weight‐recovered AN (WR) women and 69 healthy control (HC) women categorised the gender of a series of emotional faces while undergoing Functional Magnetic Resonance Imaging. The mean age of the AAN group was 19.40 (2.83), WR 18.37 (3.59) and HC 19.37 (3.36). A whole brain and psychophysical interaction connectivity approach was used. Parameter estimates from significant clusters were extracted and correlated with clinical symptoms. Whilst no group level differences in whole brain activation were demonstrated, significant group level functional connectivity differences emerged. WR participants showed increased connectivity between the bilateral occipital face area and the cingulate, precentral gyri, superior, middle, medial and inferior frontal gyri compared to AAN and HC when viewing happy valenced faces. Eating disorder symptoms and parameter estimates were positively correlated. Our findings characterise the neural basis of social–emotional processing in a large sample of individuals with AN.