The high cost of inappropriate empiric treatment of presumed Clostridium difficile-associated diarrhea

The Center for Disease Control and Prevention (CDC) estimates that more than 2 million patients annually acquire an infection while hospitalized in U.S. hospitals for other health problems, and that 88,000 die as a direct or indirect result of these infections. Infection with Clostridium difficile is the most important common cause of health care associated infectious diarrhea in industrialized countries. The purpose of this study was to explore the cost of current treatment practice of beginning empiric metronidazole treatment for hospitalized patients with diarrhea prior to identification of an infectious agent. The records of 70 hospitalized patients were retrospectively analyzed to determine the pharmacologic treatment, laboratory testing, and radiographic studies ordered and the median cost for each of these was determined. All patients in the study were tested for C. difficile and concurrently started on empiric metronidazole. The median direct cost for metronidazole was $7.25 per patient (95% CI 5.00, 12.721). The median direct cost for laboratory charges was $468.00 (95% CI 339.26, 552.58) and for radiology the median direct cost was $970.00 (95% CI 738.00, 3406.91). Indirect costs, which are far greater than direct costs, were not studied. At St. Luke's, if every hospitalized patient with diarrhea was empirically treated with metronidazole at a median cost of $7.25, the annual direct cost is estimated to be over $9,000.00 plus uncalculated indirect costs. In the U.S., the estimated annual direct cost may be as much as $21,750,000.00, plus indirect costs. ^ An unexpected and significant finding of this study was the inconsistency in testing and treatment of patients with health care associated diarrhea. A best-practice model for C. difficile testing and treatment was not found in the literature review. In addition to the cost savings gained by not routinely beginning empiric treatment with metronidazole, significant savings and improvement in patient care may result from a more consistent approach to the diagnosis and treatment of all patients with health care associated diarrhea. A decision tree model for C. difficile testing and treatment is proposed, but further research is needed to evaluate the decision arms before a validated best practice model can be proposed. ^

The economic cost of type 2 diabetes attributable to physical inactivity in the United States and Texas in 2007

Type 2 diabetes has grown to epidemic proportions in the U.S., and its prevalence has been steadily increasing in Texas. The physical activity levels in the population have remained low despite it being one of the primary preventive strategies for type 2 diabetes. The objectives of this study were to estimate the direct medical costs of type 2 diabetes attributable to not meeting physical activity Guidelines and to physical inactivity in the U.S. and Texas in 2007. This was a cross sectional study that used physical activity prevalence data from the 2007 Behavioral Risk Factor Surveillance System (BRFSS) to estimate the population attributable risk percentage (PAR%) for type 2 diabetes. These data were combined with the prevalence and cost data of type 2 diabetes to estimate the cost of type 2 diabetes attributable to not meeting Guidelines and to inactivity in the U.S. and Texas in 2007.^ The cost of type 2 diabetes in the U.S. in 2007, attributable to not meeting physical activity Guidelines was estimated to be $13.29 billion, and that attributable to physical inactivity (no leisure time physical activity) was estimated to be $3.32 billion. Depending on various assumptions, these estimates ranged from $7.61 billion to $41.48 billion for not meeting Guidelines, and $1.90 billion to $13.20 billion for physical inactivity in the U.S. in 2007. The cost of type 2 diabetes in Texas in 2007 attributable to not meeting physical activity Guidelines was estimated to be $1.15 billion, and that attributable to physical inactivity (no leisure time physical activity) was estimated to be $325 million. Depending on various assumptions, these estimates ranged from $800 million to $3.47 billion for not meeting Guidelines, and $186 million to $1.28 billion for physical inactivity in Texas in 2007. These results illustrate how much money could be saved annually just in terms of type 2 diabetes cost in the U.S. and Texas, if the entire adult population was active enough to meet physical activity Guidelines. Physical activity promotion, particularly at the environmental and policy level should be a priority in the population. ^

Apoptosis and the molecular complementation of bcl-2, myc and p53 in multistep lymphomagenesis

Follicular lymphoma is the most common lymphoid malignancy in humans. The bcl-2 transgenic mice, which mimic the human follicular lymphoma, initially exhibit a polyclonal hyperplasia due to the overriding of apoptosis by deregulated bcl-2. After a latency period of 15 month 20% of the animals developed clonal lymphomas. Approximately, 50% of these high grade lymphomas presented chromosomal translocations involving c-myc, suggesting that deregulation of this gene is important in the complementation with bcl-2. E$\mu$-myc x bcl-2 double transgenic mice were generated to assess the ability of this two genes to complement in an in vivo system. The double transgenic mice presented a shortened latency (3-4 weeks) and higher incidence of tumor development. Quantification of the extent of programmed cell death indicated that bcl-2 can abrogate the high rate of apoptotic cell death that results from myc deregulation. Bcl-2-Ig, E$\mu$-myc, and bcl-2/E$\mu$-myc lymphomas were examined using PCR-SSCP to detect the presence of p53 mutations in exons 5-9. A high incidence of p53 mutations in E$\mu$-myc lymphomas suggested that inactivating lesions of p53 may represent an important step in the genetic complementation of c-myc in lymphomagenesis. Surprisingly, p53 mutations were quite uncommon in bcl-2 lymphomas suggesting that inactivating mutations of p53 and overexpression of bcl-2 may not cooperate in lymphoma progression. To assess this question, we generated mice that contained a deregulated bcl-2 gene and were nullizygous for p53 (p53KO). No reduction in the tumor latency was observed in the p53KO/bcl-2-Ig hybrid mice when compared with p53 KO mice. Using splenic mononuclear cells isolated from p53KO mice and bcl-2 transgenic mice we demonstrated that bcl-2 suppresses p53 mediated apoptosis in response to DNA damage initiated by $\gamma$-radiation even though p53 protein is induced normally in the bcl-2 overexpressing cells. Western analysis of the expression of p53 target proteins after $\gamma$-radiation showed a correlation between the p53-dependent induction of bax protein after radiation and the ability of p53 to mediate apoptosis. ^

Physician adoption of a practice guideline: Effect on the cost of medical care for adult patients with diabetes

In the demanding environment of healthcare reform, reduction of unwanted physician practice variation is promoted, often through evidence-based guidelines. Guidelines represent innovations that direct change(s) in physician practice; however, compliance has been disappointing. Numerous studies have analyzed guideline development and dissemination, while few have evaluated the consequences of guideline adoption. The primary purpose of this study was to explore and analyze the relationship between physician adoption of the glycated hemoglobin test guideline for management of adult patients with diabetes, and the cost of medical care. The study also examined six personal and organizational characteristics of physicians and their association with innovativeness, or adoption of the guideline. ^ Cost was represented by approved charges from a managed care claims database. Total cost, and diabetes and related complications cost, first were compared for all patients of adopter physicians with those of non-adopter physicians. Then, data were analyzed controlling for disease severity based on insulin dependency, and for high cost cases. There was no statistically significant difference in any of eight cost categories analyzed. This study represented a twelve-month period, and did not reflect cost associated with future complications known to result from inadequate management of glycemia. Guideline compliance did not increase annual cost, which, combined with the future benefit of glycemic control, lends support to the cost effectiveness of the guideline in the long term. Physician adoption of the guideline was recommended to reduce the future personal and economic burden of this chronic disease. ^ Only half of physicians studied had adopted the glycated hemoglobin test guideline for at least 75% of their diabetic patients. No statistically significant relationship was found between any physician characteristic and guideline adoption. Instead, it was likely that the innovation-decision process and guideline dissemination methods were most influential. ^ A multidisciplinary, multi-faceted approach, including interventions for each stage of the innovation-decision process, was proposed to diffuse practice guidelines more effectively. Further, it was recommended that Organized Delivery Systems expand existing administrative databases to include clinical information, decision support systems, and reminder mechanisms, to promote and support physician compliance with this and other evidence-based guidelines. ^

The cost of insuring the uninsured in the U.S.

Objectives: This study included two overarching objectives. Through a systematic review of the literature published between 1990 and 2012, the first objective aimed to assess whether insuring the uninsured would result in higher costs compared to insuring the currently insured. Studies that quantified the actual costs associated with insuring the uninsured in the U.S. were included. Based upon 2009 data from the Medical Expenditure Panel Survey (MEPS), the second objective aimed to assess and compare the self-reported health of populations with four different insurance statuses. The second part of this study involved a secondary data analysis of both currently insured and currently uninsured individuals who participated in the MEPS in 2009. The null hypothesis was that there were no differences across the four categories of health insurance status for self-reported health status and healthcare service use. The alternative hypothesis was that were differences across the four categories of health insurance status for self-reported health status and healthcare service use. Methods: For the systematic review, three databases were searched using search terms to identify studies that actually quantified the cost of insuring the uninsured. Thirteen studies were selected, discussed, and summarized in tables. For the secondary data analysis of MEPS data, this study compared four categories of health insurance status: (1) currently uninsured persons who will become eligible for Medicaid under the Patient Protection and Affordable Care Act (PPACA) healthcare reforms in 2014; (2) currently uninsured persons who will be required to buy private insurance through the PPACA health insurance exchanges in 2014; (3) persons currently insured under Medicaid or SCHIP; and (4) persons currently insured with private insurance. The four categories were compared on the basis of demographic information, health status information, and health conditions with relatively high prevalence. Chi-square tests were run to determine if there were differences between the four groups in regard to health insurance status and health status. With some exceptions, the two currently insured groups had worse self-reported health status compared to the two currently uninsured groups. Results: The thirteen studies that met the inclusion criteria for the systematic review included: (1) three cost studies from 1993, 1995, and 1997; (2) four cost studies from 2001, 2003, and 2004; (3) one study of disabilities and one study of immigrants; (4) two state specific studies of uninsured status; and (5) two current studies of healthcare reform. Of the thirteen studies reviewed, four directly addressed the study question about whether insuring the uninsured was more or less expensive than insuring the currently insured. All four of the studies provided support for the study finding that the cost of insuring the uninsured would generally not be higher than insuring those already insured. One study indicated that the cost of insuring the uninsured would be less expensive than insuring the population currently covered by Medicaid, but more expensive to insure than the populations of those covered by employer-sponsored insurance and non-group private insurance. While the nine other studies included in the systematic review discussed the costs associated with insuring the uninsured population, they did not directly compare the costs of insuring the uninsured population with the costs associated with insuring the currently insured population. For the MEPS secondary data analysis, the results of the chi-square tests indicated that there were differences in the distribution of disease status by health insurance status. As anticipated, with some exceptions, the uninsured reported lower rates of disease and healthcare service use. However, for the variable attention deficit disorder, the uninsured reported higher disease rates than the two insured groups. Additionally, for the variables high blood pressure, high cholesterol, and joint pain, the currently insured under Medicaid or SCHIP group reported a lower rate of disease than the two currently insured groups. This result may be due to the lower mean age of the currently insured under Medicaid or SCHIP group. Conclusion: Based on this study, with some exceptions, the costs for insuring the uninsured should not exceed healthcare-related costs for insuring the currently uninsured. The results of the systematic review indicated that the U.S. is already paying some of the costs associated with insuring the uninsured. PPACA will expand health insurance coverage to millions of Americans who are currently uninsured, as the individual mandate and insurance market reforms will require. Because many of the currently uninsured are relatively healthy young persons, the costs associated with expanding insurance coverage to the uninsured are anticipated to be relatively modest. However, for the purposes of construing these results, it is important to note that once individuals obtain insurance, it is anticipated that they will use more healthcare services, which will increase costs. (Abstract shortened by UMI.)^