Do frail, disabled, poor, and very old Medicare beneficiaries have higher hospital charges?

To determine whether basing payments on diagnosis related groups (DRGs) results in mispayment for certain classes of patients, we examined the relation between total Medicare charges per hospitalization and eight beneficiary characteristics (including admission from a nursing home, extreme age, Medicaid enrollment, and disability). We controlled for the hospital in which care was given and the DRG to which the discharge was assigned. The largest effects were that average charges were 6.7% higher for beneficiaries who were disabled before the age of 65 years, and 6.2% higher for patients admitted from a nursing home; charges were 1.5% lower for Medicare beneficiaries who were also enrolled in Medicaid, 3.8% higher for those older than 80 years, and 1.3% lower for those older than 85 years compared with those aged from 80 to 84 years. Because these differences are very small compared with the average variation within DRGs, we conclude that using these beneficiary characteristics in the DRG classification system would only slightly improve DRGs. Medicare's DRG-based payments seem to be substantially equitable with regard to these beneficiary characteristics.     

Interpreting hospital mortality data. The role of clinical risk adjustment

This study uses national Medicare data as well as data that were abstracted to calibrate the Medicare Mortality Predictor System to assess the usefulness of a risk adjustment system in interpreting hospital mortality rates. The majority of variation in annual hospital death rates for the four conditions studied (stroke, pneumonia, myocardial infarction, and congestive heart failure) is chance variability that results from the relatively small numbers of patients treated in most hospitals in a year. For hospitals in the highest and lowest quartiles of observed death rates, the difference between observed rates and those predicted by the Medicare Mortality Predictor System is not quite on third smaller than the difference between observed rates and unadjusted national rates. Risk adjustment methods do not show whether the unexplained difference in mortality rates results from differences in effectiveness of care or unmeasured differences in patient risk at the time of admission. Risk-adjusted mortality rates, therefore, should be supplemented by review of the actual care rendered before conclusions are drawn regarding effectiveness of care.     

Predicting hospital-associated mortality for Medicare patients. A method for patients with stroke, pneumonia, acute myocardial infarction, and congestive heart failure

We created a microcomputer-based system that uses characteristics of the patient at admission to predict death within 30 days of hospital admission for Medicare patients with stroke, pneumonia, myocardial infarction, and congestive heart failure. These conditions account for 13% of discharges and 31% of 30-day mortality for Medicare patients over 64 years of age. The system was calibrated on a stratified, random sample of 5888 discharges (about 1470 for each condition) from seven states, with stratification by hospital type to make the sample nationally representative. The predictors must be specially abstracted from the medical record. The cross-validated R2 for predictions is 0.14 to 0.25, which is better than the values for other systems for which we have data. Risk-adjusted predicted group mortality rates may be useful in interpreting information on unadjusted mortality rates, and patient-specific predictions may be useful in identifying unexpected deaths for clinical review.     

Measuring quality of care under Medicare and Medicaid

The Health Care Financing Administration's (HCFA) approach to measuring quality of care uses an accepted definition of quality, explicit domains of measurement, and a formal validation procedure that includes face validity, construct validity, reliability, clinical validation, and tests for usefulness. The indicators of quality for Medicare and Medicaid patients span the range of service types, medical conditions, and payment systems and rest on a variety of data systems. Some have already been incorporated into operational systems while others are scheduled for incorporation over the next 3 years.     

On the attribution and additivity of binding energies

It can be useful to describe the Gibbs free energy changes for the binding to a protein of a molecule, A—B, and of its component parts, A and B, in terms of the “intrinsic binding energies” of A and B, ΔG_Aⁱ and ΔG_Bⁱ, and a “connection Gibbs energy,” ΔG^s that is derived largely from changes in translational and rotational entropy. This empirical approach avoids the difficult or insoluble problem of interpreting observed ΔH and TΔS values for aqueous solutions. The ΔGⁱ and ΔG^s terms can be large for binding to enzymes and other proteins.     

Systemic hematologic effects of PEG-rHuMGDF-induced megakaryocyte hyperplasia in mice

PEG-rHuMGDF injected daily in normal mice causes a rapid dose-dependent increase in megakaryocytes and platelets. At the same time that platelet numbers are increased, the mean platelet volume (MPV) and platelet distribution width (PDW) can be either decreased, normal, or increased depending on the dose and time after administration. Thus, PEG-rHuMGDF at a low dose causes decreases in MPV and PDW, MGDF at an intermediate dose causes an initial increase followed by a decrease in MPV and PDW, and PEG-rHuMGDF at higher doses causes an increase in MPV and PDW followed by a gradual normalization of these platelet indices. In addition to the expected thrombocytosis after 7 to 10 days of daily injection of high doses of PEG-rHuMGDF, a transient decrease in peripheral red blood cell numbers and hemoglobin is noted accompanied in the bone marrow by megakaryocytic hyperplasia, myeloid hyperplasia, erythroid and lymphoid hypoplasia, and deposition of a fine network of reticulin fibers. Splenomegaly, an increase in splenic megakaryocytes, and extramedullary hematopoiesis accompany the hematologic changes in the peripheral blood and marrow to complete a spectrum of pathologic features similar to those reported in patients with myelofibrosis and megakaryocyte hyperplasia. However, all the PEG-rHuMGDF-initiated hematopathology including the increase in marrow reticulin is completely and rapidly reversible upon the cessation of administration of PEG-rHuMGDF. Thus, transient hyperplastic proliferation of megakaryocytes does not cause irreversible tissue injury. Furthermore, PEG-rHuMGDF completely ameliorates carboplatin-induced thrombocytopenia at a low-dose that does not cause the hematopathology associated with myelofibrosis.     

Colorectal cancer extracellular acidosis decreases immune cell killing and is partially ameliorated by pH-modulating agents that modify tumor cell cytokine profiles

Tumor cells upregulate myriad proteins that are important for pH regulation, resulting in the acidification of the extracellular tumor microenvironment (TME). Abnormal pH is known to dampen immune function, resulting in a worsened anti-tumor immune response. Understanding how extrinsic alterations in pH modulate the interactions between immune cells and tumors cells will help elucidate opportunities for new therapeutic approaches. We observed that pH impacts the function of immune cells, both natural killer (NK) and T cells, which is relevant in the context of a highly acidic TME. Decreased NK and T cell activity was correlated with decreasing pH in a co-culture immune cell-mediated tumor cell-killing assay. The addition of pH-modulating drugs cariporide, lansoprazole, and acetazolamide to the co-culture assay was able to partially mitigate this dampened immune cell function. Treatment of colorectal cancer (CRC) cells with NHE1 inhibitor cariporide increased CRC cell-secreted cytokines involved in immune cell recruitment and activation and decreased cytokines involved in epithelial-mesenchymal transition (EMT). Cariporide treatment also decreased CRC cell shed TRAIL-R2, TRAIL-R3, and PD-L1 which is relevant in the context of immunotherapy. These experiments can help inform future investigations into how the pH of the tumor microenvironment may be extrinsically modulated to improve anti-tumor immune response in solid tumors such as colorectal cancer.     

Simultaneous measurement of gallbladder emptying with cholescintigraphy and US during infusion of physiologic doses of cholecystokinin: a comparison

Both ultrasonography (US) and cholescintigraphy are used to study gallbladder dynamics. The present study was undertaken to determine whether the two methods provide the same or different information relating to gallbladder emptying. Emptying was simultaneously studied with both methods during infusion of graded physiologic doses of cholecystokinin (CCK) in six healthy subjects. Infusion of stepwise increasing doses of CCK, ranging from 0.03 to 0.5 Ivy dog units per kilogram of body weight per hour (IDU/kg.h), induced significant dose-related increases in plasma CCK, decreases in gallbladder volume assessed with US, and gallbladder emptying assessed with cholescintigraphy. The threshold dose for inducing significant gallbladder emptying was 0.13 IDU/kg.h, as determined with both techniques, indicating similar detection limits. There was a highly significant correlation between decreases in gallbladder volume and decreases in radioactive counts over the gallbladder region, with a tendency toward greater gallbladder responses at sonography during the early phase of gallbladder contraction and toward greater responses at cholescintigraphy during the later phase of gallbladder contraction. It is concluded that these methods can be used interchangeably for the quantitation of gallbladder emptying.