Variation in expenditure for common, high cost surgical procedures in a working age population: implications for reimbursement reform.

BACKGROUND: In the move toward value-based care, bundled payments are believed to reduce waste and improve coordination. Some commercial insurers have addressed this through the use of bundled payment, the provision of one fee for all care associated with a given index procedure. This system was pioneered by Medicare, using a population generally over 65 years of age, and despite its adoption by mainstream insurers, little is known of bundled payments' ability to reduce variation or cost in a working-age population. This study uses a universally-insured, nationally-representative population of adults aged 18-65 to examine the effect of bundled payments for five high-cost surgical procedures which are known to vary widely in Medicare reimbursement: hip replacement, knee replacement, coronary artery bypass grafting (CABG), lumbar spinal fusion, and colectomy. METHODS: Five procedures conducted on adults aged 18-65 were identified from the TRICARE database from 2011 to 2014. A 90-day period from index procedure was used to determine episodes of associated post-acute care. Data was sorted by Zip code into hospital referral regions (HRR). Payments were determined from TRICARE reimbursement records, they were subsequently price standardized and adjusted for patient and surgical characteristics. Variation was assessed by stratifying the HRR into quintiles by spending for each index procedure. RESULTS: After adjusting for case mix, significant inter-quintile variation was observed for all procedures, with knee replacement showing the greatest variation in both index surgery (107%) and total cost of care (75%). Readmission was a driver of variation for colectomy and CABG, with absolute cost variation of $17,257 and $13,289 respectively. Other post-acute care spending was low overall (≤$1606, for CABG). CONCLUSIONS: This study demonstrates significant regional variation in total spending for these procedures, but much lower spending for post-acute care than previously demonstrated by similar procedures in Medicare. Targeting post-acute care spending, a common approach taken by providers in bundled payment arrangements with Medicare, may be less fruitful in working aged populations.

Effect of 5-azacytidine on gene expression in marrow stromal cells.

When exposed to 5-azacytidine, marrow stromal cells from active long-term marrow cultures and cell lines derived from simian virus 40-transformed stromal cells rapidly upregulated c-abl and interleukin-6 transcripts while downregulating the expression of collagen I, a major matrix protein. Similar effects occurred with interleukin-1 alpha and tumor necrosis factor alpha, although the time course was considerably prolonged.

Differentiation and growth modulation of chronic myelogenous leukemia cells by bryostatin.

We have examined the ability of bryostatin 1 (bryo), an activator of protein kinase C, to induce differentiation of chronic myelogenous leukemia (CML) cells obtained from peripheral blood. Bryo induced a prompt and persistent macrophage-like differentiation, as evidenced by functional, morphological, and immunological criteria. Differentiated cells remained viable for at least 21 days with little change in cell number. CML cell cultures treated in semisolid medium with bryo showed diffuse infiltration with single macrophages, as well as discrete macrophage, mixed, and granulocytic colonies. Supernatants of suspension cultures of bryo-treated CML cells contained granulocyte-macrophage colony-stimulating factor (GM-CSF) by enzyme-linked immunosorbent assay. Furthermore, colony formation could be significantly inhibited by the addition of antibodies to GM-CSF. Prolonged liquid culture of CML cells in bryo reduced colony-forming unit, granulocyte-macrophage content. Bryo-induced differentiation was associated with a decrease in lactoferrin, a marker of granulocyte differentiation, and an increase in both c-fms and interleukin-1 beta RNA, both of which are expressed by monocytes/macrophages. These data demonstrate that bryostatin 1 is capable of inducing macrophage-like differentiation in maturing CML cells. Furthermore, bryostatin induces secretion of GM-CSF by such cells in suspension and semisolid medium and also promotes clonal extinction of granulocyte-macrophage progenitors. Bryostatin may be a possible therapeutic agent for CML.

Cloning and sequencing of the human c-abl 3' untranslated region.

The human c-abl oncogene gives rise to different mRNA transcripts which vary primarily in that they possess alternative first exons. In the present study, we present the sequence for the human c-abl 3' untranslated region (3'utr) and show that while human and murine c-abl cDNA sequences are generally homologous, human c-abl transcripts unlike the murine c-abl transcripts do not differ significantly in their 3' utrs.

Sodium vanadate, a tyrosine phosphatase inhibitor, affects expression of hematopoietic growth factors and extracellular matrix RNAs in SV40-transformed human marrow stromal cells.

Protein tyrosine kinases represent a subset of proteins that mediate signal transduction between the extracellular environment and the nucleus. We have previously described a coordinated upregulation between RNA transcripts of a tyrosine kinase, c-abl, and those of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 6 (IL-6) in human marrow stromal cells (SVMSC). Moreover, an inverse relationship exists between expression of c-abl transcripts and those of extracellular matrix proteins such as type collagen I transcripts. In the present study, these inverse relationships were again seen in SVMSC when tyrosine kinase effects were enhanced by treatment of the cells with the tyrosine phosphatase inhibitor sodium orthovanadate. This suggests that tyrosine kinases are involved in the coordinate regulation of these genes.

Endogenous natural killer enhancing factor-B increases cellular resistance to oxidative stresses.

Natural killer-enhancing factor (NKEF) was identified and cloned on the basis of its ability to increase NK cytotoxicity. Two genes, NKEF-A and -B, encode NKEF proteins and sequence analysis presented suggests that each belongs to a highly conserved family of antioxidants. To examine the antioxidant potential of NKEF, we transfected the coding region of NKEF-B cDNA into the human endothelial cell line ECV304. The stable transfectant, B/1, was found to overexpress NKEF-B gene transcript and protein. We subjected B/1 to oxidative stress by either culturing them with glucose oxidase (GO), which continuously generates hydrogen peroxide, or by direct addition of hydrogen peroxide. We found that B/1 cells were more resistant than control cell lines. Resistance to hydrogen peroxide was originally thought to be mediated mainly by catalase and the glutathione cycle. Therefore, we used inhibitors to block the two pathways and found that B/1 cells were more resistant to oxidative stress than control cells when we used inhibitors to preblock either pathway. We also examined the cellular inflammatory responses to oxidized low-density lipoprotein (LDL) and bacterial lipopolysaccharide (LPS) by measuring monocyte adhesion to endothelial cells in vitro and found that B/1 cells were resistant to such responses. Lastly, we found that B/1 cells were more resistant to a novel chemotherapeutic agent CT-2584, which appears to kill tumor cells by stimulating production of reactive oxygen intermediates in mitochondria. These results demonstrate that the NKEF-B is an antioxidant that protects cells from oxidative stress, chemotherapy agents, and inflammation-induced monocyte adhesion. Furthermore, its expression may mediate cellular responses to proinflammatory molecules.

An improved method for the isolation from Naja naja venom of cobra factor (CoF) free of phospholipase A.

An improved method is reported for the isolation from cobra (Naja naja) venom of cobra factor (CoF), the anticomplementary protein which is derived from cobra C3. Sequential chromatography on DEAE-Sepharose, Sephacryl-S200, and finally hydroxylapatite yielded 6.25 mg CoF per gram of crude venom. The purified CoF had 1 unit of functional anticomplementary activity per 1--2 micrograms of protein, and was homogeneous on gradient and non-reduced sodium dodecyl sulphate (SDS) polyacrylamide gel electrophoresis (PAGE). In SDS-PAGE after reduction with mercaptoethanol there were two major bands (M.W. 75,000 and 51,000 daltons), three minor bands (M.W. 29--31,500 daltons) and two trace bands (36,500 and 41,500 daltons). By analogy with mammalian C3 it is suggested that the CoF consists of two polypeptide chains linked by disulphide bridges, one of which undergoes cleavage of the peptide chain at several points either in vivo or in vitro.

Assessment of depression in patients with brain pathology: the case of stroke.

The assessment of depression in patients with brain pathologies--a topic of considerable clinical and research interest--is complicated by a variety of factors. Among the most problematic are cognitive consequences of brain injury that can diminish the reliability and validity of information used to diagnose depression, determine its severity, ascertain its predictors, and evaluate its impact. In this article, the authors examine the challenges to depression assessment in patients who have had a stroke, the neurologically impaired population in which it has been most frequently studied. Focusing on poststroke depression research, they describe methodological limitations that may contribute to conflicting outcomes and conclusions and offer suggestions for improving the specificity, consistency, validity, and reliability of assessment methods and procedures when investigating depression in patients with brain pathologies.

Molecular cloning of two alternatively spliced forms of human phosphatidic acid phosphatase cDNAs that are differentially expressed in normal and tumor cells.

Phosphatidic acid (PA) and diacylglycerol (DG) are lipids involved in signal transduction and in structural membrane-lipid biosynthesis in cells. Phosphatidic acid phosphatase (PAP) catalyzes the conversion of PA to DG. This enzyme exists in at least two isoforms, one of which (PAP1) is presumed to be cytosolic and membrane associated and the other (PAP2) to be an integral membrane protein. Homology search of the GenBank database using a murine sequence probe enabled the cloning of several putative human isoenzymes. Two isoforms, presumed to be alternative splice variants from a single gene, designated as PAP2-alpha1 and PAP2-alpha2, have been cloned and expressed. The PAP2-alpha1 and PAP2-alpha2 have a 84% and a 72% overall match, respectively, with the published mouse PAP amino acid sequence. The area of alternative exon usage was confined to the coding region at amino acids 20 to 70. Ectopic expression of PAP2-alpha1 and PAP2-alpha2 cDNAs in ECV304 endothelial cells led to a 6- to 8-fold and a 2-fold increase in PAP activity, respectively, in cell-free extracts using an in vitro assay that measured the conversion of [14C]PA to [14C]DG. The increase in PAP activity in PAP2-alpha-transfected cells correlated with a >50% decrease in the steady-state PA level. Northern analysis showed that PAP2-alpha mRNA expression was suppressed in several tumor tissues, notably those derived from the lower alimentary tract. Subsequent analysis of colon tumor tissue derived from four donors confirmed lower expression of PAP2-alpha than in matching normal colon tissue. Considering these data and previous demonstrations that certain transformed cell lines have lower PAP activity, we suggest that human PAP cDNAs may be candidates for gene therapy for certain tumors.

Cloning and expression of two human lysophosphatidic acid acyltransferase cDNAs that enhance cytokine-induced signaling responses in cells.

Lysophosphatidic acid (LPA) and phosphatidic acid (PA) are two phospholipids involved in signal transduction and in lipid biosynthesis in cells. LPA acyltransferase (LPAAT), also known as 1-acyl sn-glycerol-3-phosphate acetyltransferase (EC 2.3.1.51), catalyzes the conversion of LPA to PA. In this study, we describe the isolation and characterization of two human cDNAs that encode proteins possessing LPAAT activities. These two proteins, designated here as LPAAT-alpha and LPAAT-beta, contain extensive sequence sequence similarities to microbial or plant LPAAT sequences. LPAAT-alpha mRNA was detected in all tissues with highest expression in skeletal muscle whereas LPAAT-beta was expressed predominantly in heart and liver tissues. Expression of these two cDNAs in an Escherichia coli strain with a mutated LPAAT gene (plsC) complements its growth defect and shifts the equilibrium of cellular lipid content from LPA to PA and other lipids. Overexpression of these two cDNAs in mammalian cells leads to increased LPAAT activity in cell-free extracts using an in vitro assay that measures the conversion of fluorescently labeled LPA to PA. This increase in LPAAT activity correlates with enhancement of transcription and synthesis of tumor necrosis factor-alpha and interleukin-6 from cells upon stimulation with interleukin-1beta, suggesting LPAAT overexpression may amplify cellular signaling responses from cytokines.

Pricing strategies for capitated delivery systems.

This article discusses alternative methods for establishing a fairer pricing mechanism for Medicare recipients who enroll in health maintenance organizations and other competitive medical plans. The current method, based upon the adjusted average per capita cost, is inadequate because it fails to adjust premium levels for differences in health status; it establishes undesirable incentives that may lead to underservice, and it is tied to costs in the fee-for-service system. Alternative methods would incorporate health status, have Medicare share the risk with HMO's, and base payment on HMO experience.

Alternative geographic configurations for Medicare payments to health maintenance organizations.

Under prevailing legislation, Medicare payments to health maintenance organizations (HMOs) are based upon projected fee-for-service reimbursement levels for enrollees' county of residence. These rates have been criticized in light of substantial variations in rates among neighboring counties and large fluctuations in rates over time. In this study, the use of nine alternative configurations and the county itself were evaluated on the basis of payment-area homogeneity, payment rate stability, and policy criteria, including the fiscal impacts of reconfiguration on HMOs. The results revealed rather modest differences among most alternative configurations and do not lend strong support for payment area reconfiguration at this time.

Bringing managed care incentives to Medicare's fee-for-service sector.

The Health Care Financing Administration (HCFA) could work with eligible physician organizations to generate savings in total reimbursements for their Medicare patients. Medicare would continue to reimburse all providers according to standard payment policies and mechanisms, and beneficiaries would retain the freedom to choose providers. However, implementation of new financial incentives, based on meeting targets called Group-Specific Volume Performance Standards (GVPS), would encourage cost-effective service delivery patterns. HCFA could use new and existing data systems to monitor access, utilization patterns, cost outcomes and quality of care. In short, HCFA could manage providers, who, in turn, would manage their patients' care.

A longitudinal study of the psychosocial impact of stroke on primary support persons.

We investigated longitudinally the effects of a stroke on the social support systems and well-being of the patient's primary support person, both acutely and as the condition stabilized. Individuals who had suffered a first stroke and a primary support person participated in two waves of data collection, carried out in 6-month intervals beginning 7 weeks after the stroke. Our data show that the prevalence of depressive symptoms is from 2 1/2 to 3 1/2 times higher than rates found among representative samples of middle-aged and elderly populations. Mean level of depression did not change over time, although level of optimism declined significantly. Multiple regression analyses showed that levels of depression and perceived burden in support persons are highly related to aspects of the stroke such as its severity, and that demographic variables such as age and income play a relatively minor role in attenuating these relations in the acute adjustment phase. However, from 7 to 9 months after the stroke, well-established demographic variables such as health, income, and age were significant predictors of depression. Individuals who were older and who had good health and higher incomes were least depressed.

Psychotropic drug use in long-term care facilities: a review of the literature.

We reviewed 19 studies of psychotropic drug use for residents of long-term care facilities, located through a MEDLINE search of the literature published between 1978 and 1990. The review compares each study in terms of its sample, research design, and findings. The studies reviewed found that a substantial proportion of nursing home residents are taking psychotropic drugs on a regular, long-term basis and this usage is accompanied by prescribing and monitoring problems and many potential adverse risks.

Right hemisphere appreciation of prosodic and linguistic indications of implicit attitude.

Appreciation of attitudes conveyed through prosodic cues and lexical content was examined in subjects with temporal lobe seizure foci. One task involved auditory judgments of the consistency of verbal and intonational meaning of sentences. Errors on judgments of consistent verbal and prosodic stimuli were not only more frequent in the right temporal group than in left temporals or controls but were strongly related to neuropsychological indices associated with extent of right temporal involvement. Answering questions based on written narratives in which multiple attitude markers were either redundant or conflicting comprised the second task. Right temporal patients as a group had difficulty in answering inferential questions about paragraphs with inconsistent indicators of attitude. Even low-scoring right temporals were able, however, to answer inferential and factual questions when the verbal context markers consistently reinforced a particular attitude.

Physician profiling in group practices.

Profiling is a technique that large, multispecialty group practices, like many insurers, can use to monitor and improve quality and efficiency. Groups can examine physician performance by calculating ratios of medical inputs to patient or population outputs. Physician control can help to achieve balance between clinical benefits and economic considerations. Profiles need to reflect a group's multiple missions, such as clinical care, research, and education; philosophy of care; and organizational ethos regarding physician compensation systems. Groups may need to customize standard approaches because of their emphasis on early utilization of specialists and the atypical case mixes often found in referral practices.

A randomized clinical trial of nursing care for recovery from cardiac surgery.

OBJECTIVE: To determine the efficacy of a psychoeducational nursing intervention in patients who receive coronary artery bypass graft and valve repair surgery. DESIGN: A cluster-randomized controlled trial design. SETTING: Two hospitals in the western United States--a large community hospital with an active cardiovascular surgery practice and a health-sciences research center. SUBJECTS: 156 patients between 25 and 75 years of age, 125 (81.1%) men, and 31 (19.9%) women, all with primary care givers. OUTCOME MEASURES: Self-efficacy expectations, activities (behavior performance), quality of life, mood state. INTERVENTION: Supplemental in-hospital education followed by telephone contact from discharge to eighth week after discharge. RESULTS: Patients in the experimental group reported significantly greater self-efficacy expectations for walking and behavior performance for walking, lifting, climbing stairs, general exertion and, where applicable, for working. CONCLUSION: This trial suggests that a low-intensity psychoeducational nursing intervention can promote self-efficacy expectations for walking in recovery and is associated with more self-reported walking and lifting behavior after cardiac surgery.

Medicare risk contracting: identifying factors associated with market exit.

Over the past few years, a number of HMOs have chosen to discontinue their Medicare risk contracts. Using logistic regression, this study sought to identify factors associated with Medicare risk contract market exit in 1988. Low AAPCC rates were found to systematically affect the market exit of only Medicare risk contractors that were regional components of a central HMO organization. The Medicare risk market exit of other HMOs was found to be principally related to two attributes suggestive of possible unfavorable risk selection: the dropping of a previously offered prescription drug benefit and higher proportions of categorically disabled Medicare enrollees.

Preferred provider organizations: options for Medicare.

Preferred Provider Organizations (PPOs) offer purchasers of care several benefits, including expenditure reduction, utilization control, improved quality of care, and efficient management. Although Medicare could benefit from these outcomes, the program lags behind the private sector in PPO development. The Health Care Financing Administration (HCFA) must address several policy issues and constraints as it develops PPOs for Medicare beneficiaries. The agency must identify services and providers to include in the PPO, develop program sponsorship and administration methods, create viable provider and beneficiary incentives to participate, identify sources of PPO cost savings, and examine the role of medigap insurance policies in PPO development. In this article we discuss three possible PPO models for Medicare: a service or population specific PPO, an integrated PPO/medigap policy, and a Medicare Part A/B PPO. We conclude by identifying several issues that require further research before these PPO models can be tested.