Pre-fracture individual characteristics associated with high total health care costs after hip fracture.

Older women with pre-fracture slow walk speed, high body mass index, and/or a high level of multimorbidity have significantly higher health care costs after hip fracture compared to those without those characteristics. Studies to investigate if targeted health care interventions for these individuals can reduce hip fracture costs are warranted. INTRODUCTION: The aim of this study is to estimate the associations of individual pre-fracture characteristics with total health care costs after hip fracture, using Study of Osteoporotic Fractures (SOF) cohort data linked to Medicare claims. METHODS: Our study population was 738 women age 70 and older enrolled in Medicare Fee for Service (FFS) who experienced an incident hip fracture between January 1, 1992 and December 31, 2009. We assessed pre-fracture individual characteristics at SOF study visits and estimated costs of hospitalizations, skilled nursing facility and inpatient rehabilitation stays, home health care visits, and outpatient utilization from Medicare FFS claims. We used generalized linear models to estimate the associations of predictor variables with total health care costs (2010 US dollars) after hip fracture. RESULTS: Median total health care costs for 1 year after hip fracture were $35,536 (inter-quartile range $24,830 to $50,903). Multivariable-adjusted total health care costs for 1 year after hip fracture were 14 % higher ($5256, 95 % CI $156 to $10,356) in those with walk speed <0.6 m/s compared to ≥1.0 m/s, 25 % higher ($9601, 95 % CI $3314 to $16,069) in those with body mass index ≥30 kg/m2 compared to 20 to 24.9 mg/kg2, and 21 % higher ($7936, 95 % CI $346 to $15,526) for those with seven or more compared to no comorbid medical conditions. CONCLUSIONS: Pre-fracture poor mobility, obesity, and multiple comorbidities are associated with higher total health care costs after hip fracture in older women. Studies to investigate if targeted health care interventions for these individuals can reduce the costs of hip fractures are warranted.

Antidepressant-like and anxiolytic-like effects following activation of the µ-δ opioid receptor heteromer in the nucleus accumbens.

Treatment-resistant major depressive disorder remains inadequately treated with currently available antidepressants. Opioid receptors (ORs) are involved in the pathophysiology of depression yet remain an untapped therapeutic intervention. The µ-δ OR heteromer represents a unique signaling complex with distinct properties compared with µ- and δ-OR homomers; however, its role in depression has not been characterized. As there are no ligands exclusively targeting the µ-δ heteromer, we devised a strategy to selectively antagonize the function of the µ-δOR complex using a specific interfering peptide derived from the δOR distal carboxyl tail, a sequence implicated in µ-δOR heteromerization. In vitro studies using a minigene expressing this peptide demonstrated a loss of the unique pharmacological and trafficking properties of δ-agonists at the µ-δ heteromer, with no effect on µ- or δ-OR homomers, and a dissociation of the µ-δOR complex. Intra-accumbens administration of the TAT-conjugated interfering peptide abolished the antidepressant-like and anxiolytic-like actions of the δ-agonist UFP-512 (H-Dmt-Tic-NH-CH(CH2-COOH)-Bid) measured in the forced swim test, novelty-induced hypophagia and elevated plus maze paradigms in rats. UFP-512's antidepressant-like and anxiolytic-like actions were abolished by pretreatment with either µOR or δOR antagonists. Overall, these findings demonstrate that the µ-δ heteromer may be a potential suitable therapeutic target for treatment-resistant depression and anxiety disorders.

Reduced striatal dopamine D1-D2 receptor heteromer expression and behavioural subsensitivity in juvenile rats.

In adult rat striatum the dopamine D1-D2 receptor heteromer is expressed selectively in a subset of medium spiny neurons (MSNs) that coexpress the dopamine D1 and D2 receptors (D1R and D2R) as well as dynorphin (DYN) and enkephalin (ENK), with higher coexpression in nucleus accumbens (NAc) and much lower in the caudate putamen (CP). In the present study we showed that in neonatal striatal cultured neurons >90% exhibited the D1R/D2R-DYN/ENK phenotype. Similarly, in the striatum of juvenile rats (age 26-28 days) coexpression of D1R and D2R was also coincident with the expression of both DYN and ENK. Quantification of the number of striatal MSNs exhibiting coexpression of D1R and D2R in juvenile rats revealed significantly lower coexpression in NAc shell, but not core, and CP than in adult rats. However, within MSNs that coexpressed D1R and D2R, the propensity to form the D1-D2 receptor heteromer did not differ between age groups. Consistent with reduced coexpression of the D1R and D2R, juvenile rats exhibited subsensitivity to D1-D2 receptor heteromer-induced grooming following activation by SKF 83959. Given the proposed role of D1R/D2R-coexpressing MSNs in the regulation of thalamic output, and the recent discovery that these MSNs exhibit both inhibitory and excitatory capabilities, these findings suggest that the functional regulation of neurotransmission by the dopamine D1-D2 receptor heteromer within the juvenile striatum may be significantly different than in the adult.

Magnetic properties of planar nanowire arrays of Co fabricated on oxidized step-bunched silicon templates.

Planar nanowire (NW) arrays of Co grown on oxidized step-bunched Si(111) templates exhibit room temperature ferromagnetic behaviour for wire widths down to 25 nm. Temperature and thickness dependent magnetization studies on these polycrystalline NW arrays show that the magnetic anisotropy of the NW array is dominated by shape anisotropy, which keeps the magnetization in-plane with easy axis parallel to the wires. This shape related uniaxial anisotropy is preserved even at low temperatures (10 K). Thickness dependent studies reveal that the magnetization reversal is governed by the curling mode reversal for thick wires whereas thinner wires exhibit a more complex behaviour which is related to thermal effects and size distribution of the crystal grains that constitute the NWs.

Agonists at the δ-opioid receptor modify the binding of µ-receptor agonists to the µ-δ receptor hetero-oligomer.

BACKGROUND AND PURPOSE: µ- and δ-opioid receptors form heteromeric complexes with unique ligand binding and G protein-coupling profiles linked to G protein α z-subunit (Gα(z) ) activation. However, the mechanism of action of agonists and their regulation of the µ-δ receptor heteromer are not well understood. EXPERIMENTAL APPROACH: Competition radioligand binding, cell surface receptor internalization in intact cells, confocal microscopy and receptor immunofluorescence techniques were employed to study the regulation of the µ-δ receptor heteromer in heterologous cells with and without agonist exposure. KEY RESULTS: Gα(z) enhanced affinity of some agonists at µ-δ receptor heteromers, independent of agonist chemical structure. δ-Opioid agonists displaced µ-agonist binding with high affinity from µ-δ heteromers, but not µ receptor homomers, suggestive of δ-agonists occupying a novel µ-receptor ligand binding pocket within the heteromers. Also, δ-agonists induced internalization of µ-opioid receptors in cells co-expressing µ- and δ-receptors, but not those expressing µ-receptors alone, indicative of µ-δ heteromer internalization. This dose-dependent, Pertussis toxin-resistant and clathrin- and dynamin-dependent effect required agonist occupancy of both µ- and δ-opioid receptors. In contrast to µ-receptor homomers, agonist-induced internalization of µ-δ heteromers persisted following chronic morphine exposure. CONCLUSIONS AND IMPLICATIONS: The µ-δ receptor heteromer may contain a novel δ-agonist-detected, high-affinity, µ-receptor ligand binding pocket and is regulated differently from the µ-receptor homomer following chronic morphine exposure. Occupancy of both µ- and δ-receptor binding pockets is required for δ-agonist-induced endocytosis of µ-δ receptor heteromers. δ-Opioid agonists target µ-δ receptor heteromers, and thus have a broader pharmacological specificity than previously identified.

Association of medication attitudes with non-persistence and non-compliance with medication to prevent fractures.

UNLABELLED: Our objective was to assess the association of self-reported non-persistence (stopping fracture-prevention medication for more than 1 month) and self-reported non-compliance (missing doses of prescribed medication) with perceived need for fracture-prevention medication, concerns regarding long-term harm from and/or dependence upon medications, and medication-use self-efficacy (confidence in one's ability to successfully take medication in the context of their daily life). INTRODUCTION: Non-persistence (stopping medication prematurely) and non-compliance (not taking medications at the prescribed times) with oral medications to prevent osteoporotic fractures is widespread and attenuates their fracture reduction benefit. METHODS: Cross-sectional survey and medical record review of 729 patients at a large multispecialty clinic in the United States prescribed an oral bisphosphonate between January 1, 2006 and March 31, 2007. RESULTS: Low perceived necessity for fracture-prevention medication was strongly associated with non-persistence independent of other predictors, but not with non-compliance. Concerns about medications were associated with non-persistence, but not with non-compliance. Low medication-use self-efficacy was associated with non-persistence and non-compliance. CONCLUSIONS: Non-persistence and non-compliance with oral bisphosphonate medication have different, albeit overlapping, sets of predictors. Low perceived necessity of fracture-prevention medication, high concerns about long-term safety of and dependence upon medication , and low medication-use self-efficacy all predict non-persistence with oral bisphosphonates, whereas low medication-use self-efficacy strongly predicts non-compliance with oral bisphosphonate medication. Assessment of and influence of these medication attitudes among patients at high risk of fracture are likely necessary to achieve better persistence and compliance with fracture-prevention therapies.

Activation of calcium/calmodulin-dependent protein kinase IIalpha in the striatum by the heteromeric D1-D2 dopamine receptor complex.

Synaptic plasticity in the striatum is a key mechanism that underlies processes such as reward related incentive learning and behavioral habit formation resulting from drugs of abuse. Key aspects of these functions are dependent on dopamine transmission as well as activation of calcium/calmodulin-dependent protein kinase IIalpha (CaMKIIalpha). In this study, we examined the ability of a recently identified heteromeric complex composed of D1 and D2 dopamine receptors coupled to Gq/11 to activate striatal CaMKIIalpha. Using the dopaminergic agonist SKF83959, which selectively activates the D1-D2 complex, we demonstrated phosphorylation of CaMKIIalpha at threonine 286, both in heterologous cells and in the murine striatum in vivo. Phosphorylation of CaMKIIalpha by activation of the receptor complex required concurrent agonism of both D1 and D2 receptors and was independent of receptor pathways that modulated adenylyl cyclase. The identification of this novel mechanism by which dopamine may modulate synaptic plasticity has implications for our understanding of striatal-mediated reward and motor function, as well as neuronal disorders in which striatal dopaminergic neurotransmission is involved.

Astrocytic energy metabolism consolidates memory in young chicks.

In a single trial discrimination avoidance learning task, chicks learn to distinguish between beads of two colors, which are dipped in either a strong or weak tasting aversant (methyl anthranilate) to induce strongly-reinforced and weakly-reinforced learning, respectively. Consolidation of strongly-reinforced learning can be prevented by inhibitors of glycolysis, such as 2-deoxyglucose and iodoacetate and by inhibitors of oxidative metabolism and the consolidation of weakly-reinforced learning can be promoted by administration of glucose. In the present study we show that bilateral, intracerebral injection of 30 nmol acetate can act like glucose to consolidate labile memory and to restore memory impaired by 2-deoxyglucose administration. Acetate is a metabolic substrate that feeds into the tricarboxylic acid cycle, it is oxidized in astrocytes, but not in neurones. Our data suggest that effects of glucose administered 15-25 min post-training on memory consolidation are mediated via astrocytes not neurons.

Diffusion indices on magnetic resonance imaging and neuropsychological performance in amnestic mild cognitive impairment.

BACKGROUND: Magnetic resonance diffusion tensor imaging (DTI) shows promise in the early detection of microstructural pathophysiological changes in the brain. OBJECTIVES: To measure microstructural differences in the brains of participants with amnestic mild cognitive impairment (MCI) compared with an age-matched control group using an optimised DTI technique with fully automated image analysis tools and to investigate the correlation between diffusivity measurements and neuropsychological performance scores across groups. METHODS: 34 participants (17 participants with MCI, 17 healthy elderly adults) underwent magnetic resonance imaging (MRI)-based DTI. To control for the effects of anatomical variation, diffusion images of all participants were registered to standard anatomical space. Significant statistical differences in diffusivity measurements between the two groups were determined on a pixel-by-pixel basis using gaussian random field theory. RESULTS: Significantly raised mean diffusivity measurements (p<0.001) were observed in the left and right entorhinal cortices (BA28), posterior occipital-parietal cortex (BA18 and BA19), right parietal supramarginal gyrus (BA40) and right frontal precentral gyri (BA4 and BA6) in participants with MCI. With respect to fractional anisotropy, participants with MCI had significantly reduced measurements (p<0.001) in the limbic parahippocampal subgyral white matter, right thalamus and left posterior cingulate. Pearson's correlation coefficients calculated across all participants showed significant correlations between neuropsychological assessment scores and regional measurements of mean diffusivity and fractional anisotropy. CONCLUSIONS: DTI-based diffusivity measures may offer a sensitive method of detecting subtle microstructural brain changes associated with preclinical Alzheimer's disease.

Progressive dysgraphia in a case of posterior cortical atrophy.

Dysgraphia (agraphia) is a common feature of posterior cortical atrophy (PCA). However, detailed analyses of these spelling and writing impairments are infrequently conducted. LM is a 59-year-old woman with dysgraphia associated with PCA. She presented with a two-year history of decline in her writing and dressmaking skills. A 3D T1-weighted MRI scan confirmed selective bi-parietal atrophy, with relative sparing of the hippocampi and other cortical regions. Analyses of LM's preserved and impaired spelling abilities indicated mild physical letter distortions and a significant spelling deficit characterised by letter substitutions, insertions, omissions, and transpositions that was systematically sensitive to word length while insensitive to real word versus nonword category, word frequency, regularity, imagery, grammatical class and ambiguity. Our findings suggest a primary graphemic buffer disorder underlies LM's spelling errors, possibly originating from disruption to the operation of a fronto-parietal network implicated in verbal working memory.

Group practice strategies to manage pharmaceutical cost in an HMO network.

OBJECTIVE: To evaluate the prevalence of various pharmaceutical cost management strategies used by group practices within a managed care network and their relationship to drug costs among enrollees. STRATEGIES STUDIED: Care management (gatekeeping, practice profiling, practice guidelines, case management), techniques for maintaining clinic medication records, and policies regulating physician interaction with pharmaceutical sales representatives (PSRs). STUDY DESIGN: Cross-sectional survey of primary care group practice organizations (n = 103) affiliated with Blue Cross Blue Shield of Minnesota in early 1996. METHODS: Multivariate linear regression analysis was performed on corresponding claims data for members continuously enrolled in these practices from January 1 to December 31, 1995 (n = 76,387), using the patient as the unit of analysis. RESULTS: Substantial variation in strategy prevalence was observed; this variation was thought to influence pharmaceutical costs. Seventy-six percent of practices had medication lists in outpatient medical records, 53% had policies limiting pharmaceutical detailing, and 44% had patients assigned to primary care gatekeepers; however, only 10% used outpatient nurse case managers. Use of outpatient nurse case managers (P < .010), primary care physician gatekeeping (P < .002), policies to control pharmaceutical detailing (P < .001), and medication lists and outpatient charts (P < .001) was found to be independently associated with lower pharmaceutical expenditures. Significant colinearity was found between group size and the strategies studied. CONCLUSIONS: Significantly lower pharmaceutical costs per member per year were observed in the groups reporting primary care gatekeeping, outpatient medication records, outpatient case managers, and policies regarding physician interactions with PSRs.

Orphan G protein-coupled receptors in the CNS.

The majority of genes encoding G protein-coupled receptors were isolated by methods based on sequence similarities found throughout this family. Experimental techniques have exploited these similarities (including low-stringency hybridization, polymerase chain reaction and electronic database searching) to identify genes encoding many pharmacologically recognized receptors and their subtypes. Homology-based searches have revealed receptors for which the endogenous ligands were unknown and these were named orphan receptors. Many orphan receptors are expressed in the brain, suggesting the existence of unidentified neurotransmitters. Methods used to identify ligands for these orphan receptors resulted in the identification of novel ligands and succeeded in pairing previously identified ligands with their receptors. Similar successful strategies are required to characterize the physiological and pathological importance of the remaining orphan receptors to facilitate the discovery of novel drugs for these systems.

Discovery and mapping of ten novel G protein-coupled receptor genes.

We report the identification, cloning and tissue distributions of ten novel human genes encoding G protein-coupled receptors (GPCRs) GPR78, GPR80, GPR81, GPR82, GPR93, GPR94, GPR95, GPR101, GPR102, GPR103 and a pseudogene, psi GPR79. Each novel orphan GPCR (oGPCR) gene was discovered using customized searches of the GenBank high-throughput genomic sequences database with previously known GPCR-encoding sequences. The expressed genes can now be used in assays to determine endogenous and pharmacological ligands. GPR78 shared highest identity with the oGPCR gene GPR26 (56% identity in the transmembrane (TM) regions). psi GPR79 shared highest sequence identity with the P2Y(2) gene and contained a frame-shift truncating the encoded receptor in TM5, demonstrating a pseudogene. GPR80 shared highest identity with the P2Y(1) gene (45% in the TM regions), while GPR81, GPR82 and GPR93 shared TM identities with the oGPCR genes HM74 (70%), GPR17 (30%) and P2Y(5) (40%), respectively. Two other novel GPCR genes, GPR94 and GPR95, encoded a subfamily with the genes encoding the UDP-glucose and P2Y(12) receptors (sharing >50% identities in the TM regions). GPR101 demonstrated only distant identities with other GPCR genes and GPR102 shared identities with GPR57, GPR58 and PNR (35-42% in the TM regions). GPR103 shared identities with the neuropeptide FF 2, neuropeptide Y2 and galanin GalR1 receptors (34-38% in the TM regions). Northern analyses revealed GPR78 mRNA expression in the pituitary and placenta and GPR81 expression in the pituitary. A search of the GenBank databases with the GPR82 sequence retrieved an identical sequence in an expressed sequence tag (EST) partially encoding GPR82 from human colonic tissue. The GPR93 sequence retrieved an identical, human EST sequence from human primary tonsil B-cells and an EST partially encoding mouse GPR93 from small intestinal tissue. GPR94 was expressed in the frontal cortex, caudate putamen and thalamus of brain while GPR95 was expressed in the human prostate and rat stomach and fetal tissues. GPR101 revealed mRNA transcripts in caudate putamen and hypothalamus. GPR103 mRNA signals were detected in the cortex, pituitary, thalamus, hypothalamus, basal forebrain, midbrain and pons.

FMRFamide-related neuropeptides are agonists of the orphan G-protein-coupled receptor GPR54.

We have isolated and determined the coding sequences of human and mouse orthologs of the rat orphan G-protein-coupled receptor GPR54. Mouse and rat GPR54 are nearly 95% identical to each other, and both are approximately 85% identical to human GPR54 at the amino acid level. Screening of agonists for GPR54 identified several invertebrate neuropeptides of the RFamide and RWamide family that were able to activate GPR54 at microM range through the G(alpha)q pathway. Substitution analysis showed that the C-terminal optimal sequence of GPR54-activating peptides is Gly-Leu-Arg-Trp-NH2. Northern analysis of human GPR54 detected expression in several peripheral tissues and many regions of the central nervous system.

A randomized clinical trial of outpatient geriatric evaluation and management.

OBJECTIVES: To measure the effects of outpatient geriatric evaluation and management (GEM) on high-risk older persons' functional ability and use of health services. DESIGN: Randomized clinical trial. SETTING: Ambulatory clinic in a community hospital. PARTICIPANTS: A population-based sample of community-dwelling Medicare beneficiaries age 70 and older who were at high risk for hospital admission in the future (N = 568). INTERVENTION: Comprehensive assessment followed by interdisciplinary primary care. MEASUREMENTS: Functional ability, restricted activity days, bed disability days, depressive symptoms, mortality, Medicare payments, and use of health services. Interviewers were blinded to participants' group status. RESULTS: Intention-to-treat analysis showed that the experimental participants were significantly less likely than the controls to lose functional ability (adjusted odds ratio (aOR) = 0.67, 95% confidence interval (CI) = 0.47-0.99), to experience increased health-related restrictions in their daily activities (aOR = 0.60, 95% CI = 0.37-0.96), to have possible depression (aOR = 0.44, 95% CI = 0.20-0.94), or to use home healthcare services (aOR = 0.60, 95% CI = 0.37-0.92) during the 12 to 18 months after randomization. Mortality, use of most health services, and total Medicare payments did not differ significantly between the two groups. The intervention cost $1,350 per person. CONCLUSION: Targeted outpatient GEM slows functional decline.

Identification of a molecular target of psychosine and its role in globoid cell formation.

Globoid cell leukodystrophy (GLD) is characterized histopathologically by apoptosis of oligodendrocytes, progressive demyelination, and the existence of large, multinuclear (globoid) cells derived from perivascular microglia. The glycosphingolipid, psychosine (d-galactosyl-beta-1,1' sphingosine), accumulates to micromolar levels in GLD patients who lack the degradative enzyme galactosyl ceramidase. Here we document that an orphan G protein-coupled receptor, T cell death-associated gene 8, is a specific psychosine receptor. Treatment of cultured cells expressing this receptor with psychosine or structurally related glycosphingolipids results in the formation of globoid, multinuclear cells. Our discovery of a molecular target for psychosine suggests a mechanism for the globoid cell histology characteristic of GLD, provides a tool with which to explore the disjunction of mitosis and cytokinesis in cell cultures, and provides a platform for developing a medicinal chemistry for psychosine.

Prolonged fear responses in mice lacking dopamine D1 receptor.

Dopamine is an important neurotransmitter involved in learning and memory including emotional memory. The involvement of dopamine in conditioned fear has been widely documented. However, little is known about the molecular mechanisms that underlie contextual fear conditioning and memory consolidation. To address this issue, we used dopamine D1-deficient mice (D1-/-) and their wild-type (D1+/+) and heterozygote (D1+/-) siblings to assess aversive learning and memory. We quantified two different aspects of fear responses to an environment where the mice have previously received unsignaled footshocks. Using one-trial step-through passive avoidance and conditioned freezing paradigms, mice were conditioned to receive mild inescapable footshocks then tested for acquisition, retention and extinction of conditioned fear responses 5 min after and up to 45-90 days post-training. No differences were observed among any of the genotypes in the acquisition of passive avoidance response or fear-induced freezing behavior. However, with extended testing, D1-/- mice exhibited prolonged retention and delayed extinction of conditioned fear responses in both tasks, suggesting that D1-/- mice are capable of acquiring aversive learning normally. These findings demonstrate that the dopamine D1 receptor is not important for acquisition or consolidation of aversive learning and memory but has an important role in modulating the extinction of fear memory.

Discovery of a novel member of the histamine receptor family.

We report the discovery, tissue distribution and pharmacological characterization of a novel receptor, which we have named H4. Like the three histamine receptors reported previously (H1, H2, and H3), the H4 receptor is a G protein-coupled receptor and is most closely related to the H3 receptor, sharing 58% identity in the transmembrane regions. The gene encoding the H4 receptor was discovered initially in a search of the GenBank databases as sequence fragments retrieved in a partially sequenced human genomic contig mapped to chromosome 18. These sequences were used to retrieve a partial cDNA clone and, in combination with genomic fragments, were used to determine the full-length open reading frame of 390 amino acids. Northern analysis revealed a 3.0-kb transcript in rat testis and intestine. Radioligand binding studies indicated that the H4 receptor has a unique pharmacology and binds [(3)H]histamine (K(d) = 44 nM) and [(3)H]pyrilamine (K(d) = 32 nM) and several psychoactive compounds (amitriptyline, chlorpromazine, cyproheptadine, mianserin) with moderate affinity (K(i) range of 33-750 nM). Additionally, histamine induced a rapid internalization of HA-tagged H4 receptors in transfected human embryonic kidney 293 cells.

Disenrollment from Medicare HMOs.

BACKGROUND: Since the program's inception, there has been great interest in determining whether beneficiaries who enter and subsequently leave Medicare health maintenance organizations (HMOs) are more or less costly than those remaining in fee-for-service (FFS) Medicare. OBJECTIVES: To examine whether relatively high-cost beneficiaries disenroll from Medicare HMOs (disenrollment bias) and whether disenrollment bias varies by Medicare HMO market characteristics. In addition, we compare rates of surgical procedures and hospitalizations for ambulatory care-sensitive conditions for disenrollees and continuing FFS beneficiaries. DESIGN: Cross-sectional analysis of 1994 Medicare data. PARTICIPANTS AND METHODS: Medicare beneficiaries were first sampled from the 124 counties with at least 1000 Medicare HMO enrollees. From this pool, HMO disenrollees and a sample of continuing FFS beneficiaries were drawn. The FFS beneficiaries were assigned dates of "pseudodisenrollment." Expenditures and inpatient service use were compared for 6 months after disenrollment or pseudodisenrollment. RESULTS: The HMO disenrollees were no more likely than the continuing FFS beneficiaries to have positive total expenditures (Part A plus Part B) or Part B expenditures in the first 6 months after disenrollment. However, disenrollees were more likely to have Part A expenditures. Among beneficiaries with spending, disenrollees had higher total and Part B expenditures than continuing FFS beneficiaries. Moreover, the disparity in total and Part B spending between disenrollees and continuing FFS beneficiaries increased with HMO market penetration. Although Part A spending was higher for disenrollees with spending, it was not sensitive to changes in market share. The HMO disenrollees received more surgical procedures and were hospitalized for more of the ambulatory care-sensitive conditions than the FFS beneficiaries. CONCLUSIONS: On several measures, Medicare HMOs experienced favorable disenrollment relative to continuing FFS beneficiaries as recently as 1994, which increased as HMO market share increased.