Cell-cell and virus-cell fusion assay-based analyses of alanine insertion mutants in the distal α9 portion of the JRFL gp41 subunit from HIV-1.

Membrane fusion is the first essential step in HIV-1 replication. The gp41 subunit of HIV-1 envelope protein (Env), a class I fusion protein, achieves membrane fusion by forming a structure called a six-helix bundle composed of N- and C-terminal heptad repeats. We have recently shown that the distal portion of the α9 helix in the C-terminal heptad repeat of X4-tropic HXB2 Env plays a critical role in the late-stage membrane fusion and viral infection. Here, we used R5-tropic JRFL Env and constructed six alanine insertion mutants, 641+A to 646+A, in the further distal portion of α9 where several glutamine residues are conserved (the number corresponds to the position of the inserted alanine in JRFL Env). 644+A showed the most severe defect in syncytia formation. Decreased fusion pore formation activity, revealed by a dual split protein assay, was observed in all mutants except 641+A. Sequence analysis and substitution of inserted 644A with Gln revealed that the glutamine residue at position 644 that forms complex hydrogen-bond networks with other polar residues on the surface of the six-helix bundle is critical for cell-cell fusion. We also developed a split NanoLuc® (Nluc) reporter-based assay specific to the virus-cell membrane fusion step to analyze several of the mutants. Interestingly syncytia-competent mutants failed to display Nluc activities. In addition to defective fusion activity, a reduction of Env incorporation into virions may further contribute to differences in cell-cell and virus-cell fusions.

Six-helix bundle completion in the distal C-terminal heptad repeat region of gp41 is required for efficient human immunodeficiency virus type 1 infection.

BACKGROUND: The native pre-fusion structure of gp120/gp41 complex of human immunodeficiency virus type 1 was recently revealed. In the model, the helices of gp41 (α6, α7, α8, and α9) form a four-helix collar underneath trimeric gp120. Gp41 is a class I fusion protein and mediates membrane fusion by forming a post-fusion structure called the six-helix bundle (6HB). The comparison of the pre- and post-fusion structures revealed the large conformational changes in gp41 during the antiparallel packing of the N- and C-terminal heptad repeats (NHRs and CHRs) in membrane fusion. Several mutagenesis studies of gp41 performed in the past were interpreted based on 6HB, the only available structure at that time. To obtain an insight about the current pre-fusion structural model and conformational changes during membrane fusion, alanine insertion mutagenesis of the NHR, CHR and connecting loop regions of HXB2 gp41 was performed. The effects of mutations on biosynthesis and membrane fusion were analyzed by immunoblotting and fusion assays, respectively. The extent of membrane fusion was evaluated by split luciferase-based pore formation and syncytia formation assays, respectively. RESULTS: Consistent with the current structural model, drastic negative effects of mutations on biosynthesis and membrane fusion were observed for NHR, loop, and proximal regions of CHR (up to amino acid position 643). The insertions in α9 after it leaves the four-helix collar were tolerable for biosynthesis. These CHR mutants showed varying effects on membrane fusion. Insertion at position 644 or 645 resulted in poor pore and syncytia formation. Efficient pore and syncytia formation almost similar to that of the wild type was observed for insertion at position 647, 648 or 649. However, recovery of virus infectivity was only observed for the insertions beyond position 648. CONCLUSIONS: The mutagenesis data for HXB2 gp41 is in agreement with the recent pre-fusion structure model. The virus infection data suggested that fusion pores sufficiently large enough for the release of the virus genome complex are formed after the completion of 6HB beyond position 648.

Out-of-pocket spending in the last five years of life.

BACKGROUND: A key objective of the Medicare program is to reduce risk of financial catastrophe due to out-of-pocket healthcare expenditures. Yet little is known about cumulative financial risks arising from out-of-pocket healthcare expenditures faced by older adults, particularly near the end of life. DESIGN: Using the nationally representative Health and Retirement Study (HRS) cohort, we conducted retrospective analyses of Medicare beneficiaries' total out-of-pocket healthcare expenditures over the last 5 years of life. PARTICIPANTS: We identified HRS decedents between 2002 and 2008; defined a 5 year study period using each subject's date of death; and excluded those without Medicare coverage at the beginning of this period (n = 3,209). MAIN MEASURES: We examined total out-of-pocket healthcare expenditures in the last 5 years of life and expenditures as a percentage of baseline household assets. We then stratified results by marital status and cause of death. All measurements were adjusted for inflation to 2008 US dollars. RESULTS: Average out-of-pocket expenditures in the 5 years prior to death were $38,688 (95 % Confidence Interval $36,868, $40,508) for individuals, and $51,030 (95 % CI $47,649, $54,412) for couples in which one spouse dies. Spending was highly skewed, with the median and 90th percentile equal to $22,885 and $89,106, respectively, for individuals, and $39,759 and $94,823, respectively, for couples. Overall, 25 % of subjects' expenditures exceeded baseline total household assets, and 43 % of subjects' spending surpassed their non-housing assets. Among those survived by a spouse, 10 % exceeded total baseline assets and 24 % exceeded non-housing assets. By cause of death, average spending ranged from $31,069 for gastrointestinal disease to $66,155 for Alzheimer's disease. CONCLUSION: Despite Medicare coverage, elderly households face considerable financial risk from out-of-pocket healthcare expenses at the end of life. Disease-related differences in this risk complicate efforts to anticipate or plan for health-related expenditures in the last 5 years of life.

HIV and STI risk behaviors, knowledge, and testing among female adult film performers as compared to other California women.

A cross-sectional structured online survey was self-administered to a convenience sample of current female adult film performers via the Internet; bivariate analyses compared HIV and other STI risk behaviors, knowledge, and testing in female adult performers to California Women's Health Survey respondents. 134 female adult film performers (mean age 27.8 years) were compared to the 1,773 female respondents (mean age 31.3 years) to the 2007 CWHS. Female performers initiated sex on average 3 years younger and had 6.8 more personal sexual partners in the prior year than other California women. The majority of performers reported HIV and Chlamydia testing (94 and 82%, respectively) in the prior 12 months. They more likely to use condoms consistently in their personal life than other California women (21 vs 17%), though this difference disappeared after controlling for other variables. Adult performers are routinely tested for HIV and Chlamydia, yet they have multiple sexual partners and use condoms inconsistently.

Disability and decline in physical function associated with hospital use at end of life.

BACKGROUND: Hospital use near the end of life is often undesirable to patients, represents considerable Medicare cost, and varies widely across regions. OBJECTIVE: To concurrently examine regional and patient factors, including disability and functional decline, associated with end-of-life hospital use. DESIGN/PARTICIPANTS: We sampled decedents aged 65 and older (n = 2,493) from the Health and Retirement Study (2000-2006), and linked data from individual Medicare claims and the Dartmouth Atlas of Health Care. Two-part regression models estimated the relationship between total hospital days in the last 6 months and patient characteristics including physical function, while adjusting for regional resources and hospital care intensity (HCI). KEY RESULTS: Median hospital days was 7 (range = 0-183). 53% of respondents had functional decline. Compared with decedents without functional decline, those with severe disability or decline had more regression-adjusted hospital days (range 3.47-9.05, depending on category). Dementia was associated with fewer days (-3.02); while chronic kidney disease (2.37), diabetes (2.40), stroke or transient ischemic attack (2.11), and congestive heart failure (1.74) were associated with more days. African Americans and Hispanics had more days (5.91 and 4.61, respectively). Those with family nearby had 1.62 fewer days and hospice enrollees had 1.88 fewer days. Additional hospital days were associated with urban residence (1.74) and residence in a region with more specialists (1.97) and higher HCI (2.27). CONCLUSIONS: Functional decline is significantly associated with end-of-life hospital use among older adults. To improve care and reduce costs, health care programs and policies should address specific needs of patients with functional decline and disability.

Determinants of medical expenditures in the last 6 months of life.

BACKGROUND: End-of-life medical expenditures exceed costs of care during other years, vary across regions, and are likely to be unsustainable. Identifying determinants of expenditure variation may reveal opportunities for reducing costs. OBJECTIVE: To identify patient-level determinants of Medicare expenditures at the end of life and to determine the contributions of these factors to expenditure variation while accounting for regional characteristics. It was hypothesized that race or ethnicity, social support, and functional status are independently associated with treatment intensity and controlling for regional characteristics, and that individual characteristics account for a substantial proportion of expenditure variation. DESIGN: Using data from the Health and Retirement Study, Medicare claims, and The Dartmouth Atlas of Health Care, relationships were modeled between expenditures and patient and regional characteristics. SETTING: United States, 2000 to 2006. PARTICIPANTS: 2394 Health and Retirement Study decedents aged 65.5 years or older. MEASUREMENTS: Medicare expenditures in the last 6 months of life were estimated in a series of 2-level multivariable regression models that included patient, regional, and patient and regional characteristics. RESULTS: Decline in function (rate ratio [RR], 1.64 [95% CI, 1.46 to 1.83]); Hispanic ethnicity (RR, 1.50 [CI, 1.22 to 1.85]); black race (RR, 1.43 [CI, 1.25 to 1.64]); and certain chronic diseases, including diabetes (RR, 1.16 [CI, 1.06 to 1.27]), were associated with higher expenditures. Nearby family (RR, 0.90 [CI, 0.82 to 0.98]) and dementia (RR, 0.78 CI, 0.71 to 0.87]) were associated with lower expenditures, and advance care planning had no association. Regional characteristics, including end-of-life practice patterns (RR, 1.09 [CI, 1.06 to 1.14]) and hospital beds per capita (RR, 1.01 [CI, 1.00 to 1.02]), were associated with higher expenditures. Patient characteristics explained 10% of overall variance and retained statistically significant relationships with expenditures after regional characteristics were controlled for. LIMITATION: The study limitations include the decedent sample, proxy informants, and a large proportion of unexplained variation. CONCLUSION: Patient characteristics, such as functional decline, race or ethnicity, chronic disease, and nearby family, are important determinants of expenditures at the end of life, independent of regional characteristics. PRIMARY FUNDING SOURCE: The Brookdale Foundation.

Deciding in the dark: advance directives and continuation of treatment in chronic critical illness.

OBJECTIVE: Chronic critical illness is a devastating syndrome for which treatment offers limited clinical benefit but imposes heavy burdens on patients, families, clinicians, and the health care system. We studied the availability of advance directives and appropriate surrogates to guide decisions about life-sustaining treatment for the chronically critically ill and the extent and timing of treatment limitation. DESIGN: Prospective cohort study. SETTING: Respiratory Care Unit (RCU) in a large, tertiary, urban, university-affiliated, hospital. PATIENTS: Two hundred three chronically critically ill adults transferred to RCU after tracheotomy for failure to wean from mechanical ventilation in the intensive care unit. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We interviewed RCU caregivers and reviewed patient records to identify proxy appointments, living wills, or oral statements of treatment preferences, resuscitation directives, and withholding/withdrawal of mechanical ventilation, nutrition, hydration, renal replacement and vasopressors. Forty-three of 203 patients (21.2%) appointed a proxy and 33 (16.2%) expressed preferences in advance directives. Do not resuscitate directives were given for 71 patients (35.0%). Treatment was limited for 39 patients (19.2%). Variables significantly associated with treatment limitation were proxy appointment prior to study entry (time of tracheotomy/RCU transfer) (odds ratio = 6.7, 95% confidence interval [CI], 2.3-20.0, p = 0.0006) and palliative care consultation in the RCU (OR = 40.9, 95% CI, 13.1-127.4, p < 0.0001). Median (interquartile range) time to first treatment limitation was 39 (31.0-45.0) days after hospital admission and 13 (8.0-29.0) days after RCU admission. For patients dying after treatment limitation, median time from first limitation to death ranged from 3 days for mechanical ventilation and hydration to 7 days for renal replacement. CONCLUSIONS: Most chronically critically ill patients fail to designate a surrogate decision-maker or express preferences regarding life-sustaining treatments. Despite burdensome symptoms and poor outcomes, limitation of such treatments was rare and occurred late, when patients were near death. Opportunities exist to improve communication and decision-making in chronic critical illness.

Study on the effects of FCu-IUD and FICu-IUD on matrix metalloproteinases in human uterine flushing and endometrium.

The activity of matrix metalloproteinases (MMPs) in the uterine flushing and endometrial tissue of normal adult women wearing FCu-IUD (fixed Cu-IUD) or FICu-IUD (indomethacin-releasing FCu-IUD) was observed by using zymography on SDS-PAGE containing gelatin. The results showed that the activity and kinds of MMPs in FCu-IUD group were increased significantly as compared with themselves before being inserted FCu-IUD. However, compared with the FCu-IUD group, the activity of some kinds of MMPs in the FICu-IUD group was decreased significantly. These data suggest that IUD can enhance the activity of MMPs in human endometrium, intermediated by prostaglandins, and MMPs may have relation to IUD-induced menorrhagia and indomethacin reduces IUD-induced menorrhagia by partly inhibiting MMPs synthesis.

Factors influencing the use of intensive procedures at the end of life.

OBJECTIVES: To examine individual and regional factors associated with the use of intensive medical procedures in the last 6 months of life. DESIGN: Retrospective cohort study. SETTING: The Health and Retirement Study (HRS), a longitudinal nationally representative cohort of older adults. PARTICIPANTS: HRS decedents aged 66 and older (N = 3,069). MEASUREMENTS: Multivariable logistic regression was used to evaluate associations between individual and regional factors and receipt of five intensive procedures: intubation and mechanical ventilation, tracheostomy, gastrostomy tube insertion, enteral and parenteral nutrition, or cardiopulmonary resuscitation in the last 6 months of life. RESULTS: Approximately 18% of subjects (n = 546) underwent at least one intensive procedure in the last 6 months of life. Characteristics significantly associated with lower odds of an intensive procedure included aged 85-94 (vs 65-74, adjusted odds ratio (AOR) = 0.67, 95% confidence interval (CI) = 0.51-0.90), Alzheimer's disease (AOR = 0.71, 95% CI = 0.54-0.94), cancer (AOR = 0.60, 95% CI = 0.43-0.85), nursing home residence (AOR = 0.70, 95% CI = 0.50-0.97), and having an advance directive (AOR = 0.71, 95% CI = 0.57-0.89). In contrast, living in a region with higher hospital care intensity (AOR = 2.16, 95% CI = 1.48-3.13) and black race (AOR = 2.02, 95% CI = 1.52-2.69) each doubled one's odds of undergoing an intensive procedure. CONCLUSION: Individual characteristics and regional practice patterns are important determinants of intensive procedure use in the last 6 months of life. The effect of nonclinical factors highlights the need to better align treatments with individual preferences.

An update: NIH research funding for palliative medicine 2006 to 2010.

BACKGROUND: Palliative care clinical and educational programs are expanding to meet the needs of seriously ill patients and their families. Multiple reports call for an enhanced palliative care evidence base. OBJECTIVE: To examine current National Institutes of Health (NIH) funding of palliative medicine research and changes since our 2008 report. METHODS: We sought to identify NIH funding of palliative medicine from 2006 to 2010 in two stages. First, we searched the NIH grants database RePorter for grants with key words "palliative care," "end-of-life care," "hospice," and "end of life." Second, we identified palliative care researchers likely to have secured NIH funding using three strategies: (1) We abstracted the first and last authors' names from original investigations published in major palliative medicine journals from 2008 to 2010; (2) we abstracted these names from a PubMed generated list of all original articles published in major medicine, nursing, and subspecialty journals using the above key words Medical Subject Headings (MESH) terms "palliative care," "end-of-life care," "hospice," and "end of life;" and (3) we identified editorial board members of palliative medicine journals and key members of palliative medicine research initiatives. We crossmatched the pooled names against NIH grants funded from 2006 to 2010. RESULTS: The NIH RePorter search yielded 653 grants and the author search identified an additional 352 grants. Compared to 2001 to 2005, 589 (240%) more grants were NIH funded. The 391 grants categorized as relevant to palliative medicine represented 294 unique PIs, an increase of 185 (269%) NIH funded palliative medicine researchers. The NIH supported 21% of the 1253 original palliative medicine research articles identified. Compared to 2001 to 2005, the percentage of grants funded by institutes other than the National Cancer Institute (NCI), the National Institute for Nursing Research (NINR), and the National Institute of Aging (NIA) increased from 15% to 20% of all grants. CONCLUSIONS: When compared to 2001-2005, more palliative medicine investigators received NIH funding; and research funding has improved. Nevertheless, additional initiatives to further support palliative care research are needed.

Hospice enrollment saves money for Medicare and improves care quality across a number of different lengths-of-stay.

Despite its demonstrated potential to both improve quality of care and lower costs, the Medicare hospice benefit has been seen as producing savings only for patients enrolled 53-105 days before death. Using data from the Health and Retirement Study, 2002-08, and individual Medicare claims, and overcoming limitations of previous work, we found $2,561 in savings to Medicare for each patient enrolled in hospice 53-105 days before death, compared to a matched, nonhospice control. Even higher savings were seen, however, with more common, shorter enrollment periods: $2,650, $5,040, and $6,430 per patient enrolled 1-7, 8-14, and 15-30 days prior to death, respectively. Within all periods examined, hospice patients also had significantly lower rates of hospital service use and in-hospital death than matched controls. Instead of attempting to limit Medicare hospice participation, the Centers for Medicare and Medicaid Services should focus on ensuring the timely enrollment of qualified patients who desire the benefit.

Risk factors for long-term brain dysfunction after chronic critical illness.

RATIONALE: Factors associated with long-term brain dysfunction (LTBD) in survivors of chronic critical illness (CCI) have not been explored but may be important for clinical practice and planning by patients, families, and providers. OBJECTIVES: To identify risk factors for LTBD after treatment for CCI and to explore the association between acute delirium and coma during hospital treatment and LTBD. METHODS: A prospective cohort study of adults admitted to a respiratory care unit for treatment of CCI. MEASUREMENTS AND MAIN RESULTS: Using the Confusion Assessment Method for ICU and the Richmond Agitation and Sedation Scale, we evaluated patients for delirium and coma during their hospital treatment for CCI. We collected data on other potential risk factors for LTBD by prospectively reviewing the patients' medical records and interviewing surrogates. We contacted survivors by telephone at 6 months after discharge to assess brain function using the telephone Confusion Assessment Method. Among 385 patients treated for CCI, 213 (56.1%) were dead at 6 months, and 108 of 167 (64.7%) of survivors were impaired. We used multinomial logistic regression in which the outcomes were (1) death, (2) brain dysfunction, and (3) survival without LTBD. Older patients, patients with higher Acute Physiology Score, and those with multiple complications during treatment for CCI were more likely to have LTBD. Acute brain dysfunction during hospital treatment was also associated with an increased risk of LTBD (odds ratio, 2.14; 95% confidence interval, 1.02-4.52). CONCLUSIONS: LTBD after treatment for CCI is associated with brain dysfunction during such treatment as well as with older age and higher severity of illness of the patients.

Comparison of the mental health of female adult film performers and other young women in California.

OBJECTIVE: This study compared self-reported mental health status and current depression of female adult film performers and other young women. METHODS: A cross-sectional structured online survey adapted from the California Women's Health Survey (CWHS) was self-administered to a convenience sample of 134 current female adult film performers via the Internet. Bivariate and multivariate analyses were used to compare data for these women with data for 1,773 women of similar ages who responded to the 2007 CWHS. Main outcome measures were self-reported mental health status, measured with the Behavioral Risk Factor Surveillance Survey core-instrument quality-of-life questions, and current depression, measured with the Patient Health Questionnaire-8. RESULTS: Performers reported a mean of 7.2 days of poor mental health in the past 30 days, compared with 4.8 days for CWHS respondents, and 33% met criteria for current depression, compared with 13% of CWHS respondents (p<.01). As children, the adult film performers were more likely to have been victims of forced sex (37% compared with 13% of CWHS respondents), to have lived in poverty (24% and 12%), and to have been placed in foster care (21% and 4%) (p<.01). In the past 12 months, 50% of the performers reported living in poverty and 34% reported experiencing domestic violence, compared with 36% and 6%, respectively, of CWHS respondents (p<.01). As adults, 27% had experienced forced sex, compared with 9% of CWHS respondents (p<.01). CONCLUSIONS: Female adult film performers have significantly worse mental health and higher rates of depression than other California women of similar ages.

Operational and quality outcomes of a mobile acute care for the elderly service.

BACKGROUND: The traditional acute care for the elderly (ACE) unit has demonstrated improved functional outcomes without increased costs or changes in length of stay (LOS). It is, however, limited in scope to patients cared for on a fixed geographical unit. OBJECTIVE: To compare operational and quality outcomes for patients cared for on a mobile ACE (MACE) service to those cared for on a unit-based ACE service and matched controls on other general medical services. DESIGN: Retrospective cohort study with propensity-score matching. SETTING: An urban academic medical center. PATIENTS: A total of 8094 hospitalized adults >64 years old admitted to an ACE, MACE, and general medical services from July 2006 to June 2009. INTERVENTION: An interdisciplinary MACE service com- posed of a geriatrician-hospitalist, fellow, nurse coordinator, and social worker. MEASUREMENTS: LOS, total cost, 7- and 30-day readmission rates, and in-hospital mortality. RESULTS: Mean LOS and total cost were significantly lower for patients in the MACE service compared with the ACE unit service (5.8 vs 7.9 days, P < 0.001, and $10,315 vs $13,187, P = 0.002) and compared with propensity-score matched controls during the second year of operation (5.6 vs 7.2 days, P < 0.001, and $10,693 vs $15,636, P < 0.001). In-hospital mortality and 7- and 30-day readmission rates were similar in all groups. CONCLUSIONS: A mobile ACE service may result in reduced LOS and lower costs with no change in in-hospital mortality or 7- or 30-day readmission rates when compared with standard medical service and a traditional unit-based ACE service.

Geographic access to hospice in the United States.

BACKGROUND: Despite a 41% increase in the number of hospices since 2000, more than 60% of Americans die without hospice care. Given that hospice care is predominantly home based, proximity to a hospice is important in ensuring access to hospice services. We estimated the proportion of the population living in communities within 30 and 60 minutes driving time of a hospice. METHODS: We conducted a cross-sectional study of geographic access to U.S. hospices using the 2008 Medicare Provider of Services data, U.S. Census data, and ArcGIS software. We used multivariate logistic regression to identify gaps in hospice availability by community characteristics. RESULTS: As of 2008, 88% of the population lived in communities within 30 minutes and 98% lived in communities within 60 minutes of a hospice. Mean time to the nearest hospice was 15 minutes and the range was 0 to 403 minutes. Community characteristics independently associated with greater geographic access to hospice included higher population density, higher median income, higher educational attainment, higher percentage of black residents, and the state not having a Certificate of Need policy. The percentage of each state's population living in communities more than 30 minutes from a hospice ranged from 0% to 48%. CONCLUSIONS: Recent growth in the hospice industry has resulted in widespread geographic access to hospice care in the United States, although state and community level variation exists. Future research regarding variation and disparities in hospice use should focus on barriers other than geographic proximity to a hospice.

Initial studies on a novel filtering-type intra-vas device in male dogs.

BACKGROUND: To relieve the side effects induced by the complete obstruction of the vas deferens, we created a filtering-type intra-vas device (IVD) which is made of materials composed of nano-SiO(2)-copper complex cross-linking polymer composites. STUDY DESIGN: Eight male beagle dogs were grouped into nonimplanted control group and IVD-implanted group. We tested the efficacy of the sperm filtering effect of the new IVD material for 12 months and examined the influence of the IVD materials on the cells of the vas deferens, epididymis and testis. RESULTS: The densities of sperm were reduced significantly after the IVD was implanted; no motile sperm were found after the third month. No obvious morphological changes were found in the cells of the vas deferens, epididymis and testis in the IVD-implanted group. CONCLUSIONS: The filtering-type nano-SiO(2)-copper complex/polymer composite IVD is able to filter the sperm of the male dogs, and the IVD material did not cause obvious damage to the cells of the male reproductive organs after 1 year of implantation.

Impact of hospice disenrollment on health care use and medicare expenditures for patients with cancer.

PURPOSE: Patients with cancer represent the largest diagnostic group of hospice users, with 560,000 referred for hospice in 2008. Oncologists rely on hospice teams to provide care for patients who have completed disease-directed treatment and desire to remain at home. However, 11% to 15% of hospice users disenroll from hospice, and little is known about their health care use and Medicare expenditures. PATIENTS AND METHODS: We used Surveillance, Epidemiology and End Results-Medicare data for hospice users who died as a result of cancer between 1998 and 2002 (N = 90,826) to compare rates of hospitalization, emergency department, and intensive care unit admission and hospital death for hospice disenrollees and those who remained with hospice until death. We also compared per-day and total Medicare expenditures across the two groups. RESULTS: Patients with cancer who disenrolled from hospice were more likely to be hospitalized (39.8% v 1.6%; P < .001), more likely to be admitted to the emergency department (33.9% v 3.1%; P < .001) or intensive care unit (5.7% v 0.1%; P < .001), and more likely to die in the hospital (9.6% v 0.2%; P < .001). Patients who disenrolled from hospice died a median of 24 days following disenrollment, suggesting that the reason for hospice disenrollment was not improved health. In multivariable analyses, hospice disenrollees incurred higher per-day Medicare expenditures than patients who remained with hospice until death (higher per-day expenditures of $124; P < .001). CONCLUSION: Hospice disenrollment is a marker for higher health care use and expenditures for care. Strategies to manage a patient's care and support family caregivers following hospice disenrollment may be beneficial and should be explored.

Hospice characteristics and the disenrollment of patients with cancer.

OBJECTIVE: To characterize the types of hospices with higher rates of patient disenrollment from the Medicare Hospice Benefit and the markets in which these hospices operate. DATA SOURCE: Secondary analyses of Surveillance, Epidemiology and End Results-Medicare data. Analyses included patients who died of cancer from 1998 to 2002 and who used hospice (n=90,826). STUDY DESIGN: We used generalized estimating equations to estimate the association of patient disenrollment with hospice size, years since Medicare certification, ownership, staff mix, competition, urban/rural status, region, and fiscal intermediary. Other covariates included patient demographic and clinical characteristics. PRINCIPAL FINDINGS: Patients were more likely to disenroll from hospice if they were served by newer hospices (OR=1.14; 95 percent CI 1.03, 1.26), by smaller hospices (OR=1.11; 95 percent CI 1.02, 1.20), or by hospices in more competitive markets (OR=1.17; 95 percent CI 1.03, 1.35). There was an independent effect of the hospice's fiscal intermediary on disenrollment, particularly disenrollment after 6 months with hospice (Wald chi(2)=21.2, p=.007). CONCLUSIONS: The reasons for higher disenrollment rates for newer hospices, for smaller hospices, and for hospices in highly competitive markets are likely complex; however, results suggest that there are organizational-level barriers to keeping patients with cancer enrolled with hospice. Variation across fiscal intermediaries may indicate that regulatory oversight, particularly of long-stay patients, influences hospice disenrollment.

Variability in access to hospital palliative care in the United States.

BACKGROUND: Hospital palliative care programs provide high-quality, comprehensive care for seriously ill patients and their families. OBJECTIVE: To examine geographic variation in patient and medical trainee access to hospital palliative care and to examine predictors of these programs. METHODS: Primary and secondary analyses of national survey and census data. Hospital data including hospital palliative care programs were obtained from the American Hospital Association (AHA) Annual Survey Databasetrade mark for fiscal year 2006 supplemented by mailed surveys. Medical school-affiliated hospitals were obtained from the American Association of Medical Colleges, Web-site review, and telephone survey. Health care utilization data were obtained from the Dartmouth Atlas of Health Care 2008. Multivariate logistic regression was used to identify characteristics significantly associated with the presence of hospital palliative care. RESULTS: A total of 52.8% of hospitals with 50 or more total facility beds reported hospital palliative care with considerable variation by state; 40.9% (144/352) of public hospitals, 20.3% (84/413) of for-profit hospitals, and 28.8% (160/554) of Medicare sole community providers reported hospital palliative care. A total of 84.5% of medical schools were associated with at least one hospital palliative care program. Factors significantly associated (p < 0.05) with hospital palliative care included geographic location, owning a hospice program, having an American College of Surgery approved cancer program, percent of persons in the county with a university education, and medical school affiliation. For-profit and public hospitals were significantly less likely to have hospital palliative care when compared with nonprofit institutions. States with higher hospital palliative care penetration rates were observed to have fewer Medicare hospital deaths, fewer intensive care unit/cardiac care unit (ICU/CCU) days and admissions during the last 6 months of life, fewer ICU/CCU admission during terminal hospitalizations, and lower overall Medicare spending/enrollee. DISCUSSION: This study represents the most recent estimate to date of the prevalence of hospital palliative care in the United States. There is wide geographic variation in access to palliative care services although factors predicting hospital palliative care have not changed since 2005. Overall, medical students have high rates of access to hospital palliative care although complete penetration into academic settings has not occurred. The association between hospital palliative care penetration and lower Medicare costs is intriguing and deserving of further study.