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The article presents a letter to the editor concerning research on patients who use Veteran Health Administration (VA) services while being simultaneously enrolled in Medicare.

Currently, vaccine development against different respiratory diseases is at its peak. It is of utmost importance to find suitajble adjuvants that can increase the potency of the vaccine candidates. This study aimed to determine the systemic and splenic immune mechanisms in mice models induced by anionic and cationic lipid adjuvants in the presence of the vaccine-candidate influenza antigen hemagglutinin (HA). In the presence of the HA antigen, the cationic adjuvant (N3) increased conventional dendritic cell 1 (cDC1) abundance with enhanced MHCI and CD80-CD86 costimulatory marker expression, and significantly higher CD8T and Th17 populations with enhanced interferon-gamma (IFNγ) expression in CD8T and CD4T populations. Conversely, the anionic adjuvant (L3) increased the cDC2 population percentage with significantly higher MHCII and DEC205 expression, along with an increase in the CD4T and regulatory T cell populations. The L3-treated group also exhibited higher percentages of activated B and plasma cell populations with significantly higher antigen-specific IgG and IgA titer and virus neutralization potential. While the anionic adjuvant induced significantly higher humoral responses than the cationic adjuvant, the latter influenced a significantly higher Th1/Th17 response. For customized vaccine development, it is beneficial to have alternative adjuvants that can generate differential immune responses with the same vaccine candidate antigen. This study will aid the selection of adjuvants based on their charges to improve specific immune response arms in the future development of vaccine formulation.

In this preclinical two-dose mucosal immunization study, using a combination of S1 spike and nucleocapsid proteins with cationic (N3)/or anionic (L3) lipids were investigated using an intranasal delivery route. The study showed that nasal administration of low amounts of antigens/adjuvants induced a primary and secondary immune response in systemic IgG, mIL-5, and IFN-gamma secreting T lymphocytes, as well as humoral IgA in nasal and intestinal mucosal compartments. It is believed that recipients will benefit from receiving a combination of viral antigens in promoting a border immune response against present and evolving contagious viruses. Lipid adjuvants demonstrated an enhanced response in the vaccine effect. This was seen in the significant immunogenicity effect when using the cationic lipid N3. Unlike L3, which showed a recognizable effect when administrated at a slightly higher concentration. Moreover, the findings of the study proved the efficiency of an intranasally mucosal immunization strategy, which can be less painful and more effective in enhancing the respiratory tract immunity against respiratory infectious diseases.

Immunotherapy is revolutionizing cancer treatment but is often restricted by toxicities. What distinguishes adverse events from concomitant antitumor reactions is poorly understood. Here, using anti-CD40 treatment in mice as a model of T H 1-promoting immunotherapy, we showed that liver macrophages promoted local immune-related adverse events. Mechanistically, tissue-resident Kupffer cells mediated liver toxicity by sensing lymphocyte-derived IFN-γ and subsequently producing IL-12. Conversely, dendritic cells were dispensable for toxicity but drove tumor control. IL-12 and IFN-γ were not toxic themselves but prompted a neutrophil response that determined the severity of tissue damage. We observed activation of similar inflammatory pathways after anti-PD-1 and anti-CTLA-4 immunotherapies in mice and humans. These findings implicated macrophages and neutrophils as mediators and effectors of aberrant inflammation in T H 1-promoting immunotherapy, suggesting distinct mechanisms of toxicity and antitumor immunity., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Background : Vaccination is commonly used to prevent and control influenza infection in humans. However, improvements in the ease of delivery and strength of immunogenicity could markedly improve herd immunity. The aim of this pre-clinical study is to test the potential improvements to existing intranasal delivery of formalin-inactivated whole Influenza A vaccines (WIV) by formulation with a cationic lipid-based adjuvant (N3). Additionally, we combined WIV and N3 with a DNA-encoded TLR5 agonist secreted flagellin (pFliC(-gly)) as an adjuvant, as this adjuvant has previously been shown to improve the effectiveness of plasmid-encoded DNA antigens. Methods : Outbred and inbred mouse strains were intranasally immunized with unadjuvanted WIV A/H1N1/SI 2006 or WIV that was formulated with N3 alone. Additional groups were immunized with WIV and N3 adjuvant combined with pFliC(-gly). Homo and heterotypic humoral anti-WIV immune responses were assayed from serum and lung by ELISA and hemagglutination inhibition assay. Homo and heterotypic cellular immune responses to WIV and Influenza A NP were also determined. Results : WIV combined with N3 lipid adjuvant the pFliC(-gly) significantly increased homotypic influenza specific serum antibody responses (>200-fold), increased the IgG2 responses, indicating a mixed Th1/Th2-type immunity, and increased the HAI-titer (>100-fold). Enhanced cell-mediated IFNγ secreting influenza directed CD4 + and CD8 + T cell responses (>40-fold) to homotypic and heterosubtypic influenza A virus and peptides. Long-term and protective immunity was obtained. Conclusions : These results indicate that inactivated influenza virus that was formulated with N3 cationic adjuvant significantly enhanced broad systemic and mucosal influenza specific immune responses. These responses were broadened and further increased by incorporating DNA plasmids encoding FliC from S. typhimurum as an adjuvant providing long lasting protection against heterologous Influenza A/H1N1/CA09pdm virus challenge.

The importance of natural IgM antibodies in protection against infections is still emerging and these antibodies have a potential role in the maintenance of homeostasis through clearance of apoptotic bodies, complement-dependent mechanisms, inflammation and exclusion of misfolded proteins. Natural IgM act as a first line of defence against unknown hazardous factors and are present in most vertebrates. We investigated the functional capacity of anti-HIV-1 IgM monoclonal antibodies, from a combinatorial Fab library derived from healthy individuals, and evaluated their protective role in inhibiting HIV-1 in vitro when passing across the human mucosal epithelial barrier. Primary HIV-1 isolates were efficiently transmitted over the tight polarized epithelial cells when added to their apical surface. Efficient inhibition of HIV-1 transmission was achieved when anti-HIV-1 IgM monoclonal antibodies were added to the basolateral side of the cells. Two of these human IgM MoAbs had the ability to neutralize HIV and reduced infection of dendritic cells in primary cervico-vaginal tissue biopsies in vitro. This indicates a potential role of natural IgM antibodies in the reduction of HIV-1 transmission in mucosal tissues and improve our understanding of how natural IgM antibodies against a neutralizing epitope could interfere with viral transmission.

Plasticity in cancer stem-like cells (CSC) may provide a key basis for cancer heterogeneity and therapeutic response. In this study, we assessed the effect of combining a drug that abrogates CSC properties with standard-of-care therapy in a Ewing sarcoma family tumor (ESFT). Emergence of CSC in this setting has been shown to arise from a defect in TARBP2-dependent microRNA maturation, which can be corrected by exposure to the fluoroquinolone enoxacin. In the present work, primary ESFT from four patients containing CD133(+) CSC subpopulations ranging from 3% to 17% of total tumor cells were subjected to treatment with enoxacin, doxorubicin, or both drugs. Primary ESFT CSC and bulk tumor cells displayed divergent responses to standard-of-care chemotherapy and enoxacin. Doxorubicin, which targets the tumor bulk, displayed toxicity toward primary adherent ESFT cells in culture but not to CSC-enriched ESFT spheres. Conversely, enoxacin, which enhances miRNA maturation by stimulating TARBP2 function, induced apoptosis but only in ESFT spheres. In combination, the two drugs markedly depleted CSCs and strongly reduced primary ESFTs in xenograft assays. Our results identify a potentially attractive therapeutic strategy for ESFT that combines mechanism-based targeting of CSC using a low-toxicity antibiotic with a standard-of-care cytotoxic drug, offering immediate applications for clinical evaluation., (©2014 American Association for Cancer Research.)

Eliciting effective immune responses using non-living/replicating DNA vaccines is a significant challenge. We have previously shown that ballistic dermal plasmid DNA-encoded flagellin (FliC) promotes humoral as well as cellular immunity to co-delivered antigens. Here, we observe that a plasmid encoding secreted FliC (pFliC(-gly)) produces flagellin capable of activating two innate immune receptors known to detect flagellin; Toll-like Receptor 5 (TLR5) and Nod-like Receptor family CARD domain-containing protein 4 (NRLC4). To test the ability of pFliC(-gly) to act as an adjuvant we immunized mice with plasmid encoding secreted FliC (pFliC(-gly)) and plasmid encoding a model antigen (ovalbumin) by three different immunization routes representative of dermal, systemic, and mucosal tissues. By all three routes we observed increases in antigen-specific antibodies in serum as well as MHC Class I-dependent cellular immune responses when pFliC(-gly) adjuvant was added. Additionally, we were able to induce mucosal antibody responses and Class II-dependent cellular immune responses after mucosal vaccination with pFliC(-gly). Humoral immune responses elicited by heterologus prime-boost immunization with a plasmid encoding HIV-1 from gp160 followed by protein boosting could be enhanced by use of pFliC(-gly). We also observed enhancement of cross-clade reactive IgA as well as a broadening of B cell epitope reactivity. These observations indicate that plasmid-encoded secreted flagellin can activate multiple innate immune responses and function as an adjuvant to non-living/replicating DNA immunizations. Moreover, the capacity to elicit mucosal immune responses, in addition to dermal and systemic properties, demonstrates the potential of flagellin to be used with vaccines designed to be delivered by various routes.

To determine the ability of antiretroviral treatment (ART) to deter viral replication in the long term, we tested autologous neutralization of HIV-1 primary isolates in sera from six chronically HIV-1-infected patients before and during such treatment. For comparison, heterologous neutralization was tested in the same samples by using a panel of eight primary HIV-1 isolates. Preceding ART, none of the patients' samples contained neutralizing antibodies against autologous HIV-1 isolates. Subsequently, despite successful ART treatment during a 12- to 19-month period and a rise in CD4 T cell counts, the patients' viral neutralizing capacity did not increase significantly. Furthermore, the partial heterologous neutralizing response was not improved in these patients. This outcome signifies the failure of an HIV-1-specific humoral immune response to improve, despite successful ART. Therefore, our results emphasize the need for immunologic intervention before cessation of ART in chronically HIV-1-infected patients to achieve sustainable control of viral replication.

Aims: The study was designed to evaluate a novel cationic lipid DNA adjuvant (N3) and its function for HIV-1gp160/rev DNA plasmid delivered intranasally. The primary N3/HIV-DNA plasmid immunizations were boosted intranasally with a gp41 peptide in a anionic L3 adjuvant. This novel prime-boost strategy of mucosal immunization provided a broad HIV-1 envelope specific immunity, and recognition of viruses of subtypes A, B and C., Conclusions: Intranasal N3-adjuvanted gp160/rev DNA prime followed by one L3-peptide boosting immunization, induced broadly neutralizing antibodies against HIV-1 in the mucosa and systemically. The needle-free intranasal prime-boost strategy using two different adjuvant formulations reduced significantly the dose of DNA needed.

An intranasal DNA vaccine prime followed by a gp41 peptide booster immunization was compared with gp41 peptide and control immunizations. Serum HIV-1-specific IgG and IgA as well as IgA in feces and vaginal and lung secretions were detected after immunizations. Long-term humoral immunity was studied for up to 12 mo after the booster immunization by testing the presence of HIV-1 gp41- and CCR5-specific Abs and IgG/IgA-secreting B lymphocytes in spleen and regional lymph nodes in immunized mice. A long-term IgA-specific response in the intestines, vagina, and lungs was obtained in addition to a systemic immune response. Mice immunized only with gp41 peptides and L3 adjuvant developed a long-term gp41-specific serum IgG response systemically, although over a shorter period (1-9 mo), and long-term mucosal gp41-specific IgA immunity. HIV-1-neutralizing serum Abs were induced that were still present 12 mo after booster immunization. HIV-1 SF2-neutralizing fecal and lung IgA was detectable only in the DNA-primed mouse groups. Intranasal DNA prime followed by one peptide/L3 adjuvant booster immunization, but not a peptide prime followed by a DNA booster, was able to induce B cell memory and HIV-1-neutralizing Abs for at least half of a mouse's life span.

Background: HIV-specific IgA is present in HIV-exposed uninfected individuals (EU) and neutralizes primary strains of HIV-1 in vitro., Objectives: To analyse the antigenic correlates of HIV-1 neutralization using HIV epitopes and IgA from EU and HIV-seropositive individuals., Methods: Sera from six heterosexual couples discordant for HIV serostatus, six age-matched HIV-infected subjects and six healthy controls (HC; as negative controls) were analysed. IgA binding on HIV Env recombinant proteins was assayed. Serum IgA was affinity purified on specific Env peptides and tested in HIV neutralization using resting and activated peripheral blood mononuclear cells as target. Monoclonal antibody 2F5 was used as neutralizing positive control. BALB/c mice were immunized with specific gp41 peptide and anti-sera were tested in syncytia formation and in HIV viral replication., Results: IgA of EU exclusively bound an epitope within gp41; this epitope was restricted to residues 582-588 (QARILAV) and corresponded to the leucine zip motif in the alpha-helical region. IgA of HIV-positive patients recognized epitopes expressed both in gp120 and gp41; these epitopes were in the N-terminal portion of the extramembrane region. Additionally, IgA of EU and antisera of QARILAV-immunized Balb/C mice blocked syncytia formation and viral replication. The dose-dependent neutralization behaviour of specific QARILAV-purified IgA was very similar to that obtained with monoclonal antibody 2F5., Conclusion: These results have important implications for the development of vaccines and therapeutical strategies against HIV infection., (Copyright 2002 Lippincott Williams & Wilkins)

There is an urgent need for a universally effective HIV-1 vaccine, but whether a vaccine will be able to protect against HIV-1 of different clades is a significant concern. IgA from HIV-1-exposed, persistently seronegative (HEPS) subjects has been shown to neutralize HIV-1 and to block epithelial HIV-1 transcytosis, and it may target novel HIV-1 epitopes. We have tested the ability of plasma and mucosal IgA purified from HEPS subjects to neutralize HIV-1 primary isolates of different viral clades and phenotypes. IgA from two groups of HEPS subjects was tested: sex workers from Nairobi, Kenya, where clades A and D predominate, and the heterosexual partners of individuals infected by clade B virus. HIV-1-infected and low-risk uninfected individuals were included as controls. IgA purified from the blood, genital tract, and saliva of most HEPS sex workers demonstrated significant cross-clade HIV-1 neutralization, whereas a more clade-restricted pattern of neutralization was found in partners of clade B-infected individuals. IgA purified from HIV-1-infected individuals also mediated cross-clade neutralization, whereas IgA from uninfected controls lacked neutralizing activity. In conclusion, mucosal and plasma IgA from HEPS subjects neutralizes HIV-1 of different clades. This ability to induce HIV-1-specific systemic and mucosal IgA may be an important feature of an effective prophylactic HIV-1 vaccine.

Objective: To examine the stability and change in oppositional defiant disorder (ODD) with onset among preschool children in a pediatric sample., Method: A total of 510 children aged 2-5 years were enrolled initially in 1989-1990 (mean age 3.42 years); 280 participated in five waves of data collection over a period of 48 to 72 months (mean wave 5 age, 8.35 years). Test batteries varied by age, but they included the Child Behavior Checklist, developmental evaluation, Rochester Adaptive Behavior Inventory, and a play session (before age 7 years) and a structured interview (Diagnostic Interview for Children and Adolescents, parent and child versions) at ages 7+ years. Consensus diagnoses were assigned by using best-estimate procedures., Results: Wave 1 single-diagnosis ODD showed a significant relationship with both single-diagnosis ODD and single-diagnosis attention-deficit hyperactivity disorder (ADHD) at subsequent waves, but not with single-diagnosis anxiety or mood disorders. Single-diagnosis ODD at wave 1 was associated with later comorbidity of ODD/ADHD, ODD/anxiety, and ODD/mood disorders. Stability across waves 2 through 5 was moderate to high for comorbid ODD/anxiety and ODD/ADHD; low to moderate stability for single-diagnosis ODD and single-diagnosis mood disorder; and low for mood disorder, single-diagnosis ADHD, and single-diagnosis anxiety disorder., Conclusions: Preschool children with ODD are likely to continue to exhibit disorder, with increasing comorbidity with ADHD, anxiety, or mood disorders.

Although HIV-specific cellular immune responses are found in a number of HIV highly-exposed, persistently seronegative (HEPS) cohorts, late seroconversion can occur despite pre-existing cytotoxic T lymphocytes (CTL), suggesting that a protective HIV vaccine may need to induce a broader range of HIV-specific immune responses. Low levels of HIV-specific IgA have been found in the genital tract and plasma of the majority of Nairobi HEPS sex workers and appeared to be independent of HIV-specific cellular responses. IgA purified from genital tract, saliva and plasma of most HEPS sex workers were able to neutralize infection of PBMC by a primary (NSI) clade B HIV isolate, as well as viral isolates from clades A and D, which predominate in Kenya. In addition, these IgA were able to inhibit transcytosis of infective HIV virions across a transwell model of the human mucosal epithelium in an HIV-specific manner. Preliminary work in other HEPS cohorts has suggested the recognition of different gp41 epitopes in HEPS and HIV-infected subjects. Although present at low levels, these IgA demonstrated cross-clade neutralizing activity and were able to inhibit HIV mucosal transcytosis, suggesting an important functional role in protection against HIV infection.

The aim of this study was to examine if an insecure coercive attachment pattern is associated with disruptive behavior in preschoolers, as well as to examine the concurrent and joint effects of attachment pattern, marital dissatisfaction, and ineffective parenting practices on disruptive behavior. Participants included 60 preschoolers and their mothers, recruited from three sites to ensure an adequate range of disruptive behavior. The Preschool Assessment of Attachment (Crittenden, 1992) was used to measure attachment pattern. Results of an analysis of variance revealed that children in the coercively attached dyads scored significantly higher on the measure of disruptive behavior than either the defended or secure children. Results of a hierarchical regression analysis indicated that the combination of a coercive pattern of attachment, marital dissatisfaction, and permissive parenting practices accounted for a significant proportion of the variance in disruptive behavior in preschoolers. These data suggest that a specific type of insecure attachment, a coercive pattern, is associated with disruptive behavior in preschoolers. Also, the data are consistent with previous findings of associations among marital dissatisfaction, ineffective parenting practices, and disruptive behavior.

HIV-1-specific IgA has been described in the genital tract and plasma of HIV-1 highly exposed, persistently seronegative (HEPS) individuals, and IgA from these sites has been shown to neutralize HIV-1. This study examines the ability of IgA isolated from HEPS individuals to inhibit transcytosis across a tight epithelial cell layer. A Transwell system was established to model HIV-1 infection across the human mucosal epithelium. The apical-basolateral transcytosis of primary HIV-1 isolates across this mucosal model was examined in the presence and the absence of IgA isolated from the genital tract, saliva, and plasma of HEPS individuals enrolled in both a sex worker cohort in Nairobi, Kenya, and a discordant couple cohort in Italy. In the absence of IgA, HIV-1 primary isolates were actively transported across the epithelial membrane and were released on the opposite side of the barrier. These transcytosed HIV-1 particles retained their ability to infect human mononuclear cells. However, IgA purified from the mucosa and plasma of HEPS individuals was able to inhibit HIV-1 transcytosis. Inhibition was seen in three of six cervicovaginal fluid samples, five of 10 saliva samples, and three of six plasma samples against at least one of the two primary HIV-1 isolates tested. IgA from low risk, healthy control subjects had no inhibitory effect on HIV-1 transcytosis. The ability of mucosal and plasma IgA to inhibit HIV-1 transcytosis across the mucosal epithelium may represent an important mechanism for protection against the sexual acquisition of HIV-1 infection in HEPS individuals.

Objective: To characterize functional properties of HIV-specific IgA in samples representing both systemic and mucosal compartments of HIV-1 highly exposed persistently seronegative (HEPS) individuals., Methods: IgA was purified from plasma and mucosal samples from HEPS individuals and tested for the ability to neutralize infection of peripheral blood mononuclear cells (PBMC) by a non-syncytium inducing HIV-1 (clade B) primary isolate. None of these individuals had measurable HIV-1-specific IgG., Results: HIV-1-specific neutralizing activity of the purified IgA from plasma (n = 15), saliva (n = 15) and cervicovaginal fluid (CVF) (n = 14) were found in the majority of samples (73, 73 and 79%, respectively). In contrast, plasma, saliva and CVF samples of low-risk, uninfected HIV-seronegative individuals lacked neutralizing IgA, with the exception of two out of 34 (6%) saliva samples., Conclusion: Mucosal and plasma IgA from HEPS individuals can neutralize HIV-1 infection.

Objective: Recent Medicare health maintenance organization (HMO) disenrollees use a high level of medical services. This study examined admissions for total hip arthroplasty (THA) and osteoarthritis-related knee replacements (OKR) among Medicare HMO disenrollees and continuously enrolled fee-for-service (FFS) beneficiaries to determine whether Medicare beneficiaries are returning to the FFS system to receive quality-of-life enhancing elective care., Study Design: Retrospective analysis of Medicare inpatient claims for elderly Medicare beneficiaries residing in South Florida between 1990 and 1993., Methods: Inpatient admission rates for THA, OKR, and for 2 acute conditions--total hip replacements related to fracture of the hip (HRF) and acute myocardial infarction (AMI)--were estimated for Medicare HMO disenrollees over the 3-month period immediately following their disenrollment. These rates were compared with standardized rates for Medicare FFS enrollees., Results: The annualized adjusted rates of both THA and OKR were 3.5 to 4 times higher among Medicare HMO disenrollees than among FFS beneficiaries (P < or = .0001 for both procedures); substantially smaller differences were noted for HRF (P < or = .05), and no difference was present for AMI. HMO disenrollees and FFS enrollees did not differ in their levels of comorbidity at the time of admission., Conclusions: These data provide indirect evidence that Medicare HMOs in South Florida are rationing THA and OKR and that beneficiaries respond by returning to the FFS system to seek care. This apparent rationing has important implications regarding for the management of serious, but nonemergent, medical conditions within the evolving Medicare system.

We investigated the immune response against a human immunodeficiency virus type 1 (HIV-1) nef DNA sequence administered epidermally in mice transgenic for the human major histocompatibility complex (MHC) class I molecule HLA-A201. Ten potential HLA-A2 binding 9-mer Nef peptides were identified by a computer-based search algorithm. By a cell surface MHC class I stabilization assay, four peptides were scored as good binders, whereas two peptides bound weakly to HLA-A2. After DNA immunization, cytotoxic T lymphocyte (CTL) responses were predominantly directed against the Nef 44-52, 81-89, and 85-93 peptides. Interestingly, the 44-52 epitope resides outside the regions of Nef where previously described CTL epitopes are clustered. Dominance among Nef-derived peptides did not strictly correlate with HLA-A2 binding, in that only one of the high-affinity binding peptides was targeted in the CTL response. The 44-52, 85-93, and 139-147 peptides also generated specific CTLs in response to peptide immunization. T helper cell proliferation was detected after stimulation with 20-mer peptides in vitro. Three Nef regions (16-35, 106-125, and 166-185) dominated the T helper cell proliferation. The implications of these results for the development of DNA-based vaccines against HIV is discussed., (Copyright 2000 Academic Press.)

An HIV-1 p24 capture enzyme linked immunosorbent assay (ELISA) was developed and used in a study of B-cell epitopes in rabbits immunised with different gag p24 antigens. Rabbits were immunised with virion HIV-1/Lai, baculovirus recombinant p24, Escherichia coli recombinant p24-15 and a mixture of synthetic peptides representing sequences of HIV-1 gag p24 protein, respectively. Five out of nine rabbits developed antibodies that could be used for an antigen capture ELISA. No significant differences in IgG titers to the whole gag protein were seen when comparing rabbits immunised with four different antigens. Three major common linear epitope regions were mapped in the rabbits immunised with virion HIV-1/Lai and baculovirus recombinant p24. The rabbit immunised with HIV-1 gag peptides had the broadest linear epitope reactive responses whereas animals immunised with E. coli recombinant antigen had the most restricted linear epitope response. The capture ELISA method thus developed using the different rabbit anti-p24 IgG preparations was shown to capture isolates from HIV-1 subtypes or clades A to G. Only rabbits immunised with virion HIV-1/Lai and baculovirus recombinant p24 developed IgG that was capable of efficiently capturing HIV-1 p24 in ELISA, indicating the importance of preparing antibodies able to recognise native or discontinuous and linear antigen configurations.

Objective: To examine whether use of the Medicare Hospice Benefit between health maintenance organization (HMO) and Fee-For-Service (FFS)-enrolled beneficiaries varies by income or race., Data Source: Medicare enrollment and claims data for South Florida., Results: In the FFS system, rate of death in hospice varied by income. In the HMO system, it did not. Time spent in hospice varied by income in the HMO system and not in the FFS system. There was little evidence that racial differences in hospice use differed between FFS and HMO options., Conclusions: These differences raise questions about whether some hospice use may be in response to system-level incentives.

This study compares use of the hospice benefit in Medicare fee-for-service (FFS) and Medicare risk-health maintenance organization (HMO) options in South Florida in 1992. A higher percentage of deaths occurred in hospice in the HMO option than in the FFS option. Compared to individuals in the FFS option, HMO-enrolled hospice users had longer lengths of hospice stay, lower 7-day mortality and higher 180-day (6 month) survival. These differences are consistent with the physician's financial incentives associated with the two programs.

Objective: To determine if home environmental hazards increase the risk of fall injury events among community-dwelling older persons., Design: Population-based case-control study., Setting: South Miami Beach, Florida., Participants: 270 persons aged 65 years and older who sought treatment at six area hospitals for injuries resulting from falls within the dwelling unit and 691 controls, frequency matched for sex and age, selected randomly from Health Care Financing Administration (Medicare) files., Main Independent Variables: The home environment of each person, assessed directly by interviewers using a standardized instrument., Results: Environmental hazards were present in nearly all dwelling units. After adjusting for important confounding factors, most of these hazards were not associated with an increased risk of fall injury events among most older persons. Increasing numbers of tripping hazards, or total hazards in the dwelling unit, did not increase the risk of fall injury events, nor was there an increasing trend in risk., Conclusions: Current fall-prevention strategies of finding and changing all environmental hazards in all community-dwelling older persons' homes may have less potential effect than previously thought. The usefulness of grab bars, however, appears to warrant further evaluation.

Medicare risk health maintenance organizations (HMOs) are an increasingly common alternative to fee-for-service Medicare. To date, there has been no examination of whether the HMO program is preferentially used by blacks or by persons living in lower-income areas or whether race and income are associated with reversing Medicare HMO selection. This question is important because evidence suggests that these beneficiaries receive poorer care under the fee-for-service-system than do whites and persons from wealthier areas. Medicare enrollment data from South Florida were examined for 1990 to 1993. Four overlapping groups of enrollees were examined: all age-eligible (age 65 and over) beneficiaries in 1990; all age-eligible beneficiaries in 1993; all age-eligible beneficiaries residing in South Florida during the period 1990 to 1993; and all beneficiaries who became age-eligible for Medicare benefits between 1990 and 1993. The associations between race or income and choice of Medicare option were examined by logistic regression. The association between the demographic characteristics and time staying with a particular option was examined with Kaplan-Meier methods and Cox Proportional Hazards modeling. Enrollment in Medicare risk HMOs steadily increased over the 4-year study period. In the overall Medicare population, the following statistically significant patterns of enrollment in Medicare HMOs were seen: enrollment of blacks was two times higher than that of non-blacks; enrollment decreased with age; and enrollment decreased as income level increased. For the newly eligible population, initial selection of Medicare option was strongly linked to income; race effects were weak but statistically significant. The data for disenrollment from an HMO revealed a similar demographic pattern. At 6 months, higher percentages of blacks, older beneficiaries (older than 85), and individuals from the lowest income area (less than $15,000 per year) had disenrolled. A small percentage of beneficiaries moved between HMOs and FFS plans multiple times. These data on Medicare HMO populations in South Florida, an area with a high concentration of elderly individuals and with one of the highest HMO enrollment rates in the country, indicate that enrollment into and disenrollment from Medicare risk HMOs are associated with certain demographic characteristics, specifically, black race or residence in a low-income area.

Serologic assays could be useful for determining circulating subtypes in different geographic regions. A total of 175 serum samples from the same number of Argentinian HIV-infected patients from Buenos Aires and Rosario were tested against a panel of peptides representing V3 consensus subtypes A through H. A V3 peptide enzyme immunoassay was used for screening the sera. Most sera were reactive with peptides representing subtypes B (58.28%), F (13.14%), and A (8.57%). Cross-reactivity between the remainder of the peptides was observed. Genotypes of eight patients from Rosario were determined and compared with serotyping. Results showed that seven of eight genotyped patients reacted with their respective consensus B peptide and one reacted with consensus B and F. V3 peptide serology proved to be useful for determining HIV-1 clades circulating in Argentina.

Background: Enrollment in Medicare health maintenance organizations (HMOs) is encouraged because of the expectation that HMOs can help slow the growth of Medicare costs. However, Medicare HMOs, which are paid 95 percent of average yearly fee-for-service Medicare expenditures, are increasingly believed to benefit from the selective enrollment of healthier Medicare recipients. Furthermore, whether sicker patients are more likely to disenroll from Medicare HMOs, thus raising average fee-for-service costs, is not clear., Methods: We used Medicare enrollment and inpatient billing records for southern Florida from 1990 through 1993 to examine differences in the use of inpatient medical services by 375,406 beneficiaries in the Medicare fee-for-service system, 48,380 HMO enrollees before enrollment, and 23,870 HMO enrollees after disenrollment. We also determined whether these differences were related to demographic characteristics and whether the pattern of use after disenrollment persisted over time., Results: The rate of use of inpatient services in the HMO-enrollment group during the year before enrollment was 66 percent of the rate in the fee-for-service group, whereas the rate in the HMO-disenrollment group after disenrollment was 180 percent of that in the fee-for-service group. Beneficiaries who disenrolled from HMOs re-enrolled at about the time that their level of use dropped to that in the fee-for-service group., Conclusions: These data show marked selection biases with respect to HMO enrollment and disenrollment. These biases undermine the effectiveness of the Medicare managed-care system and highlight the need for longitudinal and population-based studies.

Objective: To evaluate the association between selected chronic medical conditions (CMCs) and fall injury events at home among community-dwelling older persons., Design: Population-based case-control study., Setting: The general community., Participants: Persons aged 65 and older living at home, excluding those using a wheelchair; 467 cases and 691 control subjects were studied., Measurements: The main independent variables were self-reported histories of 10 CMCs: diabetes, high blood pressure, anemia, heart attack, Parkinson's disease, stroke, emphysema, cancer (other than skin), cataracts, and glaucoma., Results: The final multivariate model included variables for age, sex, body mass, dependency in activities of daily living, current exercise (three or more times per week), mental status scores, and three CMCs. Persons with a history of stroke or anemia had an increased risk of a fall injury event: for stroke the adjusted odds ratio (aOR) equalled 1.7 (95% confidence interval (CI), 1.0-3.0); for anemia the aOR equalled 1.5 (95% CI, 1.0-2.2). Those with a history of high blood pressure had decreased risk (aOR = .7, 95% CI 0.5-0.9)., Conclusions: Persons 65 and older with a self-reported history of anemia or stroke are at increased risk of a fall injury event in the home, whereas those with a self-reported history of high blood pressure are at decreased risk.

Hazards in the home are implicated in up to half of all falls among older persons. Yet, the instruments used to identify these hazards usually have been unstandardized, have lacked specific definitions of hazards, and have not been evaluated. Therefore, in 1988, as part of the Study to Assess Falls among the Elderly, in Miami Beach, Florida, the authors evaluated the reliability of a standardized instrument used for assessing the training of evaluators and assessing home environments. Based on up to 176 observations for each potential hazard, the interviewers' assessment of hazards such as throw rugs, tripping hazards, light switch hazards, and hazardous bath surfaces had good overall reliability (kappa = 0.65-0.92). Their assessment of grab-bars and hazardous furniture was unreliable (kappa = 0.18-0.35). Variations in the reliability reflect the difficulty in creating definitions that are simple to be understood and used, yet detailed enough to produce sensitive and specific survey items. Investigators studying falls among older persons should use standardized definitions to train evaluators and assess environmental hazards.

Estimations of age from tooth formation standards for a large (n = 282) sample of subadult skeletal remains from a 19th century historic cemetery sample were analyzed. The standards of Moorrees et al. (1963a,b) for the permanent and deciduous teeth, and Anderson et al. (1976) for the formation of permanent dentition were employed in a variety of combinations to calculate mean dental ages. Tests of accuracy and bias were made on a small sample (n = 17) of personally identified individuals, and age of attainment scores were compared to age of prediction scores for each individual. The resulting dental age distributions for the skeletal sample were compared to documented burial records for the cemetery to determine the representativeness of the skeletal sample. These comparisons showed little difference between age of attainment versus age of prediction methodologies. The standards of Moorrees et al. (1963a,b) were observed to provide the most accurate estimates of age with a standard deviation of one-half year. The standards of Anderson et al. (1976), while easier to use and more extensive, are problematic in that the original reference sample begins at three years of age, while the sample used by Moorrees and colleagues begins at birth. The skeletal age distributions compare well to the overall chronological age distribution for the cemetery. These results affirm that tooth formation age estimates for subadult skeletal remains from archaeological or forensic samples provide accurate assessments of age at both the individual and population level.

Objective: To determine if alcohol use is a risk factor for fall injury events among community-dwelling older persons., Design: Case-control study., Setting: South Miami Beach, Florida., Participants: 320 persons 65 or older who sought treatment at six area hospitals for injuries resulting from falls; 609 controls, matched for sex and age, selected randomly from Health Care Financing Administration (Medicare) files., Main Independent Variables: Self-reported current alcohol use., Results: No association was found between fall injury events and average weekly alcohol use., Conclusions: Further efforts at reducing injuries to older persons from falls should concentrate on other modifiable risk factors, including adequate treatment of underlying medical conditions, reducing inappropriate psychotropic medication use, and installing safety devices in the home.

The problem of how to communicate with the members of an alien society has been discussed by many authors but only one, Hans Freudenthal, has constructed a language for this purpose. Freudenthal assumes nothing other than the ability to reason as humans do and, because he assumes so little, it is necessary to communicate a great deal about the language itself before being able to communicate any interesting information. The problem is here approached differently. Since it is likely that contact between our civilization and an alien one would be via radio, potential correspondents would have a basic knowledge of science. Such beings should therefore be able to learn a language based on fundamental science. It is assumed, more specifically, that our correspondents can count, understand chemical elements, are familiar with the melting and boiling behaviour of a pure substance and understand the properties of the gaseous state. All this should be known to any society capable of developing the radio telescope. By systematically using this common knowledge one can communicate notation for numbers and chemical elements and then communicate our basic physical units; i.e., the gram, the calorie, the degree (Kelvin), etc. Once this is done more interesting information can be exchanged.

Falls are a leading cause of death from injury among older persons in the United States, and about one in three older persons falls each year. Yet, reliable estimates of the incidence of fall injury events in a population-based setting are not readily available. Therefore, the authors analyzed population-based surveillance data, between July 1985 and June 1987, from the Study to Assess Falls Among the Elderly, Miami Beach, Florida. The rate of fall injury events coming to acute medical attention increased exponentially with age for both elderly men and women (predominantly white), reaching a high for those aged 85 years or more of 138.5 per 1,000 for males and 158.8 per 1,000 for females. Compared with males, females had a higher incidence of fractures other than skull. Males were nearly twice as likely to die, however, following a fall injury event than were females. Of those fall injury events identified through the surveillance system, about 42% resulted in hospital admission. The mean length of hospital stay was 11.6 days overall and was 15.5 days for hip fracture, 9.8 days for skull fracture/intracranial injury, 11.2 days for all other fractures, and 9.1 days for all other injuries. About 50% of fall injury events that occurred at home and required hospital admission resulted in a person being discharged to a nursing home.

In June 1974, Michigan Public Law 155 was enacted. This law permits a pharmacist to exercise drug product selection under specified conditions. The intent of the legislation is to achieve savings in prescription drug costs by encouraging pharmacists to dispense less costly, generically equivalent products. For this legislation to be effective, there have to be many substitutable products for a sufficient number of drugs; there has to be minimal interference with pharmacists' judgment; and pharmacists must be aware of the products available. As part of a survey, we attempted to measure physicians' and pharmacists' knowledge of generically equivalent products. Pharmacists demonstrated a higher level of knowledge of drug products. Continuing education must respond to the needs of more complicated societal demands.

Falls are a leading cause of fatal and nonfatal injuries among the elderly in the United States. Despite the importance of fall injuries, epidemiological studies of falls among the elderly have identified neither their causes nor the methods to prevent them. Therefore, we established a community-based surveillance system in Miami Beach, Florida, as part of a study to assess falls among the elderly. A total of 1,827 fall injury events occurred in this community between July 1985 and June 1986. More than 85% (1,567) of the persons who fell and received care were seen in an emergency room. The remaining cases were identified from one of the three other sources used: fire rescue reports, inpatient medical records, or medical examiner reports. Most falls (97%) were coded as accidental (E880-E888). More than 100 people sought medical assistance for a fall each month. The time of the injury was known for 68% (1,244) of the people who fell. Seventy-four percent of these falls (921) occurred during daylight hours. Fifty-four percent of the falls (986) occurred in and around the home, and 38% of these had a particular area of the home recorded: 42% occurred in the bedroom, 34% in the bathroom, 9% in the kitchen, 5% on the stairs, 4% in the living room, and the remaining 6% in other areas. This surveillance system will help us use the study to clarify the causes of falls in the elderly and identify and evaluate appropriate prevention efforts. It will also help others in designing and implementing other injury surveillance systems.

We conducted a trial to evaluate the impact of medical self-care education on 330 elders whose average age was 71. The test group participated in a 13-session educational intervention with training in clinical medicine, life-style, and use of health services. The comparison group received a two-hour lecture-demonstration. Both groups were assessed pre-intervention, post-intervention, and one year after entry. The results indicate medical self-care instruction: produces substantial improvements, that were sustained for one year, in health knowledge, skills performance, and skills confidence; stimulates many attempts to improve life-style; and generates improvements in life quality. The program had little influence on utilization of medical care or health status.

A correlational analysis was performed to determine the relationship of anagram solving to both transition probability and word frequency. The results revealed that an index that combines solution-word and anagram transition probability by subtracting the latter from the former is significantly related to problem solution. Solution-word transition probability alone and the Thorndike-Lorge word count were both found to be uncorrelated to the solution of anagrams. A comparison of the Underwood-Schulz and Mayzner-Tresselt systems for calculating digram frequencies revealed that the two systems produced essentially comparable results except for the anagram transition probability variable where only the Mayzner-Tresselt system yielded a significant correlation.