Key Characteristics for Successful Adoption and Implementation of Home Telehealth Technology in Veterans Affairs Home-Based Primary Care: An Exploratory Study.

BACKGROUND/OBJECTIVES: The Department of Veteran Affairs (VA) Home-Based Primary Care (HBPC) program provides care to over 37,000 high-risk, high-need, medically complex, and costly patients in their home. The VA's Home Telehealth (HT) program can potentially amplify HBPC's efficiency and reach, yet scarce data on use and experience with HT in HBPC exist. This exploratory study sought to provide a glimpse of HT use in HBPC and identify drivers and barriers for HT implementation. DESIGN: National VA data were used to evaluate HBPC patients concurrently using HT. We conducted a cross-sectional survey of HBPC program directors to explore HT use, understand communication processes, and elicit open comments. Semistructured interviews were conducted of 18 HBPC program directors with varying HT use to clarify themes and understand HBPC experience with HT. RESULTS: Fifteen percent of the overall HBPC patients used HT in 2011, with a wide variation in HT use by HBPC site. The national survey and semistructured interviews revealed that most HBPC staff recognized advantages of using HT, including increased patient engagement and staff efficiency. Crucial practices among sites with successful telehealth adoption included HT staff attending HBPC meetings and evaluating all HBPC patients for HT. CONCLUSION: Much remains to be done for effective HT integration in HBPC. Improving communication between HT and HBPC programs and establishing a system for identifying suitable patients for HT are vital. Future studies need to delineate operational processes and gather data on the added value of HT in HBPC to guide evidence-based integration of HT in VA and Medicare HBPC programs.

Evaluating an Electronic Health Record Intervention for Management of Heart Failure Among Veterans.

Background:We studied the feasibility of using the Veteran Health Administration's electronic health record (EHR), My HealtheVet, as an educational and monitoring tool for veterans with heart failure (HF).Methods:We enrolled 120 HF patients with a mean age (±standard deviation): 64.8 ± 9.6, range: 41-91 years. There were 105 (87.5%) non-Hispanics, 15 (12.5%) Hispanics, 91 (75.8%) whites, and 20 (16.5%) blacks, and 62 (51.7%) were married. Study participants received educational material on managing their HF and were monitored on their weight and HF symptoms weekly. Surveys on My HealtheVet use and secondary outcomes including knowledge of their illness, quality of life (QoL), and self-efficacy were conducted at baseline and 26 weeks after enrollment.Results:Among the participants, 55 (45.8%) had used My HealtheVet. The number of weeks each user responded to the weekly messages by the care coordinator ranged from 1 (4%) to 26 (100%) with a median of 8. Secondary outcome data were available for 54 patients (24 users and 30 nonusers) who participated in both baseline and 26-week surveys. There was a significant improvement in QoL (p < 0.01) among users of My HealtheVet compared with nonusers. There were no significant differences with respect to self-efficacy or HF knowledge. Use of My HealtheVet and ease in using the HealtheVet portal increased from baseline to follow-up.Conclusions:EHR-based interventions have potential for HF monitoring and case management, and may be feasible in improving QoL for patients.

The costimulatory immunogen LPS induces the B-Cell clones that infiltrate transplanted human kidneys.

The mechanism of chronic rejection of transplanted human kidneys is unknown. An understanding of this process is important because, chronic rejection ultimately leads to loss of the kidney allograft in most transplants. One feature of chronic rejection is the infiltration of ectopic B-cell clusters that are clonal into the transplanted kidney. We now show that the antibodies produced by these B-cells react strongly with the core carbohydrate region of LPS. Since LPS is a costimulatory immunogen that can react with both the B-cell receptor (BCR) and the Toll-like receptor 4 (TLR4), these results suggest a mechanism for the selective pressure that leads to clonality of these B-cell clusters and opens the possibility that infection and the attendant exposure to LPS plays a role in the chronic rejection of human kidney transplants. If confirmed by clinical studies, these results suggest that treating patients with signs of chronic rejection with antibiotics may improve kidney allograft survival.

Phenotype-information-phenotype cycle for deconvolution of combinatorial antibody libraries selected against complex systems.

Use of large combinatorial antibody libraries and next-generation sequencing of nucleic acids are two of the most powerful methods in modern molecular biology. The libraries are screened using the principles of evolutionary selection, albeit in real time, to enrich for members with a particular phenotype. This selective process necessarily results in the loss of information about less-fit molecules. On the other hand, sequencing of the library, by itself, gives information that is mostly unrelated to phenotype. If the two methods could be combined, the full potential of very large molecular libraries could be realized. Here we report the implementation of a phenotype-information-phenotype cycle that integrates information and gene recovery. After selection for phage-encoded antibodies that bind to targets expressed on the surface of Escherichia coli, the information content of the selected pool is obtained by pyrosequencing. Sequences that encode specific antibodies are identified by a bioinformatic analysis and recovered by a stringent affinity method that is uniquely suited for gene isolation from a highly degenerate collection of nucleic acids. This approach can be generalized for selection of antibodies against targets that are present as minor components of complex systems.

Ectopic B-cell clusters that infiltrate transplanted human kidneys are clonal.

B cells and their immunoglobulin products participate in allograft rejection of transplanted human kidneys in which an interesting feature is the presence of a germinal center like B-cell clusters in the allograft. We report here that the immunoglobulin repertoires of these infiltrating B cells are highly restricted and the B cells within a cluster are clonal. Antibody libraries made from the infiltrating B cells of individual patients unexpectedly revealed that each patient utilizes a particular set of dominant germ line genes as well as dominant complementarity determining region 3. Comparison of kidney and peripheral blood from the same patient showed that the immunoglobulin genes from both compartments had dominant clones, but they differed. The lymphocytes that infiltrate the kidneys express the immunoglobulin gene somatic recombination machinery usually restricted to highly activated lymphocytes in germinal centers and lymphomas. An analogy can be made between the inescapable antigenic drive in chronic infection versus that in an allograft, both of which may lead to emergence of dominant B-cell clones and even lymphoid malignancy.

Engineering cell surfaces for orthogonal selectability.

Vectors have been constructed that express the chitin-binding domain (ChBD) on eukaryotic cell surfaces. The ChBD is linked to enhanced green fluorescent protein (EGFP) through a protein that spans the plasma membrane. This binding functionality does not have a counterpart in eukaryotes, thereby endowing the modified cell surface with a property that is orthogonal to animal cells.

Catalytic antibody degradation of ghrelin increases whole-body metabolic rate and reduces refeeding in fasting mice.

Obesity is a chronic, costly, and globally prevalent condition, with excess caloric intake a suspected etiologic factor. Nonsurgical treatments are modestly efficacious, and weight loss maintenance is hampered by anti-famine homeostatic mechanisms. Ghrelin, a gastric hormone linked to meal initiation, energy expenditure, and fuel partitioning, is hypothesized to facilitate weight gain and impede weight loss. Unique among known animal peptides, the serine-3 residue of ghrelin is posttranslationally acylated with an n-octanoic acid, a modification important for the peptide's active blood-brain transport and growth hormone secretagogue receptor-1 agonist activity. Pharmacological degradation of ghrelin would be hypothesized to reduce ghrelin's biological effects. To study endogenous ghrelin's role in appetite and energy expenditure, we generated antibodies that hydrolyze the octanoyl moiety of ghrelin to form des-acyl ghrelin. The most proficient antibody catalyst, GHR-11E11, was found to display a second-order rate constant of 18 M(-1) x s(-1) for the hydrolysis of ghrelin to des-acyl ghrelin. I.v. administration of GHR-11E11 (50 mg/kg) maintained a greater metabolic rate in fasting C57BL/6J mice as compared with mice receiving a control antibody and suppressed 6-h refeeding after 24 h of food deprivation. Indirect respiratory measures of metabolism after refeeding and relative fuel substrate utilization were unaffected. The results support the hypothesis that acylated ghrelin stimulates appetite and curbs energy expenditure during deficient energy intake, whereas des-acyl ghrelin does not potently share these functions. Catalytic anti-ghrelin antibodies might thereby adjunctively aid consolidation of caloric restriction-induced weight loss and might also be therapeutically relevant to Prader-Willi syndrome, characterized after infancy by hyperghrelinemia, hyperphagia, and obesity.

Infection control by antibody disruption of bacterial quorum sensing signaling.

Quorum sensing (QS) is the process through which bacteria communicate utilizing small diffusible molecules termed autoinducers. It has been demonstrated that QS controls a plethora of microbial processes including the expression of virulence factors. Here we report an immunopharmacotherapeutic approach for the attenuation of QS in the Gram-positive human pathogen Staphylococcus aureus. An anti-autoinducer monoclonal antibody, AP4-24H11, was elicited against a rationally designed hapten, and efficiently inhibited QS in vitro through the sequestration of the autoinducing peptide (AIP)-4 produced by S. aureus RN4850. Importantly, AP4-24H11 suppressed S. aureus pathogenicity in an abscess formation mouse model in vivo and provided complete protection against a lethal S. aureus challenge. These findings provide a strong foundation for further investigations of immunopharmacotherapy for the treatment of bacterial infections in which QS controls the expression of virulence factors.

Squaric monoamide monoester as a new class of reactive immunization hapten for catalytic antibodies.

A squaric monoester monoamide motif was employed as an effective reactive immunogen for the discovery of monoclonal antibodies with reactive residue(s) in their combining sites. Two antibodies, 2D4 and 3C8, were uncovered that enhance paraoxon hydrolysis over background. Kinetic analysis of these antibodies was performed and interestingly both undergo a single turnover event due to covalent modification within the antibody combining site. Because antibodies 2D4 and 3C8 result in covalent attachment and thus inactivation of paraoxon, they could be useful probes for investigating paraoxon intoxication.

Immunological consequences of methamphetamine protein glycation.

The drug of abuse methamphetamine has been found to participate in the aberrant glycation of proteins. The importance of this chemical process has been shown wherein mouse albumin was readily modified with methamphetamine, and injection of this protein into mice yields a significant immune response, even in the absence of adjuvants. Competition experiments revealed that although methamphetamine binds weakly to the elicited antibodies, the primary epitope is composed of both the methamphetamine moiety and glucose-derived cross-linking region. Implications of this phenonomenon in the context of drug addiction are discussed.

Catalysis of the photo-Fries reaction: antibody-mediated stabilization of high energy states.

A conformationally constrained hapten is presented that is capable of catalyzing the first antibody-mediated photo-Fries rearrangement. In this reaction, absorption of light energy by a diphenyl ether substrate results in homolytic C-O bond cleavage followed by recombination to yield biphenyl-derived products. The most proficient antibody studied converts 4-phenoxyaniline 15 into 2-hydroxy-5-aminobiphenyl 16 under high-intensity irradiation at a rate of 8.6 microM/min. These results support a recent hypothesis stating that immunization with conformationally constrained haptens provides higher titers for the acquisition of simple binding antibodies; however, in this case, conformational constraint does not ensure the development of more efficient catalysts. Using the obtained antibodies, the presence of products resulting from escape of free radicals from the solvent cage can be suppressed, altering the excited state energy surface such that free radicals are funneled into the formation of the desired biphenyl product. However, studies also show the inactivation of the antibodies as a result of photodecay of the biphenyl product. Using an isocyanate scavenging resin, the photodecay product could be removed and the inactivation of the antibody drastically reduced. Furthermore, despite the observed photodecay, turnover of the antibody was present; this represents the first case in which true turnover of a photochemical reaction using a catalytic antibody could be observed.