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Specificity of the T cells that mediate and suppress adoptive immunotherapy of established tumors.

This study was designed to investigate the specificity of the T cells that express and suppress antitumor immunity in a model of adoptive immunization against established tumors. Results obtained with the P815 mastocytoma, L5178Y lymphoma, and P388 lymphoma showed, in agreement with previous findings from this laboratory, that an intravenous infusion of splenic T cells from immunized mice can cause the regression of a tumor growing in T-cell-deficient mice. So far as specificity of adoptive immunity is concerned, reciprocal passive transfer experiments with these three tumors revealed that T cells from donor mice immunized against the P815 tumor are not capable of causing regression of the P388 tumor or L5178Y tumor, even if both the P815 and L5178Y tumors are growing in the same host. Similarly splenic T cells from mice immunized against the P388 tumor or L5178Y tumor had no effect on growth of the P815 tumor. Suppression of adoptive immunity was also specific, in that passively transferred suppressor T cells from mice bearing a progressive P815 tumor were capable of suppressing adoptive T-cell-mediated regression of the P815 tumor, but not the P388 tumor growing in T-cell-deficient recipients. Reciprocally, P388 suppressor spleen cells from mice bearing a progressive P388 tumor prevented adoptive T-cell-mediated regression of the P388 tumor, but not the P815 tumor. The results indicate, therefore, that the T cells from immunized mice that mediate adoptive antitumor immunity and the T cells from tumor-bearing mice that suppress the expression of this immunity are specific for the tumor that evokes their generation.

Animals↗

Effect of physical exercise on adoptive experimental auto-immune encephalomyelitis in rats.

The aim of the study was to determine whether different programmes of exercise influence adoptive monophasic experimental auto-immune encephalomyelitis (adoptive EAE), a paralytic disease mediated by T-cells. Adoptive EAE was induced by the transfer of activated encephalitogenic T-lymphocytes into syngeneic recipients (Lewis rats, n = 85) and its development was followed by two independent observers. The results showed that 2 days of severe exercise (250 and 300 min) performed after the adoptive transfer of EAE slightly delayed the onset of the disease (P <0.008) and the day of its maximal severity (P <0.016) without affecting the overall severity of the disease. When this programme of exercise was performed before the cell transfer, it had no effect (P > 0.05). Two more moderate exercise programmes (5 x 120 min of running at constant speed or 5 x 60 min of running at variable speed, 5 consecutive days) performed between the adoptive transfer and the onset of the disease did not modify the development of the clinical signs of adoptive EAE (P >0.05). These results showed that severe exercise slightly influenced the effector phase of monophasic EAE and confirmed that physical exercise performed before the onset of experimental auto-immune diseases did not exacerbate the clinical signs.

Animals↗

Impact of clinical trials on the adoption of new drugs within a university hospital.

To assess the influence that clinical trials may have on the introduction of new drugs into prescribing routines, the adoption of drugs has been studied in a university hospital in the Netherlands. A significant relation was found between the testing of semi-innovative drugs in clinical trials in the hospital and the introduction of these drugs into general use in the same hospital. No such relationship was found for innovative drugs. Employment in clinical trials only affected the frequency of adoption of semi-innovative drugs. It did not influence the quantity of their use once they had been adopted. The idea that the stimulating effect of clinical trials on the adoption of semi-innovative drugs is only due to acceleration of the adoption process was not confirmed. These findings support the idea that clinical trials can lower the barriers for adoption of semi-innovative drugs.

Clinical Trials as Topic↗

Suppression of experimental autoimmune encephalomyelitis by oral administration of myelin basic protein. VI. Suppression of adoptively transferred disease and differential effects of oral vs. intravenous tolerization.

Antigen-driven tolerance is an effective method of suppressing cell-mediated immune responses. We have previously shown that oral administration of myelin basic protein (MBP) suppresses experimental autoimmune encephalomyelitis (EAE) when it is actively induced by MBP emulsified in complete Freund's adjuvant. In order to further study antigen-driven tolerance in this model, we investigated the effect of oral tolerization on adoptively transferred EAE and compared oral tolerance to intravenously (i.v.) administered MBP in both actively induced EAE and adoptively transferred EAE. Although orally tolerized animals were not protected from adoptively transferred EAE, spleen cells from orally tolerized animals suppressed adoptively transferred EAE when co-transferred with encephalitogenic cells or when injected into recipient animals at a different site at the time encephalitogenic cells were transferred. This suppression was mediated by CD8+ T cells, correlated with suppression of DTH responses to MBP, and was associated with decreased inflammation in the spinal cord. Unlike oral tolerization, spleen cells from i.v. tolerized animals did not suppress adoptively transferred EAE when co-transferred with encephalitogenic cells although i.v. tolerized animals were protected from adoptively transferred EAE. MBP peptides were then utilized to further characterize differences between i.v. and oral tolerization in the actively induced disease model. Both orally and intravenously administered MBP suppressed actively induced EAE. However, EAE was only suppressed by prior i.v. tolerization with the encephalitogenic MBP peptide 71-90, but not with the non-encephalitogenic peptide 21-40, whereas prior tolerization with 21-40 did suppress actively induced EAE when administered orally. These results suggest a different mechanism of tolerance is initiated by oral vs. intravenous administered antigen. Specifically, oral tolerization suppresses primarily by the generation of active suppression whereas the dominant mechanism of suppression associated with i.v. tolerization appears most consistent with the elicitation of clonal anergy.

Administration, Oral↗

Determinants for the adoption of angiotensin II receptor blockers by general practitioners.

Results of studies conducted 10-20 years ago show the prominence of commercial information sources in the adoption process of new drugs. Over the past decade, there has been a growing emphasis on practicing evidence-based medicine in drug prescribing. This raises the question whether professional information sources currently counterbalance the influence of commercial information sources in the adoption process. The aim of this study was to identify determinants influencing the adoption of a new drug class, the angiotensin II receptor blockers (ARBs), by general practitioners (GPs) in The Netherlands. A retrospective study was conducted to assess prevalent ARB prescribing for hypertensive patients using the Integrated Primary Care Information (IPCI) database. We conducted a survey among all GPs who participated in the IPCI project in 2003 to assess their exposure to commercial and professional information sources, perceived benefits and risks of ARBs, perceived influences of the professional network, and general characteristics. Multilevel logistic regression was applied to identify determinants of ARB adoption while adjusting for patient characteristics. Data were obtained from 70 GPs and 9470 treated hypertensive patients. A total of 1093 patients received ARBs (12%). GPs who reported frequent use of commercial information sources were more likely to prescribe ARBs routinely in preference to other antihypertensives, whereas GPs who used a prescribing decision support system and those who were involved in pharmacotherapy education were less likely to prescribe ARBs. Other factors that were associated with higher levels of ARB adoption included a more positive perception of ARBs regarding their effectiveness in lowering blood pressure, and working in single-handed practices or in rural areas. Aside from determinants related to the patient population, adoption of a new drug class among Dutch GPs is still determined more by their reliance on promotional information than by their use of professional information sources.

Adult↗

Determinants of the intention to adopt hormone replacement therapy among premenopausal women.

OBJECTIVE: To identify the psychosocial factors that influence the intention to adopt hormone replacement therapy (HRT) at menopause. METHODS: Random Digit Dialing was used to recruit 644 premenopausal non-hysterectomized women aged 45-54. Data were collected using a telephone questionnaire previously developed according to the theory of planned behaviour. Variables measured were: intention to adopt HRT (INT); attitude towards HRT (Aact); perceived social norm (SN); perceived behavioural control (PBC); and personal normative belief (PNB). Socio-demographic data were also obtained. RESULTS: Stepwise multiple regression of INT on the theoretical variables yielded an R(2) of 0.70. The determinants were Aact (beta=0.39, P<0.001), PNB (beta=0.25, P<0.001), PBC (beta=0.23, P<0.001) and SN (beta=0.12, P<0.001). Women with a strong intention to adopt HRT represented 25% of the sample. These women were more likely to believe that adopting HRT would have the following positive consequences: an improvement in general well-being, the prevention of health problems, an improvement in interpersonal relationships, an increase in productivity, the regulation of mood swings and a reduction of hot flashes. They were also more likely to believe in the following negative consequences: side-effects, an increased risk of cancer, the likelihood of weight gain, and interference in the natural course of menopause (all at P<0.001). CONCLUSION: Actions that target behaviourial beliefs regarding HRT and perceived barriers to its adoption are most likely to influence adoption of HRT.

Attitude to Health↗

Maturation of B lymphocytes in the rat. I. Migration pattern, tissue distribution, and turnover rate of unprimed and primed B lymphocytes involved in the adoptive antidinitrophenyl response.

The migration pattern, tissue distribution, and turnover rate of unprimed and primed B lymphocytes involved in the adoptive anti-DNP response was studied. The adoptive primary response restored by unprimed spleen or thoracic duct cells passaged through an intermediate host (intravenous injection and subsequent collection in the thoracic duct lymph) was markedly diminished as compared with that restored by unpassaged cells. On the other hand, the adoptive response restored by passaged spleen or thoracic duct cells from DNP-primed donors was greater than or the same as that restored with unpassaged cells, respectively. This suggests that unprimed B cells change from nonrecirculating to recirculating lymphocytes after exposure to antigen. Studies of the adoptive anti-DNP response restored by unprimed or primed bone marrow cells showed little change in the time-course or amplitude of the response restored by either population of cells. The relative inability of marrow cells to carry immunological memory was related to the inability of recirculating memory cells to penetrate the marrow. The turnover rate of unprimed and primed B cells was investigated by treating the cell donors with [(3)H]thymidine for 48 h before removal of thoracic duct or spleen cells. The adoptive anti-DNP response restored by unprimed or primed cells was not affected by [(3)H]thymidine treatment. This indicates that both populations of cells turn over slowly. However, our previous studies show that unprimed B cells involved in the adoptive antibody response to ferritin turn over rapidly. The different findings are discussed in the context of antigen-dependent B-cell maturation.

Animals↗

Discourse and adoption of innovations: a study of HIV/AIDS treatments.

This article, based on a longitudinal case study, investigates the development, testing, and adoption of innovations in the treatment of HIV/AIDS. Findings indicate that distinguishing between "evidence production" and "adoption" can be difficult because the adoption of innovations is a negotiated outcome and the nature and role of evidence are not given, stable and exogenous to the adoption process. This means that changes to the distribution of discursive legitimacy and credibility in an adopting system can change evidence production and evaluation, and hence patterns of adoption of innovations.

Acquired Immunodeficiency Syndrome↗

Factors influencing health information system adoption in American hospitals.

OBJECTIVES: To study the number of health information systems (HISs), applicable to administrative, clinical, and executive decision support functionalities, adopted by acute care hospitals and to examine how hospital market, organizational, and financial factors influence HIS adoption. METHODS: A cross-sectional analysis was performed with 1441 hospitals selected from metropolitan statistical areas in the United States. Multiple data sources were merged. Six hypotheses were empirically tested by multiple regression analysis. RESULTS: HIS adoption was influenced by the hospital market, organizational, and financial factors. Larger, system-affiliated, and for-profit hospitals with more preferred provider organization contracts are more likely to adopt managerial information systems than their counterparts. Operating revenue is positively associated with HIS adoption. CONCLUSION: The study concludes that hospital organizational and financial factors influence on hospitals' strategic adoption of clinical, administrative, and managerial information systems.

Cross-Sectional Studies↗

Mechanisms of immunological eradication of a syngeneic guinea pig tumor. II. Effect of methotrexate treatment and T cell depletion of the recipient on adoptive immunity.

The influence of methotrexate on the development of immunity to the line 10 hepatoma was studied in guinea pigs. Chronic methotrexate treatment had no apparent effect on the ability of immune guinea pigs to suppress the growth of inoculated tumor cells. In contrast, the same methotrexate regimen inhibited the development of tumor immunity if started before the 8th day after immunization with a vaccine containing viable line 10 cells admixed with Bacillus Calmette-Guérin (BCG) cell walls. Thus, methotrexate selectively inhibited the afferent limb of the immune response. In adoptive transfer experiments, methotrexate-treated recipient guinea pigs were capable of being passively sensitized with immune spleen cells, indicating that the primary cell-mediated immune response of the recipient was not required for adoptive immunity. The contribution of recipient T cells in adoptive immunity was further investigated in guinea pigs deleted of T cells by thymectomy, irradiation, and bone marrow reconstitution. Despite demonstrable deficiency in T lymphocyte reactions, "B" animals were fully capable of rejecting tumors after transfer of immune cells. These results suggest that the expression of adoptive immunity was independent of recipient T cell participation. In addition, sublethal irradiation of immune spleen cells prior to adoptive transfer abolished their efficacy. Proliferation of transferred immune cells in the recipient may be essential for expression of adoptive immunity.

Animals↗

Adopting a personal digital assistant system: application of Lewin's change theory.

AIM: This paper reports a study exploring nurses' perceptions of adopting an information system using handheld computers (personal digital assistants) in their daily practice. BACKGROUND: Handheld computers have recently been used in nursing information systems for patient care, but few studies have explored their impact on users. By understanding clinicians' experiences of using this technology, strategies can be implemented to smooth the change process in adopting their use, thus achieving optimal patient outcomes. METHOD: A descriptive, exploratory approach was used to study nurses' perceptions of using personal digital assistants as part of a hospital information system. A purposive sample of 15 nurses participated in one-to-one, in-depth interviews from February to March 2004. Nurses' perceptions of the adoption process were analysed using Lewin's force field theory of change as a framework. FINDINGS: Nurses initially resisted using the personal digital assistant system (unfreezing stage), then came around to using it (moving stage), and finally adopted the system in their daily practice (re-freezing stage). However, an anticipatory stage also occurred and this could serve as a feedback mechanism to improve the system for current and future use. CONCLUSION: Educational programmes should be provided and strategic planning should be done in the early stage of implementing a policy to adopt new technology. In addition, the adoption process and learning period could be shortened by improving the system's content design. During this transition stage, dual charting should be used as a backup only for a limited time to avoid adding extra work to nurses' already heavy workload. Finally, the concept of confidentiality should be reinforced and stressed early in the educational programme to protect patient data, which can easily be accessed in computerized systems.

Adult↗

The dissemination of a smoking cessation program to 23 antenatal clinics: the predictors of initial program adoption by managers.

OBJECTIVE: To investigate whether the method of dissemination, antenatal clinic practice norms for smoking intervention and subjective evaluation of the attributes of a new smoking cessation program are associated with a nurse unit manager's initial decision to adopt the new program. METHOD: Twenty-three hospital clinics were randomly allocated to two groups which received the program either by simple or intensive dissemination methods. Simple dissemination involved a mailout of the 'Fresh Start' program and intensive dissemination involved a mailout which was enhanced by personal contact with midwifery facilitators who provided support and training for the program. It was hypothesised that intensive dissemination would improve program adoption compared to simple dissemination. It was also hypothesised that managers' perceptions of the program and clinic smoking intervention practice norms would predict program adoption. A hierarchical regression analysis was used to examine the association between these variables and the adoption of program components. RESULTS: The results indicated that the method of dissemination and the managers' perceptions of the program are significant predictors of program adoption. CONCLUSIONS: Although clinic practice norm for smoking cessation education is not a significant predictor of program adoption, it appears to mediate managers' perceptions of the program.

Female↗

Adoption of liquid-based cervical cancer screening tests by family physicians and gynecologists.

OBJECTIVE: To examine reasons for the adoption of liquid-based cervical cancer screening tests. DATA SOURCES/STUDY SETTING: A mailed survey of 250 family physicians and 250 gynecologists in Maryland in 2000. Additional data were obtained from the AMA Master File of Physicians. STUDY DESIGN: Key outcome variables in this cross-sectional survey were early adoption of a liquid-based test by the end of 1997 and overall adoption by the time of the survey. Adoption was viewed in terms of a supply and demand theoretical framework with marketing influencing physician and patient demand as well as supply by insurance companies and laboratories. DATA COLLECTION: Random samples of family physicians and gynecologists were selected from the AMA Master File of Physicians. The overall response rate was 61.9 percent. PRINCIPAL FINDINGS: By 2000, 96 percent of gynecologists and 75 percent of family physicians in Maryland were using liquid-based cervical cancer screening tests, most commonly the ThinPrep Pap Test. Gynecologists were more likely than family physicians to have been early adopters (34 percent versus 5 percent, p<.01). Part of this variation in adoption was due to aggressive marketing to gynecologists, who were more likely than family physicians to receive information in the mail from the test manufacturer (89 percent versus 56 percent, p<.01) and to have been informed by the manufacturer that a patient had inquired about physicians' use of the test (22 percent versus 8 percent, p<.01). CONCLUSIONS: The rapid diffusion of liquid-based cervical cancer screening tests occurred despite general agreement that the Pap smear has been one of the most successful cancer prevention interventions ever. Commercial marketing campaigns appear to contribute to the more rapid rate of diffusion of technology among specialists compared with generalists.

Clinical Competence↗

An analysis of the adoption of managerial innovation: cost accounting systems in hospitals.

The adoption of new medical technologies has received significant attention in the hospital industry, in part, because of its observed relation to hospital cost increases. However, few comprehensive studies exist regarding the adoption of non-medical technologies in the hospital setting. This paper develops and tests a model of the adoption of a managerial innovation, new to the hospital industry, that of cost accounting systems based upon standard costs. The conceptual model hypothesizes that four organizational context factors (size, complexity, ownership and slack resources) and two environmental factors (payor mix and interorganizational dependency) influence hospital adoption of cost accounting systems. Based on responses to a mail survey of hospitals in the Chicago area and AHA annual survey information for 1986, a sample of 92 hospitals was analyzed. Greater hospital size, complexity, slack resources, and interorganizational dependency all were associated with adoption. Payor mix had no significant influence and the hospital ownership variables had a mixed influence. The logistic regression model was significant overall and explained over 15% of the variance in the adoption decision.

Accounting↗

Accelerating U.S. EHR adoption: how to get there from here. recommendations based on the 2004 ACMI retreat.

Despite growing support for the adoption of electronic health records (EHR) to improve U.S. healthcare delivery, EHR adoption in the United States is slow to date due to a fundamental failure of the healthcare information technology marketplace. Reasons for the slow adoption of healthcare information technology include a misalignment of incentives, limited purchasing power among providers, variability in the viability of EHR products and companies, and limited demonstrated value of EHRs in practice. At the 2004 American College of Medical Informatics (ACMI) Retreat, attendees discussed the current state of EHR adoption in this country and identified steps that could be taken to stimulate adoption. In this paper, based upon the ACMI retreat, and building upon the experiences of the authors developing EHR in academic and commercial settings we identify a set of recommendations to stimulate adoption of EHR, including financial incentives, promotion of EHR standards, enabling policy, and educational, marketing, and supporting activities for both the provider community and healthcare consumers.

Diffusion of Innovation↗

Correlates of electronic health record adoption in office practices: a statewide survey.

OBJECTIVE: Despite emerging evidence that electronic health records (EHRs) can improve the efficiency and quality of medical care, most physicians in office practice in the United States do not currently use an EHR. We sought to measure the correlates of EHR adoption. DESIGN: Mailed survey to a stratified random sample of all medical practices in Massachusetts in 2005, with one physician per practice randomly selected for survey. MEASUREMENTS: EHR adoption rates. RESULTS: The response rate was 71% (1345/1884). Overall, while 45% of physicians were using an EHR, EHRs were present in only 23% of practices. In multivariate analysis, practice size was strongly correlated with EHR adoption; 52% of practices with 7 or more physicians had an EHR, as compared with 14% of solo practices (adjusted odds ratio, 3.66; 95% confidence interval, 2.28-5.87). Hospital-based practices (adjusted odds ratio, 2.44; 95% confidence interval, 1.53-3.91) and practices that teach medical students or residents (adjusted odds ratio, 2.30; 95% confidence interval, 1.60-3.31) were more likely to have an EHR. The most frequently cited barriers to adoption were start-up financial costs (84%), ongoing financial costs (82%), and loss of productivity (81%). CONCLUSIONS: While almost half of physicians in Massachusetts are using an EHR, fewer than one in four practices in Massachusetts have adopted EHRs. Adoption rates are lower in smaller practices, those not affiliated with hospitals, and those that do not teach medical students or residents. Interventions to expand EHR use must address both financial and non-financial barriers, especially among smaller practices.

Attitude to Computers↗

Factors influencing the adoption and maintenance of Canadian, facility-based worksite health promotion programs.

PURPOSE: The purpose of this study was to determine senior management's rationale for adopting and maintaining worksite health promotion programs and the congruence of this rationale with the program objectives of health professionals who manage the programs. DESIGN: A multiple case study design was used. SETTING: Nine major Canadian organizations which had adopted facility-based health promotion programs were the settings for this study. DATA COLLECTION: Semi-structured interviews (22 conducted) and two questionnaires (36 completed) were the methods used to collect data. RESPONDENTS: Senior managers involved in program adoption, senior managers responsible for program budgets, and senior health professionals responded to the interviews and questionnaires. RESULTS: Impetus for health promotion program adoption in the organizations we studied had more to do with tangential issues such as an organization moving to a new facility or having access to unused space than with employee health or organizational performance considerations. The most common program adoption rationale was related to employee recruitment/retention. Program continuance was based on process issues such as participation rates and the quality of activity offerings rather than on health or organizational outcomes. While health professionals and senior management both considered human relations and morale more important than cost savings outcomes, health professionals considered cost savings outcomes more important than did senior management. CONCLUSIONS: It is important for health promotion professionals to develop program objectives which are shared by organizational management. Future program adoptions and maintenance will be influenced by closer analyses of the effect of these programs on organizational performance.

Canada↗

Awareness and adoption of a nationally disseminated dietary curriculum.

OBJECTIVE: To identify regional, organizational, and personal characteristics that predict awareness and adoption of a dietary curriculum training and CD among educators. METHODS: A cross-sectional study of educators (n=675) representing 48 states report program awareness and factors that influenced adoption. RESULTS: Among those surveyed, 354 educators were aware (52%) of the CD and 192 educators adopted it (54%). Adopters were nearly 8 times more likely to identify training time and nearly 7 times more likely to identify CD training method as influencing adoption. CONCLUSION: Although regional and organizational characteristics are predictors of awareness, these variables were less likely to predict adoption of such programs.

Adolescent↗