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PubMed1993

Guidelines for the adoption of new technologies: a prescription for uncontrolled growth in expenditures and how to avoid the problem.

The guidelines proposed by Laupacis and associates do not stem from economic theory and are a prescription for uncontrolled growth in health care expenditure. In particular, cost-effectiveness ratios provide information relevant to allocation decisions only in very special circumstances that do not usually apply in practice. When two interventions are compared a positive cost-effectiveness ratio (the common case) can tell us, at best, what additional costs will be incurred to generate the additional outcomes. From an economic perspective the information required to determine the attractiveness of a new technology is different: the source of the additional resource requirements must be identified and the opportunity cost of their redeployment estimated. Because the cost-effectiveness ratio (cost/-QALY) is sensitive to the method chosen to calculate QALYs, guidelines that do not specify (or justify) the appropriate method for calculating outcomes are unlikely to produce comparable results (or common yardsticks). In a health care system such as Canada's in which there is always pressure to introduce more effective technology, even if it is more costly, there is a risk of using such noncomparable data to justify adoption of particular technologies. The method of technology evaluation proposed by us is consistent with the stated goal of maximizing the community's health-related well-being for a given level of resources allocated to health care and ensures that new technologies are adopted only if this adoption represents an improvement in resource allocation.

Canada↗
PubMedDate not supplied

The effects of individual and nursing-unit characteristics on willingness to adopt an innovation. A multilevel analysis.

In this study, the authors investigate the effects of efficacy and cooperativeness on willingness to adopt an innovation at the individual and nursing-unit levels. The results of a field report showed that efficacy was significantly associated with willingness to adopt an innovation at both the individual and nursing-unit levels, whereas cooperativeness was significant only at the individual level. These results suggest that examining innovation adoption at multiple levels provides more valid information than does examining it at a single level.

Adult↗
PubMed1997

Translating guidelines into practice. A systematic review of theoretic concepts, practical experience and research evidence in the adoption of clinical practice guidelines.

OBJECTIVE: To recommend effective strategies for implementing clinical practice guidelines (CPGs). DATA SOURCES: The Research and Development Resource Base in Continuing Medical Education, maintained by the University of Toronto, was searched, as was MEDLINE from January 1990 to June 1996, inclusive, with the use of the MeSH heading "practice guidelines" and relevant text words. STUDY SELECTION: Studies of CPG implementation strategies and reviews of such studies were selected. Randomized controlled trials and trials that objectively measured physicians' performance or health care outcomes were emphasized. DATA EXTRACTION: Articles were reviewed to determine the effect of various factors on the adoption of guidelines. DATA SYNTHESIS: The articles showed that CPG dissemination or implementation processes have mixed results. Variables that affect the adoption of guidelines include qualities of the guidelines, characteristics of the health care professional, characteristics of the practice setting, incentives, regulation and patient factors. Specific strategies fell into 2 categories: primary strategies involving mailing or publication of the actual guidelines and secondary interventional strategies to reinforce the guidelines. The interventions were shown to be weak (didactic, traditional continuing medical education and mailings), moderately effective (audit and feedback, especially concurrent, targeted to specific providers and delivered by peers or opinion leaders) and relatively strong (reminder systems, academic detailing and multiple interventions). CONCLUSIONS: The evidence shows serious deficiencies in the adoption of CPGs in practice. Future implementation strategies must overcome this failure through an understanding of the forces and variables influencing practice and through the use of methods that are practice- and community-based rather than didactic.

Clinical Trials as Topic↗
PubMed1976

The induction of hapten-specific immunologic tolerance and immunity in B lymphocytes. I. The effect of delayed immunization on the adoptive response to TNP-LPS.

An improved adoptive transfer procedure has been developed for the thymus-independent conjugate TNP-LPS. This technique involving delayed immunization results in increased sensivity and makes possible studies of various cell types, the response of which is normally very low or which are difficult to manipulate experimentally in situ. The standard adoptive immune response of adult spleen cells to TNP-LPS was low in comparison to the primary AFC response of intact mice. Adult bone marrow cells gave a 30-fold lower and neonatal spleen cells an 8-fold lower adoptive response than an equivalent number of adult spleen cells. If the administration of antigen was delayed past the normal time of immunization (1 hr after cell transfer), the resulting AFC response of adult spleen, adult bone marrow, and neonatal cells was enhanced. The peak response occurred with a delay interval of 4 days, and the magnitude decreased with greater delay. Part of the reason for the decline was an acceleration in the attainment of a peak response in mice given antigen past the 4-day optimum. The enhancement of the adult splenic response was not restricted to the antigen TNP-LPS, and was a transferrable phenomenon which did not require antigen to persist past the 4-day optimum delay period. The ineffectiveness of host pre-irradiation indicated that host recovery alone was not involved. Although the results are more compatible with B cell proliferation causing the enhancement, a combination of effects may be involved.

Animals↗
PubMed1998

Quality improvement measures adopted by the Italian National Health Service.

The reform process underway within the Italian National Health System is aimed at making decision makers responsible for appropriate and efficient resource utilisation and at ensuring quality of care, eliminating conflict between fairness, quality and cost control. The risk for the quality of the services provided entailed by resource rationalisation is avoidable and controllable. This article explains how the Italian NHS has managed the reform process assuring quality improvement, and describes the policy and the tools adopted. As well as involving all players and the system as a whole in constant improvement, the Italian NHS's policy in pursuing quality of care is based on the adoption of a wide range of measures: measurement of health care and of clinical outcomes, systematic data collection, team work and protocols. The tools adopted, currently under implementation, to support quality control are: an integrated system of indicators for measuring efficiency and quality of NHS structures (demand and accessibility indicators, resource related indicators, activity indicators and result indicators); compulsory accreditation as a prerequisite for health care providers; a system to monitor and control the effects of the new prospective payment system; clinical guidelines (each related to a specific clinical problem); a menu of services (Carta dei Servizi) released by all NHS accredited service providers with full information and warranties regarding the services provided and their quality.

Health Care Reform↗
PubMed2001

Stability of genetic and environmental influences on reading performance at 7, 12, and 16 years of age in the Colorado Adoption Project.

The etiology of the longitudinal stability of reading performance was assessed by analyzing data from adoptive and nonadoptive sibling pairs (206 pairs at age 7, 195 pairs at age 12, and 110 pairs at age 16) tested in the Colorado Adoption Project (CAP). Results of longitudinal behavioral genetic analyses confirmed previous findings of moderate genetic influence on individual differences in reading performance at 7 and 12 years of age (a2 = .44 and .38, respectively), with somewhat higher heritability at age 16 (a2 = .57). Corresponding shared environmental influences were negligible (c2 = .07, .09, and .07). Moreover, common genetic influences were responsible for 66% of the observed stability (rp) between ages 7 and 12 (.62), 62% of that between ages 12 and 16 (rp = .74), and 88% of that between ages 7 and 16 (rp = .55). Of particular interest, no new heritable variation was detected at either 12 or 16 years of age, suggesting that genetic influences at 7 years of age are amplified at the later ages. In contrast, new nonshared environmental influences (including measurement error) were manifested at each age, suggesting the possible importance of nonshared environmental factors (e.g., instructional methods, teachers, peers) for the development of individual differences in reading performance between 7 and 16 years of age.

Adolescent↗
PubMedDate not supplied

Generating potent Th1/Tc1 T cell adoptive immunotherapy doses using human IL-12: Harnessing the immunomodulatory potential of IL-12 without the in vivo-associated toxicity.

Interleukin (IL)-12 is a cytokine originally identified from medium conditioned by an Epstein-Barr virus transformed cell line. IL-12 has been shown to increase IFN-gamma secretion from NK and T cells, significantly enhance cytolytic activity in both of these cell types, and promote the development of Th1/Tc1 immune responses. These properties make IL-12 an attractive candidate for the development of various clinical protocols ranging from the treatment of viral diseases to tumor immunotherapy. The initial attempts to use IL-12 in the treatment of tumors demonstrated toxicity at potentially therapeutic doses. To circumvent the toxicity associated with IL-12 administration, the authors have developed an adoptive immunotherapy protocol that uses IL-12 for a brief period during ex vivo T cell activation. They show that IL-12 conditioning may be achieved without altering the growth characteristics of the in vitro expanding T cells. T cells generated in the presence of IL-12 show a shift to a Th1/Tc1 dominant phenotype. The resultant cells are more potent killers in vitro and in vivo as assessed by CTL assays and tumor regression. The ability to harness the potent Th1/Tc1 generating potential of IL-12 while avoiding its associated in vivo toxicity has the potential to benefit a large number of clinical trial protocols using adoptive transfer of T cells specific for tumors, viruses, or intracellular pathogens.

Adoptive Transfer↗
PubMedDate not supplied

Adoptive transfer of anti-idiotypic T cells cure mice of disseminated B cell lymphoma.

There is extensive interest in idiotypic vaccination as a treatment of lymphoma. An alternative approach is the adoptive transfer of in vitro generated T cells. This strategy has been used to treat posttransplantation EBV-related diseases. The ability to generate in vitro T cells to peptides derived from immunoglobulin idiotypes raises the possibility of directly using such cells as a treatment of lymphoma. Investigating the adoptive transfer of specific T cells to idiotype derived peptides in a murine lymphoma model is therefore an important part of the clinical translation of this alternative approach. We have generated an idiotype-specific T cell line, able to recognise a defined, naturally processed idiotype-derived epitope. This line has been used to successfully treat mice with disseminated lymphoma supporting the clinical use of idiotype specific T cells.

Adenoviridae↗
PubMedDate not supplied

Targeting tumours by adoptive transfer of immune cells.

1. Surgery, radiotherapy and chemotherapy are the most widely used and well-established modalities for treating malignant diseases. Surgery is used to excise solid tumours and radiotherapy/chemotherapy are used for the treatment of liquid tumours and for solid tumours where there is a risk of micrometastases. A major drawback for both radiotherapy and chemotherapy is their lack of specificity for tumour cells. Both these treatments can destroy normal bone marrow cells and result in severe side-effects. 2. The impairment of haemapoiesis due to bone marrow destruction combined with the use of toxins in chemotherapy that inhibit the proliferation of immune cells leaves many patients immunocompromised. This complicates the development of prophylactic (vaccine) strategies for tumours where patients are undergoing conventional therapy. 3. An alternative approach is to expand and activate tumour-specific immune cells in vitro that can then be adoptively transferred back in large numbers. This is defined as adoptive immunotherapy and has the advantage of potentially bypassing the immuno-inhibitory effects of conventional therapies. 4. Transferred immune cells have been shown to mediate tumour regression in patients by both direct and indirect mechanisms. The immune cells used include tumour reactive T lymphocytes and dendritic cells, which elicit tumour specific responses. 5. Many novel cell-based immunotherapeutic strategies developed in murine tumour models are now being applied in human clinical trials. The malignancies targeted include melanoma, chronic myelogenous leukaemia and breast, ovarian, colon and kidney cancers. In the present review, we discuss these novel cell-based strategies and the implications they have for the future treatment of human malignancies.

Adoptive Transfer↗
PubMed2006

Adoptive T-cell transfer in cancer immunotherapy.

Adoptive T-cell therapy has definite clinical benefit in relapsed leukaemia after allogeneic transplant and in Epstein-Barr virus-associated post-transplant lymphoproliferative disease. However, the majority of tumour targets are weakly immunogenic self-antigens and success has been limited in part by inadequate persistence and expansion of transferred T cells and by tumour-evasion strategies. Adoptive immunotherapy presents the opportunity to activate, expand and genetically modify T cells outside the tolerising environment of the host and a number of strategies to optimize the cellular product, including gene modification and modulation of the host environment, in particular by lymphodepletion, have been developed.

Adoptive Transfer↗
PubMed2006

Adoptive transfer of vaccine-induced peripheral blood mononuclear cells to patients with metastatic melanoma following lymphodepletion.

Cancer vaccines can induce the in vivo generation of tumor Ag-specific T cells in patients with metastatic melanoma yet seldom elicit objective clinical responses. Alternatively, adoptive transfer of autologous tumor-infiltrating lymphocytes (TIL) can mediate tumor regression in 50% of lymphodepleted patients, but are logistically and technically difficult to generate. In this study, we evaluated the capability of vaccine-induced PBMC to mediate tumor regression after transfer to patients receiving the same chemotherapy-induced lymphodepletion used for TIL transfer therapy. Autologous PBMC from nine gp100-vaccinated patients with metastatic melanoma were stimulated ex vivo with the gp100:209-217(210M) peptide and transferred in combination with high-dose IL-2 and cancer vaccine. Transferred PBMC contained highly avid, gp100:209-217 peptide-reactive CD8(+) T cells. One week after transfer, lymphocyte counts peaked (median of 14.3 x 10(3) cells//microl; range of 0.9-59.7 x 10(3) cells/microl), with 56% of patients experiencing a lymphocytosis. gp100:209-217 peptide-specific CD8(+) T cells persisted at high levels in the blood of all patients and demonstrated significant tumor-specific IFN-gamma secretion in vitro. Melanocyte-directed autoimmunity was noted in two patients; however, no patient experienced an objective clinical response. These studies demonstrate the feasibility and safety of using vaccine-induced PBMC for cell transfer, but suggests that they are not as effective as TIL in adoptive immunotherapy even when transferred into lymphodepleted hosts.

Adoptive Transfer↗
PubMed1988

Adoption leave.

As of 1987, a private-sector employee in Luxembourg adopting a child of primary school age is entitled to eight weeks' parental leave. The leave may be taken by either parent. The leave is increased to 12 weeks if the employee adopts more than one child.

Adoption↗
PubMed1953

Hereditary influences in relation to the problem of child adoption.

There is little exact information on the hereditary influences which are of greatest interest from the social and educational points of view. Many genes are involved in the origins of socially significant traits and there are usually many steps in the causal chain linking gene to trait. The value of genetical judgements is thus limited; they cannot be substituted for facts ascertained about the physical and mental state of the child itself at the time of adoption. Information on the family occurrence of recessive autosomal or sex-linked traits may be used for predicting the likelihood of the onset of diseases later on in life. The knowledge that a rare dominant abnormality is present in a close relative is especially important if the close relative is the subject's own parent. But most genetical problems in adoption cases concern graded characters, and here prediction can only be very tentative. A definite degree of likeness obtains within families for graded characters, but the genetical divergence may be considerable, and it can be accentuated by environment.

Adoption↗
PubMed1987

Medical problems of foreign-born adopted children.

Over 8000 foreign-born children, almost all from third-world countries, are adopted by citizens of the United States each year. Most primary care practitioners do not have enough experience to evaluate and manage their problems efficiently. We reviewed the medical care of the foreign-born adoptees followed up in a single pediatric group practice. The 128 children arrived from one of eight countries in Asia or Latin America at ages ranging from 1 month to 10 years; 57% were female. The median duration of follow-up was 20 months. The most common problems identified included deficient immunizations (37%), intestinal parasites (29%), emotional or behavioral problems (22%), skin diseases (16%), estimated age (12%), scabies and/or lice (10%), and congenital anomales (10%). Twenty-one other classes of problems were identified, including developmental delay, lactose intolerance, vision and hearing deficits, and chronic hepatitis B carrier status. At arrival or within one month, 49% of the children had acute infectious diseases, including upper respiratory tract infection, otitis media, rubeola, varicella, and mumps. Nineteen percent of the children underwent surgical procedures ranging from circumcision to cleft lip-palate repair; 46% of these children were never screened for hepatitis B. Fourteen percent were hospitalized at least once, 5% within the first month after arrival. We developed a simple protocol to screen foreign-born adopted children, allowing rapid identification of treatable problems at the least cost and inconvenience to the family. Thirty-six percent of the families made at least one preadoption visit, permitting an explanation of the protocol and potential problems before the child's arrival.

Adoption↗
PubMed1981

An independent analysis of the Copenhagen sample of the Danish adoption study of schizophrenia. II. The relationship between schizotypal personality disorder and schizophrenia.

To assess the relationship between schizophrenia and schizotypal personality disorder (SPD) as defined in DSM-III, the interviews of relatives from the Danish Adoption Study of Schizophrenia were independently and blindly reevaluated. The prevalence of SPD was significantly higher in the biologic relatives of the schizophrenic adoptees than in the biologic relatives of matched controls and was low and equal in the two groups of adoptive relatives. Compared with "borderline" and uncertain borderline schizophrenia as defined by Kety and co-workers, the criteria for SPD were more specific but less sensitive in identifying biologic relatives of schizophrenics. In this sample, SPD has a strong genetic, but no familial-environmental, relationship to schizophrenia. These results replicate the findings of Kety and co-workers on borderline schizophrenia and support the validity of the diagnosis of SPD.

Adoption↗
PubMed1982

An independent analysis of the Copenhagen sample of the Danish adoption study of schizophrenia. IV. The relationship between major depressive disorder and schizophrenia.

Genetic investigations offer one approach at evaluating the validity of Kraepelin's division of the functional psychoses into two major groups, schizophrenia and affective illness. In this study, DSM-III criteria for major depressive disorder (MDD) were blindly applied to the interviews with relatives from the Copenhagen sample of the Danish Adoption Study of Schizophrenia. No significant difference was found in the prevalence of MDD in the biological relatives of the control adoptees and the biological relatives of all the schizophrenic or only the chronic schizophrenic adoptees. Furthermore, no difference in the prevalence of MDD was found in the adoptive relatives of the schizophrenics and control subjects. These results support neither a genetic nor a familial-environmental link between schizophrenia and MDD and support the validity of the diagnostic division between them established by Kraepelin.

Adoption↗
PubMed1982

An independent analysis of the Copenhagen sample of the Danish Adoption Study of Schizophrenia. V. The relationship between childhood social withdrawal and adult schizophrenia.

This study examines the relationship between childhood behavioral disturbances and adult schizophrenia in the Copenhagen sample of the Danish Adoption Study of Schizophrenia. Using blindly rated information from interviews with adult relatives, childhood social withdrawal (CSW) and antisocial, but not anxious, traits were significantly more common in the biologic relatives of all adoptees with schizophrenia and "chronic schizophrenia" than in the biologic relatives of control adoptees. These traits were equally frequent in the adoptive relatives of schizophrenics and controls. Biologic relatives of schizophrenics with CSW were at high risk as adults for development of schizophrenia spectrum disorders. Although retrospective bias in reporting childhood traits cannot be ruled out, these results suggest that CSW and possibly antisocial traits are linked genetically to adult schizophrenia.

Adoption↗
PubMed1984

An adoption study of somatoform disorders. I. The relationship of somatization to psychiatric disability.

The relationship between psychiatric impairment and disability due to somatic complaints was studied in 859 women adopted at an early age by nonrelatives in Sweden. The clinical data were derived from the comprehensive registrations for all medical treatment and sick-leave compensation that are kept about Swedish residents by the National Health Insurance Board. The adoptees were compared with nonadopted controls who were individually matched for social and demographic variables. We identified a somatization syndrome that is consistently associated with psychiatric impairment and repeated brief periods of disability with chief complaints of headache, backache, and abdominal distress on different occasions. A method for clinically distinguishing "somatizers" from other women was derived in one sample and was shown to have a classification accuracy of 97% in a replication sample. Somatizers accounted for 36% of all cases of psychiatric disability and 48% of all sick-leave occasions in adopted women. Compared with nonadoptees, there was an excess of somatizers in adoptees, a population known to have an excess of biological parents who are criminal and/or alcoholic.

Adoption↗