191 research outputs found

    Influence of total body irradiation on bone marrow stroma

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    TBI containing regimens followed by hematopoietic stem cell transplantation in acute lymphoblastic leukemia of childhood

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    Acute lymphoblastic leukemia in childhood is the domain of chemotherapy giving rates of event free survival of up to 80% for the vast majority of children. Only 6% of well defined high risk patients during frontline treatment but on the other side the majority of children following relapse do not have a satisfying chance of cure by chemotherapy alone. The controversy persists, whether hematopoietic stem cell transplants provide a superior chance of cure. The answer can only be given by c1early defined prospective studies including patients with the intention to transplant but finally events before the transplant can be performed. The BMF group is currentlyconducting such a study during frontline therapy. Out of 3050 children with newly diagnosed ALL 197 patients fulfilled the criteria for a matched related bone marrow transplantation. An acceptable family donor was available in 53 children, which is in the expected range of 27% of HLA-identical siblings or family members in Germany. Only 30 children have been transplanted at the end, using a conditioning regimen of fractionated TBI (6 × 2 Gy) and VP16 (60 mg/kg). Although the transplanted children have an EFS of about 70% and the whole group with a donor and the intention to transplant of about 60% compared to 30% EFS in the complementary group, the transplant group is by far too small lead to furtherincrease of survival in the whole group of children with ALL. Some children received alternative conditioning regimens with obviously less chance of cure. But the major question for the future remains the donor availability for high risk frontline patients but more important for relapse patients in order to prove the transplant approach in general in such patients. Clearly autografts seem not to give any advantage in these type of children, unless any new approach of maintenance/immunotherapy is providing a significant additional effect. Unrelated grafts on the other side might be one option but still require a significant reduction of treatment risks, which are currently still in the range of 30–50% compared to 10% and less in matched related transplants. Cord blood transplants especially – in children may be superior to adult marrow or peripheral blood stem cell transplants. And finally, first steps have been done now to overcome the high rejection rate of mismatched related grafts by increasing for example the stem cell dose and thus offering another source of stem cell grafts also for ALL patients. Unfortunately, also these transplants are still associated with high transplant related risks. Almost all centers employing haploidentical stem cell transplants are using TBI containing regimens even with an increased dose. Our own approach on this fields is to understand the side effects of conditioning regimens containing TBI on the homing process of stem cells in the microenvironment of the marrow, and to overcome ex vivo as well as in vivo such critical dysfunctions with the aim to ensure engraftment and limit transplant risks by accelerating the hematopoietic and lymphopoietic reconstitution. This model will be discussed

    Phenotype correction of fanconi anemia group a hematopoietic stem cells using lentiviral vector

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    AbstractFanconi anemia (FA) is an autosomal recessive disease characterized by progressive bone marrow failure due to defective stem cell function. FA patients' cells are hypersensitive to DNA cross-linking agents such as mitomycin C (MMC), exposure to which results in cytogenetic aberrations and cell death. To date Moloney murine leukemia virus vectors have been used in clinical gene therapy. Recently, third-generation lentiviral vectors based on the HIV-1 genome have been developed for efficient gene transfer to hematopoietic stem cells. We generated a self-inactivating lentiviral vector expressing the FA group A cDNA driven by the murine stem cell virus U3 LTR promoter and used the vector to transduce side-population (SP) cells isolated from bone marrow of Fanconi anemia group A (Fanca) knockout mice. One thousand transduced SP cells reconstituted the bone marrow of sublethally irradiated Fanca recipient mice. Phenotype correction was demonstrated by stable hematopoiesis following MMC challenge. Using real-time PCR, one proviral vector DNA copy per cell was detected in all lineage-committed cells in the peripheral blood of both primary and secondary recipients. Our results suggest that the lentiviral vector transduces stem cells capable of self-renewal and long-term hematopoiesis in vivo and is potentially useful for clinical gene therapy of FA hematopoietic cells

    Consensus of German Transplant Centers on Hematopoietic Stem Cell Transplantation in Fanconi Anemia

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    Allogeneic hematopoietic stem cell transplantation (HSCT) is currently the only curative therapy for the severe hematopoietic complications associated with Fanconi anemia (FA). In Germany, it is estimated that 10–15 transplants are performed annually for FA. However, because FA is a DNA repair disorder, standard conditioning regimens confer a high risk of excessive regimen-related toxicities and mortality, and reduced intensity regimens are linked with graft failure in some FA patients. Moreover, development of graft-versus-host disease is a major contributing factor for secondary solid tumors. The relative rarity of the disorder limits HSCT experience at any single center. Consensus meetings were convened to develop a national approach for HSCT in FA. This manuscript outlines current experience and knowledge about HSCT in FA and, based on this analysis, general recommendations reached at these meetings

    Screening for Impaired Visual Acuity in Older Adults: US Preventive Services Task Force Recommendation Statement

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    DESCRIPTION: Update of the US Preventive Services Task Force (USPSTF) recommendation on screening for impaired visual acuity in older adults. METHODS: The USPSTF reviewed the evidence on screening for visual acuity impairment associated with uncorrected refractive error, cataracts, and age-related macular degeneration among adults 65 years or older in the primary care setting; the benefits and harms of screening; the accuracy of screening; and the benefits and harms of treatment of early vision impairment due to uncorrected refractive error, cataracts, and age-related macular degeneration. POPULATION: This recommendation applies to asymptomatic adults 65 years or older who do not present to their primary care clinician with vision problems. RECOMMENDATION: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for impaired visual acuity in older adults. (I statement)

    The propensity to adopt evidence-based practice among physical therapists

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    <p>Abstract</p> <p>Background</p> <p>Many authors, as well as the American Physical Therapy Association, advocate that physical therapists adopt practice patterns based on research evidence, known as evidence-based practice (EBP). At the same time, physical therapists should be capable of integrating EBP within the day-to-day practice of physical therapy. The purpose of this study was to determine the extent to which personal characteristics and the characteristics of the social system in the workplace influence the propensity of physical therapists to adopt EBP.</p> <p>Methods</p> <p>The study used a 69 item mailed self-completion questionnaire. The questionnaire had four major sections. The first three sections were each drawn from a different theoretical framework and from different authors' work. The instrument was developed to capture the propensity of physical therapists to adopt EBP, characteristics of the social system in the workplace of physical therapists, personal characteristics of physical therapists, and selected demographic variables of physical therapists. The eligible population consisted of 3,897 physical therapists licensed by the state of Georgia in the United States of America. A random sample of 1320 potential participants was drawn.</p> <p>Results</p> <p>939 questionnaires were returned for a response rate of 73%. 831 of the participants' questionnaires were useable and became the basis for the study. There was a moderate association between desire for learning (<it>r </it>= .36, <it>r</it><sup>2 </sup>= .13), highest degree held (<it>r </it>= .29, <it>r</it><sup>2 </sup>= .08), practicality (<it>r </it>= .27, <it>r</it><sup>2 </sup>= .07) and nonconformity (<it>r </it>= .24, <it>r</it><sup>2 </sup>= .06) and the propensity to adopt EBP. A negative correlation was found between age, years licensed and percentage of time in direct patient care. The findings demonstrated that the best three variables for predicting the propensity to adopt EBP in physical therapy were: desire for learning, highest degree held, and practicality.</p> <p>Conclusion</p> <p>The study confirms there is no single factor to facilitate research evidence into day-to-day practice. Multiple practice change strategies will be needed to facilitate change in practice.</p

    Using microbiological data to improve the use of antibiotics for respiratory tract infections: a protocol for an individual patient data meta-analysis

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    Background Resistance to antibiotics is rising and threatens future antibiotic effectiveness. ‘Antibiotic targeting’ ensures patients who may benefit from antibiotics receive them, while being safely withheld from those who may not. Point-of-care tests may assist with antibiotic targeting by allowing primary care clinicians to establish if symptomatic patients have a viral, bacterial, combined, or no infection. However, because organisms can be harmlessly carried, it is important to know if the presence of the virus/bacteria is related to the illness for which the patient is being assessed. One way to do this is to look for associations with more severe/prolonged symptoms and test results. Previous research to answer this question for acute respiratory tract infections has given conflicting results with studies has not having enough participants to provide statistical confidence. Aim To undertake a synthesis of IPD from both randomised controlled trials (RCTs) and observational cohort studies of respiratory tract infections (RTI) in order to investigate the prognostic value of microbiological data in addition to, or instead of, clinical symptoms and signs. Methods A systematic search of Cochrane Central Register of Controlled Trials, Ovid Medline and Ovid Embase will be carried out for studies of acute respiratory infection in primary care settings. The outcomes of interest are duration of disease, severity of disease, repeated consultation with new/worsening illness and complications requiring hospitalisation. Authors of eligible studies will be contacted to provide anonymised individual participant data. The data will be harmonised and aggregated. Multilevel regression analysis will be conducted to determine key outcome measures for different potential pathogens and whether these offer any additional information on prognosis beyond clinical symptoms and signs. Trial registration PROSPERO Registration number: CRD42023376769

    Are decision trees a feasible knowledge representation to guide extraction of critical information from randomized controlled trial reports?

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    <p>Abstract</p> <p>Background</p> <p>This paper proposes the use of decision trees as the basis for automatically extracting information from published randomized controlled trial (RCT) reports. An exploratory analysis of RCT abstracts is undertaken to investigate the feasibility of using decision trees as a semantic structure. Quality-of-paper measures are also examined.</p> <p>Methods</p> <p>A subset of 455 abstracts (randomly selected from a set of 7620 retrieved from Medline from 1998 – 2006) are examined for the quality of RCT reporting, the identifiability of RCTs from abstracts, and the completeness and complexity of RCT abstracts with respect to key decision tree elements. Abstracts were manually assigned to 6 sub-groups distinguishing whether they were primary RCTs versus other design types. For primary RCT studies, we analyzed and annotated the reporting of intervention comparison, population assignment and outcome values. To measure completeness, the frequencies by which complete intervention, population and outcome information are reported in abstracts were measured. A qualitative examination of the reporting language was conducted.</p> <p>Results</p> <p>Decision tree elements are manually identifiable in the majority of primary RCT abstracts. 73.8% of a random subset was primary studies with a single population assigned to two or more interventions. 68% of these primary RCT abstracts were structured. 63% contained pharmaceutical interventions. 84% reported the total number of study subjects. In a subset of 21 abstracts examined, 71% reported numerical outcome values.</p> <p>Conclusion</p> <p>The manual identifiability of decision tree elements in the abstract suggests that decision trees could be a suitable construct to guide machine summarisation of RCTs. The presence of decision tree elements could also act as an indicator for RCT report quality in terms of completeness and uniformity.</p
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