Tissue collection for correlative studies in childhood cancer clinical trials: ethical considerations and special imperatives.

Federal regulations prescribe distinct protections for children participating in research studies. Procedures for collecting tissue specimens from children solely for research purposes must pose no more than a minor increase over minimum risk, thereby limiting the approvable correlative biologic studies to evaluate molecularly targeted agents in children with cancer. Ethical issues arise when approvable correlative studies are a mandatory component of an early-phase pediatric clinical trial of new anticancer agents. The National Cancer Institute Cancer Therapy Evaluation Program sponsored a workshop in 2002 to discuss tissue collection for correlative biologic studies in early-phase childhood cancer clinical studies of molecularly targeted agents. Workshop participants recommended the following: (1) tissue specimens for correlative studies should provide vital clinical and scientific results to qualify for early-phase pediatric study consideration; (2) parents should receive a realistic appraisal of the risks, requirements, and potential for benefit of phase I protocol participation; (3) investigators should clearly distinguish clinically necessary procedures from research procedures of no benefit to the child to improve correlative study informed consent; and (4) participation in correlative research studies included in clinical trials generally should be voluntary. The need to acquire important biologic data regarding new molecular agents will challenge the ingenuity of pediatric cancer researchers, necessitating the application of highly sensitive laboratory assay methods, new imaging procedures, and preclinical models of childhood cancer. Such innovative methods can allow necessary scientific information to be obtained while simultaneously respecting the protections appropriately afforded to children participating in research studies and minimizing the burden of research participation for children with cancer and their families.     

Comparison of DSM-III-R and childhood autism rating scale diagnoses of autism

The purpose of this study was to clarify the issue of whether DSM-III-R (American Psychological Association [APA], 1987) over-or underdiagnoses autism by comparing this diagnostic system to a well-established objective measure of diagnosis, the Childhood Autism Rating Scale (CARS). A secondary goal was to determine which of the 16 criteria are the best discriminators of autism. DSM-III-R, CARS, and clinical diagnoses of 138 consecutive admissions to a statewide program for the diagnosis and treatment of autistic and related communication-handicapped individuals (Division TEACCH in North Carolina) were compared. Results indicated a generally high degree of agreement on the diagnosis of autism using the three systems. Within this tratment-oriented program, the CARS and clinical ratings diagnosed a greater number of cases as autistic than did the DSM-III-R criteria, suggesting that DSM-III-R slightly underdiagnosed autism. The criteria that most strongly related to the diagnosis of autism regardless of the system were lack of awareness of others, abnormal social play, an impaired ability to make friends, abnormal nonverbal communication, stereotypic body movements, and restricted range of interests.     

Technology anxiety as a potential mediating factor in response to medical technology

Technology anxiety, defined as a fear of working with medical equipment, was measured via the use of the Technology Response Questionnaire. Nurses (N=414) working on nine types of nursing units at two hospitals participated in the study. Nurses working on psychiatric units were found to be most anxious about working with medical equipment, while nurses working on surgical and adult intensive care units were least anxious. A comparison of the nurses who were highest and lowest on technology anxiety indicated that those who were most anxious about technology were less positive toward computers, felt more stressed by their work, were lower on job satisfaction, less positive toward the physicians they worked with, lower on personality scales of autonomy and adaptability, were less likely to do care planning regularly or to use nursing diagnoses, and tended to be older than less anxious nurses.     

Conference report the children (ni) order - challenges ahead

The long awaited new Children (NI) Order has yet to be implemented but there is no doubt about the significance in relation to providing an important watershed for the future development of Child Care Services in Northern Ireland. The recent conference organised by BASW (NI) in association with the Children (NI) Order Group provided a forum for the dissemination of information of the experiences of local authorities and judiciary in England since the Children Act 1989- This unique blend of the social work/legal context coupled with the keynote presentation and overview by Baroness Faithful offered the first major conference in the Province to address the main issues posed by the legislation. The conference attracted over 250 delegates from a multidisciplinary background and key Department of Health and Social Services personnel. The programme content included conference speakers from England and Northern Ireland and reflected the key roles played by the judiciary, social services management and the social services inspectorate. Baroness Faithful is well known in child care circles and recognised as a major contributor to the development of the Children Act. Her services for families and children in Northern Ireland and the potential strengths to be gained from its implementation set the tone for the conference. She also indicated the necessity of extending training to three years would be raised agin for debate. This was by An Overview of the English Experience of the Children Act 1989 with speaker Kay Birch from the Lord Chancellor's office, Mary Barnard J.P., Chairman of the Family Proceedings Committee and Judge Nigel Fricker Q.C., Designated Family Judge. They highlighted the importance of interdisciplinary training and partnership, the development of good information systems, the significant change in culture required by such aspects as the “non intervention” policy and the role of lay magistrates and the changes in court procedures.     

Repetitive, negligible force reaching in rats induces pathological overloading of upper extremity bones.

Work-related repetitive motion disorders are costly. Immunohistochemical changes in bones resulting from repetitive reaching and grasping in 17 rats were examined. After 3-6 weeks, numbers of ED1+ macrophages and osteoclasts increased at periosteal surfaces of sites of muscle and interosseous membrane attachment and metaphyses of reach and nonreach forelimbs. These findings indicate pathological overloading leading to inflammation and subsequent bone resorption. INTRODUCTION: Sixty-five percent of all occupational illnesses in U.S. private industry are attributed to musculoskeletal disorders arising from the performance of repeated motion, yet the precise mechanisms of tissue pathophysiology have yet to be determined for work-related musculoskeletal disorders. This study investigates changes in upper extremity bone tissues resulting from performance of a voluntary highly repetitive, negligible force reaching and grasping task in rats. MATERIALS AND METHODS: Seventeen rats reached an average of 8.3 times/minute for 45-mg food pellets for 2 h/day, 3 days/week for up to 12 weeks. Seven rats served as normal or trained controls. Radius, ulna, humerus, and scapula were collected bilaterally as follows: radius and ulna at 0, 3, 4, 5, 6, and 12 weeks and humerus and scapula at 0, 4, and 6 weeks. Bones were examined for ED1-immunoreactive mononuclear cells and osteoclasts. Double-labeling immunohistochemistry was performed for ED1 (monocyte/macrophage lineage cell marker) and TRACP (osteoclast marker) to confirm that ED1+ multinucleated cells were osteoclasts. Differences in the number of ED1+ cells over time were analyzed by ANOVA. RESULTS: Between 3 and 6 weeks of task performance, the number of ED1+ mononuclear cells and osteoclasts increased significantly at the periosteal surfaces of the distal radius and ulna of the reach and nonreach limbs compared with control rats. These cells also increased at periosteal surfaces of humerus and scapula of both forelimbs by 4-6 weeks. These cellular increases were greatest at muscle attachments and metaphyseal regions, but they were also present at some interosseous membrane attachments. The number of ED1+ cells decreased to control levels in radius and ulna by 12 weeks. CONCLUSIONS: Increases in ED1+ mononuclear cells and osteoclasts indicate that highly repetitive, negligible force reaching causes pathological overloading of bone leading to inflammation and osteolysis of periosteal bone tissues.     

Establishing a cancer center data bank and biorepository for multidisciplinary research.

The establishment of a biorepository with linkage to clinical and epidemiologic data will provide an invaluable resource for cancer research, including studies of cancer etiology, progression, and prognosis, as well as development of biomarkers for early detection. Developing an infrastructure for a biorepository linked to clinical, pathologic, and epidemiologic data requires significant efforts in strategic planning for efficient means to ascertain, identify, and consent participants, as well as guidelines for blood collection, processing, and storage while maintaining participant privacy rights. In this report, we present an approach to developing a Data Bank and Biorepository at our own institution, with discussion of elements to be considered when establishing such a bank.