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To evaluate the relative effectiveness of 2 theoretically-informed approaches to preventing the adverse sequelae of maltreatment in infants: Psychoeducational Home Visitation (PHV) and Infant-Parent Psychotherapy (IPP). Non-maltreated infants and their mothers serve as a comparison.~Maltreated infants and their mothers are randomly assigned to 1 of 3 types of intervention for 12 months: 1) Services routinely available in the community when a family is reported for child maltreatment (Child Protective Services, CPS); 2) CPS involvement plus weekly PHV; 3) CPS involvement plus weekly IPP. Intervention is provided until the infant's second birthday. All mother-infant dyads (including comparison non-maltreated infants and their mothers) participate in baseline assessments at the infant's age of 12 months. Subsequent assessments occur at 18, 24, 36, and 48 months of age. Assessments measure three major areas: 1) family-ecological variables; 2) maternal functioning and parenting; and 3) child functioning and stage-salient issues. CPS records are monitored annually across all groups to determine whether any reports of maltreatment have been filed.

The purpose of this study is to compare 2 approaches (interventions) to prevent child-abuse (maltreatment) in infants: Psychoeducational Home Visitation (PHV) vs Infant-Parent Psychotherapy (IPP). Non-maltreated infants and their mothers are studied as a comparison group.~Twelve-month-old infants and their mothers are assigned randomly (like tossing a coin) to receive 1 of 3 types of intervention for 12 months: 1) Services normally available in the community when a family is reported for child maltreatment (Child Protective Services, CPS); 2) CPS involvement plus weekly PHV; 3) CPS involvement plus weekly IPP. Intervention will be provided until the infant's second birthday. All mother-infant pairs (including comparison non-maltreated infants and their mothers) will be assessed when the infant is 12, 18, 24, 36, and 48 months old. Assessments will look at the effectiveness of the intervention in preventing child maltreatment, improving parenting, and reducing future abuse. The study will last for 3 years.~Eligibility includes a mother and her 12-month-old child that has been abused by her (the mother) or the father. (Non-maltreated infants and their mothers also will be enrolled.)

Participation in daily physical activity programs by young children is currently recommended as a means of promoting bone health. Results from studies of adults indicate that beneficial effects of either physical activity or calcium (Ca) intake may be apparent only when both these factors are present. Our results in infants indicate that physical activity combined with a low Ca diet may be detrimental in terms of bone mass accretion. The overall objective of this study is to determine whether Ca intake modifies the bone response to activity in young children 3 to 4 years of age.~Our hypotheses are that (1) the increase in bone mass resulting from a physical activity program will be more pronounced in children randomized to receive a Ca supplement compared to the increase in children randomized to receive a placebo; and (2) 12 months after cessation of the activity program, bone mass will remain higher in children randomized to gross motor activity compared to children randomized to fine motor activity, and the beneficial effect of Ca supplementation will persist only among children randomized to gross motor activity. We will test these hypotheses in a randomized 2 x 2 factorial trial in 3- to 4-year-old children. We will randomize children into either a gross motor or fine motor activity program that will be conducted in childcare centers 5 days a week for 1 year. We will further randomize each child into either a Ca supplement (1 g/d) or placebo group.~The primary outcomes of the study are bone mass accretion and changes in bone mineral density, which we will determine by dual energy x-ray absorptiometry at the beginning and end of the study. We will do activity assessments throughout the study period to determine whether participation in the gross motor activity group also increases spontaneous activity in these children. Anthropometric measurements and dietary information will allow us to statistically control for these potential confounders. We will obtain additional bone mass and physical activity measurements 12 months after completion of the program to determine if these interventions have long-term effects on bone mineral density and physical activity.~A finding of beneficial effects of Ca supplementation or physical activity, either independent of each other or in combination, will lay the groundwork for devising prevention strategies within the educational system that optimize bone health beginning early in life. However, we may find that increased physical activity in the presence of a low to moderate Ca intake may have a detrimental effect on bone mass accretion during periods of rapid growth.

Doctors recommend that young children participate in daily physical activity to promote bone health. However, studies in adults show that physical activity and increased calcium intake cause noticeable benefits for bone health only when both factors occur together. The goal of this study is to find out whether calcium intake changes the response of bone to activity in children 3 to 4 years old. Children will participate in one of two programs conducted in childcare centers 5 days a week for 1 year. One program will involve activities that use large muscles (gross motor activity). The other will involve activities using small muscles (fine motor activity). We will give a calcium supplement (1 gram per day) to half of the children in each program and give the other half an inactive pill. We will measure bone mass and bone mineral density at the beginning and end of the study. We will take measurements 12 months after the program's completion to see if physical activity and/or calcium supplements have long-term effects on bone mineral density and physical activity.

Background:~Cancer has an enormous impact on the psychological and social well-being of the family unit. The life-threatening connotations of cancer single out the ill child from his peer/family group as one who is different, and often unable to maintain a normal lifestyle. Physical sequelae of cancer and its treatment accentuate the differences between these children and their normal peers/siblings.~It is important that children with cancer be prepared to function outside of protected situations and begin to develop skills of separation and independence. For healthy children, some of these latter skills are acquired by a camping experience. Such an experience for the patient with cancer is frequently precluded by their dependence on medical facilities and the physical limitations of their activities.~The goal of this study will be to assess the short and long term benefits of the normalized camping experience, provided in conjunction with Special Love, Inc., on the patients and staff. In particular, we will seek to determine whether such a comprehensive experience is capable of influencing the attitudes and life experiences of patients and staff in a positive manner.~Objectives:~-To evaluate the impact of an enriched normalized camping experience on the quality of life of the pediatric cancer patient. In particular, attempts will be made to measure the manner in which this experience influences the child's sense of well-being and self-esteem as well as his or her relationship with parents, family, and peers.~Eligibility:~Children 7-17 years of age who are currently being treated for cancer or are up to 5 years post therapy OR Young adults with cancer (YACers) 18-25 years of age who are acting as counselors at Camp Fantastic and are enrolled in another NIH protocol.~All children/young adults will be selected for camp after careful screening by a multidisciplinary committee consisting of medical and program directors.~At the discretion of the multidisciplinary committee consisting of medical and program directors, special exceptions may be made for children with extenuating circumstances.~Design:~Assessment of benefit may include interviews with children and families before, during and following camp. Observational data on the child's performance at camp will be collected.~Medical and nursing personnel will consist of staff from the Pediatric Oncology Branch at the NCI, other units within the NIH, and participating institutions.~Special Love members, the Program Director at the 4-H Center camp (site of the camp) and Pediatric Oncology Branch staff at the NCI will coordinate the camp program, taking into account the medical needs of each camper.~Every attempt will be made to provide a full agenda of age appropriate activities for the patients.~The length of the camping experience for children with cancer will be for 7 days beginning on a Sunday and extending through the following Saturday morning. Patients will be transported to the camp from the NIH Clinical Center and the Virginia hospitals by bus.

Background:~Cancer has an enormous impact on the psychological and social well-being of the family unit. The life-threatening connotations of cancer single out the ill child from his peer/family group as one who is different, and often unable to maintain a normal lifestyle. Physical sequelae of cancer and its treatment accentuate the differences between these children and their normal peers/siblings.~It is important that children with cancer be prepared to function outside of protected situations and begin to develop skills of separation and independence. For healthy children, some of these latter skills are acquired by a camping experience. Such an experience for the patient with cancer is frequently precluded by their dependence on medical facilities and the physical limitations of their activities.~The goal of this study will be to assess the short and long term benefits of the normalized camping experience, provided in conjunction with Special Love, Inc., on the patients and staff. In particular, we will seek to determine whether such a comprehensive experience is capable of influencing the attitudes and life experiences of patients and staff in a positive manner.~Objectives:~-To evaluate the impact of an enriched normalized camping experience on the quality of life of the pediatric cancer patient. In particular, attempts will be made to measure the manner in which this experience influences the child's sense of well-being and self-esteem as well as his or her relationship with parents, family, and peers.~Eligibility:~Children 7-17 years of age who are currently being treated for cancer or are up to 3 years post therapy OR Young adults with cancer (YACers) 18-25 years of age who are acting as counselors at Camp Fantastic~All children/young adults will be selected for camp after careful screening by a multidisciplinary committee consisting of medical and program directors.~At the discretion of the multidisciplinary committee consisting of medical and program directors, special exceptions may be made for children with extenuating circumstances.~Design:~Assessment of benefit may include interviews with children and families before, during and following camp. Observational data on the child's performance at camp will be noted.~Medical and nursing personnel will consist of staff from the Pediatric Branch at the NCI, other units within the NIH, and participating institutions.~Special Love members, the Program Director at the 4-H Center camp (site of the camp) and Pediatric Branch staff at the NCI will coordinate the camp program, taking into account the medical needs of each camper.~Every attempt will be made to provide a full agenda of age appropriate activities for the patients.~The length of the camping experience for children with cancer will be for 7 days beginning on a Sunday and extending through the following Saturday morning. Patients will be transported to the camp from the NIH Clinical Center and the Virginia hospitals by bus.

Background:~It may be in the interest of the CCR to continue to follow and treat certain subjects after they have completed their treatment and participation on a research protocol.~Objective:~To provide continuing treatment and medical follow-up for CCR subjects who have completed their treatment and participation on a research protocol and who are not currently entered on or eligible for another active research protocol.~Eligibility:~Subjects who have been previously enrolled on and received treatment according to an approved CCR research protocol. (clinical trial)~It is in the best interest of the subject and the CCR for the subject to continue to receive standard care and follow-up at the NIH.~Design:~Medical/surgical/radiotherapeutic care, treatment and follow-up is provided for CCR subjects who have completed their treatment and participation on a research protocol and who are not currently entered on an active research protocol.~No investigational treatments will be administered. This protocol is not be used as a platform to perform pilot studies of off-label uses for standard agents.

This protocol is to provide continuing medical/surgical/radio-therapeutic care, treatment and follow-up for NCI patients not currently entered on an active research protocol. No investigational treatments will be administered on this protocol.

The present protocol seeks to advance our understanding of sclerosing glomerular and tubulointerstitial kidney diseases, including but not limited to variants of focal segmental glomerulosclerosis (FSGS) and chronic kidney disease of unknown etiology (CKDu). This protocol will encompass studies of the natural history, pathogenesis and treatment of these chronic kidney disorders. It will also allow us to: (1) provide second opinions to referring physicians about management of subjects with these relatively rare kidney diseases; (2) collect research samples (e.g., blood), urine, and kidney tissue obtained from clinically-indicated or from research renal biopsies); (3) and treat these subjects with standard or other approved therapies; or (4) invite selected subjects patients to participate in limited pilot studies of novel combinations of standard therapeutic agents, such as rituximab and cyclosporine. (5) Agricultural worker chronic kidney disease of undetermined etiology (CKDu) is a growing problem in tropical countries in the Americas and Asia, including Sri Lanka where collaborators are located. We will receive kidney tissue from 25 CKDu cases for pathologic examination and transcriptional profiling and blood, plasma, serum, urine for metabolomic and genetic analysis from 50 cases and controls. Subjects were consented and samples were collected under a protocol approved by the University of Colombo IRB. These studies may provide the opportunity to generate new hypotheses regarding pathogenesis and treatment that would be candidates for testing in other research protocols.~Subjects with known or suspected forms of sclerosing glomerular or chronic, fibrosing tubulointerstitial kidney diseases will undergo routine medical evaluation, laboratory testing, imaging procedures and kidney biopsies as medically indicated. Selected subjects will be invited to provide informed consent to undergo a kidney biopsy for research purposes. Blood, urine, and tissue samples will be evaluated both for standard diagnostic purposes and for research purposes using specialized molecular methods that may provide insights into specific disease pathogenesis. Subjects may elect to receive the results of their kidney disease evaluation, NIH treatment recommendations, and return to the care of their referring physicians. Other subjects may be treated with either conventional or approved agents, or (with separate consent) with a novel combination of conventional therapies (rituximab and cyclosporine) as part of pilot studies that would involve long-term follow-up care at the NIH.

The present protocol seeks to advance our understanding of sclerosing glomerular and tubulointerstitial kidney diseases, including but not limited to variants of focal segmental glomerulosclerosis (FSGS) and chronic kidney disease of unknown etiology (CKDu). This protocol will encompass studies of the natural history, pathogenesis and treatment of these chronic kidney disorders. It will also allow us to: (1) provide second opinions to referring physicians about management of subjects with these relatively rare kidney diseases; (2) collect research samples (e.g., blood), urine, and kidney tissue obtained from clinically-indicated or from research renal biopsies); (3) and treat these subjects with standard or other approved therapies; or (4) invite selected subjects patients to participate in limited pilot studies of novel combinations of standard therapeutic agents, such as rituximab and cyclosporine. (5) Agricultural worker chronic kidney disease of undetermined etiology (CKDu) is a growing problem in tropical countries in the Americas and Asia, including Sri Lanka where collaborators are located. We will receive kidney tissue from 25 CKDu cases for pathologic examination and transcriptional profiling and blood, plasma, serum, urine for metabolomic and genetic analysis from 50 cases and controls. Subjects were consented and samples were collected under a protocol approved by the University of Colombo IRB. These studies may provide the opportunity to generate new hypotheses regarding pathogenesis and treatment that would be candidates for testing in other research protocols.~Subjects with known or suspected forms of sclerosing glomerular or chronic, fibrosing tubulointerstitial kidney diseases will undergo routine medical evaluation, laboratory testing, imaging procedures and kidney biopsies as medically indicated. Selected subjects will be invited to provide informed consent to undergo a kidney biopsy for research purposes. Blood, urine, and tissue samples will be evaluated both for standard diagnostic purposes and for research purposes using specialized molecular methods that may provide insights into specific disease pathogenesis. Subjects may elect to receive the results of their kidney disease evaluation, NIH treatment recommendations, and return to the care of their referring physicians. Other subjects may be treated with either conventional or approved agents, or (with separate consent) with a novel combination of conventional therapies (rituximab and cyclosporine) as part of pilot studies that would involve long-term follow-up care at the NIH.

Measurements of dynamic changes in oxygen uptake (VO2 kinetics) during recovery from exercise may describe regulatory control of oxygen transport and utilization and have greater reliability and less inherent risk than assessment of maximal oxygen uptake (VO2max) in patients for whom exercise is limited by pain, excessive fatigue, dyspnea and motivation. The purpose of this pilot study is to evaluate the effect of exercise intensity on the time constant describing changes in VO2 (tauVO2) during recovery from one minute of constant work rate exercise. Five normal healthy volunteers ages 18 and older will perform a progressive maximal aerobic exercise test, using a cycle ergometer, to determine VO2max and lactate threshold (LT) estimated by gas exchange. Each subject will also complete a series of maximal constant work rate tests and submaximal constant work rate tests at 80% LT and 50% of the difference between LT and VO2max (50% delta). Breath by breath variability and VO2 span will be used to determine the number of constant work rate test repetitions, for each subject for each exercise intensity, needed to establish confidence in tauVO2. A mean response profile of VO2 recovery kinetics for each exercise intensity will be analyzed using non-linear regression to determine tauVO2. To examine the effect of exercise intensity on tauVO2, one way analysis of variance will be used to determine whether differences exist among maximal and submaximal (80% LT and 50% delta) time constants. We hypothesize that there will be no significant differences among time constants for VO2 during recovery from maximal and submaximal constant work rate exercise lasting one minute. The results of this study are expected to provide increased understanding of the measurement of VO2 kinetics during recovery.

Measurements of dynamic changes in oxygen uptake (VO2 kinetics) during recovery from exercise may describe regulatory control of oxygen transport and utilization and have greater reliability and less inherent risk than assessment of maximal oxygen uptake (VO2max) in patients for whom exercise is limited by pain, excessive fatigue, dyspnea and motivation. The purpose of this pilot study is to evaluate the effect of exercise intensity on the time constant describing changes in VO2 (tauVO2) during recovery from one minute of constant work rate exercise. Five normal healthy volunteers ages 18 and older will perform a progressive maximal aerobic exercise test, using a cycle ergometer, to determine VO2max and lactate threshold (LT) estimated by gas exchange. Each subject will also complete a series of maximal constant work rate tests and submaximal constant work rate tests at 80% LT and 50% of the difference between LT and VO2max (50% delta). Breath by breath variability and VO2 span will be used to determine the number of constant work rate test repetitions, for each subject for each exercise intensity, needed to establish confidence in tauVO2. A mean response profile of VO2 recovery kinetics for each exercise intensity will be analyzed using non-linear regression to determine tauVO2. To examine the effect of exercise intensity on tauVO2, one way analysis of variance will be used to determine whether differences exist among maximal and submaximal (80% LT and 50% delta) time constants. We hypothesize that there will be no significant differences among time constants for VO2 during recovery from maximal and submaximal constant work rate exercise lasting one minute. The results of this study are expected to provide increased understanding of the measurement of VO2 kinetics during recovery.

Acquisition of fresh tumor and normal tissue samples is necessary for the preparation of cDNA libraries, microarray chips, tissue specific probes, and proteomics development and validation. This protocol will allow acquisition of patient samples at the time of tissue sampling for surgery, diagnostic tests, or therapeutic phereses. These samples will be forwarded without patient identifiers, pathology reports, or other labels. Tissue pathology will be verified within the Laboratory of Pathology and samples used strictly for CGAP and Proteomic Initiative indications.

Acquisition of fresh tumor and normal tissue samples are necessary for the preparation of cDNA libraries, microarray chips, and tissue specific probes, and proteomics development and validation. This protocol will allow acquisition of samples at the time of tissue sampling for surgery, diagnostic tests, or therapeutic phereses. These samples will be forwarded without patient identifiers, pathology reports, or other labels. Tissue pathology will be verified within the Laboratory of Pathology and samples used strictly for CGAP and Proteomic Initiative indications.

Simultaneous use of alternative or complementary medical therapies by cancer patients undergoing conventional medical treatment is extremely common and may not always be disclosed to the patient's treating physician. Cancer patients undergoing Phase I therapy on clinical trials constitute a special population of patients, since by definition, their prescribed therapy is scientifically unproven in terms of efficacy. Phase I patients are closely monitored for adverse effects in order to identify and characterize the toxicities and to define a tolerable dose of their experimental treatment. Thus, the unrecognized use of alternative therapies by patients actively enrolled in phase I trials may potentially confound rational drug development by causing adverse side effects or by contributing to drug interactions. Examples of clinical toxicities induced by alternative medical treatments include liver dysfunction or renal failure caused by herbal preparations, or hematologic abnormalities, such as eosinophilia-myalgia syndrome caused by tryptophan food supplements. Therefore, it is important to document and determine the prevalence of alternative therapy use in this specific patient population; however, this issue has not previously been examined in a scientifically rigorous manner. We propose to conduct a survey and interview study of phase I cancer patients enrolled in ongoing clinical trials at the National Cancer Institute to determine the prevalence of alternative therapy use in this population. This study will also examine patient attitudes and perceptions regarding their use of alternative therapy as compared with their scientifically-sanctioned phase I experimental therapy. This information has important implications for drug development.

Simultaneous use of alternative or complementary medical therapies by cancer patients undergoing conventional medical treatment is extremely common and may not always be disclosed to the patient's treating physician. Cancer patients undergoing Phase I therapy on clinical trials constitute a special population of patients, since by definition, their prescribed therapy is scientifically unproven in terms of efficacy. Phase I patients are closely monitored for adverse effects in order to identify and characterize the toxicities and to define a tolerable dose of their experimental treatment. Thus, the unrecognized use of alternative therapies by patients actively enrolled in phase I trials may potentially confound rational drug development by causing adverse side effects or by contributing to drug interactions. Examples of clinical toxicities induced by alternative medical treatments include liver dysfunction or renal failure caused by herbal preparations, or hematologic abnormalities, such as eosinophilia-myalgia syndrome caused by tryptophan food supplements. Therefore, it is important to document and determine the prevalence of alternative therapy use in this specific patient population; however, this issue has not previously been examined in a scientifically rigorous manner. We propose to conduct a survey and interview study of phase I cancer patients enrolled in ongoing clinical trials at the National Cancer Institute to determine the prevalence of alternative therapy use in this population. This study will also examine patient attitudes and perceptions regarding their use of alternative therapy as compared with their scientifically-sanctioned phase I experimental therapy. This information has important implications for drug development.

Genistein is a natural product found in soy beans; its consumption has been associated with a low incidence of metastatic prostate cancer. Genistein is a known protein-tyrosine kinase inhibitor, and in preclinical studies it has been shown to increase cell adhesion. Increases in cell adhesion in vivo would phenotypically reverse the first step in the metastatic cascade, potentially preventing metastasis formation, and is consistent with epidemiologic findings. This study seeks to determine the pharmacokinetics of genistein in humans by administering a single dose of genistein and performing a pharmacokinetic analysis. Patients will be treated with two formulations of genistein (a 43% genistein preparation or a 90% preparation). This is a phase I study, and patients will be treated on one of three dosing levels. Patients will be randomly assigned to receive one formulation first, followed by a washout period, and will then receive the second preparation (i.e., a randomized cross over design). Information from this study will be used to optimally design a multiple dose study wherein patients will be treated for longer periods of time. The duration of this study is estimated to be about 4 weeks long for each patient.

Genistein is a natural product found in soy beans; its consumption has been associated with a low incidence of metastatic prostate cancer. Genistein is a known protein-tyrosine kinase inhibitor, and in preclinical studies it has been shown to increase cell adhesion. Increases in cell adhesion in vivo would phenotypically reverse the first step in the metastatic cascade, potentially preventing metastasis formation, and is consistent with epidemiologic findings. This study seeks to determine the pharmacokinetics of genistein in humans by administering a single dose of genistein and performing a pharmacokinetic analysis. Patients will be treated with two formulations of genistein (a 43% genistein preparation or a 90% preparation). This is a phase I study, and patients will be treated on one of three dosing levels. Patients will be randomly assigned to receive one formulation first, followed by a washout period, and will then receive the second preparation (i.e. a randomized cross over design). Information from this study will be used to optimally design a multiple dose study wherein patients will be treated for longer periods of time.

This project will measure magnetization transfer (MT) parameters on normal subjects using two novel approaches. The first is the investigation of asymmetric MT effects with respect to the zero or on-resonance reference point. The technique measures the difference in MT effect between two symmetrically positioned off-resonance MT pulses in the positive and negative frequency ranges. Prior research with this technique in the kidney show a difference in the macromolecular lineshape that correlates to a specific metabolite. The second approach, utilizing a subset of the acquisitions from the first approach, will test newly developed formulation to calculate the macromolecular fraction, or fraction of proton density that accounts for MT. We foresee these measurements may significantly develop our understanding of MT and introduce diagnostic and quantitative tools to study human tissue.

This project will measure magnetization transfer (MT) parameters on normal subjects using two novel approaches. The first is the investigation of asymmetric MT effects with respect to the zero or on-resonance reference point. The technique measures the difference in MT effect between two symmetrically positioned off-resonance MT pulses in the positive and negative frequency ranges. Prior research with this technique in the kidney show a difference in the macromolecular lineshape that correlates to a specific metabolite. The second approach, utilizing a subset of the acquisitions from the first approach, will test newly developed formulation to calculate the macromolecular fraction, or fraction of proton density that accounts for MT. We foresee these measurements may significantly develop our understanding of MT and introduce diagnostic and quantitative tools to study human tissues.

This study seeks to evaluate the impact of Starbright World (SBW) on hospitalized children. SBW is a virtual environment designed to link seriously ill children into an interactive online community where they can play games, learn about their condition, or talk with other ill children who are connected to the network. Our outcome evaluation of SBW will include assessments of pain, mood (anxious, depressed and energetic), anger, loneliness, and willingness to return to the NIH for treatment of children who are being treated at the NIH. They will be assessed while engaging in normal recreational activities (in one of two available playrooms) and while using Starbright World. In addition, we will conduct a process evaluation of the implementation of Starbright World.

This study seeks to evaluate the impact of Starbright World (SBW) on hospitalized children. SBW is a virtual environment designed to link seriously ill children into an interactive online community where they can play games, learn about their condition, or talk with other ill children who are connected to the network. Our outcome evaluation of SBW will include assessments of pain, mood (anxious, depressed and energetic), anger, loneliness, and willingness to return to the NIH for treatment of children who are being treated at NIH. They will be assessed while engaging in normal recreational activities (in one of two available playrooms) and while using Starbright World. In addition, we will conduct a process evaluation of the implementation of Starbright World.

Background:~-NIH and FDA intramural investigators performing in vitro studies involving human blood components have a need for a steady, reliable, consistent source of these blood components, preferably derived from screened donors documented to be free of potential transfusion-transmissible diseases.~Objectives:~To provide a mechanism, that is reviewed and approved by IRB, for the Department of Transfusion Medicine, Clinical Center to collect and process blood and blood components from paid, healthy volunteer donors for distribution to NIH intramural investigators and FDA laboratories for in vitro research use.~To provide adequate and complete informed consent to the donors of research blood samples, and to assure that the education, counseling, and protection of the study subjects (research blood donors) from research risks is performed in accordance with IRB, OPRR and other applicable Federal regulatory standards.~Eligibility:~Donors must meet the eligibility criteria for volunteer whole blood donation with the exception of foreign travel history and other requirements, some of which are outlined below:~Age greater than or equal to 18 years~Weight greater than 110 pounds~No known heart, lung, kidney disease, or bleeding disorders~No history of sickle cell disease~Female subjects should not be pregnant~Design:~Donors meeting research donor eligibility criteria will be recruited to donate blood and blood components by standard phlebotomy and apheresis techniques.~The investigational nature of the studies in which their blood will be used, and the risks and discomforts of the donation process will be carefully explained to the donors, and a signed informed consent document will be obtained.~Donors will be compensated according to an established schedule based on the duration and discomfort of the donation.~NIH and FDA investigators requesting blood components for research use will be required to submit an electronic (Web-based) memo of request, briefly describing the nature of the research, and providing assurance that samples provided through this protocol will be used solely for in vitro and not for in vivo research.~Blood components for research use will be distributed with a unique product number, and the DTM principal and associate investigators will serve as the custodians of the code that links the product with a donor s identity.

This protocol is designed to provide a mechanism for the Department of Transfusion Medicine, Clinical Center to collect and process blood components from paid, healthy volunteer donors for distribution to NIH intramural investigators and FDA researchers for in vitro laboratory use. Donors meeting research donor eligibility criteria will be recruited to donate blood and blood components by standard phlebotomy and apheresis techniques. The investigational nature of the studies in which their blood will be used, and the risks and discomforts of the donation process will be carefully explained to the donors, and a signed informed consent document will be obtained. Donors will be compensated according to an established schedule based on the duration and discomfort of the donation. NIH and FDA investigators requesting blood components for research use will be required to submit an electronic (Web-based) memo of request, briefly describing the nature of the research, and providing assurance that samples provided through this protocol will be used solely for in vitro and not for in vivo research. This protocol also provides a detailed schema for careful and frequent laboratory safety monitoring of repeat research apheresis donors.~Blood components for research use will be distributed with a unique product number, and the DTM principal and associate investigators will serve as the custodians of the code that links the product with a donor s identity. The nature of the in vitro studies in which the blood and components collected in this study will be used is not the subject of this protocol, and is not possible to describe, since it involves basic investigative efforts in greater than 170 different NIH and FDA laboratories. The intent of this protocol is not to approve the research itself, but to provide adequate and complete informed consent for the donor, and to assure that the education, counseling, and protection of the study subjects (research blood donors) is performed in accordance with IRB, OHSR, OPRR and other applicable Federal regulatory standards...

Recurrent or Stage IV Lung Cancer patients receive gradually escalating doses of intravenous Antineoplaston therapy (Atengenal + Astugenal) until the maximum tolerated dose is reached. Treatment continues up to 12 months in the absence of disease progression or unacceptable toxicity.~OBJECTIVES:~To determine the efficacy of Antineoplaston therapy in patients with Recurrent or Stage IV Lung Cancer, as measured by an objective response to therapy (complete response, partial response or stable disease).~To determine the safety and tolerance of Antineoplaston therapy in patients with Recurrent or Stage IV Lung Cancer.~To determine objective response, tumor size is measured utilizing MRI scans, which are performed every 8 weeks for the first two years, every 3 months for the third and fourth years, every 6 months for the 5th and sixth years, and annually thereafter.

Current therapies for Recurrent or Stage IV Lung Cancer provide very limited benefit to the patient. The anti-cancer properties of Antineoplaston therapy suggest that it may prove beneficial in the treatment of Recurrent or Stage IV Lung Cancer.~PURPOSE: This study is being performed to determine the effects (good and bad) that Antineoplaston therapy has on patients with Recurrent or Stage IV Lung Cancer.

This Phase I study will assess the pharmacokinetics of two botanicals, Trifolium pratense (red clover) and Cimicifuga racemosa (black cohosh). Participants will receive a single dose of one botanical preparation. The observation period will be one week. Drug toxicity, absorption, distribution, metabolism and elimination data will be collected, and dosages to be utilized in a Phase II clinical trial will be determined. The Phase II trial will examine the efficacies of red clover and black cohosh for the reduction of menopausal symptoms in healthy menopausal women. The study will be randomized, double-blinded, and placebo-controlled. Study duration will be one year.

This Phase I study will assess the pharmacokinetics of two botanicals, Trifolium pratense (red clover) and Cimicifuga racemosa (black cohosh). Participants will receive a single dose of one botanical preparation. The observation period will be one week. Drug toxicity, absorption, distribution, metabolism and elimination data will be collected, and dosages to be utilized in a Phase II clinical trial will be determined.

Stroke is the third leading cause of disability in the United States. To date, conventional rehabilitation is not able to restore normal, safe, gait for many individuals with stroke. We have identified nine gait component deficits which respond to the FNS-IM intervention. This study will test a refined treatment protocol of 3 months duration to restore volitional gait by restoring those nine gait components simultaneously. In addition, we will incorporate into the treatment protocol a promising non-invasive technique of partial body weight-supported (BWS) gait training on a treadmill. BWS and FNS-IM have the potential to provide additive effects for the patient and restore volitional gait more quickly and more completely than would otherwise be possible with one technique alone. Therefore, our first hypothesis is HYPOTHESIS I: BWS combined with FNS-IM, simultaneously applied to nine critical gait components, will restore volitional normal, safe gait to patients with chronic stroke within 3 months. An advantage of BWS gait training is that it is non-invasive. Consequently, we must demonstrate the additive advantage of FNS-IM technique alone. Therefore the second hypothesis is: HYPOTHESIS II: FNS-IM plus BWS will restore volitional gait more quickly and completely for patients with chronic stroke compared with BWS alone.~A total of thirty six chronic stroke patients will be randomly divided into two treatment groups (1) FNS-IM plus BWS; (2) BWS alone. Outcome measures for hypothesis testing will be threefold : 1) Gait normality (kinematics of nine gait components); 2) Safety (number of falls); 3) Functionality (gait speed, walking endurance, and CHART, a handicap measure of mobility and activity level). Data will be collected every four weeks during the three months of treatment. Maintenance of gains will be monitored at two additional data collections at six months and one year following the end of the treatment period. Results of this study have the potential to provide the following clinically applicable information:~1. For patients with stroke, a refined treatment protocol of 3 months duration for restoration of normal, safe, volitional gait which is practical within the current healthcare milieu. 2. A definitive recommendation regarding the most effective treatment for chronic stroke patients: (1) BWS plus FNS-IM or (2) BWS alone.~RESEARCH OBJECTIVES~Build stimulators and electrodes.~Obtain measures pre and post intervention for the two groups (FNS-IM + BWS; and BWS alone) to detect gains in: a) gait pattern; b) safety; c) functional capability; and d) quality of life.~Analyze data for the group receiving FNS-IM + BWS, in order to test~Hypothesis I.~Produce therapy protocols for FNS-IM and BWS intervention, and treatment progression.~Test Hypothesis II by comparing the two treatment groups (BWS vs BWS + FNS-IM).

To date, conventional rehabilitation is not able to restore normal, safe, gait for many individuals with stroke. We have identified nine gait component deficits which respond to the FNS-IM intervention. This study will test a refined treatment protocol of 3 months duration to restore volitional gait by restoring those nine gait components simultaneously. In addition, we will incorporate into the treatment protocol a promising non-invasive technique of partial body weight-supported (BWS) gait training on a treadmill. BWS and FNS-IM have the potential to provide additive effects for the patient and restore volitional gait more quickly and more completely than would otherwise be possible with one technique alone.

Background:~Many patients with diabetes are under sub-optimal glycemic control. Central to the clinician's task in improving glycemic control is the management of hypoglycemic medication therapy, including the use of drugs such as insulin and sulfonylureas. Clinical trials have demonstrated that more intensive hypoglycemic medication therapy results in improved glycemic control. Yet quality measures for this critical process of care have not been developed and we know little about how physicians actually manage hypoglycemic medications.~Objectives:~We propose to develop a quality measure that describes the intensity of physicians' hypoglycemic medication therapy. We will then provide feedback to VA physicians regarding their practices and access to experts in diabetes care to determine whether this intervention leads to improvements in glycemic control.~Methods:~The study was divided into two phases. During the first phase we used existing data to model the decision to increase hypoglycemic medications. At each medical visit, we determined whether an increase in medication therapy occurred. We then used recursive partitioning to develop a model that identified patient characteristics at the visit, such as recent laboratory results and diagnoses, associated with the decision to increase therapy. This model assigns a predicted probability of an increase in therapy to each visit. We used these predictions to define an intensity of hypoglycemic medication therapy for each physician that compared the actual to predicted number of increases over all patient-visits. The second phase was a randomized trial in which clinicians at experimental sites receive feedback on performance and access to expert opinion while usual care is provided at control sites. Feedback on performance was provided twice over 6 months. The change in intensity of treatment scores and glycosylated hemoglobin levels pre- and post-intervention at these sites were compared to performance of primary care physicians at control sites not receiving the intervention.~Status:~Completed.

Many patients with diabetes are under sub-optimal glycemic control. Central to the clinician's task in improving glycemic control is the management of hypoglycemic medication therapy, including the use of drugs such as insulin and sulfonylureas. Clinical trials have demonstrated that more intensive hypoglycemic medication therapy results in improved glycemic control. Yet quality measures for this critical process of care have not been developed and we know little about how physicians actually manage hypoglycemic medications.

Background:~Prior rehabilitation outcome studies had many weaknesses. They had: a) evaluated rehabilitation effects only in isolated subgroups, b) focused on functional ability rather than on quality of life, c) not used randomized control groups, and d) had inadequate sample sizes. Differences in methodological approaches have resulted in inconsistent findings. The lack of long-term benefits suggests that services may need to be continued at home or in subacute care settings to optimize their effectiveness. Unfortunately, prior research did not include behavioral outcomes. The potential benefits of rehabilitative care could thus not be evaluated by these studies in more meaningful detail, and they did not accurately reflect the psychosocial objectives of rehabilitation.~Objectives:~The goal of this study was to measure the additive effect of outpatient, subacute rehabilitation as follow-up services to acute, inpatient rehabilitation on adults diagnosed with a disabling disorder in four major diagnostic groups (nervous, circulatory, musculoskeletal, and injury).~Methods:~A randomized clinical trial was conducted to determine the effects of subacute rehabilitative care on: 1) physical function, 2) health and mental health, 3) mortality, 4) family function, 5) personal adjustment, and 6) use of health care resources. Patients hospitalized for the first time with a disabling condition [n=180] were provided inpatient rehabilitation and then randomly assigned to either subacute rehabilitation at home [n=90] or to usual outpatient follow-up [n=90] in which only medical services were provided but no scheduled rehabilitative therapies were offered. To compare the two groups, analysis of covariance was conducted for the outcome variables. The between subjects factor was subacute rehabilitative care versus usual medical services as an outpatient.~Status:~Complete.

Prior rehabilitation outcome studies had many weaknesses. They had: a) evaluated rehabilitation effects only in isolated subgroups, b) focused on functional ability rather than on quality of life, c) not used randomized control groups, and d) had inadequate sample sizes. Differences in methodological approaches have resulted in inconsistent findings. The lack of long-term benefits suggests that services may need to be continued at home or in subacute care settings to optimize their effectiveness. Unfortunately, prior research did not include behavioral outcomes. The potential benefits of rehabilitative care could thus not be evaluated by these studies in more meaningful detail, and they did not accurately reflect the psychosocial objectives of rehabilitation.

Background:~This study was designed to assess the effectiveness of a Health Education Program (HEP) for improving the well-being and reducing the health care use and cost of care of frail older outpatient veterans, and for improving the well-being of their spouse caregivers. HEP is a multi-component group program delivered in 8 weekly, 2-hour sessions, and 10 monthly 2-hour follow-up sessions, it includes emotion-focused and problem focused coping strategies, education and support.~Objectives:~The objectives of this study are to evaluate: 1) effects of HEP on the perceived health status, emotional well-being, and social support of frail veterans; 2) effects of HEP on the perceived health, emotional well-being, social support, burden levels, self-appraisal of change, pressing problems associated with caregiving, knowledge and use of community resources by caregiver; and 3) effects of HEP on the health care use and costs of care recipients.~Methods:~HEP was evaluated using a randomized control group design. The design has two levels of intervention, HEP vs. Usual Care (UC), 3 VA medical centers (VAMCs), and 4 times of measurement (at baseline, after the 8th HEP meeting, and at 1 and 2 years after baseline). Data reported here are for 8 week and 1-year psychosocial outcomes and 18 months for VA cost. Caregivers and veterans (n = 466) were randomized in 3 VAMCs, 114 to UC and 119 to HEP. The typical caregiver was 68 years old, married, white, female, with some college education and living with the veteran. The typical veteran care recipient was 74 years old, white, male with some college education, and suffered from one or more chronic health problems. Fifteen HEP groups were conducted. Caregivers and recipients were assessed on: 1) health and functional status; 2) emotional well-being; and 3) social support. In addition, caregivers were assessed for change in coping skills, change in burden level, pressing problems, and knowledge and use of community resources. Data was analyzed using random effects regression models.~Status:~Data on two-year outcomes for health and functional status, emotional well-being, and social support of caregivers and veterans, problems associated with caregiving and Medicare plus VA costs are being collected and analyzed for an amended final report.

This study was designed to assess the effectiveness of a Health Education Program (HEP) for improving the well-being and reducing the health care use and cost of care of frail older outpatient veterans, and for improving the well-being of their spouse caregivers. HEP is a multi-component group program delivered in 8 weekly, 2-hour sessions, and 10 monthly 2-hour follow-up sessions, it includes emotion-focused and problem focused coping strategies, education and support.

Background:~The decision regarding the use of post-menopausal estrogen hormone replacement therapy (HT) is complex because patients must balance the short and long-term risks and benefits. Information from new and important clinical trials must also be considered. The purpose of this research is to develop and evaluate the efficacy of a HT CD-ROM decision-aid in improving the decision making process for women considering the use of estrogen HT.~Objectives:~The objectives of the study are to: 1) develop a model of the decision-making process for postmenopausal women considering hormone (HT), based on Multi-Attribute Utility Theory (MAUT); 2) produce an interactive CD-ROM decision-aid for HT; 3) evaluate the effect of the interactive CD-ROM decision-aid on patient satisfaction with decision (SWD) and knowledge about menopause and HT; and 4) test the effect of the interactive CD-ROM decision-aid on women�s decisions regarding use of HT.~Methods:~Phase I (completed) used structured interviews and surveys in the development of a decision model for HT. In phase II, an interactive CD-ROM decision-aid was developed and a randomized controlled trial (RCT) of its effect on decision processes was conducted. Postmenopausal women, aged 45-74 were recruited from the primary care clinics of the four participating Veterans Affairs hospitals: Milwaukee, Madison, Chicago-Hines, and Chicago-Westside. The primary hypothesis was that women who use the CD-ROM decision-aid would demonstrate increased satisfaction with their decision regarding hormone replacement therapy use compared to women receiving the control intervention.~Status:~Enrollment and follow-up assessments have been completed. The study is in the analysis phase. The study was presented to the VA HSR&D Combined Monitoring Board on February 5, 2003 and the committee voted unanimously to recommend continuation of the trial. The study has had one publication and several scientific abstract presentations.

The decision regarding the use of post-menopausal estrogen hormone replacement therapy (HT) is complex because patients must balance the short and long-term risks and benefits. Information from new and important clinical trials must also be considered. The purpose of this research is to develop and evaluate the efficacy of a HT CD-ROM decision-aid in improving the decision making process for women considering the use of estrogen HT.

Background:~Smoking cessation interventions including behavioral and pharmacological components have been demonstrated to be both effective and cost-effective. Although there is a high prevalence of smoking and smoking-related disorders among veterans who use VA medical centers for health care, rates of identification of tobacco use and provision of brief and/or intensive smoking cessation services are suboptimal. Telephone outreach (TO) may serve to increase access to counseling and medications to assist smoking cessation. From the standpoint of health systems, TO provides the opportunity for centralized oversight and quality assurance, economy of scale, and dissemination strategies that are practical to implement. At the provider level, TO addresses barriers to delivery of services such as limited time and skills. From the standpoint of the smoker, attractions of TO include accessibility, convenience, and privacy.~Objectives:~The objectives of the study are to: 1) determine if TO increases successful quitting among veterans who smoke, compared to the distribution of written self-help materials; and 2) determine the cost-effectiveness of TO for smoking cessation for veterans who smoke.~Methods:~The study involved a population-based sample of veterans in VISN 13 who use one of the five Network VAMCs for primary care. 838 smokers were recruited, enrolled and randomly assigned to 1) written self-help materials + TO, or 2) written self-help materials alone. The behavioral intervention protocol included follow-up calls scheduled in a relapse-sensitive fashion. Use of nicotine replacement therapy (NRT) was encouraged, and prescriptions facilitated. Data was collected at baseline, 3 months, and 12 months by telephone. Information on demographic characteristics, medical and mental health histories, smoking history, intervention, and use of clinical services for smoking cessation was included. Cost data will be calculated from administrative databases, and will include 1) written materials, 2) counseling (personnel time, equipment, space), and 3) medications. The primary outcome was 6 months of prolonged abstinence from smoking, measured 12 months following intervention. Secondary analyses evaluated 3 month and 12 month point prevalent abstinence from smoking, quit attempts, and a formal cost-effectiveness analysis that will include total costs, total and marginal effects and cost-effectiveness ratios (average cost/quit and average cost/marginal quit) for TO and SH interventions.~Status:~Data collection and main outcome analyses have been completed. The main manuscript will be submitted to JAMA in October 2004. We are starting cost-effectiveness analyses.

Smoking cessation interventions including behavioral and pharmacological components have been demonstrated to be both effective and cost-effective. Although there is a high prevalence of smoking and smoking-related disorders among veterans who use VA medical centers for health care, rates of identification of tobacco use and provision of brief and/or intensive smoking cessation services are suboptimal. Telephone outreach (TO) may serve to increase access to counseling and medications to assist smoking cessation. From the standpoint of health systems, TO provides the opportunity for centralized oversight and quality assurance, economy of scale, and dissemination strategies that are practical to implement. At the provider level, TO addresses barriers to delivery of services such as limited time and skills. From the standpoint of the smoker, attractions of TO include accessibility, convenience, and privacy.

Background:~Smoking is a serious and common health risk among veterans. Given the press of national initiatives and local incentives to improve smoking cessation care in response to VA performance measures, this study tests a widely applicable approach to clinical practice guidelines implementation, namely evidence-based quality improvement, which is directly relevant to the translation of efficacious treatments into enhancements in VA health care policy and practice. Evidence-Based Quality Improvement (EBQI) focuses on improved provider adherence to smoking cessation guidelines and a decrease in patient smoking rates in a manner designed to produce short- and long-term health improvements and cost benefits at the organizational level.~Objectives:~Adherence to smoking cessation guidelines requires practice changes at the patient, provider, and system levels to achieve optimal quit rates. The objective of this study was to evaluate the effectiveness of evidence-based quality improvement (EBQI)�an expert-designed and locally implemented clinical reorganization of smoking cessation care�on changes in smoking cessation (SC) practice among primary care providers and health outcomes among veteran smokers.~Methods:~An evidence-based quality improvement intervention comprising provision of physician and patient educational materials, local priority setting with leadership and providers, and local adaptation of expert-designed protocols was implemented in experimental VA primary care practices (n=9). VA control sites (n=9), matched on size and academic affiliation, received smoking cessation guideline copies. We randomly sampled, consented, screened and surveyed primary care patients at all 18 sites (n=1,941 smokers) and used computer-assisted telephone interviewing to assess sociodemographics, health status, function, and smoking behavior, attitudes and treatment experience. Post-intervention 12-month follow-up interviews were completed using the same measures (n=1,080). We used multiple imputation using hotdeck techniques and applied both enrollment and attrition weights to the patient-level data. We used weighted logistic regression to evaluate intervention effects, controlling for patient-level predictors of quit attempts and quit status (e.g., level of addiction, readiness to change, age, health).~Status:~The project is completed. Analysis is ongoing for manuscripts.

Smoking is a serious and common health risk among veterans. Given the press of national initiatives and local incentives to improve smoking cessation care in response to VA performance measures, this study tests a widely applicable approach to clinical practice guidelines implementation, namely evidence-based quality improvement, which is directly relevant to the translation of efficacious treatments into enhancements in VA health care policy and practice. Evidence-Based Quality Improvement (EBQI) focuses on improved provider adherence to smoking cessation guidelines and a decrease in patient smoking rates in a manner designed to produce short- and long-term health improvements and cost benefits at the organizational level.

Background:~Among veterans, smoking is the single most important risk factor for preventable mortality and morbidity, and studies suggest a higher prevalence of smoking among veterans than the general population. The VHA has encouraged adoption of the AHCPR Guideline for Smoking Cessation, yet most hospitals have poorly developed smoking cessation programs.~Objectives:~The present study is designed to investigate the effectiveness of an organizational strategy to increase compliance with the AHCPR guideline. Short term goals of the study include increasing the rate of identification of smokers and increasing the delivery of brief smoking cessation interventions. Long term goals include reducing tobacco consumption among veterans.~Methods:~Twenty VAMC�s with active primary care clinics have been randomly assigned to either control (usual practice; UP) or intervention (organizational support; OS) groups. The intervention hospitals receive staff training and site consultation; all hospitals will receive the AHCPR guideline. Rate of identification of smokers in the medical record, smoking cessation rates, provision of smoking cessation services (e.g., NRT, counseling), and costs of NRT will be determined via telephone interviews with patients, chart review, and electronic records.~Status:~Baseline data collection is nearly complete, and the intervention period will be complete in September, 2000. We have completed telephone surveys with approximately 4500 veterans. Analysis of study data is ongoing, and manuscript preparation will begin within the next few months.

Among veterans, smoking is the single most important risk factor for preventable mortality and morbidity, and studies suggest a higher prevalence of smoking among veterans than the general population. The VHA has encouraged adoption of the AHCPR Guideline for Smoking Cessation, yet most hospitals have poorly developed smoking cessation programs.

Background:~Control of the blood sugar prevents complications and results in extra years of life in patients with diabetes. Practice Guidelines delineating specific ways physicians manage diabetes have been outlined. Missing are guidelines for health care providers to encourage patients to take responsibility for their diabetes. Traditional patient education models have been ineffective in managing diabetic persons because they have relied upon information given alone and are disease centered rather than patient centered. This study will explore the role of self-efficacy in helping veterans move toward healthy behaviors.~Objectives:~The long-term objectives are to: 1) increase recognition of veteran�s responsibility for health; 2) develop more effective skills in managing chronic conditions; and 3) explore the role of self-efficacy in facilitating improvements in health behaviors and health care utilization.~Methods:~This is a prospective, randomized controlled clinical trial of 2,068 cognitively intact, diabetic veterans. The outcome measures (health behaviors, self-efficacy, health status and health care utilization) will be measured using self-rated scales developed and tested by Lorig and colleagues from Stanford University. Glucose levels and BMI changes will be evaluated using information documented in the medical record.~Status:~Enrollment (a total of 326 patients) is closed. All necessary data have been received and are being analyzed.

Control of the blood sugar prevents complications and results in extra years of life in patients with diabetes. Practice Guidelines delineating specific ways physicians manage diabetes have been outlined. Missing are guidelines for health care providers to encourage patients to take responsibility for their diabetes. Traditional patient education models have been ineffective in managing diabetic persons because they have relied upon information given alone and are disease centered rather than patient centered. This study will explore the role of self-efficacy in helping veterans move toward healthy behaviors.

Background:~Falls are the leading cause of nonfatal injuries in the United States and the second leading cause of all unintentional injury deaths. Each year fractures of the hip account for about 200,000 hospitalizations among the elderly and falls are contributing factors in 40 percent of admissions to nursing homes. About 30 percent of community-dwelling elderly fall each year, with about 10 percent seeking emergency medical help for a fall injury. Data from CDC-funded study to assess falls among the elderly (SAFE) suggest that as many as 41 percent of elderly patients fall at home in the year following discharge from hospitalization due in part to deconditioning associated with inactivity.~Objectives:~The controlled trial of a physical restoration (PR) intervention (Geriatric Rehabilitation Intensive Program, SAFE-GRIP) is designed to improve physical functional capacity and to reduce the likelihood of falls in the elderly during the period following discharge from hospitalization or inactivity/bed rest.~Methods:~This is a four year randomized trial of SAFE-GRIP, designed to improve the physical functional capacity, to reduce the likelihood of falls and to decrease the chance of injury from falls. Patients at home or recently discharged to home will be randomly assigned to one of two groups, PR or control, upon receiving medical clearance (time=0). This project will provide mechanisms to establish well-designed innovative physical restoration (PR) protocols for the Miami VAMC and test the effects of these interventions on the rate of falling/sustaining injuries and their sequelae at home. Our anticipated sample was 105 males and 105 females aged 60+ years inactive at home or recently discharged to home from the Miami VAMC and a neighboring community hospital. Study participants will be randomly assigned to one of two groups, PR or control, upon receiving medical clearance. Baseline measures of physical function, health care utilization, ADL/IADL performance and health-related quality of life will be taken following assignment to treatment conditions. These same measures will be taken again at eight weeks following medical clearance, and again at six months. The incidence of falls will be tracked throughout the funding period for each subject. Self-report of the number of falls in the year prior to hospitalization, an assessment of in-home hazards, and an assessment of participants' post-hospitalization medication regimen will be obtained at the baseline assessment and used as covariates in the analysis of outcomes.~Status:~All subjects have completed the study intervention phase. The projected submission date of the final report is September 30, 2001. Analysis of the prospectively collected study data is underway. We have acquired the HCFA Denominator Files, and Inpatient Files, and Part B Provider Service Files for the years 1997, 1998, and 1999. The extraction of 1997, 1998, and 1999 Part B Provider Service Files is almost complete and the analysis of the Inpatient Files is underway.

Falls are the leading cause of nonfatal injuries in the United States and the second leading cause of all unintentional injury deaths. Each year fractures of the hip account for about 200,000 hospitalizations among the elderly and falls are contributing factors in 40 percent of admissions to nursing homes. About 30 percent of community-dwelling elderly fall each year, with about 10 percent seeking emergency medical help for a fall injury. Data from CDC-funded study to assess falls among the elderly (SAFE) suggest that as many as 41 percent of elderly patients fall at home in the year following discharge from hospitalization due in part to deconditioning associated with inactivity.

Background:~The goal of this research was to determine if providing specialist input to primary care providers (PCPs) by means of informal consultation could improve the process and outcomes of care for diabetes. Several studies support the role for specialists and their specific knowledge and expertise in a variety of disorders including diabetes. A variety of methods have been designed to optimize the use of specialty expertise including practice guidelines and disease management approaches as well as the consultation/referral process. The referral-consultation process is an important mechanism for obtaining clinically useful information. At one end of the spectrum of this process, informal consultation involves discussion about a patient with a colleague without the consultant seeing the patient; at the other end of the spectrum, care of the patient is transferred to another physician and the process is formalized. Because much specialist expertise resides in the specialists themselves, the expansion of primary care sites to include community-based outpatient clinics has implications for access to the specialists located elsewhere. This study was designed to evaluate a computer-assisted voice mail system which is relatively inexpensive and more convenient than video-telemedicine systems, making it more practical and more easily exportable. Diabetes care delivery was chosen as the model in which to assess informal consultation based on its frequency among veterans, management challenges, and the emphasis on improvement in diabetes care in VA. A secondary goal of the project was to better characterize the consultation process.~Objectives:~Patients with diabetes mellitus are complex and may benefit from the input of multiple specialists and PCPs must determine the need for and coordinate the input from those multiple specialists. With that in mind, the three objectives of the study are: 1) To assess the impact of computer-assisted access to specialist expertise (CASE) on process of care for patients with diabetes mellitus; 2) To assess the impact of CASE on outcomes of care at the patient level (clinical outcomes and satisfaction), provider level (satisfaction) and the system level (health services utilization and costs); and 3) To characterize the consultation-referral process in community-based outpatient clinics (CBOCs).~Methods:~Randomized controlled trial with access to the CASE system constituting the intervention and a descriptive study of the consultation process. The major outcome variables will be the consultation type, adherence to diabetes practice guidelines, clinical outcome of diabetes care (glycemic control), patient and provider satisfaction.~Status:~Project work has been completed. The final report has been submitted.

The goal of this research was to determine if providing specialist input to primary care providers (PCPs) by means of informal consultation could improve the process and outcomes of care for diabetes. Several studies support the role for specialists and their specific knowledge and expertise in a variety of disorders including diabetes. A variety of methods have been designed to optimize the use of specialty expertise including practice guidelines and disease management approaches as well as the consultation/referral process. The referral-consultation process is an important mechanism for obtaining clinically useful information. At one end of the spectrum of this process, informal consultation involves discussion about a patient with a colleague without the consultant seeing the patient; at the other end of the spectrum, care of the patient is transferred to another physician and the process is formalized. Because much specialist expertise resides in the specialists themselves, the expansion of primary care sites to include community-based outpatient clinics has implications for access to the specialists located elsewhere. This study was designed to evaluate a computer-assisted voice mail system which is relatively inexpensive and more convenient than video-telemedicine systems, making it more practical and more easily exportable. Diabetes care delivery was chosen as the model in which to assess informal consultation based on its frequency among veterans, management challenges, and the emphasis on improvement in diabetes care in VA. A secondary goal of the project was to better characterize the consultation process.

Background:~Health care organizations, including the VA, are investing substantial effort to improve quality of care. As part of this process, greater emphasis is being placed on measurement of outcomes, and in particular, functional outcomes and satisfaction as reported by patients.~Objectives:~ACQUIP was designed to determine whether quality and outcomes of health care improve when primary care providers have access to regular assessments of their patients' health and function along with routine clinical data and information about clinical guidelines.~Methods:~This study was a randomized trial conducted at the General Internal Medicine Clinics of seven VA facilities. Each participating GIMC is organized into discrete firms staffed by different groups of providers who care for different patients. One randomly selected firm received the intervention and one served as control. Patients who made at least one GIMC visit in the last year were eligible to participate. Patients were surveyed at baseline to determine active medical problems. Subsequent mailings included a general evaluation of health status (SF-36), a satisfaction questionnaire and, as appropriate, one of six condition-specific questionnaires: the Seattle Angina Questionnaire, the Seattle Obstructive Lung Disease Questionnaire, the Hopkins Symptom Checklist (depression), and questionnaires regarding diabetes, drinking, and hypertension. Clinical/utilization data were downloaded weekly from VISTA and supplemented with data from Austin. The intervention consisted of multi-faceted reports to patients' primary care providers (at the time of patient visits) showing trended physiologic and health status data and guideline-derived recommendations. Clinicians also received periodical reports displaying trends in the health status and satisfaction of their patients compared with their clinic as a whole. Reports were supplemented by training on QI and health status measures.~Status:~Data collection was completed on April 1, 2000. Analysis of trial results will be completed January, 2001.

Health care organizations, including the VA, are investing substantial effort to improve quality of care. As part of this process, greater emphasis is being placed on measurement of outcomes, and in particular, functional outcomes and satisfaction as reported by patients.

Background:~A variety of models of psychiatric hospital alternative care have been developed over the past several decades. San Diego�s Short-Term Acute Residential Treatment (START) model is one of the best established of these alternatives, comprising a network of 6 facilities with a total of 77 beds. Although veterans have been among those served at START programs for many years, no previous study of START or any other model has focused specifically on veterans.~Objectives:~The study tested the hypotheses that veterans treated in a START program would demonstrate greater improvement in symptoms and quality of life, as well as greater satisfaction with treatment and lower costs of care than veterans treated at the VA inpatient unit.~Methods:~This study includes elements of both efficacy and effectiveness studies. VA psychiatric unit treatment and START are compared in a randomized trial, with follow up of subjects at 2, 6, and 12 months as they experience real-world treatment-as-usual. Symptoms, functioning, quality of life, and satisfaction with services are assessed on multiple standardized measures, as well as by qualitative assessments.~Status:~Final report is under preparation.

A variety of models of psychiatric hospital alternative care have been developed over the past several decades. San Diego�s Short-Term Acute Residential Treatment (START) model is one of the best established of these alternatives, comprising a network of 6 facilities with a total of 77 beds. Although veterans have been among those served at START programs for many years, no previous study of START or any other model has focused specifically on veterans.

Background:~We have previously shown (IIR 95-045) that teledermatology, using store and forward technology, can result in reliable and accurate diagnostic outcomes when compared to clinic-based dermatology consultations. This investigation builds on that fundamental diagnostic information by assessing the health services implications of a teledermatology consult system.~Objectives:~To investigate health services outcomes related to teledermatology implementation. Outcomes of interest were time to diagnosis and treatment initiation, the proportion of patients that avoided the need for a clinic-based encounter, and an economic analysis.~Methods:~Patients referred from the primary care clinics to the dermatology consult service were randomized to either usual care or a teledermatology consultation. A usual care consultation consisted a conventional text-based electronic consult request. A teledermatology consultation included digital images and a standardized history, in addition to the electronic text-based consult. Consultant dermatologists, reviewing the consult requests for both modalities, decided when, and if, a referral required a clinic-based evaluation.~Status:~Final report has been prepared and is in the review process at this time.

We have previously shown (IIR 95-045) that teledermatology, using store and forward technology, can result in reliable and accurate diagnostic outcomes when compared to clinic-based dermatology consultations. This investigation builds on that fundamental diagnostic information by assessing the health services implications of a teledermatology consult system.

This research on Functional Incidental Training ( FIT) primarily involves women in community nursing homes.~Objectives:~1. test the effects of FIT on functions such as transfer ability, continence, ambulation/mobility,balance and fall risk, strength, and endurance; 2. determine the characteristics of NHCU residents who respond to FIT; 3. identify the most sensitive outcome measures related to FIT; and 4. determine the labor costs of FIT relative to usual care.~. The intervention is an individualized rehabilitative protocol intended to improve mobility, endurance, strength and continence in frail, older, functionally impaired and disabled veterans in VA nursing home care units(NHCUs).The design is a multi-site cross-over design, to be carried out in five NHCUs (Atlanta, Durham, Salisbury, Augusta, Tuscaloosa) over about eight months in each site. About 24 residents will be recruited in each NHCU: 12 each will be randomized to initial intervention and control for 8 wks and evaluated; the controls will then receive the intervention and vice versa for another 8 wks with another evaluation. Patients are seen 4x a day for FIT activities, including walking/using wheel chair, prompted toileting, strengthening exercises. Outcome measures will be made in a blinded manner by Project Manager.

This research on Functional Incidental Training ( FIT) primarily involves women residing in community nursing homes. It is an individualized rehabilitative protocol intended to improve mobility, endurance, strength and continence in frail, older, functionally impaired and disabled veterans.~Objectives of the project are as follows:~1) Test the effects of FIT on transfer ability, continence, ambulation/mobility, balance and fall risk, strength, and endurance; 2) Determine the characteristics of NHCU residents who respond to FIT; 3)Identify the most sensitive outcome measures related to FIT; and 4) Determine the labor costs of FIT relative to usual care.

OBJECTIVES: I. Determine the toxicity and MTD of LErafAON when given by weekly IV infusion for 8 weeks in patients with advanced malignancies.~II. Characterize the plasma pharmacokinetics of LErafAON after IV infusion.~III. Document in vivo inhibition of Raf-1 protein by LErafAON.~IV. Detect anti-tumor effects of intravenous LErafAON.~PROTOCOL OUTLINE: This is a Phase I Maximum Tolerated Dose (MTD) study for patients with recurrent solid tumor malignancies. Study medication will be administered by intravenous infusion over at least 60 minutes, once per week, for 8 weeks. In the absence of progression, patients may continue on weekly treatment. Pre-medications will be administered prior to each dose of study medication. Patients will be followed for one month after receiving the last dose of study medication. Patients with Complete Response (CR), Partial Response (PR), or Stable Disease (SD) at the Week 8 disease assessment may continue to receive study medication until disease progression (PD).~Cohorts of at least three patients will be entered at escalating dose-levels. Each cohort will be observed for at least ten days after receiving the first dose of treatment before additional patients are treated at a higher dose level. Patients will be followed for one month after receiving the last dose of study medication. The study will stop when a maximum tolerated dose (MTD) is identified. Dose escalation within a patient will not be allowed.~PROJECTED ACCRUAL: Estimated enrollment is 15-35 patients; 3 per dose level, expanded to 6 if DLT occurs.

LErafAON is a liposome encapsulated c-raf antisense oligonucleotide. Raf-1 is a protein produced by human cells, both normal and cancerous, which may help protect tumor cells from radiation. Antisense oligonucleotides are very specific drugs, which can decrease the amount of a certain target protein by blocking the gene that makes it. Antisense oligonucleotide to raf gene can reduce the amount of Raf-1 protein in tumor cells. Liposomes are tiny globules of fat, which can carry drugs in the body. The experimental agent LErafAON is composed of liposomes carrying antisense oligonucleotide against the Raf-1 protein. It is hoped that decreased Raf-1 in the cancer cells will make them more sensitive to the radiation therapy.~Patients with advanced solid tumors will receive IV infusions of LErafAON over at least 60 minutes, once per week, for 8 weeks. In the absence of progression, patients may continue on weekly treatment. Pre-medications will be administered prior to each dose of study medication.~Cohorts of at least three patients will be entered at escalating dose-levels. Each cohort will be observed for at least ten days after receiving the first dose of treatment before additional patients are treated at a higher dose level. Patients will be followed for one month after receiving the last dose of study medication. The study will stop when a maximum tolerated dose (MTD) is identified. Dose escalation within a patient will not be allowed.

BACKGROUND~This protocol acknowledges that it is in the interest of the NIH and ROB, as well as our participants, to continue to follow those who have been treated with radiotherapy at ROB and are not otherwise eligible for current active research protocols.~It also provides a mechanism for the correlation and interpretation of disparate data for research into the long term side effects and outcomes for a variety of disease entities and treatments, such as combined modality treatment, MoAb, PDT, radiation modifiers,~intraoperative radiotherapy, etc.~OBJECTIVE~-The primary objective of this protocol is to assess the late effects of treatment and the natural history of disease through collection of data from any standard procedures performed as part of follow up care on participants previously treated with radiotherapy in the Radiation Oncology Branch (ROB).~ELIGIBILITY~-Participants who received radiation therapy at the NCI and are not enrolled on an interventional research protocol at the time of enrollment.~DESIGN~This is a natural history protocol in which data will be collected from Radiation Oncology Branch participants receiving standard of care long-term follow up care and evaluation, including NIH consultation services as required.~It will be made clear to participants in the consent form, that data collected during their follow-up may be used anonymously for publications concerning the natural history of disease processes and long-term effects of treatment.

Background:~This protocol acknowledges that it is in the interest of the NIH and ROB, as well as our patients, to continue to follow those who have been treated with radiotherapy at ROB and are not otherwise eligible for current active research protocols.~It also provides a mechanism for the correlation and interpretation of disparate data for research into the long term side effects and outcomes for a variety of disease entities and treatments, such as combined modality treatment, MoAb, PDT, radiation modifiers, intraoperative radiotherapy, etc.~Objective:~-The primary objective of this protocol is to assess the late effects of treatment and the natural history of disease through collection of data from any standard procedures performed as part of follow up care on patients previously treated with radiotherapy in the Radiation Oncology Branch (ROB).~Eligibility:~-Patients who received radiation therapy at the NCI and are not entered on an interventional research protocol at the time of enrollment.~Design:~This is a natural history protocol in which data will be collected from Radiation Oncology Branch patients receiving standard of care long-term follow up care and evaluation, including NIH consultation services as required.~It will be made clear to patients in the consent form, that data collected during their follow-up may be used anonymously for publications concerning the natural history of disease processes and long-term effects of treatment.

Background:~-This protocol will provide a means for screening potential candidates for NCI Radiation Oncology Branch (ROB) protocols.~Objectives:~-To permit evaluation of patients referred to the NCI Radiation Oncology Branch in order to identify individuals who will be suitable candidates for Radiation Oncology Branch clinical research protocols.~Eligibility:~-Patients suspected of having, or with biopsy proven malignant disease or patients with a benign condition for whom radiotherapy is a potential treatment.~Design:~-This is a screening protocol. No investigational treatments will be administered on this protocol.

Background:~-This protocol will provide a means for screening potential candidates for NCI Radiation Oncology Branch (ROB) protocols.~Objectives:~-To permit evaluation of patients referred to the NCI Radiation Oncology Branch in order to identify individuals who will be suitable candidates for Radiation Oncology Branch clinical research protocols.~Eligibility:~-Patients suspected of having, or with biopsy proven malignant disease or patients with a benign condition for whom radiotherapy is a potential treatment.~Design:~-This is a screening protocol. No investigational treatments will be administered on this protocol.

Most bone marrow transplantations for malignant and non-malignant disease include whole body irradiation. Techniques for administering that treatment, including patient positioning, lung and soft tissue compensation, dose rate, total dose and fractionation differ between institutions. These differences are optimized at each institution to limit toxicity and maximize therapeutic outcome.~Technically complex procedures such as total body radiation are subject to equipment failures. Such failures mid-treatment could be catastrophic to the patient, since therapy must be timely and compatible therapy may not be available elsewhere in the community. The purpose of this protocol is to provide backup between George Washington University Medical Center and the Radiation Oncology Branch of the NCI to allow for orderly, safe, and compatible therapies in the event of equipment failure; or replacement of a linear accelerator or any other malfunctioning equipment necessary to deliver TBI; or any emergent situation.

Most bone marrow transplantations for malignant and non-malignant disease include whole body irradiation. Techniques for administering that treatment, including patient positioning, lung and soft tissue compensation, dose rate, total dose and fractionation differ between institutions. These differences are optimized at each institution to limit toxicity and maximize therapeutic outcome.~Technically complex procedures such as total body radiation are subject to equipment failures. Such failures mid-treatment could be catastrophic to the patient, since therapy must be timely and compatible therapy may not be available elsewhere in the community. The purpose of this protocol is to provide backup between George Washington University Medical Center and the Radiation Oncology Branch of the NCI to allow for orderly, safe, and compatible therapies in the event of equipment failure; or replacement of a linear accelerator or any other malfunctioning equipment necessary to deliver TBI; or any emergent situation.

We propose to determine the response of a newly developed laser heated, vycor glass fiberoptic radiation dosimetry system to ionizing radiation in a clinical radiotherapy environment. Present systems measure only total dose or have limitations, such as instability, non-linearity, excessive size or a decoupled measurement system, making them unsuitable in a variety of clinical applications. This fiberoptic coupled dosimetry system is a new and innovative technology application which allows on-line measurement of instantaneous dose rate and total dose never before achievable. It offers a clear advantage in patient treatment delivery, allowing on-line corrections essential to a new generation of radiotherapy treatment machines with development of beam intensity modulation as an adjunct to 3D conformal therapy. It also has the advantage of submillimeter size and is minimally invasive, making it ideal for brachytherapy.~This system has the potential for stable, accurate, reproducible, clinically feasible measurements of total dose and dose rate. The output of this system will be measured under various clinical conditions encountered in a clinical setting and compared against existing thermolumeniscent and diode dosimetry standards. Initial measurements will use a tissue equivalent phantom for depth dose and accuracy measurements. Additional studies will include dosimetric measurements of routine clinical treatment setups on patients receiving therapeutic irradiation.

We propose to determine the response of a newly developed laser heated, vycor glass fiberoptic radiation dosimetry system to ionizing radiation in a clinical radiotherapy environment. Present systems measure only total dose or have limitations, such as instability, non-linearity, excessive size or a decoupled measurement system, making them unsuitable in a variety of clinical applications. This fiberoptic coupled dosimetry system is a new and innovative technology application which allows on-line measurement of instantaneous dose rate and total dose never before achievable. It offers a clear advantage in patient treatment delivery, allowing on-line corrections essential to a new generation of radiotherapy treatment machines with development of beam intensity modulation as an adjunct to 3D conformal therapy. It also has the advantage of submillimeter size and is minimally invasive, making it ideal for brachytherapy.~This system has the potential for stable, accurate, reproducible, clinically feasible measurements of total dose and dose rate. The output of this system will be measured under various clinical conditions encountered in a clinical setting and compared against existing thermolumeniscent and diode dosimetry standards. Initial measurements will use a tissue equivalent phantom for depth dose and accuracy measurements. Additional studies will include dosimetric measurements of routine clinical treatment setups on patients receiving therapeutic irradiation.

Patients undergoing immunotherapy for advanced cancer under IRB-approved protocols, who are to receive immune cells in adoptive transfer, will have less than or equal to 50% of those cells labeled with In-111-oxine and administered along with the remainder of their unlabeled cells. They will then undergo gamma-camera imaging over the next 0-7 days and blood samples and tumor sites which are accessible with minimal surgery (low-risk biopsy) may be sampled in some patients for enumeration of radiolabeled cells. End-points will be tumor and normal organ imaging and the amount of In-111 per gram of tissue in biopsies or per ml. of blood.

Patients undergoing immunotherapy for advanced cancer under IRB-approved protocols, who are to receive immune cells in adoptive transfer, will have less than or equal to 50% of those cells labeled with In-111-oxine and administered along with the remainder of their unlabeled cells. They will then undergo gamma-camera imaging over the next 0-7 days and blood samples and tumor sites which are accessible with minimal surgery (low-risk biopsy) may be sampled in some patients for enumeration of radiolabeled cells. End-points will be tumor and normal organ imaging and the amount of In-111 per gram of tissue in biopsies or per ml. of blood.

This study evaluates a system of remote supervision of laparoscopic surgery. Laparoscopic surgery is performed through small holes in the abdomen called ports. A camera is passed through one port for visualization. Laparoscopic surgery requires an assistant to hold the camera and help the operating surgeon view the surgical field. The assistant camera holder may be a surgeon or a robotic arm. The robotic arm is usually controlled by the operating surgeon. In this study, a robotic arm holding the camera will be used, and will be controlled by a surgeon outside the operating room.

This study evaluates a system of remote supervision of laparoscopic surgery. Laparoscopic surgery is performed through small holes in the abdomen called ports. A camera is passed through one port for visualization. Laparoscopic surgery requires an assistant to hold the camera and help the operating surgeon view the surgical field. The assistant camera holder may be a surgeon or a robotic arm. The robotic arm is usually controlled by the operating surgeon. In this study, a robotic arm holding the camera will be used, and will be controlled by a surgeon outside the operating room.

The utility of PEREGRINE Monte Carlo calculations for radiation treatment planning in a clinical setting will be assessed by comparing results with other fully three-dimensional programs. ROB will investigate PEREGRINE for clinical use at NCI.

The utility of PEREGRINE Monte Carlo calculations for radiation treatment planning in a clinical setting will be assessed by comparing results with other fully three-dimensional programs. ROB will investigate PEREGRINE for clinical use at NCI in collaboration with Lawrence Livermore National Laboratory (LLNL).

Over 60 million Americans use herbal medicines; of these, one-fourth also take prescription drugs. Physicians are often unaware of herbal use and of possible drug/herb interactions in their patients. Ginseng and ginkgo, enhancers of physical and mental performance, are two of the most widely taken herbals. We propose a double-blind, randomized, prospective study of effects of ginseng and ginkgo on 1) disposition of probe drugs, 2) cognitive function, and 3) glutathione-S-transferase (GST) and quinone reductase (NQ01), enzymes implicated in chemoprevention of cancer. Probe drugs will be administered to study effects of herbs on their disposition, not for therapeutic effect. Ideal probes must be safe, well tolerated, have minimal pharmacological effect, and share known metabolic pathways with other clinically used drugs. Medically stable drug-free non-smokers will be enrolled.~During a 4-week single-blind run-in, subjects will be given a 4-drug probe cocktail: caffeine to study cytochrome P4501A2 (CYP1A2), dextromethorphan for CYP2D6, buspirone (and endogenous cortisol) for CHP3A and fexofenadine for P-glycoprotein. Losartan will be given separately for CYP2C9. These enzymes metabolize over 95% of clinically used drugs. Enzyme activities will be determined by assaying appropriate blood and urine specimens for probe drugs and metabolites. Cognitive function will be tested and blood lymphocytes collected for measuring GST and NQ01 activities. Sixty subjects will then be randomly assigned to one of 4 double-blind treatment groups of 15 each: 1) ginseng extract (Ginsana), 2) ginkgo extract (Egb761), 3) both herbs, or 4) matching placebos. Tolerability of herbs will be determined. After 6 to 8 weeks of twice daily treatment with study agents, all effect parameters will be reevaluated: probe drug pharmacokinetics, cognitive function, and GST and NQ01 in blood lymphocytes. Interactions of chronic ginseng and ginkgo with drug-metabolizing pathways and with cognitive function will thus be determined.

This study will assess the effects of ginseng and ginkgo on 1) cognitive function, 2) enzymes that process drugs, and 3) enzymes that may help prevent cancer.

This study will attempt to replicate findings suggesting that visual evoked potentials generated in one human brain (Subject A) by photostimulation can generate a correlated EEG signal in the brain of another human subject (subject B) who is located at a distance (14.5 meters) and who is not visually stimulated.~This project will occur in three stages. First we will identify pairs of subjects who have cross-correlated evoked potentials during photostimulation to Subject A at the p < .01 level of significance. If no pairs can be identified we will continue to enroll and test up to 50 pairs of subjects. If pairs of subjects that demonstrate the phenomenon cannot be identified using this p value by the end of the project time line we will reject the hypothesis that remote transfer of neural energy occurs and report failure to replicate the original study. If we detect greater than or equal to 5 pairs of subjects who meet the criteria we will attempt to replicate in those pairs using a higher criteria of p < .001. If Grinberg-Zylberbaum et al's experiment can be replicated at both stages, the project team will go to stage 3 to investigate the same phenomenon in the identified pairs of human subjects using functional magnetic resonance imaging (fMRI) as a second independent neurophysiological measure of transfer of information between two human brains. We will record fMRIs (occipital, temporal, frontal and parietal) in the remote individual while their counterpart, located in a separate chamber, is receiving light stimulation in an on-off pattern. We will determine if there are statistically significant differences in digitized fMRI during lights on vs. lights off conditions. The main outcome measures for this project will be the binary (yes-no) output from statistical analysis using cross-correlational and z-score testing for the detection of a transferred evoked signal (in both EEG and fMRI experiments) in Subject B. Appropriate controls will be used. If replicated, this study will provide a useful technology and method to quantitatively investigate the characteristics and neural mechanisms of remote effects of mental events. Such experimental methods will assist in the investigation of basic mechanisms involved in mind-body medicine.

The purpose of this study is to determine whether visual evoked potentials generated in one human brain by photostimulation can generate a correlated EEG signal in the brain of another human subject who is located at a distance and who is not visually stimulated.

Background:~The NCI Surgery Branch~Multiple risk factors for breast cancer have been identified, including family history, endocrine background, histologic changes in breast tissue, cancer in one breast, radiation exposure, obesity, and others. The histologic phenotypes of breast carcinogenesis include a spectrum of changes, beginning with normal appearing breast epithelium, progressing to hyperplasia, atypical hyperplasia, in situ carcinoma, and finally invasive carcinoma.~Our present knowledge of high risk breast tissue is based on the study of a variety of cellular sample types, which include fine needle aspirates, nipple aspirate fluid, core needle biopsies, and breast tissue from mastectomy or segmentectomy specimens.~Valid preclinical models are needed which utilize homogenous human cellular material which can be studied over time in large quantities.~A model which may be ideally suited to the metabolic and molecular studies of breast epithelial cells is an in vitro cell line model developed from high risk breast tissue.~In this study normal breast tissue will be acquired from each of the high risk sites for breast cancer in the breast. These tissues will be used to develop breast epithelial cell lines for in vitro studies, and to establish a high risk cell line and tissue repository.~Objectives:~To acquire normal breast tissue from each of the high risk sites for breast cancer in the breast.~To develop breast epithelial cell lines from the normal high risk breast tissue from each of the major high risk sites.~To establish a repository of high risk breast epithelial cell lines and high risk normal breast tissue which can be used as a resource for pilot studies at NIH and other participating centers to characterize high risk breast epithelial cells~Eligibility:~Women age 20 - 80 years who have an increased risk of breast cancer because they are members of a high risk breast or ovarian cancer family.~Women with a history of ipselateral breast cancer, either invasive or in situ, and a normal contralateral breast by mammography (within the past 12 months) and a normal physical examination of the contralateral breast and adjacent lymph node bearing areas, or be undergoing prophylactic mastectomy.~Women without breast cancer but with a Gail model estimate of 5-year risk of breast cancer of 1.67 percent or higher.~Women with bilateral breast cancer (invasive or in situ) who have not received whole breast irradiation to both breasts.~Women with a previous history of mediastinal irradiation for lymphoma before the age of 30 and who are now greater than 5 years since completing radiation therapy.~Normal women not at increased risk of breast cancer (Gail model Index of less than 1.50 percent) and without abnormal findings in the breast by physical examination and mammography to serve as normal control tissue.~Women with a mutation in a breast cancer susceptibility gene, but whose family history is not known.~Absence of significant cardiac, hepatic or renal disease, which, in the opinion of the PI, is likely to cause metabolic changes in the breast tissue.~Design:~A tissue acquisition in which Normal breast tissue will be collected from women at high risk of breast cancer at NIH and at other institutions as well. Centers collecting tissue for this protocol must have IRB approval for this study and an IRB approved Informed Consent.~All breast tissue will be obtained from surgical specimens acquired as part of planned surgical procedures. Short-term cell lines will be developed from this tissue and confirmed cytologically and by expression of cytokeratins. Multiple cell lines from each of the high risk categories will be developed.~These cell lines and the respective tissues will be used to establish a repository of high risk breast epithelial cell lines and high risk breast tissues which can be used to further define the carinogenic pathway for breast cancer. Early passages of these cell cultures and the respective normal breast tissue will be stored for future studies.~100 patients will be enrolled over a period of 5 years.

Background:~Many risk factors for breast cancer have been identified, including family history, endocrine background, changes in breast tissue, cancer in one breast, radiation exposure, obesity and others. There is a spectrum of tissue changes seen in cancerous and pre-cancerous breast tissue.~A cell line is a collection of cells that are grown in the laboratory from an original tissue specimen. Cell lines developed from high-risk breast tissue allow researchers to perform metabolic and molecular studies of breast cells over time.~Objective: To establish a repository (facility in which tissue samples can be preserved and stored for many years) of cell lines from high-risk breast tissue to allow researchers to learn more about changes in breast cells that may cause them to develop into breast cancer.~Eligibility: Women between 20 and 80 years of age who:~Have an increased risk of breast cancer because they are members of a high-risk breast or ovarian cancer family.~Have had breast cancer in one or both breasts.~Have had radiation for lymphoma before the age of 30.~Have a mutation in a breast cancer susceptibility gene, but whose family history is not known.~Are not at increased risk of breast cancer.~Design:~A small piece of breast tissue will be obtained from about 10 women without an identified risk of breast cancer and up to 100 women at high risk of developing breast cancer.~Cell lines will be developed from each high-risk category.~The cell lines and tissues will be used to establish a repository of high-risk breast cell lines and breast tissues that can be used to study how the cells develop into breast cancer.

The regimen-related toxicities associated with bone marrow transplantation (BMT) can be severe and even life threatening. The overall goal of this randomized controlled pilot study in BMT patients is to determine the effect of relaxation/stress reduction strategies on: (1) the frequency/severity of toxic side effects of marrow ablative chemotherapy, and (2) the timing of immune reconstitution. Substantial literature indicates that music therapy-based interventions are effective in inducing relaxation and also affect immune function by modulating circulating and salivary levels of such agents as cortisol, immunoglobulin A, interleukin-1, natural killer cells, and a variety of other immune system-related substances. Over the past two years, we have provided music therapy-based stress reduction/relaxation interventions to a convenience sample of patients undergoing BMT. Preliminary findings from this pilot feasibility study demonstrate that patients report significantly decreased pain (p< .004) and sense of nausea (p < .001) following an intervention. Average time-to-engraftment was 13.5 (+/- 2.85) days as compared to 15.5 (+/- 4.40) days (p < .O1) for a group of historical controls matched on diagnosis, type of transplant, conditioning regimen, date of transplant, age, and gender. Although highly promising, our data are limited by lack of randomization, an appropriate control condition, measurement of psychologic factors known to influence outcome in BMT, and systematic monitoring of early phase markers of immune reconstitution that could help explain the phenomena we have observed. This proposal corrects these shortcomings and especially highlights the potential mediational effect of cytokine release on regimen-related toxicities and the timing of immune reconstitution.

The purpose of this study is to determine the effects of music therapy-based relaxation stress/reduction strategies on the frequency/severity of toxic side-effects of marrow ablative chemotherapy and the timing of immune reconstitution in patients undergoing bone marrow/stem cell transplantation.

Intervention: No intervention.~Primary Hypothesis: It is feasible and cost-effective to create a CSP-wide facility for banking genetic tissue in CSP studies.~Study Abstract: This is a program-wide genetic tissue databank for the Department of Veterans Affairs Cooperative Studies Program (CSP). The study has five components: a central repository for DNA and other genetic tissue specimens; a Scientific Advisory Committee of individuals with expertise in the genetics and epidemiology of diseases with special importance to the VA (including cardiovascular, neurologic, respiratory, psychological and other disorders); an Ethical Oversight Committee of individuals with expertise in bioethics and the law, as they apply to the collection and use of genetic tissue, A Veteran's Advisory Group, and a Coordinating Center administers the tissue bank, coordinates the three oversight committees, maintains central access to clinical study data linked to the tissue bank, and provides statistical analysis.

This project is a program-wide genetic tissue databank for the Department of Veterans Affairs Cooperative Studies Program (CSP). The genetic tissue bank has four components: a central repository for DNA and other genetic tissue specimens; a Scientific Advisory Committee of individuals with expertise in the genetics and epidemiology of diseases with special importance to the VA (including cardiovascular, neurologic, respiratory, psychological and other disorders); an Ethics Oversight Committee of individuals with expertise in bioethics and the law, as they apply to the collection and use of genetic tissue, and a Coordinating Center that administers the tissue bank, coordinates the scientific and ethics oversight committees, maintains central access to clinical study data linked to the tissue bank, and provides statistical analysis.

Objective of this two parallel component study is to develop interventions for the visual and cognitive related health literacy disabilities of older veterans. The first component will test two interventions for improving functional health literacy performance (enhancing the design of health literacy materials and training reading skills) by using a 2 x 2 between subjects factorial design. The second component consists of patient, family, and provider focus groups who will help determine where to apply and disseminate the interventions by identifying problematic sources of text-based health materials. Finally, as a result of both components, improved health information design guidelines and training protocols will be developed as rehabilitative interventions for health literacy disability.~Specific research questions are:~Can the lower functional health literacy performance of veterans be improved by following text design directives intended to account for age-related visual and cognitive changes (enhanced version)?~Does instruction in skills and strategies for reading yield improvements in functional health literacy performance?~Does instruction in reading skills and enhanced text design improve functional health literacy to a greater extent than either intervention alone?~Are reading gains maintained over time?~What everyday sources of functional health literature are problematic for today's veterans?~How do visual, cognitive, and descriptive factors contribute to change in functional health literacy score?~What is the functional health literacy of older veterans who utilize Atlanta VA health care?~Focus Groups: Three two-hour focus groups will be composed of 15 VA health professionals, 15 outpatient veterans aged 65 and older with low functional health literacy, and 15 family members of veterans with low functional health literacy. These focus groups will identify sources of text-based health information which they find to be problematic from their respective perspectives. These sources, as well as recommendations for the application and dissemination of guidelines and directives for improved health information designs and training protocols, will be compiled using transcription and analysis of focus group sessions.~Interventions: Community dwelling veterans aged 65 and older will be recruited from the Geriatric Primary Care Clinic and the Veteran's Learning Center. Ethnicity, education, health status, general literacy, and other descriptive information will be recorded. Visual baseline measures will include assessments of visual skills for reading and visual function. Cognitive baseline measures will include assessments of word recognition, text comprehension ability, verbal working memory, perceptual speed and vocabulary level. Functional health literacy, measured by the TOFHLA, will be the main outcome measure. This objective and standardized instrument measures the ability of adults to read and understand medical instructional and health care information presented in prose passages and passages containing numerical information. Two hundred and forty participants demonstrating inadequate functional health literacy scores (by the screening instrument STOFHLA) will be randomly assigned to one of four groups: control (N=60), enhanced only (N=60), reading skills and strategies instruction only (N=60), or enhanced with reading skills and strategies instruction (N=60). All participants will receive vision and cognition testing and will then participate in two 2-hour sessions. Depending on group assignment participants will either 1) read standard health-related material (control) 2) read enhanced health-related material (enhanced) 3) receive reading skills training (training) 4) receive reading skills training with enhanced materials (training and enhanced).

The objective of this two parallel component study is to develop interventions for the visual and cognitive related health literacy disabilities of older veterans. The first component will test two interventions for improving functional health literacy performance (enhancing the design of health literacy materials and training reading skills) by using a 2 x 2 between subjects factorial design. The second component consists of patient, family, and provider focus groups who will help determine where to apply and disseminate the interventions by identifying problematic sources of text-based health materials. Finally, as a result of both components improved health information design guidelines and training protocols will be developed as rehabilitative interventions for health literacy disability.

There is growing concern about adverse developmental effects in infants and young children from prenatal exposure to environmental air pollutants, including polycyclic aromatic hydrocarbons (PAH), particulate matter (PM2.5), and environmental tobacco smoke (ETS). The proposed study combines expertise in molecular epidemiology and biomarkers, state-of- the-art pollutant monitoring techniques, and a strong theoretical framework to guide assessment of the impacts of these pollutants on fetal and child growth and development. The specific aims are: 1. To test the hypothesis that prenatal exposure to airborne polycyclic aromatic hydrocarbons (PAH) adversely affects fetal growth and early childhood growth and development, after controlling for non-PAH components of PM2.5, ETS, nutritional status (essential fatty acids and antioxidants) and other potential confounders; 2. To explore whether non-PAH components of PM2.5, and ETS have an independent effect on birth outcomes and childhood growth and development, after controlling for PAH, and to explore possible interactions between PAH, PM2.5 and ETS; and 3. To estimate the relative contribution of ambient PAH pollution vs. ETS and other indoor PAH sources to a) personal PAH exposure and PAH-DNA adducts and b) impairment of fetal growth and early child development. To achieve these aims, the international team of researchers will carry out a prospective cohort study of 400 nonsmoking pregnant women living in Krakow, Poland, and will follow their newborns for 12 months postnatally. Fetal growth will be assessed at birth by weight, length, head circumference, and size for gestational age. Childhood growth and developmental outcomes will be measured using the Fagan Test and the Bayley Scales. Strengths of the research include the combination of personal inhalation monitoring of PAH and PM2.5 with biomarkers (umbilical cord blood levels of PAH-DNA adducts, cotinine, essential fatty acids, antioxidants and lead) to estimate in utero exposure to the pollutants of interest and potential confounders. The Polish cohort provides a valuable model for study since emissions from coal burning and traffic are relatively high. However, the results will be broadly applicable since exposures to PAH, ETS and PM2.5 during pregnancy are common in virtually all industrialized regions of the world. It is anticipated that this research will provide relevant data to policymakers concerned with protecting the health of young children.

The goal of this study is to examine the effects of in utero and postnatal exposure to environmental pollutants in a cohort of pregnant women and their newborns in Krakow, Poland

This is a non-randomized, open-label, Phase I study. A modified Fibonacci dose escalation will be used to determine the MTD for subsequent Phase II trials. Study duration is expected to be 12 to 18 months. Patients with a histological or cytological diagnosis of a solid tumor who have failed standard therapy or for whom no standard therapy exists are enrolled. If there is no dose limiting toxicities and if patients meet the inclusion criteria and have none of the exclusion criteria of the protocol, they will receive further cycles of therapy if there is no evidence of disease progression.

A study for patients who have failed standard therapy. If there is no dose limiting toxicities the patients will receive further cycles of therapy if there is no evidence of disease progression.

Identify the maximum tolerated dose (MTD) and safety of CDC-501 when given in a 6-week cycle in patients with solid tumors that are refractory after standard treatment

To identify the maximum tolerated dose (MTD) and safety of CDC-501 when given in a 6-week cycle in patients with solid tumors that are refractory after standard treatment.

Motor training results in use dependent plasticity (UDP), thought to underlie recovery of motor function after brain injury. The purpose of this protocol is to determine (a) if movement observation results in encoding of a motor memory in the primary motor cortex and (b) if observation of motor training can enhance the effects of physical training in healthy volunteers. If so, this may become an important tool in rehabilitative treatment for patients who are unable or partially able to train. We will test our hypotheses by means of focal single pulse transcranial magnetic stimulation (TMS) in a group of healthy volunteers. Our outcome measure will be the change in TMS-evoked movement direction as a function of training strategy. So far we found that this is the case in healthy volunteers (see data in analysis of the study). The purpose of this protocol is to determine if action observation can elicit the same effects in adult chronic ischemic stroke patients who have had originally significant motor weakness but recovered to the point of being able to perform the motor tasks, possibly resulting in a useful rehabilitative strategy.

Motor training results in use dependent plasticity (UDP), thought to underlie recovery of motor function after brain injury. The purpose of this protocol is to determine (a) if movement observation results in encoding of a motor memory in the primary motor cortex and (b) if observation of motor training can enhance the effects of physical training in healthy volunteers. If so, this may become an important tool in rehabilitative treatment for patients who are unable or partially able to train. We will test our hypotheses by means of focal single pulse transcranial magnetic stimulation (TMS) in a group of healthy volunteers. Our outcome measure will be the change in TMS-evoked movement direction as a function of training strategy. So far we found that this is the case in healthy volunteers (see data in analysis of the study). The purpose of this amendment is to determine if action observation can elicit the same effects in adult chronic ischemic stroke patients who have had originally significant motor weakness but recovered to the point of being able to perform the motor tasks, possibly resulting in a useful rehabilitative strategy.

Background:~The adverse impact of tobacco use on disease prevalence and health care costs is well documented. Hence, finding effective ways to reduce tobacco dependence is an essential component of improving the outcomes, quality and efficiency of VHA care. The U.S. Public Health Service (PHS) Smoking Cessation Clinical Practice Guideline provides specific recommendations for treating tobacco dependence. Despite their strong evidence base, however, these recommendations have not been fully integrated into clinical practice within the VHA. Recent data suggest that logistical difficulties associated with identifying and linking smokers with appropriate treatments may explain why the PHS Smoking Cessation Guideline has not been more broadly implemented.~Objectives:~The primary objective of this study is to assess the effectiveness of an intervention for increasing the rate of tobacco dependence treatment in a population of smokers identified through the VA Pharmacy Benefits Management database. Secondary objectives of this study include (1) assessing the effect of the intervention on smoking cessation rates, and (2) developing options for overcoming potential barriers to broad implementation of the strategies.~Methods:~The effectiveness of the intervention will be evaluated using a multi-center, randomized, controlled trial. Veterans receiving a prescription for transdermal nicotine, nicotine gum, or bupropion for smoking cessation in the past year at one of the participating VHA facilities (as determined from Pharmacy Benefits Management records) will be eligible for the study. A total of 1,900 eligible veterans selected from five test sites will be randomly assigned to one of two groups: (1) patient phone call and tailored, computerized prompt to providers (intervention), or (2) usual care (control). The primary outcome is the proportion of patients receiving pharmacological or other smoking cessation treatment in the six month follow-up period, as assessed from VA pharmacy and outpatient data files. All patients will be recruited to a brief phone interview six months post-intervention to gather secondary outcome measure data related to smoking status, quit history, and use of smoking cessation assistance.~Status:~Data preparation and analysis.

The adverse impact of tobacco use on disease prevalence and health care costs is well documented. Hence, finding effective ways to reduce tobacco dependence is an essential component of improving the outcomes, quality and efficiency of VHA care. The U.S. Public Health Service (PHS) Smoking Cessation Clinical Practice Guideline provides specific recommendations for treating tobacco dependence. Despite their strong evidence base, however, these recommendations have not been fully integrated into clinical practice within the VHA. Recent data suggest that logistical difficulties associated with identifying and linking smokers with appropriate treatments may explain why the PHS Smoking Cessation Guideline has not been more broadly implemented.

BACKGROUND/RATIONALE:~The Veterans Administration system supports telemedicine (TM) to provide medical consultations between patients and physicians via videoconference. At present, little is known about the impact of such TM consultations on patient-physician communication and related health outcomes. Analyses of in-person (IP) medical encounters have shown that effective patient-physician communication is associated with improved health outcomes.~OBJECTIVE(S):~To determine whether the physical separation between patient and physician required during TM has an affect on patient-physician communication and related outcomes, including patient and physician satisfaction, patient compliance, and patient understanding of medical care.~METHODS:~In this clinical trial, 238 patients were randomized to receive either consultative care at the remote site via TM with a consultant physician located the Milwaukee VA (intervention) OR by an IP consultation with a consultant physician at the Milwaukee VA (control). The same group of consultant physicians provided both IP and TM consultations.~Patients in both study arms had their medical encounter video recorded. We compared patterns and quality of patient-physician communication for the TM and IP encounters, using the Roter Interaction Analysis System. Data on patient and physician satisfaction with the encounter and patients' understanding of their medical problems were collected at the end of each medical encounter. Patient compliance (medication refill behavior) was assessed at 90 days post visit. The frequency of communication behaviors during the TM and IP encounters was compared using the analysis of a Linear Mixed Model. Comparison of patient satisfaction, physician satisfaction, patient compliance, and patient knowledge measures between TM and IP groups were conducted with similar Linear Mixed Models.

The purpose of this study is to determine whether the physical separation between patient and physician required during telemedicine has an affect on physician-patient communication and related outcomes, including patient and physician satisfaction, patient compliance, and patient understanding of medical care.

Background:~We have previously shown that: 1) time tradeoff utilities for current health are high, indicating that patients have a strong will to live; 2) half of patients felt that their life was better now than before they were HIV-infected; and 3) certain non-health-related factors such as spirituality and concern and love for one�s children correlated with health values and a sense that life has improved.~Objectives:~1) To assess health values of veterans and non-veterans with HIV/AIDS; 2) To characterize spirituality in patients with HIV/AIDS; 3) To derive a power function relating health ratings to utilities; and 4) To assess whether society assigns higher values to health states for veterans than for non-veterans.~Methods:~We interviewed 100 representative veterans with HIV/AIDS from the Cincinnati and Pittsburgh VAMCs and, concurrently, 350 non-veterans with HIV/AIDS from Cincinnati and Washington, DC, twice over 12-18 months. The patient questionnaire included clinical and demographic data; health values measures; a question comparing life now with life before being infected with HIV; and measures of health status/health concerns, HIV symptoms, depressive symptoms, spirituality/religion, adherence, social support, self-esteem, and optimism. We also assessed how medical house officers rate and value the health state of a hypothetical patient with congestive heart failure, identified either as a 72-year-old veteran or merely as a 72-year-old male.~Status:~Data collection completed ahead of schedule. Several manuscripts published with others to be submitted soon.

We have previously shown that: 1) time tradeoff utilities for current health are high, indicating that patients have a strong will to live; 2) half of patients felt that their life was better now than before they were HIV-infected; and 3) certain non-health-related factors such as spirituality and concern and love for one�s children correlated with health values and a sense that life has improved.

There are 34 million adolescents between the ages of 11 and 17 years old in the United States. Approximately 12% of them are African American. These youths experience earlier pubertal onset and face earlier challenges to participate in sexual activity, and therefore have earlier potential for pregnancy and contraction of sexually transmitted diseases. Experts in adolescent research have recommended developing and implementing new interventions to reduce early sexual activity; these interventions should target middle school-aged youths. The purpose of this study is to evaluate the efficacy of the NIA intervention on intention to engage in early sexual behavior and actual involvement in early sexual behavior in a convenience sample of sixth and seventh grade African American girls.~NIA is a Swahili word that means having a sense of purpose. It is one of the seven principles of Kwanzaa, a holiday that celebrates African Americans' cultural roots in Africa. The intervention was named after a self-development program for African American girls to highlight the intervention's cultural basis.~The study will provide 12 weekly and 5 booster after school didactic sessions; these sessions will teach health promotion and decision making skills to help girls successfully avoid situations where sexual activity is invited. Mothers and daughters will collaborate on homework assignments on puberty, heterosexual relationships, and sexual issues. The study will provide an evening mother-daughter workshop on sexual responsibility and a Baby-Think-It-Over weekend experience for girls using a computerized doll. Finally, the study will provide five Hey Baby! role-play vignettes to teach girls how to avoid heterosexual relationships that may lead to sexual activity.~The NIA intervention will be compared against a usual after-school activity control group of sixth and seventh grade African American girls in two public middle schools in the Pittsburgh Public School system. Participants will be randomly assigned to either the NIA intervention group or the control group. Each participant will be in the study for 1 year. There will be a 12-week main intervention in the fall, a 5-week booster in the spring, and final testing 1 year after study entry. Assessments will be primarily paper and pencil tests of the study's main outcome variables: attitude toward early sexual behavior (ESB); subjective norms (mother, father, peer) toward ESB; intention to engage in ESB; and self-reported ESB. Additionally, there will be knowledge content quizzes after each main intervention or booster session and a written evaluation of the Baby-Think-It-Over weekend.

This study will evaluate the effectiveness of a program designed to prevent early sexual behavior in middle school-aged African American girls.

The purpose of this study is to learn more about the effects of gamma-hydroxybutyric acid by comparing its physiological, behavioral and subjective effects with those of several other drugs.~This trial will be conducted as a double-blind, double-dummy, placebo-controlled, counter-balanced (Latin-square design) crossover study in volunteers with histories of sedative abuse. Volunteers will be recruited through advertising and word-of-mouth.~Volunteers will reside on our residential research unit for the duration of the study and participate in a maximum of 16 experimental sessions. Sessions will be conducted five days a week (Monday through Friday). The primary subjective and behavioral measures will be taken before drug administration and at 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours after drug administration.

The purpose of this study is to learn more about the effects of gamma-hydroxybutyric acid (GHB) by comparing its physiological, behavioral and subjective effects with those of several other drugs.

Training that involves heavy loads or resistance strengthens muscles. Recent data suggest that substantial voluntary strength gains can be achieved with training involving low resistance and strong mental effort. In contrast, individuals who train with the same low intensity contractions but with low mental effort show no improvement in strength.~This study will evaluate the relationship between mental effort muscle strength improvements by comparing the improvement in muscle strength in participants who have trained with different levels of mental effort. In addition to evaluating muscle strength, this study will also examine the neural mechanisms underlying muscle strength improvements.~Four groups of volunteers (65 years old and over) will participate in a training program directed at elbow-flexor muscles. One group will be trained with an intensity near the level of maximal voluntary contraction (MVC group); a second group will be trained with high mental effort, low muscle intensity contractions (HME group); a third group will be trained with low mental effort, low muscle intensity elbow-flexion contractions (LME group); and the fourth (control) group will not be trained but will participate in the strength tests. Training will be performed every weekday for 12 weeks. Participants will be evaluated by functional MRI (fMRI), EEG-derived motor activity-related cortical potential (MRCP), surface EMG signals, and the MRI T2 relaxation time.~Preliminary analysis of results shows that the HME group gained more than 13% strength, the LME group showed a statistically insignificant 6% change, and the no-practice control group did not show any change in elbow flexor muscle strength. We expect the MVC group to have the highest strength gains among the four groups.

The purpose of this study is to determine the effect of mental effort on improving muscle strength.

This study will examine the language, reasoning, and social skills used by preschool and elementary school children when they and their parents attempt to understand, conduct, and resolve disputes in everyday family interaction. Families will be given conflict resolution training designed to promote listening and speaking skills that result in more accurate interpersonal and emotional understanding. The training may lower the emotional volatility of family interaction, lower the rate of arguing and fighting between parents and children, increase the rate and frequency of verbal negotiation, and encourage the adoption of conflict strategies that focus on future-oriented behavior and positive outcomes.~A total of 324 working class families, representative of the primary ethnic populations in Chicago (African American, Caucasian, and Mexican American), will be selected for participation. Both parents, one 4- to 6-year-old child, and one 6- to 8-year-old sibling will participate. Single parent families will also be included; the parent will be asked to nominate a second adult or an additional older sibling in place of the second parent.~Each family proceeds through three phases. The initial phase allows assessment of conflict histories, good times, self-appraisals of psychological well-being, affective and social variables that operate within the family, and the family members' ability to discuss and negotiate ongoing problems.~In the second phase, families are randomly assigned to one of three experimental conditions. One group is given conflict resolution training and then participates in a series of tasks that focus on child-parent narration, negotiation, and negotiation assessments. A second group participates in the same tasks without training. A third group undergoes only the negotiation assessments. The effectiveness of the training will be evaluated by experimentally assessing conflict resolution skills before and after training in both home and school contexts.~The third phase is a six-month follow-up visit, during which parents and children are again observed negotiating problems. Psychological well-being and affective feelings are once again assessed. The study ends with a debriefing interview for the parents.~The study consists of 14 study visits. Each member in the family will also have four training sessions. Visits are scheduled 3 to 4 times a month, depending on the family's availability.

This study will evaluate the effectiveness of conflict resolution training for families with preschool and elementary school-aged children.

Objective~The purpose of the protocol is to localize the neural regions and systems mediating the forms of knowledge representations hypothesized by the principal investigator to be stored in the human prefrontal cortex. We suspect that political attitudes can also be viewed as a type of stored knowledge. Religious attitudinal and event knowledge are also expected to be similarly represented and stored. Utilizing a variety of experimental neuropsychological tasks during functional MRI, we will investigate hypotheses regarding the role of the dorsolateral and ventromedial prefrontal cortex in social cognition and emotional processing. We will ascertain the relationship between so-called cold cognition such as event knowledge and hot social cognition such as attitude formation and specific brain regions within the prefrontal cortex.~Study Population~Normal adult volunteers will participate in experiments dealing with processing of event knowledge, general attitudes, political stereotypes and attitudes, and religious attitudes, using fMRI.~Design~All the experiments will employ within-subject event-related fMRI design to determine whether activations of different cortical areas correspond to different kind of stored knowledge.~Outcome Measures~The data that we collect in this protocol will consist of fMRI activation images corresponding to varying neuropsychological tasks. The will be of value in (1) identifying a set of neural regions and distributed networks mediating the forms of knowledge representation stored in the prefrontal cortex and (2) developing functional MRI screening measures for subjects at-risk for developing a neurological disorder.

The purpose of the protocol is to localize the neural regions and systems mediating the forms of knowledge representations hypothesized by the principal investigator to be stored in the human prefrontal cortex. Utilizing a variety of experimental neuropsychological tasks during functional MRI, we will investigate hypotheses regarding the role of the dorsolateral and ventromedial prefrontal cortex in social cognition and emotional processing. We will ascertain the relationship between so-called cold cognition such as event knowledge and hot social cognition such as attitude formation and specific brain regions within the prefrontal cortex. We will also attempt to determine the relationship between non-frontal neural structures involved in emotional expressions, such as amygdala, and those frontal neural structures involved in executive functions that may modulate emotion. The data that we collect in this protocol will be of value in (1) identifying a set of neural regions and distributed networks mediating the forms of knowledge representation stored in the prefrontal cortex and (2) developing functional MRI screening measures for subjects at-risk for developing a neurological disorder. We will also use the data obtained in these studies with healthy adult volunteers to constrain theories of frontal lobe function based on the study of patients with focal or diffuse frontal lobe lesions and to provide convergent evidence for the role of specific frontal cortex sectors in specific cognitive functions.

The postpartum period is a window of opportunity to promote behaviors that reduce the risk of chronic disease and benefit reproductive health. The Expanded Food and Nutrition Education Program (EFNEP) is an educational program delivered by community-based paraprofessional's that aims to improve dietary and activity patterns among low income, multi-ethnic women during the postpartum period. This study will evaluate the efficacy of the EFNEP to impact the diet and activity patterns of women.~Women were recruited through the Special Supplemental Food Program for Women, Infants, and Children (WIC) and randomized to either the EFNEP group or a usual care group. Women in both groups will receive standard WIC care consisting of nutrition-risk and breastfeeding educational messages at postpartum and follow-up visits. Women in the EFNEP group participated in an additional two component intervention that included five home visits and motivational telephone calls from project staff.~Primary study outcomes were assessed at Months 1 and 12. Primary outcomes included fruit and vegetable intake, saturated fat intake, and physical activity. Secondary outcomes will include Body Mass Index and indicators of fat mass and distribution. The study will also analyze mediating and modifying factors, including social support and norms, perceived health status, smoking, television viewing, food insecurity, food and activity access, and utilization of federal programs and health care.

This study will evaluate a community-based program to improve diet and physical activity in women during the first 12 months following the birth of a child. The program is designed to complement existing federal programs for low-income families and is directed toward low-income, postpartum, multi-ethnic women.

Unintended pregnancy is associated with significant public health problems, including inadequate prenatal care, low birth weight infants, infant mortality, and maternal morbidity and mortality. Children born as a result of unplanned pregnancies are at greater risk for poor outcomes such as poor mental health and developmental disabilities. This research project will determine whether providing contraception in the home can reduce the incidence of unintended pregnancy in low income and minority women. The project will also determine whether delaying a pelvic exam encourages or discourages the utilization of clinic-based preventive services to screen for sexually transmitted diseases (STDs) and cervical cancer.~Participants will be randomized to either an experimental group or a comparison group. Each participant will receive family planning counseling during a home visit by a community health nurse. Participants in the experimental group will be offered a three-month supply of oral contraceptives or a depo-provera shot; both forms of contraceptives will be delivered during home visits. Each participant will complete a survey during the initial visit and during a 1-year follow-up. The study will last approximately three years.

This study will evaluate a program that provides birth control to low income and minority women through home visits by a community health nurse. The goal of the program is to reduce unwanted pregnancies.

Vaginal acidity is thought to be one means by which the vagina prevents overgrowth or colonization by harmful microbial flora. Sperm and many STD pathogens, including HSV-1 and HSV-2, Neisseria gonorrhoeae, Treponema pallidum, Haemophilus ducreyi, and a variety of bacterial vaginosis-associated bacteria, are inactivated at pH less than 5 in vitro. BufferGel, a vaginal spermicide and microbicide, is an acidic buffer that maintains the vagina at or near its natural state of mild acidity. Formulated at vaginal pH (pH 3.9), BufferGel prevents or limits the semen-induced rise in vaginal pH. Carbopol 974P, the buffering agent in BufferGel, is a high molecular weight, cross-linked, polyacrylic acid used as a gelling or tableting agent in many pharmaceuticals; it has a well-documented record of mucosal safety in animals and humans. This study will determine the safety and contraceptive efficacy of BufferGel spermicide used with a diaphragm compared to Gynol II spermicide used with a diaphragm. The study will also measure the frequency of bacterial vaginosis, urinary tract infections, and cervical lesions in women using BufferGel compared with Gynol II.~Participants in this study will be fitted for a diaphragm and randomized to receive either BufferGel or Gynol II. All participants will be instructed on the use of the test product with the diaphragm. Participants will be followed through 6 menstrual cycles (approximately 7 months) and will have 4 study visits and one study phone call. Some participants may enroll in an extended version of the study and be followed for an additional 6 cycles and 2 additional study visits. Study visits will include a gynecologic exam, Pap smear, and blood and urine tests. Participants will be asked to keep a diary to record information on product use. Some participants may also be asked to enroll in a colposcopy substudy. These participants will undergo colposcopy at study entry and after cycles 1, 3 and 6.

BufferGel is a new contraceptive gel designed to be used with a diaphragm. In addition to preventing pregnancy, BufferGel may also prevent some types of sexually transmitted diseases (STDs). This study will compare BufferGel to Gynol II, a currently available contraceptive gel.

ECT is a safe and effective modern treatment for severe depression and other psychiatric conditions. An estimated 100,000 treatments occur per year in the United States. ECT's most bothersome adverse effect is memory loss, with all patients receiving ECT experiencing some degree of short-term cognitive impairment. At present there are no known effective pharmacologic treatments to prevent or improve ECT-induced cognitive dysfunction. Preliminary research has shown the herbal preparation GB aids cognitive function and memory in both patients with dementia and in normal volunteers. This study will investigate the utility and safety of GB to minimize the cognitive impairment typically associated with ECT.~Participants in this study will be randomly assigned to receive either twice-daily GB or placebo. Participants will begin taking GB or placebo as soon as consent is obtained and baseline testing is completed in order to reach steady-state plasma levels of GB prior to ECT. Patients will undergo cognitive testing at specified intervals following ECT. The final study visit will occur one week after a participant's final ECT treatment.

Electroconvulsive therapy (ECT) is an effective treatment for severe or medication-resistant depression and other psychiatric disorders. A common side effect of ECT is problems with short-term memory during treatment. This study will test whether taking ginkgo biloba (GB) prior to and during the course of ECT will lessen the effects of ECT on short-term memory.

Peripheral blood progenitor cells (PBPC) have become the preferred source of hematopoietic stem cells for allogeneic transplantation because of technical ease of collection and shorter time required for engraftment. Traditionally, granulocyte-colony stimulating factor (G-CSF) has been used to procure the peripheral blood stem cell graft. Although regimens using G-CSF usually succeed in collecting adequate numbers of PBPC from healthy donors, 5%-10% will mobilize stem cells poorly and may require multiple large volume apheresis or bone marrow harvesting. Although G-CSF is generally well tolerated in healthy donors, it may be associated with bone pain, headache, myalgia and rarely life threatening side effects like stroke, myocardial infarction and splenic rupture.~AMD3100 is a bicyclam compound that inhibits the binding of stromal cell derived factor-1 (SDF-1) to its cognate receptor CXCR4. CXCR4 is present on CD34+ hematopoietic progenitor cells and its interaction with SDF-1 plays a pivotal role in the homing of CD34+ cells in the bone marrow. Inhibition of the CXCR4-SDF1 axis by AMD3100 releases CD34+ cells into the circulation, which can then be collected easily by apheresis. Recently, a published report demonstrated that large numbers of CD34+ cells were rapidly mobilized in healthy volunteers following a single subcutaneous injection of AMD3100. Remarkably, the number of CD34+ cells collected by apheresis following a single injection of AMD3100 was comparable to the number of CD34+ cells collected from historical controls receiving 5 days of G-CSF prior to stem cell mobilization. Although the study population is relatively small, side-effects to this agent have been mild and transient with no serious complications having been reported. The ability to collect a large quantity of PBPC with a single injection of this drug makes this an attractive agent for mobilizing donors of allogeneic PBPC. However, the immunologic profiles of AMD3100 mobilized cells, in terms of lymphocyte content (T cell, B cell, NK cell, immuno-regulatory T cell), T cell polarization status (TH1 versus TH2), status of antigen presenting cells (DC1 versus DC2), alloreactive potential, and preservation of reactivity to infectious agents [e.g. Epstein Barr Virus (EBV), Cytomegalovirus (CMV)] are unknown. Consequently, whether AMD3100 mobilized PBPC would be suitable for use as an allograft is uncertain. In this study we will collect PBPCs following a single subcutaneous injection of AMD3100 from healthy donors who have previously had PBPC collected using standard G-CSF mobilization. The AMD3100 mobilized cells, G-CSF mobilized cells, and circulating cells prior to both AMD3100 and G-CSF mobilization will be analyzed in terms of cellular content and function of lymphocytes, NK cells, and antigen presenting cells. AMD3100 mobilized PBPC will be collected for the purpose of research studies and will not be used for therapeutic purposes.~The primary objective is to characterize the immunological properties of AMD3100 mobilized (cytokine gene expression profiles) T-cells compared to G-CSF mobilized T-cells.~Secondary endpoints include the cellular content and other immune properties of AMD3100 mobilized cells yields of hematopoietic progenitor cells, immune cells, and other cellular subsets collected by apheresis in subjects undergoing G-CSF and AMD3100 mobilization and the safety profile of AMD3100.

Peripheral blood progenitor cells (PBPC) have become the preferred source of hematopoetic stem cells for allogeneic transplantation because of technical ease of collection and shorter time required for engraftment. Traditionally, granulocyte-colony stimulating factor (G-CSF) has been used to procure the peripheral blood stem cell graft. Although regimens using G-CSF usually succeed in collecting adequate numbers of PBPC from healthy donors, 5%-10% will mobilize stem cells poorly and may require multiple large volume apheresis or bone marrow harvesting. Although G-CSF is generally well tolerated in healthy donors, it may be associated with bone pain, headache, myalgia and rarely life threatening side effects like stroke, myocardial infarction and splenic rupture.~AMD3100, is a bicyclam compound that inhibits the binding of stromal cell derived factor-1 (SDF-1) to its cognate receptor CXC- chemokine receptor 4 (CXCR4). CXCR4 is present on cluster of differentiation 34 (CD34)+ hematopoetic progenitor cells and its interaction with stromal cell derived factor 1 (SDF-1) plays a pivotal role in the homing of CD34+ cells in the bone marrow. Inhibition of the CXCR4-SDF1 axis by AMD3100 releases CD34+ cells into the circulation, which can then be collected easily by apheresis.~Recently, a published report demonstrated that large numbers of CD34+ cells were rapidly mobilized in healthy volunteers following a single subcutaneous injection of AMD3100. Remarkably, the number of CD34+ cells collected by apheresis following a single injection of AMD3100 was comparable to the number of CD34+ cells collected from historical controls receiving 5 days of G-CSF prior to stem cell mobilization.~In this study we will collect PBPCs following a single subcutaneous injection of AMD3100 from healthy donors who have previously had PBPC collected using standard G-CSF mobilization. The AMD3100 mobilized cells, G-CSF mobilized cells, and circulating cells prior to both AMD3100 and G-CSF mobilization will be analyzed in terms of cellular content and function of lymphocytes, natural killer (NK) cells, and antigen presenting cells. AMD3100 mobilized PBPC will be collected for the purpose of research studies and will not be used for therapeutic purposes.

Objectives:~The short-term objectives of this project are:~To evaluate the effectiveness of two adjunctive treatments (mood-focused exposure-based treatment, Mood Tolerance, with Nicotine Replacement Therapy [MT-NRT] and mood-focused affect-management treatment, Mood Management, with NRT [MM-NRT] aimed at reduction and cessation of smoking behavior among veterans who were previously non-responders to smoking cessation treatment.~To examine specific variables that may serve as mechanisms of action for successful treatment (i.e., mood and coping variables).~The long-term objectives of this research program are:~To advance the mission of the VA to deliver comprehensive quality healthcare that meets the needs of patients who have been unresponsive to standard smoking cessation treatment, through research and clinical care.~To reduce the exorbitant healthcare costs of nicotine dependence (ND) to the VA, and to improve veterans' physical and psychological well-being, healthcare utilization, and mortality rates.~To evaluate effectiveness of common treatments for ND.~To explore mechanisms of action related to efficacy of treatment for ND among veterans (i.e., changes in mood and coping.)~Research Design:~This is a two-cell, single-blind, randomized, treatment outcome study.~Methodology:~One hundred and twenty-eight smoking outpatients who have previously participated in standard group smoking cessation treatment (treatment non-responders, with NRT) will be recruited through the VA Boston Outpatient Health Psychology Clinic. Advertising flyers posted throughout the Boston VA Medical Center and Outpatient Clinic will be used to supplement this recruitment.~Baseline Assessment:~Interested and eligible patients will sign an informed consent form, which will be thoroughly reviewed with each participant and co-signed by the investigators. Baseline evaluation of the participants will take approximately 90 minutes. This evaluation will include assessment of smoking-related variables, moods, and affect-regulation and coping strategies, as well as carbon monoxide (CO) levels in expired breath.~Treatment:~Participants will be randomly assigned to one of the two treatments. This will involve meeting with a pharmacist, primary care physician, psychiatrist, or nurse practitioner to be screened for use of nicotine replacement therapy (NRT; transdermal patch) and to initiate NRT use. A member of the research team will continue to monitor the participant's physical health during the course of the treatment. In addition, the participant will attend treatment groups once a week for 15 weeks. These treatment groups will be conducted by a member of the research team or clinical students supervised by the PI. Each of these groups will last 90 minutes.~Follow-Up:~The first follow-up appointment will take place in the week after completion of the treatment. Additional follow-up assessments will take place at 3-, 6-, 9-, and 12-months subsequent to the first follow-up appointment. These assessments will be almost identical to the baseline assessment, and will last approximately 90 minutes.~Findings:~Thirty-four participants have been enrolled in this study; 12 of whom are currently actively involved in the protocol. No data have been analyzed or presented yet.

Objectives:~The long term objectives of this research program are:~To advance the mission of the VHA Boston Healthcare System to deliver comprehensive quality healthcare that meets the needs of patients (in this case, who have been unresponsive to standard smoking cessation treatment) through research and clinical care.~To expand upon our knowledge of the feasibility and effectiveness of commonly-used treatments for nicotine dependence.~To further explore variables related to mood and coping that may contribute to or prevent successful reduction and cessation of smoking behavior among veterans.~The short-term objectives of this project are:~To evaluate the feasibility and effectiveness of two adjunctive treatments (a mood-focused exposure-based treatment, Mood Tolerance, with Nicotine Replacement Therapy [MTNRT] and mood-focused affect-management treatment, Mood Management, with Nicotine Replacement Therapy [MMNRT]) aimed at reduction and cessation of smoking behavior among veterans who were previously non-responders to smoking cessation treatment in the VA.~To inform equivocal findings in the literature regarding the role of mood as trigger for smoking behavior.~To explore selected mood, coping, and individual difference variable that may be predictive of successful abstinence from cigarettes among veterans.

The purpose of this study is to gather a mixed racial group of relatively healthy male Veterans (for example, White, African-American, and Hispanic), who are at least 50 years of age. These men will be followed to see what types of diseases they develop and to determine if racial differences in lifestyle, blood test results, or genes are related to the types of diseases that are found. Diseases of particular interest are prostate cancer, other cancers, cardiovascular disease (for example, heart attacks and stroke), high blood pressure and diabetes. The group to be followed will consist of about 16,000 men recruited from about 40 VA Medical Centers across the country. Each man will be followed for at least five years depending on when he enters the study.~Participants are asked to complete a set of forms to provide a brief medical history, demographics, information on lifestyle such as physical activities, smoking, and drinking, information on diet, and information on quality of life.~Subjects will be seen on a biannual basis with follow-up telephone interviews conducted during the intervening years. Follow-up telephone interviews will be conducted at the MAVERIC Call Center while follow-up clinic visits will take place at each SELECT site. In addition, VA clinical and administrative databases will be used to augment follow-up and confirm reported events.~During follow-up visits, participants will be asked whether they experienced any medical events since the last study visit, with information on specific diagnoses including prostate cancer, lung cancer, colon cancer, other cancers, stroke, myocardial infarction, hypertension, diabetes mellitus, kidney disease, chronic prostatitis, and benign prostatic hypertrophy. Confirmation of self-reported diagnosis will be made by an examination of discharge summaries, medical records, and available diagnostic and laboratory information by an end-points committee.~Recruitment for this observational cohort will proceed in parallel with recruitment for SELECT and can use SELECT staff and resources with very little additional burden in cost or staff time.

The purpose of this study is to gather a mixed racial group of relatively healthy male Veterans (for example, White, African-American, and Hispanic), who are at least 50 years of age. These men will be followed to see what types of diseases they develop and to determine if racial differences in lifestyle, blood test results, or genes are related to the types of diseases that are found. Diseases of particular interest are prostate cancer, other cancers, cardiovascular disease (for example, heart attacks and stroke), high blood pressure and diabetes. The group to be followed will consist of about 16,000 men recruited from about 40 VA Medical Centers across the country. Each man will be followed for at least five years depending on when he enters the study.

OBJECTIVES:~Compare the safety and tolerability of voriconazole vs itraconazole for the prevention of fungal infections in patients undergoing allogeneic hematopoietic stem cell transplantation.~OUTLINE: This is a randomized study. Patients are stratified according to donor type (related vs unrelated). Patients are randomized to 1 of 2 treatment arms.~Arm I: Beginning after allogeneic hematopoietic stem cell transplantation (AHSCT), patients receive voriconazole IV twice daily on days 1-14 and then orally* twice daily on days 15-100.~Arm II: Beginning after AHSCT, patients receive itraconazole IV twice daily on days 1-2, once daily on days 3-14, and then orally* twice daily on days 15-100.~NOTE: *Patients unable to tolerate oral medication may continue IV medication beyond day 14.~In both arms, treatment continues in the absence of unacceptable toxicity or an invasive fungal infection. Patients requiring corticosteroid therapy for graft-versus-host disease continue to receive voriconazole or itraconazole beyond day 100.~Patients are followed until day 180 post-transplantation.~PROJECTED ACCRUAL: A total of 150 patients (75 per treatment arm) will be accrued for this study.

RATIONALE: Antifungals, such as voriconazole and itraconazole, may be effective in preventing fungal infections in patients who are undergoing allogeneic stem cell transplantation.~PURPOSE: This randomized clinical trial is studying voriconazole to see how well it works compared to itraconazole in preventing fungal infections in patients who are undergoing allogeneic hematopoietic stem cell transplantation.

OBJECTIVES:~I. Determine the maximum tolerated dose and recommended phase II dose of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) when administered with paclitaxel in patients with metastatic or unresectable solid malignancy.~II. Determine the dose-limiting and non-dose-limiting toxic effects of this regimen in these patients.~III. Determine the pharmacokinetics of this regimen in these patients. IV. Determine tumor response in patients treated with this regimen.~OUTLINE: This is a multicenter, dose-escalation study of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG). Patients receive 17-AAG IV over 1 hour on days 1*, 4, 8, 11, 15 and 18 and paclitaxel IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.~NOTE: *17-AAG is not administered on day 1 of course 1. Cohorts of 3-6 patients receive escalating doses of 17-AAG until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 6-12 patients are treated at the recommended phase II dose.

This phase I trial is studying the side effects and best dose of 17-N-allylamino-17-demethoxygeldanamycin when given together with paclitaxel in treating patients with metastatic or unresectable solid tumor. Drugs used in chemotherapy, such as 17-N-allylamino-17-demethoxygeldanamycin and paclitaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining 17-N-allylamino-17-demethoxygeldanamycin with paclitaxel may kill more tumor cells

The use of CAM is common among patients with cancer. However, there may be differences in participation, treatment preferences, and quality of life that are influenced by socioeconomic factors and ethnicity. This study will compare two distinct socioeconomic groups to determine differences in CAM use.~Participants in this study will complete a questionnaire regarding demographics, socioeconomic status, disease specifics, and facilitators and barriers to CAM use. Participation in an introductory seminar and in various CAM programs will be monitored. Participants will also complete a quality of life scale that will provide insight into the way different populations perceive and use CAM and will identify potential obstacles to integrating CAM into other cancer treatment programs.

The purpose of this study is to determine whether differences in the use of complementary and alternative medicine (CAM) are influenced by the socioeconomic status and ethnicity of cancer patients.

The primary objectives of this study are 1) to evaluate the safety of a short intravenous infusion of PT-523 when administered on days 1, 8, and 15 of a 28-day cycle to patients with solid tumors who have failed curative or survival prolonging therapy or for whom no such therapies exist; and 2) to establish the maximum tolerated dose (MTD) and identify the dose limiting toxicities (DLT) of PT-523.~The secondary objectives of this study are to determine the pharmacokinetics and to evaluate preliminary efficacy of PT-523.

The purpose of this study is to determine the safety of a short intravenous infusion of PT-523 to patients with solid tumors who have failed curative or survival prolonging therapy or for whom no such therapies exist.

Background:~BAY 43-9006 is an inhibitor of wild-type and mutant B-Raf and c-Raf kinase isoforms in vitro, but it also inhibits p38, c-kit, VEGFR-2 and PDGFR-Beta affecting tumor growth as well as possibly promoting apoptosis by events downstream of c-Raf.~Bevacizumab is a humanized IgG1 monoclonal antibody (MAb) that binds all biologically active isoforms of human vascular endothelial growth factor (VEGF, or VEGF-A) with high affinity (k(d)= 1.1nM)~The most common adverse events associated with bevacizumab of any severity include asthenia, pain, headache, hypertension, diarrhea, stomatitis, constipation, epistaxis, dyspnea, dermatitis and proteinuria.~This Phase I trial is open to patients with all solid tumors.~Objectives:~Determine the safety and toxicity of the combination of BAY 43-9006 (Sorafenib) and bevacizumab.~Determine estimates of biochemical changes in the Ras-Raf-MAPK and VEGF signal transduction pathways in tumor and stromal cells in response to treatment at the MTD, at least in a pilot fashion, if those changes are statistically significant.~Eligibility:~Adults with histologically documented solid tumor malignancy that is metastatic or unresectable and for which standard curative therapies do not exist or are no longer effective.~Patients must be off prior chemotherapy, radiation therapy, hormonal therapy, or biological therapy for at least 4 weeks.~All patients enrolling in cohort 2 must have at least one lesion amenable to biopsy.~ECOG performance status 0 or 1 and adequate organ and marrow function.~Design:~Cohort I will receive BAY 43-9006 and bevacizumab together at the start of study in a dose escalation fashion.~Cohort II will be randomized as to which agent they receive for cycle one. Cycles 2 and beyond are treated using both agents.~Tumor biopsies will be obtained from patients in Cohort II before treatment, two weeks into mono-therapy, and two weeks into combinatorial therapy.~DCE-MRI studies will be obtained on patients in Cohort II before treatment, two weeks into monotherapy, four weeks into monotherapy, and two weeks into combinatorial therapy.~FDG-PET studies will be obtained on patients in Cohort II before treatment, two weeks into mono-therapy, and two weeks into combinatorial therapy.~Patients will be evaluated for toxicity in clinic every 2 weeks for Cycles 1 and 2, and then every 4 weeks.~Patients will be evaluated for response every 8 weeks using the RECIST criteria.~Approximately 62 patients will be needed to achieve the objectives of the trial.

Background:~BAY 43-9006 is an inhibitor of wild-type and mutant B-Raf and c-Raf kinase isoforms in vitro, but it also inhibits p38, c-kit, VEGFR-2 and PDGFR-Beta affecting tumor growth as well as possibly promoting apoptosis by events downstream of c-Raf.~Bevacizumab is a humanized IgG1 monoclonal antibody (MAb) that binds all biologically active isoforms of human vascular endothelial growth factor (VEGF, or VEGF-A) with high affinity (k(d)= 1.1nM)~The most common adverse events associated with bevacizumab of any severity include asthenia, pain, headache, hypertension, diarrhea, stomatitis, constipation, epistaxis, dyspnea, dermatitis and proteinuria.~This Phase I trial is open to patients with all solid tumors.~Objectives:~Determine the safety and toxicity of the combination of BAY 43-9006 (Sorafenib) and bevacizumab.~Determine estimates of biochemical changes in the Ras-Raf-MAPK and VEGF signal transduction pathways in tumor and stromal cells in response to treatment at the MTD, at least in a pilot fashion, if those changes are statistically significant.~Eligibility:~Adults with histologically documented solid tumor malignancy that is metastatic or unresectable and for which standard curative therapies do not exist or are no longer effective.~Patients must be off prior chemotherapy, radiation therapy, hormonal therapy, or biological therapy for at least 4 weeks.~All patients enrolling in cohort 2 must have at least one lesion amenable to biopsy.~ECOG performance status 0 or 1 and adequate organ and marrow function.~Design:~Cohort I will receive BAY 43-9006 and bevacizumab together at the start of study in a dose escalation fashion.~Cohort II will be randomized as to which agent they receive for cycle one. Cycles 2 and beyond are treated using both agents.~Tumor biopsies will be obtained from patients in Cohort II before treatment, two weeks into mono-therapy, and two weeks into combinatorial therapy.~DCE-MRI studies will be obtained on patients in Cohort II before treatment, two weeks into monotherapy, four weeks into monotherapy, and two weeks into combinatorial therapy.~FDG-PET studies will be obtained on patients in Cohort II before treatment, two weeks into mono-therapy, and two weeks into combinatorial therapy.~Patients will be evaluated for toxicity in clinic every 2 weeks for Cycles 1 and 2, and then every 4 weeks.~Patients will be evaluated for response every 8 weeks using the RECIST criteria.~Approximately 62 patients will be needed to achieve the objectives of the trial.

The Phase 1 clinical trial is designed as a single-center, open-label, non-randomized study to evaluate the safety, tolerability and immunogenicity of a two-dose schedule of rBV A/B in healthy volunteers at three ascending dosage levels, 5 ug, 10 ug and 20 ug serotype-specific antigen (10 ug, 20 ug and 40 ug total immunizing protein) in three dosing cohorts and a two-dose regimen (Day 0 and Day 28) of a formulation containing only antigens at the 40 ug total immunizing protein dosage level. Approximately 44 volunteers (11 per cohort) are expected to be enrolled. Cohorts will enroll consecutively beginning with the lowest dosage level. Volunteers in each cohort will receive a two injection series at the assigned dosage level given as a 0.5 mL intramuscular (i.m.) injection on Day 0 and Day 28. Potential volunteers for study participation will undergo qualification screening for this study during the 21 days prior to the date scheduled for vaccination. After successful completion of the informed consent process and all screening assessments, volunteers will be scheduled for vaccination. Volunteers will report acute adverse events daily for 28 days after each vaccination and return to the clinic at regular intervals according to the Schedule of Study Assessments with the last scheduled follow-up 168 days (± 7 days) after the initial vaccination (Day 0).

The purpose of this trial is to evaluate the safety and tolerability of a two-dose regimen (Day 0 and Day 28) of recombinant Botulinum Vaccine (rBV) A/B in healthy volunteers when given intramuscularly at three ascending dosage levels by cohort and a two-dose regimen (Day 0 and Day 28) of a formulation containing only antigens at the 40 ug total immunizing protein dosage level.

Information on fetal well-being during labor is of great importance to the managing physician. The current use of the fetal heart rate monitor provides some information on fetal condition, and is the primary tool used to determine if immediate operative delivery is required. The fetal pulse oximeter can provide additional information regarding fetal oxygen saturation.~Intervention: A fetal oxygen saturation sensor is placed in the uterus, between the fetal cheek or forehead and the uterine wall. In half of the patients, the managing physician will have access to fetal oxygen saturation and fetal heart rate monitoring. In the other half of the patients, labor will be monitored by fetal heart rate alone.~Study hypothesis: The additional information provided by the use of the fetal pulse oximeter will reduce the chances of a cesarean delivery. The primary outcome is cesarean section for any indication and secondary outcomes are cesarean delivery for non-reassuring fetal heart rate or dystocia, and neonatal morbidity.

The purpose of this study is to determine if the information provided to the physician by a fetal pulse oximeter during labor will reduce the chances of a cesarean delivery.

Educational programs to promote the adoption of healthy behaviors and to decrease the onset of risky behaviors in pre-adolescents are far more likely to be successful than attempts to alter established patterns of high-risk behaviors. The project involves an evaluation of a comprehensive 4-year elementary school prevention initiative starting in 3rd grade. The prevention initiative, grounded in social cognitive, influence, and development theories is embedded within a pre-existing comprehensive elementary school social development program and will employ an evidence-based social skills curriculum (PATHS) in selected schools. The aim of the program is to teach children to use problem-solving and communication skills to negotiate and prevent high-risk behaviors.~Students attending schools that will receive the enhanced social development program will be compared to students attending schools that will receive the current, standard social development curriculum. The study hypothesizes that students who participate in the 4-year enhanced social development program will self-report fewer risk behaviors when surveyed by the school system in grades 6-8.

This project will evaluate the benefit of an enhanced social development program in grades 3-6 to decrease the onset of risky behaviors in pre-adolescents.

For the past 20 years, Japanese women have reported fewer menopausal symptoms than their North American counterparts. One explanation for the disparity is the differences in diet. Evidence suggests that Japanese women consume large amounts of soy, a phytoestrogen that is structurally similar to the hormone estrogen. However, there is a lack of menopause-related research data from non-Western populations. This study will be a long-term observation of the effects of soy consumption in menopausal Japanese women.~This study will last 6 months. Participants will complete a dietary log and a menopausal symptom checklist daily. There will be three or four study visits. During these visits, participants will complete a diet questionnaire, have a blood sample collected, and be interviewed about their menopausal symptoms. Six months after study completion, participants will be sent a questionnaire about any recent menopausal symptoms they may have experienced.

The purpose of this study is to examine the way soy consumption affects menopausal symptoms in middle-aged Japanese women.

One of the principal safeguards mandated by the Federal Regulations governing clinical research with children is the assent requirement: children who are capable must provide an affirmative agreement to participate unless the research holds out a prospect of direct benefit that is important to the health or well-being of the children and is available only in the context of the research (46.408). Despite the importance of the assent requirement, the Federal regulations offer no guidelines on its implementation. In the present study, we propose to survey children and one of their parents in order to obtain information concerning children's role in making decisions concerning their participation in clinical research. Five elements of children's involvement in the decision-making process with respect to their participation in clinical research will be assessed: 1) receipt of information concerning the available options; 2) understanding of this information; 3) assessment of the available options; 4) expression of a preferred option; and 5) coordination with parental decision-making.~Three groups will be enrolled: 1. Minor/Parent pairs where the minor is participating in, or is in follow-up for, a drug treatment research study for cancer 2. Minor/Parent pairs where the minor is participating in, or is in follow-up for, a drug treatment research study for asthma, and 3. Minor/Parent pairs where the minor is receiving on-going clinical care for asthma. Children 7-14 years of age will be enrolled. Total enrollment will be 400 subject pairs, approximately 150 in cancer research, 150 in asthma research and 100 involved in clinical care for asthma, with approximate balance between the sites. Two formalized survey instruments - research/clinical minor, research/clinical parent - will be developed in consultation with Research Triangle Institute (RTI).

One of the principal safeguards mandated by the Federal Regulations governing clinical research with children is the assent requirement: children who are capable must provide an affirmative agreement to participate unless the research holds out a prospect of direct benefit that is important to the health or well-being of the children and is available only in the context of the research (46.408). Despite the importance of the assent requirement, the Federal regulations offer no guidelines on its implementation. In the present study, we propose to survey children and one of their parents in order to obtain information concerning children's role in making decisions concerning their participation in clinical research. Five elements of children's involvement in the decision-making process with respect to their participation in clinical research will be assessed: 1) receipt of information concerning the available options; 2) understanding of this information; 3) assessment of the available options; 4) expression of a preferred option; and 5) coordination with parental decision-making.~Three groups will be enrolled: 1. Minor/Parent pairs where the minor is participating in, or is in follow-up for, a drug treatment research study for cancer 2. Minor/Parent pairs where the minor is participating in, or is in follow-up for, a drug treatment research study for asthma, and 3. Minor/Parent pairs where the minor is receiving on-going clinical care for asthma. Children 7-14 years of age will be enrolled. Total enrollment will be 400 subject pairs, approximately 150 in cancer research, 150 in asthma research and 100 involved in clinical care for asthma, with approximate balance between the sites. Two formalized survey instruments - research/clinical minor, research/clinical parent - will be developed in consultation with Research Triangle Institute (RTI).

Our prior work shows that d-amphetamine and the dopamine precursor levodopa markedly improve word learning success in healthy subjects. In this randomized, placebo-controlled, double-blind clinical trial, we probe whether a mixed d1/d2 dopamine agonist (pergolid) or cholinergic neuromodulation (rivastigmine) or a general centrally arousing substance (modafinil) will yield a learning enhancement comparable to using levodopa in healthy subjects.~Our results show that the dopamine agonist pergolide impaired learning in healthy subjects compared to placebo, whereas cholinergic neuromodulation had no effect.

The purpose of this study is to determine whether levodopa, pergolid, rivastigmine, or modafinil are effective in boosting semantic language acquisition in healthy subjects.

The purposes of this study are:~To evaluate the tolerability of two cangrelor regimens of bolus plus infusion (A and B).~To characterize the pharmacokinetics of Cangrelor (A and B).~To compare the pharmacodynamics of cangrelor regimens with that of an oral 600 mg dose of clopidogrel (A, B, C and D).~To determine the effect of prior cangrelor treatment on the pharmacodynamics of clopidogrel (C and D).~To determine the effect of prior clopidogrel treatment on the pharmacodynamics of cangrelor (Group D).~To determine the effects of concomitant clopidogrel and cangrelor exposure on the pharmacodynamics of clopidogrel (Group D).

The purposes of this study are to:~Evaluate the tolerability of two cangrelor regimens.~Compare the PD of cangrelor regimens with oral clopidogrel.

Background:~This study of the FairCare Program (FC) is designed to address end of life (EOL) care delivery issues by reducing barriers to effective EOL care among health care providers, family members, surrogates, and Chronic Heart Failure (CHF) patients using a comprehensive, multi-pronged approach delivered by a care coordinator and supported by an interdisciplinary team.~Objectives:~Evaluate the impact of FC on: 1) improving the quality of life (QOL) and health care delivery for CHF patients with advanced illness, (i.e. ejection fractions of 35% or less, or assessed as level III or IV on the NYS Heart Association Classification System); 2) addressing their fears about dying; 3) increasing their use of Advance Directives (ADs); and 4) improving provider compliance with ADs. Also, describe trends that may occur in disease-specific QOL, survival, and health care use and cost.~Methods:~The study employs a randomized control group design. There are two treatment arms, the FC treatment condition, and the usual care (UC) control condition. Assessments for improving quality of life (QOL), and quality of care delivery are taken at baseline, and at three and six months. Assessments of AD use, i.e. frequency of formulation and documentation of ADs, are taken at baseline, three and six months at one year and 18 months. Because data about compliance with ADs and utilization and cost may not be fully comprehensive until patients' deaths, to maximize the sample size for these variables, and hence the power of the study to detect difference in these outcomes, data on compliance with ADs will be collected in the final year of the study, and data on utilization and cost will be aggregated in monthly intervals and collected from baseline to 18 months. One year of VA pre-intervention health care utilization and cost data will also be collected to assess baseline utilization and to control for any pre-existing differences in the propensity of patients to use health care services. Also, an intention to treat methodology will be used during data analyses.~Status:~The study ends 9-30-04, data for VA cost, Medicare cost, consistency of medical care with patient preferences, and survival, are being collected and analyzed for the final report.

This study of the FairCare Program (FC) is designed to address end of life (EOL) care delivery issues by reducing barriers to effective EOL care among health care providers, family members, surrogates, and Chronic Heart Failure (CHF) patients using a comprehensive, multi-pronged approach delivered by a care coordinator and supported by an interdisciplinary team.

Background / Rationale: Improving end-of-life care is of critical importance to the VA as it faces an increasingly aging and dying veteran population. In FY2000 approximately 104,000 enrolled veterans died in the U.S. including 27,200 that died as inpatients in VA acute or chronic care medical wards. Previous work within and outside of the VA has identified serious deficiencies in the quality of care delivered near the end of life. A pilot program of a collaborative care intervention in patients with advanced illness suggests that palliative care management may lead to improvements in processes and outcomes of care at reduced costs.~Objective(s): The purpose of this project is to test the effectiveness of a chronic illness model-based palliative care intervention that utilizes prognosis-based palliative care evaluation and longitudinal nurse care management on the processes and outcomes of end-of-life care at one VA medical center.~Methods: The study uses a randomized, controlled design. All patients admitted to the inpatient medical service during the enrollment period are screened for survival prognosis by their admitting resident physician. Patients estimated to have at least a 25% risk of dying over the following year and who meet other basic inclusion criteria are invited to participate. Consenting patients are randomized to intervention or usual care. The intervention entails initial palliative evaluation followed by nurse care management designed to promote informed goal-setting, symptom management, psycho/socio/spiritual support, and family support. Data collection activities include patient and caregiver surveys, chart reviews, and reviews of administrative databases. Primary study outcomes include caregiver-rated quality of death and dying, hospital-based resource use, and costs; secondary outcomes include patient quality of life, satisfaction with care, continuity and coordination of care, and patient self-determination~Status: Enrollment and follow up of veterans/patients in the study is complete. Follow up with the caregivers of patients who died is ongoing and projected to end in February 2008. Subject enrollment began on 08/04/04 and target enrollment of 400 patients was reached in November 2006. Of the 1354 non-duplicated patients admitted to the hospital and prognostically eligible for the study, 795 (59%) were excluded; 400 (30%) were enrolled; 142(10%) refused; and 17 (1%) were missed or did not respond to recruitment efforts. To date, 257 of 400 enrolled veterans (64%) have died and 152 after-death interviews have been conducted with caregivers.~Impact: If shown to be effective, the palliative care program tested in this study will be the first of its type to demonstrate success in a controlled trial, and it will be ready for larger-scale implementation studies that will inform models of end-of-life care delivery both within and outside of the VA. Administrators at VAs nationwide, including chiefs of service, chiefs of staff, hospital directors, and VISN directors will be able to use the plans and protocols developed in this project to develop programs at their own institutions. Nurses, generalist physicians, and specialists can gain important insights about the special needs of seriously ill patients and the role of care systems in delivering high-quality end of life care. Finally, the project has immediate relevance to the healthcare system at large, as it struggles to find effective end-of-life care delivery models.

Improving end-of-life care is of critical importance to the VA as it faces an increasingly aging and dying veteran population. Previous work within and outside of the VA has demonstrated serious deficiencies in the quality of care delivered near the end of life. Moreover, veterans in the VA system suffer from a higher rate of chronic and life-limiting illnesses and decrements in health-related quality of life compared with the age-matched controls. In FY2000 approximately 104,000 enrolled veterans died in the U.S. including 27,200 that died as inpatients in VA acute or chronic care medical wards. The care model on which the proposed study is based is theoretically sound and has been piloted in a study that suggested its use can help the VA achieve substantial quality improvement at reduced costs.

While significant progress has been made in reducing preschool child mortality in developing countries over the past 20 years, much less progress has been made in reducing neonatal mortality and morbidity. Neonatal mortality rates are high in Nepal; a significant proportion of which are due to sepsis. In addition, the vast majority of women deliver babies at home without a skilled birth attendant and early neonatal care is routinely used in rural areas. Previous hospital-based research in Malawi suggested that newborn cleansing with a dilute chlorhexidine solution could reduce early infant mortality. This project evaluates the use of a simple intervention at the community level and the impact on neonatal mortality.~Comparisons: Two nested community-based randomized trials are being conducted. The first compares the neonatal mortality rates between newborn infants randomized to receive a whole body skin cleansing soon after birth with baby wipes impregnated with 0.25% chlorhexidine compared with newborns cleaned with baby wipes with a placebo solution. The second trial compares the rates of umbilical cord infections among children assigned to three groups:~education of the mother on clean cord care alone;~education of the mother plus routine washing of the cord and stump with soap and water solution for the first 10 days of life; -OR-~education of the mother plus routine washing of the cord and stump with a 4% chlorhexidine solution.~Enrolled infants are visited on a regular basis during the first month of life to record vital status and grade the cord for signs of infection.

Neonatal mortality and morbidity is common in Nepal and the vast majority of women deliver babies at home without a skilled birth attendant.~The purpose of this project is two-fold: 1) to evaluate whether washing a newborn child with a dilute antiseptic solution soon after birth can reduce mortality in the first 4 weeks of life and 2) to evaluate whether cleaning the umbilical cord and stump with either soap and water or an antiseptic solution for the first few days of life can reduce umbilical cord infections.

Finger-stick based self-testing (SBGM), as well as diagnostic continuous glucose monitoring (CGMS®) allow diabetic patients to find a balance between the two hyper- and hypoglycemic extremes. Nevertheless, there are still patients who fail to achieve good control due to fear of hypoglycemia, or who underestimate post-prandial hyperglycemias.~The Guardian® RT Telemetered Glucose Monitoring System is indicated for continuous or periodic monitoring of real-time interstitial blood glucose values and low/high blood glucose alarms (when pre-set levels are reached) in persons with diabetes mellitus. The glucose values calculated by the device will be used to trigger hypo- and hyperglycemia alerts and will be displayed every 5 minutes. The Guardian® RT stores up to 21 days of data.~The overall primary objective of the study is to determine whether patients with poor glycemic control as evidenced by HbA1c > 8.1% can achieve improved metabolic control using the real-time values of the Guardian® RT compared to conventional self-monitoring blood glucose finger-sticks (control group) after 12 weeks of continuous use.

The objective of the study is to determine whether patients with poor glycemic control can improve metabolic control using the real-time values of the Guardian® RT compared to conventional self-monitoring blood glucose finger-sticks.

Studies suggest that testosterone (T) replacement in healthy elderly men has beneficial effects on body composition, muscle, bone, memory, and behavior, but the risks of chronic treatment, especially on the prostate, heart, and sleep quality, are not entirely clear. Therefore, it is most desirable to supplement into the lowest effective range in elderly men. However, the effects of lower than usual replacement T doses have not been well studied. Furthermore, the possible important interaction of exercise to enhance the positive effects of T supplementation, yet mitigate the possible side effects, has not been studied in older men.~This one-year study will enroll 150 men with low-normal to slightly below normal serum total T levels. Participants will be randomized into one of 6 treatment groups to receive T supplementation (AndroGel) of 25mg/day, 50 mg/day or a placebo crossed with progressive resistance training (PRT) exercise 3 times a week versus none. At the end of the study, participants in the exercise-control group will be offered PRT.~Please see link below for updated version of full protocol.

The purpose of this study is to evaluate the effects of testosterone supplementation (AndroGel) on body composition, strength, endurance, cognition, and function in older men.

A 2 arm (1 Active, 1 Active Control) study is to compare the safety and efficacy of different induction agents (alemtuzumab, basiliximab or rabbit anti-thymocyte globulin) in renal transplant recipients treated with tacrolimus, MMF and a rapid steroid withdrawal.

The purpose of this study is to compare the safety and efficacy of different induction agents (alemtuzumab, basiliximab or rabbit anti-thymocyte globulin) in renal transplant recipients treated with tacrolimus, mycophenolate mofetil (MMF) and a rapid steroid withdrawal.

Numerous studies have shown that many surgical site infections (SSI) are preventable with appropriately timed antimicrobial prophylaxis. Patients receiving prophylaxis either well-before or well after surgery are up to 5 times more likely to develop an SSI than those receiving appropriate therapy (Classen et al, 1992). Unfortunately, errors in antimicrobial prophylaxis timing are extremely common with error rates typically reported to be between 35 and 40%. Given that errors in antimicrobial prophylaxis are common and the consequences of error so grave, identifying methods to assist hospitals in improving prophylaxis must be a high priority. TRAPE will evaluate a multifaceted, theory-based intervention to assist hospitals in progressing through stages of organizational change to improve the prophylaxis process. We will test the impact of the intervention using a rigorous group-randomized, nested, pretest-posttest design (Murray, 1998).~Our specific aims over the 4 year project period are:~determine the incidence of medication errors related to antimicrobial prophylaxis for cardiovascular surgery, joint replacement surgery, and hysterectomies in 44 hospitals recruited to participate in the study;~identify organizational and system factors associated with error rates;~randomize the 44 hospitals to evaluate the effectiveness of a multifaceted intervention.~The interventions consist of: a) the promotion of specific process changes likely to reduce error rates, b) a site-visit, c) customized process feedback, d) facilitated benchmarking, and e) peer consultation. The 22 intervention hospitals will be compared to 22 hospitals that receive written feedback of their error rates only. The study has 80% power to detect a 12-15% improvement in the timing of prophylaxis in the full intervention group compared to the written feedback only group. Data collection will be done at each participating hospital, and the medical records of 100 surgical patients before and after the intervention will be abstracted at each hospital to establish performance rates. Changes in the processes of care, and the evolution through stages of organizational change will also be assessed.

The specific aims are to determine the incidence of medication errors related to antimicrobial prophylaxis for cardiovascular surgery, joint replacement surgery, and hysterectomies across a heterogeneous sample of hospitals; identify organizational and practitioner factors associated with error rates, and evaluate the effectiveness of a multifaceted intervention in reducing prophylaxis error rates compared to written feedback alone in a sample of 44 hospitals enrolled in the study using a rigorous group-randomized design.

Cigarette smoking remains the number one cause of preventable premature death in the U.S., annually killing more than 400,000 Americans. Without reversal of adolescent smoking trends, five million of today's youth will die prematurely of smoking-related illnesses. The 16-year Hutchinson Smoking Prevention Project (HSPP) was conducted in 1984-1999 to (1) address challenges of trial design and execution in school-based smoking prevention by developing the most rigorous school-based randomized trial possible, and (2) use the trial to answer the scientific questions, To what extent can a theory-based, social-influences smoking prevention intervention spanning elementary, middle and high school grades reduce smoking among youth at 12th grade and two years post-high-school?~The HSPP trial used a group-randomized, matched pair design with the school district as the experimental unit. Of 40 participating school districts, 20 were randomly assigned to the experimental (intervention) condition and 20 were assigned to the control (no HSPP intervention) condition. No restrictions were placed on the health promotion or tobacco use prevention activities of the control districts, thus enabling schools to continue whatever health curricula were normally offered. Main endpoints were daily smoking at 12th grade and 2 years after high school (Plus-2). Study participants (N=8,388) were two consecutive third grade enrollments in each of the 40 school districts. All third graders were followed to endpoint, including those who dropped out of school or otherwise left their school districts. The study achieved a 94% follow-up rate at the Plus-2 endpoint.~The HSPP intervention was a teacher-led, grades 3-10 tobacco use prevention curriculum plus unit-specific teacher training. There were 65 classroom lessons in the HSPP curriculum: 9 lessons in each of grades 3-5, 10 lessons in each of grades 6-7, 8 lessons in grade 8, and 5 lessons in each of grades 9-10, for a total number of 46.75 hours of classroom instruction time in grades 3-10. The HSPP uses an enhanced social influences approach that includes the 15 NCI-endorsed essential elements for school-based tobacco prevention and meets the CDC's best practices guidelines. The intervention's behavioral components featured skills for identifying and resisting social influences to smoke, correcting erroneous normative perceptions regarding smoking, promoting tobacco-free norms, and building self-efficacy for tobacco-free lifestyle choices. The intervention was developed to be practical for the school setting, emphasizing ease of use by teachers, good fit into school routines and with schools' existing educational objectives, and incorporation of topics/activities that are interesting, engaging and developmentally-appropriate for students.

The Hutchinson Smoking Prevention Project is a 16-year, group-randomized trial to determine the extent to which a school-based (grades 3-10), theory-based, social-influences tobacco use prevention intervention can deter youth tobacco use throughout and beyond high school.

Ghrelin is a recently described acylated peptide hormone produced by the enteroendocrine cells of the mucosal epithelial layer in the ventricle. Ghrelin is the endogenous ligand for the growth hormone (GH) secretagogue receptor (GHS-R).~Ghrelin stimulates pituitary GH release by binding to the GHS-R at both hypothalamic and pituitary levels.~Several studies show that bolus injections of ghrelin have positive effects on cardiac function in healthy humans as well as in humans with cardiac disease. We investigate the changes in cardiac function during ghrelin infusion in healthy subjects.~The pharmacokinetics of ghrelin is described in few studies only, and we aim to elucidate this aspect further.~Comparisons: In a double blind, placebo controlled, cross over study we investigate the effect of 180 minutes ghrelin infusion on 1. cardiac function (tissue Doppler, stroke-velocity index), 2. vascular tone (a. brachialis dilatation), 3. ghrelin-half-life (acylated and des-acylated) and other pharmacokinetic parameters and 4. effect on appetite.

The main purpose of this study is to determine the half life of the hormone ghrelin in the human body. Other purposes are to investigate the effect of ghrelin on appetite and cardiovascular function.

The primary objective of this Phase I study is to evaluate the safety and tolerability of escalating single SC doses of MEDI-528 administered to healthy adult volunteers in four dose groups.

A Phase I studyto evaluate the safety and tolerability of escalating subcutaneous (SC) doses of MEDI-528 in to healthy adult volunteers.

When women are in labour, they firstly undergo the first stage of labour where the cervix (neck of the womb) progresses to full dilatation. Once this occurs, they have reached the second stage, where the mother can start pushing to deliver the baby. It is accepted practice to allow mothers to actively push for a maximum of one hour.~In most cases, the baby will deliver spontaneously. However, in about 30% of cases of those who manage to labour to the second stage (fully dilated cervix), the obstetrician will have to assist delivery by the use of forceps or vacuum extraction (instrumental delivery). There are two main situations where delivery needs assistance; 'fetal distress' where the baby is suspected to be compromised, or failure to progress where the baby has not delivered after one hour of pushing. Unfortunately, instrumental delivery is associated with increased maternal and fetal problems, particularly arising from trauma to the tissues. Therefore, the identification of any new ways to increase the spontaneous delivery rate may decrease future complications.~Shoulder dystocia is a rare but dangerous scenario where the baby's head is delivered, but the shoulders are trapped behind the pubic bones. The McRoberts' position is used in this situation to deliver the baby. The mother's legs are flexed, and pushed up and out, lateral to her abdomen. It is believed that this helps by flattening out the sacral bone (tail bone), thereby widening the bony opening and allowing the shoulders to become free.~A recent paper (1) reported the novel finding that McRoberts' position also doubled the pressure generated by contractions compared to normal pushing. The authors believed that this increase in pressure was caused by the fact that the uterus was brought closer to the diaphragm that provides the power generated with pushing.~Our group wondered whether this substantial increase in pressure could be harnessed beyond the rare setting of shoulder dystocia. We therefore propose to conduct a randomised-controlled study to investigate whether adopting McRoberts' position, after 45 minutes of active pushing with no signs of progress, can increase the probability of vaginal delivery, preventing the need for forceps or vacuum assistance. Studies have shown that after one hour of active pushing, the fetus shows signs of increasing distress. In our study we will allow 45 minutes of pushing before a further 45 minutes of either the same, or our intervention (McRoberts' manoeuvre).~Women in their first pregnancy will be approached at 36 weeks in the antenatal clinic and advised of our study in the form of written information. The majority of women will not be approached again since they will not be relevant to this study, most having already delivered. However, women who have been pushing for 45 minutes will be invited to participate in the study.~The second stage of labour is a demanding process where it may not be practicable to obtain written consent. Therefore, having given information about the trial at their 36 week antenatal visit, we will enrol women after obtaining informed verbal consent. They will be specifically asked whether they have read and understood the prior information given to them at clinic.~Those consenting will be randomised to either continue in their current position or be placed in McRoberts' position. The woman will be allowed to push for a further 45 minutes. After this time, women in both groups who have not yet delivered will be aided by instrumental delivery, if deemed necessary. A few days after delivery, we will provide women with a questionnaire to determine patient satisfaction and how well they tolerated the procedure they ended up having (i.e. Operative delivery or McRoberts position).~We hope to find a significant reduction in the number of instrumental deliveries in the group of women placed in McRoberts' position as compared with the other group. A positive finding may be immediately, and widely applicable.~References:~Catalin, SB et al, Use of McRoberts' position during delivery and increase in pushing efficiency, The Lancet (2001); 358: 470-471~Nordstrom L et al, Fetal and maternal lactate increase during active second stage of labour, British Journal of Obstetrics and Gynaecology, (2001); 108;263-268.

We propose to conduct a randomised-controlled study to investigate whether adopting McRoberts' position, after 45 minutes of active pushing with no signs of progress, can increase the probability of vaginal delivery, preventing the need for forceps or vacuum assistance. In our study we will allow 45 minutes of pushing before a further 45 minutes of either the same, or our intervention (McRoberts' manoeuvre).

Caffeine ingestion increases the endurance of young people exercising at 60%-85% of their maximal oxygen uptake, and it also seems to improve endurance as measured by repeated sub-maximal isometric contraction and decreases the rate of perceived exertion during exercise. Although caffeine increases endurance in young people, an increase in endurance may be of greater interest in the elderly as the population of older adults with a physically active lifestyle is growing rapidly or for increasing endurance fitness through an exercise or rehabilitation program. Therefore the main hypothesis was that caffeine would improve cycling endurance at 65% of expected maximal heart rate, and the secondary hypotheses were that caffeine would improve postural stability, reaction and movement times, isometric arm flexion endurance, and walking speed, and would reduce the rate of perceived exertion after 5 minutes of cycling in healthy elderly citizens.

The study investigated the effect of caffeine on physical performance in healthy citizens aged over 70 years. The main hypothesis was that 6 mg/kg caffeine would improve cycling endurance at 65% of expected maximal heart rate.

It has been difficult to identify specific nutrients or food groups associated with breast cancer risk from epidemiological studies done in the U.S. Attention is now turning to the importance of overall eating patterns. A Greek-Mediterranean dietary pattern has great potential for cancer prevention. Two distinct aspects of this eating pattern are the type of fat consumed and a high fruit/vegetable intake relative to average intakes in the United States. We propose to develop and test an exchange list Greek-Mediterranean diet that could be used in future clinical trials of breast cancer prevention in women at increased risk. In this proposed study, women will be randomized to either continue their own usual diet or follow an intervention diet for 6 months. The intervention diet will be designed to decrease polyunsaturated (P) and saturated (S) fat intakes while increasing monounsaturated (M) fat intake. The P:S:M ratio of a typical American diet is about 1.0:1.5:1.7, and the goal for this intervention diet will be 1:2:5, which is much closer to that of the traditional Greek diet. A predominant source of fat will be olive oil. The fruit and vegetable goal will be 7-9 servings/day, depending on energy intake. These dietary changes will be achieved using individualized telephone counseling and a monthly group session with a dietitian. Menus will be provided as examples, but the diets will be self-selected. Compliance to the dietary goals will be assessed by food records and levels of plasma fatty acids, lipids and carotenoids. As a feasibility investigation for the planning of larger trials, plasma 8-isoprostane, oxidized lycopene, insulin and glucose levels will also be assessed since these may lend insight into two possible mechanisms that may be responsible for the cancer preventive effects of this diet. This dietary trial will provide important data on the ability of women following typical American eating patterns to change their dietary intakes to reflect a Greek-Mediterranean pattern. This intervention approach can then be tested for its effects on markers of breast cancer risk in future studies.

Epidemiological observations indicate that a Greek-Mediterranean dietary pattern has great potential for cancer prevention, but more definitive data on the preventive effects of this diet are needed. Two distinct aspects of this eating pattern are the type of fat consumed and a high fruit/vegetable intake. If the diet is feasible, it could be used in future clinical trials of breast cancer prevention. In this study, women randomly receive either a control diet or an intervention diet for 6 months. The intervention diet replaces half of the typical American fat intake with foods such as olive oil and nuts. The fruit and vegetable goal is 7-9 servings/day and includes several categories of fruits, vegetables, and herbs. Blood samples are drawn and analyzed for fatty acids derived from fats, micronutrients from fruits and vegetables, and markers of oxidative stress. This dietary trial will provide important data on the ability of women following typical American eating patterns to change their dietary intakes to reflect a Greek-Mediterranean pattern.

Mifepristone medical abortion has been available in France for a decade and a half and in the United States since 2001. Over this time, it has been demonstrated to be as safe as or safer than either surgical abortion or carrying a pregnancy to term. Furthermore, as medical abortion employs medications rather than surgery to terminate a pregnancy, it has the potential to greatly increase the availability of locations providing abortion services in the US, eliminating as it does the need for expensive equipment and surgical training.~Unfortunately, however, although the availability of medical abortion in the US has increased with time, it has yet to achieve its full potential. In large part this appears to be due to two factors which inhibit providers from offering, and women from choosing, the procedure: 1) Although the approved US medical abortion regimen does not require providers to use ultrasound examination as part of the procedure, it has become common practice for providers to do so. This both increases the cost of the procedure and limits the number of facilities that can offer it. 2) While surgical abortion typically requires only one clinic visit, medical abortion requires (officially) three or (in practice) two visits, making it more expensive, less convenient, and less attractive to women.~There is already a great deal of evidence that medical abortion can be safely offered with two (or even fewer) office visits, and without routine ultrasonography. Most medical abortions in the United States, in fact, currently require only two visits, and the possibility exists that women could self-screen at home, based on a symptom checklist, to determine if the second of these (the follow-up visit) is necessary - an approach that could spare the large majority of medical abortion clients who have uncomplicated courses an extra trip to the clinic. There are, in addition, several less-expensive and less technology-intensive approaches to gathering the diagnostic information currently being provided, pre- and post-procedure, by ultrasonography.~The purpose of the current study is to test the feasibility and efficacy of an approach to medical abortion that forgoes the routine use of ultrasonography. It will also provide evidence on the feasibility of eliminating the requirement for a universal follow-up visit based on self-screening by medical abortion clients. In providing data to make these tests, however, the study protocol will not in any way abridge the medical abortion care currently received by clients at the participating facilities. The study will permit clients to receive standard care (including a follow-up visit and pre- and post-procedure ultrasound examinations in all cases) while gathering valuable information which, we hope, will provide a basis for simplifying standard care in the future.~The research questions to be answered by the study are:~Do an interview with the abortion client, a pregnancy test and a physical exam provide adequate information to determine which abortion clients are eligible for the medical abortion procedure and which should be referred for sonography (or other diagnostic tests) before making such a determination?~Can a self-administered symptom diary and a follow-up low-sensitivity pregnancy test provide an adequate basis to determine whether a woman has undergone a successful medical abortion or whether she requires a sonographic exam (or other diagnostic test) in order to make this determination?~Does a post-abortion pelvic examination provide valuable additional information for determining whether a woman has undergone a successful medical abortion or whether she requires a sonographic exam (or other diagnostic test) in order to make this determination?~Can a self-administered symptom diary and a low-sensitivity pregnancy test provide an adequate basis for determining which medical abortion clients require a follow-up visit?~The research hypotheses are:~Practitioners themselves, based on history and examination but without sonography, are able to dependably and correctly determine which patients are eligible for medical abortion and which patients either are not eligible or require further evaluation to determine eligibility.~Practitioners themselves, based on a symptom diary and low-sensitivity pregnancy test but without sonography, are able to dependably and correctly determine when a successful medical abortion has taken place and when referral for other possible outcomes should be made.~A symptom diary and low-sensitivity pregnancy test are safe and effective means of separating those women who could benefit from a follow-up visit from those who do not need one.

This study will investigate the possibility that medical abortion using mifepristone and misoprostol - a safe, proven therapy for terminating early first trimester pregnancy - can be administered in a manner that is simpler and less costly than that routinely employed in the United States.~The researchers hypothesize that:~Practitioners themselves, based on history and examination but without sonography, are able to dependably and correctly determine which patients are eligible for medical abortion and which patients either are not eligible or require further evaluation to determine eligibility.~Practitioners themselves, based on a symptom diary and low-sensitivity pregnancy test but without sonography, are able to dependably and correctly determine when a successful medical abortion has taken place and when referral for other possible outcomes should be made.~A symptom diary and low-sensitivity pregnancy test are safe and effective means of separating those women who could benefit from a follow-up visit from those who do not need one.

MI-CP117 was a Phase 3, randomized, double-blind, placebo-controlled trial designed to determine if motavizumab is more effective than placebo in reducing RSV hospitalization in otherwise healthy Native American infants during their first RSV season.~Participants were randomized in a 2:1 ratio to receive either 15 mg/kg motavizumab or placebo by intramuscular (IM) injection every 30 days during the RSV season for a maximum of 5 injections.~During their first RSV season, participants were evaluated monthly just prior to each injection of study drug for adverse events (AEs) (including medically attended otitis media), with a final post-dosing follow up evaluation at Study Day 150. During Seasons 1, 2, and 3, blood was to be collected prior to the first and last dose of study drug for serum chemistry evaluations, motavizumab serum concentrations, and anti-motavizumab antibodies. Efficacy and safety outcomes were examined through Study Day 150 and wheezing outcomes were evaluated from the time of randomization until the third birthday.

MI-CP117 was a Phase 3, randomized, double-blind, placebo-controlled trial designed to determine if motavizumab is more effective than placebo in reducing RSV hospitalization in otherwise healthy Native American Infants in the Southwestern United States during their first RSV season.

Smoking is regarded as one of the few potentially preventable factors associated with low birth weight, very preterm birth and perinatal death. In an effort to determine the prevalence of tobacco use (smoking and smokeless tobacco) and to collect relevant data in support of a potential smoking prevention or cessation intervention, a multi-site tobacco use survey is being conducted in several countries. The survey will be used to obtain information on knowledge, attitudes and behaviors among pregnant women in diverse populations regarding tobacco products.~The primary outcome is tobacco use status during pregnancy. Secondary outcomes include: knowledge and attitudes regarding tobacco products, health hazards of tobacco use and environmental tobacco smoke (ETS) exposure.~Sample size of 750 per country was calculated under the assumptions that the prevalence of tobacco use could be as low as 0.05 with a coefficient of variation of approximately 15% and a prevalence of 0.10 with a CV of approximately 11%.

Smoking can contribute to many health problems for mothers and their babies. In developing countries, there is little information about the number of pregnant women that smoke and the reasons why some pregnant women choose to smoke. The purpose of this multi-site tobacco use survey is to obtain information on knowledge, attitudes and behaviors among pregnant women in diverse populations regarding tobacco products.

Preemptive analgesia is defined as analgesic intervention provided before surgery to prevent or reduce subsequent pain. By preventing central sensitization using nociceptive blockers by regional analgesia we may able to produce a painless postsurgical state. The use of preemptive analgesia was reported in various surgical procedures, such as in limb surgeries, laparoscopic procedures, mastectomy and vaginal hysterectomy. Regarding abdominal hysterectomy there are only few reports, however both, malignancies and benign cases were included and conflicting results were obtained regarding the value of preemptive analgesia. Since hysterectomy is the most frequent major surgical procedure performed in gynecology, and it is estimated that by age 64 years, 40 % of women will have had a hysterectomy, it would be of great value to optimize pain treatment in these patients.~The aim of the present study was to evaluate the effectiveness of preemptive analgesia in women who undergo a transabdominal hysterectomy for benign uterine abnormalities.~Material and Methods:~The study was approved by the Institutional Review Board in accordance with the Helsinki declaration. Rambam Medical Center is a public hospital, with no private patients and women are treated according to the same standard of guidelines. Women with a benign uterine myoma with or without menometrorrhagia are considered for the study. Patients are excluded if they have a systemic vascular or neurological disease, diabetes or more than two previous abdominal surgeries. A written informed consent, is obtained from the patients prior to randomization into two treatment groups. In the first group 20 ml of 1 % lidocaine were injected subcutaneously in the incisional region 15 minutes prior to the start of operation. In the second group 20 ml of normal saline are injected subcutaneously in the incisional area 15 minutes prior to operation. The syringes containing Lidocaine or Saline solution are prepared and coded by the pharmacist of the hospital. The surgeons, anesthetists and the nursing staff are all blinded to the type of solution, which is injected. The code is disclosed only at the end of the study. The anesthetic technique is standardized. A transverse lower abdominal incision is used in all patients. After completion of operation all patients are treated in the postoperative care unit for two hours. The time of arrival in the postoperative care unit is defined as time zero. Analgesia with morphine and pethidine was provided only on patient request. Thereafter patients are transferred to the Gynecological department.~The standard care for postoperative pain in our department is as follows: three fixed doses of Ibuprofen 400 mg at three hour intervals with the first dose administrated at arrival to the department (2 hours after operation). Women are informed, that they can receive a rescue dose of another medication for breakthrough pain if further analgesia is needed before the three hours elapses. In such cases they receive an intramuscular injection of 10 mg morphine. After completion of the fixed interval analgesic regimen, patients are allowed to receive four more doses of oral analgesics upon their request at 3-hour intervals. Starting from the second postoperative day, only oral analgesia is provided, on patient request. Pain intensity is evaluated in the first 24 postoperative hours, before the administration of each dose of analgesic medication. The self-report of pain is assessed by measurement on a 100 mm Visual Analogue Scale (VAS), ranging from No Pain (0), to The most pain imaginable (100). Patients are instructed to place a mark on the line that indicates the level of pain experienced. In addition, overall satisfaction with post surgical pain treatment was evaluated by patients 72 hours after surgery, with use of the same visual analogue scale but with phrasing of very satisfactory and not satisfactory at all The VAS results during the 24 hours and the number of doses of analgesia consumption during hospitalization will be compared between two groups using x test.

Preemptive analgesia is defined as analgesic intervention provided before surgery to prevent or reduce subsequent pain. By preventing central sensitization using nociceptive blockers by regional analgesia we may able to produce a painless postsurgical state. The use of preemptive analgesia was reported in various surgical procedures, such as in limb surgeries, laparoscopic procedures, mastectomy and vaginal hysterectomy. Regarding abdominal hysterectomy there are only few reports, however both, malignancies and benign cases were included and conflicting results were obtained regarding the value of preemptive analgesia. Since hysterectomy is the most frequent major surgical procedure performed in gynecology, and it is estimated that by age 64 years, 40 % of women will have had a hysterectomy, it would be of great value to optimize pain treatment in these patients.~The aim of the present study was to evaluate the effectiveness of preemptive analgesia in women who undergo a transabdominal hysterectomy for benign uterine abnormalities.~Hypothesis: Lidocaine (5%) injection to the scar area before incision is effective in pain reduction among women who undergo a transabdominal hysterectomy for benign uterine abnormalities .

Background:~Complications resulting from medications, or adverse drug events (ADEs), are prevalent and are a major source of excess morbidity and costs. ADEs are particularly problematic in older patients because of their higher burden of comorbidity and diminished physiologic reserve. In addition, older patients are more likely to be exposed to polypharmacy, a major risk factor for ADEs. While ADEs may be idiosyncratic, many result from medical errors and inadequate systems for ensuring the safe and effective use of medications.~The goal of the proposed study is to test the efficacy of a potentially potent intervention to improve the use of medications in older outpatients enrolled in VA primary care clinics. The intervention-Enhanced Pharmacy Care-involves a formal, multi-dimensional evaluation of patients� medication regimens by a trained clinical pharmacist and board-certified geriatrician.~Objectives:~The study has the following six aims: 1) Compare changes in prescribing practices-as measured by medication appropriateness, number of medications, and cost of prescribed medications-between baseline and follow-up in patients randomized to Enhanced Pharmacy Care and patients randomized to usual care; 2) Compare other medication-based endpoints in the two groups, including the occurrence of potential ADEs, medication compliance, and patient knowledge of medications; 3) Compare changes in health-related-quality-of-life in the two groups; 4) Compare patient perceptions of the quality of VA outpatient care in the two groups; 5) Compare health care utilization during the one-year study period in the two groups; and 6) Examine attitudes of primary care providers (PCPs) about the intervention.~Methods:~Patients were eligible for the trial if they were 65 years and older and receiving prescriptions for > 5 medications in a VA primary care clinic. Patients were randomized to usual care or to the intervention, which included a structured medication history and medical records review. For intervention patients, therapeutic recommendations were developed and presented to primary care providers. Baseline and 3-month measures were obtained and change was assessed by analysis of covariance.~Status:~493 patients have been enrolled in the trial and 12-month follow-up has been completed on over 95% of patients. Preliminary results have been evaluated and abstracts have been submitted to national meetings, including the 2004 VA HSR&D and 2004 SGIM Annual Meetings where it will be presented as an oral presentation. We are completing all the data cleaning and will be performing final analyses on the data, with manuscript preparation. Final outcome assessment using the Medication Appropriateness Index is in the final stage.

Complications resulting from medications, or adverse drug events (ADEs), are prevalent and are a major source of excess morbidity and costs. ADEs are particularly problematic in older patients because of their higher burden of comorbidity and diminished physiologic reserve. In addition, older patients are more likely to be exposed to polypharmacy, a major risk factor for ADEs. While ADEs may be idiosyncratic, many result from medical errors and inadequate systems for ensuring the safe and effective use of medications.~The goal of the proposed study is to test the efficacy of a potentially potent intervention to improve the use of medications in older outpatients enrolled in VA primary care clinics. The intervention-Enhanced Pharmacy Care-involves a formal, multi-dimensional evaluation of patients� medication regimens by a trained clinical pharmacist and board-certified geriatrician.

Large core image-guided breast biopsy is a well established tool for diagnosing breast cancer. Using ultrasound or X-ray guidance, a large hollow needle is inserted through the skin into the breast and abnormal tissue is removed for diagnosis. Although this procedure is much less invasive than open surgery, it can induce pain and anxiety that can tax the coping mechanism of even the highest functioning individuals. Unrelieved stress during a medical procedure not only interferes with smooth progression of the ongoing procedure, but can also have deleterious effects when patients need additional procedures and feel dread in anticipation. The long-term objective of this research is to provide patients with a simple coping strategy at the time of large core biopsy, when they need it most. The hope is that this newly learned ability to handle distress will carry over to recovery and to future medical procedures. In a prior clinical trial (Lancet 2000:335:1486-1489), the largest prospective randomized study of its kind, the researchers showed that a self-hypnotic intervention during image-guided interventions of the blood vessels and the kidneys resulted in less pain and anxiety, fewer worrisome increases and decreases of blood pressure and heart rate, and fewer procedure interruptions. The positive effects of the short initial hypnotic intervention, which was structured in the procedure room, became more pronounced the longer the procedure lasted and carried over into the immediate post-procedure recovery. Based on these past findings, the researchers therefore predict to show evidence contrary to the current thinking that long-lasting effects require intensive presurgical preparation.~The researchers propose to pursue three interrelated specific aims:~(Aim 1): Determine the acute effects of self-hypnotic relaxation on pain and anxiety. Strictly defined methods of self-hypnotic relaxation (Group I), will be tested against empathic attention (Group II) and the routine standard of care (Group III) in a prospective randomized study with 240 patients undergoing large core breast biopsy. The impact of the treatment will be validated by comparing during the procedure among groups subjective measures of pain and anxiety as well as objective physiologic indicators of pain and anxiety (frequency of significant increases in heart rate and blood pressure).~(Aim 2): Determine the delayed effects of self-hypnotic relaxation. Patients' levels of pain, anxiety, and stress will be recorded through days 1-5 after the biopsy and compared among groups. Stress levels measurements will be based on an objective test (the amount of the stress hormone cortisol in the patient's saliva).~(Aim 3): Determine the effect of the initial self-hypnotic relaxation on distress with upcoming subsequent surgery in women with proven breast cancer. When patients have to return for surgery because their biopsy revealed malignant cells, they will be given questionnaires assessing their degree of perceived stress , anxiety, and preoccupation with their upcoming surgery. Comparison among groups will show the durability of the initial hypnotic intervention.~The researchers hypothesize that:~Self-hypnotic relaxation reduces pain and anxiety during large core breast biopsy~Self-hypnotic relaxation at the time of biopsy reduces post-biopsy stress~Teaching patients coping skills at the critical time of the breast biopsy reduces the patients' distress with upcoming breast surgery.~Upon completion, a short periprocedural self-hypnotic intervention will be validated by rigorous and practical assessment in 240 patients. The relative performance of self-hypnotic relaxation will be known compared to standard care and empathic controls in a well-characterized population of patients with a standardized biopsy wound. The durability of an intervention given at the earliest possible moment of breast cancer diagnosis will be established. This opens the way to future study designs addressing long-term effects on health behavior and psycho-physiologic phenomena.

Percutaneous large core image-guided breast biopsy is a well established tool in diagnosing breast cancer, but the associated anxiety and pain can tax the coping mechanism of even well functioning individuals. Unabated stress during an invasive procedure not only interferes with smooth progression of the ongoing procedure, but can also have deleterious effects when patients need additional procedures and dread recurrent medical traumatization. The long-term objective of this research is to provide patients with a simple coping strategy at the vulnerable time of large core biopsy in the hope that this behavioral intervention will carry over to recovery and future medical procedures. In the largest prospective randomized study of its kind, the researchers showed that a self-hypnotic intervention during percutaneous, image-guided vascular and renal interventions resulted in less pain and anxiety, greater hemodynamic stability, and fewer procedure interruptions. The positive effects of the short initial hypnotic intervention, which was structured in the procedure room, became more pronounced the longer the procedure lasted and carried over into the immediate post-procedure recovery. The investigators therefore challenge the current paradigms that long-lasting effects require intensive presurgical preparation.

Type II diabetes mellitus is an increasingly common condition among adults in the United States and is associated with substantial morbidity and mortality. The microvascular and macrovascular complications of diabetes lead to significant disability and early mortality, in addition to tremendous costs to the healthcare system. It has been clearly demonstrated, that both microvascular and macrovascular complications can be reduced through specific interventions that can be carried out by office-based primary care physicians. Despite the accumulation of evidence regarding specific interventions that can reduce diabetes-related morbidity and mortality, multiple studies have shown that the care provided for diabetic patients frequently falls short of recommended standards.~The researcher's goal is to investigate a comprehensive, provider-focused intervention to improve the quality of care for diabetic patients in a large, primary care practice at Brigham and Women's Hospital. This will be accomplished through pharmacist-delivered recommendations provided to primary care providers prior to routine scheduled office visits for diabetic patients.~Adult diabetic patients age 18 years and older receiving primary care in the Brigham Internal Medicine Associates (BIMA) practice will be randomized to intervention and control groups, based on the practice subset (Suite) within BIMA in which they receive their ongoing care. Patients who receive care from providers in Suites A, B, E, and F will be assigned to the intervention group, while patients who receive care from providers in Suites C, D, G, and H will be assigned to the control group. Patients will not be contacted regarding the study; providers who practice in the intervention Suites will receive specific written recommendations regarding optimal diabetes care parameters from our study pharmacist prior to each patient's visit. Providers who practice in the control Suites will not be contacted. Pre- and post-intervention compliance with multiple diabetes quality-of-care measures (eg, Hemoglobin A1c measurement, LDL cholesterol measurement, pneumococcal vaccination, etc.) will be assessed in the intervention and control groups.

The goal of this study is to investigate a comprehensive provider-focused intervention to improve the quality of care for diabetic patients in a large primary care practice at Brigham and Women's Hospital. This will be accomplished through pharmacist recommendations provided to primary care providers prior to routine scheduled office visits for diabetic patients.

Background:~Despite 40 years of progress, smoking remains the leading preventable cause of death in the United States, responsible for 435,000 deaths per year. Smoking is a particular problem within the VA, as VA users smoke substantially more than the general population across all categories of sex, age, and race. When adjusted for age and gender, the rate of smoking among VA users is 10% higher than the general US population - 33% vs. 23%. The prevalence of heavy tobacco users (defined as >20 cigarettes per day) in the VA is more than double that of the non-VA U.S. population (7.4% vs. 3.5%).~Current VA policy and new VA/DoD guidelines both mandate that patients be offered treatment (medications and counseling), regardless of whether they attend a smoking cessation program. Thus it is essential to treat patients within primary care, since most smokers interested in quitting cannot or will not attend a cessation program.~Objectives:~This project sought to make smoking cessation an area of excellence for two VA networks by adapting and expanding the primary care-based Telephone Care Coordination Program (TCCP) throughout Sierra Pacific Healthcare Network (VISN 21) and Greater Los Angeles Healthcare System (VISN 22).~This regional expansion built on the TCCP, a very successful VA Substance Use Disorder QUERI demonstration project implemented at two facilities. In the demonstration project, across the 10 intervention sites, there were 2,900 referrals for smoking cessation in 10 months. VA care coordinators proactively contacted patients and connected them with the California Smokers' Helpline. About 45% of patients starting treatment were abstinent six months later--equal to or better than smoking cessation clinics. A cost analysis showed substantial savings per quitter compared to provider-based and clinic-based programs.~Methods:~We developed a telephone-based smoking cessation program that was integrated as a routine clinical care option at five VISN 21 and VISN 22 facilities (38 clinic sites). Referrals to the program were generated by a provider during a visit through a brief consult in CPRS. Program staff then recruited patients and, after obtaining consent, enrolled the patients into treatment. Data were collected at the site level (quantity of referrals, service origins, etc.) and at the patient level (demographics, enrollment rates, abstinence rates at six months, etc.).~This project was a group randomized trial testing of whether telephone care coordination increases the rate of smoking cessation treatment. At the patient level, two questions are addressed:~Is proactive care coordination (counselor initiates the call to the patient) more effective than reactive coordination (coordinator waits for the patient to call)?~Is multi-session counseling more effective than brief primary care-based counseling plus self-help materials?~We randomly allocated all participating sites within VISNs 21 and 22 to either self-help or intensive counseling treatment arms. We randomly allocated each week of program referrals to either proactive or reactive care coordination. All patients received brief smoking cessation counseling from their primary care physician, smoking cessation medications (after study enrollment by the VA care coordinator), and a follow-up call at 6 months. Care coordination was provided by VA clinical staff (donated as in-kind support from the participating facilities). Intensive counseling was provided by the California Smokers' Helpline.~Status:~Complete except for ongoing data analysis.

TeleQuit is a group randomized trial testing whether a telephone care coordination program increases the rate of smoking cessation treatment for VA patients at study sites. We are testing whether proactive care coordination (counselor initiates the call to the patient) is more effective than reactive coordination (coordinator waits for the patient to call); and whether multi-session counseling is more effective than brief primary care-based counseling plus self-help materials. We randomly assigned study sites to either quitline counseling or brief counseling only. All patients receive brief smoking cessation counseling from their primary care physician, smoking cessation medications (once they are in contact with the VA care coordinator), and a follow-up call at 6 months. Care coordination will be provided by VA clinical staff. Intensive counseling is provided by the California Smokers' Helpline.

This study aims to assess the changes in physical characteristics, food intake, eating behavior, vomiting, and dumping in 100 patients who undergo bariatric surgery. Patients are put into one of two conditions; they will either receive standard postoperative care or biweekly counseling sessions with a dietician that will help them with the postoperative diet. Patients who receive dietary counseling are anticipated to experience greater weight loss and report less consumption of sugar and fat as compared to patients who do not receive dietary counseling. Moreover, patients who receive dietary counseling are predicted to report less frequent nausea, vomiting, and gastric dumping, as compared to patients who do not receive postoperative dietary counseling. This is predicted to result as a consequence of increased dietary adherence evidenced by the former group.

This study aims to assess the changes in physical characteristics, food intake, eating behavior, vomiting, and dumping in 100 patients who undergo bariatric surgery. Patients are put into one of two conditions; they will either receive standard postoperative care or biweekly counseling sessions with a dietician that will help them with the postoperative diet. Patients who receive dietary counseling are anticipated to experience greater weight loss and report less consumption of sugar and fat as compared to patients who do not receive dietary counseling. Moreover, patients who receive dietary counseling are predicted to report less frequent nausea, vomiting, and gastric dumping, as compared to patients who do not receive postoperative dietary counseling. This is predicted to result as a consequence of increased dietary adherence evidenced by the former group.

Patients will participate in two arms of the trial, one in which morphine will be administered transdermally, and, after a 3 day wash out period, one in which morphine will be administered subcutaneously. Blood draws will be done after both dosing methods in order to compare blood levels of morphine by the different routes.

Patients will participate in two arms of the trial, one in which morphine will be administered transdermally, and, after a 3 day wash out period, one in which morphine will be administered subcutaneously.

Despite the availability of nicotine replacement therapies and sustained-relapse bupropion for the treatment of nicotine dependence, there is still a significant proportion of cigarette smokers who are unable to quit smoking. Therefore, new and effective pharmacotherapies for smoking cessation are needed. The primary aim of this study is to determine the safety and efficacy of selegiline as an aid to smoking cessation.~In this study, 200 nicotine-dependent cigarette smokers will participate in an 8-week, double-blind, placebo-controlled trial and then will be followed over 4 years. Participants will be randomly assigned to receive either selegiline or placebo. Selegiline doses of 5 mg will be taken once a day during the first week. This will be increased to 5 mg twice daily for the remaining 7 weeks. The target smoking quit date will be Day 15. All smokers will receive brief weekly manualized smoking cessation counseling from the Mayo Clinic's Smoke Free and Livin' It program. The primary smoking cessation outcome measure will be 7-day point prevalence smoking abstinence at the 6-month follow-up. Secondary cessation outcome measures will include continuous smoking abstinence during the last four weeks of the trial (Days 29-56) and 7-day point prevalence abstinence at the end of the 8-week trial (Days 49-56).

Despite the widespread use of nicotine replacement therapies for the treatment of nicotine dependence, many smokers are still unable to quit smoking. The purpose of this study is to determine the safety and effectiveness of selegiline as an aid to help smokers quit smoking.

BACKGROUND INFORMATION~At least one in three people aged sixty five and over are reported to fall in the community each year and in the very elderly this figure is nearer 40 % (1,2). The morbidity and mortality resulting from falls in the elderly is substantial and the costs associated with such falls are likely to rise with the predicted growth in the elderly population. The Health of the Nation document recognises that falls are an important cause of disability and use of the health service in older people (3). More than 50% of accidental deaths in those aged sixty five years and over are due to falls, and survivors of falls have a tow-fold increased chance of being hospitalised (4). The target of the Health of the Nation is to reduce the death rate for accidents among people aged sixty five and over by at least 33% by the year 2005 (3). Prevention of falls and fall-related injuries will be a major factor in achieving such targets. It is therefore wise that approaches which are appropriate and likely to be effective are adequately researched and implemented if indicated. There have been a number of approaches to studying the prevention of falls, and their sequelae, in the elderly and these are explored in the accompanying literature review.~AIM~To determine whether multidisciplinary assessment of community-based patients, who have had at least one previous fall, reduces the rate of further falls and fall-related problems. The study also aims to determine whether such an intervention, if effective, is best carried out in a primary or secondary care setting.~STUDY DESIGN~A secondary prevention randomised controlled trial of two different settings for the multidisciplinary intervention versus usual care.~Randomisation will be done prior to allocation on a cluster basis. This means that the principal liaising General Practitioner in each practice will sign consent to volunteering their cluster involvement in the study (this will also set out their duties to their patients). The reason for this type of randomisation is to avoid contamination of usual care patients which would be likely if a General Practitioner were receiving regular information about patients who were in an intervention arm of the trial. Assent to study participation would also be sought from all individuals, without their first knowing the precise nature of the intervention (5) so as to allow follow up of the control group. Subjects recruited to the intervention groups would receive an information sheet outlining the study and what the intervention would involve and assent would be sought.~STUDY SIZE~It is thought that the trial will involve approximately 516 patients in total. A recent local pilot study of a smaller falls related project identified 70 patients in 9 months in a practice with a list of 17,000 patients. It is expected that the total population base from which patients will be identified will be 60,000. It is likely that the number required to participate will be identified over a one year period. Power calculations indicate that to provide a good chance of achieving a statistically significant result approximately 150 individuals will be needed in each of the three arms of the study.~INTERVENTION~There are two intervention groups.~The first intervention group will undergo a multidisciplinary assessment by a physician, occupational therapist and physiotherapist (see enclosed assessment form) based in a falls clinic at the Royal Hampshire County Hospital (RHCH). All patients will have full blood count, urea and electrolytes, liver function tests, thyroid function tests, Vitamin D level, bone profile, electrocardiogram and urinalysis. Further investigation, treatment modification and onward referral will be made as appropriate and relevant to each individual. The patient's General Practitioner will receive written communication regarding the visit, outcome and further recommendations.~The second intervention group will under go a Community-based process. All identified fallers will undergo an assessment by a health worker in each participating practice. This individual, identified within the practice, and trained in the assessment of fallers by staff at the RHCH Falls Clinic, will administer a questionnaire, and make referrals to physiotherapy, Occupational Therapy and the patients own General Practitioner as deemed necessary. Individuals who score particularly highly or are considered appropriate by the Primary Care team may still be referred onward to the Hospital Falls Clinic.~SUBJECTS~Patients aged over 65 years of age who are identified in the community as having had at least one fall in the preceding month and who live in one of the participating areas. Subject identification will be opportunistic and also through the ambulance service notifying the key worker in a practice when a patient has fallen at home but not been transferred elsewhere.~A fall is defined as inadvertently coming to rest on the ground or other lower level with or without loss of consciousness and other than as a consequence of sudden onset of paralysis, epileptic seizure, excess alcohol intake or overwhelming external force (as per Close et al (6)).~EXCLUSION CRITERIA~Abbreviated mental test score of less than 7 out of 10~Not living in the participating areas~Planning to move from the area within the next year~Not expected to survive for the follow up period of one year~Non-English speakers who do not have a relative/carer who could interpret~METHODOLOGY~Patients will be identified by a key worker in each participating General Practice Surgery. A baseline assessment will then be done either in the patient's own home or the local surgery by the key worker (district nurse/practice nurse/health visitor). The assessment will be mostly questionnaire based and will seek information on basic demographic data, living circumstances, Barthel score, abbreviated mental test score, circumstances of most recent (index) fall and injuries sustained, information regarding previous falls in the last year, risk factors for osteoporosis, 5 point Geriatric Depression Score, and Elderly Falls Test Score score. A timed get up and go will also be done. All assessors will be trained in the administration of the assessment to reduce inter-assessor variability.~The patients in the intervention groups will attend for assessment in the Falls Clinic or in the primary care setting as described above.~Those in the conventional management group will receive usual care from their primary care team.~All subjects will be sent a paid reply postcard monthly on which to record any falls and fall injuries. If this is not returned the subject will be telephoned (when possible). If a fall has been recorded the patient will be contacted by telephone for further details.~After one year the baseline assessment will be repeated. Data will be analysed on an intention to treat basis.~PRIMARY ENDPOINT~Proportion of participants in each group to have at least one further fall during follow up year~SECONDARY ENDPOINTS~Death~Move to institutional care~Change in Barthel score~Change in Get up and go score~Fall related admissions during follow-up period~Fall related fractures~DISSEMINATION~It is intended that this trial will be subject to peer review and publication will be sought. Dissemination of information to local practices and interested parties via presentations.~REFERENCES:~Tinetti ME et al. Risk Factors for Falls Among Elderly Persons Living in the Community. NEJM, Vol 319:No26;1701-1707.~Prudham D et al. Factors Associated with Falls in the Elderly: A Community Study. Age & Ageing 1981:10, 141-6.~Health of the Nation Document. DOH~Askham J et al. Home and Leisure Accident Research: A Review of Research on Falls Among Elderly People. DTI Consumer Safety Unit/Age Concern Institute of Gerontology, London, 1990.~Edwards SJL et al. Ethical issues in the design and conduct of cluster randomised controlled trials. BMJ 1999;318:1407 -1409 (22 May).~Close J et al. Prevention of falls in the elderly tial (PROFET): a randomised controlled trial. Lancet 1999;353;93 - 9

The study aims to determine whether multidisciplinary assessment of community-based patients, who have had at least one previous fall, reduces the rate of further falls and fall-related problems. The study also aims to determine whether such an intervention, if effective, is best carried out in a primary or secondary care setting.

Inserting a needle into a child's vein is a distressing experience for children. Reducing the pain of injection and avoiding the child's discomfort remains an important aim for both parents and health care workers. Withdrawing blood and intravenous insertion (IV) in children is also time consuming, especially when the child is uncooperative and stressed.~We, the researchers at Children's Hospital of Eastern Ontario, have been searching for an effective, rapid and inexpensive method to alleviate the distress associated with venipuncture and IV insertion.~Medications by mouth, such as anti-anxiety drugs, are helpful but usually do not significantly reduce the pain. The most commonly used anti-anxiety drug at our institution is midazolam, but unfortunately onset of action takes 20-30 minutes. There are various forms of topical creams that can numb the skin. EMLA, a mixture of two local anesthetics (Lidocaine 2.5% and Prilocaine 2.5%), is applied as a topical cream and is covered with an occlusive dressing. It requires at least 1 hour to be effective. It is not only time consuming but expensive (~$1.30 per application). Ametop (Tetracaine PH. Eur.4%w/w) is another effective topical cream, which works in 30 minutes, but it is more expensive than EMLA (~$3.00 per application). Vapocoolant sprays applied for ~10 seconds immediately before injection have been shown to be faster, less expensive and as effective as EMLA in reducing pain at the site of injection during immunization.~The current investigation will evaluate the quality, efficacy and costs associated with the use of a new vapocoolant spray, Pain Ease, in reducing pain associated with IV insertion for school age children.

The purpose of this study is to investigate the use of a new vapocoolant spray, Pain Ease, to reduce intravenous (IV) insertion pain in school-aged children receiving treatment in the Emergency Department.