Blood-based gene expression signatures of infants and toddlers with autism.

OBJECTIVE: Autism spectrum disorders (ASDs) are highly heritable neurodevelopmental disorders that onset clinically during the first years of life. ASD risk biomarkers expressed early in life could significantly impact diagnosis and treatment, but no transcriptome-wide biomarker classifiers derived from fresh blood samples from children with autism have yet emerged. METHOD: Using a community-based, prospective, longitudinal method, we identified 60 infants and toddlers at risk for ASDs (autistic disorder and pervasive developmental disorder), 34 at-risk for language delay, 17 at-risk for global developmental delay, and 68 typically developing comparison children. Diagnoses were confirmed via longitudinal follow-up. Each child's mRNA expression profile in peripheral blood mononuclear cells was determined by microarray. RESULTS: Potential ASD biomarkers were discovered in one-half of the sample and used to build a classifier, with high diagnostic accuracy in the remaining half of the sample. CONCLUSIONS: The mRNA expression abnormalities reliably observed in peripheral blood mononuclear cells, which are safely and easily assayed in infants, offer the first potential peripheral blood-based, early biomarker panel of risk for autism in infants and toddlers. Future work should verify these biomarkers and evaluate whether they may also serve as indirect indices of deviant molecular neural mechanisms in autism.

The comparative effectiveness of a team-based versus group-based physical activity intervention for cancer survivors.

PURPOSE: Physical activity benefits cancer survivors, but the comparative effectiveness of a team-based delivery approach remains unexplored. The hypothesis tested was that a team-based physical activity intervention delivery approach has added physical and psychological benefits compared to a group-based approach. A team-based sport accessible to survivors is dragon boating, which requires no previous experience and allows for diverse skill levels. METHODS: In a non-randomized trial, cancer survivors chose between two similarly structured 8-week programs, a dragon boat paddling team (n = 68) or group-based walking program (n = 52). Three separate intervention rounds were carried out in 2007-2008. Pre-post testing measured physical and psychosocial outcomes. RESULTS: Compared to walkers, paddlers had significantly greater (all p < 0.01) team cohesion, program adherence/attendance, and increased upper-body strength. For quality-of-life outcomes, both interventions were associated with pre-post improvements, but with no clear-cut pattern of between-intervention differences. CONCLUSIONS: These hypothesis-generating findings suggest that a short-term, team-based physical activity program (dragon boat paddling) was associated with increased cohesion and adherence/attendance. Improvements in physical fitness and psychosocial benefits were comparable to a traditional, group-based walking program. Compared to a group-based intervention delivery format, the team-based intervention delivery format holds promise for promoting physical activity program adherence/attendance in cancer survivors.

Detecting, studying, and treating autism early: the one-year well-baby check-up approach.

OBJECTIVES: To determine the feasibility of implementing a broadband screen at the 1-year check-up to detect cases of autism spectrum disorders (ASD), language delay (LD), and developmental delay (DD). STUDY DESIGN: The Communication and Symbolic Behavior Scales Developmental Profile Infant-Toddler Checklist was distributed at every 1-year pediatric check-up; 137 pediatricians and 225 infants participated. Screens were scored immediately, and failures referred for further evaluation. RESULTS: Pediatricians screened 10 479 infants at the 1-year check-up; 184 infants who failed the screen were evaluated and tracked. To date, 32 infants received a provisional or final diagnosis of ASD, 56 of LD, nine of DD, and 36 of "other." Five infants who initially tested positive for ASD no longer met criteria at follow-up. The remainder of the sample was false positive results. Positive predictive value was estimated to be .75. CONCLUSIONS: The 1-Year Well-Baby Check-Up Approach shows promise as a simple mechanism to detect cases of ASD, LD, and DD at 1 year. This procedure offers an alternative to the baby sibling design as a mechanism to study autism prospectively, the results of which will enrich our understanding of autism at an early age.

Factors associated with cancer survivors' selection between two group physical activity programs.

INTRODUCTION: Physical activity programs have health benefits for cancer survivors, but little is known about factors that influence cancer survivors' actual choices between different physical activity programs. To address this knowledge gap, we examined factors associated with selecting between two group physical activity programs. METHODS: The present study is nested in a non-randomized trial. After attending an orientation to learn about the programs offered, cancer survivors (n=133) selected between a dragon boat paddling team and group walking program. We measured the association between physical activity program chosen and demographic, clinical, physical and psychosocial characteristics. RESULTS: Roughly equal proportions chose to participate in dragon boat paddling or walking (55% versus 45%). Of the many variables studied, few were associated with program selection. Compared to those who chose the walking program, those who chose the dragon boat paddling team were more likely to be Caucasians (p= .015) and younger (p= .027), and marginally significantly more like to have cancers other than breast cancer (p= .056) and have greater lower-body strength (.062). DISCUSSIONS/CONCLUSIONS: Among a cohort of cancer survivors who were interested in physical activity programs who chose between two markedly different group physical activity programs, the two programs attracted groups of approximately the same size and with remarkably similar characteristics overall. The two most notable associations were that Caucasians and younger adults were significantly more likely to choose the dragon boat paddling program. IMPLICATIONS FOR CANCER SURVIVORS: To meet the needs of cancer survivors, a menu of physical activity program options may be optimal.

Barriers to genetic testing among persons at risk for alpha-1 antitrypsin deficiency.

The alpha coded testing (ACT) study offers free and confidential testing for alpha-1 antitrypsin deficiency (AATD) and includes surveys to provide data to study the psychosocial correlates of genetic testing. The purpose of the current study is to better understand reasons why some individuals complete genetic testing while others do not. Survey measures were compared between participants who requested and returned a genetic test for AATD (n = 703), and a random sample of individuals who requested a test kit, but did not return it within 3 months of their request (n = 83). Increasing decile of age (odds ratio [OR] = 0.74 [95% confidence interval = 0.60-0.82]) and fingerstick fear (OR = 0.74 [0.60-0.93]) were associated with a decreased likelihood of returning the test, while assurance of confidentiality was associated with an increased likelihood (OR = 1.26 [1.01-1.57]) of returning the genetic test. General anxiety as measured by the Beck Anxiety Inventory, family functioning as measured by the general functioning subscale of the Family Assessment Device, and stress induced by genetic testing as measured by the Impact of Events Scale did not significantly differ between responder groups (p = not significant). Results of this study help characterize factors driving genetic testing in AATD and may offer insight into population responses with other genetic tests.

Employing the treatment-free interval of intermittent androgen ablation to screen candidate prostate cancer therapies.

BACKGROUND: Because neither continuous nor intermittent hormonal therapy is curative, we designed a clinical model to screen new drugs for additive or synergistic effects with hormonal therapy and used IM862, a naturally occurring dipeptide with antiangiogenic and immunomodulatory properties, to test it. METHODS: Patients with prostate cancer who had rising PSA levels after radical prostatectomy and/or radiation therapy were given combined androgen ablation for 3 months. After 2 months' treatment, patients were randomly assigned in a double-blind fashion to receive intranasal IM862 or placebo daily. Treatment continued for 6 months or until disease progression, which was defined by a rising serum PSA level, the appearance of new skeletal or extraskeletal metastatic disease, or new symptoms requiring intervention. RESULTS: Seventy-one patients were evaluable for response. Median time to PSA progression was not reached in either group. At 6 months, disease had progressed in 14 (41%) of the 34 patients receiving treatment and 18 (49%) of the 37 receiving placebo (P = 0.39). No significant toxicities emerged. CONCLUSIONS: The model was demonstrated to be an efficient platform for new drug screening; however, IM862, though well tolerated, failed to demonstrate superiority over placebo in prolonging time to PSA progression.

Lack of concordance between physician and patient: reports on end-of-life care discussions.

OBJECTIVE: To study the effectiveness of patient physician communications regarding health care choices at the end of life. We studied communications occurring between physicians and their patients who had either terminal cancer or congestive heart failure, with less than 6 months to live. METHODS: This pilot study used in-person interviews with 22 physicians and 71 of their (matched) patients. Subjects provided paired responses to questions regarding their conversations related to end-of-life care, including resources, attitudes, and preferences. We calculated the concordance of patient and physician reports about these discussions. We examined the physicians' and the patients' agreement on the patient's diagnosis, and on whether a variety of care options were discussed. We then measured whether physicians' were aware of their patients' preferences for pain management and for place of death. Finally, we measured physicians' knowledge of whether religious/spiritual concerns or financial concerns had affected their patients' decisions regarding end-of-life care. Both bivariate and multivariate models were used. RESULTS: As a whole, the concordance scores were poor; however, concordance varied across domains of issues discussed. Patients with less education had significantly lower concordance scores. DISCUSSION: We have identified domains in which the physicians and patients may be least effective in discussing end-of-life care options. Findings may help in designing interventions to improve communication, especially for patients with less education.

Does genetic testing result in behavioral health change? Changes in smoking behavior following testing for alpha-1 antitrypsin deficiency.

BACKGROUND: As genetic testing for health risk becomes increasingly available, it becomes important to study the prospective impact of testing on modifiable health behavior. PURPOSE: This study examines the impact of genetic testing for alpha-1 antitrypsin (AAT) deficiency, a condition that usually results in emphysema in individuals exposed to cigarette smoke. We evaluated whether AAT testing, performed in the home and with minimal contact (reading materials including advice on cessation), results in quit attempts and abstinence. METHODS: Identified smokers (N = 199) from a larger study of genetic testing were surveyed 3 months following receipt of their AAT genotype. The primary endpoint was the incidence of quit attempts. RESULTS: Smokers who tested severely AAT deficient were significantly more likely to report a 24-hr quit attempt (59%) than were those who tested normal (26%). Carriers had a 34% quit attempt rate. Severely AAT deficient smokers were more likely than both carriers and normals to seek information on treatment, use pharmacotherapy for smoking cessation, and report greater reductions in their smoking. There were no group differences in 3-month abstinence rates. CONCLUSIONS: Knowledge of severe AAT deficiency, but not carrier status, may motivate smokers toward cessation. The AAT testing experience may have consequences for outcomes of other genetic conditions with modifiable health behaviors.

Attitudes towards screening for lung cancer among smokers and their non-smoking counterparts.

BACKGROUND: There has been resurgence of interest in lung cancer screening using low-dose computed tomography. The implications of directing a screening programme at smokers has been little explored. METHODS: A nationwide telephone survey was conducted. Demographics, certain clinical characteristics and attitudes about screening for lung cancer were ascertained. Responses of current, former and never smokers were compared. RESULTS: 2001 people from the US were interviewed. Smokers were significantly (p < 0.05) more likely than never smokers to be male, non-white, less educated, and to report poor health status or having had cancer, and less likely to be able to identify a usual source of healthcare. Compared with never smokers, current smokers were less likely to believe that early detection would result in a good chance of survival (p < 0.05). Smokers were less likely to be willing to consider computed tomography screening for lung cancer (71.2% (current smokers) v 87.6% (never smokers) odds ratio (OR) 0.48; 95% confidence interval (CI) 0.32 to 0.71). More never smokers as opposed to current smokers believed that the risk of disease (88% v 56%) and the accuracy of the test (92% v 71%) were important determinants in deciding whether to be screened (p < 0.05). Only half of the current smokers would opt for surgery for a screen-diagnosed cancer. CONCLUSION: The findings suggest that there may be substantial obstacles to the successful implementation of a mass-screening programme for lung cancer that will target cigarette smokers.

Measurement in group interventions for women with breast cancer.

Instrumentation is a critical component of intervention research. This article discusses a review of measurement tools used in research on group interventions for women with breast cancer. The wide variety of instruments used in research studies is listed. The criteria for instrument selection are compared with the most commonly used instrument, the Profile of Mood States. The authors summarize directions for future research related to instrumentation use.

Care at the end of life: focus on communication and race.

OBJECTIVE: To profile communication and recommendations reported by adults with terminal illness and explore differences by patient and physician characteristics. METHOD: This pilot was a cross-sectional study sample of 90 patients (39 Caucasian, 51 African American) with advanced heart failure or cancer. Participants completed an in-person, race-matched interview. RESULTS: Participation was high (94%). DISCUSSION: For example, only 30% reported discussion of advance directives, and 22% reported their physician inquired about spiritual support. Participants with cancer were significantly more likely to be receiving pain and/or symptom management at home, aware of prognosis, and participating in hospice. African American participants who were under the care of African American physicians were less likely to report pain and/or symptom management than other racial matches.Discussion: Although additional research on factors related to communication is important, initiation of patient-centered counseling by all physicians with seriously ill patients is essential.

Physician perspectives on end-of-life care: factors of race, specialty, and geography.

OBJECTIVES: To describe physicians' end-of-life practices, perceptions regarding end-of-life care and characterize differences based upon physician specialty and demographic characteristics. To illuminate physicians' perceptions about differences among their African-American and Caucasian patients' preferences for end-of-life care. DESIGN AND METHODS: Twenty-four African-American and 16 Caucasian physicians (N=40) participated in an in-person interview including 23 primary care physicians, 7 cardiologists, and 10 oncologists. Twenty-four practices were in urban areas and 16 were in rural counties. RESULTS: Physicians perceived racial differences in preferences for end-of-life care between their Caucasian and African-American patients. Whereas oncologists and primary care physicians overwhelmingly reported having working relationships with hospice, only 57% of cardiologists reported having those contacts. African-American physicians were more likely than Caucasian physicians to perceive racial differences in their patients preferences for pain medication. SIGNIFICANCE OF RESULTS: Demographic factors such as race of physician and patient may impact the provider's perspective on end-of-life care including processes of care and communication with patients.

Outcome expectations and self-regulation in cancer patients: reliability, initial factor structure, and relationships with benefit finding.

OBJECTIVE: The purpose of this research was to investigate outcome expectation and self-regulation measures within a sample of cancer patients and to explore relationships of these variables with benefit finding. The outcome expectation and self-regulation measures were evaluated for reliability and initial factor structure. METHOD: A convenience sample of 141 cancer patients completed study measures while waiting for appointments at a cancer center. RESULTS: The measures demonstrated good reliability (alphas = .88 and .92, for outcome expectation and self-regulation respectively). Initial factor structure suggested six outcome expectation factors (managing symptoms, expressing emotions, talking about cancer, learning about cancer, managing self-image, and managing needs) and one self-regulation factor. Gender and treatment status were related to outcome expectations but not self-regulation. Outcome expectations and self-regulation were significant predictors of benefit-finding, F(8, 80) = 3.1, p = .005. SIGNIFICANCE OF THE RESEARCH: Measures of outcome expectations and self-regulation are reliable, are related to gender and clinical variables, and may be useful as predictors of cancer patients' ability to find benefits in their cancer experience.

Genetic testing for alpha1-antitrypsin deficiency.

PURPOSE: The Alpha Coded Testing Study investigated the risks, benefits, and psychological impact of home genetic testing for alpha1-antitrypsin deficiency. METHODS: In the study, 996 adult individuals requested and returned a home-administered, confidential, fingerstick blood test. RESULTS: Individuals highly rated the benefits of establishing a diagnosis (82%), helping family members (86%), and anticipating peace of mind (79%). 78% of 239 current smokers reported a high likelihood of smoking cessation if diagnosed with AATD. After testing, more than 60% indicated that they would share the results with family and physicians but < 30% would share results with insurance companies. CONCLUSIONS: Confidential home testing for genetic disorders requires a comprehensive program of participant support.

Family-focused smoking cessation:enhanced efficacy by the addition of partner support and group therapy.

While partner support has been found to be an important factor in smoking cessation, programs with partner training have not demonstrated improved efficacy. The goal of this project was to evaluate the effectiveness of a smoking cessation treatment program that included partner support in an innovative education/therapy model similar to alcohol and drug treatment programs. Subjects included 23 smokers, 71% with a support partner. The program consisted of a smoking cessation curriculum, combined with facilitated group therapy for participants and partners, and individualized medication evaluation. Smoking abstinence was 87% at program completion and 80% at one month follow up, 100% abstinence in participants with support and 50% in participants without support (p < 0.05). Smoking Stage of Change at enrollment was: contemplation 22%, preparation 70%, and action 8%, with 87% movement toward action stage. In the present study, partner support enhanced short-term abstinence from smoking.

Quality of life pilot intervention for breast cancer patients: use of social cognitive theory.

OBJECTIVE: The purpose of this article is to evaluate an 8-week pilot intervention based on Social Cognitive Theory to improve quality of life for women with breast cancer. METHODS: A total of 32 breast cancer patients were randomized to either the intervention or standard care. Outcome variables included quality of life, mood, self-efficacy, outcome expectations, and self-regulation. RESULTS: Effect sizes were calculated to examine the impact of the intervention, with moderate to large effect sizes found for several subscales of the outcome expectations variable: learning about cancer and treatment (d = 0.85), having a positive attitude (d = 0.54), talking about cancer (d = 1.02), engaging in relaxation (d = 0.62), and setting goals (d = 1.58). SIGNIFICANCE OF RESULTS: A nonparametric sign test was conducted, indicating that women in the intervention condition either improved more or showed less decline than the women in standard care, p = .034, two-tailed. Implications and suggestions for the content and delivery of future psychosocial interventions with cancer patients are reviewed.

Patient and caregiver interest in internet-based cancer services.

PURPOSE: The primary goal of this study was to identify the needs for, the interest in, and the feasibility of the implementation of an Internet-based cancer services web site. Additionally, group differences (racial, patient vs caregiver, or rural vs urban) were identified that might influence the implementation of such a project. DESCRIPTION OF STUDY: Patients with cancer and caregivers (N = 319) in the waiting rooms of a cancer center located within a southeastern medical university completed questionnaires regarding their interest in Internet-based services. Topics included the likelihood of using Internet-based services, interest in home healthcare services delivered via a personal computer, and knowledge about and use of the Internet. RESULTS: Results indicated that most patient and caregiver respondents were interested in Internet-based cancer-related services such as information related to treatment (80%), conversations with physicians via the Internet (70%), and online support groups (65%). In addition, respondents reported that they would be likely to use such services (70%) and were interested in home healthcare services delivered via personal computers (60%). No group differences were found across ethnic groups, geographic settings, and patient status (patient vs caregivers) on these variables. Minorities, older individuals, and less educated individuals were less likely to have knowledge of and to have used the Internet. CLINICAL IMPLICATIONS: Patients with cancer and their caregivers are interested in supplementing in-person services with Internet-based services relating to their cancer treatment. Special efforts need to be made to reach ethnic minorities, the elderly, and those with less education with Internet-based programs.

Guidelines for evaluation of patients at risk for inherited breast and ovarian cancer: recommendations of the Department of Defense Familial Breast/Ovarian Cancer Research Project.

Patients at high risk for inherited breast and/or ovarian cancer are frequently encountered in all medical specialties. Department of Defense, Health Affairs funding as part of the Breast Cancer Education and Awareness Program was used to develop a comprehensive program for the identification, counseling, genetic testing, and long-term follow-up of such high-risk patients. This article reports the recommendations for high-risk patient management based on 4 years of evaluation and care, including discussions of the approach to counseling, indications for genetic testing, post-testing counseling, patient surveillance with examination, imagining, and laboratory testing, and suggested options for surgical and chemoprophylaxis as well as lifestyle modifications.