Investigating neonatal health risk variables through cell-type specific methylome-wide association studies.

Adverse neonatal outcomes are a prevailing risk factor for both short- and long-term mortality and morbidity in infants. Given the importance of these outcomes, refining their assessment is paramount for improving prevention and care. Here we aim to enhance the assessment of these often correlated and multifaceted neonatal outcomes. To achieve this, we employ factor analysis to identify common and unique effects and further confirm these effects using criterion-related validity testing. This validation leverages methylome-wide profiles from neonatal blood. Specifically, we investigate nine neonatal health risk variables, including gestational age, Apgar score, three indicators of body size, jaundice, birth diagnosis, maternal preeclampsia, and maternal age. The methylomic profiles used for this research capture data from nearly all 28 million methylation sites in human blood, derived from the blood spot collected from 333 neonates, within 72 h post-birth. Our factor analysis revealed two common factors, size factor, that captured the shared effects of weight, head size, height, and gestational age and disease factor capturing the orthogonal shared effects of gestational age, combined with jaundice and birth diagnosis. To minimize false positives in the validation studies, validation was limited to variables with significant cumulative association as estimated through an in-sample replication procedure. This screening resulted in that the two common factors and the unique effects for gestational age, jaundice and Apgar were further investigated with full-scale cell-type specific methylome-wide association analyses. Highly significant, cell-type specific, associations were detected for both common effect factors and for Apgar. Gene Ontology analyses revealed multiple significant biologically relevant terms for the five fully investigated neonatal health risk variables. Given the established links between adverse neonatal outcomes and both immediate and long-term health, the distinct factor effects (representing the common and unique effects of the risk variables) and their biological profiles confirmed in our work, suggest their potential role as clinical biomarkers for assessing health risks and enhancing personalized care.

Genes implicated by a methylome-wide schizophrenia study in neonatal blood show differential expression in adult brain samples.

Schizophrenia is a disabling disorder involving genetic predisposition in combination with environmental influences that likely act via dynamic alterations of the epigenome and the transcriptome but its detailed pathophysiology is largely unknown. We performed cell-type specific methylome-wide association study of neonatal blood (N = 333) from individuals who later in life developed schizophrenia and controls. Suggestively significant associations (P < 1.0 × 10-6) were detected in all cell-types and in whole blood with methylome-wide significant associations in monocytes (P = 2.85 × 10-9-4.87 × 10-9), natural killer cells (P = 1.72 × 10-9-7.82 × 10-9) and B cells (P = 3.8 × 10-9). Validation of methylation findings in post-mortem brains (N = 596) from independent schizophrenia cases and controls showed significant enrichment of transcriptional differences (enrichment ratio = 1.98-3.23, P = 2.3 × 10-3-1.0 × 10-5), with specific highly significant differential expression for, for example, BDNF (t = -6.11, P = 1.90 × 10-9). In addition, expression difference in brain significantly predicted schizophrenia (multiple correlation = 0.15-0.22, P = 3.6 × 10-4-4.5 × 10-8). In summary, using a unique design combining pre-disease onset (neonatal) blood methylomic data and post-disease onset (post-mortem) brain transcriptional data, we have identified genes of likely functional relevance that are associated with schizophrenia susceptibility, rather than confounding disease associated artifacts. The identified loci may be of clinical value as a methylation-based biomarker for early detection of increased schizophrenia susceptibility.

Patient-centered communication and diagnostic testing.

PURPOSE: Although patient-centered communication is associated with improved health and patient trust, information about the impact of patient-centered communication on health care costs is limited. We studied the relationship between patient-centered communication and diagnostic testing expenditures. METHODS: We undertook an observational cross-sectional study using covert standardized patient visits to study physician interaction style and its relationship to diagnostic testing costs. Participants were 100 primary care physicians in the Rochester, NY, area participating in a large managed care organization (MCO). Audio recordings of 2 standardized patient encounters for each physician were rated using the Measure of Patient-Centered Communication (MPCC). Standardized diagnostic testing and other expenditures, adjusted for patient demographics and case-mix, were derived from the MCO claims database. Analyses were adjusted for demographics and standardized patient detection. RESULTS: Compared with other physicians, those who had MPCC scores in the lowest tercile had greater standardized diagnostic testing expenditures (11.0% higher, 95% confidence interval [CI], 4.5%-17.8%) and greater total standardized expenditures (3.5% higher, 95% CI, 1.0%-6.1%). Whereas lower MPCC scores were associated with shorter visits, adjustment for visit length and standardized patient detection did not affect the relationship with expenditures. Total (testing, ambulatory and hospital care) expenditures were also greater for physicians who had lower MPCC scores, an effect primarily associated with the effect on testing expenditures. CONCLUSIONS: Patient-centered communication is associated with fewer diagnostic testing expenditures but also with increased visit length. Because costs and visit length may affect physicians' and health systems' willingness to endorse and practice a patient-centered approach, these results should be confirmed in future randomized trials.

The effectiveness of family interventions for physical disorders.

This article reviews the evidence for the effectiveness of family interventions in the prevention and treatment of physical disorders. Pathways by which families influence physical health and a typology of family interventions are described. Family intervention studies, particularly randomized clinical trials, are reviewed in four clinical areas: family caregiving of elders, childhood chronic illness, spouse involvement in chronic adult illnesses, and health promotion/disease prevention. Implications for family clinicians and recommendations for future research are presented.

Family interviewing: a review of the literature in primary care.

BACKGROUND: Interviewing families is an essential skill for family physicians, but there is little research on the process or outcomes of family interviewing in primary care. METHODS: We conducted a search of MEDLINE and PsychINFO using a wide range of terms related to family interviewing. The studies obtained were grouped into one of four categories: physicians' family orientation or level of family involvement, family genograms, family members who accompany patients to routine visits, and family conferences. RESULTS: Family history and other family information are commonly collected, and family issues are often discussed in office visits. Genograms can be reliably and accurately obtained during brief visits, but they are not commonly used, and their impact is uncertain. Family members frequently accompany patients to office visits and serve various roles. The potential benefits and risks of these visits are not fully understood. Family conferences are infrequently used but are well accepted by patients and may be a cost-effective method for reducing unnecessary health care utilization. CONCLUSIONS: Physicians use a wide range of family interviewing approaches with individual patients, with family members who accompany patients to office visits, and in family conferences. More research is needed to examine the process and outcome of these different types of family interviewing.