Primary care delivery of behavioral weight loss services for adults with cardiovascular risk factors: development of pragmatic practice components and results of a randomized feasibility trial.

Background: Intensive lifestyle interventions (ILI) improve weight loss and cardiovascular risk factors, but health systems face challenges implementing them. We engaged stakeholders to cocreate and evaluate feasibility of primary care implementation strategies and of a pragmatic randomization procedure to be used for a future effectiveness trial. Methods: The study setting was a single, urban primary care office. Patients with BMI ≥ 27 and ≥ 1 cardiovascular risk factor were sent a single electronic health record (EHR) message between December 2019 and January 2020 offering services to support an initial weight loss goal of about 10 pounds in 10 weeks. All patients who affirmed weight loss interest were pragmatically enrolled in the trial and offered "Basic Lifestyle Services" (BLS), including a scale that transmits weight data to the EHR using cellular networks, a coupon to enroll in lifestyle coaching resources through a partnering fitness organization, and periodic EHR messages encouraging use of these resources. About half (n = 42) of participants were randomized by an automated EHR algorithm to also receive "Customized Lifestyle Services" (CLS), including weekly email messages adapted to individual weight loss progress and telephonic coaching by a nurse for those facing challenges. Interventions and assessments spanned January to July 2020, with interference by the coronavirus pandemic. Weight measures were collected from administrative sources. Qualitative analysis of stakeholder recommendations and patient interviews assessed acceptability, appropriateness, and sustainability of intervention components. Results: Over 6 weeks, 426 patients were sent the EHR invitation message and 80 (18.8%) affirmed interest in the weight loss goal and were included for analysis. EHR data were available to ascertain a 6-month weight value for 77 (96%) patients. Overall, 62% of participants lost weight; 15.0% exhibited weight loss ≥ 5%, with no statistically significant difference between CLS or BLS arms (p = 0.85). CLS assignment increased participation in daily self-weighing (43% versus 21% of patients through 12 weeks) and enrollment in referral-based lifestyle support resources (52% versus 37%). Conclusions: This preliminary study demonstrates feasibility of implementation strategies for primary care offices to offer and coordinate ILI core components, as well as a pragmatic randomization procedure for use in a future randomized comparative trial.

Primary care delivery of behavioral weight loss services for adults with cardiovascular risk factors: development of pragmatic implementation strategies and results of a randomized feasibility trial.

Background: Intensive lifestyle interventions (ILI) improve weight loss and cardiovascular risk factors, but health systems face challenges implementing them. We engaged stakeholders to cocreate and evaluate feasibility of primary care implementation strategies and of a pragmatic randomization procedure to be used for a future effectiveness trial. Methods: The study setting was a single, urban primary care office. Patients with BMI ≥ 27 and ≥ 1 cardiovascular risk factor were sent a single electronic health record (EHR) message between December 2019 and January 2020 offering services to support an initial weight loss goal of about "10 pounds in 10 weeks." All patients who affirmed weight loss interest were pragmatically enrolled in the trial and offered "Basic Lifestyle Services" (BLS), including a scale that transmits weight data to the EHR using cellular networks, a coupon to enroll in lifestyle coaching resources through a partnering fitness organization, and periodic EHR messages encouraging use of these resources. About half (n = 42) of participants were randomized by an automated EHR algorithm to also receive "Customized Lifestyle Services" (CLS), including weekly email messages adapted to individual weight loss progress and telephonic coaching by a nurse for those facing challenges. Interventions and assessments spanned January to July 2020, with interference by the coronavirus pandemic. Weight measures were collected from administrative sources. Qualitative analysis of stakeholder recommendations and patient interviews assessed acceptability, appropriateness, and sustainability of intervention components. Results: Over 6 weeks, 426 patients were sent the EHR invitation message and 80 (18.8%) affirmed interest in the weight loss goal and were included for analysis. EHR data were available to ascertain a 6-month weight value for 77 (96%) patients. Overall, 62% of participants lost weight; 15.0% exhibited weight loss ≥ 5%, with no statistically significant difference between CLS or BLS arms (p = 0.85). CLS assignment increased participation in daily self-weighing (43% versus 21% of patients through 12 weeks) and enrollment in referral-based lifestyle support resources (52% versus 37%). Conclusions: This preliminary study demonstrates feasibility of implementation strategies for primary care offices to offer and coordinate ILI core components, as well as a pragmatic randomization procedure for use in a future randomized comparative trial.

Recovering from Intimate Partner Violence through Strengths and Empowerment (RISE): Initial Evaluation of the Clinical Effects of RISE Administered in Routine Care in the US Veterans Health Administration.

Intimate partner violence (IPV) is a common concern among military Veterans that negatively impacts health. The United States' Veterans Health Administration (VHA) has launched a national IPV Assistance Program (IPVAP) to provide comprehensive services to Veterans, their families and caregivers, and VHA employees who use or experience IPV. Grounded in a holistic, Veteran-centered psychosocial rehabilitation framework that guides all facets of the program, the IPVAP initiated the pilot implementation of a novel intervention called Recovering from IPV through Strengths and Empowerment (RISE). This evidence-based, person-centered, trauma-informed, and empowerment-oriented brief counseling intervention is designed to support those who experience IPV and to improve their psychosocial wellbeing. This program evaluation study describes clinical outcomes from patients who participated in a pilot implementation of RISE in routine care. We examined changes in general self-efficacy, depression, and valued living, as well as treatment satisfaction among patients who received RISE and completed program evaluation measures at VHA facilities during the pilot. Results from 45 patients (84% women) indicate that RISE was associated with significant pretreatment to posttreatment improvements in self-efficacy, depression, and valued living (Cohen's d s of 0.97, 1.09, and 0.51, respectively). Patients reported high satisfaction with treatment. Though preliminary results were similar across gender and IPV types, findings from the evaluation of the pilot implementation of RISE demonstrate the intervention's feasibility, acceptability, and clinical utility in routine VHA care and inform the scalability of RISE. Additionally, findings provide preliminary support for the effectiveness and acceptability of RISE with men. Modification to RISE and its implementation are discussed, which may be useful to other settings implementing IPV interventions.

Implementation of health literacy training for clinicians in a federally qualified health center.

Objective: The objective of this quality improvement project was to evaluate the effectiveness of a succinct health literacy training for providers at a demanding federally qualified health center. Methods: One group, pretest-posttest design was used to measure for a change in knowledge regarding the effects of limited health literacy, a change in self-reported measure of routine screening for limited health literacy and a change in self-reported utilization of patient-centered communication techniques. Results: The average percentage of correct responses on the Health Literacy Knowledge Check showed significant improvement from 23.6% (SD = 18.1%) to 63.9% (SD = 25.3%), p < .001. There were no significant changes in median responses at pre- and post-intervention for self-reported use of screening and communication techniques (all p > .05). Conclusion: This brief training was effective at improving participants' knowledge of health literacy but did not improve use of recommended communication techniques or screening for health literacy. The results suggest that emphasizing a universal precautions approach to health literacy may be more effective with participants who work in high-volume clinics. Practice implications: For high-volume clinics, a brief training may improve participants' knowledge but does not increase use of actual communication techniques based on self-report.

A data-driven approach links microglia to pathology and prognosis in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that lacks a predictive and broadly applicable biomarker. Continued focus on mutation-specific upstream mechanisms has yet to predict disease progression in the clinic. Utilising cellular pathology common to the majority of ALS patients, we implemented an objective transcriptome-driven approach to develop noninvasive prognostic biomarkers for disease progression. Genes expressed in laser captured motor neurons in direct correlation (Spearman rank correlation, p < 0.01) with counts of neuropathology were developed into co-expression network modules. Screening modules using three gene sets representing rate of disease progression and upstream genetic association with ALS led to the prioritisation of a single module enriched for immune response to motor neuron degeneration. Genes in the network module are important for microglial activation and predict disease progression in genetically heterogeneous ALS cohorts: Expression of three genes in peripheral lymphocytes - LILRA2, ITGB2 and CEBPD - differentiate patients with rapid and slowly progressive disease, suggesting promise as a blood-derived biomarker. TREM2 is a member of the network module and the level of soluble TREM2 protein in cerebrospinal fluid is shown to predict survival when measured in late stage disease (Spearman rank correlation, p = 0.01). Our data-driven systems approach has, for the first time, directly linked microglia to the development of motor neuron pathology. LILRA2, ITGB2 and CEBPD represent peripherally accessible candidate biomarkers and TREM2 provides a broadly applicable therapeutic target for ALS.

Distribution and Quantity of Sites of John Cunningham Virus Persistence in Immunologically Healthy Patients: Correlation With John Cunningham Virus Antibody and Urine John Cunningham Virus DNA.

Importance: Although seroepidemiological studies indicate that greater than 50% of the population has been infected with John Cunningham virus (JCV), the sites of JCV persistence remain incompletely characterized. Objective: To determine sites of JCV persistence in immunologically healthy individuals. Design, Setting, and Participants: Tissue specimens from multiple sites including brain, renal, and nonrenal tissues were obtained at autopsy performed in the Department of Pathology at the University of Kentucky from 12 immunologically healthy patients between February 9, 2011, and November 27, 2012. Quantitative polymerase chain reaction was performed on the tissue specimens and urine. Serum JCV antibody status was determined by enzyme-linked immunosorbent assay. Main Outcomes and Measures: The detection and quantification of JCV from the tissues by quantitative polymerase chain reaction illuminated sites of viral persistence. These results were correlated with JCV antibody levels. Results: Autopsies were performed on 12 individuals, 10 men and 2 women, ranging in age from 25 to 75 years (mean, 55.3 years). Seven of 12 individuals were JCV antibody seropositive based on absorbance units. Serostatus was associated with amounts of JCV DNA in urine and its tissue distribution. John Cunningham virus DNA was found in 75% of genitourinary tissue samples from donors (18 of 24) with high JCV antibody levels, 13.3% of donors with low levels i(4 of 30), and 0% of seronegative persons (0 of 32). In nongenitourinary tissues, JCV DNA was detected in 45.1% of tissue samples of donors (32 of 71) with high JCV, 2.2% of donors with low JCV serostatus (2 of 93), and 0% of seronegative persons (0 of 43). Genitourinary tissues had higher copy numbers than other sites. John Cunningham virus DNA was detected in urine of seronegative individuals in a research-grade assay. Conclusions and Relevance: Persistent (latent or actively replicating) JCV infection mostly predominates in genitourinary tissues but distributes in other tissues at low copy number. The distribution and copy numbers of the virus appear to correlate with urinary JCV shedding and serostatus.

JC Polyomavirus Abundance and Distribution in Progressive Multifocal Leukoencephalopathy (PML) Brain Tissue Implicates Myelin Sheath in Intracerebral Dissemination of Infection.

Over half of adults are seropositive for JC polyomavirus (JCV), but rare individuals develop progressive multifocal leukoencephalopathy (PML), a demyelinating JCV infection of the central nervous system. Previously, PML was primarily seen in immunosuppressed patients with AIDS or certain cancers, but it has recently emerged as a drug safety issue through its association with diverse immunomodulatory therapies. To better understand the relationship between the JCV life cycle and PML pathology, we studied autopsy brain tissue from a 70-year-old psoriasis patient on the integrin alpha-L inhibitor efalizumab following a ~2 month clinical course of PML. Sequence analysis of lesional brain tissue identified PML-associated viral mutations in regulatory (non-coding control region) DNA, capsid protein VP1, and the regulatory agnoprotein, as well as 9 novel mutations in capsid protein VP2, indicating rampant viral evolution. Nine samples, including three gross PML lesions and normal-appearing adjacent tissues, were characterized by histopathology and subject to quantitative genomic, proteomic, and molecular localization analyses. We observed a striking correlation between the spatial extent of demyelination, axonal destruction, and dispersion of JCV along white matter myelin sheath. Our observations in this case, as well as in a case of PML-like disease in an immunocompromised rhesus macaque, suggest that long-range spread of polyomavirus and axonal destruction in PML might involve extracellular association between virus and the white matter myelin sheath.

Tympanometric and acoustic stapedius reflex measures in older adults: the Blue Mountains Hearing Study.

Tympanometric peak pressure, peak compensated static acoustic admittance (peak Ytm) and acoustic stapedius reflex (ASR) thresholds were obtained for a representative sample of 1565 older Australians who were participants in the Blue Mountains Hearing Study (BMHS). No significant age or gender effects were found for tympanometric peak pressure. Peak Ytm measures, however, decreased with age in the left ear only across all age groups and were consistently higher for men than for women. After allowing for hearing loss, the effect of age on ASR thresholds was inconsistent. An increase in ASR thresholds with age was observed at selected frequencies but only when measured contralaterally, and these changes were not clinically significant. Overall, our findings suggest that current normative data for peak Ytm is too restricted for application in the older population, but there is insufficient evidence to warrant alternative normative data for the ASR threshold range in this same population.

Social network characteristics and cognition in middle-aged and older adults.

We examined the relationship between social network characteristics and global cognitive status in a community-based sample of 354 adults aged 50+ and with Mini-Mental State Examination (MMSE) scores of 28+ at baseline. Multivariate analyses indicated that interaction in larger social networks related to better maintenance of MMSE scores and reduced odds of decline to population-based lower quartile MMSE scores at follow-up 12 years later. At follow-up, higher levels of interpersonal activity (more frequent contacts in larger social networks) and exposure to emotional support independently related positively to MMSE. The findings suggest that interaction in larger social networks is a marker that portends less cognitive decline, and that distinct associational paths link interpersonal activity and emotional support to cognitive function.

Cell-intrinsic requirement for pRb in erythropoiesis.

Retinoblastoma (Rb) and family members have been implicated as key regulators of cell proliferation and differentiation. In particular, accumulated data have suggested that the Rb gene product pRb is an important controller of erythroid differentiation. However, current published data are conflicting as to whether the role of pRb in erythroid cells is cell intrinsic or non-cell intrinsic. Here, we have made use of an in vitro erythroid differentiation culture system to determine the cell-intrinsic requirement for pRb in erythroid differentiation. We demonstrate that the loss of pRb function in primary differentiating erythroid cells results in impaired cell cycle exit and terminal differentiation. Furthermore, we have used coculture experiments to establish that this requirement is cell intrinsic. Together, these data unequivocally demonstrate that pRb is required in a cell-intrinsic manner for erythroid differentiation and provide clarification as to its role in erythropoiesis.

Positive events as a stress buffer for children and adolescents in families in transition.

This study examined whether positive events mitigated the relation between negative events and maladjustment in samples of children and adolescents experiencing family transitions. The study examined this relation in two samples, used multiple reporters of maladjustment, and employed "tailor-made" checklists to measure events. The first sample included 86 stepfamilies with adolescents 10 to 17 years of age. The second sample included 171 divorced families with children 8 to 15 years of age. Evidence that positive events are protective for children and adolescents experiencing high levels of negative events was found across the 2 samples and across mother and child report of adjustment. These findings have implications for theory and intervention development.

Fear of abandonment as a mediator of the relations between divorce stressors and mother-child relationship quality and children's adjustment problems.

This study examines whether fear of abandonment mediates the prospective relations between divorce stressors and mother-child relationship quality and adjustment problems of children of divorce. Participants were 216 children, ages 8-12, and their primary residential mothers. Children reported on divorce stressors and fear of abandonment; mothers and children reported on mother-child relationship quality and internalizing and externalizing problems. Structural equation models indicated that Time 1 fear of abandonment mediated the relation between Time 1 divorce stressors and Time 2 internalizing and externalizing problems. Time 1 fear of abandonment also mediated the relation between Time 1 mother-child relationship quality and Time 2 internalizing and externalizing problems. Implications of these results for understanding variability in children's postdivorce adjustment problems and interventions for divorced families are discussed.

Development of the stepfamily events profile.

This project developed and examined the validity of a tailor-made life events checklist specific to the experiences of adolescents in stepfamilies (i.e., the Stepfamily Events Profile; STEP). The STEP was developed from information gathered in focus groups and interviews and includes positive and negative events that are meaningful to adolescents in stepfamilies. The STEP was given to 90 adolescents residing with their biological mother and stepfather. Negative events were significantly related to adolescent report of maladjustment, and positive events were significantly related to mother and adolescent report of internalizing problems, above and beyond the effects of several covariates. Also, the effects of negative and positive events were uniquely predictive of adolescent maladjustment. Events reflecting interactions within the adolescent's dyadic family relationships were most strongly predictive of adolescent maladjustment.