Ask and Ask Again: Repeated Screening for Smoking Increases Likelihood of Prescription for Cessation Treatment Among Women Veterans.

BACKGROUND: Preventive screening at the point of care can increase desired clinical outcomes. However, the impact of repeated screening for tobacco use on receiving smoking cessation treatment among women Veteran population has not been documented. OBJECTIVE: To examine screening for tobacco use using clinical reminders and the association between the number of screenings and prescription for cessation treatment. DESIGN: A retrospective analysis using data from a 5-year implementation trial for cardiovascular risk identification conducted between December 2016 and March 2020. SUBJECTS: Women patients who had at least one primary care visit with a women's health provider during the study period at five primary care clinics in the Veterans Affairs (VA) Healthcare System. MEASURES: The outcome is prescription of pharmacotherapy or referral to behavioral counseling for smoking cessation on or after the screening date. The exposure is the number of screenings for tobacco use from the trial and the annual VA national clinical reminders during the study period. RESULTS: Of 6009 eligible patients, 5788 (96.3%) were screened at least once for tobacco use over five calendar years, and 2784 of those screened (48.1%) were reported as current and former smokers. Among current and former smokers, 709 (25.5%) received a prescription and/or referral for smoking cessation. In the adjusted model, the average predicted probability of prescription and/or referral for smoking cessation was 13.7% among current and former smokers screened once over 5 years, 18.6% among screened twice, 26.5% among screened thrice, 32.9% among screened four times, and 41.7% among screened five or six times. CONCLUSIONS: Repeated screening was associated with higher predicted probabilities of being prescribed smoking cessation treatment.

Evidence-Based Intervention Adaptations Within the Veterans Health Administration: a Scoping Review.

BACKGROUND: Veterans receiving care within the Veterans Health Administration (VA) are a unique population with distinctive cultural traits and healthcare needs compared to the civilian population. Modifications to evidence-based interventions (EBIs) developed outside of the VA may be useful to adapt care to the VA healthcare system context or to specific cultural norms among veterans. We sought to understand how EBIs have been modified for veterans and whether adaptations were feasible and acceptable to veteran populations. METHODS: We conducted a scoping review of EBI adaptations occurring within the VA at any time prior to June 2021. Eligible articles were those where study populations included veterans in VA care, EBIs were clearly defined, and there was a comprehensive description of the EBI adaptation from its original context. Data was summarized by the components of the Framework for Reporting Adaptations and Modifications to Evidence-based interventions (FRAME). FINDINGS: We retrieved 922 abstracts based on our search terms. Following review of titles and abstracts, 49 articles remained for full-text review; eleven of these articles (22%) met all inclusion criteria. EBIs were adapted for mental health (n = 4), access to care and/or care delivery (n = 3), diabetes prevention (n = 2), substance use (n = 2), weight management (n = 1), care specific to cancer survivors (n = 1), and/or to reduce criminal recidivism among veterans (n = 1). All articles used qualitative feedback (e.g., interviews or focus groups) with participants to inform adaptations. The majority of studies (55%) were modified in the pre-implementation, planning, or pilot phases, and all were planned proactive adaptations to EBIs. IMPLICATIONS FOR D&I RESEARCH: The reviewed articles used a variety of methods and frameworks to guide EBI adaptations for veterans receiving VA care. There is an opportunity to continue to expand the use of EBI adaptations to meet the specific needs of veteran populations.

Demographic Differences Among US Department of Veterans Affairs Patients Referred for Genetic Consultation to a Centralized VA Telehealth Program, VA Medical Centers, or the Community.

Importance: Telehealth enables access to genetics clinicians, but impact on care coordination is unknown. Objective: To assess care coordination and equity of genetic care delivered by centralized telehealth and traditional genetic care models. Design, Setting, and Participants: This cross-sectional study included patients referred for genetic consultation from 2010 to 2017 with 2 years of follow-up in the US Department of Veterans Affairs (VA) health care system. Patients were excluded if they were referred for research, cytogenetic, or infectious disease testing, or if their care model could not be determined. Exposures: Genetic care models, which included VA-telehealth (ie, a centralized team of genetic counselors serving VA facilities nationwide), VA-traditional (ie, a regional service by clinical geneticists and genetic counselors), and non-VA care (ie, community care purchased by the VA). Main Outcomes and Measures: Multivariate regression models were used to assess associations between patient and consultation characteristics and the type of genetic care model referral; consultation completion; and having 0, 1, or 2 or more cancer surveillance (eg, colonoscopy) and risk-reducing procedures (eg, bilateral mastectomy) within 2 years following referral. Results: In this study, 24 778 patients with genetics referrals were identified, including 12 671 women (51.1%), 13 193 patients aged 50 years or older (53.2%), 15 639 White patients (63.1%), and 15 438 patients with cancer-related referrals (62.3%). The VA-telehealth model received 14 580 of the 24 778 consultations (58.8%). Asian patients, American Indian or Alaskan Native patients, and Hawaiian or Pacific Islander patients were less likely to be referred to VA-telehealth than White patients (OR, 0.54; 95% CI, 0.35-0.84) compared with the VA-traditional model. Completing consultations was less likely with non-VA care than the VA-traditional model (OR, 0.45; 95% CI, 0.35-0.57); there were no differences in completing consultations between the VA models. Black patients were less likely to complete consultations than White patients (OR, 0.84; 95% CI, 0.76-0.93), but only if referred to the VA-telehealth model. Patients were more likely to have multiple cancer preventive procedures if they completed their consultations (OR, 1.55; 95% CI, 1.40-1.72) but only if their consultations were completed with the VA-traditional model. Conclusions and Relevance: In this cross-sectional study, the VA-telehealth model was associated with improved access to genetics clinicians but also with exacerbated health care disparities and hindered care coordination. Addressing structural barriers and the needs and preferences of vulnerable subpopulations may complement the centralized telehealth approach, improve care coordination, and help mitigate health care disparities.

What Drives Women Veterans' Trust in VA Healthcare Providers?

INTRODUCTION: Little is known about women veterans' trust in Veterans Affairs (VA) health care and what factors promote trust in VA providers. We examined provider behaviors and characteristics of women veterans associated with trust in their VA providers. METHODS: We used a 2015 survey of women veterans who were routine users of primary care at 12 VA medical centers (n = 1,395). Patient trust in their VA provider was measured on a seven-item scale. We used multiple logistic regression to examine associations of patient-provider communication and gender appropriateness with complete trust in VA provider (100 [complete trust] vs. <100 [less than complete trust]), controlling for patient characteristics. RESULTS: On average, 39.7% of women veterans reported complete trust in their VA providers. Those with complete trust reported greater patient-provider communication and gender appropriateness of VA services than those with less-than-complete trust (all ps ≤ .001). In multiple logistic regression models, higher ratings of provider communication (adjusted odds ratio, 2.37), gender-appropriate care (adjusted odds ratio, 1.93), and trauma-sensitive communication (adjusted odds ratios, 1.79-6.08) were associated with a higher likelihood of reporting complete trust in their VA provider. CONCLUSIONS: Women veterans reported high levels of trust in their VA providers. Provider communication, gender-appropriate care, and trauma-sensitive communication were associated with greater patient trust. Although it is important to highlight the steps already taken by VA to increase the quality of care for women veterans, current findings suggest that women veterans' trust may be further increased by interventions to improve trauma-informed care by VA providers.

Benefits of Cognitive Behavioral Therapy for Insomnia for Women Veterans with and without Probable Post-Traumatic Stress Disorder.

OBJECTIVE: This study compared the benefits of cognitive-behavioral therapy for insomnia for sleep, mental health symptoms, and quality of life (QoL) in a sample of women veterans with and without probable post-traumatic stress disorder (PTSD) comorbid with insomnia disorder. METHODS: Seventy-three women veterans (30 with probable PTSD) received a manual-based 5-week cognitive-behavioral therapy for insomnia treatment as part of a behavioral sleep intervention study. Measures were completed at baseline, post-treatment, and 3-month follow-up. Sleep measures included the Insomnia Severity Index, Pittsburgh Sleep Quality Index, sleep efficiency measured by actigraphy, and sleep efficiency and total sleep time measured by sleep diary. Mental health measures included the PTSD Checklist-5, nightmares per week, Patient Health Questionnaire-9, and Generalized Anxiety Disorder-7 scale. QoL was measured with the Short Form-12. Linear mixed models compared changes over time across groups. Independent t tests examined PTSD symptom changes in women veterans with probable PTSD. RESULTS: Both groups demonstrated improvements across sleep (ps < .001-.040), mental health symptoms (ps < .001), and QoL measures (ps < .001). The probable PTSD group reported greater improvements in diary sleep efficiency (p = .046) and nightmares per week (p = .001) at post-treatment and in total sleep time (p = .029) and nightmares per week (p = .006) at follow-up. Most participants with probable PTSD experienced clinically significant reductions in PTSD symptoms at post-treatment (66.7%) and follow-up (60.0%). Significant reductions in intrusive and arousal/reactivity symptoms were maintained at follow-up. CONCLUSIONS: Cognitive-behavioral therapy for insomnia improves insomnia, mental health symptoms, and QoL among women veterans, with greater improvement in those with probable PTSD.

Getting Routine Intimate Partner Violence Screening Right: Implementation Strategies Used in Veterans Health Administration (VHA) Primary Care.

BACKGROUND: Evidence supports the clinical effectiveness of intimate partner violence (IPV) screening programs, but less is known about implementing and sustaining them. This qualitative study identified implementation strategies used to integrate IPV screening programs within Veterans Health Administration (VHA) women's health primary care. METHODS: Thirty-two administrators and clinician key informants from 11 VHA facilities participated in semistructured interviews. Implementation strategies were identified using established definitions from implementation science literature, through multistep content analysis, involving site comparisons by implementation status. RESULTS: We identified 8 implementation strategies. Three were present across all sites: (1) conduct ongoing IPV trainings, (2) conduct educational meetings and outreach visits, and (3) develop and distribute educational materials. Five strategies were unique to early adopting sites: (4) identify and prepare champions, (5) change record systems to remind clinicians, (6) create a learning collaborative through advisory boards or workgroups, (7) audit and provide feedback with relay of clinical data to providers, and (8) access new funding. DISCUSSION: Strategies align with and extend literature addressing barriers to screening. Evidence shows that effective IPV screening implementation in primary care requires a bundle of well-defined, carefully selected strategies. CONCLUSIONS: Implementation strategies used collectively can enable integration of IPV screening programs in primary care.

Aß oligomers induce pathophysiological mGluR5 signaling in Alzheimer's disease model mice in a sex-selective manner.

The prevalence, presentation, and progression of Alzheimer's disease (AD) differ between men and women, although ß-amyloid (Aß) deposition is a pathological hallmark of AD in both sexes. Aß-induced activation of the neuronal glutamate receptor mGluR5 is linked to AD progression. However, we found that mGluR5 exhibits distinct sex-dependent profiles. Specifically, mGluR5 isolated from male mouse cortical and hippocampal tissues bound with high affinity to Aß oligomers, whereas mGluR5 from female mice exhibited no such affinity. This sex-selective Aß-mGluR5 interaction did not appear to depend on estrogen, but rather Aß interaction with cellular prion protein (PrPC), which was detected only in male mouse brain homogenates. The ternary complex between mGluR5, Aß oligomers, and PrPC was essential to elicit mGluR5-dependent pathological suppression of autophagy in primary neuronal cultures. Pharmacological inhibition of mGluR5 reactivated autophagy, mitigated Aß pathology, and reversed cognitive decline in male APPswe/PS1ΔE9 mice, but not in their female counterparts. Aß oligomers also bound with high affinity to human mGluR5 isolated from postmortem donor male cortical brain tissue, but not that from female samples, suggesting that this mechanism may be relevant to patients. Our findings indicate that mGluR5 does not contribute to Aß pathology in females, highlighting the complexity of mGluR5 pharmacology and Aß signaling that supports the need for sex-specific stratification in clinical trials assessing AD therapeutics.

Intimate Partner Violence Screening Programs in the Veterans Health Administration: Informing Scale-up of Successful Practices.

OBJECTIVES: Screening women for intimate partner violence (IPV) is increasingly expected in primary care, consistent with clinical prevention guidelines (e.g., United States Preventive Services Task Force). Yet, little is known about real-world implementation of clinical practices or contextual factors impacting IPV screening program success. This study identified successful clinical practices, and barriers to and facilitators of IPV screening program implementation in the Veterans Health Administration (VHA). DESIGN: Descriptive, qualitative study of a purposeful sample of 11 Veterans Affairs Medical Centers (VAMCs) categorized as early and late adopters of IPV screening programs within women's health primary care clinics. VAMCs were categorized based on performance measures collected by VHA operations partners. PARTICIPANTS: Thirty-two administrators and clinician key informants (e.g., Women's Health Medical Directors, IPV Coordinators, and physicians) involved in IPV screening program implementation decisions from six early- and five late-adopting sites nationwide. MAIN MEASURES: Participants reported on IPV screening and response practices, and contextual factors impacting implementation, in individual 1-h semi-structured phone interviews. Transcripts were analyzed using rapid content analysis with key practices and issues synthesized in profile summaries. Themes were identified and iteratively revised, utilizing matrices to compare content across early- and late-adopting sites. KEY RESULTS: Five successful clinical practices were identified (use of two specific screening tools for primary IPV screening and secondary risk assessment, multilevel resource provision and community partnerships, co-location of mental health/social work, and patient-centered documentation). Multilevel barriers (time/resource constraints, competing priorities and mounting responsibilities in primary care, lack of policy, inadequate training, and discomfort addressing IPV) and facilitators (engaged IPV champions, internal and external supports, positive feedback regarding IPV screening practices, and current, national attention to violence against women) were identified. CONCLUSIONS: Findings advance national efforts by highlighting successful clinical practices for IPV screening programs and informing strategies useful for enhancing their implementation within and beyond the VHA, ultimately improving services and women's health.

Neuronal scaffolding protein spinophilin is integral for cocaine-induced behavioral sensitization and ERK1/2 activation.

Spinophilin is a scaffolding protein enriched in dendritic spines with integral roles in the regulation of spine density and morphology, and the modulation of synaptic plasticity. The ability of spinophilin to alter synaptic strength appears to involve its scaffolding of key synaptic proteins, including the important structural element F-actin, AMPA/NMDA modulator protein phosphatase 1, and neuromodulatory G-protein coupled receptors, including dopamine receptor D2 and metabotropic glutamate receptor 5. Additionally, spinophilin is highly expressed in the striatum, a brain region that is fundamentally involved in reward-processing and locomotor activity which receives both glutamatergic and dopaminergic inputs. Therefore, we aimed to investigate the role of spinophilin in behavioral responses to cocaine, evaluating wild-type and spinophilin knockout mice followed by the examination of underlying molecular alterations. Although acute locomotor response was not affected, deletion of spinophilin blocked the development and expression of behavioral sensitization to cocaine while maintaining normal conditioned place preference. This behavioral alteration in spinophilin knockout mice was accompanied by attenuated c-Fos and ∆FosB expression following cocaine administration and blunted cocaine-induced phosphorylation of ERK1/2 in the striatum, with no change in other relevant signaling molecules. Therefore, we suggest spinophilin fulfills an essential role in cocaine-induced behavioral sensitization, likely via ERK1/2 phosphorylation and induction of c-Fos and ∆FosB in the striatum, a mechanism that may underlie specific processes in cocaine addiction.

Direct health-care costs for children diagnosed with genetic diseases are significantly higher than for children with other chronic diseases.

PURPOSE: We aimed to estimate direct health-care costs and physician utilization for a cohort of children diagnosed with genetic diseases. METHODS: Retrospective cohort study using population-based provincial health administrative data for children with genetic diseases (n = 255) compared with three matched cohorts (asthma n = 1275, diabetes n = 255, general population n = 1275). We estimated direct health-care costs and resource use 5 years after diagnosis in five categories: physician billing, same day surgery, emergency, inpatient hospitalizations, and home care. RESULTS: During the postdiagnostic period, annual mean total costs for the genetic disease cohort were significantly higher than all other cohorts. Annual mean total costs for all cohorts were highest in the year after diagnosis with costs for the genetic disease cohort between 4.54 and 19.76 times higher during the 5 years. Inpatient hospitalizations and physician billing accounted for the majority of costs. The genetic disease cohort received more care from specialists, whereas the chronic disease cohorts received more care from general practitioners. CONCLUSION: Direct health-care costs for children with genetic diseases are significantly higher than children with/without a chronic disease, particularly in the year after diagnosis. These findings are important when considering resource allocation and funding prioritization for children with genetic diseases.

Stakeholders' views on the value of outcomes from clinical genetic and genomic interventions.

PURPOSE: Robust evidence about the value of clinical genomic interventions (CGIs), such as genetic/genomic testing or clinical genetic evaluation, is limited. We obtained stakeholders' perspectives on outcomes from CGIs to help inform their value. METHODS: We used an adapted Delphi expert panel process. Two anonymous survey rounds assessed the value of 44 CGI outcomes and whether a third party should pay for them, with discussion in between rounds. RESULTS: Sixty-six panelists responded to the first-round survey and 60 to the second. Policy-makers/payers gave the lowest ratings for value and researchers gave the highest. Patients/consumers had the most uncertainty about value and payment by a third party. Uncertainty about value was observed when evidence of proven health benefit was lacking, potential harms outweighed benefits for reproductive outcomes, and outcomes had only personal utility for individuals or family members. Agreement about outcomes for which a third party should not pay included prevention through surgery with unproven health benefits, establishing ancestry, parental consanguinity, and paternity. CONCLUSION: Research is needed to understand factors contributing to uncertainty and stakeholder differences about the value of CGI outcomes. Reaching consensus will accelerate the creation of metrics to generate the evidence needed to inform value and guide policies that promote availability, uptake, and coverage of CGIs.

A clustered controlled trial of the implementation and effectiveness of a medical home to improve health care of people with serious mental illness: study protocol.

BACKGROUND: People with serious mental illness (SMI) die many years prematurely, with rates of premature mortality two to three times greater than the general population. Most premature deaths are due to "natural causes," especially cardiovascular disease and cancer. Often, people with SMI are not well engaged in primary care treatment and do not receive high-value preventative and medical services. There have been numerous efforts to improve this care, and few controlled trials, with inconsistent results. While people with SMI often do poorly with usual primary care arrangements, research suggests that integrated care and medical care management may improve treatment and outcomes, and reduce treatment costs. METHODS: This hybrid implementation-effectiveness study is a prospective, cluster controlled trial of a medical home, the SMI Patient-Aligned Care Team (SMI PACT), to improve the healthcare of patients with SMI enrolled with the Veterans Health Administration. The SMI PACT team includes proactive medical nurse care management, and integrated mental health treatment through regular psychiatry consultation and a collaborative care model. Patients are recruited to receive primary care through SMI PACT based on having a serious mental illness that is manageable with treatment, and elevated risk for hospitalization or death. In a site-level prospective controlled trial, this project studies the effect, relative to usual care, of SMI PACT on provision of appropriate preventive and medical treatments, health-related quality of life, satisfaction with care, and medical and mental health treatment utilization and costs. Research includes mixed-methods formative evaluation of usual care and SMI PACT implementation to strengthen the intervention and assess barriers and facilitators. Investigators examine relationships among organizational context, intervention factors, and patient and clinician outcomes, and identify patient factors related to successful patient outcomes. DISCUSSION: This will be one of the first controlled trials of the implementation and effectiveness of a patient centered medical home for people with serious mental illness. It will provide information regarding the value of this strategy, and processes and tools for implementing this model in community healthcare settings. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01668355 . Registered August 20, 2012.

Autophagy is increased following either pharmacological or genetic silencing of mGluR5 signaling in Alzheimer's disease mouse models.

Alzheimer's disease (AD) is characterized by neurotoxicity mediated by the accumulation of beta amyloid (Aß) oligomers, causing neuronal loss and progressive cognitive decline. Genetic deletion or chronic pharmacological inhibition of mGluR5 by the negative allosteric modulator CTEP, rescues cognitive function and reduces Aß aggregation in both APPswe/PS1ΔE9 and 3xTg-AD mouse models of AD. In late onset neurodegenerative diseases, such as AD, defects arise at different stages of the autophagy pathway. Here, we show that mGluR5 cell surface expression is elevated in APPswe/PS1ΔE9 and 3xTg-AD mice. This is accompanied by reduced autophagy (accumulation of p62) as the consequence of increased ZBTB16 expression and reduced ULK1 activity, as we have previously observed in Huntington's disease (HD). The chronic (12 week) inhibition of mGluR5 with CTEP in APPswe/PS1ΔE9 and 3xTg-AD mice prevents the observed increase in mGluR5 surface expression. In addition, mGluR5 inactivation facilitates the loss of ZBTB16 expression and ULK1 activation as a consequence of ULK-Ser757 dephosphorylation, which promotes the loss of expression of the autophagy marker p62. Moreover, the genetic ablation of mGluR5 in APPswe/PS1ΔE9 mice activated autophagy via similar mechanisms to pharmacological blockade. This study provides further evidence that mGluR5 overactivation contributes to inhibition of autophagy and can result in impaired clearance of neurotoxic aggregates in multiple neurodegenerative diseases. Thus, it provides additional support for the potential of mGluR5 inhibition as a general therapeutic strategy for neurodegenerative diseases such as AD and HD.

Coordinating Care Across Health Care Systems for Veterans With Gynecologic Malignancies: A Qualitative Analysis.

BACKGROUND: Veterans concurrently using both Veterans Affairs (VA) and community providers and facilities have increased coordination needs related to bridging their care across health care settings. Women Veterans commonly require a combination of VA and community care if they have women-specific specialty care needs, such as gynecologic malignancies. OBJECTIVES: We assessed VA women's health providers' and administrators' perceptions of coordination challenges for Veterans' gynecologic cancer care, and potential approaches for addressing these challenges. RESEARCH DESIGN AND PARTICIPANTS: We carried out semistructured qualitative interviews with field-based key informants (VA gynecologists, women's health medical directors, and other staff directly involved in women's health care coordination) at 15 VA facilities. Transcripts were summarized in a template to capture key points. Themes were identified and iteratively revised (inductively/deductively) via a collaborative decision-making process utilizing matrices to compare content across interviews. RESULTS: Key informants (n=23) noted that services for patients with gynecologic cancers are provided through a combination of VA and community care with wide variation in care arrangements by facility. Care coordination challenges included care fragmentation, lack of role clarity and care tracking, and difficulties associated with VA and community provider communication, patient communication, patient records exchange, and authorizations. Care coordination roles suggested for addressing challenges included: care tracker, provider point-of-contact, patient liaison, and records administrator. CONCLUSIONS: Experiences in coordinating care for women Veterans with gynecologic malignancies receiving concurrent VA and community cancer care reveal challenges inherent in delivering care across health care systems, as well as potential approaches for addressing them.

Challenges in referral communication between VHA primary care and specialty care.

BACKGROUND: Poor communication between primary care providers (PCPs) and specialists is a significant problem and a detriment to effective care coordination. Inconsistency in the quality of primary-specialty communication persists even in environments with integrated delivery systems and electronic medical records (EMRs), such as the Veterans Health Administration (VHA). OBJECTIVE: The purpose of this study was to measure ease of communication and to characterize communication challenges perceived by PCPs and primary care personnel in the VHA, with a particular focus on challenges associated with referral communication. DESIGN: The study utilized a convergent mixed-methods design: online cross-sectional survey measuring PCP-reported ease of communication with specialists, and semi-structured interviews characterizing primary-specialty communication challenges. PARTICIPANTS: 191 VHA PCPs from one regional network were surveyed (54% response rate), and 41 VHA PCPs and primary care staff were interviewed. MAIN MEASURES/APPROACH: PCP-reported ease of communication mean score (survey) and recurring themes in participant descriptions of primary-specialty referral communication (interviews) were analyzed. KEY RESULTS: Among PCPs, ease-of-communication ratings were highest for women's health and mental health (mean score of 2.3 on a scale of 1-3 in both), and lowest for cardiothoracic surgery and neurology (mean scores of 1.3 and 1.6, respectively). Primary care personnel experienced challenges communicating with specialists via the EMR system, including difficulty in communicating special requests for appointments within a certain time frame and frequent rejection of referral requests due to rigid informational requirements. When faced with these challenges, PCPs reported using strategies such as telephone and e-mail contact with specialists with whom they had established relationships, as well as the use of an EMR-based referral innovation called "eConsults" as an alternative to a traditional referral. CONCLUSIONS: Primary-specialty communication is a continuing challenge that varies by specialty and may be associated with the likelihood of an established connection already in place between specialty and primary care. Improvement in EMR systems is needed, with more flexibility for the communication of special requests. Building relationships between PCPs and specialists may also facilitate referral communication.

Delivery of clinical genetic consultative services in the Veterans Health Administration.

OBJECTIVE: To characterize the delivery of genetic consultative services for adults, we examined the prevalence and organizational determinants of genetic consult availability and the organization of these services in the Veterans Health Administration. METHODS: We conducted a Web-based survey of Veterans Health Administration clinical leaders. We summarized facility characteristics using descriptive statistics. Multivariate logistic regression assessed associations between organizational characteristics and consult availability. RESULTS: We received 353 survey responses from key informants representing 141 Veterans Affairs Medical Centers. Clinicians could obtain genetic consults at 110 (78%) Veterans Affairs Medical Centers. Cancer genetic and neurogenetic consults were most common. Academic affiliation (odds ratio = 3.0; 95% confidence interval: 1.1-8.6) and provider education about genetics (odds ratio = 2.9; 95% confidence interval: 1.1-7.8) were significantly associated with consult availability. The traditional model of multidisciplinary specialty clinics or coordinated services between geneticists and other providers was most prevalent, although variability in the organization of these services was described, with consults available on-site, at another Veterans Affairs Medical Center, via telegenetics, or at non-Veterans Health Administration facilities. The emerging model of nongeneticists integrating genetics into their practices was also reported, with considerable variability by specialty. CONCLUSION: Both traditional and emerging models for genetic consultation are available in the Veterans Health Administration; however, there is variability in service organization that could influence quality of care.

A cancer genetics toolkit improves access to genetic services through documentation and use of the family history by primary-care clinicians.

PURPOSE: We developed, implemented, and evaluated a multicomponent cancer genetics toolkit designed to improve recognition and appropriate referral of individuals at risk for hereditary cancer syndromes. METHODS: We evaluated toolkit implementation in the women's clinics at a large Veterans Administration medical center using mixed methods, including pre-post semistructured interviews, clinician surveys, and chart reviews, and during implementation, monthly tracking of genetic consultation requests and use of a reminder in the electronic health record. We randomly sampled 10% of progress notes 6 months before (n = 139) and 18 months during implementation (n = 677). RESULTS: The toolkit increased cancer family history documentation by almost 10% (26.6% pre- and 36.3% postimplementation). The reminder was a key component of the toolkit; when used, it was associated with a twofold increase in cancer family history documentation (odds ratio = 2.09; 95% confidence interval: 1.39-3.15), and the history was more complete. Patients whose clinicians completed the reminder were twice as likely to be referred for genetic consultation (4.1-9.6%, P < 0.0001). CONCLUSION: A multicomponent approach to the systematic collection and use of family history by primary-care clinicians increased access to genetic services.

Factors influencing organizational adoption and implementation of clinical genetic services.

PURPOSE: We sought to identify characteristics of genetic services that facilitate or hinder adoption. METHODS: We conducted semi-structured key informant interviews in five clinical specialties (primary care, medical oncology, neurology, cardiology, pathology/laboratory medicine) within 13 Veterans Administration facilities. RESULTS: Genetic services (defined as genetic testing and consultation) were not typically characterized by informants (n = 64) as advantageous for their facilities or their patients; compatible with organizational norms of low cost and high clinical impact; or applicable to patient populations or norms of clinical care. Furthermore, genetic services had not been systematically adopted in most facilities because of their complexity: knowledge of and expertise on genetic testing was limited, and organizational barriers to utilization of genetic services were formidable. The few facilities that had some success with implementation of genetic services had knowledgeable clinicians interested in developing services and organizational-level facilitators such as accessible genetic test-ordering processes. CONCLUSION: Adoption and implementation of genetic services will require a multilevel effort that includes education of providers and administrators, opportunities for observing the benefits of genetic medicine, strategies for reducing the complexity of genomic medicine, expanded strategies for accessing genetics expertise and streamlining utilization, and resources dedicated to assessing the value of genetic information for the outcomes that matter to health-care organizations.

The JNK- and AKT/GSK3ß- signaling pathways converge to regulate Puma induction and neuronal apoptosis induced by trophic factor deprivation.

The AKT, GSK3 and JNK family kinases have been implicated in neuronal apoptosis associated with neuronal development and several neurodegenerative conditions. However, the mechanisms by which these kinase pathways regulate apoptosis remain unclear. In this study we have investigated the role of these kinases in neuronal cell death using an established model of trophic factor deprivation induced apoptosis in cerebellar granule neurons. BCL-2 family proteins are known to be central regulators of apoptosis and we have determined that the pro-apoptotic family member Puma is transcriptionally up-regulated in trophic factor deprived neurons and that Puma induction is required for apoptosis in vitro and in vivo. Importantly, we demonstrate that Puma induction is dependent on both JNK activation and AKT inactivation. AKT is known to regulate a number of downstream pathways, however we have determined that PI3K-AKT inactivation induces Puma expression through a GSK3ß-dependent mechanism. Finally we demonstrate that the JNK and AKT/GSK3ß pathways converge to regulate FoxO3a-mediated transcriptional activation of Puma. In summary we have identified a novel and critical link between the AKT, GSK3ß and JNK kinases and the regulation of Puma induction and suggest that this may be pivotal to the regulation of neuronal apoptosis in neurodegenerative conditions.