Integrating Behavioral Health & Primary Care in New Hampshire: A Path Forward to Sustainable Practice & Payment Transformation

New Hampshire residents face challenges with behavioral and physical health conditions and the interplay between them. National studies show the costs and the burden of illness from behavioral health conditions and co-occurring chronic health conditions that are not adequately treated in either primary care or behavioral health settings. Bringing primary health and behavioral health care together in integrated care settings can improve outcomes for both behavioral and physical health conditions. Primary care integrated behavioral health works in conjunction with specialty behavioral health providers, expanding capacity, improving access, and jointly managing the care of patients with higher levels of acuity In its work to improve the health of NH residents and create effective and cost-effective systems of care, the NH Citizens Health Initiative (Initiative) created the NH Behavioral Health Integration Learning Collaborative (BHI Learning Collaborative) in November of 2015, as a project of its Accountable Care Learning Network (NHACLN). Bringing together more than 60 organizations, including providers of all types and sizes, all of the state’s community mental health centers, all of the major private and public insurers, and government and other stakeholders, the BHI Learning Collaborative built on earlier work of a NHACLN Workgroup focused on improving care for depression and co-occurring chronic illness. The BHI Learning Collaborative design is based on the core NHACLN philosophy of “shared data and shared learning” and the importance of transparency and open conversation across all stakeholder groups. The first year of the BHI Learning Collaborative programming included shared learning on evidence-based practice for integrated behavioral health in primary care, shared data from the NH Comprehensive Healthcare Information System (NHCHIS), and work to develop sustainable payment models to replace inadequate Fee-for-Service (FFS) revenues. Provider members joined either a Project Implementation Track working on quality improvement projects to improve their levels of integration or a Listen and Learn Track for those just learning about Behavioral Health Integration (BHI). Providers in the Project Implementation Track completed a self-assessment of levels of BHI in their practice settings and committed to submit EHR-based clinical process and outcomes data to track performance on specified measures. All providers received access to unblinded NHACLN Primary Care and Behavioral Health attributed claims data from the NHCHIS for provider organizations in the NH BHI Learning Collaborative. Following up on prior work focused on developing a sustainable model for integrating care for depression and co-occurring chronic illness in primary care settings, the BHI Learning Collaborative engaged consulting experts and participants in understanding challenges in Health Information Technology and Exchange (HIT/HIE), privacy and confidentiality, and workforce adequacy. The BHI Learning Collaborative identified a sustainable payment model for integrated care of depression in primary care. In the process of vetting the payment model, the BHI Learning Collaborative also identified and explored challenges in payment for Substance Use Disorder Screening, Brief Intervention and Referral to Treatment (SBIRT). New Hampshire’s residents will benefit from a health care system where primary care and behavioral health are integrated to support the care of the whole person. New Hampshire’s current opiate epidemic accentuates the need for better screening for behavioral health issues, prevention, and treatment referral integrated into primary care. New Hampshire providers and payers are poised to move towards greater integration of behavioral health and primary care and the Initiative looks forward to continuing to support progress in supporting a path to sustainable integrated behavioral and primary care

Hemizygous Deletion on Chromosome 3p26.1 Is Associated with Heavy Smoking among African American Subjects in the COPDGene Study

Many well-powered genome-wide association studies have identified genetic determinants of self-reported smoking behaviors and measures of nicotine dependence, but most have not considered the role of structural variants, such as copy number variation (CNVs), influencing these phenotypes. Here, we included 2,889 African American and 6,187 non-Hispanic White subjects from the COPDGene cohort (http://www.copdgene.org) to carefully investigate the role of polymorphic CNVs across the genome on various measures of smoking behavior. We identified a CNV component (a hemizygous deletion) on chromosome 3p26.1 associated with two quantitative phenotypes related to smoking behavior among African Americans. This polymorphic hemizygous deletion is significantly associated with pack-years and cigarettes smoked per day among African American subjects in the COPDGene study. We sought evidence of replication in African Americans from the population based Atherosclerosis Risk in Communities (ARIC) study. While we observed similar CNV counts, the extent of exposure to cigarette smoking among ARIC subjects was quite different and the smaller sample size of heavy smokers in ARIC severely limited statistical power, so we were unable to replicate our findings from the COPDGene cohort. But meta-analyses of COPDGene and ARIC study subjects strengthened our association signal. However, a few linkage studies have reported suggestive linkage to the 3p26.1 region, and a few genome-wide association studies (GWAS) have reported markers in the gene (GRM7) nearest to this 3p26.1 area of polymorphic deletions are associated with measures of nicotine dependence among subjects of European ancestry

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD

Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p 10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10−392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the differences observed between pQTLs and eQTLs SNPs, we recommend that protein biomarker-disease association studies take into account the potential effect of common local SNPs and that pQTLs be integrated along with eQTLs to uncover disease mechanisms. Large-scale blood biomarker studies would also benefit from close attention to the ABO blood group

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

BACKGROUND: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. METHODS: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). FINDINGS: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29-146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0- 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25-1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39-1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65-1·60]; p=0·92). INTERPRETATION: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention. FUNDING: British Heart Foundation

Driving the brain towards creativity and intelligence: A network control theory analysis

High-level cognitive constructs, such as creativity and intelligence, entail complex and multiple processes, including cognitive control processes. Recent neurocognitive research on these constructs highlight the importance of dynamic interaction across neural network systems and the role of cognitive control processes in guiding such a dynamic interaction. How can we quantitatively examine the extent and ways in which cognitive control contributes to creativity anf intelligence? To address this question, we apply a computational network control theory (NCT) approach to structural brain imaging data acquired via diffusion tensor imaging in a large sample of participants, to examine how NCT relates to individual differences in distinct measures of creative ability and intelligence. Recent application of this theory at the neural level is built on a model of brain dynamics, which mathematically models patterns of inter-region activity propagated along the structure of an underlying network. The strength of this approach is its ability to characterize the potential role of each brain region in regulating whole-brain network function based on its anatomical fingerprint and a simplified model of node dynamics. We find that intelligence is related to the ability to “drive” the brain system into easy to reach neural states by the right inferior parietal lobe and lower integration abilities in the left retrosplenial cortex. We also find that creativity is related to the ability to “drive” the brain system into difficult to reach states by the right dorsolateral prefrontal cortex (inferior frontal junction) and higher integration abilities in sensorimotor areas. Furthermore, we found that different facets of creativity—fluency, flexibility, and originality—relate to generally similar but not identical network controllability processes. We relate our findings to general theories on intelligence and creativity