A Cluster Randomized Trial of Primary Care Practice Redesign to Integrate Behavioral Health for Those Who Need It Most: Patients With Multiple Chronic Conditions.

PURPOSE: Patient outcomes can improve when primary care and behavioral health providers use a collaborative system of care, but integrating these services is difficult. We tested the effectiveness of a practice intervention for improving patient outcomes by enhancing integrated behavioral health (IBH) activities. METHODS: We conducted a pragmatic, cluster randomized controlled trial. The intervention combined practice redesign, quality improvement coaching, provider and staff education, and collaborative learning. At baseline and 2 years, staff at 42 primary care practices completed the Practice Integration Profile (PIP) as a measure of IBH. Adult patients with multiple chronic medical and behavioral conditions completed the Patient-Reported Outcomes Measurement Information System (PROMIS-29) survey. Primary outcomes were the change in 8 PROMIS-29 domain scores. Secondary outcomes included change in level of integration. RESULTS: Intervention assignment had no effect on change in outcomes reported by 2,426 patients who completed both baseline and 2-year surveys. Practices assigned to the intervention improved PIP workflow scores but not PIP total scores. Baseline PIP total score was significantly associated with patient-reported function, independent of intervention. Active practices that completed intervention workbooks (n = 13) improved patient-reported outcomes and practice integration (P ≤ .05) compared with other active practices (n = 7). CONCLUSION: Intervention assignment had no effect on change in patient outcomes; however, we did observe improved patient outcomes among practices that entered the study with greater IBH. We also observed more improvement of integration and patient outcomes among active practices that completed the intervention compared to active practices that did not. Additional research is needed to understand how implementation efforts to enhance IBH can best reach patients.

Syntaxin 1 Ser14 phosphorylation is required for nonvesicular dopamine release.

Amphetamine (AMPH) is a psychostimulant that is commonly abused. The stimulant properties of AMPH are associated with its ability to increase dopamine (DA) neurotransmission. This increase is promoted by nonvesicular DA release mediated by reversal of DA transporter (DAT) function. Syntaxin 1 (Stx1) is a SNARE protein that is phosphorylated at Ser14 by casein kinase II. We show that Stx1 phosphorylation is critical for AMPH-induced nonvesicular DA release and, in Drosophila melanogaster, regulates the expression of AMPH-induced preference and sexual motivation. Our molecular dynamics simulations of the DAT/Stx1 complex demonstrate that phosphorylation of these proteins is pivotal for DAT to dwell in a DA releasing state. This state is characterized by the breakdown of two key salt bridges within the DAT intracellular gate, causing the opening and hydration of the DAT intracellular vestibule, allowing DA to bind from the cytosol, a mechanism that we hypothesize underlies nonvesicular DA release.

Co-creating the Patient Partner Guide by a Multiple Chronic Conditions Team of Patients, Clinicians, and Researchers: Observational Report.

BACKGROUND: Engaging patients as partners can influence research, with rewards and deterrents. The authors are researchers and patient co-investigators who collaborated on a comparative effectiveness, randomized controlled study of a structured quality improvement (QI) process to improve behavioral health and primary care integration for people managing multiple chronic conditions (MCC). Patient co-investigators responded to a gap in available resources to support study clinics in partnering with their own patients in QI and co-created the Patient Partner Guide (PPG). OBJECTIVE: Describe the development of the PPG, its use by clinics undertaking the QI project, and research team partnerships. DESIGN: Observational report of study intervention component. PARTICIPANTS: Diverse patients and family members managing MCC and members of their primary care clinics. INTERVENTION: The PPG component of the study intervention is a five-step workbook providing practical tools and resources to sustain partnerships across clinic QI team members, including patient partners. The process of developing the PPG relied on relationship-building tools that were iteratively assessed, practiced, improved, and incorporated into the PPG under the leadership of patient co-investigators. MAIN MEASURES: Observations related to PPG use and patient partner inclusion in clinic QI; impact on the research team. KEY RESULTS: Of 20 clinics, 6 engaged patients as full partners on QI teams. Clinics found resistance in partnering and challenges in using the PPG but valued the material and their partners' contributions. Similarly, engagement of patient co-investigators in research brought a shift in perspective to team members. The PPG is available and was adapted for use by research teams. CONCLUSIONS: Engagement of patients and other stakeholders in research can be transformative and productive. Building relationships through meaningful work benefits others, and in turn, the research process. This approach can enhance clinical care QI and may result in substantial contributions to the conduct of research. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02868983.

Development and validation of the patient centeredness index for primary care.

AIMS AND OBJECTIVES: To describe the development of the Patient Centeredness Index (PCI), evaluate its psychometric characteristics and evaluate the relationships between scores on the PCI and an established measure of empathy. BACKGROUND: Patient centeredness helps patients manage multiple chronic conditions with their providers, nurses and other team members. However, no instrument exists for evaluating patient centeredness within primary care practices treating this population. DESIGN: Multi-site instrument development and validation. STROBE reporting guidelines were followed. METHODS: To identify themes, we consulted literature on patient centeredness and engaged stakeholders who had or were caring for people with multiple chronic conditions (n = 7). We composed and refined items to represent those themes with input from clinicians and researchers. To evaluate reliability and convergent validity, we administered surveys to participants (n = 3622) with chronic conditions recruited from 44 primary care practices for a large-scale cluster randomised clinical trial of the effects of a practice-level intervention on patient and practice-level outcomes. Participants chose to complete the 16-item survey online, on paper or by phone. Surveys assessed demographics, number of chronic conditions and ratings of provider empathy. We conducted exploratory factor analysis to model the interrelationships among items. RESULTS: A single factor explained 93% of total variance. Factor loadings ranged from 0.55-0.85, and item-test correlations were ≥.67. Cronbach's alpha was .93. A moderate, linear correlation with ratings of provider's empathy (r = .65) supports convergent validity. CONCLUSIONS: The PCI is a new tool for obtaining patient perceptions of the patient centeredness of their primary care practice. The PCI shows acceptable reliability and evidence of convergent validity among patients managing chronic conditions. RELEVANCE TO CLINICAL PRACTICE: The PCI rapidly identifies patients' perspectives on patient centeredness of their practice, making it ideal for administration in busy primary care settings that aim to efficiently address patient-identified needs. TRIAL REGISTRATION: Clinicaltrials.org Protocol ID: WLPS-1409-24372. TITLE: Integrating Behavioural Health and Primary Care for Comorbid Behavioural and Medical Problems (IBHPC).

Integrating behavioral health & primary care for multiple chronic diseases: Clinical trial of a practice redesign toolkit.

Context: Most patients in need of behavioral health (BH) care are seen in primary care, which often has difficulty responding. Some practices integrate behavioral health care (IBH), with medical and BH providers at the same location, working as a team. However, it is difficult to achieve high levels of integration. Objective: Test the effectiveness of a practice intervention designed to increase BH integration. Study Design: Pragmatic, cluster-randomized controlled trial. Setting: 43 primary care practices with on-site BH services in 13 states. Population: 2,460 adults with multiple chronic medical and behavioral conditions. Intervention: 24-month practice change process including an online curriculum, a practice redesign and implementation workbook, remote quality improvement coaching services, and an online learning community. Outcomes: Primary outcomes were changes in the 8 Patient-Reported Outcomes Measurement Information System (PROMIS-29) domain scores. Secondary outcomes were changes in medication adherence, self-reported healthcare utilization, time lost due to disability, cardiovascular capacity, patient centeredness, provider empathy, and several condition-specific measures. A sample of practice staff completed the Practice Integration Profile at each time point to estimate the degree of BH integration in that site. Practice-level case studies estimated the typical costs of implementing the intervention. Results: The intervention had no significant effect on any of the primary or secondary outcomes. Subgroup analyses showed no convincing patterns of effect in any populations. COVID-19 was apparently not a moderating influence of the effect of the intervention on outcomes. The intervention had a modest effect on the degree of practice integration, reaching statistical significance in the Workflow domain. The median cost of the intervention was $18,204 per practice. In post-hoc analysis, level of BH integration was associated with improved patient outcomes independent of the intervention, both at baseline and longitudinally. Conclusions: The specific intervention tested in this study was inexpensive, but had only a small impact on the degree of BH integration, and none on patient outcomes. However, practices that had more integration at baseline had better patient outcomes, independent of the intervention. Although this particular intervention was ineffective, IBH remains an attractive strategy for improving patient outcomes.

Integrating Behavioral Health and Primary Care (IBH-PC) to improve patient-centered outcomes in adults with multiple chronic medical and behavioral health conditions: study protocol for a pragmatic cluster-randomized control trial.

BACKGROUND: Chronic diseases that drive morbidity, mortality, and health care costs are largely influenced by human behavior. Behavioral health conditions such as anxiety, depression, and substance use disorders can often be effectively managed. The majority of patients in need of behavioral health care are seen in primary care, which often has difficulty responding. Some primary care practices are providing integrated behavioral health care (IBH), where primary care and behavioral health providers work together, in one location, using a team-based approach. Research suggests there may be an association between IBH and improved patient outcomes. However, it is often difficult for practices to achieve high levels of integration. The Integrating Behavioral Health and Primary Care study responds to this need by testing the effectiveness of a comprehensive practice-level intervention designed to improve outcomes in patients with multiple chronic medical and behavioral health conditions by increasing the practice's degree of behavioral health integration. METHODS: Forty-five primary care practices, with existing onsite behavioral health care, will be recruited for this study. Forty-three practices will be randomized to the intervention or usual care arm, while 2 practices will be considered "Vanguard" (pilot) practices for developing the intervention. The intervention is a 24-month supported practice change process including an online curriculum, a practice redesign and implementation workbook, remote quality improvement coaching services, and an online learning community. Each practice's degree of behavioral health integration will be measured using the Practice Integration Profile. Approximately 75 patients with both chronic medical and behavioral health conditions from each practice will be asked to complete a series of surveys to measure patient-centered outcomes. Change in practice degree of behavioral health integration and patient-centered outcomes will be compared between the two groups. Practice-level case studies will be conducted to better understand the contextual factors influencing integration. DISCUSSION: As primary care practices are encouraged to provide IBH services, evidence-based interventions to increase practice integration will be needed. This study will demonstrate the effectiveness of one such intervention in a pragmatic, real-world setting. TRIAL REGISTRATION: ClinicalTrials.gov NCT02868983 . Registered on August 16, 2016.

Rare autism-associated variants implicate syntaxin 1 (STX1 R26Q) phosphorylation and the dopamine transporter (hDAT R51W) in dopamine neurotransmission and behaviors.

BACKGROUND: Syntaxin 1 (STX1) is a presynaptic plasma membrane protein that coordinates synaptic vesicle fusion. STX1 also regulates the function of neurotransmitter transporters, including the dopamine (DA) transporter (DAT). The DAT is a membrane protein that controls DA homeostasis through the high-affinity re-uptake of synaptically released DA. METHODS: We adopt newly developed animal models and state-of-the-art biophysical techniques to determine the contribution of the identified gene variants to impairments in DA neurotransmission observed in autism spectrum disorder (ASD). OUTCOMES: Here, we characterize two independent autism-associated variants in the genes that encode STX1 and the DAT. We demonstrate that each variant dramatically alters DAT function. We identify molecular mechanisms that converge to inhibit reverse transport of DA and DA-associated behaviors. These mechanisms involve decreased phosphorylation of STX1 at Ser14 mediated by casein kinase 2 as well as a reduction in STX1/DAT interaction. These findings point to STX1/DAT interactions and STX1 phosphorylation as key regulators of DA homeostasis. INTERPRETATION: We determine the molecular identity and the impact of these variants with the intent of defining DA dysfunction and associated behaviors as possible complications of ASD.

Effects of plant gross morphology on predator consumption rates.

We find that spatial structure, and in particular, differences in gross plant morphology, can alter the consumption rates of generalist insect predators. We compared Asian lady beetle, Harmonia axyridis Pallas, and green lacewing larvae, Chrysoperla carnea Stephens, consumption rates of pea aphids, Acyrthosiphon pisum Harris, in homogeneous environments (petri dishes) and heterogeneous environments (whole plants). Spatial complexity is often described as reducing predator success, and we did find that predators consumed significantly more aphids on leaf tissue in petri dishes than on whole plants with the same surface area. However, subtle differences in plant morphology may have more unexpected effects. A comparison of consumption rates on four different isogenic pea morphs (Pisum sativum L.) controlled for surface area indicated that both lady beetles and lacewings were more successful on morphologies that were highly branched. We speculate that predators move more easily over highly branched plants because there are more edges to grasp.

Effects of plant gross morphology on predator searching behaviour.

Plant morphology influences insect predators' abilities to capture prey and control pest populations. Several mechanisms for this effect of plants on predator foraging have been proposed. In particular, it is often claimed that increased complexity of plant structures may increase search time and reduce foraging success. Using time-lapse photography we recorded search paths, and compared the total path lengths, percentages of plants searched, and path tortuosity of adult multicolored Asian lady beetles (Harmonia axyridis Pallas) and green lacewing larvae (Chrysoperla carnea Stephens) foraging for pea aphids (Acyrthosiphon pisum Harris) on pea near-isolines (Pisum sativum L.) that differed in shape. We found that H. axyridis searched leafy morphologies less thoroughly than those with more branches, while C. carnea larvae search paths did not differ on any of the pea morphologies. In addition, the ability of H. axyridis to attach to plants and maneuver was increased on morphologies with many branches and edges, while C. carnea was able to attach to all morphologies. Both species, however, had significantly reduced predation success on inverted leaf surfaces. We conclude that undersides of leaves, far from the leaf margin, may serve as partial prey refugia. In addition, we find increased plant branching or an increase in other morphological features which provide predator attachment points may promote foraging success.

Deficits in syntaxin 1 phosphorylation in schizophrenia prefrontal cortex.

BACKGROUND: Schizophrenia has been described as a disease of the synapse. On the basis of previous studies reporting reductions in the levels and activity of CK2 (also know as casein kinase 2 or II) in the brain of subjects with schizophrenia, we hypothesized that CK2-mediated phosphorylation of the presynaptic protein syntaxin 1 (Stx 1) is deficient in schizophrenia. This in turn could affect the binding of Stx 1 to its protein partners and result in abnormal neurotransmitter release and synaptic transmission. METHODS: We analyzed post mortem prefrontal cortex samples from 15 schizophrenia cases and matched controls by quantitative immunoblotting. RESULTS: In addition to replicating previous findings of reduced CK2 levels, we show that as predicted, the deficit in CK2 correlates with a deficit in phospho-Stx 1. In contrast, we find that these deficits are not present in depression cases. Further, we show that the reduced levels of CK2 and phospho-Stx 1 are not due to treatment with antipsychotic drugs (APDs). In fact, APDs seem to increase both CK2 and phospho-Stx 1, suggesting that their therapeutic action may be associated with the reversal of these deficits. Finally, we show that lower phospho-Stx 1 levels are associated with reduced binding of Stx 1 to SNAP-25 and MUNC18 and decreased SNARE complex formation. CONCLUSIONS: Our findings constitute the first report of altered phosphorylation of a key component for neurotransmitter release in humans and suggest that regulation of Stx 1 by CK2-mediated phosphorylation could play a role in the pathophysiology of schizophrenia.

Pediatric hospital dying trajectories: what we learned and can share.

Diverse settings, diagnoses, and time constraints challenge a small hospital's ability to provide comprehensive care to all dying children and their families. Children who died at a regional hospital in southeast Georgia were studied to document the circumstances under which they died and the palliative and end-of-life care provided. The most common causes of death were injury and circulatory events. At the time of death, 56% of the children studied were in the care of the Emergency Department. Seventy-two percent were previously healthy children; 78% were hospitalized for less than 24 hours prior to death. Based on previous medical history and length of final hospitalization, four hospital dying trajectories were defined. Hospital dying trajectories provide a basis for planning comprehensive hospital pediatric palliative and end-of-life care program by identifying the settings, time limitations, and key personnel.