Behavioral Therapy for Functional Heartburn: Recommendation Statements.

BACKGROUND & AIMS: Brain-gut behavior therapies (BGBT) are increasingly recognized as effective therapeutic interventions for functional heartburn. However, recommendations regarding candidacy for treatment, initial treatment selection, and navigating treatment non-response have not been established for functional heartburn specifically. The aim of this study was to establish expert-based recommendations for behavioral treatment in patients with functional heartburn. METHODS: The validated RAND/University of California, Los Angeles Appropriateness Method was applied to develop recommendations. A 15-member panel composed of 10 gastrointestinal psychologists and 5 esophageal specialists ranked the appropriateness of a series of statements on a 9-point interval scale over 2 ranking periods. Statements were within the following domains: pre-therapy evaluation, candidacy criteria for BGBT, selection of initial BGBT, role of additional therapy for initial non-response to BGBT, and role of pharmacologic neuromodulation. The primary outcome was appropriateness of each intervention based on the recommendation statements. RESULTS: Recommendations for psychosocial assessment (eg, hypervigilance, symptom-specific anxiety, health-related quality of life), candidacy criteria (eg, motivated for BGBT, acknowledges the role of stress in symptoms), and treatment were established. Gut-directed hypnotherapy or cognitive behavioral therapy were considered appropriate BGBT for functional heartburn. Neuromodulation and/or additional BGBT were considered appropriate in the context of non-response. CONCLUSIONS: Gut-directed hypnotherapy and/or cognitive behavioral therapy are recommended as appropriate behavioral interventions for heartburn symptoms, depending on clinical indication, specific gut-brain targets, and preferred treatment modality (pharmacologic vs non-pharmacologic). Pre-therapy evaluation of psychosocial processes and candidacy for BGBT are important to determine eligibility for referral to psychogastroenterology services.

Pediatric oncology services in Nepal: A special focus on pharmacy practice.

The role of clinical pharmacists or oncology pharmacists in pediatric oncology has been established as important in anticancer regimen review, dose calculation, recommendation, chemocounseling, identification of drug-related problems, its resolution, and, prevention and monitoring of adverse drug reactions within high-income countries. With several hospitals providing pediatric oncology services in Nepal, clinical pharmacist involvement in these hospitals is very poor. Upon reviewing the reputed organization and association focused on pediatric oncology pharmacy practice, it looks imperative for Nepal to initiate clinical pharmacy services which will further help in improving patient health outcomes. As such in this commentary, we try to accentuate the pediatric oncology services and pediatric pharmacy practice within Nepal and try to pinpoint the potential areas for clinical pharmacists to focus if they intend to provide services in pediatric oncology pharmacy practice.

Protein dynamics and lipid affinity of monomeric, zeaxanthin-binding LHCII in thylakoid membranes.

The xanthophyll cycle in the antenna of photosynthetic organisms under light stress is one of the most well-known processes in photosynthesis, but its role is not well understood. In the xanthophyll cycle, violaxanthin (Vio) is reversibly transformed to zeaxanthin (Zea) that occupies Vio binding sites of light-harvesting antenna proteins. Higher monomer/trimer ratios of the most abundant light-harvesting protein, the light-harvesting complex II (LHCII), usually occur in Zea accumulating membranes and have been observed in plants after prolonged illumination and during high-light acclimation. We present a combined NMR and coarse-grained simulation study on monomeric LHCII from the npq2 mutant that constitutively binds Zea in the Vio binding pocket. LHCII was isolated from 13C-enriched npq2 Chlamydomonas reinhardtii (Cr) cells and reconstituted in thylakoid lipid membranes. NMR results reveal selective changes in the fold and dynamics of npq2 LHCII compared with the trimeric, wild-type and show that npq2 LHCII contains multiple mono- or digalactosyl diacylglycerol lipids (MGDG and DGDG) that are strongly protein bound. Coarse-grained simulations on npq2 LHCII embedded in a thylakoid lipid membrane agree with these observations. The simulations show that LHCII monomers have more extensive lipid contacts than LHCII trimers and that protein-lipid contacts are influenced by Zea. We propose that both monomerization and Zea binding could have a functional role in modulating membrane fluidity and influence the aggregation and conformational dynamics of LHCII with a likely impact on photoprotection ability.

When Is Patient Behavior Indicative of Avoidant Restrictive Food Intake Disorder (ARFID) Vs Reasonable Response to Digestive Disease?

BACKGROUND & AIMS: Dietary modification is common in patients with digestive diseases to improve symptoms; however, food avoidance can become problematic. Avoidant Restrictive Food Intake Disorder (ARFID) is characterized as failure to meet one's nutritional needs owing to sensory hypersensitivity, lack of interest in eating, or fear of aversive consequences from eating, and is associated with negative medical and psychosocial outcomes. This study characterizes ARFID behaviors in adults with achalasia, celiac sprue, eosinophilic esophagitis, and inflammatory bowel disease. METHODS: In this cross-sectional study, 289 adults aged 18 and older completed self-report measures evaluating use of dietary treatment, ARFID symptoms, and psychosocial outcomes. Primary analyses investigated the occurrence of ARFID in patients with achalasia, celiac, eosinophilic esophagitis, and inflammatory bowel disease. Secondary analyses explored the associations between ARFID symptoms and clinical and psychosocial outcomes. RESULTS: More than half (53.7%) of the total sample met the diagnostic criteria for ARFID based on the Nine-Item ARFID Screen (NIAS), with 78.4% of patients with achalasia meeting criteria. Patients on a physician-directed diet showed greater fear of gastrointestinal symptoms (P = .025), less interest in food (P = .046), and a higher total NIAS score (P = .045). For patients using dietary therapy, those who had met with a dietitian reported higher NIAS scores (P = .039). Food avoidance/restriction was associated with increased anxiety and depression, and diminished health-related quality of life. CONCLUSIONS: It is likely that ARFID rates, as measured by the NIAS, are inflated in these 4 patient groups. These findings highlight the need for updated assessments of ARFID in patients with complex digestive diseases.

A screening method for binding synthetic metallo-complexes to haem proteins.

The introduction of a second coordination sphere, in the form of a protein scaffold, to synthetic catalysts can be beneficial for their reactivity and substrate selectivity. Here we present semi-native polyacrylamide gel electrophoresis (semi-native PAGE) as a rapid screening method for studying metal complex-protein interactions. Such a screening is generally performed using electron spray ionization mass spectrometry (ESI-MS) and/or UV-Vis spectroscopy. Semi-native PAGE analysis has the advantage that it does not rely on spectral changes of the metal complex upon protein interaction and can be applied for high-throughput screening and optimization of complex binding. In semi-native PAGE non-denatured protein samples are loaded on a gel containing sodium dodecyl sulphate (SDS), leading to separation based on differences in structural stability. Semi-native PAGE gel runs of catalyst-protein mixtures were compared to gel runs obtained with native and denaturing PAGE. ESI-MS was additionally realised to confirm protein-complex binding. The general applicability of semi-native PAGE was investigated by screening the binding of various cobalt- and ruthenium-based compounds to three types of haem proteins.

Structural dynamics of light harvesting proteins, photosynthetic membranes, and cells observed by spectral editing solid-state NMR.

Photosynthetic light-harvesting complexes have a remarkable capacity to perform robust photo-physics at ambient temperatures and in fluctuating environments. Protein conformational dynamics and membrane mobility are processes that contribute to the light-harvesting efficiencies and control photoprotective responses. This short review describes the application of magic angle spinning nuclear magnetic resonance (NMR) spectroscopy for characterizing the structural dynamics of pigment, protein, and thylakoid membrane components related to light harvesting and photoprotection. I will discuss the use of dynamics-based spectral editing solid-state NMR for distinguishing rigid and mobile components and assessing protein, pigment, and lipid dynamics on sub-nanosecond to millisecond timescales. Dynamic spectral editing NMR has been applied to investigate light-harvesting complex II protein conformational dynamics inside lipid bilayers and in native membranes. Furthermore, we used the NMR approach to assess thylakoid membrane dynamics. Finally, it is shown that dynamics-based spectral editing NMR for reducing spectral complexity by filtering motion-dependent signals enabled us to follow processes in live photosynthetic cells.

Real-Time NMR Recording of Fermentation and Lipid Metabolism Processes in Live Microalgae Cells.

Non-invasive and real-time recording of processes in living cells has been limited to detection of small cellular components such as soluble proteins and metabolites. Here we report a multiphase NMR approach using magic-angle spinning NMR to synchronously follow microbial processes of fermentation, lipid metabolism and structural dynamic changes in live microalgae cells. Chlamydomonas reinhardtii green algae were highly concentrated, introducing dark fermentation and anoxia conditions. Single-pulse NMR experiments were applied to obtain temperature-dependent kinetic profiles of the formed fermentation products. Through dynamics-based spectral editing NMR, simultaneous conversion of galactolipids into TAG and free fatty acids was observed and rapid loss of rigid lipid structures. This suggests that lipolysis under dark and anoxia conditions finally results in the breakdown of cell and organelle membranes, which could be beneficial for recovery of intracellular microbial useful products.

Conformational Dynamics of Light-Harvesting Complex II in a Native Membrane Environment.

Photosynthetic light-harvesting complexes (LHCs) of higher plants, moss, and green algae can undergo dynamic conformational transitions, which have been correlated to their ability to adapt to fluctuations in the light environment. Herein, we demonstrate the application of solid-state NMR spectroscopy on native, heterogeneous thylakoid membranes of Chlamydomonas reinhardtii (Cr) and on Cr light-harvesting complex II (LHCII) in thylakoid lipid bilayers to detect LHCII conformational dynamics in its native membrane environment. We show that membrane-reconstituted LHCII contains selective sites that undergo fast, large-amplitude motions, including the phytol tails of two chlorophylls. Protein plasticity is also observed in the N-terminal stromal loop and in protein fragments facing the lumen, involving sites that stabilize the xanthophyll-cycle carotenoid violaxanthin and the two luteins. The results report on the intrinsic flexibility of LHCII pigment-protein complexes in a membrane environment, revealing putative sites for conformational switching. In thylakoid membranes, fast dynamics of protein and pigment sites is significantly reduced, which suggests that in their native organelle membranes, LHCII complexes are locked in specific conformational states.

In vivo NMR as a tool for probing molecular structure and dynamics in intact Chlamydomonas reinhardtii cells.

We report the application of NMR dynamic spectral editing for probing the structure and dynamics of molecular constituents in fresh, intact cells and in freshly prepared thylakoid membranes of Chlamydomonas reinhardtii (Cr.) green algae. For isotope labeling, wild-type Cr. cells were grown on 13C acetate-enriched minimal medium. 1D 13C J-coupling based and dipolar-based MAS NMR spectra were applied to distinguish 13C resonances of different molecular components. 1D spectra were recorded over a physiological temperature range, and whole-cell spectra were compared to those taken from thylakoid membranes, evaluating their composition and dynamics. A theoretical model for NMR polarization transfer was used to simulate the relative intensities of direct, J-coupling, and dipolar-based polarization from which the degree of lipid segmental order and rotational dynamics of the lipid acyl chains were estimated. We observe that thylakoid lipid signals dominate the lipid spectral profile of whole algae cells, demonstrating that with our novel method, thylakoid membrane characteristics can be detected with atomistic precision inside intact photosynthetic cells. The experimental procedure is rapid and applicable to fresh cell cultures, and could be used as an original approach for detecting chemical profiles, and molecular structure and dynamics of photosynthetic membranes in vivo in functional states.

Older Adult Preferences of Mobile Application Functionality Supporting Medication Self-Management.

Health systems and insurers alike are increasingly interested in leveraging mHealth (mobile health) tools to support patient health-related behaviors including medication adherence. However, these tools are not widely used by older patients. This study explores patient preferences for functionality in a smartphone application (app) that supports medication self-management among older adults with multiple chronic conditions. We conducted six discussion groups in Chicago, Miami, and Denver (N = 46). English-speaking older adults (55 and older) who owned smartphones and took five or more prescription medicines were invited to participate. Discussions covered familiarity with and use of current apps and challenges with taking multidrug regimens. Participants reviewed a range of possible mobile app functions and were asked to give feedback regarding the acceptability and desirability of each to support medication management. Very few participants (n = 3) reported current use of a mobile app for medication support, although all were receptive. Challenges to medication use were forgetfulness, fear of adverse events, and managing medication information from multiple sources. Desired features included (1) a list and consolidated schedule of medications, (2) identification and warning of unsafe medication interactions, (3) reminder alerts to take medicine, and (4) the ability record when medications were taken. Features relating to refill ordering, pharmacy information, and comparing costs for medication were not considered to be as important for an app.

Protein and lipid dynamics in photosynthetic thylakoid membranes investigated by in-situ solid-state NMR.

Photosynthetic thylakoid membranes contain the protein machinery to convert sunlight in chemical energy and regulate this process in changing environmental conditions via interplay between lipid, protein and xanthophyll molecular constituents. This work addresses the molecular effects of zeaxanthin accumulation in thylakoids, which occurs in native systems under high light conditions through the conversion of the xanthophyll violaxanthin into zeaxanthin via the so called xanthophyll cycle. We applied biosynthetic isotope labeling and 13C solid-state NMR spectroscopy to simultaneously probe the conformational dynamics of protein, lipid and xanthophyll constituents of thylakoids isolated from wild type (cw15) and npq2 mutant of the green alga Chlamydomonas reinhardtii, that accumulates zeaxanthin constitutively. Results show differential dynamics of wild type and npq2 thylakoids. Ordered-phase lipids have reduced mobility and mobile-phase lipids have enlarged dynamics in npq2 membranes, together spanning a broader dynamical range. The fraction of ordered lipids is much larger than the fraction of mobile lipids, which explains why zeaxanthin appears to cause overall reduction of thylakoid membrane fluidity. In addition to the ordered lipids, also the xanthophylls and a subset of protein sites in npq2 thylakoids have reduced conformational dynamics. Our work demonstrates the applicability of solid-state NMR spectroscopy for obtaining a microscopic picture of different membrane constituents simultaneously, inside native, heterogeneous membranes.

Disentangling protein and lipid interactions that control a molecular switch in photosynthetic light harvesting.

In the photosynthetic apparatus of plants and algae, the major Light-Harvesting Complexes (LHCII) collect excitations and funnel these to the photosynthetic reaction center where charge separation takes place. In excess light conditions, remodeling of the photosynthetic membrane and protein conformational changes produces a photoprotective state in which excitations are rapidly quenched to avoid photodamage. The quenched states are associated with protein aggregation, however the LHCII complexes are also proposed to have an intrinsic capacity to shift between light harvesting and fluorescence-quenched conformational states. To disentangle the effects of protein-protein and protein-lipid interactions on the LHCII photoprotective switch, we compared the structural and fluorescent properties of LHCII lipid nanodiscs and proteoliposomes with very low protein-to-lipid ratios. We demonstrate that LHCII proteins adapta fully fluorescent state in nanodiscs and in proteoliposomes with highly diluted protein densities. Increasing the protein density induces a transition into a mildly-quenched state that reaches a plateau at a molar protein-to-lipid ratio of 0.001 and has a fluorescence yield reminiscent of the light-harvesting state in vivo. The low onset for quenching strongly suggests that LHCII-LHCII attractive interactions occur inside membranes. The transition at low protein densities does not involve strong changes in the excitonic circular-dichroism spectrum and is distinct from a transition occurring at very high protein densities that comprises strong fluorescence quenching and circular-dichroism spectral changes involving chlorophyll 611 and 612, correlating with proposed quencher sites of the photoprotective mechanisms.

The Role of Patient Activation in Preferences for Shared Decision Making: Results From a National Survey of U.S. Adults.

Studies investigating preferences for shared decision making (SDM) have focused on associations with sociodemographic variables, with few investigations exploring patient factors. We aimed to investigate the relationship between patient activation and preferences for SDM in 6 common medical decisions among a nationally representative cross-sectional survey of American adults. Adults older than 18 were recruited online (n = 2,700) and by telephone (n = 700). Respondents completed sociodemographic assessments and the Patient Activation Measure. They were also asked whether they perceived benefit (yes/no) in SDM in 6 common medical decisions. Nearly half of the sample (45.9%) reached the highest level of activation (Level 4). Activation was associated with age (p < .001), higher income (p = .001), higher education (p = .010), better self-rated health (p < .001), and fewer chronic conditions (p = .050). The proportion of people who agreed that SDM was beneficial varied from 53.1% (deciding the necessity of a diagnostic test) to 71.8% (decisions associated with making lifestyle changes). After we controlled for participant characteristics, higher activation was associated with greater perceived benefit in SDM across 4 of the 6 decisions. Preferences for SDM varied among 6 common medical scenarios. Low patient activation is an important barrier to SDM that could be ameliorated through the development of behavioral interventions.

Proton-Coupled Electron Transfer Constitutes the Photoactivation Mechanism of the Plant Photoreceptor UVR8.

UVR8 is a novel UV-B photoreceptor that regulates a range of plant responses and is already used as a versatile optogenetic tool. Instead of an exogenous chromophore, UVR8 uniquely employs tryptophan side chains to accomplish UV-B photoreception. UV-B absorption by homodimeric UVR8 induces monomerization and hence signaling, but the underlying photodynamic mechanisms are not known. Here, by using a combination of time-resolved fluorescence and absorption spectroscopy from femto- to microseconds, we provide the first experimental evidence for the UVR8 molecular signaling mechanism. The results indicate that tryptophan residues at the dimer interface engage in photoinduced proton coupled electron transfer reactions that induce monomerization.

The association between patient activation and accessing online health information: results from a national survey of US adults.

BACKGROUND: There are increasing opportunities for the public to access online health information, but attitudinal barriers to use are less well-known. Patient activation is associated with key health outcomes, but its relationship with using online health information is not known. OBJECTIVE: We examined the relationship between patient activation and the likelihood of accessing a range of different types of online health information in a nationally representative US sample. DESIGN: Cross-sectional nationally representative survey. SETTING AND PARTICIPANTS: Data were from an online (n = 2700) and random digit dial telephone survey (n = 700) of US adults (total n = 3400). MAIN VARIABLES STUDIED: Respondent characteristics and the Patient Activation Measure. MAIN OUTCOME MEASURES: Self-reported access of five types of online health information in the past 12 months (online medical records, cost estimation tools, quality comparison tools, health information about a specific condition, preventive health information). RESULTS: Approximately, one-fifth of the sample had accessed their medical record (21.6%), treatment cost estimation tools (17.3%) and hospital and physician quality comparison tools (21.8%). Nearly half of the sample had accessed information about medical conditions or treatments (48.3%) or preventive health and well-being (45.9%). In multivariable analyses adjusted for participant characteristics, respondents with greater patient activation were more likely to have accessed all types of health information other than cost estimation tools. DISCUSSION AND CONCLUSIONS: Activated people are more likely to make use of online heath information. Increasing patient activation could improve the public's ability to participate in health care and personal health self-management by encouraging health information seeking.

Insights into the photoprotective switch of the major light-harvesting complex II (LHCII): a preserved core of arginine-glutamate interlocked helices complemented by adjustable loops.

Light-harvesting antennae of the LHC family form transmembrane three-helix bundles of which two helices are interlocked by conserved arginine-glutamate (Arg-Glu) ion pairs that form ligation sites for chlorophylls. The antenna proteins of photosystem II have an intriguing dual function. In excess light, they can switch their conformation from a light-harvesting into a photoprotective state, in which the excess and harmful excitation energies are safely dissipated as heat. Here we applied magic angle spinning NMR and selective Arg isotope enrichment as a noninvasive method to analyze the Arg structures of the major light-harvesting complex II (LHCII). The conformations of the Arg residues that interlock helix A and B appear to be preserved in the light-harvesting and photoprotective state. Several Arg residues have very downfield-shifted proton NMR responses, indicating that they stabilize the complex by strong hydrogen bonds. For the Arg Cα chemical shifts, differences are observed between LHCII in the active, light-harvesting and in the photoprotective, quenched state. These differences are attributed to a conformational change of the Arg residue in the stromal loop region. We conclude that the interlocked helices of LHCII form a rigid core. Consequently, the LHCII conformational switch does not involve changes in A/B helix tilting but likely involves rearrangements of the loops and helical segments close to the stromal and lumenal ends.

An NMR comparison of the light-harvesting complex II (LHCII) in active and photoprotective states reveals subtle changes in the chlorophyll a ground-state electronic structures.

To protect the photosynthetic apparatus against photo-damage in high sunlight, the photosynthetic antenna of oxygenic organisms can switch from a light-harvesting to a photoprotective mode through the process of non-photochemical quenching (NPQ). There is growing evidence that light-harvesting proteins of photosystem II participate in photoprotection by a built-in capacity to switch their conformation between light-harvesting and energy-dissipating states. Here we applied high-resolution Magic-Angle Spinning Nuclear Magnetic Resonance on uniformly (13)C-enriched major light-harvesting complex II (LHCII) of Chlamydomonas reinhardtii in active or quenched states. Our results reveal that the switch into a dissipative state is accompanied by subtle changes in the chlorophyll (Chl) a ground-state electronic structures that affect their NMR responses, particularly for the macrocycle (13)C4, (13)C5 and (13)C6 carbon atoms. Inspection of the LHCII X-ray structures shows that of the Chl molecules in the terminal emitter domain, where excited-state energy accumulates prior to further transfer or dissipation, the C4, 5 and 6 atoms are in closest proximity to lutein; supporting quenching mechanisms that involve altered Chl-lutein interactions in the dissipative state. In addition the observed changes could represent altered interactions between Chla and neoxanthin, which alters its configuration under NPQ conditions. The Chls appear to have increased dynamics in unquenched, detergent-solubilized LHCII. Our work demonstrates that solid-state Nuclear Magnetic Resonance is applicable to investigate high-resolution structural details of light-harvesting proteins in varied functional conditions, and represents a valuable tool to address their molecular plasticity associated with photoprotection.

Patient factors that affect quality of colonoscopy preparation.

BACKGROUND & AIMS: Optimal colonoscopy preparation requires patients to adhere to written instructions and be activated to complete the task. Among patients with chronic disease, health literacy and patient activation have been associated with outcome, but these factors have not been studied for colonoscopy. We examined the association between health literacy, patient activation, and quality of bowel preparation. METHODS: We analyzed outpatient colonoscopy results from 462 adults, 55-74 years old (mean, 62 ± 6 years), who previously completed extensive neurocognitive assessments as part of a prospective study (Health Literacy and Cognitive Function in Older Adults). We collected information on cecal intubation, polyp detection, bowel preparation quality, and histopathology. RESULTS: One-third of the patients (n = 134) had suboptimal quality of bowel preparation; 15% (n = 62) had fair quality, and 17% (n = 72) had poor quality. Limited health literacy was associated with a lower level of education (P < .001), diabetes (P < .001), and a higher number of chronic conditions (P < .001), but not quality of colonoscopy preparation. No baseline characteristics were associated with patient activation. In multivariable analysis, after adjusting for demographics and clinical characteristics, diabetes (odds ratio [OR], 2.45; 95% confidence interval [CI], 1.14-5.25) and patient activation (OR, 2.12; 95% CI, 1.30-3.45) were independent predictors of suboptimal bowel preparation quality, but limited health literacy was not (OR, 0.76; 95% CI, 0.38-1.52). CONCLUSIONS: We investigated the relationship between health literacy, patient activation, and colonoscopy preparation quality. Lower patient activation was an independent predictor of suboptimal bowel preparation quality. Interventions to improve colonoscopy preparation quality should consider the importance of patient activation within their design.

Clinic-based versus outsourced implementation of a diabetes health literacy intervention.

BACKGROUND: We compared two implementation approaches for a health literacy diabetes intervention designed for community health centers. METHODS: A quasi-experimental, clinic-randomized evaluation was conducted at six community health centers from rural, suburban, and urban locations in Missouri between August 2008 and January 2010. In all, 486 adult patients with type 2 diabetes mellitus participated. Clinics were set up to implement either: 1) a clinic-based approach that involved practice re-design to routinely provide brief diabetes education and counseling services, set action-plans, and perform follow-up without additional financial resources [CARVE-IN]; or 2) an outsourced approach where clinics referred patients to a telephone-based diabetes educator for the same services [CARVE-OUT]. The fidelity of each intervention was determined by the number of contacts with patients, self-report of services received, and patient satisfaction. Intervention effectiveness was investigated by assessing patient knowledge, self-efficacy, health behaviors, and clinical outcomes. RESULTS: Carve-out patients received on average 4.3 contacts (SD = 2.2) from the telephone-based diabetes educator versus 1.7 contacts (SD = 2.0) from the clinic nurse in the carve-in arm (p < 0.001). They were also more likely to recall setting action plans and rated the process more positively than carve-in patients (p < 0.001). Few differences in diabetes knowledge, self-efficacy, or health behaviors were found between the two approaches. However, clinical outcomes did vary in multivariable analyses; carve-out patients had a lower HbA1c (ß = -0.31, 95 % CI -0.56 to -0.06, p = 0.02), systolic blood pressure (ß = -3.65, 95 % CI -6.39 to -0.90, p = 0.01), and low-density lipoprotein (LDL) cholesterol (ß = -7.96, 95 % CI -10.08 to -5.83, p < 0.001) at 6 months. CONCLUSION: An outsourced diabetes education and counseling approach for community health centers appears more feasible than clinic-based models. Patients receiving the carve-out strategy also demonstrated better clinical outcomes compared to those receiving the carve-in approach. Study limitations and unclear causal mechanisms explaining change in patient behavior suggest that further research is needed.