Outcomes of a Blended Care Coaching Program for Clients Presenting With Moderate Levels of Anxiety and Depression: Pragmatic Retrospective Study.

BACKGROUND: Depression and anxiety are leading causes of disability worldwide, but access to quality mental health care is limited by myriad factors. Cognitive-behavioral coaching is rooted in evidence-based principles and has the potential to address some of these unmet care needs. Harnessing technology to facilitate broader dissemination within a blended care model shows additional promise for overcoming barriers to care. OBJECTIVE: The aim of this study is to evaluate the outcomes of a blended care coaching (BCC) program for clients presenting with moderate levels of anxiety and depression in real-world settings. METHODS: This study examined retrospective data from US-based individuals (N=1496) who presented with moderate levels of depression and anxiety symptoms and who received blended care coaching services. Using a short-term framework, clients met with coaches via a secure video conference platform and also received digital video lessons and exercises. To evaluate the effectiveness of the BCC program, mixed effects modeling was used to examine growth trajectories of anxiety and depression scores over the course of care. RESULTS: Out of the total sample of 1496 clients, 75.9% (n=1136) demonstrated reliable improvement, and 88.6% (n=1326) recovered based on either the Generalized Anxiety Disorder-7 scale (anxiety) or Patient Health Questionnaire-9 (depression). On average, clients exhibited a significant decline in anxiety and depression symptoms during the initial weeks of coaching, with a continued decline over subsequent weeks at a lower rate. Engaging in a coaching session was associated with lower anxiety (b=-1.04) and depression (b=-0.79) symptoms in the same week, as well as lower anxiety (b=-0.74) and depression (b=-0.91) symptoms the following week (P<.001). CONCLUSIONS: The BCC program demonstrated strong outcomes in decreasing symptomology for clients presenting with moderate levels of anxiety and depression. When clients received coaching sessions, significant decreases in symptoms were observed, reflecting the importance of session attendance. Additionally, the steepest declines in symptoms tended to occur during the initial weeks of coaching, emphasizing the importance of client buy-in and early engagement. Collectively, these findings have implications for addressing unmet mental health care needs in a more accessible, cost-effective manner.

2,5-Disubstituted pyridines as potent GPR119 agonists.

A series of 2-piperazinyl-5-alkoxypyridines were synthesized and screened against human GPR119 receptor. Through SAR analysis, compounds containing 2-alkylsulfonylpiperazinyl-5-alkoxypyridines were discovered and found to be potent agonists of the human GPR119 receptor.

Discovery of 6,7-dihydro-5H-pyrrolo[2,3-a]pyrimidines as orally available G protein-coupled receptor 119 agonists.

GPR119 is a 7-transmembrane receptor that is expressed in the enteroendocrine cells in the intestine and in the islets of Langerhans in the pancreas. Indolines and 6,7-dihydro-5H-pyrrolo[2,3-a]pyrimidines were discovered as G protein-coupled receptor 119 (GPR119) agonists, and lead optimization efforts led to the identification of 1-methylethyl 4-({7-[2-fluoro-4-(methylsulfonyl)phenyl]-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl}oxy)-1-piperidinecarboxylate (GSK1104252A) (3), a potent and selective GPR119 agonist. Compound 3 showed excellent pharmacokinetic properties and sufficient selectivity with in vivo studies supporting a role for GPR119 in glucose homeostasis in the rodent. Thus, 3 appeared to modulate the enteroinsular axis, improve glycemic control, and strengthen previous suggestions that GPR119 agonists may have utility in the treatment of type 2 diabetes.

Miniaturization of the structure elucidation of novel natural products--two trace antibacterial acylated caprylic alcohol glycosides from Arctostaphylos pumila.

High-throughput isolation, purification and analysis methods applied to natural products libraries from plants gave rise to the discovery of two novel acylated caprylic alcohol glycosides (1, 2) produced by Arctostaphylos pumila. The NMR spectra were acquired using the CapNMR probe and performed on mass-limited samples, which enabled us to elucidate the structures of 2,6-diacetyl-3,4-diisobutyl-1- O-octylglucopyranoside (1, 200 microg) and 2,6-diacetyl-3,4-dimethylbutyl-1- O-octylglucopyranosid (2, 70 microg). Compounds 1 and 2 exhibited antibacterial activity against Gram-positive methicillin-resistant Staphylococcus aureus with an MIC of 128 microg/mL and 64 microg/mL, respectively.

High-throughput method for the production and analysis of large natural product libraries for drug discovery.

High-throughput methods were applied to the production, analysis, and characterization of libraries of natural products in order to accelerate the drug discovery process for high-throughput screening in the pharmaceutical and biotechnology industries. Library production integrates automated flash chromatography, solid-phase extraction, filtration, and high-throughput parallel four-channel preparative high-performance liquid chromatography to obtain the libraries in 96- or 384-well plates. Libraries consist of purified fractions with approximately one to five compounds per well. Libraries are analyzed prior to biological screening by a high-throughput parallel eight-channel liquid chromatography-evaporative light scattering detection-mass spectrometry system to determine the molecular weight, number, and quantity of compounds in a fraction. After biological screening, active fractions are rapidly purified at the microgram level and individual compounds are rescreened for confirmation of activity. Structures of active compounds are elucidated by NMR spectroscopy and mass spectrometry. Utilization of a novel microcoil probe allows NMR data to be gathered on 50 microg. As a demonstration, a library was made from the stem bark of Taxus brevifolia. Biological screening in the National Cancer Institute's in vitro panel of three cancer cell lines demonstrates that the process enables the discovery of active anticancer compounds not detected in the flash fractions from which the library originates.