Mental health, substance abuse, and health behavior services in patient-centered medical homes.

PURPOSE: The purpose of this study was to understand mental health, substance use, and health behavior activities within primary care practices recognized by the National Committee for Quality Assurance as patient-centered medical homes (PCMHs). METHODS: We identified 447 practices with all levels of National Committee for Quality Assurance PCMH recognition as of March 1, 2010. We selected the largest practice from multisite groups, and 238 practices were contacted. We received 123 responses, for a 52% response rate. A 40-item web-based survey was collected. RESULTS: Of PCMH practices, 42% have a behavioral health clinician on site; social workers were the most frequent category of provider delivering behavioral services. There are also were care managers-distinct from behavioral health clinician-at 62% of practices. Surveyed practices were less likely to have procedures for referrals, communication, and patient scheduling for responding to mental health and substance use services than for other medical subspecialties (50% compared with 73% for cardiology and 69% for endocrinology). More than half of practices (62%) reported using electronic, standardized depression screening and monitoring; practices were less likely to screen for substance use than mental health. Among the practices, 54% used evidence-based health behavior protocols for mental health and substance use conditions. Practices reported that lack of reimbursement, time, and sufficient knowledge were obstacles. Practices serving a higher proportion of low-income patients performed more mental health organizational and clinical activities. CONCLUSIONS: In PCMHs, practice organization and response to behavioral issues seem to be less well developed than other types of medical care. These results support further efforts to develop whole-person care in the PCMH, with greater emphasis on access to and coordination of mental health, substance abuse, and health behavior services. Focusing primary care practices on this aspect of whole-person care will benefit from program sponsors' support and rewarding better integration with behavioral health.

TRIPPD: a practice-based network effectiveness study of postpartum depression screening and management.

PURPOSE: Postpartum depression is common but inadequately recognized and undertreated. Continuing depressive symptoms are associated with adverse outcomes for the woman, her infant, and family. We wanted to determine the effect of a practice-based training program for screening, diagnosis, and management of depression in postpartum mothers. METHODS: In this practice-based effectiveness study, 28 practices were randomized to usual care (n = 14) or intervention (n = 14), and 2,343 women were enrolled between 5 and 12 weeks' postpartum. The intervention sites received education and tools for postpartum depression screening, diagnosis, initiation of therapy, and follow-up within their practices. Usual-care practices received a 30-minute presentation about postpartum depression. Screening information for the usual care was obtained from baseline surveys sent directly to the central site but was not available for patient care. Outcomes were based on patient-reported outcomes (level of depressive symptoms) from surveys at 6 and 12 months, plus medical record review (diagnosis and therapy initiation). RESULTS: Among the 2,343 women enrolled, 1,897 (80.1%) provided outcome information, and were included in the analysis. Overall, 654 (34.5% of 1,897) women had elevated screening scores indicative of depression, with comparable rates in the intervention and usual-care groups. Among the 654 women with elevated postpartum depression screening scores, those in the intervention practices were more likely to receive a diagnosis (P = .0006) and therapy for postpartum depression (P = .002). They also had lower depressive symptom levels at 6 (P = .07) and 12 months' (P=.001) postpartum. CONCLUSIONS: Primary care-based screening, diagnosis, and management improved mother's depression outcomes at 12 months. This practical approach could be implemented widely with modest resources.

Fluorescence properties of green fluorescent protein FRET pairs concatenated with the small G protein, Rac, and its interacting domain of the kinase, p21-activated kinase.

Many diseases are caused by aberrant cell signalling controlled by intracellular protein-protein interactions. Inhibitors of such interactions thus have enormous potential as chemotherapeutic agents. It is advantageous to test for such inhibitors using cell-based screens in which modulation of the interaction gives a rapid response. Fluorescence resonance energy transfer (FRET) systems, based on interacting donor and acceptor green fluorescent proteins (GFPs), have potential in such screens. Here, we describe experiments aimed at using a FRET system to monitor the interaction between the small G protein Rac and a region of its binding partner, the Ser/Thr kinase, p21-activated kinase (PAK). Initial attempts to use a previously described construct, enhanced GFP-PAK-enhanced blue fluorescent protein, failed because of the difficulty of obtaining equal and high expression levels of both the fusion protein and Rac in mammalian cells. Here, three proteins in which Rac, PAK, and the two GFPs were concatenated in different combinations on a single protein were expressed and characterised. In each construct, however, intramolecular interaction of PAK and Rac was observed. As this was of extremely high affinity, presumably because of entropy effects from the interacting partners being tethered, these molecules were not suitable for detection of inhibitors of the interaction. Molecular modelling was used to investigate the way in which the concatenated constructs might form intramolecular interactions. As this explained key properties of these proteins, it is likely that this approach could be used to design constructs where the unwanted intramolecular protein-protein interactions are prevented, whilst allowing the desired intermolecular Rac/PAK interaction. This would provide constructs that are useable for drug discovery.

Phase II trial of pyrazoloacridine in advanced non-small cell carcinoma of the lung--a Kansas Cancer Institute and Thompson Cancer Survival Center Study.

BACKGROUND: More active agents are needed in the treatment of metastatic non-small cell lung cancer. Pyrazoloacridine (PZA) is a 9-methoxy acridine compound containing a reducible 5-nitro substituent. Although the mechanism of action of PZA is unknown, the acridine compounds are known to cause cytotoxicity by interaction with DNA and RNA. METHODS: Eighteen patients with metastatic non-small cell lung carcinoma were treated with pyrazoloacridine. Pyrazoloacridine was administered as a three-hour infusion at 750 mg/M2 every 21 days. RESULTS: There were no objective responses. One patient maintained stable disease for 20 months. Median survival was 4.8 months. The primary toxicity was granulocytopenia with 5 patients experiencing severe infections. CONCLUSIONS: Pyrazoloacridine has no demonstrable activity in patients with metastatic non-small cell carcinoma of the lung when given at this dose and schedule.

MgF(3)(-) as a transition state analog of phosphoryl transfer.

The formation of complexes between small G proteins and certain of their effectors can be facilitated by aluminum fluorides. Solution studies suggest that magnesium may be able to replace aluminum in such complexes. We have determined the crystal structure of RhoA.GDP bound to RhoGAP in the presence of Mg(2+) and F(-) but without Al(3+). The metallofluoride adopts a trigonal planar arrangement instead of the square planar structure of AlF(4)(-). We have confirmed that these crystals contain magnesium and not aluminum by proton-induced X-ray emission spectroscopy. The structure adopted by GDP.MgF(-) possesses the stereochemistry and approximate charge expected for the transition state. We suggest that MgF3(-) may be the reagent of choice for studying phosphoryl transfer reactions.