On-demand mobile hypertension training for primary health care workers in Nigeria: a pilot study.

BACKGROUND: Only one out of every ten Nigerian adults with hypertension has their blood pressure controlled. Health worker training is essential to improve hypertension diagnosis and treatment. In-person training has limitations that mobile, on-demand training might address. This pilot study evaluated a self-paced, case-based, mobile-optimized online training to diagnose and manage hypertension for Nigerian health workers. METHODS: Twelve hypertension training modules were developed, based on World Health Organization and Nigerian guidelines. After review by local academic and government partners, the course was piloted by Nigerian health workers at government-owned primary health centers. Primary care physician, nurse, and community health worker participants completed the course on their own smartphones. Before and after the course, hypertension knowledge was evaluated with multiple-choice questions. Learners provided feedback by responding to questions on a Likert scale. RESULTS: Out of 748 users who sampled the course, 574 enrolled, of whom 431 (75%) completed the course. The average pre-test score of completers was 65.4%, which increased to 78.2% on the post-test (P < 0.001, paired t-test). Health workers who were not part of existing hypertension control programs had lower pre-test scores and larger score gains. Most participants (96.1%) agreed that the training was applicable to their work, and nearly all (99.8%) agreed that they enjoyed the training. CONCLUSIONS: An on-demand mobile digital hypertension training increases knowledge of hypertension management among Nigerian health workers. If offered at scale, such courses can be a tool to build health workforce capacity through initial and refresher training on current clinical guidelines in hypertension and other chronic diseases in Nigeria as well as other countries.

Development of a simple and effective online training for health workers: results from a pilot in Nigeria.

BACKGROUND: Health workers (HWs) in Africa face challenges accessing and learning from existing online training opportunities. To address these challenges, we developed a modular, self-paced, mobile-ready and work-relevant online course covering foundational infection prevention and control (IPC) concepts. Here, we evaluate the first pilot of this course, conducted with HWs in Nigeria. METHODS: We used a learner-centered design and prototyping process to create a new approach to delivering online training for HWs. The resulting course comprised 10 self-paced modules optimized for use on mobile devices. Modules presented IPC vignettes in which learning was driven by short assessment questions with feedback. Learners were recruited by distributing a link to the training through Nigeria-based email lists, WhatsApp groups and similar networks of HWs, managers and allied professionals. The course was open to learners for 8 weeks. We tracked question responses and time on task with platform analytics and assessed learning gains with pre- and post-testing. Significance was evaluated with the Wilcoxon signed-rank test, and effect size was calculated using Cohen's d. RESULTS: Three hundred seventy-two learners, with roles across the health system, enrolled in the training; 59% completed all 10 modules and earned a certificate. Baseline knowledge of foundational IPC concepts was low, as measured by pre-test scores (29%). Post-test scores were significantly higher at 54% (effect size 1.22, 95% confidence interval 1.00-1.44). Learning gains were significant both among learners with low pre-test scores and among those who scored higher on the pre-test. We used the Net Promoter Score (NPS), a common user experience metric, to evaluate the training. The NPS was + 62, which is slightly higher than published scores of other self-paced online learning experiences. CONCLUSIONS: High completion rates, significant learning gains and positive feedback indicate that self-paced, mobile-ready training that emphasizes short, low-stakes assessment questions can be an effective, scalable way to train HWs who choose to enroll. Low pre-test scores suggest that there are gaps in IPC knowledge among this learner population.

Rapid Conversion to Telemental Health Services in Response to COVID-19: Experiences of Two Outpatient Mental Health Clinics.

Background: The COVID-19 pandemic triggered changes across health care systems, with many sectors seeing significant drops in patient visits. Rapid transition to telemental health (TMH) allowed for the continued delivery of mental health care. Although several guidelines and best practices are available for the methodical development of a TMH service, there are few documented procedures on rapidly converting to fully virtualized services. We discuss how two outpatient mental health clinics at the University of Colorado Anschutz Medical Campus rapidly virtualized clinical services during the COVID-19 pandemic. Methods: All current clinical appointments were converted to virtual, and all new clinical intakes were scheduled as virtual visits starting March 16, 2020. Virtualization included a modified needs assessment, updated clinic procedures, focused patient and staff training on TMH, and increased frequency of team meetings. We conducted a retrospective evaluation of clinic log and electronic health record data to examine the number of appointments and no-shows before and after COVID-19 virtualization. Results: Virtualization was operational within two business days. Scheduled appointments decreased 10.6% immediately postvirtualization, followed by an increase of 17.8% across the 6 months postvirtualization. No-show rates dropped from 11.9% pre- to 6.8% postvirtualization, leading to a 26.2% increase in completed visits. Discussion: Rapid virtualization of mental health services can occur effectively. Wider use and acceptance of TMH, especially to patient-homes, is likely in the foreseeable future as health care providers and systems reconceptualize service delivery. Future research must include analyzing the impact such changes make on clinical outcomes and patient visit volumes.

Evaluation of Telepsychiatry-Enabled Perinatal Integrated Care.

OBJECTIVE: The purpose of this article is to describe the implementation of the first known telepsychiatry-enabled model of perinatal integrated care and to report initial results following implementation. METHODS: Behavioral health screening data were collected from 712 patients at an urban women's clinic, and a more in-depth set of process and outcome measures, including treatment engagement, services utilized, and delivery and postpartum patient outcomes, was collected from 135 patients referred for behavioral health services. Using nationally published metrics to provide context, the authors applied a descriptive design to evaluate and conduct analyses of program outcomes. RESULTS: The telehealth-enabled integrated care model was successfully implemented within a specialty obstetrics practice. Identification and treatment of behavioral health issues exceeded nationally published rates. The model was also associated with positive indices related to birth weight and breastfeeding behavior. CONCLUSIONS: These initial results point to telepsychiatry as an effective tool for expanding perinatal integrated care and lay the foundation for further study and model refinement. The results also add to the growing body of evidence for the use of telepsychiatry-supported integrated care across diverse clinical settings and patient populations.

Low income countries have the highest percentages of open access publication: A systematic computational analysis of the biomedical literature.

Open access publication rates have been steadily increasing over time. In spite of this growth, academics in low income settings struggle to gain access to the full canon of research literature. While the vast majority of open access repositories and funding organizations with open access policies are based in high income countries, the geographic patterns of open access publication itself are not well characterized. In this study, we developed a computational approach to better understand the topical and geographical landscape of open access publications in the biomedical research literature. Surprisingly, we found a strong negative correlation between country per capita income and the percentage of open access publication. Open access publication rates were particularly high in sub-Saharan Africa, but vastly lower in the Middle East and North Africa, South Asia, and East Asia and the Pacific. These effects persisted when considering papers only bearing authors from within each region and income group. However, papers resulting from international collaborations did have a higher percentage of OA than single-country papers, and inter-regional collaboration increased OA publication for all world regions. There was no clear relationship between the number of open access policies in a region and the percentage of open access publications in that region. To understand the distribution of open access across topics of biomedical research, we examined keywords that were most enriched and depleted in open access papers. Keywords related to genomics, computational biology, animal models, and infectious disease were enriched in open access publications, while keywords related to the environment, nursing, and surgery were depleted in open access publications. This work identifies geographic regions and fields of research that could be priority areas for open access advocacy. The finding that open access publication rates are highest in sub-Saharan Africa and low income countries suggests that factors other than open access policy strongly influence authors' decisions to make their work openly accessible. The high proportion of OA resulting from international collaborations indicates yet another benefit of collaborative research. Certain applied fields of medical research, notably nursing, surgery, and environmental fields, appear to have a greater proportion of fee-for-access publications, which presumably creates barriers that prevent researchers and practitioners in low income settings from accessing the literature in those fields.

The geographic and topical landscape of medical education research.

BACKGROUND: Whether medical education research (MER) is primarily conducted in wealthy countries (in the "Realm of the Rich") is the subject of an ongoing debate. Previous studies of the geography of MER publication output have relied upon proprietary databases, have not compared MER with other fields of study, and have not studied the relationship between authorship geography and topics of study. This study was designed to evaluate the geographic distribution of MER authorship and to relate this to the topics studied in MER. METHODS: Authors' countries of affiliation were identified from PubMed records by parsing and cleaning the text of affiliations and submitting them to the google maps geocoding API. The geography of publication output in MER was compared to other fields using the chi-square goodness-of-fit test. Country income classifications and medical subject heading (MeSH) terms were used to evaluate the topical contributions of countries at different income levels, and simulation was used to compute significance of MeSH term enrichment in MER papers from low income and lower middle income countries. RESULTS: The vast majority of MER papers were contributed by authors based in high income countries. The top four countries were the United States, the United Kingdom, Canada, and Australia, with listed author affiliations in 80% of all MER papers. This percentage was greater in MER than in several other categories, including Biological Science Disciplines (48%), Medicine (69%) and Education (74%), which is a parent category of MER. Authors from low income countries contributed significantly to the topical diversity of MER. MeSH terms associated with government, community health, and health delivery were enriched in papers from low income countries, while terms associated with specialty and clinical training, technology in teaching, and professional obligations (such as workload, burnout, and empathy) were enriched in papers from high income countries. CONCLUSIONS: Geographic disparities in publication output are greater in MER than in any other field examined. The historical origins of MER in North America might explain disproportionate publication output by authors from this region. This study suggests that the MER field benefits from research contributed by authors from low income countries, and also points to potential gaps in MER (and medical education as a whole) in the developing world.

Using Telepsychiatry to Enrich Existing Integrated Primary Care.

Background: Integrated care is characterized by evolving heterogeneity in models. Using telepsychiatry to enhance these models can increase access, quality, and efficiencies in care. Introduction: The purpose of this report is to describe the process and outcomes of adapting telepsychiatry into an existing integrated care service. Materials and Methods: Telepsychiatry was implemented into an existing integrated care model in a high-volume, urban, primary care clinic in Colorado serving patients with complex physical and behavioral needs. Consultative, direct care, educational/training encounters, provider-to-provider communication, process changes, and patient-level descriptive measures were tracked as part of ongoing quality improvement. Results: Telepsychiatry was adapted into the existing behavioral health services using an iterative team meeting process within a stepped care model. Over 35% of the requests for psychiatry services were medication related-and medication changes (type/dose) were the most frequent referral outcome of psychiatric consultation. Forty percent of patients in the service had multiple behavioral health diagnoses, in addition to physical health diagnoses. Discussion: Telehealth will become an increasingly necessary component in building hybrid/blended integrated care teams. Examples of flexible model implementation will support clinics in tailoring effective applications for their unique patient panels. Conclusions: An adapted integrated care model leveraging telepsychiatry is successfully serving the complex deep end of a primary care patient population in Colorado. Lessons learned in implementing this model include the importance of team attitudes.

Pou4f2 knock-in Cre mouse: A multifaceted genetic tool for vision researchers.

PURPOSE: A transgenic mouse that expresses Cre recombinase under control of the Pou4f2-promoter (also referred to as Brn-3b and Brn-3.2) was characterized. Pou4f2 expression has been reported in a subset of retinal ganglion cells (RGCs) in the retina, in the midbrain, and in the germline. In this study, we characterize the expression pattern of this Cre-recombinase line and report its utility in targeted deletion, temporal deletion, RGC depletion, and germline targeting, which can be regulated by the sex of the Cre-carrying mouse. METHODS: Pou4f2(Cre) was mapped by using a combination of PCR and sequencing of PCR products to better understand the construct and to locate where it was inserted within the Pou4f2 locus. Cre expression patterns were examined by crossing Pou4f2(Cre/+) mice to Cre reporter mice. Immunohistochemistry was used to further define the pattern of Cre expression and Cre-mediated recombination within the retina, brain, and other tissues. RESULTS: An internal ribosome entry site (IRES)-Cre cassette was inserted into the Pou4f2 gene disrupting normal gene function, as verified by the depletion of RGCs in mice homozygous for the insert. Pou4f2(Cre) expression was observed in the retina, brain, peripheral neurons, and male germ cells. Germline recombination was observed when the sire carried the Cre and the target for recombination. In all other breeding schemes, recombination was observed within subsets of cells within the retina, brain, intestines, heart, and gonads. In the retina, Cre efficiently targets recombination in neurons within the RGC layer (RGL), the inner nuclear layer (INL), and a small percentage of photoreceptors, activity that has not been previously reported. Unlike most other Cre lines active in the inner retina, recombination in Müller and other glia was not observed in mice carrying Pou4f2(Cre) . Within the visual centers of the brain, Cre targets recombination in about 15% of cells within the superchiasmatic nucleus, lateral geniculate nucleus, and superior colliculus. CONCLUSIONS: Pou4f2(Cre) provides multiple uses for the vision researcher's genetic toolkit. First, Pou4f2(Cre) is a knock-in allele that can be used to eliminate Pou4f2, resulting in depletion of RGCs. Second, expression of Cre in male germ cells makes this strain an efficient germline activator of recombination, for example, to target LoxP-flanked sequences in the whole mouse. Third, Pou4f2(Cre) efficiently targets RGCs, amacrine cells, bipolar cells, horizontal cells, and a small number of photoreceptors within the retina, as well as the visual centers in the brain. Unlike other Cre recombinase lines that target retinal neurons, no recombination was observed in Müller or other retinal glia. These properties make this Cre recombinase line a useful tool for vision researchers.

Correlates of Emergency Department Use by Individuals With Bipolar Disorder Enrolled in a Collaborative Care Implementation Study.

OBJECTIVE: The study assessed correlates of emergency department use among participants in a collaborative care program for bipolar disorder. METHODS: Community-based clinics from two states implemented Life Goals-Collaborative Care (LG-CC), an evidence-based model that includes self-management sessions and care management contacts. Logistic regression determined participant factors associated with emergency department use between six and 12 months after LG-CC implementation. RESULTS: Of 219 participants with baseline and 12-month data, 24% reported at least one emergency department visit. Participants with a recent homelessness history (odds ratio [OR]=3.76, p=.01) or five or more care management contacts (OR=2.62, p=.05) had a higher probability of visiting an emergency department, after the analyses were adjusted for demographic and clinical factors, including physical health score and hospitalization history. CONCLUSIONS: Participants in a collaborative care program who had a history of homelessness were more likely to use the emergency department, suggesting a greater need for more intensive care coordination.

Review of key telepsychiatry outcomes.

AIM: To conduct a review of the telepsychiatry literature. METHODS: We conducted a systematic search of the literature on telepsychiatry using the search terms, "telepsychiatry", "telemental health", "telecare", "telemedicine", "e-health", and "videoconferencing". To meet criteria for inclusion, studies had to: (1) be published in a peer-reviewed journal after the year 2000; (2) be written in English; (3) use videoconferencing technology for the provision of mental health assessment or treatment services; and (4) use an adequately-powered randomized controlled trial design in the case of treatment outcome studies. Out of 1976 studies identified by searches in PubMed (Medline database), Ovid medline, PsychInfo, Embase, and EBSCO PSYCH, 452 met inclusion criteria. Studies that met all inclusion criteria were organized into one of six categories: (1) satisfaction; (2) reliability; (3) treatment outcomes; (4) implementation outcomes; (5) cost effectiveness; and (6) and legal issues. All disagreements were resolved by reassessing study characteristics and discussion. RESULTS: Overall, patients and providers are generally satisfied with telepsychiatry services. Providers, however, tend to express more concerns about the potentially adverse of effects of telepsychiatry on therapeutic rapport. Patients are less likely to endorse such concerns about impaired rapport with their provider. Although few studies appropriately employ non-inferiority designs, the evidence taken together suggests that telepsychiatry is comparable to face-to-face services in terms of reliability of clinical assessments and treatment outcomes. When non-inferiority designs were appropriately used, telepsychiatry performed as well as, if not better than face-to-face delivery of mental health services. Studies using both rudimentary and more sophisticated methods for evaluating cost-effectiveness indicate that telepsychiatry is not more expensive than face-to-face delivery of mental health services and that telepsychiatry is actually more cost-effective in the majority of studies reviewed. Notwithstanding legal concerns about loss of confidentiality and limited capacity to respond to psychiatric emergencies, we uncovered no published reports of these adverse events in the use of telepsychiatry. CONCLUSION: A large evidence base supports telepsychiatry as a delivery method for mental health services. Future studies will inform optimal approaches to implementing and sustaining telepsychiatry services.

G3BP-Caprin1-USP10 complexes mediate stress granule condensation and associate with 40S subunits.

Mammalian stress granules (SGs) contain stalled translation preinitiation complexes that are assembled into discrete granules by specific RNA-binding proteins such as G3BP. We now show that cells lacking both G3BP1 and G3BP2 cannot form SGs in response to eukaryotic initiation factor 2α phosphorylation or eIF4A inhibition, but are still SG-competent when challenged with severe heat or osmotic stress. Rescue experiments using G3BP1 mutants show that phosphomimetic G3BP1-S149E fails to rescue SG formation, whereas G3BP1-F33W, a mutant unable to bind G3BP partner proteins Caprin1 or USP10, rescues SG formation. Caprin1/USP10 binding to G3BP is mutually exclusive: Caprin binding promotes, but USP10 binding inhibits, SG formation. G3BP interacts with 40S ribosomal subunits through its RGG motif, which is also required for G3BP-mediated SG formation. We propose that G3BP mediates the condensation of SGs by shifting between two different states that are controlled by the phosphorylation of S149 and by binding to Caprin1 or USP10.

Telepsychiatry: Benefits and costs in a changing health-care environment.

In the USA, the high cost and inefficiencies of the health care system have prompted widespread demand for a better value on investment. Reform efforts, focused on increasing effective, cost-efficient, and patient-centred practices, are inciting lasting changes to health care delivery. Integrated care, providing team-based care that addresses both physical and behavioural health needs is growing as an evidence-based way to provide improved care with lower overall costs. This in turn, is leading to an increasing demand for psychiatrists to work with primary care physicians in delivering integrated care. Telepsychiatry is an innovative platform that has a variety of benefits to patients, providers, and systems. Associated costs are changing as technology advances and policies shift. The purpose of this article is to describe the changing role of psychiatry within the environment of U.S. healthcare reform, and the benefits (demonstrated and potential) and costs (fixed, variable, and reimbursable) of telepsychiatry to providers, patients and systems.

Antipsychotic-Induced Movement Disorder: Screening via Telemental Health.

BACKGROUND: The purpose of this brief report is to make clinical and research recommendations to advance current knowledge and practices related to the assessment of antipsychotic drug-induced movement disorders (DIMDs) via live interactive videoconferencing. MATERIALS AND METHODS: The authors provide an overview of the frequent neurological side effects of antipsychotic drugs and review relevant telemedicine research. DIMD prevention is critical, but these disorders remain underdetected and under-reported. Although there are not yet formal recommendations for specific screening tools or screening frequency, baseline and annual assessments are generally agreed-upon minimums. As DIMD awareness increases and more specific guidelines are developed to steer assessments, telemental health may aid practitioners in efficiently and regularly monitoring onset and severity. Research shows that videoconferencing can be used for effective psychiatric treatments and assessment, with at least one study validating the use of videoconference assessment for a subset of movement disorders. RESULTS AND CONCLUSIONS: Clinical recommendations include developing practice-level protocols and procedures that include regular DIMD assessment (either in-person or via telemedicine) for the full spectrum of possible movement disorders for all patients taking antipsychotic medications. Research and evaluation recommendations include replicating and expanding upon the existing study using videoconferencing to assess movement disorder symptoms, using asynchronous telemental health assessments of DIMDs, and pilot-testing facial and movement recognition software to allow for clinical comparison of patients' movement patterns over time.

Apoptosis Triggers Specific, Rapid, and Global mRNA Decay with 3' Uridylated Intermediates Degraded by DIS3L2.

Apoptosis is a tightly coordinated cell death program that damages mitochondria, DNA, proteins, and membrane lipids. Little is known about the fate of RNA as cells die. Here, we show that mRNAs, but not noncoding RNAs, are rapidly and globally degraded during apoptosis. mRNA decay is triggered early in apoptosis, preceding membrane lipid scrambling, genomic DNA fragmentation, and apoptotic changes to translation initiation factors. mRNA decay depends on mitochondrial outer membrane permeabilization and is amplified by caspase activation. 3' truncated mRNA decay intermediates with nontemplated uridylate-rich tails are generated during apoptosis. These tails are added by the terminal uridylyl transferases (TUTases) ZCCHC6 and ZCCHC11, and the uridylated transcript intermediates are degraded by the 3' to 5' exonuclease DIS3L2. Knockdown of DIS3L2 or the TUTases inhibits apoptotic mRNA decay, translation arrest, and cell death, whereas DIS3L2 overexpression enhances cell death. Our results suggest that global mRNA decay is an overlooked hallmark of apoptosis.

Meaningful use: a national framework for integrated telemedicine.

INTRODUCTION: The Centers for Medicare and Medicaid Services has incentivized electronic health records (EHRs) implementation through meaningful use (MU) to improve healthcare quality and efficacy. Telemedicine is a key tool that has shown its ability to facilitate MU through technological innovation with cost savings and has shown promise in the area of integrated behavioral healthcare. The purpose of this article is to propose a model of MU to frame the incentivized implementation of an integrated telemedicine (ITM)-specific model to effect system-level change. MATERIALS AND METHODS: We reviewed the background, principles, and a justification for the ITM Model including cost issues, the development and structure of MU in the context of EHRs, the benefits of integrated behavioral healthcare and telemedicine, and the case for their combined implementation in the form of ITM. RESULTS: The model proposed, the ITM Incentive Program, parallels the current MU program and is composed of three stages. Stage 1 focuses on incentivizing current and new Medicaid providers to adapt, implement, and upgrade technology needed to conduct virtual meetings with patients and other healthcare professionals. Stage 2 is a tiered incentive system with process-focused and track metrics related to increasing the number of consultations with patients. In Stage 3, providers are encouraged to continue use of ITM by meeting thresholds for several objectives focused on clinical outcomes. Recommendations for implementing this model within a payment waiver system are discussed. CONCLUSIONS: The ITM Model offers a needed union of integrated care and telemedicine through the combination of technology, business, and clinical processes. The success of MU as a tiered incentive program for EHRs, as well as the precedent of using waiver opportunities for incentive funding repayments, sets forth a strategic framework to successful implementation of ITM to address cost issues and improve quality and access to care in the healthcare system.

Long-Term Clinical Outcomes from a Randomized Controlled Trial of Two Implementation Strategies to Promote Collaborative Care Attendance in Community Practices.

This randomized controlled implementation study compared the effectiveness of a standard versus enhanced version of the replicating effective programs (REP) implementation strategy to improve the uptake of the life goals-collaborative care model (LG-CC) for bipolar disorder. Seven community-based practices (384 patient participants) were randomized to standard (manual/training) or enhanced REP (customized manual/training/facilitation) to promote LG-CC implementation. Participants from enhanced REP sites had no significant changes in primary outcomes (improved quality of life, reduced functioning or mood symptoms) by 24 months. Further research is needed to determine whether implementation strategies can lead to sustained, improved participant outcomes in addition to program uptake.

Protocol: Adaptive Implementation of Effective Programs Trial (ADEPT): cluster randomized SMART trial comparing a standard versus enhanced implementation strategy to improve outcomes of a mood disorders program.

BACKGROUND: Despite the availability of psychosocial evidence-based practices (EBPs), treatment and outcomes for persons with mental disorders remain suboptimal. Replicating Effective Programs (REP), an effective implementation strategy, still resulted in less than half of sites using an EBP. The primary aim of this cluster randomized trial is to determine, among sites not initially responding to REP, the effect of adaptive implementation strategies that begin with an External Facilitator (EF) or with an External Facilitator plus an Internal Facilitator (IF) on improved EBP use and patient outcomes in 12 months. METHODS/DESIGN: This study employs a sequential multiple assignment randomized trial (SMART) design to build an adaptive implementation strategy. The EBP to be implemented is life goals (LG) for patients with mood disorders across 80 community-based outpatient clinics (N = 1,600 patients) from different U.S. regions. Sites not initially responding to REP (defined as < 50% patients receiving ≥ 3 EBP sessions) will be randomized to receive additional support from an EF or both EF/IF. Additionally, sites randomized to EF and still not responsive will be randomized to continue with EF alone or to receive EF/IF. The EF provides technical expertise in adapting LG in routine practice, whereas the on-site IF has direct reporting relationships to site leadership to support LG use in routine practice. The primary outcome is mental health-related quality of life; secondary outcomes include receipt of LG sessions, mood symptoms, implementation costs, and organizational change. DISCUSSION: This study design will determine whether an off-site EF alone versus the addition of an on-site IF improves EBP uptake and patient outcomes among sites that do not respond initially to REP. It will also examine the value of delaying the provision of EF/IF for sites that continue to not respond despite EF. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02151331.

Training to use motivational interviewing techniques for depression: a cluster randomized trial.

OBJECTIVE: The goal of this study was to assess the effects of training primary care providers (PCPs) to use Motivational Interviewing (MI) when treating depressed patients on providers' MI performance and patients' expressions of interest in depression treatment ("change talk") and short-term treatment adherence. METHODS: This was a cluster randomized trial in urban primary care clinics (3 intervention, 4 control). We recruited 21 PCPs (10 intervention, 11 control) and 171 English-speaking patients with newly diagnosed depression (85 intervention, 86 control). MI training included a baseline and up to 2 refresher classroom trainings, along with feedback on audiotaped patient encounters. We report summary measures of technical (rate of MI-consistent statements per 10 minutes during encounters) and relational (global rating of "MI Spirit") MI performance, the association between MI performance and number of MI trainings attended (0, 1, 2, or 3), and rates of patient change talk regarding depression treatments (physical activity, antidepressant medication). We report PCP use of physical activity recommendations and antidepressant prescriptions and patients' short-term physical activity level and prescription fill rates. RESULTS: Use of MI-consistent statements was 26% higher for MI-trained versus control PCPs (P = .005). PCPs attending all 3 MI trainings (n = 6) had 38% higher use of MI-consistent statements (P < .001) and were over 5 times more likely to show beginning proficiency in MI Spirit (P = .036) relative to control PCPs. Although PCPs' use of physical activity recommendations and antidepressant prescriptions was not significantly different by randomization arm, patients seen by MI-trained PCPs had more frequent change talk (P = .001). Patients of MI-trained PCPs also expressed change talk about physical activity 3 times more frequently (P = .01) and reported more physical activity (3.05 vs 1.84 days in the week after the visit; P = .007) than their counterparts visiting untrained PCPs. Change talk about antidepressant medication and fill rates were similar by randomization arm (P > .05 for both). CONCLUSIONS: MI training resulted in improved MI performance, more depression-related patient change talk, and better short-term adherence.

Leukocyte protease binding to nucleic acids promotes nuclear localization and cleavage of nucleic acid binding proteins.

Killer lymphocyte granzyme (Gzm) serine proteases induce apoptosis of pathogen-infected cells and tumor cells. Many known Gzm substrates are nucleic acid binding proteins, and the Gzms accumulate in the target cell nucleus by an unknown mechanism. In this study, we show that human Gzms bind to DNA and RNA with nanomolar affinity. Gzms cleave their substrates most efficiently when both are bound to nucleic acids. RNase treatment of cell lysates reduces Gzm cleavage of RNA binding protein targets, whereas adding RNA to recombinant RNA binding protein substrates increases in vitro cleavage. Binding to nucleic acids also influences Gzm trafficking within target cells. Preincubation with competitor DNA and DNase treatment both reduce Gzm nuclear localization. The Gzms are closely related to neutrophil proteases, including neutrophil elastase (NE) and cathepsin G. During neutrophil activation, NE translocates to the nucleus to initiate DNA extrusion into neutrophil extracellular traps, which bind NE and cathepsin G. These myeloid cell proteases, but not digestive serine proteases, also bind DNA strongly and localize to nuclei and neutrophil extracellular traps in a DNA-dependent manner. Thus, high-affinity nucleic acid binding is a conserved and functionally important property specific to leukocyte serine proteases. Furthermore, nucleic acid binding provides an elegant and simple mechanism to confer specificity of these proteases for cleavage of nucleic acid binding protein substrates that play essential roles in cellular gene expression and cell proliferation.