Specialized secretion systems of pathogenic bacteria commonly transport multiple effectors that act in concert to control and exploit the host cell as a replication-permissive niche. Both the Mycobacterium marinum and the Mycobacterium tuberculosis genomes contain an extended region of difference 1 (extRD1) locus that encodes one such pathway, the early secretory antigenic target 6 (ESAT-6) system 1 (ESX-1) secretion apparatus. ESX-1 is required for virulence and for secretion of the proteins ESAT-6, culture filtrate protein 10 (CFP-10), and EspA. Here, we show that both Rv3881c and its M. marinum homolog, Mh3881c, are secreted proteins, and disruption of RD1 in either organism blocks secretion. We have renamed the Rv3881c/Mh3881c gene espB for ESX-1 substrate protein B. Secretion of M. marinum EspB (EspBM) requires both the Mh3879c and Mh3871 genes within RD1, while CFP-10 secretion is not affected by disruption of Mh3879c. In contrast, disruption of Mh3866 or Mh3867 within the extRD1 locus prevents CFP-10 secretion without effect on EspBM. Mutants that fail to secrete only EspBM or only CFP-10 are less attenuated in macrophages than mutants failing to secrete both substrates. EspBM physically interacts with Mh3879c; the M. tuberculosis homolog, EspBT, physically interacts with Rv3879c; and mutants of EspBM that fail to bind Mh3879c fail to be secreted. We also found interaction between Rv3879c and Rv3871, a component of the ESX-1 machine, suggesting a mechanism for the secretion of EspB. The results establish EspB as a substrate of ESX-1 that is required for virulence and growth in macrophages and suggests that the contribution of ESX-1 to virulence may arise from the secretion of multiple independent substrates.

IMPORTANCE: Intensive lifestyle change (e.g., the Diabetes Prevention Program) and metformin reduce type 2 diabetes risk among patients with prediabetes. However, real-world uptake remains low. Shared decision-making (SDM) may increase awareness and help patients select and follow through with informed options for diabetes prevention that are aligned with their preferences. OBJECTIVE: To test the effectiveness of a prediabetes SDM intervention. DESIGN: Cluster randomized controlled trial. SETTING: Twenty primary care clinics within a large regional health system. PARTICIPANTS: Overweight/obese adults with prediabetes (BMI ≥ 24 kg/m 2 and HbA1c 5.7-6.4%) were enrolled from 10 SDM intervention clinics. Propensity score matching was used to identify control patients from 10 usual care clinics. INTERVENTION: Intervention clinic patients were invited to participate in a face-to-face SDM visit with a pharmacist who used a decision aid (DA) to describe prediabetes and four possible options for diabetes prevention: DPP, DPP ± metformin, metformin only, or usual care. MAIN OUTCOMES AND MEASURES: Primary endpoint was uptake of DPP (≥ 9 sessions), metformin, or both strategies at 4 months. Secondary endpoint was weight change (lbs.) at 12 months. RESULTS: Uptake of DPP and/or metformin was higher among SDM participants (n = 351) than controls receiving usual care (n = 1028; 38% vs. 2%, p < .001). At 12-month follow-up, adjusted weight loss (lbs.) was greater among SDM participants than controls (− 5.3 vs. − 0.2, p < .001). LIMITATIONS: Absence of DPP supplier participation data for matched patients in usual care clinics. CONCLUSIONS AND RELEVANCE: A prediabetes SDM intervention led by pharmacists increased patient engagement in evidence-based options for diabetes prevention and was associated with significantly greater uptake of DPP and/or metformin at 4 months and weight loss at 12 months. Prediabetes SDM may be a promising approach to enhance prevention efforts among patients at increased risk. TRIAL REGISTRATION: This study was registered at clinicaltrails.gov (NCT02384109)).

a b s t r a c tBackground: Improving medication management is an important component of comprehensive care coordination for health systems. The Managing Your Medication for Education and Daily Support (MyMeds) medication management program at the University of California Los Angeles addresses medication management issues by embedding trained clinical pharmacists in primary care practice teams. Objectives: The aim of this work was to examine and explore physician opinions about the clinical pharmacist program and identify common themes among physician experiences as well as barriers to integration of clinical pharmacists into primary care practice teams. Methods: We conducted a mixed quantitativeequalitative methods study consisting of a crosssectional physician survey (n ¼ 69) as well as semistructured one-on-one physician interviews (n ¼ 13). Descriptive statistics were used to summarize survey responses, and standard qualitative content-analysis methods were used to identify major themes from the interviews. Results: The survey response rate was 61%; 13 interviews were conducted. Ninety percent of survey respondents agreed or strongly agreed that having the pharmacist in the office makes management of the patient's medication more efficient, 93% agreed or strongly agreed that pharmacist recommendations are clinically helpful, 71% agreed or strongly agreed that having access to a pharmacist has increased their knowledge about medications they prescribe, and 75% agreed or strongly agreed that having a pharmacist as part of the primary care team has made their job easier. Qualitative interviews corroborated survey findings, and physicians highlighted the value of the clinical pharmacist's communication, team care and expanded roles, and medication management. Conclusion: Primary care physicians valued the integrated pharmacy program highly, particularly its features of strong communication, expanded roles, and medication management. Pharmacists were viewed as integral members of the health care team.

Targeting specific omitted medication classes can produce relatively specific alerts that may reduce alert fatigue, and using a "chart closure" hard stop may prompt providers to take action without excessively disrupting their workflow.

Background: Pharmacists are effective at improving control of cardiovascular risk factors, but it less clear whether these improvements translate into less emergency department (ED) use and fewer hospitalizations. The UCMyRx program embed pharmacists in primary care. Objective: The objective of this study was to examine if the integration of pharmacists into primary care was associated with lower ED and hospital use for patients with diabetes. Design: This was a quasi-experimental study with a comparator group. Subjects: The analytic sample included patients with diabetes with uncontrolled cardiovascular risk factors (A1C >9%, blood pressure >140/90 mm Hg, low-density lipoprotein–cholesterol >130 mg/dL) who had 1 or more visits in either a UCMyRx (648 patients, 14 practices) or usual care practice (1944 patients, 14 practices). Measures: Our outcomes were ED and hospitalization rates as measured before and after the consultations between UCMyRx and usual care. Our predictor variable was the pharmacist consultation. Poisson generalized estimating equations model was used to estimate the adjusted predicted change in utilization before and after the pharmacist consultation. The Average Treatment Effect on the Treated was estimated. Results: In models adjusted, the adjusted mean predicted number of emergency department visits/month during the year before the consultation was 0.09 among UCMyRx patients. During the year after initiating the care with the pharmacists, this rate decreased to an adjusted mean monthly rate of 0.07, with an Average Treatment Effect on the Treated=0.021 (P=0.035), a predicted reduction of 21% in emergency department visits associated with the clinical pharmacist consults. There was a nonsignificant predicted 3.2% reduction in hospitalizations over time for patients in the UCMyRx program. Conclusion: Clinical pharmacists are an important addition to clinical care teams in primary care practices and significantly decreased utilization of the ED among patients with poorly controlled diabetes.