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Integrated behavioral health is a population-based approach that acknowledges the chronic nature of most mental illnesses and the need for services beyond those delivered in face-to-face visits. These services have been referred to by different and confusing names with over 40 definitions of care coordination concepts in the literature. Kilbourne et al. in a recent article in this journal divided these tasks into three groups: care coordination, care management and case management with associated definitions provided as used in the veterans affairs system. In this commentary, while drawing on over a decade of experience in implementing care management models in the Mayo clinic system of care, I will suggest we need to be even more specific with these definitions. I propose these terms be linked to critical and measurable tasks in the management of chronic conditions, thus allowing those administrating or researching these interventions to better assess fidelity, processes and outcomes when a model is applied to a population of patients with chronic conditions in an integrated setting., (© Society of Behavioral Medicine 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Conducting systematic case reviews (SCRs) is a critical skill for psychiatrists leveraging their expertise to provide collaborative care in a primary care setting; however, there is little literature to guide best practices for executing an SCR. This column offers guidance to psychiatrists on best practices for conducting SCRs by drawing on experience from psychiatrists who teach collaborative care and who directly observe SCRs in established programs. Furthermore, it describes several common threats to successful SCR and presents potential solutions to assist programs in implementing indirect psychiatric care, an essential component of collaborative care.

Background: Care coordination has been a common tool for practices seeking to manage complex patients, yet there remains confusion about the most effective and sustainable model. Research exists on opinions of providers of care coordination but there is limited information on perspectives of those in the insurance industry about key elements. We sought to gather opinions from primary care providers and administrators in Minnesota who were involved in a CMS (Center for Medicare and Medicaid Services) transformational grant implementing COMPASS (Care Of Mental, Physical And Substance-use Syndromes), an evidence-based model of care coordination for depressed patients comorbid with diabetes and/or cardiovascular disease. We then sought to compare these views with those of private insurance representatives in Minnesota., Methods: We used qualitative methods to conducted forty-two key informant interviews with primary care providers (n = 15); administrators (n = 15); and insurers (n = 12). We analyzed the recorded and transcribed data, once de-identified, using a frameworks analysis approach., Results: We identified six primary themes: 1) a defined scope, rationale, and key partnerships for building comprehensive care coordination programs, 2) effective information exchange, 3) a trained and available workforce, 4) the need for a business model and a financially justifiable program, 5) a need for evaluation and ongoing improvement of care coordination, and 6) the importance of patient and family engagement. Overall consensus across stakeholder groups was high including a call for payment reform to support a valued service. Despite their role in paying for care, insurance representatives did not stress reduced utilization as more important than other outcomes., Conclusions: Primary care providers and administrators from different organizations and backgrounds, all with experience in COMPASS, in large part agreed with insurance representatives on the main elements of a sustainable model and the need for health reform to sustain this service.

The ability to aggregate clinical data across multiple diverse organizations and to use it for performance measurement, quality improvement, evaluation, and research is rapidly becoming a national necessity, but there are few examples of how to do that. This article uses lessons from a national effort to implement the collaborative care management model for patients with both depression and diabetes or heart disease across 8 partner organizations, 18 medical groups, and more than 170 clinics in 8 states to identify the challenges and provide experience-based recommendations for those tasks. The challenges are divided into those needed for (1) collecting similar data, (2) aggregating those data across care systems, and (3) using the data to both improve and evaluate care. Start with agreement on goals, methods, transparency, and a data system integrated into the electronic medical record while promptly addressing all the legal, regulatory, and human subject requirements.

Background: The comparative effectiveness of non-pharmacological treatments of depression remains unclear., Methods: We conducted an overview of systematic reviews to identify randomised controlled trials (RCTs) that compared the efficacy and adverse effects of non-pharmacological treatments of depression. We searched multiple electronic databases through February 2016 without language restrictions. Pairs of reviewers determined eligibility, extracted data and assessed risk of bias. Meta-analyses were conducted when appropriate., Result: We included 367 RCTs enrolling ∼20 000 patients treated with 11 treatments leading to 17 unique head-to-head comparisons. Cognitive behavioural therapy, naturopathic therapy, biological interventions and physical activity interventions reduced depression severity as measured using standardised scales. However, the relative efficacy among these non-pharmacological interventions was lacking. The effect of these interventions on clinical response and remission was unclear. Adverse events were lower than antidepressants., Limitation: The quality of evidence was low to moderate due to inconsistency and unclear or high risk of bias, limiting our confidence in findings., Conclusions: Non-pharmacological therapies of depression reduce depression symptoms and should be considered along with antidepressant therapy for the treatment of mild-to-severe depression. A shared decision-making approach is needed to choose between non-pharmacological therapies based on values, preferences, clinical and social context., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Several promising therapies assessed in the adult critically ill in large, multicenter randomized controlled trials (RCTs) were associated with significantly increased mortality in the intervention arms. Our hypothesis was that there would be wide ranges in sponsorship (industry or not), type(s) of intervention(s), use of DSMBs, presence of interim analyses and early stopping rules, absolute risk increase (ARI), and whether or not adequate prior proof-of-principle Phase II studies were done of RCTs that found increased mortality rates of the intervention compared to control groups. We reviewed RCTs that showed a statistically significant increased mortality rate in the intervention compared to control group(s). We recorded source of sponsorship, sample sizes, types of interventions, mortality rates, ARI (as well as odds ratios, relative risks and number needed to harm), whether there were pre-specified interim analyses and early stopping rules, and whether or not there were prior proof-of-principle (also known as Phase II) RCTs. Ten RCTs (four industry sponsored) of many interventions (high oxygen delivery, diaspirin cross-linked hemoglobin, growth hormone, methylprednisolone, hetastarch, high-frequency oscillation ventilation, intensive insulin, NOS inhibition, and beta-2 adrenergic agonist, TNF-α receptor) included 19,126 patients and were associated with wide ranges of intervention versus control group mortality rates (25.7-59 %, mean 29.9 vs 17-49 %, mean 25 %, respectively) yielding ARIs of 2.6-29 % (mean 5 %). All but two RCTs had pre-specified interim analyses, and seven RCTs were stopped early. All RCTs were preceded by published proof-of-principle RCT(s), two by the same group. Seven interventions (except diaspirin cross-linked hemoglobin and the NOS inhibitor) were available for use clinically at the time of the pivotal RCT. Common, clinically available interventions used in the critically ill were associated with increased mortality in large, pivotal RCTs even though safety was often addressed by interim analyses and early stopping rules.

Background: Collaborative care management (CCM) has been shown to have superior outcomes to usual care (UC) for depressed patients with a fixed end point. This study was a survival analysis over time comparing CCM with UC using remission (9-item Patient Health Questionnaire [PHQ-9] score <5) and persistent depressive symptoms (PDSs; PHQ-9 score ≥10) as end points., Methods: A retrospective cohort study of 7340 patients with depression cared for at 4 outpatient primary care clinics was conducted from March 2008 through June 2013. All adult patients diagnosed with depression (International Classification of Diseases, 9th Revision [ICD-9], codes 296.2-3) or dysthymia (ICD-9 code 300.4) with an initial PHQ-9 score ≥10 were included. CCM was implemented at all clinics between 2008 and 2010. Kaplan-Meyer survival curves for time to remission and PDSs were plotted. A Cox proportional hazards model was used to adjust for expected differences between patients choosing CCM versus UC., Results: Median time to remission was 86 days (95% confidence interval [CI], 81-91 days) for the CCM group versus 614 days (95% CI, 565-692 days) for the UC group. Likewise, median duration of PDSs was 31 days (95% CI, 30-33 days) for the CCM group versus 154 days (95% CI, 138-182 days) for the UC group. In the Cox proportional hazards model, which controlled for covariates such as age, sex, race, diagnosis, and initial PHQ-9 score, CCM was associated with faster remission (hazard ratio of the CCM group [HRCCM], 2.48; 95% CI, 2.31-2.65)., Conclusions: This study demonstrated that patients enrolled in CCM have a faster rate of remission and a shorter duration of PDSs than patients choosing UC., (© Copyright 2016 by the American Board of Family Medicine.)

Importance: For antidepressants, the translation of evidence of comparative effectiveness into practice is suboptimal. This deficit directly affects outcomes and quality of care for patients with depression. To overcome this problem, we developed the Depression Medication Choice (DMC) encounter decision aid, designed to help patients and clinicians consider the available antidepressants and the extent to which they improved depression and other issues important to patients., Objective: Estimate the effect of DMC on quality of the decision-making process and depression outcomes., Design, Setting, and Participants: We conducted a cluster randomized trial of adults with moderate to severe depression considering treatment with an antidepressant. Primary care practices in 10 rural, suburban, and urban primary care practices across Minnesota and Wisconsin were randomly allocated to treatment of depression with or without use of the DMC decision aid., Intervention: Depression Medication Choice, a series of cards, each highlighting the effect of the available options on an issue of importance to patients for use during face-to-face consultations., Main Outcomes and Measures: Decision-making quality as judged by patient knowledge and involvement in decision making, patient and clinician decisional comfort (Decisional Conflict Scale) and satisfaction, encounter duration, medication adherence, depression symptoms, and the Patient Health Questionnaire for depression (PHQ-9)., Results: We enrolled 117 clinicians and 301 patients (67% women; mean [SD] age, 44 [15] years; mean [SD] PHQ-9 score, 15 [4]) into the trial. Compared with usual care (UC), use of DMC significantly improved patients' decisional comfort (DMC, 80% vs UC, 75%; P = .02), knowledge (DMC, 65% vs UC, 56%; P = .03), satisfaction (risk ratio [RR], from 1.25 [P = .81] to RR, 2.4 [P = .002] depending on satisfaction domain), and involvement (DMC, 47% vs UC, 33%; P<.001). It also improved clinicians' decisional comfort (DMC, 80% vs UC, 68%; P < .001) and satisfaction (RR, 1.64; P = .02). There were no differences in encounter duration, medication adherence, or improvement of depression control between arms., Conclusions and Relevance: The DMC decision aid helped primary care clinicians and patients with moderate to severe depression select antidepressants together, improving the decision-making process without extending the visit. On the other hand, DMC had no discernible effect on medication adherence or depression outcomes. By translating comparative effectiveness into patient-centered care, use of DMC improved the quality of primary care for patients with depression., Trial Registration: clinicaltrials.gov Identifier: NCT01502891.

Background: Patients requiring interpreters may utilize the health care system differently or more frequently than patients not requiring interpreters; those with mental health issues may be particularly difficult to diagnose., Objective: To determine whether adult patients requiring interpreters exhibit different health care utilization patterns and rates of mental health diagnoses than their counterparts., Design: Retrospective cohort study examining patient visits to primary care (PC), express care (EC), or the emergency department (ED) of a large group practice within 1 year., Patients: Adult outpatients (n = 63,525) with at least one visit within the study interval and information regarding interpreter need., Main Measures: Mean visit counts, counts of mental disorders, and somatic symptom diagnoses between patients requiring interpreters (IS patients) and not requiring interpreters (non-IS patients)., Key Results: IS patients (n = 1,566) had a higher mean number of visits overall (3.10 vs. 2.52), in PC (2.54 vs. 1.95), and in ED (0.53 vs. 0.44) than non-IS patients (all p < 0.01). IS patients had a lower mean number of visits in EC than non-IS patients (0.03 vs. 0.13; p < 0.01). Interpreter need remained a significant predictor of visit count in multivariate analyses including age, sex, insurance, and clinical complexity. A greater proportion of IS patients were high utilizers (10+ visits) than non-IS patients (3.6 % vs. 1.7 %; p < 0.01). IS patients had a lower frequency of mental health diagnoses (13.9 % vs. 16.7 %), but a higher frequency of diagnoses recognized as potential somatic symptoms including diseases of the nervous (29.3 % vs. 24.2 %), digestive (22.6 % vs. 14.5 %), and musculoskeletal systems (43.2 % vs. 34.5 %), and ill-defined conditions (61 % vs. 49.9 %), all p < 0.01., Conclusions: IS patients visited PC more often than their counterparts and were more often high utilizers of care. Two sources of high utilization, mental health diagnoses and somatic symptoms, differed appreciably between our populations and may be contributing factors.

In 2008, the Institute for Clinical Systems Improvement (ICSI) in Minnesota implemented a model of collaborative care management (CCM) for treatment of depression in primary care. This resulted in significant improvements on both clinical response and remission over usual care, although an increase in utilization metrics has been observed. Mental health comorbidities have previously been significantly associated with an increased likelihood of not responding to initial treatment. This retrospective study hypothesized that patients with mental health comorbidities are more likely to be associated with patients who were readmitted into CCM with recurrent depression. A total of 145 patients who had completed CCM were studied; of these, 32 were diagnosed with recurrent depression and were readmitted to CCM, and 113 were in remission for at least 4 months. There were no statistically significant demographic differences between the 2 groups. The initial screening GAD-7 score for anxiety was significantly increased in the readmission group (12.81 vs 9.20, P = .001) as was the average length of treatment from initial diagnosis to remission (168.09 vs 120.99 days, P = .002). All other initial screening tests were not different between the groups. When controlling for the independent variables by multiple logistic regression, the odds ratio for GAD-7 was 1.1156 (CI = 1.0.192 to 1.2212, P = .0177) and for days of treatment in CCM was 1.0123 (CI = 1.0041 to 1.0206, P = .0033). Patients who are readmitted to CCM for recurrent depression have a statistically increased risk of associated anxiety and a longer treatment course than those who have remained in remission for at least 4 months.

Background: in the current healthcare system in the USA, common mental health conditions are frequently undertreated. As a result, unacceptable disability, morbidity and mortality rates occur. Various stakeholders define, provide, monitor and may reward providers of mental health care, but based on differing interests and agendas. Examples of the implementation of evidence-based practice in general care, accompanied by changes in fiscal incentives, are rare outside of research endeavours., Methods: we review as a case study a Minnesota state-wide effort to introduce collaborative care into 80 primary care clinics in order to improve the outcomes of depressed patients. This effort has been named the DIAMOND project (Depression Initiative Across Minnesota, Offering a New Direction) and it may illustrate several key steps towards creating value at the interface between primary care and specialty mental health care. Outcomes were defined and will be examined for a three-year period from when the initiative began in March 2008., Results: to date the results are encouraging. All 80 clinics have introduced a new measurement tool into their practices, trained and hired care managers, and have developed an ongoing relationship with a psychiatrist. Over 4800 patients have been screened for depression, have received treatment and have been followed to ensure compliance and better outcomes. Remission rates (averaging 27%) are at levels comparable to research studies which have more stringent inclusion and exclusion criteria. Challenges including the loss of eligible patients are described., Conclusion: to create value in depression management, not only was a viable model required, but also a process for implementation and a structure for ongoing support of the model. The case study presented offers lessons that might be applied elsewhere toward creating value at the mental health and primary care interface.

Protein C is a plasma serine protease that when activated plays a central role in modulating the function of the vascular endothelium and its interface with the innate immune system. Activated protein C (APC) has a dual mechanism of action via the feedback inhibition of thrombin generation, and as an agonist of protease activated receptor-1 (PAR-1). Through different cofactor interactions, this dual mechanism of antithrombotic and cytoprotective activity results in the ability of APC to modulate endothelial dysfunction by blocking cytokine signaling, functional cell adhesion expression, vascular permeability, apoptosis, and modulating leukocyte migration and adhesion. Deficiency in protein C, which occurs during systemic inflammatory activation, is highly associated with organ dysfunction. APC has shown efficacy in a number of preclinical models of thrombosis and ischemia, and the recombinant human APC drotrecogin alfa (activated), reduces mortality in patients with high-risk severe sepsis. The ability of APC to suppress pro-inflammatory pathways and enhance cellular survival suggests that APC plays a key role in the adaptive response to protect the vessel wall from insult and to enhance endothelial, cellular, and organ survival. The focus of this review will be to summarize the emerging data suggesting the potential therapeutic benefit of APC and related members of the pathway in the prevention and treatment of acute kidney injury.

Rationale: Patients with severe sepsis frequently receive prophylactic heparin during drotrecogin alfa (activated) (DrotAA) treatment due to risk of venous thromboembolic events (VTEs). Biological plausibility exists for heparin to reduce DrotAA efficacy and/or increase bleeding., Objectives: Primary: demonstrate in adult patients with severe sepsis receiving DrotAA treatment that 28-day mortality was equivalent for patients treated with concomitant prophylactic heparin compared with placebo; secondary: safety and VTE incidence., Methods: International, randomized, double-blind, phase 4, equivalence-design trial (n = 1994). Patients were eligible if indicated for and receiving DrotAA treatment under the country's approved label. Study drug (low molecular weight/unfractionated heparin) or placebo (saline) was administered every 12 hours during DrotAA infusion (24 ug/kg/hr for 96 hr). In patients on baseline heparin and randomized to placebo, heparin was stopped., Measurements and Main Results: Twenty-eight-day mortality was not equivalent between treatment groups. Heparin mortality was numerically lower (28.3 vs. 31.9%; p = 0.08). In the prospectively defined subgroup of patients exposed to heparin at baseline, patients receiving placebo experienced higher mortality (35.6 vs. 26.9%; p = 0.005). For safety, significant differences were observed during Days 0-6 for any bleeding event (placebo, n = 78; heparin, n = 105; p = 0.049) and ischemic stroke during Days 0-6 (placebo, n = 12; heparin, n = 3; p = 0.02) and Days 0-28 (placebo, n = 17; heparin, n = 5; p = 0.009). The VTE rate was low, with no statistical difference between groups (0-6 d, p = 0.60; 0-28 d, p = 0.26)., Conclusions: Compared with placebo, concomitant prophylactic heparin was not equivalent, did not increase 28-day mortality, and had an acceptable safety profile in patients with severe sepsis receiving DrotAA. Heparin discontinuation should be carefully weighed in patients considered for DrotAA treatment. XPRESS clinical trial registered with www.clinicaltrials.gov (NCT 00049777). The study ID numbers are 6743; F1K-MC-EVBR.

It has been hypothesized that the protein C pathway is a pivotal link between the inflammation and coagulation cascades. The demonstration that a survival benefit is associated with administration of drotrecogin alfa (activated) (recombinant human activated protein C [APC]) in severe sepsis patients has provided new insights into the protein C pathway. APC was originally identified based on its antithrombotic properties, which result from the inhibition of activated Factors V and VIII. In the early 1990s, any potential anti-inflammatory properties of APC were thought to relate primarily to its inhibition of thrombin generation. However, the mid-1990s saw the identification of the endothelial protein C receptor (EPCR), which has subsequently been shown to be neither endothelial specific nor protein C specific, but has a primary function as a cofactor for enhancing the generation of APC or behaving as an APC receptor. Thus, the potential biologic activities of APC can be classed into two categories related either to the limiting of thrombin generation or to cellular effects initiated by binding to the EPCR. Intracellular signaling initiated by binding of APC to its receptor appears to be mediated by interaction with an adjacent protease-activated receptor (PAR), or by indirect activation of the sphingosine 1-phosphate pathway. Based mostly on in vitro studies, binding of APC to its receptor on endothelial cells leads to a decrease in thrombin-induced endothelial permeability injury, while such binding on blood cells, epithelial cells, and neurons has been shown to inhibit chemotaxis, be anti-apoptotic, and be neuroprotective, respectively. In the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study, drotrecogin alfa (activated) was associated with improved cardiovascular function, respiratory function, and a prevention of hematologic dysfunction. This article discusses the way in which the interactions of APC may alter the microcirculation.

Background: Trauma care is a well-known financial burden for hospitals, yet reimbursement for the surgeon has not been reported., Methods: For 1999, the percent of the surgeons' bills reimbursed for general surgery services (gPR) was compared with that for trauma services (tPR). Mean tPR for various groups were compared. Factors predictive of tPR lower than gPR were identified., Results: The gPR was 49%, and, for 371 trauma patients, tPR was 45% (P = 0.03). The mean tPR for injury severity score (ISS) < or =10 was 48%, and for ISS > or =11, 57% (P = 0.03). Patients transferred from outside facilities did not have a significantly lower mean tPR. Penetrating trauma (odds ratio 3.7, P = 0.008) was predictive of tPR lower than gPR., Conclusions: Surgeon reimbursements for trauma care was significantly, yet only slightly less than for all general surgery care. Surgeons should not be reluctant to take trauma call based on perceptions of low reimbursement.

Introduction: Infection is an important complication in cancer patients, which frequently leads to or prolongs hospitalization, and can also lead to acute organ dysfunction (severe sepsis) and eventually death. While cancer patients are known to be at higher risk for infection and subsequent complications, there is no national estimate of the magnitude of this problem. Our objective was to identify cancer patients with severe sepsis and to project these numbers to national levels., Methods: Data for all 1999 hospitalizations from six states (Florida, Massachusetts, New Jersey, New York, Virginia, and Washington) were merged with US Census data, Centers for Disease Control vital statistics and National Cancer Institute, Surveillance, Epidemiology, and End Results initiative cancer prevalence data. Malignant neoplasms were identified by International Classification of Disease (ninth revision, clinical modification) (ICD-9-CM) codes (140-208), and infection and acute organ failure were identified from ICD-9-CM codes following Angus and colleagues. Cases were identified as a function of age and were projected to national levels., Results: There were 606,176 cancer hospitalizations identified, with severe sepsis present in 29,795 (4.9%). Projecting national estimates for the US population, cancer patients account for 126,209 severe sepsis cases annually, or 16.4 cases per 1000 people with cancer per year. The inhospital mortality for cancer patients with severe sepsis was 37.8%. Compared with the overall population, cancer patients are much more likely to be hospitalized (relative risk, 2.77; 95% confidence interval, 2.77-2.78) and to be hospitalized with severe sepsis (relative risk, 3.96; 95% confidence interval, 3.94-3.99). Overall, severe sepsis is associated with 8.5% (46,729) of all cancer deaths at a cost of 3.4 billion dollars per year., Conclusion: Severe sepsis is a common, deadly, and costly complication in cancer patients.