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After fluid administration for vasodilatory shock, vasopressors are commonly infused. Causes of vasodilatory shock include septic shock, post-cardiovascular surgery, post-acute myocardial infarction, postsurgery, other causes of an intense systemic inflammatory response, and drug -associated anaphylaxis. Therapeutic vasopressors are hormones that activate receptors-adrenergic: α1, α2, β1, β2; angiotensin II: AG1, AG2; vasopressin: AVPR1a, AVPR1B, AVPR2; dopamine: DA1, DA2. Vasopressor choice and dose vary widely because of patient and physician practice heterogeneity. Vasopressor adverse effects are excessive vasoconstriction causing organ ischemia/infarction, hyperglycemia, hyperlactatemia, tachycardia, and tachyarrhythmias. To date, no randomized controlled trial (RCT) of vasopressors has shown a decreased 28-day mortality rate. There is a need for evidence regarding alternative vasopressors as first-line vasopressors. We emphasize that vasopressors should be administered simultaneously with fluid replacement to prevent and decrease duration of hypotension in shock with vasodilation. Norepinephrine is the first-choice vasopressor in septic and vasodilatory shock. Interventions that decrease norepinephrine dose (vasopressin, angiotensin II) have not decreased 28-day mortality significantly. In patients not responsive to norepinephrine, vasopressin or epinephrine may be added. Angiotensin II may be useful for rapid resuscitation of profoundly hypotensive patients. Inotropic agent(s) (e.g., dobutamine) may be needed if vasopressors decrease ventricular contractility. Dopamine has fallen to almost no-use recommendation because of adverse effects; angiotensin II is available clinically; there are potent vasopressors with scant literature (e.g., methylene blue); and the novel V1a agonist selepressin missed on its pivotal RCT primary outcome. In pediatric septic shock, vasopressors, epinephrine, and norepinephrine are recommended equally because there is no clear evidence that supports the use of one vasoactive agent. Dopamine is recommended when epinephrine or norepinephrine is not available. New strategies include perhaps patients will be started on several vasopressors with complementary mechanisms of action, patients may be selected for particular vasopressors according to predictive biomarkers, and novel vasopressors may emerge with fewer adverse effects. [ABSTRACT FROM AUTHOR]

Background: Comparative effectiveness research (CER) documents important differences in antidepressants in terms of efficacy, safety, cost, and burden to the patient. Decision aids can adapt this evidence to help patients participate in making informed choices. In turn, antidepressant therapy will more likely reflect patients' values and context, leading to improved adherence and mood outcomes. Methods/Design: The objective of this study is to develop the Depression Medication Choice decision aid for use during primary care encounters, and to test its efficacy by conducting a clustered practical randomized trial comparing the decision aid to usual depression care in primary care practices. We will use a novel practice-based, patient-centered approach based on participatory action research that involves a multidisciplinary team of designers, investigators, clinicians, patient representatives, and other stakeholders for the development of the decision aid. We will then conduct a clustered practical randomized trial enrolling clinicians and their patients (n = 300) with moderate to severe depression from rural, suburban and inner city primary care practices (n = 10). The intervention will consist of the use of the depression medication choice decision aid during the clinical encounter. This trial will generate preliminary evidence of the relative impact of the decision aid on patient involvement in decision making, decision making quality, patient knowledge, and 6-month measures of medication adherence and mental health compared to usual depression care. Discussion: Upon completion of the proposed research, we will have developed and evaluated the efficacy of the decision aid depression medication choice as a novel translational tool for CER in depression treatment, engaged patients with depression in their care, and refined the process by which we conduct practice-based trials with limited research footprint. [ABSTRACT FROM AUTHOR]

Background Collaborative care management (CCM) is effective for improving depression outcomes. However, a subset of patients will still have symptoms after 6 months. This study sought to determine whether routinely obtained baseline clinical, demographic, and self-assessment variables would predict which patients endorse persistent depressive symptoms (PDS) after 6 months. By estimating the relative risk associated with the patient variables, we aimed to outline the combinations of factors predictive of PDS after CCM enrollment. Methods We retrospectively reviewed 1,110 adult primary care patients with the diagnosis of major depressive disorder enrolled in a CCM program and evaluated those with PDS (defined as Patient Health Questionnaire-9score ≥10) 6 months after enrollment. Results At baseline, an increased depression severity, worsening symptoms of generalized anxiety, an abnormal screening on the Mood Disorder Questionnaire (MDQ) and the diagnosis of recurrent episode of depression were independent predictors of PDS. A patient with severe, recurrent depression, an abnormal MDQ screen, and severe anxiety at baseline had a predicted 42.1% probability of PDS at 6 months. In contrast, a patient with a moderate, first episode of depression, normal MDQ screen, and no anxiety symptoms had a low probability of PDS at 6.6%. Conclusions This study identified several patient self-assessment scores and clinical diagnosis that markedly predicted the probability of PDS 6 months after diagnosis and enrollment into CCM. Knowledge of these high-risk attributes should alert the clinician to monitor select patients more closely and consider altering therapy appropriately. [ABSTRACT FROM AUTHOR]

Summary Background Drotrecogin alfa (activated) (DrotAA) is used for the treatment of adults with severe sepsis who have a high risk of dying. A phase lb open-label study has indicated that the pharmacokinetics and pharmacodynamics of DrotAA are similar in children and adults. We initiated the RESOLVE (Researching severe Sepsis and Organ dysfunction in children: a gLobal perspectiVE) trial to investigate the efficacy and safety of the drug in children. Methods Children aged between 38 weeks' corrected gestational age and 17 years with sepsis-induced cardiovascular and respiratory failure were randomly assigned to receive placebo or DrotAA (24 ug/kg/h) for 96 h. We used a prospectively defined, novel primary endpoint of Composite Time to Complete Organ Failure Resolution (CTCOFR) score. Secondary endpoints were 28-day mortality, major amputations, and safety. Analysis was by intention-to-treat. This trial is registered with dinicaltrials.gov, number NCT00049764. Findings 477 patients were enrolled; 237 received placebo, and 240 DrotAA. Our results showed no significant difference between groups in CTCOFR score (p=0 o 72) or in 28-day mortality (placebo 17 o 5%; DrotAA, 17 o 2%; p=0 o 93). Although there was no difference in overall serious bleeding events during the 28-day study period (placebo 6 o 8%; DrotAA 6-7%; p=0-97), there were numerically more instances of CNS bleeding in the DrotAA group (11 [4-6%], vs. 5 [2 o 1%] in placebo, p=0 o 13), particularly in children younger than 60 days. For CTCOFR score days 1-14, correlation coefficient was -0 016 (95% CI -0 106 to 0-74); relative risk for 28-day mortality was 106 (95% CI 0-66 to 146) for DrotAA compared with placebo. Interpretation Although we did not record any efficacy of DrotAA in children with severe sepsis, serious bleeding events were similar between groups and the overall safety profile acceptable, except in children younger than 60 days. However, we gained important insights into clinical and laboratory characteristics of childhood severe sepsis, and have identified issues that need to be addressed in future trials in critically ill children. [ABSTRACT FROM AUTHOR]

Purpose: Routine assessment was made of tumor metabolic activity as measured by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in Stage I non–small-cell lung cancer (NSCLC). This report describes PET correlates prospectively collected after stereotactic body radiotherapy (SBRT) for patients with medically inoperable NSCLC. Methods and Materials: 14 consecutive patients with medically inoperable Stage I NSCLC were enrolled. All patients received SBRT to 60–66 Gy in three fractions. Patients underwent serial planned FDG-PET/computed tomography fusion imaging before SBRT and at 2, 26, and 52 weeks after SBRT. Results: With median follow-up of 30.2 months, no patients experienced local failure. One patient developed regional failure, 1 developed distant failure, and 1 developed a second primary. The median tumor maximum standardized uptake value (SUVmax) before SBRT was 8.70. The median SUVmax values at 2, 26, and 52 weeks after SBRT were 6.04, 2.80, and 3.58, respectively. Patients with low pre-SBRT SUV were more likely to experience initial 2-week rises in SUV, whereas patients with high pre-SBRT SUV commonly had SUV declines 2 weeks after treatment (p = 0.036). Six of 13 patients had primary tumor SUVmax >3.5 at 12 months after SBRT but remained without evidence of local disease failure on further follow-up. Conclusions: A substantial proportion of patients may have moderately elevated FDG-PET SUVmax at 12 months without evidence of local failure on further follow-up. Thus, slightly elevated PET SUVmax should not be considered a surrogate for local treatment failure. Our data do not support routine serial FDG-PET/computed tomography for follow-up of patients receiving SBRT for Stage I NSCLC. [Copyright &y& Elsevier]