Comparative Effectiveness of a Technology-Facilitated Depression Care Management Model in Safety-Net Primary Care Patients With Type 2 Diabetes: 6-Month Outcomes of a Large Clinical Trial.

BACKGROUND: Comorbid depression is a significant challenge for safety-net primary care systems. Team-based collaborative depression care is effective, but complex system factors in safety-net organizations impede adoption and result in persistent disparities in outcomes. Diabetes-Depression Care-management Adoption Trial (DCAT) evaluated whether depression care could be significantly improved by harnessing information and communication technologies to automate routine screening and monitoring of patient symptoms and treatment adherence and allow timely communication with providers. OBJECTIVE: The aim of this study was to compare 6-month outcomes of a technology-facilitated care model with a usual care model and a supported care model that involved team-based collaborative depression care for safety-net primary care adult patients with type 2 diabetes. METHODS: DCAT is a translational study in collaboration with Los Angeles County Department of Health Services, the second largest safety-net care system in the United States. A comparative effectiveness study with quasi-experimental design was conducted in three groups of adult patients with type 2 diabetes to compare three delivery models: usual care, supported care, and technology-facilitated care. Six-month outcomes included depression and diabetes care measures and patient-reported outcomes. Comparative treatment effects were estimated by linear or logistic regression models that used generalized propensity scores to adjust for sampling bias inherent in the nonrandomized design. RESULTS: DCAT enrolled 1406 patients (484 in usual care, 480 in supported care, and 442 in technology-facilitated care), most of whom were Hispanic or Latino and female. Compared with usual care, both the supported care and technology-facilitated care groups were associated with significant reduction in depressive symptoms measured by scores on the 9-item Patient Health Questionnaire (least squares estimate, LSE: usual care=6.35, supported care=5.05, technology-facilitated care=5.16; P value: supported care vs usual care=.02, technology-facilitated care vs usual care=.02); decreased prevalence of major depression (odds ratio, OR: supported care vs usual care=0.45, technology-facilitated care vs usual care=0.33; P value: supported care vs usual care=.02, technology-facilitated care vs usual care=.007); and reduced functional disability as measured by Sheehan Disability Scale scores (LSE: usual care=3.21, supported care=2.61, technology-facilitated care=2.59; P value: supported care vs usual care=.04, technology-facilitated care vs usual care=.03). Technology-facilitated care was significantly associated with depression remission (technology-facilitated care vs usual care: OR=2.98, P=.04); increased satisfaction with care for emotional problems among depressed patients (LSE: usual care=3.20, technology-facilitated care=3.70; P=.05); reduced total cholesterol level (LSE: usual care=176.40, technology-facilitated care=160.46; P=.01); improved satisfaction with diabetes care (LSE: usual care=4.01, technology-facilitated care=4.20; P=.05); and increased odds of taking an glycated hemoglobin test (technology-facilitated care vs usual care: OR=3.40, P<.001). CONCLUSIONS: Both the technology-facilitated care and supported care delivery models showed potential to improve 6-month depression and functional disability outcomes. The technology-facilitated care model has a greater likelihood to improve depression remission, patient satisfaction, and diabetes care quality.

Systemic delivery of chTNT-3/CpG immunoconjugates for immunotherapy in murine solid tumor models.

CpG oligodeoxynucleotides (CpG) potently activate the immune system by mimicking microbial DNA. Conjugation of CpG to chTNT-3, an antibody targeting the necrotic centers of tumors, enabled CpG to accumulate in tumors after systemic delivery, where it can activate the immune system in the presence of tumor antigens. CpG chemically conjugated to chTNT-3 (chTNT-3/CpG) were compared to free CpG in their ability to stimulate the immune system in vitro and reduce tumor burden in vivo. In subcutaneous Colon 26 adenocarcinoma and B16-F10 melanoma models in BALB/c and C57BL/6 mice, respectively, chTNT-3/CpG, free CpG, or several different control constructs were administered systemically. Intraperitoneal injections of chTNT-3/CpG delayed tumor growth and improved survival and were comparable to intratumorally administered CpG. Compared to saline-treated mice, chTNT-3/CpG-treated mice had smaller average tumor volumes by as much as 72% in Colon 26-bearing mice and 79% in B16-bearing mice. Systemically delivered free CpG and CpG conjugated to an isotype control antibody did not reduce tumor burden or improve survival. In this study, chTNT-3/CpG retained immunostimulatory activity of the CpG moiety and enabled delivery to tumors. Because systemically administered CpG rapidly clear the body and do not accumulate into tumors, chTNT-3/CpG provide a solution to the limitations observed in preclinical and clinical trials.

The use of inhaled antibiotic therapy in the treatment of ventilator-associated pneumonia and tracheobronchitis: a systematic review.

BACKGROUND: Ventilator-associated respiratory infections (tracheobronchitis, pneumonia) contribute significant morbidity and mortality to adults receiving care in intensive care units (ICU). Administration of broad-spectrum intravenous antibiotics, the current standard of care, may have systemic adverse effects. The efficacy of aerosolized antibiotics for treatment of ventilator-associated respiratory infections remains unclear. Our objective was to conduct a systematic review of the efficacy of aerosolized antibiotics in the treatment of ventilator-associated pneumonia (VAP) and tracheobronchitis (VAT), using the Cochrane Collaboration guidelines. METHODS: We conducted a search of three databases (PubMed, Web of Knowledge and the Cochrane Collaboration) for randomized, controlled trials studying the use of nebulized antibiotics in VAP and VAT that measured clinical cure (e.g., change in Clinical Pulmonary Infection Score) as an outcome measurement. We augmented the electronic searches with hand searches of the references for any narrative review articles as well as any article included in the systematic review. Included studies were examined for risk of bias using the Cochrane Handbook's "Risk of Bias" assessment tool. RESULTS: Six studies met full inclusion criteria. For the systemic review's primary outcome (clinical cure), two studies found clinically and statistically significant improvements in measures of VAP cure while four found no statistically significant difference in measurements of cure. No studies found inferiority of aerosolized antibiotics. The included studies had various degrees of biases, particularly in the performance and detection bias domains. Given that outcome measures of clinical cure were not uniform, we were unable to conduct a meta-analysis. CONCLUSIONS: There is insufficient evidence for the use of inhaled antibiotic therapy as primary or adjuvant treatment of VAP or VAT. Additional, better-powered randomized-controlled trials are needed to assess the efficacy of inhaled antibiotic therapy for VAP and VAT.

Randomized control trial to evaluate the effects of acute testosterone administration in men on muscle mass, strength, and physical function following ACL reconstructive surgery: rationale, design, methods.

BACKGROUND: The anterior cruciate ligament (ACL) is one of four major ligaments in the knee that provide stability during physical activity. A tear in the ACL is characterized by joint instability that leads to decreased activity, knee dysfunction, reduced quality of life and a loss of muscle mass and strength. While rehabilitation is the standard-of-care for return to daily function, additional surgical reconstruction can provide individuals with an opportunity to return to sports and strenuous physical activity. Over 200,000 ACL reconstructions are performed in the United States each year, and rehabilitation following surgery is slow and expensive. One possible method to improve the recovery process is the use of intramuscular testosterone, which has been shown to increase muscle mass and strength independent of exercise. With short-term use of supraphysiologic doses of testosterone, we hope to reduce loss of muscle mass and strength and minimize loss of physical function following ACL reconstruction compared to standard-of-care alone. METHODS/DESIGN: This study is a double-blinded randomized control trial. Men 18-50 years of age, scheduled for ACL reconstruction are randomized into two groups. Participants randomized to the testosterone group receive intramuscular testosterone administration once per week for 8 weeks starting 2 weeks prior to surgery. Participants randomized to the control group receive a saline placebo intramuscularly instead of testosterone. Lean mass, muscle strength and physical function are measured at 5 time points: 2 weeks pre-surgery, 1 day pre-surgery, and 6, 12, 24 weeks post-surgery. Both groups follow standard-of-care rehabilitation protocol. DISCUSSION: We believe that testosterone therapy will help reduce the loss of muscle mass and strength experienced after ACL injury and reconstruction. Hopefully this will provide a way to shorten the rehabilitation necessary following ACL reconstruction. If successful, testosterone therapy may also be used for other injuries involving trauma and muscle atrophy. TRIAL REGISTRATION: NCT01595581, REGISTRATION: May 8, 2012.

Geldanamycin inhibits hemorrhage-induced increases in caspase-3 activity: role of inducible nitric oxide synthase.

Hemorrhage has been shown to increase inducible nitric oxide synthase (iNOS) and deplete ATP levels in tissues and geldanamycin limits both processes. Moreover, it is evident that inhibition of iNOS reduces caspase-3 and increases survival. Thus we sought to identify the molecular events responsible for the beneficial effect of geldanamycin. Hemorrhage in mice significantly increased caspase-3 activity and protein while treatment with geldanamycin significantly limited these increases. Similarly, geldanamycin inhibited increases in proteins forming the apoptosome (a complex of caspase-9, cytochrome c, and Apaf-1). Modulation of the expression of iNOS by iNOS gene transfection or siRNA treatment demonstrated that the level of iNOS correlates with caspase-3 activity. Our data indicate that geldanamycin limits caspase-3 expression and protects from organ injury by suppressing iNOS expression and apoptosome formation. Geldanamycin, therefore, may prove useful as an adjuvant in fluids used to treat patients suffering blood loss.

Applications of Whole Brain Tractography and Implications for Clinical Practice.

The complicated nature of neurological diseases-and the importance of accurate diagnosis and treatment for patient quality of life-have made the need for more advanced imaging techniques more urgent than ever. Automated whole brain tractography promises to increase the knowledge that neurologists have of a variety of disease processes, including schizophrenia, age-related changes to white matter, brain tumors, and epilepsy.

Redefining Health: The Evolution of Health Ideas from Antiquity to the Era of Value-Based Care.

The current healthcare system in the United States (US) is characterized by high costs and poor patient outcomes. A value-based healthcare system, centered on providing the highest quality of care for the lowest cost, is the country's chosen solution for its healthcare crisis. As the US transitions to a value-based model, a new definition of health is necessary to clearly define what constitutes a healthy state. However, such a definition is impossible to develop without a proper understanding of what "health" actually means. To truly understand its meaning, one must have a thorough historical understanding of the changes in the concept of health and how it has evolved to reflect the beliefs and scientific understanding of each time period. Thus, this review summarizes the changes in the definition of health over time in order to provide a context for the definition needed today. We then propose a new definition of health that is specifically tailored to providers working in the era of value-based care.

Genotype vs. Phenotype and the Rise of Non-Communicable Diseases: The Importance of Lifestyle Behaviors During Childhood.

Despite continued research and growing public awareness, the incidence of non-communicable diseases (NCD) continues to accelerate. While a person may have a genetic predisposition to certain NCDs, the rapidly changing epidemiology of NCDs points to the importance of environmental, social, and behavioural determinants of health. Specifically, three lifestyle behaviours expose children to important environmental cues and stressors: physical activity, nutritional intake, and sleep behaviour. Failure to expose children to proper gene-environment interactions, through the aforementioned lifestyle behaviours, can and will predispose children to the development of NCDs. Reengineering the environments of children can induce a paradigm shift, from a predominantly biomedical health model of treating symptomology, to a more holistic model based on encouraging appropriate behavioral decisions and optimal health.

Geldanamycin treatment inhibits hemorrhage-induced increases in KLF6 and iNOS expression in unresuscitated mouse organs: role of inducible HSP70.

The aim of this study was to determine whether hemorrhage affects the levels of a variety of stress-related proteins and whether changes can be inhibited by drugs reported to provide protection from ischemia and reperfusion injury. Male Swiss Webster mice were subjected to a 40% hemorrhage without resuscitation. Western blot analysis indicated that c-Jun (an AP-1 protein), Kruppel-like factor 6 (KFL6), and inducible nitric oxide synthase (iNOS) were upregulated sequentially in that order. Pretreatment of mice with geldanamycin (GA) 16 h before hemorrhage effectively inhibited the expression of the proteins KLF6 and iNOS, whereas caffeic acid phenethyl ester did not. GA pretreatment increased inducible heat shock protein (HSP) 70 but not HSP90 in both sham and hemorrhagic tissues. The overexpressed inducible HSP70 formed complexes with KLF6 and iNOS. These results suggest that GA may be therapeutically useful for reducing hemorrhage-induced injury when used as a presurgical treatment or when added to resuscitation fluids.

Cytoreductive chemotherapy improves the biodistribution of antibodies directed against tumor necrosis in murine solid tumor models.

Current strategies in cancer treatment employ combinations of different treatment modalities, which include chemotherapy, radiotherapy, immunotherapy, and surgery. Consistent with that approach, the present study demonstrates how chemotherapeutic agents can potentiate the delivery of radiolabeled, necrosis-targeting antibodies (chTNT-3, NHS76) to tumor. All chemotherapeutics in this study (5-fluorouracil, etoposide, vinblastine, paclitaxel, and doxorubicin) resulted in statistically significant increases in tumor uptake of radiolabeled antibodies and their F(ab')2 fragments compared to no pretreatment with chemotherapy. Labeled antibodies were administered at various time points following a single dose of chemotherapy in multiple tumor models, and the biodistribution of the antibodies was determined by measuring radioactivity in harvested tissues. MicroPET/CT was also done to demonstrate clinical relevancy of using chemotherapy pretreatment to increase antibody uptake. Results of biodistribution and imaging data reveal specific time frames following chemotherapy when necrosis-targeting antibodies are best delivered, either for imaging or radiotherapy. Thus, the present work offers the prospect of using cytoreductive chemotherapy to increase tumor accumulation of select therapeutic antibodies, especially when combined with other forms of immunotherapy, for the successful treatment of solid tumors.