Brian Wu

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

BackgroundVentilator-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.MethodsWe 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.ResultsSix 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.ConclusionsThere 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.

Collaborative Depression Care Among Latino Patients in Diabetes Disease Management, Los Angeles, 2011-2013

Introduction The prevalence of comorbid diabetes and depression is high, especially in low-income Hispanic or Latino patients. The complex mix of factors in safety-net care systems impedes the adoption of evidence-based collaborative depression care and results in persistent disparities in depression outcomes. The Diabetes–Depression Care-Management Adoption Trial examined whether the collaborative depression care model is an effective approach in safety-net clinics to improve clinical care outcomes of depression and diabetes. Methods A sample of 964 patients with diabetes from 5 safety-net clinics were enrolled in a quasi-experimental study that included 2 arms: usual care, in which primary medical providers and staff translated and adopted evidence-based depression care; and supportive care, in which providers of a disease management program delivered protocol-driven depression care. Because the study design established individual treatment centers as separate arms, we calculated propensity scores that interpreted the probability of treatment assignment conditional on observed baseline characteristics. Primary outcomes were 5 depression care outcomes and 7 diabetes care measures. Regression models with propensity score covariate adjustment were applied to analyze 6-month outcomes. Results Compared with usual care, supportive care significantly decreased Patient Health Questionnaire-9 scores, reduced the number of patients with moderate or severe depression, improved depression remission, increased satisfaction in care for patients with emotional problems, and significantly reduced functional impairment. Conclusion Implementing collaborative depression care in a diabetes disease management program is a scalable approach to improve depression outcomes and patient care satisfaction among patients with diabetes in a safety-net care system.

The use of shear rate–diameter dose–response curves as an alternative to the flow-mediated dilation test

The brachial artery flow-mediated dilation test (FMD) is the non-invasive gold-standard used to test endothelial function. Reduced FMD precedes the development of atherosclerosis and provides an early marker for predicting future cardiovascular disease events. Although, this test is of high potential, it is somewhat limited by poor reproducibility. By utilizing hand warming and grip exercise combined with hierarchical linear modeling, shear rate-diameter dose-response curves may provide a novel and more accurate way to assess endothelial function in humans. Shear rate-diameter dose-response curves could potentially improve upon the traditional FMD measurement and serve as a superior clinical and research tool for assessing cardiovascular disease risk in a variety of populations. The current paper presents testable hypotheses and methodology for assessing the validity and reliability of an alternative to the current FMD test.

Perioperative Testosterone Supplementation Increases Lean Mass in Healthy Men Undergoing Anterior Cruciate Ligament Reconstruction: A Randomized Controlled Trial:

Background: Rehabilitation after repair of the anterior cruciate ligament (ACL) is complicated by the loss of leg muscle mass and strength. Prior studies have shown that preoperative rehabilitation may improve muscle strength and postoperative outcomes. Testosterone supplementation may likewise counteract this muscle loss and potentially improve clinical outcomes. Purpose: The purpose was to investigate the effect of perioperative testosterone administration on lean mass after ACL reconstruction in men and to examine the effects of testosterone on leg strength and clinical outcome scores. It was hypothesized that testosterone would increase lean mass and leg strength and improve clinical outcome scores relative to placebo. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Male patients (N = 13) scheduled for ACL reconstruction were randomized into 2 groups: testosterone and placebo. Participants in the testosterone group received 200 mg of intramuscular testosterone weekly for 8 weeks beginning 2 weeks before surgery. Participants in the placebo group received saline following the same schedule. Both groups participated in a standard rehabilitation protocol. The primary outcome was the change in total lean body mass at 6 and 12 weeks. Secondary outcomes were extensor muscle strength, Tegner activity score, and Knee injury and Osteoarthritis Outcome Score. Results: There was an increase in lean mass of a mean 2.7 ± 1.7 kg at 6 weeks postoperatively in the testosterone group compared with a decrease of a mean 0.1 ± 1.5 kg in the placebo group (P = .01). Extensor muscle strength of the uninjured leg also increased more from baseline in the testosterone group (+20.8 ± 25.6 Nm) compared with the placebo group (–21.4 ± 36.7 Nm) at 12 weeks (P = .04). There were no significant between-group differences in injured leg strength or clinical outcome scores. There were no negative side effects of testosterone noted. Conclusion: Perioperative testosterone supplementation increased lean mass 6 weeks after ACL reconstruction, suggesting that this treatment may help minimize the effects of muscle atrophy associated with ACL injuries and repair. This study was not powered to detect differences in strength or clinical outcome scores to assess the incidence of testosterone-related adverse events. Clinical Relevance: Supraphysiological testosterone supplementation may be a useful adjunct therapy for counteracting muscle atrophy after ACL reconstruction. Further investigation is necessary to determine the safety profile and effects of perioperative testosterone administration on leg strength and clinical outcomes after surgery. Registration: NCT01595581 (ClinicalTrials.gov).

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.

Blood pressure lowering and cardiovascular risk.

1746 www.thelancet.com Vol 384 November 15, 2014 The meta-analysis by the Blood Pressure Lowering Treatment Trialists’ Collaboration sought to ascertain whether the predicted absolute risk of cardiovascular events should be used to inform blood pressure-lowering treatment decisions, rather than a single risk factor (ie, blood pressure thresholds). This Article is particularly timely, considering the fact that the revised blood pressure guidelines from the Eighth Joint National Committee ( JNC8) maintains a focus on blood pressure in isolation. The revised guidelines have led to some controversy, particularly the recommendation for less conservative treatment for older populations and for patients with diabetes and renal disease. The less conservative recommen dations stem from the lack of randomised control trials to confi rm blood pressure threshold targets. Collectively, these works indicate an opportunity for a shift. Specifically, peripheral blood pressure measurements could have little usefulness as a single risk factor because they do not accurately show the effects of peak blood pressure on centrally located organs. Alternatively, central blood pressure has been reported to be a stronger determinant of cardiovascular events than are peripheral blood pressure, and a recent study reported that monitoring central blood pressure, compared with peripheral monitering methods, led to decreased use of blood pressure-lowering drug without adverse eff ects of left ventricular mass. Oscillometric pulse wave analysis devices have emerged, which are user friendly and suitable for routine measurements of central blood pressure in clinical practice. Therefore, given the known limitations of peripheral blood pressure measurements, the absence of randomised controlled trials that support specific thresholds, and the availability of oscillometric pulse wave analysis devices, perhaps it is time to advocate longitudinal randomised trials to assess the comparative clinical usefulness of central blood pressure. We declare no competing interests.

The weight of fatherhood: identifying mechanisms to explain paternal perinatal weight gain

ABSTRACT Men appear to gain weight during the transition to parenthood, and fathers are heavier than non-fathers. Paternal perinatal weight gain may set weight trajectories in midlife and have long-term health implications. Since men do not undergo the physical demands of pregnancy and breastfeeding, the specific mechanisms underlying weight gain in new fathers warrant investigation. This review aims to stimulate research on paternal perinatal weight gain by suggesting testable potential mechanisms that (1) show change across the transition to parenthood and (2) play a role in weight and body composition. We identify seven mechanisms, within three categories: behavioural mechanisms (sleep, physical activity, and diet), hormonal mechanisms (testosterone and cortisol), and psychological mechanisms (depression and stress). We also discuss direct effects of partner pregnancy influences (e.g., ‘couvade syndrome’) on men’s body weight. In presenting each mechanism, we discuss how it may be affected by the transition to parenthood, and then review its role in body composition and weight. Next, we describe bidirectional and interactive effects, discuss timing, and present three broad research questions to propel theoretical development.

Testosterone Supplementation Increases Lean Mass in Men Undergoing Anterior Cruciate Ligament Reconstruction: A Randomized Controlled Trial

Objectives: Surgical reconstruction of the anterior cruciate ligament (ACL) is essential for those who wish to resume athletic activity following ACL rupture. However, the trauma of surgical repair and post-operative immobility can exacerbate muscle loss and strength. This study investigated the effect of perioperative testosterone administration on lean mass recovery following ACL reconstruction in men. The effects of testosterone on leg strength and clinical outcome scores were also investigated. We hypothesized that testosterone would increase lean mass and leg strength, and improve clinical outcome scores 6 and 12 weeks after surgery to a greater degree than placebo. Methods: This was a randomized, controlled, double blinded clinical trial comparing testosterone and placebo for recovery from ACL repair. Thirteen male subjects scheduled for ACL reconstruction were randomized into two groups, testosterone (n=6) and placebo (n=7). Participants in the testosterone group received 200 mg of testosterone administration weekly for 8 weeks starting 2 weeks prior to surgery. Participants in the control group received a saline placebo intramuscularly following the same schedule. Both intervention groups underwent standard physical rehabilitation. The primary outcome was change in total lean body mass at 6 and 12 weeks, measured by whole-body dual-energy x-ray absorptiometry. Secondary outcomes were extensor muscle strength measured using a Cybex Dynamometer, and the Tegner Activity Score (TAS) and Knee Injury and Osteoarthritis Outcome Score (KOOS). Results: Total testosterone levels in the blood increased from baseline to an average of 860 ± 254 ng/dL by 1 day prior to surgery and 746 ± 173 ng/dL at 6 weeks post-surgery for the testosterone group. The differences in serum testosterone levels between the placebo and testosterone groups at 1 day prior to surgery and 6 weeks post-surgery were both statistically significant (p<0.001). We found that testosterone increased lean mass by 2.8 ± 1.7 kg from baseline at 6 weeks following surgery, while the placebo group had a decrease in lean muscle mass of 0.1 ± 1.5 kg (p=0.01) (Figure 1). Extensor strength of the non-injured leg had a greater increase from baseline in the testosterone group (20.8 ± 25.6 Nm) than the placebo group (-21.4 ± 36.7 Nm) at 12 weeks (p=0.02). There were no significant differences in injured leg strength or clinical outcome scores throughout the study period. Conclusion: Despite a catabolic environment, acute testosterone supplementation increased lean mass 6 weeks after ACL reconstruction, and strength of the non-injured leg 12 weeks after surgery, to a greater degree than placebo. These results suggest that testosterone may be a novel, useful adjunct to physical therapy for knee surgery rehabilitation by offsetting perioperative muscle loss from surgery and immobility. Larger studies are now necessary to elucidate the effects of perioperative testosterone administration on injured leg strength and clinical outcomes following surgery.

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.

Effect of tourniquet use during total knee arthroplasty on global inflammatory cytokine changes associated with ischemia- reperfusion injury

The use of tourniquets during total knee arthroplasties has been debated given the possibility that prolonged application of a tourniquet may result in ischemia-reperfusion injury, potentially contributing to post-operative muscle atrophy. The goal of this study is to elucidate the influence that tourniquet use may have on the induction of ischemia-reperfusion injury in muscle tissue following total knee arthroplasties surgeries. We hypothesize that prolonged operative use of a tourniquet will cause global increases in pro-inflammatory cytokines indicating the occurrence of ischemia-reperfusion injury, which may contribute to post-operative muscle atrophy. Fifty patients undergoing total knee arthroplasties surgeries were separated into three groups: no tourniquet (n = 17), operative tourniquet (n = 15), and tourniquet during implant cementation (n = 18). Induction of ischemia-reperfusion injury was evaluated by measuring changes in inflammatory cytokines in blood samples collected from an antecubital vein before and after surgery. Analysis suggests statistically significant differences in the concentrations of specific cytokines depending on variable tourniquet application. Overall, both pro-inflammatory and anti-inflammatory cytokines (including tumor necrosis factor-α, interleukin 1β, 4, 5, 12, and monocyte chemtactic protein-1) were found to increase upon application of tourniquets during cementation and decrease without tourniquet use or upon application of operative tourniquets. In general only slight changes in inflammatory cytokines occurred based on altered tourniquet use during total knee arthroplasties. Using global changes in inflammatory cytokine levels as an indicator of ischemia-reperfusion injury, these data may suggest that the use of a tourniquet does not significantly contribute to induction of ischemia-reperfusion injury in total knee arthroplasty surgeries. However, additional studies comparing local plasma cytokine changes near the tourniquet site and utilizing larger sample sizes are necessary to determine if tourniquets can be used in total knee arthroplasty without inducing ischemia-reperfusion injury.