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High-dose melphalan and autologous stem cell transplantation (HDM/SCT) can induce hematologic responses and prolong survival in selected patients with Immunoglobulin light chain (AL) amyloidosis.1 Complications related to cardiac events surrounding HDM/SCT remain an ongoing concern in patients with Immunoglobulin light chain (AL) amyloidosis. Prior studies have shown that atrial fibrillation (AF) can complicate SCT in up to 22% of cases,2, 3, 4, 5, 6, 7 and that pre-existing cardiac involvement may lead to a further increase in the risk of AF during SCT.2 Factors that may predispose patients with amyloid cardiomyopathy to develop AF include advanced age, heart failure, a low left ventricular ejection fraction, an enlarged left atrial diameter and a high-mean right atrial pressure; however, these risk factors are independent of SCT.8 Other studies have suggested that although AF can be successfully treated in these patients, the presence of AF can lead to more complicated hospital admissions with greater lengths of stay and increased mortality.2, 3 Although AF has been described in general as a complication of SCT, the factors specifically predisposing patients with AL amyloidosis to develop AF in the period surrounding SCT have yet to be established. This is the first report to describe the incidence, risk factors and outcomes related to AF in patients with AL amyloidosis undergoing SCT.

Background Cobalt ions from some orthopaedic implants induce a dose-dependent cytotoxic and pro-inflammatory response. Recent studies show that sub-toxic levels of cobalt influence actin organisation regulating fibroblasts and macrophages behaviour. However little is known about the influence of sub-toxic levels of cobalt on articular cartilage biology and biomechanics. Previously, we have reported that IL-1β signalling in chondrocytes, is regulated by primary cilia and associated intraflagellar transport. Since primary cilia expression is modulated by actin organisation, we set out to test the hypothesis that sub-toxic levels of cobalt regulate cilia expression and IL-1β signalling thereby influencing articular cartilage degradation. Methods Isolated chondrocytes and bovine cartilage explants were subjected to Co2+ in the presence and absence of IL-1β. Primary cilia were monitored by confocal immunofluorescence. Nitric oxide and PGE2 release were used to monitor IL-1β signalling. Degradation of cartilage matrix was assessed by the release of sGAG and the biomechanical properties of the tissue in uniaxial unconfined compression. Findings Sub-toxic levels of Co2+ (50 μM) blocked IL-1β-induced primary cilia elongation in isolated chondrocytes. This was associated with disruption of pro-inflammatory signalling in both isolated chondrocytes and cartilage explants, and inhibition of cartilage matrix degradation and loss of biomechanical properties. Interpretation This study reveals that low levels of cobalt ions are anti-inflammatory, preventing cartilage degradation in response to IL-1β. This mechanism is associated with regulation of primary cilia elongation. These observations provide new insight into the potential beneficial role of cobalt and may lead to novel mechanisms for controlling cartilage inflammation.

BackgroundMechanical conditioning has been widely used to attempt to enhance chondrocyte metabolism for the evolution of functionally competent cartilage. However, although upregulation of proteoglycans have been reported through the application of uniaxial compression, minimal collagen has been produced. The study is designed to examine whether alternative loading regimens, equivalent to physiological conditions, involving shear in addition to compression can enhance collagen production.MethodsFinite element models were developed to determine how the local chondrocyte environments within agarose constructs were influenced by a range of static and dynamic loading regimens. 3-D poro-viscoelastic models were validated against experimental data. In particular, these models were used to characterise chondrocyte deformation in compression with and without shear superimposed, with special reference to the formation of pericellular matrix around the cells.FindingsThe models of the hydrogel constructs under stress relaxation and dynamic cyclic compression conditions were highly correlated with the experimental data. The cell deformation (y/z) in the constructs was greatest in the centre of the constructs, increasing with magnitude of compression up to 25%. The superposition of shear however did not produce significant additional changes in deformation, with the presence of PCM reducing the chondrocyte deformation.InterpretationThe use of FE models can prove important in the definition of appropriate, optimised mechanical conditioning regimens for the synthesis and organisation of mature extra cellular matrix by chondrocyte-seeded constructs. They will also provide insight into the mechanisms relating cell deformation to mechanotransduction pathways, thereby progressing the development of functionally competent tissue engineered cartilage.

Pharmacogenomic tests used to guide clinical treatment for major depressive disorder (MDD) must be thoroughly validated. One important assessment of validity is the ability to predict medication blood levels, which reflect altered metabolism. Historically, the metabolic impact of individual genes has been evaluated; however, we now know that multiple genes are often involved in medication metabolism. Here, we evaluated the ability of individual pharmacokinetic genes (CYP2C19, CYP2D6, CYP3A4) and a combinatorial pharmacogenomic test (GeneSight Psychotropic®; weighted assessment of all three genes) to predict citalopram/escitalopram blood levels in patients with MDD. Patients from the Genomics Used to Improve DEpression Decisions (GUIDED) trial who were taking citalopram/escitalopram at screening and had available blood level data were included (N=191). In multivariate analysis of the individual genes and combinatorial pharmacogenomic test separately (adjusted for age, smoking status), the F statistic for the combinatorial pharmacogenomic test was 1.7 to 2.9-times higher than the individual genes, showing that it explained more variance in citalopram/escitalopram blood levels. In multivariate analysis of the individual genes and combinatorial pharmacogenomic test together, only the combinatorial pharmacogenomic test remained significant. Overall, this demonstrates that the combinatorial pharmacogenomic test was a superior predictor of citalopram/escitalopram blood levels compared to individual genes.

This chapter covers antidepressants that fall into the class of serotonin (5-HT) and norepinephrine (NE) reuptake inhibitors. That is, they bind to the 5-HT and NE transporters with varying levels of potency and binding affinity ratios. Unlike the selective serotonin (5-HT) reuptake inhibitors (SSRIs), most of these antidepressants have an ascending rather than a flat dose-response curve. The chapter provides a brief review of the chemistry, pharmacology, metabolism, safety and adverse effects, clinical use, and therapeutic indications of each antidepressant. Venlafaxine, a phenylethylamine, is a relatively weak 5-HT and weaker NE uptake inhibitor with a 30-fold difference in binding of the two transporters. Therefore, the drug has a clear dose progression, with low doses predominantly binding to the 5-HT transporter and more binding of the NE transporter as the dose ascends. Venlafaxine is metabolized to the active metabolite O-desmethylvenlafaxine (ODV; desvenlafaxine) by CYP2D6, and it therefore is subject to significant inter-individual variation in blood levels and response dependent on variations in CYP2D6 metabolism. The half-life of venlafaxine is short at about 5 h, with the ODV metabolite being 12 h. Both parent compound and metabolite have low protein binding and neither inhibit CYP enzymes. Therefore, both venlafaxine and desvenlafaxine are potential options if drug-drug interactions are a concern, although venlafaxine may be subject to drug-drug interactions with CYP2D6 inhibitors. At low doses, the adverse effect profile is similar to an SSRI with nausea, diarrhea, fatigue or somnolence, and sexual side effects, while venlafaxine at higher doses can produce mild increases in blood pressure, diaphoresis, tachycardia, tremors, and anxiety. A disadvantage of venlafaxine relative to the SSRIs is the potential for dose-dependent blood pressure elevation, most likely due to the NE reuptake inhibition caused by higher doses; however, this adverse effect is infrequently observed at doses below 225 mg per day. Venlafaxine also has a number of potential advantages over the SSRIs, including an ascending dose-antidepressant response curve, with possibly greater overall efficacy at higher doses. Venlafaxine is approved for MDD as well as generalized anxiety disorder, social anxiety disorder, and panic disorder. Desvenlafaxine is the primary metabolite of venlafaxine, and it is also a relatively low-potency 5-HT and NE uptake inhibitor. Like venlafaxine it has a favorable drug-drug interaction profile. It is subject to CYP3A4 metabolism, and it is therefore vulnerable to enzyme inhibition or induction. However, the primary metabolic pathway is direct conjugation. It is approved in the narrow dose range of 50-100 mg per day. Duloxetine is a more potent 5-HT and NE reuptake inhibitor with a more balanced profile of binding at about 10:1 for 5HT and NE transporter binding. It is also a moderate inhibitor of CYP2D6, so that modest dose reductions and careful monitoring will be needed when prescribing duloxetine in combination with drugs that are preferentially metabolized by CYP2D6. The most common side effects identified in clinical trials are nausea, dry mouth, dizziness, constipation, insomnia, asthenia, and hypertension, consistent with its mechanisms of action. Clinical trials to date have demonstrated rates of response and remission in patients with major depression that are comparable to other marketed antidepressants reviewed in this book. In addition to approval for MDD, duloxetine is approved for diabetic peripheral neuropathic pain, fibromyalgia, and musculoskeletal pain. Milnacipran is marketed as an antidepressant in some countries, but not in the USA. It is approved in the USA and some other countries as a treatment for fibromyalgia. It has few pharmacokinetic and pharmacodynamic interactions with other drugs. Milnacipran has a half-life of about 10 h and therefore needs to be administered twice per day. It is metabolized by CYP3A4, but the major pathway for clearance is direct conjugation and renal elimination. As with other drugs in this class, dysuria is a common, troublesome, and dose-dependent adverse effect (occurring in up to 7% of patients). High-dose milnacipran has been reported to cause blood pressure and pulse elevations. Levomilnacipran is the levorotary enantiomer of milnacipran, and it is pharmacologically very similar to the racemic compound, although the side effects may be milder within the approved dosing range. As with other NE uptake inhibitors, it may increase blood pressure and pulse, although it appears to do so less than some other medications. All medications in the class can cause serotonin syndrome when combined with MAOIs.

Dense breast notification laws enacted in over 35 states mandate written disclosure of information to women with high mammographic breast density (high MBD), as defined by the heterogeneously or extremely dense breast classification of the Breast Imaging-Reporting and Data System. In most states, the notification informs women with high MBD about higher breast cancer (BC) risk and lower sensitivity of mammography in women with dense breasts. It also advises women to consult their doctors about their risk and any need for additional imaging. We examined personal history of high MBD in relation to breast density awareness, and BC-related emotional (BC worry) and cognitive (perceived BC risk and mammogram benefits) factors. We further investigated whether these associations varied by race/ethnicity, educational attainment and language proficiency in 649 women presenting for screening mammography (40-60 years, 80% Hispanic, 47% high school or less education, 70% Spanish speaking). Only 24% of women reported having heard of breast density (awareness), of whom, 68% correctly reported a personal history of high MBD, but only 23% reported having initiated a discussion about breast density with their physicians. In multivariable models, breast density awareness was higher for women with a history of high MBD (OR=2.4, 95% CI: 1.5, 4.0), a history of follow-up after screening mammography for any reason (e.g., multiple recalls vs none OR=4.2, 95% CI: 1.9, 9.6), and family history of BC (OR=2.0, 95% CI: 1.0, 3.9). In the same multivariable model, awareness was lower for women who were foreign-born (e.g., OR=0.3, 95% CI: 0.2, 0.6 vs U.S.-born), Spanish speaking (OR=0.2, 95% CI: 0.1, 0.4 vs English speaking), and had lower education (e.g., OR=0.1, 95% CI: 0.1, 0.3 high school or less vs college vs higher degree). High MBD was associated with increased breast density awareness in all racial/ethnic, nativity, educational, and language proficiency groups. Breast cancer-related psychological outcomes differed only by breast density awareness but not by high MBD history. Women with breast density awareness reported higher worry (e.g., OR=2.5, 95% CI: 1.6, 3.9 for sometimes vs rarely/never worry), and higher absolute and comparative perceived BC risk (e.g., OR=2.8, 95% CI: 1.6, 5.0 for more risk vs less risk compared to average women). Women who knew about breast density also perceived less mammography benefits for earlier detection of breast tumors (OR=0.2, 95% CI: 0.1, 0.5) and reduced BC mortality (OR=0.4, 95% CI: 0.2, 0.6). In conclusion, dense breast notification to women with high MBD increases general and personal awareness of breast density; however, awareness remains low in women with racial/ethnic minority and lower socioeconomic backgrounds due to lower prevalence of dense breasts in these population groups. Dense breast notification increases feelings of worry and perceptions of future risk of breast cancer and reduces perceptions of mammography benefits, which may affect breast cancer screening participation. Citation Format: Mariangela D. Agovino, Carmen B. Rodriguez, Mary Beth Terry, Rachel Shelton, Karen Schmitt, Elise Desperito, Ying Wei, Rita Kukafka, Parisa Tehranifar. Dense breast notification, breast density awareness, and breast cancer-related cognition and emotions in a predominantly Hispanic screening population [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr C095.

The recent conference Turning the Tide: A New Generation of Public Health Interventions highlighted the need to utilize innovative and emergent methodologies to confront increasingly complex public health challenges. In this commentary, we discuss three dominant themes from the conference: addressing multiple levels of causality in reducing health problems; technology-based methodologies to enhance health promotion; and improving translation and sustainment of effective health promotion programs. The subsequent articles, included in this supplement issue of AJPH, provide compelling examples and arguments supporting these progressive approaches to public health promotion. We recommend that public health researchers draw inspiration from these examples and embrace interdisciplinary, innovative methods within their future work.

Controlled studies have shown short-term efficacy of esketamine for treatment-resistant depression (TRD), but long-term effects remain to be established.To assess the efficacy of esketamine nasal spray plus an oral antidepressant compared with an oral antidepressant plus placebo nasal spray in delaying relapse of depressive symptoms in patients with TRD in stable remission after an induction and optimization course of esketamine nasal spray plus an oral antidepressant.In this phase 3, multicenter, double-blind, randomized withdrawal study conducted from October 6, 2015, to February 15, 2018, at outpatient referral centers, 705 adults with prospectively confirmed TRD were enrolled; 455 entered the optimization phase and were treated with esketamine nasal spray (56 or 84 mg) plus an oral antidepressant. After 16 weeks of esketamine treatment, 297 who achieved stable remission or stable response entered the randomized withdrawal phase.Patients who achieved stable remission and those who achieved stable response (without remission) were randomized 1:1 to continue esketamine nasal spray or discontinue esketamine treatment and switch to placebo nasal spray, with oral antidepressant treatment continued in each group.Time to relapse was examined in patients who achieved stable remission, as assessed using a weighted combination log-rank test.Among the 297 adults (mean age [SD], 46.3 [11.13] years; 197 [66.3%] female) who entered the randomized maintenance phase, 176 achieved stable remission; 24 (26.7%) in the esketamine and antidepressant group and 39 (45.3%) in the antidepressant and placebo group experienced relapse (log-rank P = .003, number needed to treat [NNT], 6). Among the 121 who achieved stable response, 16 (25.8%) in the esketamine and antidepressant group and 34 (57.6%) in the antidepressant and placebo group experienced relapse (log-rank P .001, NNT, 4). Esketamine and antidepressant treatment decreased the risk of relapse by 51% (hazard ratio [HR], 0.49; 95% CI, 0.29-0.84) among patients who achieved stable remission and 70% (HR, 0.30; 95% CI, 0.16-0.55) among those who achieved stable response compared with antidepressant and placebo treatment. The most common adverse events reported for esketamine-treated patients after randomization were transient dysgeusia, vertigo, dissociation, somnolence, and dizziness (incidence, 20.4%-27.0%), each reported in fewer patients (7%) treated with an antidepressant and placebo.For patients with TRD who experienced remission or response after esketamine treatment, continuation of esketamine nasal spray in addition to oral antidepressant treatment resulted in clinically meaningful superiority in delaying relapse compared with antidepressant plus placebo.ClinicalTrials.gov identifier: NCT02493868.

This study assessed the solute permeability of a family of UV and moisture cured acrylates-based adhesives during in vitro ageing in pH 7.4 buffer. Acrylates have a potential role in bone fracture fixation, but their inability to allow microsolute exchange between the fractured bone surfaces may contribute to ineffective healing. Cyclic voltammetry and chronoamperometry were used to determine the diffusion coefficients for various electrochemically active probe molecules (O2, H2O2, acetaminophen, catechol, uric acid and ascorbic acid) at proprietary acrylic, urethane – acrylate and cyanoacrylate adhesives. All adhesives proved to be impermeable for up to 9 days ageing, following which a near-exponential increase in permeability resulted for all solutes. At 18 days, the diffusion coefficients were in the range of 10−5 cm2s−1 for O2 and H2O2 and 10−6 cm2s−1 for the organic solutes; no transport selectivity was seen between the latter. Adhesive joint strength showed a direct, inverse, correlation with permeability, with the more hydrophilic cyanoacrylates showing the greatest loss of strength. Adhesive permeabilisation does not appear to be compatible with the retention of bonding strength, but it serves as a new non-destructive predictor of adhesion strength change during ageing and practical use., Graphical abstract Image 1

The CRUZA trial tested the efficacy of an organizational-level intervention to increase capacity among Catholic parishes to implement evidence-based interventions (EBIs) for cancer control. This paper examines the external generalizability of the CRUZA study findings by comparing characteristics of parishes that agreed to participate in the intervention trial versus those that declined participation. Sixty-five Roman Catholic parishes that offered Spanish-language mass in Massachusetts were invited to complete a four-part survey assessing organization-level characteristics that, based on the Consolidated Framework for Implementation Research (CFIR), may be associated with EBI implementation. Forty-nine parishes (75%) completed the survey and were invited to participate in the CRUZA trial, which randomized parishes to either a “capacity enhancement intervention” or a “standard dissemination” group. Of these 49 parishes, 31 (63%) agreed to participate in the trial, whereas 18 parishes (37%) declined participation. Parishes that participated in the CRUZA intervention trial were similar to those that did not participate with respect to “inner organizational setting” characteristics of the CFIR, including innovation and values fit, implementation climate, and organizational culture. Change commitment, a submeasure of organizational readiness that reflects the shared resolve of organizational members to implement an innovation, was significantly higher among the participating parishes (mean = 3.93, SD = 1.08) as compared to nonparticipating parishes (mean = 3.27, SD = 1.08) (Z = −2.16, p = .03). Parishes that agreed to participate in the CRUZA intervention trial were similar to those that declined participation with regard to organizational characteristics that may predict implementation of EBIs. Pragmatic tools to assess external generalizability in community-based implementation trials and to promote readiness among faith-based organizations to implement EBIs are needed to enhance the reach and impact of public health research. Clinical Trial information: The CRUZA trial identifier number with clinicaltrials.gov is NCT01740219.

The growth of dissemination and implementation (D&I) research over the last decade has produced a wealth of theories, frameworks, methods, strategies, and resources to inform the translation of evidence into wider practice. This article seeks to frame and orient researchers from the behavioral sciences to the rapidly growing interdisciplinary field of D&I science. We describe five domains across D&I research and practice: context assessment and intervention selection, dissemination, adaptation, implementation, and sustainability. We also discuss evaluation and communication as critical processes to drive ongoing learning and improvement across the five domains. In each section, we include widely cited literature and resources that readers may use to orient themselves to the field, and identify areas that they may want to explore further. This article organizes major areas of D&I science focusing on key definitions, approaches, and commonly used resources. It provides an introduction to researchers new to this area on how to conceptualize and navigate the field of D&I science, with the ultimate goal of increasing the reach and impact of evidence-based interventions.

INTRODUCTION: Depressive episodes are often prevalent among patients with bipolar disorder, but little is known regarding the differential patterns of development over time. We aimed to determine and characterize trajectories of depressive symptoms among adults with bipolar disorder during 6 months of systematic treatment.METHODS: The pragmatic clinical trial, Bipolar Clinical Health Outcomes Initiative in Comparative Effectiveness (CHOICE), randomized 482 outpatients with bipolar disorder to lithium or quetiapine. Depressive symptoms were rated at up to 9 visits using the Montgomery-Asberg Depression Rating Scale (MADRS). Growth mixture modeling was utilized to identify trajectories and multinomial regression analysis estimated associations with potential predictors.RESULTS: Four distinct trajectories of depressive symptoms were identified. The responding class (60.3%) with a rapid reduction and subsequent low level; the partial-responding class (18.4%) with an initial reduction followed by an increase during the remaining weeks; the fluctuating class (11.6%) with a fluctuation in depressive symptoms; and the non-responding class (9.7%) with sustained moderate-severe depressive symptoms. Bipolar type I predicted membership of the non-responding class and randomization to quetiapine predicted membership of either the responding or the non-responding class.CONCLUSION: Approximately 30% experienced a partial or fluctuating course, and almost 10% had a chronic course with moderate-severe depression during 6 months. Patients diagnosed with bipolar type 1 had higher risk of being categorized into a class with a worse outcome. While no differences in average overall outcomes occurred between the lithium and quetiapine groups, trajectory analysis revealed that the lithium group had more variable courses.

Background: Childhood social risk has been associated with increased risk of childhood obesity. However, little is known about early exposure of cumulative social risk on BMI percentile (BMIp) trajectories in early childhood. Methods: Public data from the Fragile Families and Child Wellbeing Study were analyzed (N = 3809). Maternal reports of experiences of multiple social risk factors were obtained at age 1 and 3 assessments of children. Two cumulative social risk scores were calculated by summing social factors assessed at age 1 and at age 3. Child BMIp was assessed at ages 3, 5, and 9. Linear mixed models were used to examine the effect of cumulative social risk on sex-specific BMIp trajectories. Results: Compared with girls experiencing low social risk at either age 1 or 3, girls experiencing high social risk (≥ 2 factors) at age 1 or 3 only had higher initial BMIp at age 3 [β(0) = 5.70 (95% confidence interval, CI: 0.15–1.26) and 1.37 (95% CI: −2.25 to 4.99), respectively] and had nonsignificantly greater BMIp growth rate [β(1) = 0.39 (95% CI: −0.86 to 1.63) and 0.32 (95% CI: −0.86 to 1.63)]. Girls experiencing high social risk at both ages had nonsignificantly but consistently lower BMIp [β(1) = −1.24 (95% CI: −2.93 to 0.46)]. In addition, girls experiencing a sum of ≥4 risk factors at both ages had lower BMIp growth rate [β(1) = −1.77 (95% CI: −3.39 to −0.15)] compared to girls experiencing no risk factor. No associations were observed among boys. Conclusions: Early exposure to cumulative social risk may have long-term impact on BMIp trajectories among girls, depending on timing of exposure. Understanding the effect of cumulative social risk in different contexts, including sex, chronicity, and timing of exposure, may have practical implications for informing effective intervention to combat childhood obesity.

Poster abstracts are evaluated based on the following criteria: significance of the problem to healthy aging or medication management; innovativeness of ideas, methods, and/or approach; methodological rigor of methods and approach; presentation of finding; implications identified for future research, practice, and/or policy; and clarity of writing. Submissions are not evaluated through the peer-reviewed process used by

BACKGROUND Depressed patients presenting to emergency departments with acute suicidal ideation are a major public health concern. Ketamine, a rapidly acting antidepressant with antisuicidal properties, might offer relief. METHODS In a randomized, double-blind, placebo-controlled, proof-of-concept trial, 18 depressed subjects with acute suicidal ideation, who required hospitalization, were randomized to either an intravenous ketamine 0.2 mg/kg group or a saline placebo group. Safety and efficacy evaluations were scheduled for 15, 30, 60, 90, 120, 180, and 240 min, and on Days 1, 2, 3, 7, and 14 after infusion. The main outcome measure was suicidal ideation with secondary measures of depression. RESULTS Nine subjects were randomized to each group. There were no differences between groups at baseline in any demographic or assessment scales. A reduction in suicidal ideation was noted at 90-180 min (p

Background Patient advocacy has led to state-level legislative mandates for the release of personal mammographic breast density information to women undergoing screening mammography. More research is needed to understand the impact of this information on women's perceptions and mammography screening behavior. Methods Semistructured interviews were conducted in English and Spanish with 24 self-identified Hispanic women who had undergone at least 1 mammogram since breast density notification was enacted in New York State. The women ranged in age from 43 to 63 years. Women were asked about their understanding and perceptions of the communication of New York State-mandated breast density information, and any actions they have taken or would take in response to this information. A content analysis of the qualitative data from the translated and transcribed interviews was conducted. Results The majority of participants had no prior knowledge of breast density and expressed confusion and apprehension regarding the meaning of dense breasts when presented with the notification information. Many participants understood having dense breasts to be a serious and abnormal condition, and reported feelings of worry and vulnerability. Participants mostly expressed a strong interest in learning about breast density and obtaining additional and more frequent breast cancer screening tests. These behavioral intentions were consistent with participants' overall favorable view of breast cancer screening and a belief that their faith, as well as regular screening, can help to protect them from breast cancer morbidity and mortality. Conclusions Hispanic women conveyed proactive breast cancer screening intentions in response to breast density notification, despite inadequate comprehension of this information and negative emotional responses.

Many studies report the adverse responses to metal-on-metal (MoM) hip prostheses, with tissues surrounding failed MoM hip prostheses revealing abundant tissue necrosis and fibrosis. These local effects appear to be initiated by metal ions released from the prosthesis causing the secretion of inflammatory mediators. However, little is known about the effect of the metal ions on tissue remodelling and pseudotumor formation, which are also associated with the failure of MoM hip prostheses. The peri-prosthetic soft tissue masses can lead to pain, swelling, limited range of joint movement and extensive tissue lesion. To elucidate this cellular response, a multidisciplinary approach using both two- and three-dimensional (2D and 3D) in vitro culture systems was employed to study the effects of Co2+ and Cr3+ on human fibroblast activation and mechanobiology. Co2+ induced a fibrotic response, characterised by cytoskeletal remodelling and enhanced collagen matrix contraction. This was associated with increased cell stiffness and contractile forces as measured by atomic force microscopy and traction force microscopy, respectively. These effects were triggered by the generation of reactive oxygen species (ROS). Moreover, this fibrotic response was enhanced in the presence of macrophages, which increased the prevalence of a-smooth muscle actin (a-SMA)-positive fibroblasts and collagen synthesis. Cr3+ did not show any significant effect on fibroblast activation. Co2+ promoted matrix remodelling by fibroblasts that was further enhanced by macrophage signalling. Use of alternative implant materials or manipulation of this fibrotic response could provide an opportunity for enhancing the success of prostheses utilising CoCr alloys.

Data analysis is one of the most important, yet least understood, stages of the qualitative research process. Through rigorous analysis, data can illuminate the complexity of human behavior, inform interventions, and give voice to people’s lived experiences. While significant progress has been made in advancing the rigor of qualitative analysis, the process often remains nebulous. To better understand how our field conducts and reports qualitative analysis, we reviewed qualitative articles published in Health Education & Behavior between 2000 and 2015. Two independent reviewers abstracted information in the following categories: data management software, coding approach, analytic approach, indicators of trustworthiness, and reflexivity. Of the 48 ( n = 48) articles identified, the majority ( n = 31) reported using qualitative software to manage data. Double-coding transcripts was the most common coding method ( n = 23); however, nearly one third of articles did not clearly describe the coding approach. Although the terminology used to describe the analytic process varied widely, we identified four overarching trajectories common to most articles ( n = 37). Trajectories differed in their use of inductive and deductive coding approaches, formal coding templates, and rounds or levels of coding. Trajectories culminated in the iterative review of coded data to identify emergent themes. Few articles explicitly discussed trustworthiness or reflexivity. Member checks ( n = 9), triangulation of methods ( n = 8), and peer debriefing ( n = 7) were the most common procedures. Variation in the type and depth of information provided poses challenges to assessing quality and enabling replication. Greater transparency and more intentional application of diverse analytic methods can advance the rigor and impact of qualitative research in our field.

Approximately 86-89% of patients with BD have a comorbid anxiety disorder associated with poor quality of life and reduced likelihood of recovery from an acute mood episode. The purpose of this study is to assess the prevalence and impact of comorbid anxiety using the Bipolar Inventory of Symptoms Scale (BISS) in patients with BD who participated in a 6-month pragmatic trial.Participants (N = 482) in the Bipolar Clinical Health Outcomes Initiative in Comparative Effectiveness (CHOICE) study were adults with BD I or II. Anxiety diagnoses were assessed with the MINI. Global illness severity was assessed using the Clinical Global Impression-Bipolar Version. Mood symptoms and anxiety severity were assessed using the BISS.61% of the study sample met criteria for a current anxiety disorder. Patients with a higher BISS anxiety score at baseline had a higher overall BD illness severity, depressive severity, and manic episode severity (p 0.001). A single cutoff value of BISS anxiety had great sensitivity, yet poor specificity for determining a comorbid anxiety diagnosis. There were no significant differences in outcomes for individuals treated for anxiety disorders with anxiolytics compared with those who were not treated with anxiolytics.Sample size limitations prevented an analysis of whether the BISS cutoff score of 10 performed differently across varied anxiety disorders.Given its ability to identify patients with co-occurring anxiety, the BISS anxiety subscale shows clinical utility as a screening measure though its application as a clinical assessment measure may not be advisable.

Introduction Not all patients with bipolar depression have suicidal ideation (SI). This study examines some factors that link bipolar depression to SI. Methods 482 individuals with bipolar I or II were randomized to either lithium or quetiapine plus adjunctive personalized therapy in a 24 week comparative effectiveness trial. Severity of depression and SI were assessed with the Bipolar Inventory of Symptoms Scale (BISS). We examined potential moderators (age, gender, age of illness onset, bipolar type, comorbid anxiety, substance use, past suicide attempts, childhood abuse and treatment arm) and mediators (severity of anxiety, mania, irritability, impairment in functioning (LIFE-RIFT) and satisfaction and enjoyment of life (Q-LES-Q)) of the effect of depression on SI. Statistical analyses were conducted using generalized estimating equations with repeated measures. Results Bipolar type and past suicide attempts moderated the effect of depression on SI. Life satisfaction mediated the effect of depression and SI. The relationship between anxiety, depression and SI was complex due to the high level of correlation. Treatment with lithium or quetiapine did not moderate the effect of depression on SI. Limitations Suicide assessment was only done using an item on BISS. Patient population was not specifically chosen for high suicide risk. Discussion Individuals with Bipolar II experienced more SI with lower levels of depression severity. A history of suicide predisposed patients to higher levels of SI given the same severity of depression. Reduced life satisfaction mediates the effect of depression on SI and may be a target for therapeutic interventions.

More than half of the stars in the solar neighborhood reside in binary/multiple stellar systems, and recent studies suggest that gas giant planets may be more abundant around binaries than single stars. Yet, these multiple systems are usually overlooked or discarded in most direct imaging surveys, as they prove difficult to image at high-contrast using coronographs. This is particularly the case for compact binaries (less than 1" angular separation) with similar stellar magnitudes, where no existing coronagraph can provide high-contrast regime. Here we present preliminary results of an on-going Palomar pilot survey searching for low-mass companions around ~15 young challenging binary systems, with angular separation as close as 0".3 and near-equal K-band magnitudes. We use the Stellar Double Coronagraph (SDC) instrument on the 200-inch Telescope in a modified optical configuration, making it possible to align any targeted binary system behind two vector vortex coronagraphs in cascade. This approach is uniquely possible at Palomar, thanks to the absence of sky rotation combined with the availability of an extreme AO system, and the number of intermediate focal-planes provided by the SDC instrument. Finally, we expose our current data reduction strategy, and we attempt to quantify the exact contrast gain parameter space of our approach, based on our latest observing runs., 12 pages, 8 figures, to appear in Proceedings of the SPIE, paper 10702-147

Standard community-engaged research methods involve reporting research findings back to study participants. Project HEAL is an implementation trial conducted in 14 African American churches. This paper reports on a strengths-based approach to reporting Project HEAL organizational capacity data back to church leadership, through use of individualized church reports. Pastors in each church completed a church organizational capacity assessment. The study team, including community partners representing church leadership, co-created a channel and content to disseminate the capacity data back to Project HEAL church leaders. This consisted of a 4-page lay report that included the church's capacity scores, and recommendations for future evidence-based health promotion programming matched to their capacity. The study team was able to meet with nine of the 14 churches to review the report, which took an average of six and a half weeks to schedule. The individualized church reports were well-received by pastors, who expressed an intention to share the information with others in the church and to sustain health promotion activities in their organizations. Though the individualized reports were embraced by the pastors, it is unknown whether this process will result in sustainable health promotion in these organizations without further follow-up.

High-dose melphalan and autologous stem cell transplantation (HDM/SCT) have been used in patients with immunoglobulin light chain (AL) amyloidosis for over 2 decades now with durable responses, prolonged survival, and decreasing treatment-related mortality. Historically, patients with poorer baseline functional status, advanced age, renal compromise, and cardiac involvement have been treated with a risk-adapted modified conditioning dose of melphalan (mHDM) of 100 to 140 mg/m2 before SCT. In part because of these baseline characteristics, patients receiving mHDM/SCT have had poorer outcomes compared with patients receiving full-dose melphalan at 200 mg/m2. With the advent of novel therapeutic agents such as proteasome inhibitors, immunomodulatory agents, and monoclonal antibodies for the treatment of AL amyloidosis, it is imperative to understand the long-term effects of mHDM/SCT. Here we report the long-term outcomes of 334 patients with AL amyloidosis treated with mHDM/SCT. Median overall survival was 6.1 years and median event-free survival 4.3 years, with median overall survival reaching 13.4 years for patients who had achieved a hematologic complete response (CR). Overall hematologic response rate was 69%, and treatment-related mortality was 3% after 2010. Thus, mHDM/SCT leads to prolonged survival and favorable outcomes, especially if a hematologic CR is achieved.

Objective To evaluate remission and recovery, safety, and tolerability for up to 12 months of open-label adjunctive L-methylfolate calcium 15 mg. Method Subjects in this analysis were adult outpatients (18-65 years) enrolled from 2 acute, double-blind, placebo-controlled trials comparing adjunctive L-methylfolate and placebo for DSM-IV major depressive disorder (MDD) with an inadequate response to monotherapy selective serotonin reuptake inhibitor (SSRI). Subjects who completed the acute trial were offered to enroll in a 12-month, open-label treatment phase with L-methylfolate and continued SSRI treatment, with scheduled visits for efficacy, safety, and tolerability every 12 weeks. Subjects were enrolled between September 2006 and February 2010. Efficacy outcomes included predefined criteria for response, remission, recovery, relapse, and recurrence. Subjects treated with adjunctive L-methylfolate 15 mg were included in the efficacy analysis. Results Of 68 subjects who met criteria for the 12-month open-label phase, 38% (n = 26) achieved full recovery, and none experienced a recurrence of MDD. For subjects entering the open-label phase in remission (n = 11), 91% (n = 10) achieved full recovery with L-methylfolate 15 mg, and none experienced a relapse or recurrence. Among 57 subjects who entered the open-label phase as nonremitted, 61% (n = 35) achieved remission. Of subjects who entered the open-label phase with a response without remission (n = 4), 50% (n = 2) had full recovery, and of subjects entering the open-label phase with no response (n = 53), 26% (n = 14) met recovery criteria. Conclusions Adjunctive L-methylfolate 15 mg/d may be an early option in patients who fail to adequately respond to antidepressant monotherapy, with preliminary evidence demonstrating sustained remission and sustained recovery. Trial registration ClinicalTrials.gov identifier: NCT00321152.

Background Few brief, self-report measures exist that can reliably predict adverse suicidality outcomes in patients with BD. This study utilized the Concise Health Risk Tracking Self-Report (CHRT) to assess suicidality in patients with BD and examined its psychometric performance, clinical correlates, and prospective value in predicting adverse events related to suicidality. Methods The CHRT was administered at baseline and follow-up to 482 adult patients in Bipolar CHOICE, a 6-month randomized comparative effectiveness trial. The Columbia Suicide Severity Rating Scale (CSSRS) was used at baseline to assess lifetime history of suicide attempts and related behaviors. Clinician-rated measures of mood (Bipolar Inventory of Symptoms Scale) and bipolar symptoms (Clinical Global Impressions-Bipolar Version) were conducted at baseline and follow-up. Results The CHRT showed excellent internal consistency and construct validity and was highly correlated with clinician ratings of depression, anxiety, and overall functioning at baseline and throughout the study. Baseline CHRT scores significantly predicted risk of subsequent suicidality-related Serious Adverse Events (sSAEs), after controlling for mood and comorbidity. Specifically, the hazard of a sSAE increased by 76% for every 10-point increase in baseline CHRT score. Past history of suicide attempts and related behaviors, as assessed by the CSSRS, did not predict subsequent sSAEs. Limitations The CSSRS was used to assess static risk factors in terms of past suicidal behaviors and may have been a more powerful predictor over longer-term follow-up. Conclusions The CHRT offers a quick and robust self-report tool for assessing suicidal risk and has important implications for future research and clinical practice.

Simulation of wear in total hip replacements has been recognised as an important factor in determining the likelihood of clinical success. However, accurate measurement of wear can be problematic with factors such as number and morphology of wear particles produced as well as ion release proving more important in the biological response to hip replacements than wear volume or wear rate alone. In this study, hard-on-hard (CoCr alloy, AgCrN coating) and hard-on-soft (CoCr alloy and CrN coating on vitamin E blended highly cross-linked polyethylene) bearing combinations were tested in an orbital hip simulator under standard and some adverse conditions. Gravimetric wear rates were determined for all bearings, with cobalt and where applicable, silver release determined throughout testing. Isolation of wear particles from the lubricating fluid was used to determine the influence of different bearing combinations and wear conditions on particle morphology. It was found that cobalt and silver could be measured in the lubricating fluid even when volumetric wear was not detectable. In hard-on-hard bearings, Pearson’s correlation of 0.98 was established between metal release into the lubricating fluid and wear volume. In hard-on-soft bearings, coating the head did not influence the polyethylene wear rates measured under standard conditions but did influence the cobalt release; the diameter influenced both polyethylene wear and cobalt release, and the introduction of adverse testing generated smaller polyethylene particles. While hip simulators can be useful to assess the wear performance of a new material or design, measurement of other outcomes may yield greater insight into the clinical behaviour of the bearings in vivo.

OBJECTIVE To examine the effects of treatment on functioning impairments and quality of life and assess baseline functioning and employment status as predictors of treatment response in symptomatic individuals from the Bipolar Clinical Health Outcomes Initiative in Comparative Effectiveness (Bipolar CHOICE) study. METHOD Bipolar CHOICE was an 11-site, 6-month randomized effectiveness study comparing lithium to quetiapine, each with adjunctive personalized treatments (APTs). We examined post hoc (1) the effects of treatment on functioning, (2) how changes in functioning differed between treatment responders and nonresponders, and (3) whether functioning and employment status mediated treatment response in 482 participants with DSM-IV-TR bipolar I or II disorder from September 2010 to September 2013. RESULTS Treatment was associated with significant improvements in functioning and quality of life, regardless of treatment group (P values < .0001). Responders showed greater improvements in quality of life (Quality of Life Enjoyment and Satisfaction Questionnaire P values < .05) and functioning (Longitudinal Interval Follow-up Evaluation-Range of Impaired Functioning Tool P values < .05) than nonresponders. Unemployed or disabled participants at baseline had significantly greater illness severity at baseline than employed participants (P values < .05). Over the study duration, employed participants reported greater improvements in physical health and quality of life in leisure activities than both unemployed and disabled participants (P values < .05). Individuals who saw greater improvement in functioning and quality of life tended to show greater improvements in depressive and anxiety symptoms (P values ≤ .0001), as well as overall illness severity (P values < .001). Early (8 weeks) and very early (4 weeks) clinical changes in mood symptoms predicted changes in functioning and quality of life at 6 months (P values < .001). CONCLUSIONS Prior disability status was associated with a worse treatment response and prospective illness course. Results implicate functioning and employment status as important markers of illness severity and likelihood of recovery in bipolar disorder, suggesting that interventions that target functional impairment may improve outcomes. TRIAL REGISTRATION ClinicalTrials.gov identifier for the Bipolar CHOICE study: NCT01331304.

The continuing obesity epidemic in the USA calls for the examination of antecedents to the well-known risk factors of physical activity and diet. The neighborhood built environment has been extensively studied in relation to obesity noting an increased risk of development and prevalence of obesity in relation to numerous built environment characteristics (lack of green spaces, higher number of fast food restaurants, low walkability indices). The neighborhood social environment, however, has been less extensively studied but is perhaps an equally important component of the neighborhood environment. The neighborhood social environment, particularly constructs of social capital, collective efficacy, and crime, is associated with obesity among both adults and children. Several studies have identified physical activity as a potential pathway of the neighborhood social environment and obesity association. Further work on social networks and norms and residential segregation, as well as the examination of dietary behaviors and mental health as potential mediating pathways, is necessary. Given the existing evidence, intervening on the neighborhood social environment may prove to be an effective target for the prevention on obesity. Intervention studies that promote healthy behaviors and prevent obesity while addressing aspects of the neighborhood social environment are necessary to better identify targets for obesity prevention.

Background: Even when patients experience remission with antidepressants, many continue to report anger attacks and excessive irritability despite continued treatment. Iloperidone antagonizes 5-HT-2a, D2, and alpha-1 receptors, which can have anti-aggressive effects. We examined iloperidone’s safety and efficacy as an augmentation agent in outpatients with partially remitted major depressive disorder (MDD) with residual symptoms of anger and irritability. Methods: A total of 13 outpatients with partially remitted MDD [currently treated with selective serotonin reuptake inhibitors (SSRIs)] received four weeks of iloperidone or placebo, followed by one week of washout. Patients were then crossed over to the other treatment arm for 4 weeks. Treatment arms were randomized and double blind; and two sites were used for the study. Analyses compared treatment response using the Symptom Questionnaire (SQ) Anger/Hostility Subscale as the primary outcome measure. Results: There was no significant differential effect of iloperidone × weeks on the SQ Anger/Hostility Subscore over the course of the study, compared with placebo × weeks, regardless of administration order ( p = 0.77). Conclusions: Iloperidone did not significantly outperform placebo on measures of anger or irritability in patients with partially remitted MDD and residual anger/irritability.

OBJECTIVE Adjunctive treatment with L-methylfolate calcium significantly improved treatment outcomes in patients with major depressive disorder (MDD) and an inadequate response to antidepressants. This post hoc exploratory analysis evaluated baseline concentrations of cytokines (interleukin [IL]-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, and IL-17; tumor necrosis factor α [TNF-α]; and interferon γ [IFN-γ]), high-sensitivity C-reactive protein (hsCRP), insulin, adiponectin and leptin and body mass index (BMI [kg/m2]) on L-methylfolate calcium treatment response. METHOD Adults with DSM-IV MDD and an inadequate response to a selective serotonin reuptake inhibitor (SSRI) were eligible. Patients were randomized 3:3:2 according to the sequential parallel comparison design to placebo versus placebo, placebo versus L-methylfolate calcium (15 mg/d), or L-methylfolate calcium versus L-methylfolate calcium (15 mg/d) during two 30-day phases. The primary outcome was change on the 17-item Hamilton Depression Rating Scale (HDRS-17). Treatment effect with 95% CIs was estimated from baseline concentrations of individual biomarkers and combinations. Cytokines were measured by immunoassay; adiponectin, insulin, and leptin by radioimmunoassay; and hsCRP by a standard turbidimetric assay. The effects of baseline biomarker levels (above and below the median) on outcome were analyzed. The first participant was enrolled July 14, 2009, and the last participant completed April 28, 2011. RESULTS Mean change on HDRS-17 from baseline was significantly improved with L-methylfolate calcium versus placebo (pooled treatment effect, -2.74; 95% CI, -4.99 to -0.48; P = .017) overall and for those with baseline BMI ≥ 30 (pooled treatment effect, -4.66; 95% CI, -7.22 to -1.98; P = .001) but not BMI < 30. Pooled mean changes in depression across treatment for baseline levels of individual markers above median were significant (L-methylfolate calcium vs placebo) for TNF-α, IL-8, hsCRP, and leptin (pooled treatment effects, -4.33 to -3.94 [P ≤ .02]) and for combinations of BMI ≥ 30 with elevated levels of TNF-α, IL-6, IL-8, hsCRP, and leptin (pooled treatment effects, -6.31 to -3.98 [P ≤ .05]). CONCLUSIONS In this exploratory analysis, inflammatory and obesity-related factors were associated with greater symptom improvement with L-methylfolate calcium. Combinations of BMI ≥ 30 with elevated IL-6, IL-8, hsCRP, TNF-α, and leptin predicted improved response to L-methylfolate calcium in MDD patients with an inadequate antidepressant response. Further studies are necessary to confirm these findings. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT00955955.

Many people with major depressive disorder (MDD) show evidence of systemic inflammation, including elevations in inflammatory factors, but the cause is unclear. The purpose of this analysis was to determine if obesity might contribute to the pro-inflammatory state in MDD patients. Blood was obtained from 135 MDD patients and 50 controls. Serum was extracted and assayed for interleukin (IL) -1β, IL-2, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17, interferon-γ (IFNγ), tumor necrosis factor α (TNFα), C-reactive protein (CRP), leptin, and adiponectin using single- or multi-plex human immunoassay kits. The primary analysis contrasted IL-6, TNFα, and CRP between MDD and control groups with body mass index (BMI) as a covariate. The other analytes were compared in an exploratory fashion. IL-6 (but not TNFα or CRP) showed significant differences between MDD and controls even after covarying for BMI. Obese controls and obese MDD groups were significantly higher in IL-6 than both lean groups, but the two obese groups did not differ from each other. In the exploratory analyses, the IL-2 level showed robust and significant differences between MDD and controls even after covarying for BMI. Both lean and obese MDD were higher than lean and obese controls. Adiponectin levels were also lower in the MDD sample than controls. Prior findings of higher IL-6, and CRP in MDD patients may be explained, at least in part, based on obesity. High IL-2, however, was associated with depression and not obesity. The results have significant implications for the understanding of pathophysiology and, potentially treatment of MDD.

Two phase 2B, randomized, double-blind studies assessed the efficacy and safety of fixed or flexible dose of triple monoamine uptake inhibitor BMS-820836 in patients with treatment-resistant depression to demonstrate whether switching to BMS-820836 was superior to the continuation of standard antidepressant treatment. Patients with a history of inadequate response to 1 to 3 adequate trials of antidepressant therapies were prospectively treated with duloxetine 60 mg/d for 8 weeks (CN162-006) or duloxetine 60 mg/d or escitalopram 20 mg/d for 7 weeks (CN162-007). Inadequate responders were randomized to continue their prospective phase treatment or switch to flexible-dose (0.5-2 mg/d; CN162-006) or fixed-dose (0.25, 0.5, 1, or 2 mg/d; CN162-007) BMS-820836 for 6 weeks. The primary end point in both studies was mean change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score from randomization to study end point. BMS-820836 flexible (0.5-2 mg/d) or fixed dose of 1 mg/d or greater showed efficacy similar to the continuation of antidepressant treatment, with no statistically significant or clinically meaningful differences. In the CN162-006 study, the adjusted mean (SE) change in MADRS total score was -8.7 (0.661) and -8.1 (0.656) for BMS-820836 and duloxetine, respectively (P = 0.526). In the CN162-007 study, the adjusted mean (SE) change in MADRS total score was -7.3 (0.830) and -6.6 (0.842) for BMS-820836 of 1 and 2 mg, respectively, and -6.9 (0.602) for the continuation group (P = 0.910). Thus, BMS-820836 was well tolerated, with no evidence of dose-dependent discontinuations due to adverse events, but it failed to demonstrate superiority to the continuation of an existing antidepressant in patients with treatment-resistant depression.

Little is known about Latina breast cancer survivors’ social networks or their perceived social support to achieve and maintain a healthy diet. This paper describes the social networks and perceived support for healthy eating in a sample of breast cancer survivors of predominantly Dominican descent living in New York City. Spanish-speaking Latina breast cancer survivors enrolled in a randomized controlled trial of a culturally tailored dietary intervention. Social networks were assessed using Cohen’s Social Network Index and a modified General Social Survey Social Networks Module that included assessments of shared health promoting behaviors. Perceived social support from family and friends for healthy, food-related behaviors was assessed. Participants’ networks consisted predominantly of family and friends. Family members were more likely than other individuals to be identified as close network members. Participants were more likely to share food-related activities than exercise activities with close network members. Perceived social support for healthy eating was high, although perceived support from spouses and children was higher than support from friends. Despite high levels of perceived support, family was also identified as a barrier to eating healthy foods by nearly half of women. Although friends are part of Latina breast cancer survivors’ social networks, spouses and children may provide greater support for healthy eating than friends. Involving family members in dietary interventions for Latina breast cancer survivors may tap into positive sources of support for women, which could facilitate uptake and maintenance of healthy eating behaviors.

McElroy SL, Kemp DE, Friedman ES, Reilly-Harrington NA, SylviaLG, Calabrese JR, Rabideau DJ, Ketter TA, Thase ME, Singh V,Tohen M, Bowden CL, Bernstein EE, Brody BD, Deckersbach T,Kocsis JH, Kinrys G, Bobo WV, Kamali M, McInnis MG, Leon AC,Faraone S, Nierenberg AA, Shelton RC. Obesity, but not metabolicsyndrome, negatively affects outcome in bipolar disorder.Objective: Examine the effects of obesity and metabolic syndrome onoutcome in bipolar disorder.Method: The Comparative Effectiveness of a Second GenerationAntipsychotic Mood Stabilizer and a Classic Mood Stabilizer forBipolar Disorder (Bipolar CHOICE) study randomized 482participants with bipolar disorder in a 6-month trial comparing lithium-and quetiapine-based treatment. Baseline variables were comparedbetween groups with and without obesity, with and without abdominalobesity, and with and without metabolic syndrome respectively. Theeffects of baseline obesity, abdominal obesity, and metabolic syndromeon outcomes were examined using mixed effects linear regressionmodels.Results: At baseline, 44.4% of participants had obesity, 48.0% hadabdominal obesity, and 27.3% had metabolic syndrome; neitherobesity, nor abdominal obesity, nor metabolic syndrome wereassociated with increased global severity, mood symptoms, orsuicidality, or with poorer functioning or life satisfaction. Treatmentgroups did not differ on prevalence of obesity, abdominal obesity, ormetabolic syndrome. By contrast, among the entire cohort, obesity wasassociated with less global improvement and less improvement in totalmood and depressive symptoms, suicidality, functioning, and lifesatisfaction after 6 months of treatment. Abdominal obesity wasassociated with similar findings. Metabolic syndrome had no effect onoutcome.Conclusion: Obesity and abdominal obesity, but not metabolicsyndrome, were associated with less improvement after 6 months oflithium- or quetiapine-based treatment.

This study examines differences in the resources, information, and support parents coping with pediatric cancer accessed from different types of network contacts. Using interviews with parents of childhood cancer patients (N = 80 parents), we examine (1) if parents rely on different types of network ties to access tailored information, resources or support; (2) differences in the nature or utility of information, resources, and support offered by different types of network contacts; and (3) the role of health-related professionals in brokering new network ties. Findings show that after a child's cancer diagnosis, parents received support from a broad portfolio of network members, which included preexisting network ties to friends and families as well as the formation of new ties to other cancer families and health-related professionals. Family, friends, and neighbors offered logistical support that aided balancing preexisting work and household responsibilities with new obligations. Parents formed new ties to other families coping with cancer for tailored health-related emotional and informational support. Health-related professionals served as network brokers, who fostered the development of new network ties and connected parents with supportive resources.

With the marked increase of the Latino population in the United States during the past 20 years, there has been growing interest in the social, cultural, and structural factors that may impede breast cancer screening among Latino women, especially among those subgroups that have been understudied. Acculturation and fatalism are central cultural constructs in these growing fields of research. However, there is great debate on the extent to which acculturation and fatalism affect breast cancer screening among Latinas relative to other social or structural factors or logistical barriers. Moreover, little theoretical work specifies or tests pathways between social, structural, and cultural determinants of screening. This study tests a theoretical model of social and structural (socioeconomic status and access to health care) and cultural factors (acculturation and fatalism) as correlates of mammography screening among Dominican Latinas, a group that has been understudied. The study expands prior work by examining other factors identified as potential impediments to mammography screening, specifically psychosocial (e.g., embarrassment, pain) and logistical (e.g., not knowing how to get a mammogram, cost) barriers. Interview-administered surveys were conducted with 318 Latinas from the Dominican Republic aged 40 years or older. Fatalistic beliefs were not associated with mammogram screening. Greater acculturation assessed as language use was associated with decreased screening. The strongest predictor of decreased screening was perceived barriers. Results highlight the importance of assessing various self-reported psychosocial and logistical barriers to screening. Possible avenues for screening interventions include intensifying public health campaigns and use of personalized messages to address barriers to screening. Results add to a limited body of research on Dominicans, who constitute the fifth largest Latino group in the United States.

Organic growers face unique challenges when raising sweet corn, and benefit from varieties that maintain high eating quality, germinate consistently, deter insect pests, and resist diseases. Genotype by environment rank changes can occur in the performance of cultivars grown on conventional and organic farms, yet few varieties have been bred specifically for organic systems. The objective of this experiment was to evaluate the changes made to open-pollinated sweet corn populations using recurrent selection and a participatory plant breeding (PPB) methodology. From 2008 to 2011, four cycles of two open-pollinated (OP) sweet corn populations were selected on a certified organic farm in Minnesota using a modified ear-to-row recurrent selection scheme. Selections were made in collaboration with an organic farmer, with selection criteria based on traits identified by the farmer. In 2012 and 2013, the population cycles were evaluated in a randomized complete block design in two certified organic locations in Wisconsin, with multiple replications in each environment. Significant linear trends were found among cycles of selection for quantitative and qualitative traits, suggesting the changes were due to recurrent selection and PPB methodology for these populations. However, further improvement is necessary to satisfy the requirements for a useful cultivar for organic growers.

BackgroundDepression can adversely affect employment status.AimsTo examine whether there is a relative advantage of cognitive therapy or antidepressant medication in improving employment status following treatment, using data from a previously reported trial.MethodRandom assignment to cognitive therapy (n = 48) or the selective serotonin reuptake inhibitor paroxetine (n = 93) for 4 months; treatment responders were followed for up to 24 months. Differential effects of treatment on employment status were examined.ResultsAt the end of 28 months, cognitive therapy led to higher rates of full-time employment (88.9%) than did antidepressant medication among treatment responders (70.8%), χ21 = 5.78, P = 0.02, odds ratio (OR) = 5.66, 95% CI 1.16–27.69. In the shorter-term, the main effect of treatment on employment status was not significant following acute treatment (χ21 = 1.74, P = 0.19, OR = 1.77, 95% CI 0.75–4.17); however, we observed a site×treatment interaction (χ21 = 6.87, P = 0.009) whereby cognitive therapy led to a higher rate of full-time employment at one site but not at the other.ConclusionsCognitive therapy may produce greater improvements in employment v. medication, particularly over the longer term.

Large diameter total hip replacements using polyethylene liners have been proposed due to low wear and oxidative stability observed in the latest generation of this material. Concerns exist with large diameter metal bearing surfaces and ceramic heads are generally expensive to manufacture. A ceramic chromium nitride (CrN) coating on a metal head may be an alternative bearing surface, maintaining low polyethylene wear and minimising cobalt release. Vitamin-E blended highly crosslinked polyethylene liners (52 mm diameter) paired with electron beam physical vapour deposited (EBPVD) CrN coated and uncoated CoCrMo heads were tested in a hip simulator. Under standard conditions no difference was observed in polyethylene wear rates (9.2 and 9.5 mm 3 /mc) but the coating prevented cobalt release. Alumina particles produced substantial damage on the uncoated heads but did not damage the coated heads. Further testing without abrasive particles increased the polyethylene wear (469 mm 3 /mc) and cobalt release (847 ppb/mc) in the uncoated bearings yet remained low in the coated components (13 mm 3 /mc wear, 17 ppb/mc cobalt). Additionally, the coating reduced the generation of nanometre sized polyethylene particles by an order of magnitude under all adverse test conditions. This CrN coating may have the potential to reduce clinical wear allowing for large diameter components.

Nephrogenic diabetes insipidus is a condition characterized by polyuria with dilute urine due to the inability of the principal cells of the renal collecting ducts to respond to antidiuretic hormone and concentrate urine. Nephrogenic diabetes insipidus can be drug induced, and several chemotherapeutic agents have been reported to cause it. Bendamustine is a traditional chemotherapeutic agent being studied for treatment for relapsed systemic AL amyloidosis. We report a case of a 59-year-old man with AL amyloidosis who developed partial nephrogenic diabetes insipidus after receiving bendamustine for treatment of AL amyloidosis. The nephrogenic diabetes insipidus responded well to sodium restriction, hydrochlorothiazide, and desmopressin treatment, allowing the patient to receive subsequent bendamustine cycles without polyuria. Nephrogenic diabetes insipidus resolved shortly after completion of bendamustine therapy.

Interest in conceptualizing, measuring, and applying social network analysis (SNA) in public health has grown tremendously in recent years. While these studies have broadened our understanding of the role that social networks play in health, there has been less research that has investigated the application of SNA to inform health-related interventions. This systematic review aimed to capture the current applied use of SNA in the development, dissemination, implementation, and sustainability of health behavior interventions for adults. We identified 52 articles published between 2004 and 2016. A wide variety of study settings were identified, most commonly in the US context and most often related to sexual health and HIV prevention. We found that 38% of articles explicitly applied SNA to inform some aspect of interventions. Use of SNA to inform intervention development (as opposed to dissemination, implementation, or sustainability) was most common. The majority of articles represented in this review (n = 39) were quantitative studies, and 13 articles included a qualitative component. Partial networks were most represented across articles, and over 100 different networks measures were assessed. The most commonly described measures were network density, size, and degree centrality. Finally, very few articles defined SNA and not all articles using SNA were theoretically-informed. Given the nascent and heterogeneous state of the literature in this area, this is an important time for the field to coalesce on terminology, measures, and theoretical frameworks. We highlight areas for researchers to advance work on the application of SNA in the design, dissemination, implementation and sustainability of behavioral interventions.

There is strong interest in implementation science to address the gap between research and practice in public health. Research on the sustainability of evidence-based interventions has been growing rapidly. Sustainability has been defined as the continued use of program components at sufficient intensity for the sustained achievement of desirable program goals and population outcomes. This understudied area has been identified as one of the most significant translational research problems. Adding to this challenge is uncertainty regarding the extent to which intervention adaptation and evolution are necessary to address the needs of populations that differ from those in which interventions were originally tested or implemented. This review critically examines and discusses conceptual and methodological issues in studying sustainability, summarizes the multilevel factors that have been found to influence the sustainability of interventions in a range of public health and health care settings, and highlights key areas for future research.

This chapter covers antidepressants that fall into the class of serotonin (5-HT) and norepinephrine (NE) reuptake inhibitors. That is, they bind to the 5-HT and NE transporters with varying levels of potency and binding affinity ratios. Unlike the selective serotonin (5-HT) reuptake inhibitors (SSRIs), most of these antidepressants have an ascending rather than a flat dose–response curve. The chapter provides a brief review of the chemistry, pharmacology, metabolism, safety and adverse effects, clinical use, and therapeutic indications of each antidepressant. Venlafaxine, a phenylethylamine, is a relatively weak 5-HT and weaker NE uptake inhibitor with a 30-fold difference in binding of the two transporters. Therefore, the drug has a clear dose progression, with low doses predominantly binding to the 5-HT transporter and more binding of the NE transporter as the dose ascends. Venlafaxine is metabolized to the active metabolite O-desmethylvenlafaxine (ODV; desvenlafaxine) by CYP2D6, and it therefore is subject to significant inter-individual variation in blood levels and response dependent on variations in CYP2D6 metabolism. The half-life of venlafaxine is short at about 5 h, with the ODV metabolite being 12 h. Both parent compound and metabolite have low protein binding and neither inhibit CYP enzymes. Therefore, both venlafaxine and desvenlafaxine are potential options if drug–drug interactions are a concern, although venlafaxine may be subject to drug–drug interactions with CYP2D6 inhibitors. At low doses, the adverse effect profile is similar to an SSRI with nausea, diarrhea, fatigue or somnolence, and sexual side effects, while venlafaxine at higher doses can produce mild increases in blood pressure, diaphoresis, tachycardia, tremors, and anxiety. A disadvantage of venlafaxine relative to the SSRIs is the potential for dose-dependent blood pressure elevation, most likely due to the NE reuptake inhibition caused by higher doses; however, this adverse effect is infrequently observed at doses below 225 mg per day. Venlafaxine also has a number of potential advantages over the SSRIs, including an ascending dose–antidepressant response curve, with possibly greater overall efficacy at higher doses. Venlafaxine is approved for MDD as well as generalized anxiety disorder, social anxiety disorder, and panic disorder. Desvenlafaxine is the primary metabolite of venlafaxine, and it is also a relatively low-potency 5-HT and NE uptake inhibitor. Like venlafaxine it has a favorable drug–drug interaction profile. It is subject to CYP3A4 metabolism, and it is therefore vulnerable to enzyme inhibition or induction. However, the primary metabolic pathway is direct conjugation. It is approved in the narrow dose range of 50–100 mg per day. Duloxetine is a more potent 5-HT and NE reuptake inhibitor with a more balanced profile of binding at about 10:1 for 5HT and NE transporter binding. It is also a moderate inhibitor of CYP2D6, so that modest dose reductions and careful monitoring will be needed when prescribing duloxetine in combination with drugs that are preferentially metabolized by CYP2D6. The most common side effects identified in clinical trials are nausea, dry mouth, dizziness, constipation, insomnia, asthenia, and hypertension, consistent with its mechanisms of action. Clinical trials to date have demonstrated rates of response and remission in patients with major depression that are comparable to other marketed antidepressants reviewed in this book. In addition to approval for MDD, duloxetine is approved for diabetic peripheral neuropathic pain, fibromyalgia, and musculoskeletal pain. Milnacipran is marketed as an antidepressant in some countries, but not in the USA. It is approved in the USA and some other countries as a treatment for fibromyalgia. It has few pharmacokinetic and pharmacodynamic interactions with other drugs. Milnacipran has a half-life of about 10 h and therefore needs to be administered twice per day. It is metabolized by CYP3A4, but the major pathway for clearance is direct conjugation and renal elimination. As with other drugs in this class, dysuria is a common, troublesome, and dose-dependent adverse effect (occurring in up to 7% of patients). High-dose milnacipran has been reported to cause blood pressure and pulse elevations. Levomilnacipran is the levorotary enantiomer of milnacipran, and it is pharmacologically very similar to the racemic compound, although the side effects may be milder within the approved dosing range. As with other NE uptake inhibitors, it may increase blood pressure and pulse, although it appears to do so less than some other medications. All medications in the class can cause serotonin syndrome when combined with MAOIs.