Evolution of the HALT-C Trial: pegylated interferon as maintenance therapy for chronic hepatitis C in previous interferon nonresponders

The Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial was designed to determine whether maintenance interferon therapy could slow disease progression in patients who had failed to eradicate hepatitis C virus (HCV) during prior interferon treatment (nonresponders). Ten clinical sites, a virological testing center, and a data coordinating center (DCC) were selected to collaborate in the design and implementation of the final protocol. Eligible patients had been treated previously with interferon for at least 12 weeks, with or without another antiviral, ribavirin, but still had persistent viremia. Because patients had received a variety of prior treatments, and as a perceived benefit of enrollment, we incorporated a Lead-in period of treatment with long-acting pegylated interferon alfa-2a plus ribavirin into the study design, a combination believed to be more effective but not approved by the Food and Drug Administration at the Trial's inception. If patients failed to achieve clearance of virus from the blood after 20 weeks of this Lead-in therapy, they were entered into the main trial at week 24 and randomized to receive either a lower dose of pegylated interferon weekly alone or no further therapy for an additional 3 1/2 years. The original protocol was amended later in three respects to improve enrollment and to adapt to Food and Drug Administration approval of the Lead-in therapy, including allowing patients to proceed directly to the randomized part of the study if treatment resembling the Lead-in had been completed. The protocol changes enhanced enrollment while upholding the original goals of the study and its integrity.     

Someone to talk to: the association of mentorship and cyberbullying with suicidality among US high school students

Objective

Suicide is the second-leading cause of death in youth. We tested whether having a mentoring relationship associated with lower risks for suicidality, particularly among youth at higher risk due to cyberbullying.

Methods

This study pooled the 2017 Youth Risk Behavior Survey (YRBS) data from five jurisdictions that asked students if there was at least one teacher or other adult in their school that they could talk with, if they have a problem (mentorship). Students self-reported cyberbullying exposure and suicidality in the past 12 months. Odds of suicidal ideation, planning, and attempts were estimated using multivariable weighted logistic regression in overall and sex-stratified stepwise models. Interactions between mentorship and cyberbullying were also tested.

Results

Of the 25,527 student respondents, 87% reported having a mentoring relationship. Mentoring relationships were associated with lower odds of suicidal ideation (aOR, 0.44; 95% CI 0.33–0.57), planning (aOR, 0.59; 95% CI 0.41–0.85), and suicide attempts (aOR, 0.42; 95% CI 0.31–0.56). Stratified analyses showed a significant interaction between cyberbullying and mentorship with suicidal attempts among males, and a near-significant association between cyberbullying and mentorship with suicidal thoughts among females. Compared to male students with no cyberbullying and no mentorship, odds of attempting suicide were lower for males with no cyberbullying and mentorship (aOR, 0.55, 95% CI 0.32–0.92), higher for males with cyberbullying and no mentorship (aOR, 7.78, 95% CI 3.47–17.47), but not significantly different for males with cyberbullying and mentoring relationships (aOR, 1.49, 95% CI 0.86–2.48). Similarly, compared with females with no cyberbullying and no mentorship, odds of having suicidal thoughts were lower for females with no cyberbullying and mentorship (aOR, 0.40, 95% CI 0.28–0.57), and higher for females with cyberbullying and no mentorship (aOR, 2.54, 95% CI 1.59–4.07).

Conclusion

School-based mentoring may mitigate risk of suicidality among adolescents and limit the toxic effects of cyberbullying.

     

A Qualitative Exploration of the Views of Policymakers and Policy Advisors on the Impact of Mental Health Stigma on the Development and Implementation of Mental Health Policy in Singapore

Few studies have examined the views of policy makers regarding the impact of mental health stigma on the development and implementation of mental health policies. This study aimed to address this knowledge gap by exploring policymakers’ and policy advisors’ perspectives regarding the impact of mental health stigma on the development and implementation of mental health programmes, strategies, and services in Singapore. In all 13 participants were recruited for the study comprising practicing policymakers, senior staff of organisations involved in implementing the various mental health programmes, and policy advisors. Data was collected through semi-structured interviews, which were transcribed verbatim and analysed using reflexive thematic analysis. Data analysis revealed three superordinate themes related to challenges experienced by the policymakers/advisors when dealing with mental health policy and implementation of programmes. These themes included stigma as a barrier to mental health treatment, community-level barriers to mental health recovery, and mental health being a neglected need. Policymakers/advisors demonstrated an in-depth and nuanced understanding of the barriers (consequent to stigma) to mental healthcare delivery and access. Policymakers/advisors were able to associate the themes related to the stigma towards mental illness with help-seeking barriers based on personal experiences, knowledge, and insight gained through the implementation of mental health programmes and initiatives.

     

Pseudooutbreak of Candida versatilitis fungemia in a microbiology laboratory

Candida versatilitis was isolated from 10 blood cultures that had been supplemented with olive oil to promote the growth of Malassezia spp., and from the stock olive oil bottle in the laboratory. This unusual non-pathogenic yeast isolate was readily identified by DNA sequencing methodology. This report also points out that care must be taken to ensure the sterility of supplements added to blood culture media.     

Transplant allograft vasculopathy: Role of multimodality imaging in surveillance and diagnosis

Cardiac allograft vasculopathy (CAV) is a challenging long-term complication of cardiac transplantation and remains a leading long-term cause of graft failure, re-transplantation, and death. CAV is an inflammatory vasculopathy distinct from traditional atherosclerotic coronary artery disease. Historically, the surveillance and diagnosis of CAV has been dependent on serial invasive coronary angiography with intravascular imaging. Although commonly practiced, angiography is not without significant limitations. Technological advances have provided sophisticated imaging techniques for CAV assessment. It is now possible to assess the vascular lumen, vessel wall characteristics, absolute blood flow, perfusion reserve, myocardial contractile function, and myocardial metabolism and injury in a noninvasive, expeditious manner with little risk. The current article will review key imaging modalities for the surveillance, diagnosis, and prognosis of CAV and discuss coronary physiology of transplanted hearts with emphasis on the clinical implications for provocative and vasodilator stress testing.     

Construct damage and loosening around glenoid implants: A longitudinal micro‐CT study of five cadaver specimens

The evolution of failure of bone and cement leading to loosening of glenoid components following shoulder arthroplasty is not well understood. The purpose of this study was to identify and visualize potential mechanisms of mechanical failure within cadavers, cemented with two types of components, and subject to cyclic loading. Five glenoid cadaver bones were implanted with either a three‐pegged polyethylene component, or prototype posteriorly augmented component which addresses posterior bone loss. Specimens were loaded by constant glenohumeral compression combined with cyclic anterior–posterior displacement of the humeral head relative to the glenoid. At six time points across 100,000 cycles, implant loosening micromotions were optically measured, and specimens were imaged by micro‐computed tomography. Scans were 3D registered and inspected for crack initiation and progression, and micro‐CT based time‐lapse movies were created. Cement cracking initiated at stress concentrations and progressed with additional cyclic loading. Failure planes within trabecular bone and the bone–cement interface were identified in four of the five specimens. Implant subsidence increased to greater than 1.0 mm in two specimens. Cemented glenoid structural failure can occur within the cement, along planes of trabecular bone, or at the bone cement interface. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1053–1060, 2016.