Use and outcomes of contemporary combination antiretroviral therapy in people living with HIV

The introduction of antiretroviral therapy (ART) has transformed HIV from a fatal illness into a manageable, chronic condition. As there is currently no cure for HIV, ART, typically including three antiretroviral drugs (ARVs), is a lifelong commitment, and there are concerns around long-term toxicities. Integrase strand transfer inhibitors (INSTIs) are one of the latest ARV classes to be approved and treatment guidelines uniformly recommend them as first-line treatment for people living with HIV (PLWH). However, limited data exist on long-term clinical outcomes associated with contemporary ART, including INSTIs, and contemporary ART regimens, including two-drug regimens. In this thesis, I use data from the International Cohort Consortium of Infectious Diseases (RESPOND) to assess the use and outcomes of contemporary ART, with a focus on two-drug regimens and INSTIs, including the association between INSTI use and incident cancer. I also assess temporal trends in cancer incidence across different ART-eras. RESPOND is a collaboration of 17 cohort studies, including approximately 30,000 PLWH from across Europe and Australia. I found that uptake of dolutegravir compared to cobicistat-boosted elvitegravir or raltegravir has increased over time. INSTI discontinuation was low overall and mainly due to toxicity in the first 6 months of use. Discontinuation was higher for raltegravir, primarily due to treatment simplification, whilst discontinuation due to nervous system toxicities was highest on dolutegravir. Virological and immunological outcomes were similar between those on two-drug and three-drug regimens. Additionally, after accounting for baseline characteristics, there was a similar incidence of severe clinical events on both regimen types. When assessing cancer trends from 2006-2019, I found that whilst the age-standardised incidence of AIDS-related and infection-related cancers has decreased over time, body mass index-related cancers have increased, whilst non-AIDS-related cancers and smoking-related cancers remained constant. Overall, there was no association between cancer risk and INSTI exposure

The “Deeming Rule”: The FDA’s Destruction of the Vaping Industry

The FDA has recently passed sweeping regulations, which classifies and then regulates electronic cigarettes as “tobacco products” in the same manner as traditional cigarettes. Though the agency reasons that unknowing adults and children may easily turn to e-cigarettes without fully understanding the potential health effects, there is a lack of conclusive evidence in this field to justify such a comprehensive regulatory scheme. Through the far-reaching “Deeming Rule,” e-cigarette manufacturers are forced to comply with financially burdensome and time-consuming requirements before taking most of their products to market. The channels by which the FDA proposes manufacturers and retailers gain permission from the agency to sell their products on the market in the first place threaten to put them out of business completely. Courts read a cost-benefit analysis into their interpretation of the Administrative Procedure Act, and the FDA has failed to conduct a fair and full cost-benefit analysis before the passage of the new Deeming Rule. By violating the Administrative Procedure Act, consumers are unable to turn to a safe alternative to traditional cigarettes, and manufacturers are unfairly put out of business. Instead of heavily regulating an entire industry with such limited research to support it, the FDA should step out and cease regulation until adequate research has been conducted. If the agency is unwilling to completely delay the regulation, weakening the burdensome approval process and stringent requirements until more research is completed would allow companies to still supply the market while protecting consumers

Leveraging Positive Psychology to Support First Year College Students: The ROCK Goes to College

Each spring, students in the Master of Applied Positive Psychology (MAPP) program at the University of Pennsylvania complete service learning projects in partnership with nonprofits from around the world. For this specific project, MAPP students collaborated with the ROCK Center for Youth Development, a nonprofit currently providing positive education and programming to middle and high school students in Midland, Michigan. The ROCK is about to begin offering its services to local universities as well and requested assistance adapting an existing workshop to better address the social and cognitive impediments to student success in college. Our literature review indicated that college students commonly struggle with stress, time management issues, and belonging uncertainty, and all three are correlated with poor outcomes across a variety of academic and well-being metrics. In contrast, social connectedness and sense of purpose are overwhelming linked to positive outcomes at college. Based on this research, our application plan for the ROCK recommends that they retain the sections of their existing workshop covering stress management and building positive relationships while adding three evidence-based activities detailed herein. The first activity mitigates belonging uncertainty, the second assesses and develops time management skills, and the third cultivates students’ sense of academic purpose

Clinicians have several therapeutic relationships and patients only one: the effect on their assessments of relationships

Objectives Little attention has been given to the common assessment problem that clinicians assess outcomes of several patients and may rate them in comparison to one another, whereas patients assess only their own outcomes without any comparison. We explored empirically whether this would lead to a greater variability of clinician ratings as compared to patient ratings. Methods Data from two independent samples in which clinicians and patients, using consistent instruments, rated their therapeutic relationships. We present descriptive statistics of variability and intracluster correlation coefficients. Results The Helping Alliance Scale was completed at baseline and follow‐up by 20 clinicians and 103 patients in an observational study and by 88 clinicians and 431 patients in a trial. Patients tended to rate their relationship 5–10% more highly than their clinicians, but with 50–100% more variability. Intraclinician Helping Alliance Scale ratings were more correlated than those by patients (intracluster correlation coefficients 0.3–0.7 vs. 0.0–0.2). Conclusion Contrary to our assumption, clinicians' ratings of therapeutic relationships were in both samples less variable than those of their patients. When clinicians rate outcomes of several patients, a cluster effect of ratings may have to be considered in the design and analysis

The Effects of Test Mode and Contiguity of Material on Geometry Test Scores, Cognitive Load, and Self-Efficacy

In recent years, the development and usage of computer-based tests for educational assessment has grown. The computer-based tests are typically derived from paper-based tests, with the assumption the tests being administered in different modes are equivalent. Studies examining this test mode effect have mainly focused on the test scores, but few have examined other factors important to test performance. The current study examines the test mode effect for geometry test problems, while also putting in perspective the factors of self-efficacy and cognitive load as both are significant components in performance. The results suggest test scores and cognitive load for geometry problems are similar across the test modes, however learners’ self-efficacy significantly decreases when performing the geometry test problems in computer-based test mode. The findings provide insight into the test mode literature and give direction for future lines of research. Keywords: Computer-based testing, Self-efficacy, Test mode effect, Geometry, Cognitive load DOI: 10.7176/JEP/11-12-03 Publication date: April 30th 202

A pilot randomized controlled trial comparing the efficacy of problem-solving therapy to enhanced treatment as usual for reducing high blood pressure

High blood pressure is a highly prevalent and modifiable risk factor for cardiovascular disease that has substantially contributed to disability, morbidity, mortality, health disparities and economic burden in the United States. Although relatively easy to diagnosis and inexpensive to treat, controlling high blood pressure, thereby reducing its sequelae, remains difficult, particularly for Black individuals, due to a host of psychosocial, biological, and environmental factors. There is a need to identify an efficacious stress-reduction intervention for lowering uncontrolled high blood pressure that can be effectively translated into practice. In the current pilot study, the preliminary efficacy and feasibility of Problem-Solving Therapy (PST), compared to telephone-delivered enhanced treatment as usual (ETAU), were evaluated on measures of blood pressure, social problem solving ability, medication adherence, perceived stress, depression, and health-related quality of life (HRQOL) at baseline, posttreatment, and three-month follow up. Recruitment from outpatient medical clinics yielded a sample of 14 participants, predominantly Black and female, with uncontrolled high blood pressure, who were randomly assigned to PST or ETAU. Mean differences between conditions from baseline to posttreatment assessments were examined using a series of intent-to-treat (N = 12) t-tests and repeated measures ANOVAs, none of which were statistically significant. Inspection of effect sizes and clinical significance indicated a trend toward efficacy of PST to improve medication adherence [F(1, 10) = 2.54, p = 0.14, ηp2 = 0.20] and physical HRQOL [F(1,10) = 2.54, p = 0.14, ηp2 = 0.20], as well as slightly more frequent clinically meaningful changes in systolic blood pressure, mental HRQOL, and depression for those who received PST. In terms of feasibility, about 13% of 108 recruited patients were enrolled, the rate of attrition was below 20% for treatment initiators, retention of treatment initiators was 100% for PST (nPST = 6) and 83.3% (nETAU = 5) for ETAU at posttreatment, and about 80% of participants rated the treatments as credible and effective. Three-month follow up assessments were too few to conduct meaningful analyses. Although a trend toward efficacy of PST was indicated, challenges in recruitment limited sample size, and, therefore, the aforementioned preliminary results must be interpreted with caution.Ph.D., Psychology -- Drexel University, 201

Preschool children’s coping responses and outcomes in the vaccination context: child and caregiver transactional and longitudinal relationships

This article, based on 2 companion studies, presents an in-depth analysis of preschoolers coping with vaccination pain. Study 1 used an autoregressive cross-lagged path model to investigate the dynamic and reciprocal relationships between young children’s coping responses (how they cope with pain and distress) and coping outcomes (pain behaviors) at the preschool vaccination. Expanding on this analysis, study 2 then modeled preschool coping responses and outcomes using both caregiver and child variables from the child’s 12-month vaccination (n 5 548), preschool vaccination (n 5 302), and a preschool psychological assessment (n 5 172). Summarizing over the 5 path models and post hoc analyses over the 2 studies, novel transactional and longitudinal pathways predicting preschooler coping responses and outcomes were elucidated. Our research has provided empirical support for the need to differentiate between coping responses and coping outcomes: 2 different, yet interrelated, components of “coping.”Among our key findings, the results suggest that a preschooler’s ability to cope is a powerful tool to reduce pain-related distress but must be maintained throughout the appointment; caregiver behavior and poorer pain regulation from the 12-month vaccination appointment predicted forward to preschool coping responses and/or outcomes; robust concurrent relationships exist between caregiver behaviors and both child coping responses and outcomes, and finally, caregiver behaviors during vaccinations are not only critical to both child pain coping responses and outcomes in the short- and long-term but also show relationships to broader child cognitive abilities as well

Integrase Strand Transfer Inhibitor Use and Cancer Incidence in a Large Cohort Setting

BACKGROUND Limited data exist examining the association between incident cancer and cumulative integrase inhibitor (INSTI) exposure. METHODS Participants were followed from baseline (latest of local cohort enrollment or January 1, 2012) until the earliest of first cancer, final follow-up, or December 31, 2019. Negative binomial regression was used to assess associations between cancer incidence and time-updated cumulative INSTI exposure, lagged by 6 months. RESULTS Of 29 340 individuals, 74% were male, 24% were antiretroviral treatment (ART)-naive, and median baseline age was 44 years (interquartile range [IQR], 36-51). Overall, 13 950 (48%) individuals started an INSTI during follow-up. During 160 657 person-years of follow-up ([PYFU] median 6.2; IQR, 3.9-7.5), there were 1078 cancers (incidence rate [IR] 6.7/1000 PYFU; 95% confidence interval [CI], 6.3-7.1). The commonest cancers were non-Hodgkin lymphoma (n = 113), lung cancer (112), Kaposi's sarcoma (106), and anal cancer (103). After adjusting for potential confounders, there was no association between cancer risk and INSTI exposure (≤6 months vs no exposure IR ratio: 1.15 [95% CI, 0.89-1.49], >6-12 months; 0.97 [95% CI, 0.71-1.32], >12-24 months; 0.84 [95% CI, 0.64-1.11], >24-36 months; 1.10 [95% CI, 0.82-1.47], >36 months; 0.90 [95% CI, 0.65-1.26] [P = .60]). In ART-naive participants, cancer incidence decreased with increasing INSTI exposure, mainly driven by a decreasing incidence of acquired immune deficiency syndrome cancers; however, there was no association between INSTI exposure and cancer for those ART-experienced (interaction P < .0001). CONCLUSIONS Cancer incidence in each INSTI exposure group was similar, despite relatively wide CIs, providing reassuring early findings that increasing INSTI exposure is unlikely to be associated with an increased cancer risk, although longer follow-up is needed to confirm this finding