Pre-pandemic cognitive function and COVID-19 vaccine hesitancy: cohort study

BACKGROUND: Whereas several predictors of COVID-19 vaccine hesitancy have been reported, the role of cognitive function is largely unknown. Accordingly, our objective was to evaluate the association between scores from an array of cognitive function tests and self-reported vaccine hesitancy after the announcement of the successful testing of the first COVID-19 vaccine (Oxford University/AstraZeneca). METHODS: We used individual-level data from a pandemic-focused study ('COVID Survey'), a prospective cohort study nested within United Kingdom Understanding Society ('Main Survey'). In the week immediately following the announcement of successful testing of the first efficacious inoculation (November/December 2020), data on vaccine intentionality were collected in 11,740 individuals (6702 women) aged 16-95 years. Pre-pandemic scores on general cognitive function, ascertained from a battery of six tests, were captured in 2011/12 wave of the Main Survey. Study members self-reported their intention to take up a vaccination in the COVID-19 Survey. RESULTS: Of the study sample, 17.2% (N = 1842) indicated they were hesitant about having the vaccine. After adjustment for age, sex, and ethnicity, study members with a lower baseline cognition score were markedly more likely to be vaccine hesitant (odds ratio per standard deviation lower score in cognition; 95% confidence interval: 1.76; 1.62, 1.90). Adjustment for mental and physical health plus household shielding status had no impact on these results, whereas controlling for educational attainment led to partial attenuation but the probability of hesitancy was still elevated (1.52; 1.37, 1.67). There was a linear association for vaccine hesitancy across the full range of cognition scores (p for trend: p < 0.0001). CONCLUSIONS: Erroneous social media reports might have complicated personal decision-making, leading to people with lower cognitive ability being vaccine-hesitant. With individuals with lower cognition also experiencing higher rates of COVID-19 in studies conducted prior to vaccine distribution, these new findings are suggestive of a potential additional disease burden

A comparative evaluation of the process of developing and implementing an emergency department HIV testing program

<p>Abstract</p> <p>Background</p> <p>The 2006 Centers for Disease Control and Prevention (CDC) HIV testing guidelines recommend screening for HIV infection in all healthcare settings, including the emergency department (ED). In urban areas with a high background prevalence of HIV, the ED has become an increasingly important site for identifying HIV infection. However, this public health policy has been operationalized using different models. We sought to describe the development and implementation of HIV testing programs in three EDs, assess factors shaping the adoption and evolution of specific program elements, and identify barriers and facilitators to testing.</p> <p>Methods</p> <p>We performed a qualitative evaluation using in-depth interviews with fifteen 'key informants' involved in the development and implementation of HIV testing in three urban EDs serving sizable racial/ethnic minority and socioeconomically disadvantaged populations. Testing program HIV prevalence ranged from 0.4% to 3.0%.</p> <p>Results</p> <p>Three testing models were identified, reflecting differences in the use of existing ED staff to offer and perform the test and disclose results. Factors influencing the adoption of a particular model included: whether program developers were ED providers, HIV providers, or both; whether programs took a targeted or non-targeted approach to patient selection; and the extent to which linkage to care was viewed as the responsibility of the ED. A common barrier was discomfort among ED providers about disclosing a positive HIV test result. Common facilitators were a commitment to underserved populations, the perception that testing was an opportunity to re-engage previously HIV-infected patients in care, and the support and resources offered by the medical setting for HIV-infected patients.</p> <p>Conclusions</p> <p>ED HIV testing is occurring under a range of models that emerge from local realities and are tailored to institutional strengths to optimize implementation and overcome provider barriers.</p

Purifying Selection in Deeply Conserved Human Enhancers Is More Consistent than in Coding Sequences

(c) 2014 De Silva et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Patient recruitment to a randomized clinical trial of behavioral therapy for chronic heart failure

BACKGROUND: Patient recruitment is one of the most difficult aspects of clinical trials, especially for research involving elderly subjects. In this paper, we describe our experience with patient recruitment for the behavioral intervention randomized trial, "The relaxation response intervention for chronic heart failure (RRCHF)." Particularly, we identify factors that, according to patient reports, motivated study participation. METHODS: The RRCHF was a three-armed, randomized controlled trial designed to evaluate the efficacy and cost of a 15-week relaxation response intervention on veterans with chronic heart failure. Patients from the Veterans Affairs (VA) Boston Healthcare System in the United States were recruited in the clinic and by telephone. Patients' reasons for rejecting the study participation were recorded during the screening. A qualitative sub-study in the trial consisted of telephone interviews of participating patients about their experiences in the study. The qualitative study included the first 57 patients who completed the intervention and/or the first follow-up outcome measures. Factors that distinguished patients who consented from those who refused study participation were identified using a t-test or a chi-square test. The reason for study participation was abstracted from the qualitative interview. RESULTS: We successfully consented 134 patients, slightly more than our target number, in 27 months. Ninety-five of the consented patients enrolled in the study. The enrollment rate among the patients approached was 18% through clinic and 6% through telephone recruitment. The most commonly cited reason for declining study participation given by patients recruited in the clinic was 'Lives Too Far Away'; for patients recruited by telephone it was 'Not Interested in the Study'. One factor that significantly distinguished patients who consented from patients who declined was the distance between their residence and the study site (t-test: p < .001). The most frequently reported reason for study participation was some benefit to the patient him/herself. Other reasons included helping others, being grateful to the VA, positive comments by trusted professionals, certain characteristics of the recruiter, and monetary compensation. CONCLUSIONS: The enrollment rate was low primarily because of travel considerations, but we were able to identify and highlight valuable information for planning recruitment for future similar studies

Effects of jump and balance training on knee kinematics and electromyography of female basketball athletes during a single limb drop landing: pre-post intervention study

<p>Abstract</p> <p>Background</p> <p>Some research studies have investigated the effects of anterior cruciate ligament (ACL) injury prevention programs on knee kinematics during landing tasks; however the results were different among the studies. Even though tibial rotation is usually observed at the time of ACL injury, the effects of training programs for knee kinematics in the horizontal plane have not yet been analyzed. The purpose of this study was to determine the effects of a jump and balance training program on knee kinematics including tibial rotation as well as on electromyography of the quadriceps and hamstrings in female athletes.</p> <p>Methods</p> <p>Eight female basketball athletes participated in the experiment. All subjects performed a single limb landing at three different times: the initial test, five weeks later, and one week after completing training. The jump and balance training program lasted for five weeks. Knee kinematics and simultaneous electromyography of the rectus femoris and Hamstrings before training were compared with those measured after completing the training program.</p> <p>Results</p> <p>After training, regarding the position of the knee at foot contact, the knee flexion angle for the Post-training trial (mean (SE): 24.4 (2.1) deg) was significantly larger than that for the Pre-training trial (19.3 (2.5) deg) (p < 0.01). The absolute change during landing in knee flexion for the Post-training trial (40.2 (1.9) deg) was significantly larger than that for the Pre-training trial (34.3 (2.5) deg) (p < 0.001). Tibial rotation and the knee varus/valgus angle were not significantly different after training. A significant increase was also found in the activity of the hamstrings 50 ms before foot contact (p < 0.05).</p> <p>Conclusions</p> <p>The jump and balance training program successfully increased knee flexion and hamstring activity of female athletes during landing, and has the possibility of producing partial effects to avoid the characteristic knee position observed in ACL injury, thereby preventing injury. However, the expected changes in frontal and transverse kinematics of the knee were not observed.</p

Adjuvant Sorafenib for Renal Cell Carcinoma at Intermediate or High Risk of Relapse: Results From the SORCE Randomized Phase III Intergroup Trial

PURPOSE: SORCE is an international, randomized, double-blind, three-arm trial of sorafenib after surgical excision of primary renal cell carcinoma (RCC) found to be at intermediate or high risk of recurrence. / PATIENTS AND METHODS: We randomly assigned participants (2:3:3) to 3 years of placebo (arm A), 1 year of sorafenib followed by 2 years of placebo (arm B), or 3 years of sorafenib (arm C). The initial sorafenib dose was 400 mg twice per day orally, amended to 400 mg daily. The primary outcome analysis, which was revised as a result of external results, was investigator-reported disease-free survival (DFS) comparing 3 years of sorafenib versus placebo. / RESULTS: Between July 2007 and April 2013, we randomly assigned 1,711 participants (430, 642, and 639 participants in arms A, B, and C, respectively). Median age was 58 years, 71% of patients were men, 84% had clear cell histology, 53% were at intermediate risk of recurrence, and 47% were at high risk of recurrence. We observed no differences in DFS or overall survival in all randomly assigned patients, patients with high risk of recurrence, or patients with clear cell RCC only. Median DFS was not reached for 3 years of sorafenib or for placebo (hazard ratio, 1.01; 95% CI, 0.83 to 1.23; P = .95). We observed nonproportional hazards; the restricted mean survival time (RMST) was 6.81 years for 3 years of sorafenib and 6.82 years for placebo (RMST difference, 0.01 year; 95% CI, −0.49 to 0.48 year; P = .99). Despite offering treatment adaptations, more than half of participants stopped treatment by 12 months. Grade 3 hand-foot skin reaction was reported in 24% of participants on sorafenib. / CONCLUSION: Sorafenib should not be used as adjuvant therapy for RCC. Active surveillance remains the standard of care for patients at intermediate or high risk of recurrence after nephrectomy and is the appropriate control of our current international adjuvant RCC trial, RAMPART

Informing the design of a national screening and treatment programme for chronic viral hepatitis in primary care: qualitative study of at-risk immigrant communities and healthcare professionals

n Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise statedThis paper presents independent research funded by the National Institute for Health Research (NIHR) under the Programme Grants for Applied Research programme (RP-PG-1209-10038).

RAMPART: A model for a regulatory-ready academic-led phase III trial in the adjuvant renal cell carcinoma setting

The development of therapeutics in oncology is a highly active research area for the pharmaceutical and biotechnology industries, but also has a strong academic base. Many new agents have been developed in recent years, most with specific biological targets. This has mandated the need to look at different ways to streamline the evaluation of new agents. One solution has been the development of adaptive trial designs that allow the evaluation of multiple agents, concentrating on the most promising agents while screening out those which are unlikely to benefit patients. Another way forward has been the growth of partnerships between academia and industry with the shared goal of designing and conducting high quality clinical trials which answer important clinical questions as efficiently as possible. The RAMPART trial (NCT03288532) brings together both of these processes in an attempt to improve outcomes for patients with locally advanced renal cell carcinoma (RCC), where no globally acceptable adjuvant strategy after nephrectomy currently exist. RAMPART is led by the MRC CTU at University College London (UCL), in collaboration with other international academic groups and industry. We aim to facilitate the use of data from RAMPART, (dependent on outcomes), for a future regulatory submission that will extend the license of the agents being investigated. We share our experience in order to lay the foundations for an effective trial design and conduct framework and to guide others who may be considering similar collaborations

RAMPART: A phase III multi-arm multi-stage trial of adjuvant checkpoint inhibitors in patients with resected primary renal cell carcinoma (RCC) at high or intermediate risk of relapse

Background: 20–60% of patients with initially locally advanced Renal Cell Carcinoma (RCC) develop metastatic disease despite optimal surgical excision. Adjuvant strategies have been tested in RCC including cytokines, radiotherapy, hormones and oral tyrosine-kinase inhibitors (TKIs), with limited success. The predominant global standard-of-care after nephrectomy remains active monitoring. Immune checkpoint inhibitors (ICIs) are effective in the treatment of metastatic RCC; RAMPART will investigate these agents in the adjuvant setting. // Methods/design: RAMPART is an international, UK-led trial investigating the addition of ICIs after nephrectomy in patients with resected locally advanced RCC. RAMPART is a multi-arm multi-stage (MAMS) platform trial, upon which additional research questions may be addressed over time. The target population is patients with histologically proven resected locally advanced RCC (clear cell and non-clear cell histological subtypes), with no residual macroscopic disease, who are at high or intermediate risk of relapse (Leibovich score 3–11). Patients with fully resected synchronous ipsilateral adrenal metastases are included. Participants are randomly assigned (3,2:2) to Arm A - active monitoring (no placebo) for one year, Arm B - durvalumab (PD-L1 inhibitor) 4-weekly for one year; or Arm C - combination therapy with durvalumab 4-weekly for one year plus two doses of tremelimumab (CTLA-4 inhibitor) at day 1 of the first two 4-weekly cycles. The co-primary outcomes are disease-free-survival (DFS) and overall survival (OS). Secondary outcomes include safety, metastasis-free survival, RCC specific survival, quality of life, and patient and clinician preferences. Tumour tissue, plasma and urine are collected for molecular analysis (TransRAMPART)

Detection of regulator genes and eQTLs in gene networks

Genetic differences between individuals associated to quantitative phenotypic traits, including disease states, are usually found in non-coding genomic regions. These genetic variants are often also associated to differences in expression levels of nearby genes (they are "expression quantitative trait loci" or eQTLs for short) and presumably play a gene regulatory role, affecting the status of molecular networks of interacting genes, proteins and metabolites. Computational systems biology approaches to reconstruct causal gene networks from large-scale omics data have therefore become essential to understand the structure of networks controlled by eQTLs together with other regulatory genes, and to generate detailed hypotheses about the molecular mechanisms that lead from genotype to phenotype. Here we review the main analytical methods and softwares to identify eQTLs and their associated genes, to reconstruct co-expression networks and modules, to reconstruct causal Bayesian gene and module networks, and to validate predicted networks in silico.Comment: minor revision with typos corrected; review article; 24 pages, 2 figure