Population-Level Effects of Human Papillomavirus Vaccination Programs on Infections with Nonvaccine Genotypes

We analyzed human papillomavirus (HPV) prevalences during prevaccination and postvaccination periods to consider possible changes in nonvaccine HPV genotypes after introduction of vaccines that confer protection against 2 high-risk types, HPV16 and HPV18. Our meta-analysis included 9 studies with data for 13,886 girls and women ≤19 years of age and 23,340 women 20–24 years of age. We found evidence of cross-protection for HPV31 among the younger age group after vaccine introduction but little evidence for reductions of HPV33 and HPV45. For the group this same age group, we also found slight increases in 2 nonvaccine high-risk HPV types (HPV39 and HPV52) and in 2 possible high-risk types (HPV53 and HPV73). However, results between age groups and vaccines used were inconsistent, and the increases had possible alternative explanations; consequently, these data provided no clear evidence for type replacement. Continued monitoring of these HPV genotypes is important

Clustering of Unhealthy Behaviors in the Aerobics Center Longitudinal Study

Background Clustering of unhealthy behaviors has been reported in previous studies; however the link with all-cause mortality and differences between those with and without chronic disease requires further investigation. Objectives To observe the clustering effects of unhealthy diet, fitness, smoking, and excessive alcohol consumption in adults with and without chronic disease and to assess all-cause mortality risk according to the clustering of unhealthy behaviors. Methods Participants were 13,621 adults (aged 20–84) from the Aerobics Center Longitudinal Study. Four health behaviors were observed (diet, fitness, smoking, and drinking). Baseline characteristics of the study population and bivariate relations between pairs of the health behaviors were evaluated separately for those with and without chronic disease using cross-tabulation and a chi-square test. The odds of partaking in unhealthy behaviors were also calculated. Latent class analysis (LCA) was used to assess clustering. Cox regression was used to assess the relationship between the behaviors and mortality. Results The four health behaviors were related to each other. LCA results suggested that two classes existed. Participants in class 1 had a higher probability of partaking in each of the four unhealthy behaviors than participants in class 2. No differences in health behavior clustering were found between participants with and without chronic disease. Mortality risk increased relative to the number of unhealthy behaviors participants engaged in. Conclusion Unhealthy behaviors cluster together irrespective of chronic disease status. Such findings suggest that multi-behavioral intervention strategies can be similar in those with and without chronic disease

Safety and immunogenicity of a self-amplifying RNA vaccine against COVID-19: COVAC1, a phase I, dose-ranging trial

Background: Lipid nanoparticle (LNP) encapsulated self-amplifying RNA (saRNA) is a novel technology formulated as a low dose vaccine against COVID-19. Methods: A phase I first-in-human dose-ranging trial of a saRNA COVID-19 vaccine candidate LNP-nCoVsaRNA, was conducted at Imperial Clinical Research Facility, and participating centres in London, UK, between 19th June to 28th October 2020. Participants received two intramuscular (IM) injections of LNP-nCoVsaRNA at six different dose levels, 0.1-10.0μg, given four weeks apart. An open-label dose escalation was followed by a dose evaluation. Solicited adverse events (AEs) were collected for one week from enrolment, with follow-up at regular intervals (1-8 weeks). The binding and neutralisation capacity of anti-SARS-CoV-2 antibody raised in participant sera was measured by means of an anti-Spike (S) IgG ELISA, immunoblot, SARS-CoV-2 pseudoneutralisation and wild type neutralisation assays. (The trial is registered: ISRCTN17072692, EudraCT 2020-001646-20). Findings: 192 healthy individuals with no history or serological evidence of COVID-19, aged 18-45 years were enrolled. The vaccine was well tolerated with no serious adverse events related to vaccination. Seroconversion at week six whether measured by ELISA or immunoblot was related to dose (both p<0.001), ranging from 8% (3/39; 0.1μg) to 61% (14/23; 10.0μg) in ELISA and 46% (18/39; 0.3μg) to 87% (20/23; 5.0μg and 10.0μg) in a post-hoc immunoblot assay. Geometric mean (GM) anti-S IgG concentrations ranged from 74 (95% CI, 45-119) at 0.1μg to 1023 (468-2236) ng/mL at 5.0μg (p<0.001) and was not higher at 10.0μg. Neutralisation of SARS-CoV-2 by participant sera was measurable in 15% (6/39; 0.1μg) to 48% (11/23; 5.0μg) depending on dose level received. Interpretation: Encapsulated saRNA is safe for clinical development, is immunogenic at low dose levels but failed to induce 100% seroconversion. Modifications to optimise humoral responses are required to realise its potential as an effective vaccine against SARS-CoV-2. Funding: This study was co-funded by grants and gifts from the Medical Research Council UKRI (MC_PC_19076), and the National Institute Health Research/Vaccine Task Force, Partners of Citadel and Citadel Securities, Sir Joseph Hotung Charitable Settlement, Jon Moulton Charity Trust, Pierre Andurand, Restore the Earth

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

Incidental findings in UK healthy volunteers screened for a COVID-19 vaccine trial.

The safety of novel therapeutics and vaccines are typically assessed in early phase clinical trials involving "healthy volunteers." Abnormalities in such individuals can be difficult to interpret and may indicate previously unrecognized medical conditions. The frequency of incidental findings (IFs) in healthy volunteers who attend for clinical trial screening is unclear. To assess this, we retrospectively analyzed data for 1838 "healthy volunteers" screened for enrolment in a UK multicenter, phase I/II severe acute respiratory syndrome-coronavirus 2 (SARS-COV-2) vaccine trial. Participants were predominantly White (89.7%, 1640/1828) with a median age of 34 years (interquartile range [IQR] = 27-44). There were 27.7% of participants (510/1838) who had at least one IF detected. The likelihood of identifying evidence of a potential, new blood-borne virus infection was low (1 in 238 participants) compared with identification of an elevated alanine transaminase (ALT; 1 in 17 participants). A large proportion of participants described social habits that could impact negatively on their health; 21% consumed alcohol in excess, 10% were current smokers, 11% described recreational drug use, and only 48% had body weight in the ideal range. Our data demonstrate that screening prior to enrollment in early phase clinical trials identifies a range of IFs, which should inform discussion during the consent process. Greater clarity is needed to ensure an appropriate balance is struck between early identification of medical problems and avoidance of exclusion of volunteers due to spurious or physiological abnormalities. Debate should inform the role of the trial physician in highlighting and advising about unhealthy social habits

Does practicing hatha yoga satisfy recommendations for intensity of physical activity which improves and maintains health and cardiovascular fitness?

Background: Little is known about the metabolic and heart rate responses to a typical hatha yoga session. The purposes of this study were 1) to determine whether a typical yoga practice using various postures meets the current recommendations for levels of physical activity required to improve and maintain health and cardiovascular fitness; 2) to determine the reliability of metabolic costs of yoga across sessions; 3) to compare the metabolic costs of yoga practice to those of treadmill walking. Methods: In this observational study, 20 intermediate-to-advanced level yoga practitioners, age 31.4 ± 8.3 years, performed an exercise routine inside a human respiratory chamber (indirect calorimeter) while wearing heart rate monitors. The exercise routine consisted of 30 minutes of sitting, 56 minutes of beginner-level hatha yoga administered by video, and 10 minutes of treadmill walking at 3.2 and 4.8 kph each. Measures were mean oxygen consumption (VO2), heart rate (HR), percentage predicted maximal heart rate (%MHR), metabolic equivalents (METs), and energy expenditure (kcal). Seven subjects repeated the protocol so that measurement reliability could be established. Results: Mean values across the entire yoga session for VO2, HR, %MHR, METs, and energy/min were 0.6 L/kg/min; 93.2 beats/min; 49.4%; 2.5; and 3.2 kcal/min; respectively. Results of the ICCs (2,1) for mean values across the entire yoga session for kcal, METs, and %MHR were 0.979 and 0.973, and 0.865, respectively. Conclusion: Metabolic costs of yoga averaged across the entire session represent low levels of physical activity, are similar to walking on a treadmill at 3.2 kph, and do not meet recommendations for levels of physical activity for improving or maintaining health or cardiovascular fitness. Yoga practice incorporating sun salutation postures exceeding the minimum bout of 10 minutes may contribute some portion of sufficiently intense physical activity to improve cardio-respiratory fitness in unfit or sedentary individuals. The measurement of energy expenditure across yoga sessions is highly reliable

Health enhancing strength training in nonagenarians (STRONG): rationale, design and methods

<p>Abstract</p> <p>Background</p> <p>The Health Enhancing Strength Training in Nonagenarians (STRONG) is a randomised control trial to assess the effectiveness of an aerobic and strength training program for improving muscle strength, functional capacity and quality of life in nonagenarians.</p> <p>Methods</p> <p>Sixty (51 women) nonagenarians (age range: 90–102 years) who live in a geriatric nursing home will be randomly assigned to either a usual care (control) group (n = 30) or an intervention (training) group (n = 30). Participants allocated in the usual care group will receive general physical activity guidelines and participants allocated in the intervention group will also enrol in three weekly non-consecutive individualized training sessions (~45–50 min each) during 8 weeks. The exercise program will consist of muscular strength [with a special focus on leg press at 30% (start of the program) to 70% 1 repetition maximum (end)] and aerobic exercises (cycle-ergometry during 3–5 to 15 minutes at 12–14 points in the rate of perceived exertion scale).</p> <p>Results</p> <p>Results from STRONG will help to better understand the potential of regular physical activity for improving the well-being of the oldest population groups.</p> <p>Conclusion</p> <p>The increase in life expectancy together with the dramatic decrease in birth rates in industrialized countries calls the attention to health care systems and public health policymakers to focus attention on promoting healthy lifestyle in the highest sector of the population pyramid. Our study attempts to improve functional capacity and QOL of nonagenarians by implementing an individualised aerobic and strength training program in a geriatric residential care. Results from STRONG will help to better understand the potential of regular physical activity for improving the well being even in persons aged 90 years or over.</p> <p>Trail Registration</p> <p>ClinicalTrials.gov ID: NCT00848978</p

Required muscle mass for preventing lifestyle-related diseases in Japanese women

Research articl

Quantitative EEG findings in patients with acute, brief depression combined with other fluctuating psychiatric symptoms: a controlled study from an acute psychiatric department

<p>Abstract</p> <p>Background</p> <p>Patients with brief depressive episodes and concurrent rapidly fluctuating psychiatric symptoms do not fit current diagnostic criteria and they can be difficult to diagnose and treat in an acute psychiatric setting. We wanted to study whether these patients had signs of more epileptic or organic brain dysfunction than patients with depression without additional symptomatology.</p> <p>Methods</p> <p>Sixteen acutely admitted patients diagnosed with a brief depressive episode as well as another concurrent psychiatric diagnosis were included. Sixteen patients with major depression served as controls. Three electroencephalographic studies (EEG) were visually interpreted and the background activity was also analysed with quantitative electroencephalography (QEEG).</p> <p>Results</p> <p>The group with brief depression and concurrent symptoms had multiple abnormal features in their standard EEG compared to patients with major depression, but they did not show significantly more epileptiform activity. They also had significantly higher temporal QEEG delta amplitude and interhemispheric temporal delta asymmetry.</p> <p>Conclusion</p> <p>Organic brain dysfunction may be involved in the pathogenesis of patients with brief depressive episodes mixed with rapidly fluctuating psychiatric symptoms. This subgroup of depressed patients should be investigated further in order to clarify the pathophysiology and to establish the optimal evaluation scheme and treatment in an acute psychiatric setting.</p