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Background. Healthy volunteer wild-type influenza challenge models offer a unique opportunity to evaluate multiple aspects of this important virus. Such studies have not been performed in the United States in more than a decade, limiting our capability to investigate this virus and develop countermeasures. We have completed the first ever wild-type influenza A challenge study under an Investigational New Drug application (IND). This dose-finding study will lead to further development of this model both for A(H1N1)pdm09 and other strains of influenza. Methods. Volunteers were admitted to an isolation unit at the National Institutes of Health Clinical Center for a minimum of 9 days. A reverse genetics, cell-based, Good Manufacturing Practice (GMP)–produced, wild-type A (H1N1)pdm09 virus was administered intranasally. Escalating doses were given until a dose was reached that produced disease in a minimum of 60% of volunteers. Results. An optimal dose of 107 tissue culture infectious dose 50 was reached that caused mild to moderate influenza disease in 69% of individuals with mean viral shedding for 4–5 days and significant rises in convalescent influenza antibody titers. Viral shedding preceded symptoms by 12–24 hours and terminated 2–3 days prior to symptom resolution, indicating that individuals may be infectious before symptom development. As expected, nasal congestion and rhinorrhea were most common, but interestingly, fever was observed in only 10% of individuals. Conclusions. This study represents the first healthy volunteer influenza challenge model using a GMP-produced wild-type virus under an IND. This unique clinical research program will facilitate future studies of influenza pathogenesis, animal model validation, and the rapid, efficient, and cost-effective evaluation of efficacy of novel vaccines and therapeutics.

ObjectiveThis systematic review evaluated the measurement properties of current self-report physical activity questionnaires (SRPAQs) completed within healthy adult populations.DesignTwo reviewers independently searched seven electronic databases and hand searched for articles investigating measurement properties of a SRPAQ evaluating physical activity over the previous 6 months. Articles published from 1 May 2001 to 4 December 2014 were systematically screened and eligible studies were not limited to English language sources. Articles investigating specific race, gender or socioeconomic populations were excluded.Results10 studies investigating 10 SRPAQs were included. The methodological quality of the included studies was evaluated using COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) and ranged from ‘poor’ to ‘good’. The Recent Physical Activity Questionnaire, International Physical Activity Questionnaires and Physical Activity Assessment Tool demonstrated good/excellent test–retest reliability (intra-class coefficient (ICC)=0.76, p<0.0001; r=0.627–0.91; r=0.618, p<0.001, respectively), but variable criterion validity (r=0.67, p<0.0001; r=−0.02–0.43; r=0.392, p<0.01, respectively). The single-item measure showed significant criterion validity against an accelerometer (for moderate to vigorous physical activity (MVPA) k=0.23, 95% CI 0.05 to 0.41; and physical activity ≥10 min bouts 0.39 (95% CI 0.14 to 0.64). Construct validity of the six-point scale and Human Activity Profile varied significantly with age, marital status and presence of comorbidities (p<0.05, <0.01, <0.000 and p<0.05, <0.05, <0.000, respectively). The 1 week Godlin-Shephard recall demonstrated ‘moderate’ validity with the gold standard measure of accelerometry (r=0.43).ConclusionsInconclusive evidence exists. Further investigation of criterion validity of the short-form International Physical Activity Questionnaire is required, as it demonstrated excellent test–retest reliability.PROSPERO numberCRD42012002484.

To investigate the effect of the time spent on quarantine on distress, anxiety, depression, and somatization of chronic disease patients during the COVID-19 quarantine in Greece and the differences in these parameters between healthy individuals and chronic disease patients. The sample consisted of 943 healthy individuals and 163 patients (respiratory, autoimmune, cardiovascular, endocrine, patients with other diseases, and patients with more than one disease) completing sociodemographic assessments as well as the 4-Dimensional Symptom Questionnaire (4DSQ) during March 30, 2020 to May 3, 2020. Pearson's correlation was used to search for the association between time spent on quarantine and the 4DSQ subscales (distress, anxiety, depression, and somatization). Independent sample T-test and Glass's Δ were used for differences between healthy individuals and chronic disease patients in these subscales, an analysis also carried out between healthy individuals and all patient subgroups. No statistically significant correlations were noted between the 4DSQ subscales and the quarantine duration, both for the patient and the healthy individuals' group. Chronic disease patients had significantly higher levels of distress (p = 0.001, Δ = 0.28) and somatization (p = 0.000, Δ = 0.47), but not there were no significant differences in anxiety (p = 0.098, Δ = 0.14) and depression (p = 0.052, Δ = 0.19). Concerning head-to-head comparisons between the healthy individuals' group and each patient group, significantly higher scores in distress were found only for patients with respiratory diseases (p = 0.028, Δ = 0.42). Regarding somatization, significantly higher scores were noted for the healthy individuals' group compared with patients with autoimmune diseases (p = 0.010, Δ = 0.62), respiratory diseases (p = 0.027, Δ = 0.42), other diseases (p = 0.003, Δ = 0.55), and more than one disease (p = 0.012, Δ = 0.60). No statistically significant differences were found in anxiety and depression. The results of this study indicate that interventional programs for chronic disease patients during quarantine should focus on distress and somatization, not on anxiety and depression. Respiratory patients might have more supportive care needs compared with patients with other diseases.

Background Effective education for health volunteers plays a pivotal role, considering their contribution to promoting community health. Given the aging population and its associated challenges, it is crucial to develop effective and low-cost programs to enhance the knowledge and attitudes of health volunteers and improve the quality of life for older adults. Aim This study investigated the effect of active aging education on the knowledge and attitudes of health volunteers. Methods This study was conducted from November 2023 to February 2024 on 86 health volunteers at comprehensive health centers in Shiraz City. The volunteers were randomly divided into two groups: intervention and control. The data collection tool was a questionnaire. Following the pre-test, the content was delivered in six training sessions. Post-tests were administered to both groups immediately after the intervention and two months later. The data were analyzed using SPSS version 23, employing frequency analysis, the Chi-square test, the t-test, and repeated measures tests. A significance level of 0.05 was considered. Results The findings revealed that health volunteers' knowledge significantly increased after the educational intervention. There was a statistically significant difference in the mean knowledge score in the intervention group at the three-time points (before, immediately after, and two months after the intervention) based on the repeated measures test ( P  < 0.001). Additionally, the attitude of health volunteers improved significantly following the educational intervention ( P  < 0.001). Conclusion Trained volunteers can effectively convey critical health and cultural messages, make informed decisions, and enhance the local population's access to primary healthcare. The results of this study demonstrate that the active aging educational intervention improved the knowledge and attitudes of health volunteers. Therefore, leveraging the potential of health volunteers to teach active aging can improve the health and well-being of the elderly population.

BackgroundsHealthy volunteers play a key role in clinical trials and it is crucial to develop recruitment strategies that capitalise on their motivations and maximise their participation. The COVID-19 pandemic has shown the importance of finding motivated healthy volunteers for the development of new vaccines. Public registers represent a promising way to promote the participation of healthy volunteers in the research field, but their adoption is still limited. The current study aimed to explore the motivations of healthy volunteers to enrol in an Italian public register for clinical trials during the COVID-19 pandemic and their attitude toward participating in a phase 1 COVID-19 vaccine clinical trial. The impacts of different enrolling interview modalities (in person, by phone, by mail) on motivation, understanding of information and trust in researchers were also investigated.MethodsAn online survey investigating experience with COVID-19, motivations to enrol, trust in researchers, political and healthcare authorities and pharmacological companies was presented to people applying as healthy volunteers in the public register for clinical trials at Phase 1 Unit Research Centre of ASST Monza, Italy, and considering to participate in a COVID-19 vaccine clinical trial. Data were collected in June 2021.ResultsAltruistic motivations were the main driver for enrolling in the public register, while self-interested motivations were secondary. No gender differences were found. As for enrolling modalities, no differences emerged between in-person and interviews for motivation to enrol, understanding of information and trust in researchers. Email modality led to significantly lower volunteers’ satisfaction and understanding of information but similar trust in research.ConclusionsThis study supports the validity of different interview modalities (in person and by phone) for the enrolment of healthy volunteers for clinical trials and highlights the positive role of public registers for the recruitment procedures.

N -methyl-D-aspartate glutamate receptor (NMDA-R) antagonists produce schizophrenia-like positive and negative symptoms in healthy human subjects. Preclinical research suggests that NMDA-R antagonists interfere with the function of gamma-aminobutyric acid (GABA) neurons and alter the brain oscillations. These changes have been hypothesized to contribute to psychosis. In this investigation, we evaluated the hypothesis that the NMDA-R antagonist ketamine produces alterations in cortical functional connectivity during rest that are related to symptoms. We administered ketamine to a primary sample of 22 subjects and to an additional, partially overlapping, sample of 12 subjects. Symptoms before and after the experimental session were rated with the Positive and Negative Syndrome Scale (PANSS). In the primary sample, functional connectivity was measured via functional magnetic resonance imaging almost immediately after infusion began. In the additional sample, this assessment was repeated after 45 min of continuous ketamine infusion. Global, enhanced functional connectivity was observed at both timepoints, and this hyperconnectivity was related to symptoms in a region-specific manner. This study supports the hypothesis that pathological increases in resting brain functional connectivity contribute to the emergence of positive and negative symptoms associated with schizophrenia.

Background Chronic diseases are known to detrimentally impact an individual’s quality of life (QOL) and well-being. Therefore, this study aims to evaluate the QOL and overall well-being among both healthy individuals and those with diverse primary diagnoses. Methods This is a cross-sectional study and data collection took place from May 2022 to May 2023. Information regarding healthy participants was gathered from healthcare workers without any comorbidities. Data for non-healthy participants were collected from individuals diagnosed with various conditions across four specialist clinics: nephrology, oncology, psychiatry, and cardiology. All participants completed the Significant Quality of Life Measures (SigQOLM), a comprehensive assessment tool consisting of 69 items that evaluate 18 domains of QOL and well-being. Results The study included a total of 452 participants, with 284 (62.8%) classified as healthy. Among the non-healthy participants, 41 (9.1%) had end-stage renal diseases (ESRD), 48 (10.6%) were diagnosed with cancer, 40 (8.8%) had depressive disorder, and the remaining had heart disease (8.6%). Statistical analysis revealed significant differences ( p  < 0.001) between healthy and non-healthy participants in both overall SigQOLM scores and across all 18 domains of SigQOLM. Conclusion Generally, healthy participants also experienced excellent QOL and well-being. However, disparities in both QOL and overall well-being were evident among patients with various diagnoses. These findings provide valuable insights for medical practitioners and policy makers by enabling them to tailor interventions to enhance the QOL and well-being of their patients.

Abstract Background The development of vaccines and therapeutics has relied on healthy volunteer influenza challenge studies. A validated human infection model with wild-type A(H1N1)pdm09 was reported previously. Our objective was to characterize a wild-type influenza A/Bethesda/MM1/H3N2 challenge virus in healthy volunteers. Methods Participants received a single dose of a cell-based, reverse-genetics, Good Manufacturing Practices–produced wild-type influenza A(H3N2)2011 virus intranasally and were isolated at the National Institutes of Health Clinical Center for ≥9 days. Dose escalation was performed from 104 to 107 TCID50 (50% tissue culture infectious dose). Viral shedding and clinical disease were evaluated daily. Results Of 37 participants challenged, 16 (43%) had viral shedding and 27 (73%) developed symptoms, with 12 (32%) participants experiencing mild to moderate influenza disease (MMID), defined as shedding and symptoms. Only participants receiving 106 and 107 TCID50 experienced MMID at 44% and 40%, respectively. Symptom severity peaked on day 3, whereas most viral shedding occurred 1–2 days after challenge. Only 10 (29%) participants had a ≥4-fold rise in hemagglutination inhibition antibody titer after challenge. Conclusions The A/Bethesda/MM1/H3N2 challenge virus safely induced MMID in healthy volunteers, but caused less MMID than the A(H1N1)pdm09 challenge virus even at the highest dose. There was less detection of shedding though the incidence of symptoms was similar to A(H1N1)pdm09. Fewer serum anti-hemagglutinin (HA) antibody responses with less MMID indicate that preexisting immunity factors other than anti-HA antibody may limit shedding in healthy volunteers. This A/Bethesda/MM1/H3N2 challenge virus can be utilized in future studies to further explore pathogenesis and immunity and to evaluate vaccine candidates. Clinical Trials Registration NCT02594189 We successfully characterized an influenza A/Bethesda/MM1/H3N2 challenge virus and show that it can be administered safely to induce mild to moderate influenza disease.

Psychological distress is prevalent in students and can predispose to psychiatric disorders. Recent findings indicate that distress might be linked to impaired cognitive performance in students. Experimental findings in healthy participants suggest that placebo interventions can improve cognition. However, whether non-deceptive (i.e., open-label, OLP) placebos can enhance cognitive function and emotional well-being is unclear. Using a randomized-controlled design we demonstrate a positive impact of OLP on subjective well-being (i.e., stress, fatigue, and confusion) after a 21-day OLP application in healthy students during midterm exams. OLP did not improve test performance, but, within the OLP group, test performance was positively correlated with measures of general belief in the benefit of medication. These results show that OLP can counteract negative effects of acute stress on psychological well-being and might improve cognitive performance if supported by positive treatment expectations. Additionally, our findings in healthy volunteers warrant further investigation in exploring the potential of OLP in reducing stress-related psychological effects in patients. The trial was preregistered at the German Clinical Trials Register on December 20, 2017 (DRKS00013557).

Background Parenteral artesunate is the first-line therapy for severe malaria. Artesunate, in its current formulation, must be prepared immediately before administration by first dissolving in sodium bicarbonate solution and then diluting in saline. A novel solvent for rapid and stable single step reconstitution of artesunate was recently developed showing improved solubility and stability. This study aimed to compare the safety and pharmacokinetic properties of the currently available and newly developed parenteral formulation of artesunate in healthy Thai volunteers. Methods This was an open-label, randomized, 4 periods, 4-treatments, 24-sequence, single-dose, cross-over study in 72 male and female healthy Thai volunteers. Frequent pharmacokinetic samples were collected in all volunteers at each dose occasion. Observed concentration–time profiles were analysed with a non-compartmental approach followed by a bioequivalence evaluation. Results Both intramuscular and intravenous administrations of the new parenteral formulation of artesunate were safe and well-tolerated, with no additional safety signals compared to the currently used formulation. The pharmacokinetic properties of artesunate and its active metabolite, dihydroartemisinin, were well-characterized, and showed rapid conversion of artesunate into dihydroartemisinin. Intramuscular administration of the newly formulated artesunate resulted in almost complete bioavailability of dihydroartemisinin. The pharmacokinetic properties were similar between the old and new formulation. Conclusions The new and more easily prepared formulation of artesunate was safe and well-tolerated, with similar pharmacokinetic properties compared to the currently used formulation. Dihydroartemisinin, the active metabolite responsible for the majority of the anti-malarial effect, showed equivalent exposure after both intravenous and intramuscular administration of artesunate, suggesting that both routes of administration should generate comparable therapeutic effects. Trial registration : The study was registered to clinicaltrials.gov (#TCTR20170907002).