The health benefits of 150 min a week of moderate-to-vigorous-intensity physical activity (MVPA) in older adults, as currently recommended, are well established, but the suggested dose in older ...adults is often not reached.
We aimed to determine whether a lower dose of MVPA was effective in reducing mortality, in participants older than 60 years.
The PubMed and Embase databases were searched from inception to February 2015. Only prospective cohorts were included. Risk ratios of death were established into four doses based on weekly Metabolic Equivalent of Task (MET)-minutes, defined as inactive (reference), low (1-499), medium (500-999) or high (≥1000). Data were pooled and analysed through a random effects model using comprehensive meta-analysis software.
Of the 835 reports screened, nine cohort studies remained, totalling 122 417 participants, with a mean follow-up of 9.8±2.7 years and 18 122 reported deaths (14.8%). A low dose of MVPA resulted in a 22% reduction in mortality risk (RR=0.78 (95% CI 0.71 to 0.87) p<0.0001). MVPA beyond this threshold brought further benefits, reaching a 28% reduction in all-cause mortality in older adults who followed the current recommendations (RR=0.72 (95% CI 0.65 to 0.80) p<0.0001) and a 35% reduction beyond 1000 MET-min per week (RR=0.65 (95% CI 0.61 to 0.70) p<0.0001).
A dose of MVPA below current recommendations reduced mortality by 22% in older adults. A further increase in physical activity dose improved these benefits in a linear fashion. Older adults should be encouraged to include even low doses of MVPA in their daily lives.
Ebola epidemics constitute serious public health emergencies. Multiple vaccines are under development to prevent these epidemics and avoid the associated morbidity and mortality. Assessing the ...potential impact of these vaccines on morbidity and mortality of Ebola is essential for devising prevention strategies. A mean-field compartmental stochastic model was developed for this purpose and validated by simulating the 2014 Sierra Leone epidemic. We assessed the impacts of prophylactic vaccination of healthcare workers (HCW) both alone and in combination with the vaccination of the general population (entire susceptible population other than HCW). The model simulated 8,706 (95% confidence intervals CI: 478-21,942) cases and 3,575 (95%CI: 179-9,031) deaths in Sierra Leone, in line with WHO-reported statistics for the 2014 epidemic (8,704 cases and 3,587 deaths). Relative to this base case, the model then estimated that prophylactic vaccination of only 10% of HCW will avert 12% (95% CI: 6%-14%) of overall cases and deaths, while vaccination of 30% of HCW will avert 34% of overall cases (95% CI: 30%-64%) and deaths (95% CI: 30%-65%). Prophylactic vaccination of 1% and 5% of the general population in addition to vaccinating 30% of HCW was estimated to result in reduction in cases by 44% (95% CI: 39%-61%) and 72% (95% CI: 68%-84%) respectively, and deaths by 45% (95% CI: 40%-61%) and 74% (95% CI: 70%-85%) respectively. Prophylactic vaccination of even small proportions of HCW is estimated to significantly reduce incidence of Ebola and associated mortality. The effect is greatly enhanced by the additional vaccination even of small percentages of the general population. These findings could be used to inform the planning of prevention strategies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Decisions about prevention of and response to Ebola outbreaks require an understanding of the macroeconomic implications of these interventions. Prophylactic vaccines hold promise to mitigate the ...negative economic impacts of infectious disease outbreaks. The objective of this study was to evaluate the relationship between outbreak size and economic impact among countries with recorded Ebola outbreaks and to quantify the hypothetical benefits of prophylactic Ebola vaccination interventions in these outbreaks.
The synthetic control method was used to estimate the causal impacts of Ebola outbreaks on per capita gross domestic product (GDP) of five countries in sub-Saharan Africa that have previously experienced Ebola outbreaks between 2000 and 2016, where no vaccines were deployed. Using illustrative assumptions about vaccine coverage, efficacy, and protective immunity, the potential economic benefits of prophylactic Ebola vaccination were estimated using the number of cases in an outbreak as a key indicator.
The impact of Ebola outbreaks on the macroeconomy of the selected countries led to a decline in GDP of up to 36%, which was greatest in the third year after the onset of each outbreak and increased exponentially with the size of outbreak (i.e., number of reported cases). Over three years, the aggregate loss estimated for Sierra Leone from its 2014-2016 outbreak is estimated at 16.1 billion International$. Prophylactic vaccination could have prevented up to 89% of an outbreak's negative impact on GDP, reducing the outbreak's impact to as little as 1.6% of GDP lost.
This study supports the case that macroeconomic returns are associated with prophylactic Ebola vaccination. Our findings support recommendations for prophylactic Ebola vaccination as a core component of prevention and response measures for global health security.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Current serological tests for HIV screening and confirmation of infection present challenges to the adoption of HIV vaccines. The detection of vaccine-induced HIV-1 antibodies in the absence of HIV-1 ...infection, referred to as vaccine-induced seropositivity/seroreactivity, confounds the interpretation of test results, causing misclassification of HIV-1 status with potential affiliated stigmatization. For HIV vaccines to be widely adopted with high community confidence and uptake, tests that are agnostic to vaccination status (i.e., only positive for true HIV-1 infection) of tested individuals are needed. Successful development and deployment of such tests will require HIV vaccine developers to work in concert with diagnostic developers. Such tests will need to match today's high-performance standards (accuracy, cost-effectiveness, simplicity) for use in both vaccinated and unvaccinated populations, especially in low- and middle-income countries with high HIV burden. Herein, we discuss the challenges and strategies for developing modified serological HIV tests for concurrent deployment with HIV vaccines.
•Heterologous vaccine regimens provide a new approach for disease prevention.•Anticipating licensure of such vaccines, perceived benefits and challenges for acceptance were assessed.•Respondents ...rated improved efficacy and duration of protection, compared to established vaccines, as expected benefits.•Logistics, protocol adherence, and compliance were considered key areas for roll-out.•A clear communication strategy, adjusted to different stakeholders, was considered critical for smooth implementation.
Heterologous vaccine regimens deliver antigens through different vaccine components or vector types at sequential time points. Clinical development shows promising results and several candidates may be progressing to licensure in the coming years. This study aimed at exploring future acceptance and uptake of such regimens (also called heterologous prime-boost) and to identify implementation-associated benefits and challenges. Survey tools were developed based on findings from a previous literature search shared with the study team, and exploratory interviews with global stakeholders. An online survey and key informant interviews in six countries were conducted with stakeholders at national and sub-national level, including policy-makers, regulators and implementers. The interview guide and the online survey covered: (a) awareness of, and knowledge about, heterologous vaccine regimens; (b) rating of regimen-associated perceived benefits and challenges; (c) anticipation of possible challenges in relation to four hypothetical introduction scenarios; (d) potential acceptance benefits and challenges at the policy, health facility and recipient level. Sixty-two interviews were conducted at national level. The online survey was completed by 50 participants. Across the four introduction scenarios, respondents considered the highest potential for the introduction of heterologous regimens for immunoprophylaxis was among adolescents/adults for diseases against which no vaccines are currently available. Most reservations were related to logistics, record keeping, and recipient compliance. Adding a new heterologous vaccine regimen to the routine immunization calendar for children was considered feasible if it could generate an increased and longer-term immune response. Introduction in preparation of or following a disease outbreak was considered less favourably, with respondents stressing the difficulty of logistics in emergency situations, and the potential lag in the onset of protection. The recent approval of the first heterologous vaccine regimen for the prevention of Ebola Virus Disease will soon bring new light to the topic.
•Existing Ebola interventions are implemented after an outbreak is declared. Preventive vaccination may provide a complementary option to help protect against unpredictable outbreaks.•Our novel ...individual-based Ebola transmission model accounted for important disease transmission factors, such as human movement and contact heterogeneity.•Targeted preventive vaccination reduced Ebola cases, hospitalizations, and deaths.•Preventive vaccination flattened epidemic curves, protecting healthcare systems and providing more time to implement additional interventions.
Nonpharmaceutical interventions (NPI) and ring vaccination (i.e., vaccination that primarily targets contacts and contacts of contacts of Ebola cases) are currently used to reduce the spread of Ebola during outbreaks. Because these measures are typically initiated after an outbreak is declared, they are limited by real-time implementation challenges. Preventive vaccination may provide a complementary option to help protect communities against unpredictable outbreaks. This study aimed to assess the impact of preventive vaccination strategies when implemented in conjunction with NPI and ring vaccination.
A spatial-explicit, individual-based model (IBM) that accounts for heterogeneity of human contact, human movement, and timing of interventions was built to represent Ebola transmission in the Democratic Republic of the Congo. Simulated preventive vaccination strategies targeted healthcare workers (HCW), frontline workers (FW), and the general population (GP) with varying levels of coverage (lower coverage: 30% of HCW/FW, 5% of GP; higher coverage: 60% of HCW/FW, 10% of GP) and efficacy (lower efficacy: 60%; higher efficacy: 90%).
The IBM estimated that the addition of preventive vaccination for HCW reduced cases, hospitalizations, and deaths by ∼11 % to ∼25 % compared with NPI + ring vaccination alone. Including HCW and FW in the preventive vaccination campaign yielded ∼14 % to ∼38 % improvements in epidemic outcomes. Further including the GP yielded the greatest improvements, with ∼21 % to ∼52 % reductions in epidemic outcomes compared with NPI + ring vaccination alone. In a scenario without ring vaccination, preventive vaccination reduced cases, hospitalizations, and deaths by ∼28 % to ∼59 % compared with NPI alone. In all scenarios, preventive vaccination reduced Ebola transmission particularly during the initial phases of the epidemic, resulting in flatter epidemic curves.
The IBM showed that preventive vaccination may reduce Ebola cases, hospitalizations, and deaths, thus safeguarding the healthcare system and providing more time to implement additional interventions during an outbreak.
Protection by preventive Ebola vaccines has been demonstrated in clinical trials, but a complete picture of real-world effectiveness is lacking. Our previous study modeling the impact of preventively ...vaccinating healthcare workers (HCW) alone or with a proportion of the general population (GP) estimated significant reductions in incidence and mortality. The model assumed 100% vaccine efficacy, which is unlikely in the real world. We enhanced this model to account for lower vaccine efficacy and to factor in reduced infectiousness and lower case fatality rate in vaccinated individuals with breakthrough infections. The previous model was enhanced to still permit a risk, although lower, for vaccinated individuals to become infected. The enhanced model, calibrated with data from epidemics in Sierra Leone (SL) and North Kivu, Democratic Republic of the Congo, helped evaluate the impact of preventive Ebola vaccination in different scenarios based on different vaccine efficacy rates (90% and 30% reductions in infection risk in the base and conservative scenarios, respectively; additionally, both scenarios with 50% reductions in infectiousness and mortality) and vaccination coverage among HCWs (30%, 90%) and GP (0%, 5%, and 10%). The base scenario estimated that, depending upon the proportions of vaccinated HCWs and GP, 33-85% of cases and 34-87% of deaths during the 2014 SL epidemic and 42-89% of cases and 41-89% of deaths during the 2018 North Kivu epidemic would be averted versus no vaccination. Corresponding estimates for the conservative scenario were: 23-74% of cases and 23-77% of deaths averted during the SL epidemic and 31-80% of both cases and deaths averted during the North Kivu epidemic. Preventive vaccination targeting HCW alone or with GP may significantly reduce the size and mortality of an EVD outbreak, even with modest efficacy and coverage. Vaccines may also confer additional benefits through reduced infectiousness and mortality in breakthrough cases.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
ABSTRACT
Introduction
The importance of exercise electrocardiogram (ECG) is still controversial in the prevention of cardiovascular events among sportsmen and sportswomen. The aim of this study was ...to assess the relevance of exercise ECG as a screening tool to prevent cardiovascular events when any cardiovascular disease (CVD) risk factors are present.
Methods
The study included leisure time asymptomatic sportsmen and sportswomen over age 35 evaluated from 2011 to 2016 at the University Hospital of Saint‐Etienne (France). Major adverse cardiovascular events (MACE) and atrial fibrillation were collected at 3 years.
Results
Of the cohort of 2457 sportsmen and sportswomen (mean age 50.2 ± 9.4 years), 50 (2%) had a high‐risk SCORE2. A total of 256 exercise ECGs (10%) were defined as positive, most of them due to silent myocardial ischemia (SMI) (n = 196; 8%). These 196 SMI cases led to 33 coronary angiograms (1%), which revealed 23 significant coronary stenoses requiring revascularization. In multivariate logistic regression analysis, having at least two CVD risk factors was independently associated with (1) positive exercise ECG (OR = 1.80 95% CI: 1.29–2.52, p = 0.0006), with (2) suspected SMI (OR = 2.57 95% CI: 1.10–6.02, p = 0.0304), with (3) confirmed SMI (OR = 8.20 95% CI: 3.46–19.46, p < 0.0001) and with (4) cardiovascular events (MACE or atrial fibrillation) (OR = 6.95 95% CI: 3.49–13.81, p < 0.0001) at 3 years (median).
Conclusions
The study supports the European recommendations for the use of exercise ECG in evaluation of asymptomatic leisure time sportsmen over age 35. Having at least two CVD risk factors was the best predictor for presence of coronary artery stenosis that may increase the risk for adverse events.
Trial Registration: ClinicalTrials.gov Identifier: NCT06024863
Background
Despite advances in human immunodeficiency virus (HIV) prevention methods, such as the advent of pre-exposure prophylaxis (PrEP), the number of people with newly acquired HIV remains high, ...particularly in at-risk groups. A prophylactic HIV vaccine could contribute to reduced disease prevalence and future transmission and address limitations of existing options, such as suboptimal long-term adherence to PrEPs.
Methods
This qualitative study aimed to capture perceptions towards and acceptance of prophylactic HIV vaccination in three adult populations in the United States: the general population, ‘at-risk’ individuals (e.g. men who have sex with men, transgender individuals, gender-nonconforming individuals, and individuals in a sexual relationship with a person living with HIV), and parents/caregivers of children aged 9–17 years. Interviews were conducted with 55 participants to explore key drivers and barriers to HIV vaccine uptake, and a conceptual model was developed.
Results
The sample was diverse; participants were 51% female, aged 20–57 years (mean 37 years), 33% with high school diploma as highest education level, and identified as White (42%), Black or African American (35%), of Hispanic, Latino, or Spanish origin (22%), or other races/ethnicities (8%) groupings are not mutually exclusive. Perceptions were influenced by individual, interpersonal, community, institutional, and structural factors. Overall, 98% of participants thought vaccination would be beneficial in preventing HIV. Key considerations/barriers included perceived susceptibility, i.e. whether participants felt there was a risk of contracting HIV (discussed by 90%); the clinical profile of the vaccine (e.g. the adverse effect profile 98%, and vaccine efficacy 85%, cost 73% and administration schedule 88%); and concerns around potential vaccine-induced seropositivity (VISP; 62%). Stigma was not found to be an important barrier, with a general view that vaccination status was personal. Participants in the ‘at-risk’ group were the most likely to accept an HIV vaccine (70%). Unique concerns in the subgroups included how a potential vaccine’s clinical profile compared with PrEP, voiced by those receiving/considering PrEP, and considerations of children’s views on the topic, voiced by parents/caregivers.
Conclusions
Understanding these factors could help develop HIV vaccine research strategies and contribute toward public health messaging to support future HIV vaccination programs.
Vaccine-induced seroreactivity/positivity (VISR/P) poses a significant and common challenge to HIV vaccine implementation, as up to 95% of vaccine recipients may be misclassified as having HIV ...infection by current HIV screening and confirmatory serological assays. We investigated whether internal HIV proteins could be used to overcome VISR and discovered a set of 4 antigens (gp41 endodomain, p31 integrase, p17 matrix protein, and Nef) that are recognized by antibodies produced in individuals with HIV infection but not in vaccinated individuals. When evaluated in a multiplex double-antigen bridging ELISA, this antigen combination had specificities of 98.1% prevaccination and 97.1% postvaccination, demonstrating the assay is minimally impacted by vaccine-induced antibodies. The sensitivity was 98.5%, further increasing to 99.7% when p24 antigen testing was included. Results were similar across HIV-1 clades. Although more technical advancements will be desired, this research provides the groundwork for the development of new fourth-generation HIV tests unaffected by VISR.
While the detection of HIV infection is accomplished by several methods, the most common are serological tests that detect host antibodies produced in response to viral infection. However, the use of current serological tests may present a significant challenge to the adoption of an HIV vaccine in the future because the antibodies to HIV antigens detected in currently available tests also tend to be included as antigens in the HIV vaccines in development. The use of these serological tests may thus result in the misclassification of vaccinated HIV-negative individuals, which can have potential for significant harms for individuals and could prevent the widespread adoption and implementation of HIV vaccines. Our study aimed to identify and evaluate target antigens for inclusion in new serological tests that can be used to identify HIV infections without interference from vaccine-induced antibodies but also fit within existing platforms for HIV diagnostics.
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