Reported COVID-19 cases and associated mortality remain low in many sub-Saharan countries relative to global averages, but true impact is difficult to estimate given limitations around surveillance and mortality registration. In Lusaka, Zambia, burial registration and SARS-CoV-2 prevalence data during 2020 allow estimation of excess mortality and transmission. Relative to pre-pandemic patterns, we estimate age-dependent mortality increases, totalling 3212 excess deaths (95% CrI: 2104–4591), representing an 18.5% (95% CrI: 13.0–25.2%) increase relative to pre-pandemic levels. Using a dynamical model-based inferential framework, we find that these mortality patterns and SARS-CoV-2 prevalence data are in agreement with established COVID-19 severity estimates. Our results support hypotheses that COVID-19 impact in Lusaka during 2020 was consistent with COVID-19 epidemics elsewhere, without requiring exceptional explanations for low reported figures. For more equitable decision-making during future pandemics, barriers to ascertaining attributable mortality in low-income settings must be addressed and factored into discourse around reported impact differences. Estimates of COVID-19 impacts in many low- and middle-income countries remain very uncertain, with lack of high-quality data. Here, the authors reconstruct epidemic dynamics in Lusaka, Zambia and estimate that, when accounting for demographic patterns, the epidemic severity is comparable with global norms. As of April 24th 2023, confirmed global cases and deaths total 763,740,140 and 6,908,554 respectively2. This recorded impact has occurred despite the implementation of often stringent non-pharmaceutical interventions (NPIs) that frequently proved capable of controlling the epidemic while in place4. The subsequent development of numerous vaccines has also mitigated the potential impact of COVID-19 through decreasing the rates of severe disease in all known genetic variants8 and, to a lesser-extent, lowering transmission10.Following the emergence of COVID-19 in 2019, SARS-CoV-2 has spread across the world, causing the highest level of social and economic disruption due to an infectious disease in living memory2. Common hypotheses for a perceived low impact of COVID-19 in Africa include a younger population structure21, protection through exposure to pre-existing coronaviruses and other endemic diseases22, climate-related protections23, effective use of NPIs developed from disease-control expertise24, and genetic factors25. Some hypotheses (low population density and climate-associated outdoor lifestyles23) suggest a landscape of reduced disease transmission, whilst others assume high transmission with an associated implication of lower severity . However, it is widely acknowledged that recorded cases and deaths substantially underestimate the total number of SARS-CoV-2 infections and COVID-19 attributable deaths in many settings, corresponding with regional testing capacities30. This raises a fundamental question: once ascertainment biases are accounted for, to what extent are any of these alternative hypotheses needed? Understanding whether there was any so-called “Africa paradox”17 (the perception of lower COVID-19 impacts across many African countries compared with expectations) and if so, which, if any, of these hypotheses have justifiable basis can help ensure that the correct conclusions and lessons are learned from the pandemic in Africa.Relative to a global average of 8128.8 reported cases and 84.6 reported deaths per 100,000 (as of April 24th 2023), reported COVID-19 impact in Africa remains notably low 31, similar data from 2020, when the concept of low impact in Africa gained traction, remain exceptionally scarce. Of 134 high-quality large-scale community-based seroprevalence surveys from 2020, only five were from African countries32. Meanwhile, capturing trends in excess mortality (as a proxy for COVID-19 impact) in Africa during the pandemic is challenging due to a lack of robust civil and vital registration systems in many countries. In a recent global study of excess mortality, the World Health Organisation (WHO) found that 41 of 47 of the WHO’s Africa region countries had no data suitable for inclusion, resulting in a wide uncertainty interval for the Africa region33. Furthermore, when excess mortality trends can be well-quantified, it is critical to identify where changes in overall pandemic mortality have indirect  or direct causes 35. Further delineating differences in direct impact between regions due to spread  and severity  is then critical to understanding the need for and impact of control measures. IFR estimation in African countries has been challenging due to difficulties in the ascertainment of SARS-CoV-2 infections and COVID-19 deaths, resulting in estimates that vary substantially as different mortality estimates are used36.While an increasing amount of evidence, as of late 2022, suggests that SARS-CoV-2 has spread widely in many African countries37. These results represent a 92-fold increase in infection rates relative to reported case number within the country at the time37. Meanwhile, post-mortem sampling of the mortuary at the University Teaching Hospital (UTH), the largest morgue in Lusaka, the capital of Zambia, found 15% of deaths tested positive by PCR (CT < 40) during June-October 202027, proportions that were exceeded during subsequent pandemic waves in 202138. All-cause burial registrations were also collected from official registries39 by the post-mortem sampling team, dating from mid-2017 to mid-2021. These data provide opportunity for inference of SARS-CoV-2 spread and COVID-19 severity in Lusaka that can be compared with estimates from elsewhere.Research conducted in Zambia generated important insights into the true impact of the pandemic in Africa during 2020. In July 2020, during the first pandemic wave in Zambia, a population-based survey found that 2.1% (95% CI: 1.1–3.1%) of the population had evidence of previous infection based on an IgG serological assay while 7.6% (95% CI: 4.7–10.6%) tested positive for active infection by polymerase chain reaction (PCR)In this study we build upon this combined research effort to ask: “Is there evidence that age-patterns of COVID-19 severity in Lusaka were substantially different from patterns in other countries during the first wave of the pandemic?”. To answer this, we place existing WHO excess mortality estimates during the pandemic in Zambia in a global context, explicitly accounting for the protective effect of its relatively young population. We then develop a statistical framework to obtain estimates of pandemic impact upon Lusaka mortality patterns, focusing upon the burial registration age-distribution during 2020–2021. We combine these mortality estimates with data from the Lusaka population-based PCR- and sero-survey and UTH post-mortem PCR testing to assess whether patterns of excess mortality reflect likely patterns of spread. Finally, we use this approach to provide inference on key parameters such as the reproduction number, cumulative attack rate and IFR within Lusaka during 2020, comparing these with estimates throughout the world  and of the Europe and the Americas WHO regions. Meanwhile, its lower bound of -230 deaths per million exceeds the upper bound of estimates for Seychelles, Mauritius, Kenya, Togo and encompasses the region-level estimates for the Western Pacific region. Seychelles and Mauritius, two more developed island nations in the Africa region, are known to have experienced lower-than-typical rates of overall 2020 mortality (likely driven by suppression measures involving stringent border controls41). Aside from these comparisons, little can be said about the actual excess mortality in any country with similarly wide confidence intervals.The WHO’s mean per-capita excess mortality estimate of 290 deaths per million in Zambia during 2020 ranks 26th highest of the 47 WHO Africa region countries Fig. . The est42 by population age-structure. According to this measure of demographic vulnerability to severe disease, Zambia ranked 2nd lowest in both Africa and the world, with only Uganda’s demographic structure producing a lower estimate  high indirect pandemic impact; (ii) greater disease severity, due to health-care limitations, SARS-CoV-2 variants of greater severity or any other factor not accounted for which contribute to higher IFRs by age than those used in our analysis; (iii) substantial burden associated with reinfection.To help place these estimates in the context of differing underlying demography, we first weighted globally-derived estimates of age-specific IFRate Fig. . From thOur estimates Fig.  highligh43 and burial registration data39 during January 2018–June 2021. NPIs restricting international travel, closing educational and social establishments, limiting gatherings to 50, and encouraging social distancing, hand sanitation and mask wearing were implemented in Zambia in late March 202046, concurrently with the country’s first reported COVID-19 cases 19th March 202047. Very few confirmed COVID-19 deaths occurred whilst these measures were maintained  of 6.7 and 6.6 Zambian deaths per 1000 in 2018 and 201955 suggest these registration rates could constitute 85.7% and 88.6% of total Lusaka deaths respectively. From a median of 302 registrations per week, these data show substantial pre-pandemic volatility , approximately 50% higher than the pre-pandemic median. These increases were similarly driven by sharp rises in older-aged registrations, peaking at an average age at death of 45.9 and 51.1 years during these respective waves.57), but essentially no gendered differences are seen in relative registration changes throughout the pandemic compared with the pre-pandemic median  Fig. . This scThese numbers therefore correspond to the most optimistic registration system assumptions , yielding 1551.5 (95% CrI: 1090.0–2097.2) deaths per million Lusakans throughout the study period. Though accurately quantifying this system coverage, herein referred to as ‘capture rate’, is impossible with available data, we make a baseline assumption, using local knowledge and census-based total mortality projections in Zambia, that approximately 90% of pre-pandemic deaths were registered Fig. . With th58, parameterised to Zambia’s demographic structure, to our estimates of mortality patterns and available data on infection prevalence within Lusaka during the first pandemic wave. The model was fit to burial registry data by combining our non-COVID-19 baseline registration estimates with modelled COVID-19 deaths, scaling those modelled deaths using weekly U5 registrations relative to their 2018–2019 median, and using a default assumption of 90% capture of deaths within the Lusaka registration system. The model was also fit to post-mortem PCR prevalence by age and week27, accounting for likely patterns of PCR positivity in individuals whose deaths were not caused by COVID-19, and to population-based PCR prevalence and seroprevalence survey data37. We fitted a time-varying reproduction number  and by ±20% .We found that a 10% rate increase or decrease produced only nuanced impact upon the distribution of the fit to different IFR patterns, with our default parameters remaining well within the envelope of best-fitting values  and were highly predictive of trends across all age groups when NPIs were implemented, with similar results using the 5–14 year age group as a reference category, suggesting that mortality changes due to behavioural factors may have been relatively nuanced in the short term.Our results strongly suggest that the first COVID-19 wave in Lusaka had a direct and heavy impact, shifting the age-distribution of mortality towards older ages in a manner highly characteristic of COVID-19 severity patterns observed elsewhere. Assuming U5 burial registration declines represent registration process rather than underlying mortality changes, our estimates of 3220 (95% CrI: 2256–4393) excess deaths in 2020 represent a per-capita rate of 1256.2 (95% CrI: 880.1–1713.8) excess deaths per million, approaching the highest affected Africa-region countries (South Africa: 920 (95% CI: 830–1000) per million, and Algeria: 1270 (95% CI: 1210–1340) per million). After accounting for the protective effect of Lusaka’s young population, these estimates far exceeded those measured for Europe and the Americas (DVWI: 1.149 (95% CrI: 0.805–1.568) compared with 0.171 (95% CI: 0.167–0.176) and 0.240 (95% CI: 0.233–0.248), respectively). Assuming, instead, that registration declines are driven by underlying mortality changes decreased our excess 2020 mortality estimates by 48.7%, although estimates accounting for Lusaka’s population demographic remained well above those in the aforementioned countries (DVWI: 0.589 (95% CrI: 0.431–0.742)). In contrast, our default estimates may be conservative if, for example, disruptions to burial registrations were mirrored by, and subsequently mask any impact thereof, any disruption to maternal and neonatal services42, we show that these mortality patterns correspond well to community and post-mortem mortuary prevalence data, with these IFR patterns well within the range of our best-fitting models. Consequently, we find no evidence that age-specific severity was markedly different from estimates in other geographies, or any support for a so-called “Africa paradox”17. Our results do not, however, preclude relatively nuanced IFR differences in Lusaka relative to those observed elsewhere, with our results showing a plausible relative severity range between 50 and 250% of our default assumptions across numerous sensitivity analyses. Indeed, given the high non-hospital death prevalence27, we might expect to see greater severity in Lusaka compared with estimates from settings with high hospital access under the same intrinsic disease pathogenicity assumptions. IFR patterns toward our uncertainty interval’s higher end would also bring our estimates more in line with others from low- and middle-income settings outside of Africa36. Alternatively, IFR patterns toward the interval’s lower end could suggest relatively nuanced intrinsic severity differences in Lusaka that remain unexplained. However, given the widespread low hospital-care access across large parts of Africa, such an observation would not support a low direct pandemic impact across the continent. Meanwhile, COVID-19 treatment advances throughout 202063, largely benefitting high-income-country patients, are likely to mean that, even at the most optimistic end of our uncertainty, prioritising prevention efforts in higher-income-setting individuals over equivalently-aged Lusakans could have no equitable justification.Using a transmission model parameterised by IFR patterns estimated from available global 2020 data42, calculated using data matching our main study period time-frame . As with all severity studies during the initial pandemic stages, this study included data representing a trade-off between study-design quality and the representation of a wide range of contexts, leading to data inclusion with some potential measurement error. Bias may therefore be present in some population exposure data  and COVID-19 mortality data . However, the included data come from countries with strong testing systems, and crude IFR estimates from convenience-sample sources are not dissimilar to other included estimates. Other studies have suggested a higher IFR for very young children relative to older children66, which might account for the high observed U5 post-mortem prevalence, though at levels (<0.01%) that would make negligible difference to the fit of our model to the data. A plausible explanation for this U5 prevalence, though not one quantifiable in our framework, could be comparatively extensive SARS-CoV-2 spread within communities of high non-COVID-19-associated infant mortality. Overall, Brazeau et al. IFR estimates are central within the range of other estimates42. Thus, it seems plausible that an ensemble approach could broaden our uncertainty but would be unlikely to alter our central conclusion that, when analysing one of the best-characterised epidemics in sub-Saharan Africa, there is no evidence to support any substantial differences between innate COVID-19 severity in Lusaka relative to estimates from other parts of the world.Our default IFR assumptions are based on results from Brazeau et al.71 but that initial dynamics were comparable to those in South Africa72, with NPIs implemented at a very nascent stage in the epidemic, delaying the emergence of a first observable wave until restriction relaxation began in mid-2020. Following this initial exponential growth period, our estimates suggest that control of the epidemic was re-established around August 2020, showing patterns that closely resemble trends in Malawian prevalence data73. As a result, whilst our estimates suggest substantial direct pandemic impact, they also suggest that greater potential impact was mitigated by measures taken by the Lusakan population throughout 2020, despite the relaxation of official restrictions51.When considering SARS-CoV-2 spread, our estimates suggest that the potential transmissibility in Lusaka was comparable to estimates from earlier epidemics in China, Europe and America74, were lost later in 2020 and 2021. Given vaccine availability delays in Zambia throughout 202176, maintaining these early gains would have involved maintaining costly suppression measures well beyond the duration they needed to be maintained in higher-income countries where vaccine distribution was prioritised. The unsubstantiated perception of a low COVID-19 severity across Africa seems unlikely to have helped advocacy for equitable vaccine access, nor combat vaccine hesitancy in many African countries when vaccines were introduced78. In this context, a global inequity in our ability to measure mortality patterns and disease spread in 2020 likely contributed substantially to global inequity in the impact of the pandemic.Unfortunately, our estimates suggest that by the year’s end most of the population remained entirely immune-naïve, suggesting that Lusakans remained highly vulnerable to future waves, even in the absence of the variants that subsequently emerged. Our estimates of subsequent peaks in excess mortality suggest that many gains achieved by control measures during 2020, similarly implemented in many African countries33 and plotted per million population with 95% confidence intervals at global and WHO-region level, and at national level within the Africa WHO region. Confirmed WHO COVID-19 mortality data for countries and regions are plotted alongside for ref. 2.Estimates of excess mortality during 2020 were sourced from the WHO42 (without seroreversion), which we weighted by the specified population structure and summed to generate an overall value with 95% credible intervals. Population demographic estimates were sourced from the UN World Population Prospects79 and grouped into 5-year age brackets, then summarised at the global, regional and country level .Population-weighted country and region specific overall IFR were calculated and plotted using 100,000 samples from the age-specific IFR distribution, derived by Brazeau et al.DVWI was defined as the cumulative population attack rate required to directly generate the estimated excess mortality impact, given the median global, region or country-specific overall IFR and assuming an even spread of infection by age . We calculated these DVWI values by dividing estimates of excess mortality by median overall area-specific IFR estimates to generate a population infection level reflective of area demography and mortality.43, while details of NPIs were obtained from situation reports from the Zambia National Public Health Institute website80 and governmental statements on the COVID-19 pandemic51. Calculations involving Lusaka population size and demography were obtained from the Zambia Statistics Agency81, which are recently updated census-based projections.Official reported deaths for Lusaka Province were obtained from the Zambia COVID-19 Dashboard39 with predictions of baseline registration based on pre-pandemic registrations (2018–2019). Although the burial registration dataset begins in 2017, we found that registrations in 2017 increase from low numbers, only reaching greater stability and reliability from 2018, and therefore censored registrations during 2017 in our analysis. Based upon local knowledge of the study team, estimates from the literature54 and a comparison of recorded burials in 2019 with census-based projections81 we made a default assumption of a 90% burial registration rate . We used a Bayesian framework and Metropolis-Hastings Markov chain Monte Carlo (MCMC) to model baseline registrations as a function of weekly 2020–2021 registrations in the youngest age group and age-specific relative rates of registration trained on 2018–2019 data, using the drjacoby R package82. We assume that non-COVID-19 related registrations in each age-week group follow a Poisson distribution, verifying no better fit could be obtained using a Negative Binomial distribution with various assumed levels of over-dispersion  within the dataset83. As is generally the case in data collected from lower-income countries84, this matrix produces attack rates throughout an epidemic which are much flatter by age then any equivalent simulation using data from higher-income settings. For validation, PCR prevalence and seroprevalence patterns by age as observed in the population-based survey in Lusaka were compared with those estimated contemporaneously by the model. We also adjusted standard parameterisation to account for some uncertainties in treatment access in Lusaka (see SARS-CoV-2 transmission in Lusaka’s first wave of the pandemic (June-October 2020) was modelled using an age-structured SARS-CoV-2 SEIR model27, age-specific weekly burial registrations  and Lusaka-specific population level PCR prevalence and seroprevalence surveys in July, 2020, shared by the Centers for Disease Control and Prevention, Lusaka, Zambia37.The model was fitted to age-specific weekly post-mortem PCR prevalence, collected at UTH during the first pandemic wave  and shared by the COVID-19 extension of the ZPRIME studyWe again assume that all-cause burial registrations follow a Poisson distribution . We also assume that post-mortem PCR prevalence follows a binomial distribution  and that positive population-level PCR and serological tests both follow Binomial distributions  and by slope . For each intercept-slope combination, we ran our model fitting as described above, comparing the mean likelihood and posterior values of 100 draws from eight chains, each of 30,000 MCMC samples , to identify the combination that allowed the best fit to the data. A range of sensitivity analyses  and to contribute to a two-week modelling course designed to help support Zambian-based researchers to conduct their own modelling analyses. Most recently, SLC has visited the Department of Infectious Disease Epidemiology at Imperial College to share insights into the impact of COVID-19 more broadly across Zambia and to promote further collaboration in the form of twice-monthly meetings between study teams on an ongoing basis.We are not aware of any restrictions or prohibitions that have applied to the work of local researchers in this analysis.27 were provided by the institutional review boards at Boston RESEARCH University and the University of Zambia. Written informed consent was obtained from the deceased’s family members or representatives.Ethical oversight for ZPRIME and the COVID-19 expansion that generated post-mortem PCR prevalence data from UTH37 was approved by the Zambia National Health Research Authority and the University of Zambia Biomedical Research Ethics Committee. The study was reviewed in accordance with the Centers for Disease Control and Prevention (CDC) human research protection procedures and was determined to be non-research. Written informed consent was obtained for adults (aged ≥18 years) and emancipated minors, parental consent was obtained for participants aged 17 years and younger, and assent was obtained for participants aged 7–17 years, before the study.The population level SARS-CoV-2 prevalence studyThe work was granted approval via Imperial’s Research Governance Integrity framework on the basis of the above pre-existing ethics approvals.We are not aware of any personal risks to participants, but we are eternally grateful to them. In particular, we are grateful to the families who consented to the collection of post-mortem samples from loved ones during some of the hardest times imaginable and to these data being used within secondary analyses such as ours.This analysis prominently cites and builds directly upon, world-leading locally-generated research, already published in leading peer-reviewed journals and would not have been possible without it.Further information on research design is available in the Supplementary InformationPeer Review FileReporting Summary


Sedentary time was also recorded. Seroprevalence of anti-SARS-CoV-2 antibodies was assessed. Multivariable logistic regression models controlling for sociodemographic, lifestyle, anthropometric data, health status, and adherence to recommended protective anti-SARS-CoV-2 behaviours were computed. From 22,165 participants included, 21,074 (95.1%) and 1091 (4.9%) had a negative and positive ELISA-S test result, respectively. Total PA, vigorous PA, leisure-time PA, household PA, outdoor PA and indoor PA were all associated with lower probability of SARS-CoV-2 infection. Observations made in such a setting shed light on PA possibilities in a context of restricted mobility, where the health benefits of PA should not be overlooked. Along with already well-established benefits of PA for non-communicable disease prevention, these findings provide additional evidence for policies promoting all types of PA as a lever for population health.Lockdown imposed in the early phase of the SARS-CoV-2 outbreak represented a specific setting where activity was restricted but still possible. The aim was to investigate the cross-sectional associations between physical activity (PA) and SARS-CoV-2 infection in a French population-based cohort. Participants completed a PA questionnaire. PA was classified into: ( There is currently less evidence regarding the protective role of lifestyle factors including physical activity (PA).Following the worldwide pandemic caused by the (Severe acute respiratory syndrome associated coronavirus-2 (SARS-CoV-2) virus, there has been great interest in identifying risk or protective factors for the resulting coronavirus disease (COVID-19) and related health consequences. Improving our understanding of factors associated with COVID-19-related outcomes is much needed for designing present and future global and national health prevention policies. Through a number of systematic reviews and meta-analyses, there is strong evidence of links between individual characteristics , heavy current smoking, presence of chronic disease such as obesity, diabetes, hypertension, cardiovascular and respiratory diseases, or cancer) and increased risk of SARS-CoV-2 infection, morbidity, severity and related death6, a protective role of regular PA is well documented against infectivity and severity of respiratory infections8. A systematic review and meta‑analysis concluded that regularly engaging in moderate to vigorous PA (MVPA) is associated with a 31% risk reduction of community-acquired infectious disease and 37% risk reduction in infectious disease mortality9. It is therefore highly relevant to delineate the role of PA towards COVID-19 risk. Even if one study on a large sample showed a protective effect of PA regarding severe COVID-19 illness and mortality, the body of knowledge in this field rely on a still relatively limited number of studies14.Beyond the established health-enhancing effects of regular PA regarding non-communicable diseases (NCDs) and associated risk factors15. First, studies only used data on leisure-time PA and did not address the potential contribution of other important PA domains such as occupation- or household-related PA. Then, authors stressed the fact that no study accounted for factors such as social distancing, mask wearing and hand washing, while individual hygiene and the respect of protective barrier behaviours may seriously confound studied associations with risk of SARS-CoV-2 infection. In addition, drastic measures  imposed during lockdown resulted in an unprecedented disruption of daily life, leading to an unplanned natural experiment that may be used to understand the effects of an enforced limitation of movement on health. To address these limitations, we decided to perform a cross-sectional study in a large French cohort assessing the relationships between PA, including detailed information on multiple domains of PA and types, assessed during the first French lockdown (April–May 2020), and the SARS-CoV-2 infection obtained by seroprevalence from March 2020 to following 6 months, taking into account protective barrier behaviours.Some limitations of previous work on relations between PA and COVID-19 risk were outlined in a recent systematic review and meta-analysisTherefore, the aim of this study was to investigate the relationship between PA domains and types during the lockdown and the SARS-CoV-2 infection in a large French population-based sample.The current report is based on data collected from the multi-cohort SAPRIS  survey involving the NutriNet-Santé study. The SAPRIS survey started at the beginning of the first French lockdown, in April 2020 to assess the main epidemiological, social and behavioural challenges of the COVID-19 epidemic in France in relation to social inequalities in health and healthcare. Data were collected between April 1st, 2020 and May 12th, 2020. It was approved by the INSERM  Ethics Evaluation Committee .16. Volunteers aged 15 years or older living in France and having access to the Internet fill in self-administered web-based questionnaires at baseline as well as at regular time points during follow-up using a dedicated website. The NutriNet-Santé study is conducted in accordance with the Declaration of Helsinki, and all procedures were approved by the Institutional Review Board of the French Institute for Health and Medical Research (IRB INSERM #0000388FWA00005831) and by the National Commission on Informatics and Liberty . All participants provided informed consent and an electronic signature. The study is registered at ClinicalTrials.gov (NCT03335644).The NutriNet-Santé study is an ongoing web-based cohort launched in France in May 2009. The aim of this web-based cohort is to assess the relationships between nutrition and health along with the determinants of nutrition-related behaviours. A detailed description has been published elsewhere17. Participants were asked to report time spent in various types of PA during the past 7 days, as previously described17. Participants were asked to fill in the PA questionnaire at the same time that they completed the SAPRIS questionnaire, between April and May 2020. Activities surveyed included: brisk walking, walking a pet, jogging, cycling (outdoor and indoor), treadmill walking/running, rowing, aerobics, dancing, strength training, yoga, stretching, active play with children, household chores (cleaning), gardening and craft activities, and other relevant activity. PA was classified into several categories: (i) total PA; (ii) aerobic PA by intensity ; (iii) strengthening PA; (iv) PA by type ; and (vii) by location . Time spent was collected for each PA domain and expressed as min/week. In addition, we classified PA according to metabolic equivalent task (MET) score to take into account PA intensity. A MET is the ratio of the working metabolic rate of an activity divided by the resting metabolic rate. One MET represents the metabolic rate of an individual at rest (sitting quietly) and is set at 3.5 ml of oxygen consumed per kg body mass per minute, or approximately 1 kcal/kg/h18. PA of light, moderate, and vigorous intensities were rated as > 1.5, > 3, and > 7 METs, respectively. We calculated the MET-minutes per week by multiplying the standard MET score by PA duration and frequency per week18. Sedentary time (min/day), including screen time and sedentary behaviour  was also recorded.During the first lockdown , a set of ad hoc questionnaires was sent to the NutriNet-Santé participants to collect extensive data on health status and lifestyle, including PA at the beginning of lockdown19. Volunteer participants received self-sampling dried-blood spot kits by mail between May and October 2020. After processing, serological analyses were performed using commercial Enzyme-linked immunosorbent assay (ELISA) tests  to detect anti-SARS-CoV-2 antibodies  directed against the spike protein S1 domain (ELISA-S). The ELISA-S test was considered positive for values of optical density ratio ≥ 1.1, indeterminate for values between 0.8 and 1.1, and negative for values < 0.8. The main outcome was a positive ELISA-S test. Participants with ELISA-S results in the indeterminate range were excluded from the analyses.To determine whether participants have been infected by SARS-CoV-2, we invited participants who completed the COVID-19-related SAPRIS questionnaires to take part in the SAPRIS-SERO project 22. For the present analysis, we used the last questionnaires completed by participants before the lockdown, except for energy intake. Food consumption and nutrient intakes were calculated as an average per day, 24-h dietary records available (minimum: 6) from January 1st, 2018, to February 1st, 2020, i.e., the 2 years preceding the start of the COVID-19 pandemic in France.NutriNet-Santé participants regularly complete web-based questionnaires. Upon inclusion and then every year or 6 months, a set of five questionnaires related to sociodemographic and lifestyle characteristics , anthropometric data (height and weight), health status , dietary intakes (using three non-consecutive web-based 24-h dietary records randomly assigned over a two-week period including two weekdays and one weekend day) and PA  are sent to the participants19. From these questionnaires, a composite score reflecting the adherence to recommended protective behaviours against SARS-CoV-2 infection was computed23. The index was calculated as the average sum of points attributed to hand washing when going back home , mask-wearing , and physical distancing  and ranged from 0 to 9. All NutriNet-Santé questionnaires are available online (in French) at https://info.etude-nutrinet-sante.fr.In addition, a specific COVID-19 research protocol was set up in April 2020 as part of the SAPRIS nationwide multi-cohort project, including several questionnaires repeatedly collecting information about participants’ SARS-CoV-2 infection/diagnosis and experience of lockdown From 26,002 patients with a dried blood spot, 22,165 participants completed the PA questionnaire at the beginning of lockdown with either a positive or a negative ELISA-S test and were thus included in the analyses  and 95% confidence intervals (CI) were computed for an increment of 30-min per week. Sedentary time were also handled as continuous variables and the odds ratios (OR) and 95% confidence intervals (CI) were computed for an increment of 420-min per week. Additionally, only for PA duration, the OR (95% CI) were computed for an increment of 250 MET-minutes per week. Models were adjusted for the following characteristics, assessed in April 2020 : sex, age, educational level, employment status, smoking status, presence of children and/or grandchildren aged under 18 years at home, residential area, geographical area, frequency of going out over the past week and prevalent chronic disease , close relatives with COVID-19 symptoms, body mass index (BMI) and the month of blood draw. Models also included a composite index reflecting the adherence to 3 recommended protective behaviours when going out, assessed twice (questionnaires in April and May 2020).Associations between PA domains and types at the beginning of lockdown and the probability of SARS-CoV-2 infection (positive vs. negative ELISA-S test) were assessed using multivariable logistic regression models. According to previous studies on dose–response associations between PA and sedentary time and mortality, specific increments were defined for PA duration and sedentary timeIn sensitivity analyses on a subsample with available data, energy intake  and daily PA levels, assessed by IPAQ, before the lockdown were included into the models. We also tested restricting our study sample to a nested case–control design, with matching for age, sex, and residential area (4 controls per case).P < 0.05 was considered statistically significant. Analyses were carried out using SAS 9.4 .All tests were two-sided and The NutriNet-Santé study is conducted in accordance with the Declaration of Helsinki, and all procedures were approved by the Institutional Review Board of the French Institute for Health and Medical Research (IRB INSERM #0000388FWA00005831) and by the National Commission on Informatics and Liberty . All participants provided informed consent and an electronic signature. The study is registered at ClinicalTrials. gov (#NCT03335644). The SAPRIS protocol was approved by the Inserm ethics committee . The SAPRIS-SERO study was approved by the Sud-Mediterranée III ethics committee  and electronic informed consent was obtained from all participants for dried-blood spot testing.Characteristics of included participants according to ELISA-S tests status are described in Table PA domains and types according to ELISA-S status are shown in Table p < 0.0001), vigorous PA , leisure-time PA , household PA , outdoor PA  and indoor PA  were all associated with lower odds of SARS-CoV-2 infection  became associated with lower odds of SARS-CoV-2 infection  and the risk of SARS-CoV-2 infection. These data reinforce the importance of PA promotion and wide dissemination of PA guidelines to citizens as part of general measures for counteracting the spread of COVID-19 and attempting to minimize its adverse consequences. Overall, these findings provide support to the importance of PA at population level to mitigate the effects of acute health crisis such as the COVID-19 pandemic, in addition to the well-established protective effects of PA in the fight against NCDs.13. For example, in a recent systematic review and meta-analysis, authors reported that performing regular PA was associated with an 11% lower prospective risk of infection by SARS-CoV-215. Similar results were also found for the association between regular PA and infectious diseases and acute respiratory infections9. Authors concluded that having a higher daily PA leads to a lowered risk of community-acquired infectious diseases and an increase in the strength of the mucosal immune barrier9. Therefore, this first result on total PA was rather expected. To continue improving the understanding of the links between PA and risk of infection by SARS-CoV-2 and to be able to draw recommendations, it was important to explore in more detail the PA domains and types that may have potential protective effects.A first result of this study is that time spent in total PA during the first French lockdown was associated with a lower risk of SARS-CoV-2 infection. This finding brings new information compared to previous observations in the literature, which suggested that adults engaged in regular PA prior to the COVID-19 pandemic had a lower risk of SARS-CoV-2 infection28. Our study clearly showed that adults who performed vigorous PA had a lower infection risk whereas associations for moderate PA did not reach statistical significance. Even if an association with moderate PA was found after adjustment for energy intake, it remained tangential. Importantly, most previous studies did not account for PA intensity13. Only, Cho et al.12 investigated PA by intensity with infection risk of SARS-CoV-2 using self-report. Authors reported a significant inverse association for both moderate and vigorous PA12. Methodological disparities with our study relating to sample size and adjustment for confounding factors might explain the discrepancies between our results and those from this previous study. Another possible explanation relies on the specific activities classified as of moderate intensity, such as walking. It could be hypothesized that total walking, which we did not find associated with infection risk, mitigates the association with moderate PA. When looking at PA domains and types, we found that higher time spent in leisure-time PA, as well as household, outdoor and indoor PA was associated with a decreased risk of infection. Results were unaltered after additional adjustment for lifestyle habits, such as daily PA levels assessed at least 6 months prior to the pandemic crisis. These findings illustrate the importance to take into account various domains and types, and to assess their specific relationships with the SARS-CoV-2 infection.Results from our study bring new evidence showing that various categories of PA—but not all—may play a role in the reduction of SARS-CoV-2 risk of infection. Of note is the fact that our study is the first to investigate the associations between different PA intensity , different PA domains  and different PA types  during the lockdown and the risk of infection by SARS-CoV-2. Findings obtained with PA intensity and those with PA domains and types provide different views of relations with PA. First, there is major interest in analysing PA by intensity, especially for MVPA. Some studies showed that vigorous PA is beneficial on a number of cardiometabolic health outcomes, independent of moderate PA7 indicated that regular PA may be considered as an important immune system adjuvant to stimulate the ongoing exchange of distinct and highly active immune cell subtypes between the circulation and tissues. PA enhances immune defence by increased immunoglobulins, anti-inflammatory cytokines, neutrophils, NK cells, cytotoxic T cells, and immature B cells and reduced chronic inflammation7. In a previous epidemiological study, authors reported that the number of days with upper respiratory tract infection during the 12-week period was significantly reduced by 43% in subjects engaging in an average of 5 or more days per week of aerobic exercise (20 min bouts or longer) compared to those who were minimally active (≤ 1 day/week)29. Single bouts of moderate PA are also beneficial for the immune system and considered as immuno-enhancing30. Nevertheless, very intense and prolonged PA seem to have adverse effects on the immune system with a temporary immunodepression leading to an increased risk of infection7. This fact is well established in elite athletes31. We found that vigorous PA was significantly associated to a low odd of SARS-CoV-2 infection. However, this difference between our results and previous literature may be explained by the population studied and the definition of vigorous PA level. Indeed, the majority of this previous literature is devoted to the acute effect of exercises and focuses only on athletes with highest PA levels. Authors reported that training sessions at high intensity and a high participation to several tournaments in a short term leading a transient immune perturbation in elite athletes7. Lastly, engaging in regular PA have a potent anti-inflammatory effect and also reduce the risk of overweight and obesity, strongly associated with SARS-CoV-2 infection32.Several potential mechanisms could explain our results. There is robust evidence of causative links between PA, improved immunity, and disease prevention. In a review on the link between PA and the body’s defense system, Niemans and Wentz33. However, the social desirability bias may be reduced in web-based research compared to the traditional paper-and-pencil method34. Second, since participation to the NutriNet-Santé cohort is made on a voluntary basis, individuals tended to be healthier, including more women and with higher education compared to the general French population35. Thus, caution is needed in the extrapolation of our results. Next, the cross-sectional observational design of the study does not allow us to draw conclusions in terms of causality of observed relationships. Indeed, our study design does not allow for the examination of the temporal relationship, between physical activity and SARS-Cov2 infection. However, our models included thorough adjustments for a wide range of potential confounders, they are consistent with previous studies on total PA and SARS-CoV-2 infection and are supported by plausible mechanistic interpretation, which are important argument in favor of causality. Last, studies have suggested that the ELISA test has imperfect sensitivity (85–90%) and that anti-SARS-CoV-2 antibodies may decrease over time, which may have resulted in misclassification in a way that a person who has been infected with the virus might have not been tested as positive according to the ELISA test37. However, the date of collection of dried-blood spots was between May and October 2020 . In addition, we were unable to know the date of infection with limits of seroprevalence analyses, and therefore could be prior to PA assessment. The main strength is that the first study with a large sample size of French adults to assess relationships between different PA domains and types and the risk of SARS-CoV-2 infection. Another strength of this study is the inclusion of several confounding factors in the statistical analyses which was not included in previous studies, such as protective barriers behaviours , as well as the possibility to test adjustment for energy intake. Lastly, our study was based on a comprehensive assessment of SARS-CoV-2 seroprevalence with highly sensitive assays, independent of whether or not the participant sought testing  or even had symptoms (that might not be specific to SARS-CoV-2 infections).Our study presented several strengths and limitations. First, PA was assessed by a self-reported questionnaire. Thus, classification errors from social desirability, lack of awareness, or perceptual bias could not be ruled out. This may lead to over or underreporting of PA level, and by consequence, may mislead the estimation of the magnitude of studied associationsIn conclusion, our results indicate an inverse association between not only overall PA but several PA domains and types and SARS-CoV-2 infection. These findings contribute to an enhanced understanding of the relationships between PA domains and types during the specific lockdown setting and SARS-CoV-2 infection. Along with the already well-established benefits of PA for non-communicable disease prevention, these findings provide additional evidence for policies promoting all types of PA as a lever for improved population health.Supplementary Figures.


Recent trials provide evidence that HER2 is a potential new target for patients with colorectal cancer. While HER2-positive tumors do not show a very encouraging response to anti-HER2-positive agents like trastuzumab alone, promising results have been observed when combined with other synergistically acting tyrosine kinase inhibitors (TKIs). Our meta-analysis was conducted following the Cochrane Handbook and written following the PRISMA guidelines. The protocol was registered on PROSPERO with the registration number CRD42022338935. After a comprehensive search for relevant articles, 14 CTs were identified and uploaded to Rayyan, and six trials were ultimately selected for inclusion. The meta-analysis revealed that a median of three prior lines of therapy was used before enrolling in the six trials comprising 238 patients with HER2-positive metastatic colorectal cancer (mCRC). The pooled objective response rate (ORR) and disease control rate (DCR) were 31.33%  and 74.37% (95% CI 64.57–84.17), respectively. The pooled weighted progression-free survival (PFS) was 6.2 months. The pooled ORR and DCR meta-analysis indicate a significant response to HER2-targeted therapy in this patient in HER2-positive mCRC. Additionally, a pooled PFS of 6.2 months suggests that HER2-targeted treatment regimens are associated with a meaningful improvement in survival outcomes in this population. Colorectal cancer (CRC) is the second leading cause of cancer-related deaths globally, according to the World Health Organization (WHO), and the third most common cancer diagnosed in the United States . AlthougThe standard treatment for CRC, like most tumors, involves surgery, chemotherapy, and radiotherapy ,10,11,12A small subset of patients has a HER2-positive oncogene expressing CRC, allowing targeted therapy ,20. In tOur meta-analysis aims to comprehensively compile information on newly studied targeted therapies, including trastuzumab in combination with TKIs, or trastuzumab-based antibody–drug conjugate (ADC) regimens, with an emphasis on their merits, demerits, and most common adverse effects. This article underscores the need for further investigation into different HER2-targeting treatment modalities for HER2-positive CRC.Our meta-analysis was conducted in accordance with the Cochrane Handbook for systematic reviews of interventions . It was This study included trials involving patients with (1) HER2-positive mCRC, (2) of any age, (3) any sex, and (4) from any geographical area. (5) We focused our study on clinical trials. (6) The therapeutic agent used in these trials must be an anti-HER2 agent, such as trastuzumab, with a TKI or ADC. We excluded studies that involved (1) non-HER2-positive CRC, (2) all other solid tumors, (3) systematic reviews, meta-analyses, or papers other than clinical trials (CTs), and (4) trials that did not have a drug targeting an anti-HER2 agent.Clinicaltrials.gov and the WHO international registry of trials. We started to search for relevant trials on 25 June 2022.Studies were selected by searching through electronic databases and clinical trial registries. Electronic databases included CENTRAL, MEDLINE (via PubMed), and Embase. Clinical trial registries included The terms used to search through the databases included “anti-HER2-positive agents and HER2-positive CRC”, “trastuzumab plus adjuvants against CRC,” “treatment of HER2-positive CRC”, “HER2-positive CRC management”, “trastuzumab deruxtecan against HER2-positive CRC”, “trastuzumab and tyrosine kinase inhibitors,” “antibody-drug conjugates against HER2-positive CRC” and “antibody-drug conjugates and tyrosine kinase inhibitors”.After conducting a comprehensive search for relevant articles, 14 CTs were identified and uploaded to Rayyan. Following de-duplication using the inbuilt software of Rayyan, 12 articles were incorporated into the final analysis.Multiple reviewers conducted a simultaneous review of the articles, and two articles were found to be duplicates. One article was deemed irrelevant and excluded. Of the remaining nine, three contained only preliminary data. We could retrieve data from one of these studies by contacting the researchers, but the researchers of the remaining two studies did not respond, so their data were discarded. One trial was a short-term outcome of another long-term study and was removed as a duplicate.After reading the full-length papers, six trials were ultimately selected for inclusion in our analysis. Any discrepancies during the screening process were resolved through mutual discussion among the reviewers. The details of the screening process are provided in the PRISMA flow sheet, as shown in After a review of the trials, data were extracted and saved on an Excel sheet. There were two types of data: (1) information like author ID, study design, the type of intervention, and the number of patients; (2) outcome variables like the objective response rate (ORR), disease control rate (DCR), and other relevant primary and secondary outcomes.The primary outcome of this study was based on the efficacy of the study drug judged by the following variables: ORR, DCR, and PFS. We also enlisted the complete response to the drug (CR), partial response to the drug (PR), and stable disease (SD); the disease has neither progressed nor regressed and progressive disease (PD).Any additional effects of the study drug on patients that were not part of the primary outcome but deemed appropriate as an outcome, such as adverse events, were considered secondary outcomes of the study.The RoB (Risk of Bias) tool developed by the Cochrane Library of Systematic Reviews was used for quality assessment ,28. NHLBp-value < 0.05.Quantitative data were extracted and collected in a tabulated manner in an Excel sheet, and based on the tabulated data, a meta-analysis was performed. A random-effects model was used for DCR and ORR, and statistical heterogeneity was indicated by a In single-arm studies, there is only one intervention group, so comparing the risk of an event between two groups is impossible. Therefore, hazard ratio (HR) is not applicable in single-arm studies. Still, other statistical measures, such as the ORR, DCR, and PFS, are commonly used to evaluate the effectiveness of treatment. These measures can provide valuable information about the efficacy of treatment, but they do not allow for a direct comparison between different groups. It is important to note that single-arm studies have some limitations, and their results must be interpreted cautiously. Without a comparison group, it is difficult to determine whether any observed treatment effects are due to the treatment itself or other factors such as natural disease progression, regression to the mean, or placebo effects. Therefore, single-arm studies are often followed by more extensive randomized controlled trials to confirm the efficacy and safety of treatment .Calculate the weighted average of ORR: calculate the weighted average of ORR by weighing the ORR estimates from each study by their sample size using the formula:We calculated the pooled ORR for these six single-arm studies through the following steps:2.Calculate the standard error of the weighted average of ORR: calculate the standard error of the weighted average of ORR using the formula:3.Calculate the 95% confidence interval: calculate the 95% confidence interval for the weighted average of ORR using the formula:4.The pooled ORR provides an overall estimate of the treatment effect in single-arm studies and can be used to inform clinical decision making and guide further research. Nonetheless, it is essential to emphasize that the pooled ORR is only as valid as each study’s individual ORR estimates and may be subject to confounders or biases.This methodology was also utilized to estimate our study’s DCR and PFS. Two other reviewers validated all the data extraction and calculations. Additionally, interpreting these measures may require clinical expertise and careful consideration of the study design and patient population.Two of the six trials selected evaluated trastuzumab deruxtecan, and one evaluated trastuzumab plus lapatinib. One trial evaluated pertuzumab plus trastuzumab emtansine, while one evaluated trastuzumab plus tucatinib, and one evaluated trastuzumab plus pyrotinib . RegardiA narrative synthesis was conducted using the data collected from the selected studies. The CR, PR, SD, and PD of the selected studies are shown in In Bianchi et al., patients with tumors displaying a higher HER2 IHC score (3+) had better PFS compared to those with a lower score (2+); patients with a score of 3+ had a PFS of 5.7 months, while those with a score of 2+ had a PFS of 1.9 months . A higheIn the study Siena et al. recently published in June 2023 showed that more patients with high HER2 expression levels (IHC3+) had an objective response than those with IHC2+ and ISH-positive tumors . HoweverFu et al.  evaluateThe meta-analysis revealed that a median of three prior lines of therapy was used before enrolling in the trial. Outcome data were available for all six studies, comprising 238 patients with HER2-positive metastatic colorectal cancer (mCRC) who received HER2-targeted treatment regimens. The pooled ORR and DCR were 31.33%  and 74.37% (95% CI 64.57–84.17), respectively. The pooled weighted PFS was 6.2 months. These findings suggest that HER2-targeted treatment regimens improve PFS and lead to a higher ORR and DCR than chemotherapy in patients with HER2-positive mCRC.Our meta-analysis investigated the adverse effects of all drug combinations. Among patients receiving trastuzumab deruxtecan, the most common adverse events were nausea and vomiting (64.3%) . FatigueColorectal carcinoma is associated with significant morbidity and mortality, underscoring the need for new therapeutic interventions based on prior treatment knowledge. While HER2-positive overexpression/mutations are only present in 3–5% of cases of metastatic colorectal carcinoma, recent targeted therapies using monoclonal antibodies and ADCs have made HER2 a promising target for research.This meta-analysis is the first to investigate the efficacy of HER2-targeted therapies for HER2-positive CRC using data from recently completed and ongoing clinical trials. All trials included patients with heavily pre-treated metastatic CRC who received the trial regimen after the confirmation of HER2 receptor positivity via immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH). The MOUNTAINEER-03 trial investigating tucatinib with trastuzumab and mFOLFOX6 versus mFOLFOX in first-line HER2-positive mCRC is ongoing, and we are awaiting the results . The comThis analysis of studies identified trastuzumab deruxtecan as the most effective anti-HER2 agent, with the highest DCR (more than 80%) and ORR . AlthougThe meta-analysis results provide essential insights into the efficacy of HER2-targeted treatment regimens in patients with HER2-positive mCRC. The pooled ORR and DCR of 31.33% and 74.37%, respectively, indicate a significant response to HER2-targeted therapy in this patient population. Additionally, the pooled PFS of 6.2 months suggests that HER2-targeted treatment regimens are associated with a meaningful improvement in survival outcomes. These findings have significant clinical implications and are supported by the recently accelerated FDA approval of the tucatinib plus trastuzumab regimen for RAS wild-type HER2-positive unresectable or mCRC . This hiDespite these encouraging findings, it is important to note that statistical heterogeneity was observed in the analysis of ORR and DCR. This heterogeneity may be due to differences in study design, patient characteristics, or other factors not accounted for in this analysis. The main limitation of this estimate is that it always centers the 95% CI around the point estimate and essentially assumes a symmetric distribution. Further research is needed to better understand the factors contributing to the observed variability and type of distribution in response to HER2-targeted therapy in patients with HER2-positive mCRC.Most studies in our analysis did not examine outcomes in HER2 low-expression variants. The HERACLES diagnostic criteria utilized for colorectal cancer  were used to select patients for trial enrollment in three studies including Fu et al., Bianchi et al. and Tosi et al. ,31,33. IResistance against HER2-targeted treatments in the initial and acquired stages is common across tumor types ,37,38. WMost studies in our analysis excluded RAS mutant patients. Only three trials by Fu et al., Tsurutani et al. and Siena et al. included RAS mutant patients ,32,34. PHER2 overexpression/mutation’s prognostic utility remains unclear in colorectal cancer. However, mutations or the amplification of HER2 in these cancers are becoming more readily identified due to the increasing use of next-generation sequencing (NGS). We expect that mapping the genomic landscape and the signaling network of HER2-amplified tumors could provide a foundation understanding clonal evolution, tumor heterogeneity, and resistance to HER2-directed therapies.Regarding our study limitations, the single-arm design of the analyzed studies lacks a control group, and randomization is one limiting feature. Another limitation is the small sample size of these trials, which is too small to allow subgroup analysis to compare therapeutic effects across HER2 levels, HER2 alterations, and the status of other proto-oncogenes. Despite limitations in the selection and drug administration process observed in the analyzed trials, these results highlight the potential of HER2-targeted therapy as an effective treatment option for patients with HER2-positive mCRC and underscore the need for continued research in this area.In conclusion, this meta-analysis on HER2-targeted therapies demonstrates the potential for a targeted and effective treatment option for patients with HER2-positive mCRC. The results indicate a significant response to HER2-targeted treatment in this patient population with a meaningful improvement in survival outcomes. These findings are particularly noteworthy given the limited treatment options available for this patient population and the historically poor prognosis associated with this disease. Further research is needed to better understand the factors contributing to observed variability in the response to HER2-targeted therapy and to improve this analysis’s validity in patients with HER2-positive mCRC.


Racially minoritized groups are more likely to experience COVID-19 vaccine hesitancy and have lower vaccination rates.  As part of a multi-phase community-engaged project, we developed a train-the-trainer program in response to a needs assessment. “Community vaccine ambassadors” were trained to address COVID-19 vaccine hesitancy. We evaluated the program’s feasibility, acceptability, and impact on participant confidence for COVID-19 vaccination conversations. Of the 33 ambassadors trained, 78.8% completed the initial evaluation; nearly all reported gaining knowledge (96.8%) and reported a high confidence with discussing COVID-19 vaccines (93.5%). At two-week follow-up, all respondents reported having a COVID-19 vaccination conversation with someone in their social network, reaching an estimated 134 people. A program that trains community vaccine ambassadors to deliver accurate information about COVID-19 vaccines may be an effective strategy for addressing vaccine hesitancy in racially minoritized communities. Vaccination against the novel coronavirus COVID-19) plays a critical role in reducing the morbidity and mortality caused by the ongoing pandemic. Currently, 67% of the US population is fully vaccinated against COVID-19 9 plays a. Raciall” identifies the use of trusted messengers as a vital community-based strategy for overcoming vaccine hesitancy [The Centers for Disease Control and Prevention’s (CDC) framework to support vaccination, “Vaccinate with Confidence,esitancy . This stesitancy , 7. Thesesitancy .Our multidisciplinary team  chose to implement this community vaccine ambassador strategy with the goal of increasing the spread of accurate information about COVID-19 vaccines in the local Black and Latino/a/x communities. Our goal was to ultimately increase COVID-19 vaccination rates. Here, we report on the feasibility, acceptability, and impact of our community COVID-19 vaccine ambassador train-the-trainer pilot. We hypothesized that the program would be feasible and acceptable, and that ambassadors would report confidence in having COVID-19 vaccine-related conversations with others in their community. We set a goal that each ambassador would report having conversations with at least 5 individuals.This program was conducted in Cincinnati, Ohio, a city with a population that is 41% Black and 4% Latino/a/x. The median household income for Hamilton County residents is $42,663. The Latino/a/x population in the Cincinnati metro area grew nearly 50% from 2010 to 2020 . At the The lead partner on the program was Cincinnati Children’s Hospital Medical Center (CCHMC), a large, free-standing academic pediatric hospital.Using a 2020 COVID-19 community needs assessment, common vaccine hesitations and myths in both communities were identified. Community stakeholders and the public health education team met to design vaccine education goals and objectives based on hesitancy data, preferred information sources and messengers and identify education modalities to empower community advocates. This work was reviewed and determined to be exempt by the Institutional Review Board at CCHMC (IRB ID# 2020-0465).We aimed to train at least 25 community residents and people from community-based organizations  with an expressed interest in learning more about COVID-19 vaccination. Recruitment occurred via existing partnerships, word of mouth, organizational/collaborative meetings, and fliers. Interested individuals registered for the event and were emailed a Zoom link for the program.The 90-minute train-the-trainer program was held in June 2021 and delivered in English with Spanish interpretation available via video. The program included a review of ambassador expectations . During the training, one Black community member and 1 Latino/a/x community member along with their adolescent children shared their reasons for getting vaccinated. In addition, an infectious disease physician provided information and answered questions about COVID-19 vaccines. Families and experts also addressed common myths identified by community partners. The training ended with talking points for ambassadors, using scenarios for demonstration.To assess feasibility, registration and attendance were tracked. Immediately following the program, acceptability  was assessed using a computer-based evaluation survey. Two weeks after the training, ambassadors were emailed a follow-up survey asking for information about any conversations about COVID-19 they had with friends, family, or colleagues since the training. Descriptive statistics summarized quantitative survey data. Open-ended questions were iteratively coded using computer-assisted content analysis completed by authors AMSC and SG. Consensus was reached for code application, and then codes were grouped into categories.Of the 41 participants who registered for training, 33 (80%) attended (Table Twenty-six attendees (79%) completed the initial evaluation and 17 of 26 (65%) completed the two-week follow-up survey (n = 17)  that the content addressed COVID-19 vaccine concerns in their community. Nearly all participants who attended the training reported increased knowledge about COVID-19 and vaccination (96.8%), as well as confidence to have vaccine-related conversations with family and peers (93.5%). At two-week follow-up, all community vaccine ambassadors had engaged in a conversation with a colleague, friend, or family member about COVID-19 vaccination. An estimated 134 people (7.9 people per ambassador) were reached by these follow-up conversations, many of whom planned to get vaccinated following the interaction with their community vaccine ambassador. Family members appeared to be most accessible to trained ambassadors; 88% of our participants had a follow-up conversation with someone in their family within two weeks of our training. Qualitative comments revealed that community vaccine ambassadors would continue to use knowledge and skills they obtained from the training to have COVID-19 vaccine conversations.This paper describes the evaluation of a train-the-trainer community ambassador program to address COVID-19 vaccine misinformation in Black and Latino/a/x communities. Data indicate that the program was feasible and acceptable. Ambassadors reported increased knowledge and confidence, and felt the information was useful for addressing specific COVID-19 vaccine concerns in their communities.Two weeks after our training, ambassadors reported having successful conversations about vaccine benefits and risks with approximately 134 people in their social networks. Qualitative data indicated that ambassadors felt confident even if the individuals they educated remained hesitant; ambassadors also felt they were building trust and might influence future COVID-19 vaccine intention. It is notable that most participants recruited as vaccine ambassadors in this study were trusted stakeholders of community-based organizations serving minoritized communities, positioning them as reliable resources based on a previous needs assessment . This daLimitations of this study include that this was a one-time pilot program with limited recruitment and participation; it is possible that ambassadors who did not complete the follow-up evaluation did not find the program beneficial or did not have conversations in their community. Data was not collected on the age group or gender identity of the ambassadors, further limiting the generalizability of our findings. Future studies with larger sample sizes and a more comprehensive data collection strategy are recommended to determine the impact of this program on vaccination knowledge, intention, and rates in Black and Latino/a/x communities. Future efforts may also allow for collection of additional variables; our work captured myths and misinformation, but there is also room to learn about community strengths and resilience that may facilitate vaccination.The Community COVID-19 Vaccine Ambassador Program was developed to increase access to trustworthy, accurate information about COVID-19 vaccinations by training trusted messengers to have informed conversations. As evidenced by an increase in knowledge and confidence, the engagement of trusted messengers in this train-the-trainer model holds promise for application of this strategy for addressing COVID-19 vaccination hesitancy in marginalized communities. This community vaccine ambassador model could serve as an archetype for mitigating future challenges during the COVID-19 pandemic and addressing hesitancy with other health behaviors.


Current chemotherapy-induced peripheral neuropathy (CIPN) assessment tools mostly have poor sensitivity and weak anti-interference, so that it is sometimes difficult to provide substantive guidance for clinical intervention. This study aimed to develop an assessment tool dedicated for oxaliplatin to address these limitations.This study screened 445 OIPN-related literatures for producing a symptom list, and developed the questionnaire module through expert supplement, item generation, content correlation analysis, pre-testing, and item improvement. The validation phase used a Chinese population-based prospective cohort study from June 2021 to July 2022. Patients were requested to complete the tested questionnaire, QLQ-CIPN20 and the CTCAE grading one day before cycles 2–6 of chemotherapy. Cronbach’s α coefficient and intraclass correlation coefficient (ICC) were calculated for the internal consistency and stability analysis, respectively. Exploratory factor analysis was conducted to investigate the construct validity. The correlations among the tested questionnaire, QLQ-CIPN20 and CTCAE were compared for the criterion validity analysis. Wilcoxon signed-rank sum test was utilized to compare the sensitivity between the tested questionnaire and QLQ-CIPN20.p < 0.01). Besides, the total score of CIPNIA-OS was mostly higher than QLQ-CIPN20, with an average difference of 2.189 (CI 95% 2.056 to 2.322), and the difference gradually expanded with the progress of chemotherapy (p < 0.05).A 20-item CIPN assessment tool named chemotherapy-induced peripheral neuropathy integrated assessment – oxaliplatin subscale (CIPNIA-OS) was developed. The validation phase included 186 patients. Cronbach's α coefficient of CIPNIA-OS was 0.764 (> 0.7), and ICC was 0.997 (between 0.9 and 1). The structure of CIPNIA-OS containing seven factors was examined. The correlation coefficient between CIPNIA-OS and CTCAE was 0.661 (95%CI 0.623 to 0.695), which was significantly higher than that between QLQ-CIPN20 and CTCAE (0.417, 95%CI 0.363 to 0.469, This study developed an original CIPN questionnaire which was dedicated for OIPN assessment. It was a comprehensive tool that covered acute OIPN symptoms and integrated features from several proven CIPN assessment tools. The validation results supported that CIPNIA-OS had satisfactory reliability, stability, construct, criterion validity, and was more accuracy and sensitive than QLQ-CIPN20 in the evaluation of OIPN.The online version contains supplementary material available at 10.1186/s12885-023-11541-7. Chemotherapy-induced peripheral neuropathy (CIPN) has always been a concern in the course of cancer therapy, as well as the main reason leading to the suspension or termination of chemotherapy . Over thEarly assessment tools for CIPN mainly based on clinician-reported outcome (CRO), including World Health Organization (WHO) Scale , EasternAs oxaliplatin is the core agent in chemotherapy regimens such as FOLFOX, XELOX, SOX, oxaliplatin-induced peripheral neuropathy (OIPN) has become one of the most common adverse effects of the gastrointestinal cancer treatment, as well as the most noteworthy one in CIPN. OIPN can be subdivided into acute and chronic forms. About 89% of patients would experience acute OIPN, which mainly manifested as sensitivity to touching or swallowing cold items, throat discomfort, and muscle cramps, appeared within a day after the infusion of oxaliplatin, peaked in severity at day 3, and then alleviated. Chronic OIPN presents dose accumulation, mainly manifested in paresthesia symptoms including numbness and tingling at the extremities of the limbs, and a small number of proprioceptive disturbance and ataxia. Symptoms persist during treatment and can be aggravated after drug withdrawal (known as "coasting" phenomenon). The recovery is so slow that even 18 months after completing chemotherapy, 19% of patients still suffer from severe neuropathic symptoms . In the In order to standardize the development of the questionnaire module, the EORTC questionnaire module development guidelines were used as references . The devA keyword search was conducted in Pubmed, MEDLINE and CNKI. Keywords included "oxaliplatin" or "platinum" together with "neuropathy" or "neurotoxic", and the time frame was from 2004 to 2023. Literature with no or insufficiently precise description of OIPN-related clinical symptoms was excluded. A total of 445 literatures were searched, and 22 literatures with relatively detailed descriptions of OIPN-related symptoms were retained after screening, including 10 reviews, 8 prospective clinical studies, 3 retrospective analyses, and 1 mechanism research, as shown in Supplementary Table SThe expert panel put forward some suggestions according to the symptom list before drafting, which can be summarized as follows: a) medical terms need to be replaced with readily comprehensible and realistic descriptions; b) symptoms that have similar meanings or contain each other need to be merged; c) attributes of symptoms need to be more precise.The expert panel also put forward five points of controversy. First, is it necessary to distinguish between upper and lower limbs according to the distribution of symptoms? Previous study recommended that symptoms in the upper and lower extremities should be distinguished distinctly as they are not identical , so it wSecond, is it necessary to distinguish between left and right limbs according to the distribution of symptoms? OIPN symptoms are mostly symmetrically distributed, and the difference between the left and right limbs, which may be caused by different habits of using the left and right limbs , does not affect the evaluation of the severity. In fact, patients tend to pay more attention to the more severe side, which is more valuable for the description of the severity of OIPN. So it does not need to distinguish between left and right.Third, is it necessary to distinguish between acute and chronic symptoms? The clinical manifestations of acute and chronic OIPN are similar in many aspects, but differ only in terms of location, duration, and influence on daily life. Therefore, acute and chronic symptoms can be distinguished by adding items evaluating location, duration and influence on daily life.Fourth, is it necessary to evaluate the attributes of each symptom ? In fact, the early symptoms of OIPN are mostly single. Even if more than two symptoms are present at the same time, attention to the most severe symptom is more valuable for evaluation.Fifth, should objective assessment items be included, such as quantitative sensory testing (QST)? Given the objective tests had high requirements in assessing time point, skills and instrumentation or equipment, it was difficult to conduct frequent monitoring and widespread clinical application as the gold standard , so thatThe evaluation of content validity mainly adopts the content validity index (CVI) based on experts' understanding of content correlation with the evaluation object as customary, which includes the item-level content validity index (I-CVI) and the scale-level content validity index (S-CVI). Items with excellent content validity should be composed of I-CVIs of 0.78 or higher . HoweverThe pre-test was conducted in Jiangsu Province Hospital and Affiliated Hospital of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, both located in Nanjing, China. Sixteen colorectal cancer patients with different clinical and demographic characteristics  were selected from the two centers as subject representatives. Each subject was interviewed and the content was recorded. The interview questions included: a) Do you understand the symptoms or conditions described in the questionnaire? If not, which item or items make you confused? b) Are you willing to answer the questions truthfully? If not, what is your concern or scruple? c) Do you have any suggestion or supplement for the questionnaire? The item-level positive response rate  and the interview content would be analyzed for the basis of item improvement.The field test was performed among patients from 30 centers of the TIMEPOINT study from June 2021 to July 2022. The center list was shown in Supplementary Table SThe sample size was set at 200 based on the internal consistency criteria (‘Excellent’) for sample size (number of items × 7 and ≥ 100 subjects) in the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines . ConsideAll analyses were conducted using SPSS Statistics Software version 27 (IBM). Cronbach's α coefficient was calculated for the internal consistency, and intraclass correlation coefficient (ICC) was calculated for the stability of the questionnaire. As a new developed questionnaire, exploratory factor analysis (EFA) was more suitable for investigating the construct validity. Before conducting EFA, Kaiser–Meyer–Olkin (KMO) measures of sampling adequacy and Bartlett's test of sphericity were used to evaluate whether it was suitability for factor analysis. Principal component analysis method was used to extract common factors, and factors with eigenvalues > 1 and variance interpretation rate ≥ 5% would be retained. Factor rotation was performed using varimax rotation to find the corresponding relationship between the factors and items, and to give reasonable factor interpretations of the tested questionnaire. CTCAE was used as the gold standard for the criterion validity analysis, and the Pearson correlation coefficients between the tested questionnaire, QLQ-CIPN20 and CTCAE were calculated and compared to evaluate the accuracy. As the two questionnaires (the tested questionnaire and QLQ-CIPN20) have the same item number and the scoring algorithm, they can be homogeneously compared. Wilcoxon signed-rank sum test was used to compare the difference in results between the test questionnaire and QLQ-CIPN20 to demonstrate sensitivity.The list of OIPN-related symptoms reported in previous literature was listed, as shown in Supplementary Table SAccording to the suggestions put forward by the expert panel and the subject representatives, we formulated a 32-item questionnaire named "Chemotherapy-induced peripheral neuropathy Integrated Assessment – oxaliplatin subscale (preliminary version)" (CIPNIA-OS), as shown in Supplementary Fig. SItem improvement mainly depended on the results of CCI and pre-test I-PRR. The distributions of the expert-cognitive clinical incidence and severity of symptoms affecting chemotherapy adjustment of each item in the preliminary version were shown in Supplementary Fig. SA total of 207 patients were included in this study. 21 patients failed to complete 6 cycles of chemotherapy during treatment and were excluded, including 9 patients whose oxaliplatin-based chemotherapy regimen was adjusted due to disease progression, and 12 patients who voluntarily terminated chemotherapy due to adverse reactions other than peripheral neuropathy . Finally, data from 186 subjects were analyzed for the reliability, validity, and sensitivity of CIPNIA-OS.2. The average total scores of CIPNIA-OS and QLQ-CIPN20 were 5.12 (95% CI 4.91 to 5.33) and 2.93 (95% CI 2.77 to 3.09), respectively.The clinical and demographic characteristics of the subjects were shown in Table The results of the reliability analysis were shown in Table 2 = 5726.739, p < 0.05). Seven common factors were extracted by principal component analysis method, explaining 64.21% of the cumulative variance, as shown in Supplementary Table SIn the construct validity analysis, we did not analyze the last three items together in order to make the contents of the items in the same dimension. The KMO coefficient was 0.694 > 0.5), indicating strong correlation between variables. Bartlett's test of sphericity indicated that each variable was independent and the correlation matrix was factorable . The Pearson correlation coefficient between CIPNIA-OS and CTCAE was 0.661, which was significantly higher than that between QLQ-CIPN20 and CTCAE , indicating that CIPNIA-OS was closer to the evaluation results of CTCAE than QLQ-CIPN20.The Pearson correlation coefficient between CIPNIA-OS, QLQ-CIPN20 and CTCAE were calculated, as shown in Table p < 0.01), and the average difference between them was 2.19 (CI 95% 2.056 to 2.322), as shown in Tables p < 0.01), and the difference gradually expanded with the progress of chemotherapy (p < 0.05), as shown in Fig. Wilcoxon signed-rank sum test showed that, the total score of CIPNIA-OS was generally higher than that of QLQ-CIPN20  in practical application settings. Timely and precise intervention of OIPN depends on a sensitive and targeted evaluation system. Current commonly used assessment tools, whether CTCAE based on CRO , or QLQ-First of all, through literature search and expert supplement, OIPN-related symptoms were made into a list. We noted that the symptoms reported in the literature mostly contained or caused each other, for example, persistent paresthesia may be the cause of ataxia, and limb weakness may be the cause of functional impairment, so systematic induction and summary is necessary. Secondly, following the suggestions of the expert panel, symptoms were translated into easy-to-understand description items, so that a preliminary version questionnaire containing 32 items was developed, named CIPNIA-OS. With the purpose of accurately characterizing neuropathic symptom attributes, we were inspired by PRO-CTCAE , and desp < 0.01), indicating that CIPNIA-OS could be closer to objective evaluation results. This might be the result of CIPNIA-OS excluding items that were susceptible to underlying diseases, such as blurred vision and difficulty hearing. Secondly, Wilcoxon signed-rank sum test showed that, the total score of CIPNIA-OS was generally higher than that of QLQ-CIPN20 , and the average difference was 2.19 (CI 95% 2.056 to 2.322). This was apparently due to the high O-PRR of CIPNIA-OS, which made it easier to distinguish between mild and severe cases. Meanwhile, the mean score of CIPNIA-OS in each cycle was significantly higher than that of QLQ-CIPN20 (p < 0.01), and the difference gradually expanded with the chemotherapy cycle progressed, indicating that CIPNIA-OS had higher sensitivity.Subsequently, the modified version was put into field testing. Data from 186 subjects were analyzed for the reliability, validity and sensitivity of CIPNIA-OS. Cronbach's α coefficient was 0.764 (> 0.7), indicating that the overall internal consistency reliability was considerable. ICC from the test–retest results was 0.997 (close to 1), supporting good reliability of CIPNIA-OS. Seven common factors were obtained in EFA, basically distributing according to the symptoms of upper and lower limbs . These factors explained 64.21% of the cumulative variance, more than 50%, indicating passable construct validity of the questionnaire. The total scores of CIPNIA-OS and QLQ-CIPN20 were further compared to demonstrate which of them was more superior. Firstly, correlation comparison was conducted using CTCAE as the gold standard, and the results showed that the Pearson correlation coefficient between CIPNIA-OS and CTCAE was 0.661, which was significantly higher than that between QLQ-CIPN20 and CTCAE , so as to make it systematic and really universal.Additional file 1: Supplementary Table S1. List of literature detailing OIPN-related symptoms. Supplementary Table S2. TIMEPOINT clinical centers in China. Supplementary Table S3. Previously Reported OIPN-Related Symptoms. Supplementary Table S4. Current assessment tools of OIPN. Supplementary Table S5. Total variance explained.Additional file 2: Supplementary Fig. S1. Chemotherapy-induced Peripheral Neuropathy Integrated Assessment – Oxaliplatin Subscale . Scoring standard: "Not at all"=0, "A little bit"=1, "Quite a bit"=2, "Very much"=3. The symptom location was classified according to the Total Neuropathy Score (TNS). The symptom duration was classified according to the Levi’s scale. The influence was classified according to the National Cancer Institute Common Toxicity Criteria Adverse Events (NCI-CTCAE). Supplementary Fig. S2. Distributions of expert-cognitive clinical incidence and severity of symptoms affecting chemotherapy adjustment. The numbers in the column represent the number of experts who gave the evaluation corresponding to the color. (a) Expert-cognitive clinical incidence of oxaliplatin-induced neuropathic symptoms . (b) Expert-cognitive severity of oxaliplatin-induced neuropathic symptoms affecting chemotherapy adjustment . Supplementary Fig. S3. Pre-testing item-level positive response rate (I-PRR) of the original version. Supplementary Fig. S4. Chemotherapy-induced Peripheral Neuropathy Integrated Assessment –Oxaliplatin Subscale (modified version). Scoring standard: "Not at all"=0, "A little bit"=1, "Quite a bit"=2, "Very much"=3. The symptom location was classified according to the Total Neuropathy Score (TNS). The symptom duration was classified according to the Levi’s scale. The influence was classified according to the National Cancer Institute Common Toxicity Criteria Adverse Events (NCI-CTCAE).


Analysis of covariance demonstrated a significant reduction (improvement) in cfPWV between BL and PI for O-RAGT , whilst the control group remained unchanged . The improvement in cfPWV was maintained 3 months after completing the O-RAGT program. There were no significant Condition by Time interactions for all PWA and carotid arterial stiffness measures (p > 0.05). A significant increase in physical activity, as determined by the time spent stepping, was observed for O-RAGT between baseline and post-intervention assessments  but not for CON (p < 0.05). The improvement in cfPWV, in combination with an increase in physical activity whilst wearing the O-RAGT and concomitant reduction in sedentary behavior, are important positive findings when considering the application of this technology for “at home” rehabilitation therapy for stroke survivors. Further research is needed to determine whether implementing “at home” O-RAGT programs should be a part of the stroke treatment pathway.Overground robotic-assisted gait training (O-RAGT) has been shown to improve clinical functional outcomes in people living with stroke. The purpose of this study was to identify whether a home-based O-RAGT program, in combination with usual care physiotherapy, would demonstrate improvements in vascular health in individuals with chronic stroke, and, whether any changes in vascular outcomes would be sustained 3 months after completing the program. Thirty-four participants with chronic stroke (between 3 months and 5 years post-stroke) were randomized to either a 10-week O-RAGT program in combination with usual care physiotherapy, or to a usual care physiotherapy only control group. Participants' (https://clinicaltrials.gov, identifier NCT03104127. RecoverOver-ground robotic-assisted gait training devices (O-RAGT) allow the patient to walk in a real-world environment, enabling substantial kinematic variability while ensuring successful task execution . The homElevated brachial blood pressure, an important risk factor for stroke , is wideThe purpose of this study was to identify whether: (i) a home-based O-RAGT program, in combination with usual care physiotherapy, would demonstrate improvements in cardiovascular health  in individuals with chronic stroke, and, (ii) any changes in cardiovascular health outcomes would be sustained for 3 months. It was hypothesized that regular participation in a 10-week O-RAGT program would improve vascular health in individuals living with stroke.ClinicalTrials.gov Protocol Registration and Results System .This study was a parallel group, randomized controlled clinical trial, reported in accordance with Consolidated Standards of Reporting Trials (CONSORT) guidelines . The stuParticipants with chronic stroke (>3 months since stroke diagnosis) were recruited from a single neuro-physiotherapy practice . All participants were diagnosed with stroke by a specialist neurologist/stroke consultant from a UK National Health Service Trust and had completed rehabilitation activities  in accordance with recommended guidelines . Written2, major arrhythmias, unresolved deep vein thrombosis, recent fractures of the symptomatic limb, open wounds, severe osteoporosis, and/or individuals who were non-weight bearing.Inclusion criteria included: Individuals between 3 months and 5 years post-stroke, who were living in the community, medically stable, and cognitively capable, able to stand and step with an aid or with assistance  , and whoParticipants were tested between 07:00 and 10:00 am in the physiology laboratory at the University of Winchester. Participants refrained from intense physical activity for 24 h prior to testing, and could only consume water for the 12 h before testing. Following an initial Functional Ambulation Classification and Modified Rankin Scale assessment to provide an indication of the degree of disability, participants lay supine for 15 min. Thereafter, pulse wave analysis (PWA), and regional (cfPWV) and local (common carotid) measures of arterial stiffness were assessed. Participants were randomized using covariate adaptive randomization  to eitheThe SphygmoCor XCEL device enables simultaneous assessment of proximal and distal arterial waveforms using a tonometer and volume-displacement cuff, respectively, to determine arterial pulse transit time. Carotid–femoral pulse transit time was measured as the time between diastolic feet of the proximal (tonometer) and distal (cuff) arterial pulse waveforms . PWV wasFor PWA, oscillometric pressure waveforms were recorded on the left upper arm by a single observer using the SphygmoCor XCEL device , following standard manufacturer guidelines . Each siA trained ultrasound operator with extensive experience (>10 years) collected all common carotid arterial stiffness measurements using a portable uSmart 3,300 Ultrasound system  equipped with a 13–6 MHz bandwidth transducer that provided high resolution brightness mode measurements. The left common carotid artery of the participants was examined, in a supine position, and with their head tilted at 45° (angled to the right) on completion of PWA and PWV measurements. The left common carotid artery was assessed 1–2 cm beneath the bifurcation . MagnifiParticipants wore an ActivPAL3™ device  for seven consecutive days and nights at baseline, PI and 3PI. The ActivPAL3 device was wrapped in a protective Tegaderm™  and attached to the anterior aspect of the upper third of the thigh, on the asymptomatic side. The ActivPAL3 provided a daily measure of the:  percentaThe O-RAGT device  is a battery-operated, externally-wearable, dynamic device worn by stroke patients during rehabilitation. The device provides sensory inputs , mobility assistance for users with reduced lower-limb function, and is fitted and worn in a manner similar to an orthopedic knee brace. The orthosis shell functions as the user interface that transfers the assistive torque to the human body, while an actuation unit assists the movement of the limb.Participants were familiarized with the O-RAGT device before commencing the 10-week home-based program. Participants were encouraged to undertake at least 30 min per day of continuous or non-continuous bouts of walking and sit-to-stand exercises, at a moderate ratings of perceived of exertion (RPE 12–13). There was no maximum daily wear-time. O-RAGT settings associated with a participant's weight, assistance, resistance, threshold and knee extension angle settings were individualized and re-assessed every 2 weeks. Participants reported their number of steps, duration of use, activities undertaken and RPE for each day of activity. During this time, participants also continued their “usual care.”Participants in both the control group and O-RAGT program undertook one-to-one, “usual care” physiotherapy sessions for the duration of the study. This included stretching and muscle strengthening exercises, functional movement activities  and soft-tissue massage. There were also group therapy activities which were based on the same principles but with less therapist engagement. For the duration of the 10-week program participants were advised to engage in at least 30 min of physical activity each day, undertaking similar functional movement patterns as those reported above.t-tests  and chi-square tests , as appropriate.Demographical and clinical comparisons between Conditions  was undertaken at baseline with independent sample 2) was used to demonstrate the strength of the effect of exercise on the various outcome measures with 0.0099, 0.0588 and 0.1379 representing a small, medium and large effect, respectively , Condition  x Time , adjusted for baseline measures and age, were used to assess all PWA, cfPWV, carotid artrial stiffness and accelerometry outcomes. For PWV analysis, Mean Arterial Pressure was also used as a covariate. Partial eta squared . The improvement in cfPWV, in combination with an increase in wear-time and physical activity whilst wearing the O-RAGT, are important positive findings when considering the application of this technology for “at home” rehabilitation therapy for stroke survivors.2 = 0.135) indicates a robust and promising impact on regional arterial stiffness.Carotid-femoral PWV predicts mortality in patients with essential hypertension  and is aIn the present study there were no statistical changes in central haemodynamic (PWA) or local carotid arterial stiffness parameters . Past reLong-term outcomes are of utmost importance when evaluating the clinical importance of interventions. An important characteristic of successful behavior change is that individuals continue to engage in lifestyle modifications once the stimulus  has been removed. A recent meta-analysis for stroke patients revealed that end-of-intervention benefits gained from regular physical fitness training do not persist following completion of an intervention . In non-The encouraging findings surrounding cfPWV is unique as the O-RAGT program focused on walking, a low-intensity activity, with RPEs of 11 to 13 typically recorded in the activity diaries . Past ren = 13 per group). Secondly, regional (cfPWV) and local (carotid) measures of arterial stiffness were only investigated on participants' left-side. As the stroke diagnosis (and hemisphere affected) varied between participants  . Howevericipants , the assIn conclusion, the present study has demonstrated that participation in a 10-week, home-based, O-RAGT program, in combination with weekly, usual care physiotherapy, can elicit greater improvements in regional (cfPWV) measures of arterial stiffness in people with stroke than “usual care” alone. Importantly, the changes reported in cfPWV were maintained at 3PI assessment suggesting this may be a sustainable and efficacious treatment option once access to the O-RAGT device has been removed. Individuals randomized to the O-RAGT program also demonstrated increases in physical activity which could have the potential to improve quality of life. However, larger randomized controlled trials are required to identify whether the use of O-RAGT is appropriate to recommend as a part of usual care, while further research is also needed to determine whether implementing “at home” O-RAGT programs should be a part of the stroke treatment pathway.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by University of Winchester (RKE/10/2015-16). The patients/participants provided their written informed consent to participate in this study.JF and LM conceptualized the study. JF, AW, KS, SF, DL, and EP collected the data for the study. JF and LS were responsible for the formal analysis. JF was responsible for the original draft preparation. All authors reviewed, edited, approved the final manuscript, read, and agreed to the published version of the manuscript.