Compared to other aerobic trainings, WB-HIIT has a lower effect on CRF , a similar effect on fat-free mass  and fat mass , and a larger effect on musculoskeletal fitness . WB-HIIT overall effect and specific effect on CRF and fat mass were associated with total training time. The systematic review did not provide evidence of metabolic risk improvement. Despite a slightly lower effect on CRF, WB-HIIT is equally effective as traditional aerobic trainings to improve body composition and more effective to enhance musculoskeletal fitness, which is essential for execution of daily tasks.Due to its versatility, whole-body high-intensity interval training (WB-HIIT) can be proposed to the general population and patients to improve health-related fitness. However, its effectiveness compared to traditional aerobic continuous or interval trainings has yet to be determined. A search of four electronic databases was conducted. Studies reporting the effects of WB-HIIT on cardiorespiratory fitness (CRF), fat mass, fat-free mass, musculoskeletal fitness and metabolic risk factors were included. Standardized mean differences (SMD) between WB-HIIT and no exercise or traditional aerobic trainings were calculated. A meta-regression assessed the effect of total training time on the different outcomes. Twenty-two studies were included in the systematic review and nineteen in the meta-analysis. Compared to no exercise, WB-HIIT improves CRF (SMD: 0.75; 95%CI: 0.28, 1.23;  Among the barriers to physical activity, environmental context, cost, access to gym facilities, lack of time or bad weather are often mentioned . AlternaHigh-intensity functional training protocols consist of: (1) whole-body high-intensity interval training (WB-HIIT) using only the body weight as resistance  and 2) weightlifting exercises   weightli and presDespite these advantages, the actual effectiveness of WB-HIIT to improve health-related fitness, especially when compared to traditional forms of aerobic training, has yet to be determined. Traditional aerobic forms of training include HIIT and moderate- or vigorous-intensity continuous training (MICT or VICT) in which intensity remains constant. MICT is generally performed at an intensity between 64% and 77% of maximal heart rate (HRmax), while in VICT, intensity exceeds 77% of HRmax .In 2020, a meta-analysis compared the effect of WB-HIIT to MICT and HIIT on CRF in healthy individuals . The aimThis review was prospectively registered with PROSPERO (registration number: CRD42021266221). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) provided support in guiding this review .Potentially relevant studies were identified from four databases  up to March 2022. MeSH terms and free words referring to different training modalities were used . References from selected papers and from other relevant articles were screened for additional studies in accordance with the snowball principle. The search was limited to peer-reviewed journal articles published in English.®, step, elastic band, etc.) was accepted, but not the use of weightlifting exercises. Thus, protocols using CrossFit, heavy weight bearing, Olympic weightlifting, and functional training combined with aerobic training or strength training were excluded. This choice was made for the following reasons: the focus on health-related fitness, the accessibility of WB-HIIT to a large audience and in various settings, and to facilitate comparison with traditional aerobic trainings. Trials in which the training intervention was not defined or in which investigators did not design the exercise program were excluded. Studies had to include a comparator group, either traditional aerobic training  or no exercise. Studies using a comparator group of combined training  or comparing different forms of WB-HIIT without any other comparator group were excluded.Only randomized controlled trials on humans with a longitudinal design were eligible for inclusion. Animal studies, abstracts, case reports, study protocols, reviews or trials investigating acute effects of training were excluded. To be included, studies had to use a WB-HIIT intervention without diet modification or supplementation and test at least one of the following outcomes: CRF, fat mass, fat-free mass, musculoskeletal fitness or metabolic risk factors . Only WBArticles found in the different databases were collated using Endnote X9. Duplicates were removed by the software and verified by a reviewer. A first selection was made based on title and abstract and then on the full text by two reviewers.2max)), total fat mass, fat-free mass (including lean mass and muscle mass), musculoskeletal fitness (muscle strength and endurance) and metabolic risk factors (high- and low-density lipoproteins (HDL and LDL) cholesterol levels, fasting plasma glucose, visceral fat and blood pressure at rest) were extracted. Detailed data extraction was undertaken independently by two researchers and encoded in an Excel sheet including first author’s name, publication year, title, population, exercise and control groups, number and age of the participants, male/female ratio, outcomes and related results. When two papers were published [To investigate health-related fitness components, data related to CRF  and 95% CI were calculated for statistical analysis. SMD was defined as the between group difference in mean values divided by the pooled SD computed using the Hedge’s g method. Heterogeneity between the studies was assessed using I2. If the required data were not available in numeric text, authors were contacted to obtain the numerical data. If data could not be provided, the study was excluded from the meta-analysis. Data were then pooled using random-effect meta-analysis with subgroup analyses to evaluate the effect on each component: CRF, fat-free mass, fat mass and musculoskeletal fitness. A fixed-effect model was then performed to assess the overall effect of training on the different health-related fitness components. This model was chosen to give the same weight to each component, regardless of the number of individual observations. A first analysis was made between WB-HIIT and no exercise and a second one between WB-HIIT and traditional aerobic trainings .For each component, a minimum of three studies was required to be included in the meta-analysis , compariFor studies comparing WB-HIIT to no exercise, random-effects meta-regression analyses were computed to assess the association between the magnitude of effects  and total training time. Studies were weighted by the inverse of the sum of within- and between-study variance. Total training time was calculated by multiplying session duration by training frequency and by the number of weeks . Since nOf the 1959 trials retrieved from databases, twenty-two studies were selected for the systematic review and meta-analysis. Two studies ,17 were Characteristics of included studies are presented in Seventeen of the twenty-two initially selected studies had a PEDro score between 6 and 7, considered as “good” . Four hap = 0.054; WB-HIIT vs. traditional: p = 0.58), suggesting that there is no publication bias . When analyzing the different components, WB-HIIT statistically improved CRF , fat-free mass , fat mass  and musculoskeletal fitness . The forest plot summarizing the results is presented in Of the twelve studies ,31,32,33No meta-analysis was carried out for metabolic risk factors since only two studies assessed those ,22. TheyOf the eight ,26,27,34p = 0.22). Regarding CRF, a small effect was observed in favor of traditional aerobic training . In contrast, a small effect was observed in favor of WB-HIIT for musculoskeletal fitness . No difference was found between WB-HIIT and other training modalities for fat-free mass  or fat mass . The forest plot summarizing the results is presented in The overall effect on health-related fitness of WB-HIIT was not statistically different from traditional aerobic training  with total training time (p = 0.001) and fat mass (p < 0.001), but not for fat-free mass and musculoskeletal fitness  are predominant in improving these components.Since the WB-HIIT protocols included in the meta-analysis were designed to reach high intensities during the exercise phases, the greater effect of WB-HIIT on CRF, compared to no exercise, is consistent with previous findings . A novel2max [2max in HIIT protocols. Only one study reported peak and mean HR reached during training sessions, and they were lower for WB-HIIT compared to HIIT [When compared to traditional forms of aerobic training, our results show a lower effect of WB-HIIT to improve CRF. The lower effectiveness as compared to VICT could be explained by the shorter total training time in WB-HIIT and the high intensity of VICT, resulting in a greater training volume (time × intensity) for the latter. This hypothesis is supported by the observation that the study that compared WB-HIIT to MICT, characterized by a lower intensity than VICT, showed similar improvement after both training types . The HII2max ,36. Targ to HIIT . The finCompared to no exercise, the meta-analysis indicates a significant decrease in fat mass for WB-HIIT. The impact of total training time on fat mass loss supports the existence of a dose–response relationship. This finding is consistent with previous observations showing that HIIT with a sufficient energy expenditure is required to reduce body fat mass .When comparing WB-HIIT to traditional forms of aerobic training, the effect on fat mass is not different. As mentioned above, the intensity reached during WB-HIIT protocols was probably lower compared to HIIT and VICT, resulting in a lower training volume. Therefore, the similar effect on fat mass could at first be surprising. However, compared to traditional HIIT and VICT, WB-HIIT induces a greater muscle mass recruitment through exercises involving lower and upper limbs and core muscles, which would increase energy expenditure despite a lower training intensity. Unfortunately, no study compared energy expenditure between traditional aerobic trainings and WB-HIIT protocols. Nevertheless, WB-HIIT appears to be as effective as traditional aerobic training to decrease body fat mass when the amount of training is sufficient.Although resistance training using high loads is generally considered as the gold standard to induce muscle hypertrophy, emerging evidence suggests that interval training, such as HIIT or sprint interval training, has the potential to upregulate cellular mechanisms underlying lean mass increases . The enhThe effect of WB-HITT on fat-free mass was not different from traditional forms of aerobic training. The selected WB-HIIT and traditional aerobic training protocols were designed to elicit cardiovascular impact and were not optimized to improve muscle mass. This could explain the low effect on fat-free mass ,27,34 foOur results revealed that WB-HIIT is more effective than no exercise and traditional aerobic trainings to improve musculoskeletal fitness. To assess musculoskeletal fitness, strength tests  and muscular endurance tests  were used. Improvements in strength tests are known for being mainly related to greater muscle recruitment,  while muThe greater improvement in musculoskeletal fitness after WB-HIIT seems intrinsically linked to the training modality. Traditional forms of aerobic training are generally unimodal , while WB-HIIT is multimodal  and invoOnly two studies assessed metabolic risk factors after WB-HIIT vs. no exercise, and two compared WB-HIIT to other aerobic training. Except for the increased HDL levels with WB-HIIT in one study , and theThere are some limitations to this meta-analysis. First, session number and frequency and intervention duration differed greatly between studies. Only one study  recordedSome practical recommendations could be formulated based on our results. Since the effect of WB-HIIT appears to be related to total training time, and because previous studies have reported that intensity influences body composition and CRF changes ,37,43, WWB-HIIT is a low-cost, easy to implement, and effective way for improving CRF, body composition and musculoskeletal fitness. Although traditional forms of aerobic training are more effective at improving CRF, WB-HIIT induces equivalent improvements in body composition and has greater effects on musculoskeletal fitness required for execution of daily tasks. Importantly, our results highlight the dose–response relationship between WB-HIIT effects on CRF and fat mass and total training time. Since intensity affects training-related changes, it is essential that future studies systematically assess this parameter. Further studies are needed to establish if WB-HIIT improves autonomy and cardio-metabolic health in patients with physical limitations and metabolic risk factors, and to define the most effective WB-HITT protocols to improve specific components of health-related fitness.


Sparse model identification enables the discovery of nonlinear dynamical systems purely from data; however, this approach is sensitive to noise, especially in the low-data limit. In this work, we leverage the statistical approach of bootstrap aggregating (bagging) to robustify the sparse identification of the nonlinear dynamics (SINDy) algorithm. First, an ensemble of SINDy models is identified from subsets of limited and noisy data. The aggregate model statistics are then used to produce inclusion probabilities of the candidate functions, which enables uncertainty quantification and probabilistic forecasts. We apply this ensemble-SINDy (E-SINDy) algorithm to several synthetic and real-world datasets and demonstrate substantial improvements to the accuracy and robustness of model discovery from extremely noisy and limited data. For example, E-SINDy uncovers partial differential equations models from data with more than twice as much measurement noise as has been previously reported. Similarly, E-SINDy learns the Lotka Volterra dynamics from remarkably limited data of yearly lynx and hare pelts collected from 1900 to 1920. E-SINDy is computationally efficient, with similar scaling as standard SINDy. Finally, we show that ensemble statistics from E-SINDy can be exploited for active learning and improved model predictive control. A wide range of data-driven model discovery methods exist, including equation-free modelling , normal  (SINDy)  algorith (SINDy)  to produThe SINDy algorithm  providesModel discovery algorithms are sensitive to noise because they rely on the accurate computation of derivatives, which is especially challenging for PDEs where noise can be strongly amplified when computing higher-order spatial derivatives. There have been two key innovations to improve the noise robustness of SINDy: control volume formulations and ensemble methods. The integral formulation of SINDy  has provWhen dealing with noise-compromised data, it is also critical to provide uncertainty estimates of the discovered models. In this direction, recent innovations of SINDy use sparse Bayesian inference for probabilistic model discovery –60. Such1 to SINDy to identify models of nonlinear ODEs of the formIn this work, we unify and extend recent innovations in ensembling and the weak formulation of SINDy to develop and characterize a more robust ensemble-SINDy (E-SINDy) algorithm. Furthermore, we show how this method can be useful for active learning and control. In particular, we apply b(r)aggingsampling , which t. 2Here, we describe SINDy , a data- (a)The SINDy algorithm  identifiequation . SINDy uWe must also compute the time derivatives of the state equation  may thens (STLS)  uses R(ΞSTRidge)  uses Rpartial differential equation functional identification of nonlinear dynamics (PDE-FIND) algorithm. PDE-FIND is similar to SINDy, but with the library including partial derivatives. Spatial time-series data are arranged into a column vector et al. [SINDy was recently generalized to identify PDEs ,29 in thy et al.  takes deequation  is writtFor most PDEs, integral  and weakintegral ,54 were . 3In this work, we introduce E-SINDy, which incorporates ensembling techniques into data-driven model discovery. Ensembling is a well-established machine learning technique that combines multiple models to improve prediction. A range of ensembling methods exist, such as bagging (bootstrap aggregation) , bragginHere, we propose two new ensemble model discovery methods: the first method is called b(r)agging E-SINDy, and the second method is called library E-SINDy. A general schematic of E-SINDy is shown in The second method proposed, library bagging E-SINDy, samples library terms instead of data pairs. We sample E-SINDy provides inclusion probabilities and uncertainty estimates for the discovered model coefficients, thus connecting to Bayesian model identification techniques. The identified ensemble of model coefficients can be used to compute coefficient probability density functions, which form a posterior distribution . 4We now apply E-SINDy to challenging synthetic and real-world datasets to identify ODEs and PDEs. We apply library bagging E-SINDy to a real-world ecological dataset, showing its performance in the very low data limit. For PDEs, we use the recent weak-SINDy (WSINDy)  as a bas (a)We apply E-SINDy to a challenging real-world dataset from the Hudson Bay Company, which consists of the yearly number of lynx and hare pelts collected from 1900 to 1920. These pelt counts are thought to be roughly proportional to the population of the two species . Lynx ar (b)In this section, we present results applying E-SINDy to discover PDEs from noisy data. We use the recent WSINDy implementation  as the bWe apply E-WSINDy to identify PDEs from synthetic data for the inviscid Burgers, Korteweg de Vries, nonlinear Schroedinger, Kuramoto–Sivashinsky and reaction–diffusion equations. Details on the numerical methods for creating the data are discussed in appendix B and in our E-SINDy data and code repository. We quantify the accuracy and robustness of the model identification by assessing the success rate and model coefficient errors for a number of noise realizations. The success rate is defined as the rate of identifying the correct non-zero and zero terms in the library, averaged over all realizations. The model coefficient error  (c)We now present results exploiting the ensemble statistics for active learning ,81. Actia, we show five illustrative ensemble forecasts from different initial conditions after initializing the algorithm. In total, at each iteration, we compute ensemble forecasts at 200 different initial conditions. We found that at each initial condition, integrating a single time step forward in time is informative enough to compute ensemble forecasting variance. In figure 5b, we show the probability density functions of the identified model coefficients at initialization have wide distributions, and after 80 active learning steps the variance of the distributions is significantly reduced. Figure 5c also shows the improved data efficiency of the model discovery using active learning E-SINDy compared with E-SINDy. Through active E-SINDy, we reduce the variance of the identified model coefficients, increase the success rate of identifying the correct model structure and reduce the model coefficient error compared with standard E-SINDy.Here, we test active E-SINDy on the Lorenz system dynamics introduced in figure 5 (d)et al. [It is also possible to use E-SINDy to improve model predictive control (MPC) –86. MPC et al.  showed tet al. [a, we show the sensitivity of the mean MPC cost to training data length. We run 1000 noise realizations and average the mean MPC cost of all runs. Figure 6b shows trajectories of the controlled Lorenz system for models trained with E-SINDy and SINDy, using 50 and 150 time-step data points. E-SINDy significantly improves the MPC performance in the low data limit compared with SINDy.We use E-SINDy to identify a model of the forced Lorenz system dynamics and use MPC to stabilize one of the two unstable fixed points r et al. . We desc. 5This work has developed and demonstrated a robust variant of the SINDy algorithm based on ensembling. The proposed E-SINDy algorithm significantly improves the robustness and accuracy of SINDy for model discovery, reducing the data requirements and increasing noise tolerance. E-SINDy exploits foundational statistical methods, such as bootstrap aggregating, to identify ensembles of ODEs and PDEs that govern the dynamics from noisy data. From this ensemble of models, aggregate model statistics are used to generate inclusion probabilities of candidate functions, which promotes interpretability in model selection and provides probabilistic forecasts. We show that ensembling may be used to improve several standard SINDy variants, including the integral formulation for PDEs. Combining ensembling with the integral formulation of SINDy enables the identification of PDE models from data with more than twice as much measurement noise as has been previously reported. These results are promising for the discovery of governing equations for complex systems in neuroscience, power grids, epidemiology, finance or ecology, where governing equations have remained elusive. Importantly, the computational effort to generate probabilistic models using E-SINDy is low. E-SINDy produces accurate probabilistic models in seconds, compared with existing Bayesian inference methods that take several hours. Library bagging has the additional advantage of making the least-squares computation more efficient by sampling only small subsets of the library. E-SINDy has also been incorporated into the open-source PySINDy package ,63 to prWe also present results exploiting the ensemble statistics for active learning and control. Recent active exploration methods  and acti


During the first year of the COVID-19 pandemic, U.S. companies were seeking ways to support their employees to return to the workplace. Nonetheless, the development of strategies to support the access, use, and interpretation of SARS-CoV-2 testing was challenging. In the present study, we explore, from the perspective of owners and company leadership, the barriers to SARS-CoV-2 testing among U.S. companies. Key informant interviews with company representatives were conducted during January–April 2021 about SARS-CoV-2 testing. A pre-interview survey assessed respondent socio-demographic and organizational characteristics. Interview sessions were transcribed, coded, and analyzed using MaxQDA. A total of twenty interviews were completed with at least two interviews conducted in each major U.S. industry sector. Ninety percent of participants represented companies in business >10 years, comprising both small and large workforces. Using a grounded theory approach, six themes emerged: (1) access to and knowledge of SARS-CoV-2 tests; (2) strategies for symptomatic and asymptomatic testing of workers; (3) type/availability of personal protective equipment to mitigate coronavirus exposures; (4) return-to-work policies; (5) guidance and communication of SARS-CoV-2 Testing; and (6) use of contact tracing and SARS-CoV-2 vaccination. Various modifiable and non-modifiable challenges for SARS-CoV-2 testing among U.S. companies were identified and can inform work-related SARS-CoV-2 testing strategies. Following lockdowns during the first year of the COVID-19 pandemic, U.S. companies were increasingly asking their employees to return to the workplace. Nonetheless, the development of strategies to support the access, use, and interpretation of SARS-CoV-2 testing was challenging . Small bIn April 2020, the U.S. White House provided broad guidance as to whether and how frequently employers should test workers for SARS-CoV-2 . This guThere were two phases to this study, a qualitative phase, and a quantitative phase. A mixed-methods sequential exploratory study design was used to initially characterize through qualitative data and subsequently quantifying, through survey data, facilitators and barriers for SARS-CoV-2 testing among U.S. businesses . In thisThe project team, supported by CDC’s National Institute for Occupational Safety and Health (NIOSH), used its existing professional networks to identify company owners, upper-level managers, human resource leaders, or health and safety officers for in-depth interviews. The recruitment goal was to identify and conduct semi-structured key informant interviews with company leaders. Eligibility criteria for participation in the study were adults age ≥18 years who speak and write in English and work for, or own, a U.S. business principally operating in the United States. Company leaders of all races and ethnicities were encouraged to participate. To achieve diversity of responses across U.S. sectors, existing NIOSH National Occupational Research Agenda (NORA) networks were used to invite and conduct interviews with members from the following industry sectors: Agriculture, Forestry & Fishing (except Wildland Firefighting and including seafood processing); Construction; Healthcare & Social Assistance ; Manufacturing (except seafood processing); Mining; Oil and Gas Extraction; Public Safety (including Wildland Firefighting); Services ; Transportation, Warehousing & Utilities; and Wholesale and Retail Trade. Interviewees were not provided any compensation for participation in the study. Twenty interviews were conducted from January through April 2021 using a virtual meeting platform that allowed for audio recording and transcription of the interview . ParticiFrequency and descriptive statistics for all 17 items in the pre-interview survey were tabulated. Categorical variables were expressed as frequency and percent. Statistical analysis of survey data was performed using the Statistical Package for the Social Sciences . The transcribed files were exported as documents and uploaded into MaxQDA Analytics Pro 2020 , a computer-assisted qualitative data analysis program . A preliAmong the 20 participating companies, 11 (55%) offered SARS-CoV-2 testing to their employees. Of those, five (46%) used partnerships with local labs or healthcare providers for testing .Among the 11 companies whose representative reported providing SARS-CoV-2 testing, on average, two types of tests were offered, of which real-time reverse transcriptase polymerase chain reaction (RT-PCR) (63.6%) was the most frequent. Turn-around time for SARS-CoV-2 test results was usually three or more days (62.5%). Over the course of the pandemic, company representatives reported in the pre-interview survey using various methods for return-to-work , with some type of non-test-based strategy, such as in-person screening for SARS-CoV-2 signs/symptoms (45.5%), being a slightly more common approach than SARS-CoV-2 test-based strategies (36.4%), such as antigen or antibody tests.Key informant interview respondents provided rich descriptions of the facilitators and barriers to SARS-CoV-2 testing encountered during the early months  of the pandemic. Employers encountered numerous challenges in implementing SARS-CoV-2 testing, whether doing it themselves , or sending employees out for tests. The challenges can be categorized as “Initial and Resolved” versus “Ongoing,” and within those two groups, by problems related to the test/testing procedure, logistics of testing workers, employee management, or broader organizational concerns. About half of the employers have resolved many of their initial problems with locating testing facilities or vendors, accessing testing supplies, or encouraging their workers to take SARS-CoV-2 testing seriously. Respondents indicated that the most serious ongoing problems included reductions in workforce due to positive test results, waiting for test results, or quarantine and isolation protocols. This creates a concomitant burden on other staff or curtails company production or service. Some respondents indicated their respective companies were not doing, and could not do, routine testing of asymptomatic employees due to the cost, lack of interest from employees, or lack of perceived ‘value’ to the company, compared to other measures such as employee screenings and quarantine. This varied over time, with some organizations becoming more dependent on testing, whereas others discontinued the use of testing in favor of screening employees for symptoms. Several respondents described protocols for guiding employees to testing depending on where exposure possibly took place, i.e., at the worksite or in the community. Responsibility for testing was seen to be an employer burden if the exposure was acquired while working. Respondents indicated that employees who believed they were exposed elsewhere were asked to use their own healthcare providers and resources for SARS-CoV-2 testing. Many respondents described using temperature checks in the workplace at the outset of the pandemic, but retired those in favor of self-reported symptoms, some based on questionnaires. Those whose workers interacted directly with the public  reported a perception of doing more routine testing than other sectors in their area. However, only one of the 20 interviewees, an educational organization, was continuing to test asymptomatic employees at the time of the survey. Such testing was considered cost-prohibitive, and the tests were not available at that scale. Several respondents described collaborations with local health departments or clinics, or the availability of on-site or nearby laboratories, which greatly facilitated testing. During the first year of the pandemic, respondents without such arrangements tended to send employees to their own healthcare providers or wherever tests were being offered .The perception of SARS-CoV-2 risk and exposure was greatest early in the pandemic as all companies were learning about transmission routes. As understanding of hazard and mitigation strategies improved, most respondents in this qualitative study  reported that they felt their employees were at no additional risk, beyond what employees experienced in the community, of contracting SARS-CoV-2 on the job. Mitigation strategies mentioned included testing, physical distancing, cleaning, use of negative pressure rooms , and use of PPE. There was general awareness of the higher risk associated with confined indoor spaces versus outdoor spaces, and of the importance of employee participation in developing safety and health protocols. Once protocols were put in place to deal with exposures, concern decreased over time. Use of PPE prior to the pandemic varied by NORA sector, with heavy industries  accustomed to protective equipment for handling hazardous materials. Other industries that routinely used PPE prior to SARS-CoV-2 included construction workers wearing hard hats and boots; grocery retail involving raw meat and cutting using cut-resistant gloves and face masks; agricultural workers using respiratory protection for grain dust and pesticides; and health and safety workers accustomed to masks and gloves. Many stated that while such protections were common on the job, the idea of wearing masks outside of work was new. Some study participants described how SARS-CoV-2 transformed the use of PPE, and this factor seemed relatively unimportant in decisions pertaining to testing except in the healthcare area, where PPE was thought to prevent transmission of SARS-CoV-2 from potentially infected workers to patients, and vice versa. U.S. companies employed varying guidelines for SARS-CoV-2 return-to-work (RTW), for workers who tested positive, and workers exposed to a positive individual, based on the industry and sources of information guiding RTW policies. Eighty percent of respondents required a negative test initially until this was perceived as impractical due to the long wait periods to receive results, or they doubted the validity of test results . Respondents from healthcare sectors reported having employees returning to work while testing positive (if symptom free) as the company leadership felt their PPE prevented transmission. Most interviewees reported that they stopped requiring employees to be symptom-free (particularly no fever) for three days following a period of quarantine after possible exposure to COVID-19, which they then reported moving from 14 to 10 to seven days. Some mentioned this was following quarantine reductions issued by the CDC. Some respondents in this study reported that there was division between those believing employees took advantage of test results and quarantine guidelines to have paid time off, and others (mostly those using hourly workers) who were concerned that employees would not get tested if it meant they had to miss work, i.e., they would come to work SARS-CoV-2-positive or sick rather than miss a day’s pay. Respondents indicated there were clear tensions between the operational and production needs of companies and the limits set on time away from work for those who tested positive or who came into contact with positive workers. Most respondents claimed to follow the guidance from either the CDC or their state/local health department. However, they had different interpretations of the same guidance. Respondents from two larger organizations mentioned the need to adhere to guidance from multiple states or counties, and this made management more difficult. Several respondents did not mention any clear sources of guidance. Others reported difficulties following guidelines, either because guidelines were unclear, were perceived as conflicting or changing rapidly, or did not meet their needs or facilitate their processes. Respondents indicated that their companies experienced a wide variation in the amount of information that was communicated to them by federal, state, and local governmental bodies about testing and vaccines. Not all employers communicated about both; some communicated about testing but not vaccines, and vice versa. Several participants reported discrepancies between federal and state recommendations which resulted in confusing communications from the employers. One respondent suggested involving the health department or medical personnel in helping organizations interpret guidance and communicate it more effectively.A related theme that emerged from the interviews on SARS-CoV-2 testing was contact tracing. Twelve of 20 respondents said their company was doing some form of contact tracing, and one was unsure what the company was doing. Others described procedures ranging from informal notification  to descriptions equivalent to the definition provided by the interviewer ; three company representatives mentioned more formal methods of notification, but lack of referrals or long-term follow-up. There were no reasons provided for not doing tracing; it was merely said that it did not seem necessary , or that it was turned over to the health department. Eight of 20 respondents indicated tracing beyond employees or suggested strong collaborations with health departments. Interviewees indicated that responsibility for contact tracing by a company seemed to depend on whether the primary exposure was thought to have occurred at work  or elsewhere .Some interviewees mentioned challenges with the implementation of SARS-CoV-2 vaccination within their companies, efforts to conduct SARS-CoV-2 vaccination campaigns, and barriers to scheduling appointments to get vaccinated. These interviewees, similar to other participating companies, reported that finding dates and times to release employees for vaccination at sites located at the county- or city-level was challenging. Several factors, both facilitators of, and barriers to, SARS-CoV-2 testing, were identified in this initial qualitative phase of the ETCH study. Since the start of the SARS-CoV-2 pandemic, U.S. companies have struggled with access to and understanding of information about SARS-CoV-2 testing. This study documented that the company leaders interviewed were confused about reliable and consistent sources of SARS-CoV-2 information. Respondents also perceived conflicting information about SARS-CoV-2 testing requirements between local and federal guidelines. These findings are consistent with research by McElfish et al., who found unclear guidance and uncertainty regarding SARS-CoV-2 testing guidelines among residents from the State of Arkansas . CompanyWe found that participating company leaders were challenged by testing symptomatic and asymptomatic individuals, particularly in companies with larger workforce sizes. Some U.S. sectors and companies, during the study observation period, sought to devise strategies for testing and return to work to maintain a functional workforce. Our study findings are similar to those reported by Lecouturier et al. in a qualitative study of the general public, including working and non-working adults . They foThe current study had limitations. We had a very small sample of U.S. companies reporting on their challenges and approaches to SARS-CoV-2 testing. Our recruitment approach used the NORA sectors network, which supported the inclusion of a diversity of companies, but there are also likely variations in the facilitators and barriers to SARS-CoV-2 testing by size of company and geography. Saturation (repetition of similar responses) was achieved in this sample of interviewees, supporting a transition to the subsequent phase of this study to identify SARS-CoV-2 testing factors that could be quantified in a survey with a larger, more diverse sample of U.S. companies. Not all interviewees were owners of the company. Respondents included human resource leaders and medical, health, and safety officers who may not have had full awareness of their company’s challenges in SARS-CoV-2 testing. Additional limitations include that a majority of participating companies had been operational for over 10 years and that most participating companies had a workforce size of 50 or more employees, limiting perspectives from newer and smaller businesses. Nonetheless, this non-probabilistic sample included some responses across all employee workforce size ranges. Lastly, the responses in this pilot study are not generalizable to all U.S. industries and should not be interpreted to provide generalizable information on factors that impact SARS-CoV-2 testing among U.S. companies. Despite these limitations, this pilot study had several strengths, including a diversity of responses across U.S. industry sectors that allowed for the identification of several factors affecting use of SARS-CoV-2 testing. Using a key informant interview format allowed for the in-depth exploration of perspectives and responses from company leadership on factors, processes, and information sources that hindered or supported their businesses’ ability to offer testing and contact tracing.U.S. companies have experienced several challenges since the start of the SARS-CoV-2 pandemic with offering regular and consistent SARS-CoV-2 testing. We identified six major themes about SARS-CoV-2 testing that spanned access to and knowledge of SARS-CoV-2 testing, strategies for symptom-based testing, availability of PPE, RTW policies, authoritative guidance on SARS-CoV-2 testing, as well as how contact tracing and emerging SARS-CoV-2 vaccination options would impact SARS-CoV-2 testing. This study sheds light on potentially modifiable and non-modifiable factors that could inform SARS-CoV-2 testing strategies for U.S. companies. Future studies might be able to quantify these identified themes in a larger sample of U.S. companies to inform the prioritization of factors to support U.S. businesses by sector and size in offering SARS-CoV-2 testing to their employees.


Most chemotherapy regimens used in the setting of non-metastatic breast cancer are myelosuppressive and are associated with toxicities with significant clinical implications, including febrile neutropenia. The use of granulocyte colony-stimulating factor (G-CSF) reduces the severity and duration of febrile neutropenia, following the initiation of myelosuppressive chemotherapy. The practice of G-CSF prophylaxis is a proven form of supportive care that is shifting with the introduction of biosimilars. As published data are limited, we characterized the patterns and predictors of G-CSF use in a large real-world Canadian cohort over an 11-year period. Our results demonstrate that G-CSF use can be further optimized to align with current guidelines and to improve supportive care for patients with breast cancer.n = 3477) versus filgrastim only . G-CSF use increased linearly more than two-fold over the 11-year study period. Predictors of G-CSF use included younger age, south zone of residence, higher neighborhood education, inferior disease stage, highly neutropenic risk chemotherapy, and more recent chemotherapy initiation. Conclusions: Despite increasing G-CSF usage over time, an appreciable proportion of patients for whom G-CSF prophylaxis is recommended did not receive it. G-CSF use could be further optimized to align with supportive care clinical guidelines and reduce the impact of neutropenia and its associated complications.Background: There are limited published data in the Canadian healthcare system on the use of granulocyte colony-stimulating factor (G-CSF) among patients with breast cancer. This study characterized real-world G-CSF use during the period surrounding the introduction of filgrastim biosimilar. Methods: Electronic medical records were reviewed retrospectively for patients with breast cancer who received moderately or highly myelosuppressive (neo)adjuvant chemotherapy from 2008 to 2019 in Alberta, Canada. Trends in G-CSF usage were plotted to elucidate temporal variations and multivariable regression models were constructed to identify clinical factors associated with G-CSF use. Results: We included 6662 patients in our analyses. G-CSF was used in 57.1% of patients during their treatment trajectory. Among the 3801 patients who were treated with G-CSF, the majority received pegfilgrastim only (91.5%;  The primary curative intent treatment modality for non-metastatic breast cancer is surgery, but patients with high-risk clinical or pathological features are commonly also offered neoadjuvant or adjuvant therapy as a standard of care. Most chemotherapy regimens used in this setting are myelosuppressive and are associated with a variety of hematological toxicities, including neutropenia and febrile neutropenia (FN). In particular, FN represents the most important dose-limiting toxicity of myelosuppressive chemotherapy, posing significant issues in the management of patients and contributing to a heightened risk of significant morbidity and mortality, increased healthcare resource use, and potential dose modifications with a subsequent failure to achieve optimal relative dose intensity (RDI) ,2. ApproThe use of granulocyte colony-stimulating factor (G-CSF) reduces the severity and duration of neutropenia following myelosuppressive chemotherapy, and prophylaxis has been shown to significantly decrease the risk of FN in patients ,5. G-CSFInternational guidelines have a high degree of consensus and uniformly recommend prophylactic use of G-CSF when there is a high risk (>20%) of FN ,12. FN rSince the use of supportive care medications in real-world clinical practice varies from the guideline recommendations, and these medications are not uniformly reimbursed in Canada, there are concerns that G-CSF use may be suboptimal or overall under-utilized . In 2017This was a retrospective, population-based study conducted in Alberta, Canada, which represents the country’s fourth-largest province, with a population of over four million residents. The Alberta Cancer Registry (ACR) was the primary data source for patient demographics, tumor characteristics, and treatment patterns, which were collected prospectively for all patients diagnosed with cancer in the province. Additional data sources included ambulatory care records, physician billing claims, and hospital discharge abstracts, based on previously validated coding algorithms of the International Classification of Diseases and Related Health Problems (ICD). The study protocol was reviewed and approved by the research ethics committee prior to data collection and analysis. This study’s design, analysis, and reporting all adhere to the STROBE  guidelines .Included patients were those aged 18 years or older, newly diagnosed with stage I to III breast cancer in Alberta, from January 2008 to December 2017, who received at least one cycle of moderately or highly myelosuppressive chemotherapy in the neoadjuvant or adjuvant setting. Patients who were diagnosed with multiple cancers were excluded. Patients were also excluded if they had received G-CSF as part of a clinical study protocol or if they were treated with myelosuppressive.The main outcome of interest was the receipt of either filgrastim or pegfilgrastim during the study period, January 2008 to November 2019. The date of initiation of the first cycle of chemotherapy was considered the study index date. Primary prophylaxis was defined as G-CSF administration within seven days of the start of a chemotherapy cycle. Chemotherapy regimens with high neutropenic risk included AC-T (doxorubicin hydrochloride and cyclophosphamide followed by paclitaxel), DC (docetaxel and cyclophosphamide), ddAC (dose-dense doxorubicin and cyclophosphamide), FEC-D , and TCH , whereas those with moderate neutropenic risk were CMF , 3-weekly docetaxel, and FEC  [Demographic information retrieved from the ACR comprised age at treatment initiation and residential postal code. Postal codes were used to derive information on neighborhood-level socioeconomic status, including educational attainment and annual household income, based on 2011 census data, which represented the most recent year of available data. Descriptive statistics were used to analyse the baseline demographic- and treatment-related characteristics. To elucidate differences in baseline characteristics between groups, the Wilcoxon rank-sum test was used for continuous variables, whereas Pearson’s Chi-squared test or Fisher’s exact test were used for categorical variables. Additionally, standardized mean difference (SMD) was computed to reinforce comparisons of baseline characteristics, with SMD > 0.1 considered indicative of imbalance. Multivariable logistic regression analyses were performed to assess the likelihood of receiving G-CSF as a binary variable (yes/no) and that of receiving filgrastim over pegfilgrastim. All statistical tests were two-sided, and the significance level was defined a priori as <0.05. All analyses were performed using R.In total, we identified 6662 patients diagnosed with early-stage breast cancer from 2008 to 2017 who received either moderately or highly myelosuppressive (neo)adjuvant chemotherapy . Among tp < 0.001, SMD > 0.1 for each). Among the 3801 patients who received G-CSF, the vast majority received pegfilgrastim only , whereas the others received either filgrastim only  or both pegfilgrastim and filgrastim . Patients who received filgrastim only were more likely to have a younger age, Calgary zone of residence, higher neighborhood education, advanced disease stage, or more recent year of chemotherapy initiation  (n = 3323), but those who did were more likely to receive filgrastim versus pegfilgrastim .Of the entire study cohort, 3801 (57.1%) patients received G-CSF at some point during the chemotherapy treatment trajectory . Patientor each) . Among tExamining treatment patterns by calendar year, G-CSF use over the 11-year study period appeared to increase linearly from 34.2% in 2008 to 78.0% in 2018 . Among pp < 0.01 for all)   . In the for all) .This was a large retrospective study of a population-based cohort of patients with early-stage breast cancer to describe the use of G-CSF over an 11-year period in Alberta, Canada. Overall, we observed that G-CSF was not used consistently in the setting of myelosuppressive chemotherapy with a high or moderate risk of FN, where only approximately half of the study cohort had a record of at least one G-CSF prescription. In most of these cases, G-CSF was not used as primary prophylaxis for the first chemotherapy cycle. Despite guidelines that recommend primary G-CSF prophylaxis for chemotherapy regimens with an FN risk of >20%, other longitudinal real-world evidence studies have also reported an underutilization of G-CSF in patients with cancer, including patients with non-metastatic breast cancer at high risk of FN based on chemotherapy and patient-related factors . A retrospective study by Fine et al. included 395 patients who initiated G-CSF in the oncology outpatient setting between January 2008 and January 2009 in the Canadian provinces of Ontario and Quebec . OverallEven though G-CSF use was suboptimal overall, we observed sizeable and consistent growth in G-CSF use from 2008 to 2018, both graphically and through regression analysis. These temporal trends were concordant with the analysis of a US Medicare population of older women receiving adjuvant chemotherapy for early-stage breast cancer between 2002 and 2012 . HoweverThe introduction of biosimilars, such as Grastofil, may further improve G-CSF use. This biosimilar of filgrastim was introduced in Alberta in 2017, toward the end of our study period. While the change in overall G-CSF use was linear throughout our study period, we observed an increase in the proportion of patients receiving filgrastim, compared to pegfilgrastim around 2017. This may indicate a shifting treatment paradigm, attributed to the introduction of Grastofil and to the fact that some private insurance plans implemented a preferential listing of Grastofil over pegfilgrastim in fall 2016. The role of biosimilars in improving access by reducing cost-associated barriers is well-supported. The launch of biosimilar filgrastim in Europe was associated with initial cost savings of 14–27%, increased access, and decreased rates of FN-related hospitalization ,24,25. MWe found certain patient factors to be associated with the increased use of G-CSF and the preference of one G-CSF type over another. Of the demographic characteristics analysed, zone of residence, neighborhood education, and age were significant predictors of G-CSF use. Since southern-most zones of residence are also those with relatively higher population density, we hypothesize that geographic barriers to care may have contributed to the variations in the rates of G-CSF use across the province. Neighborhood education may serve as a surrogate measure of health literacy, which has well-established links with access to care and health outcomes ,29. Low Our study design has inherent limitations. We focused on patients with breast cancer due to the high incidence of FN in this population, but we inevitably excluded other patients treated with myelosuppressive chemotherapy, who may benefit from G-CSF. We extracted data for G-CSF and chemotherapy administration from pharmacy dispensing records, rather than usage records; thus, we could not assess G-CSF use after the first cycle of chemotherapy. Lastly, our retrospective approach to data collection may have introduced unknown variables with the potential to confound the relationship between patient factors and G-CSF use.There was a consistent rise in G-CSF use in the Alberta healthcare system from 2008 to 2018, yet an appreciable proportion of patients with breast cancer for whom G-CSF prophylaxis is recommended did not receive it. Opportunities exist to further optimize G-CSF use to align with current supportive care clinical guidelines and to reduce the impact of neutropenia and its associated complications. Characteristics of the patient and their cancer treatment should be carefully taken into consideration when planning strategies for supportive care. Potential directions for future research include expanding the evaluation of G-CSF use into other cancer sites and unpacking the impact of biosimilars on improving G-CSF access at a pan-Canadian level.


One of the recent advances in solid organ transplantation has been the definition of molecular mismatching between donors and recipients’ Human Leukocyte Antigens (HLA). While not fully integrated in standard clinical care, cumulative molecular mismatch at the level of eplets (EMM) as well as the PIRCHE-II score have shown promise in predicting transplant outcomes. In this manuscript, we sought to study whether certain T-cell molecular mismatches (TcEMM) were highly predictive of death-censored graft failure (DCGF).Kidney transplantation is the optimal treatment in end-stage kidney disease, but We studied a retrospective cohort of kidney donor:recipient pairs from the Scientific Registry of Transplant Recipients (2000-2015). Allele level HLA-A, B, C, DRB1 and DQB1 types were imputed from serologic types using the NMDP algorithm. TcEMMs were then estimated using the PIRCHE-II algorithm. Multivariable Accelerated Failure Time (AFT) models assessed the association between each TcEMM and DCGF. To discriminate between TcEMMs most predictive of DCGF, we fit multivariable Lasso penalized regression models. We identified co-expressed TcEMMs using weighted correlation network analysis (WGCNA). Finally, we conducted sensitivity analyses to address PIRCHE and IMGT/HLA version updates.A total of 118,309 donor:recipient pairs meeting the eligibility criteria were studied. When applying the PIRCHE-II algorithm, we identified 1,935 distinct TcEMMs at the population level. A total of 218 of the observed TcEMM were independently associated with DCGF by AFT models. The Lasso penalized regression model with post selection inference identified a smaller subset of 86 TcEMMs  to be highly predictive of DCGF. Of the observed TcEMM, 38.14% appeared as profiles of highly co-expressed TcEMMs. In addition, sensitivity analyses identified that the selected TcEMM were congruent across IMGT/HLA versions.In this study, we identified subsets of TcEMMs highly predictive of DCGF and profiles of co-expressed mismatches. Experimental verification of these TcEMMs determining immune responses and how they may interact with EMM as predictors of transplant outcomes would justify their consideration in organ allocation schemes and for modifying immunosuppression regimens. Solid organ transplantation is the definitive treatment for eligible patients with end stage organ failure . Among aImmune-related injury is less likely when HLA compatibility is greater between patients and donors. Yet, the fact that more than 32,000 HLA alleles have been identified makes complete HLA allelic matching of unrelated donors and patients exceedingly difficult . HLAMatcIt is also important to recall that most EMM were envisioned to explain immune recognition by B-cells, which represents only part of the sequence of events leading to donor-specific antibody (DSA) development and allograft rejection. While the B-cell response is pivotal in DSA development, the T-cell response is also of importance . To addrLike EMM, the analysis of PIRCHE-II is highly susceptible to the complexities of high dimensionality and relatedness between PIRCHE-II peptides. The relatedness (measured by correlation) is, at least in part, due to the tendency of HLA genes to be in linkage disequilibrium, and for PIRCHE-II peptides to be present in relation to multiple HLA molecules . ConsequThis study used data from the Scientific Registry of Transplant Recipients (SRTR). The SRTR data system includes data on all donors, wait-listed candidates, and transplant recipients in the US, submitted by the members of the Organ Procurement and Transplantation Network (OPTN). The Health Resources and Services Administration (HRSA), U.S. Department of Health and Human Services provides oversight to the activities of the OPTN and SRTR contractors. The McGill University Health Center research ethics board approved the study.st, 2000 to January 1st, 2015. We excluded KTR who received multi-organ transplants or who had prior transplants. We also excluded KTRs who exhibited preformed antibodies (based on peak panel reactive antibody (PRA) above 0% irrespective of the cause for sensitization, those missing PRA, and those who experienced primary graft non-function.We performed a retrospective cohort study in kidney transplant recipients (KTRs) transplanted from January 1Allele-level HLA-A, -B, -C, -DRB1, and -DQB1 genotypes were imputed using the National Marrow Donor Program algorithm as previously described . This coThe primary outcome was time to DCGF, defined as return to dialysis or re-transplantation. All baseline characteristics of recipients , donors  and transplants  were considered as potential covariates  regression using an Accelerated Failure Time (AFT) model (under a Weibull distribution) of the log-transformed PIRCHE-II score. Missing values for covariates were previously imputed by Multiple Imputation by Chained Equations (MICE)  . In accos (MICE) . As we fs (MICE) . FinallyTo identify a subset of TcEMMs highly predictive of DCGF, while considering highly co-expressed TcEMM, we fitted penalized Cox regression models. We used the Least Absolute Shrinkage and Selection Operator (Lasso) method for feature selection and regularization of data , 26. LasLasso penalized regression identifies, from a group of potential variables, the most informative predictors in relation to an outcome of interest. In this process, one of several correlated variables could be selected as the important predictor. Yet, either the selected predictor, or the variables correlated with it, could be causally related to the outcome. To represent the interrelatedness between TcEMMs, we used Weighted Correlation Network Analysis (WGCNA) and computed the predictor’s correlation matrix. Using a correlation threshold of 0.74 (corresponding to an adjacency threshold of 0.3 ), we genWe performed a sensitivity analysis to evaluate how the output of the PIRCHE-II algorithm may vary when considering the most recent update to the IMGT/HLA version 3.47 (PIRCHE-II 3.3) in comparison to the prior version 3.46 (PIRCHE-II 3.2). We compared the mismatched TcEMMs generated by the PIRCHE-II algorithm and evaluated the impact of this change on the identity of TcEMM at the population and at the donor-recipient pair level. Statistical analyses were performed using several packages [WGCNA , 28, glmUpon application of the exclusion criteria, we identified 118,309 eligible KTR  donor:recipient pairs. Of the possible multivariable AFT models considering each TcEMM as the main exposure, the Weibull distribution offered the best fit as measured by the AIC score, and all distributions were better than the fit from CoxPH models (-03 (8.45x10-06 - 2.26x10-01) and 9.44x10-03 (8.45x10-06 - 2.02x10-01), respectively).When assessing whether the frequencies of TcEMM differed between those TcEMM that were predictive of DCGF and those that were not, we observed overlapping distributions (median (range): 6.27x10To fit a parsimonious model including the selection of TcEMM most predictive of DCGF, we fit regression models and applied a Lasso penalization term. A subset of 104 Class I and 82 Class II derived TcEMM were identified as predictors of DCGF (https://wlemieux03.github.io/TcEMM/for interactive graphs).Co-expressed TcEMMs observed in the entire cohort when undergoing WGCNA are presented in We conducted sensitivity analyses to address IMGT/HLA version updates. Realising the PIRCHE-II algorithm is likely to yield distinct TcEMM as the IMGT/HLA database is updated, we evaluated the differences between the TcEMM observed in the IMGT/HLA version the PIRCHE-II algorithm relied on for our main analyses (3.46) with those observed with the most recent version (3.47) , our analyses sought to distinguish between TcEMMs associated with an increased risk of DCGF and those that were not. AFT models followed by penalized regression models and post-selection inference informed an up to 20-fold reduction in the number of TcEMMs associated with DCGF. These findings pave the way to more targeted experimental verification of TcEMMs. Such experimental verification will then lend support to their consideration in decisions on organ allocation and personalized management of KTR.There is a need for novel biomarkers informing risk for immune and non-immune-mediated outcomes in kidney transplantation , 35. WitIt has been proposed that the frequency of TcEMM among donor:recipient pairs may affect the likelihood of it being predictive of DCGF. Inevitably, rare albeit high risk TcEMM are likely to yield imprecise relative risk estimates Figure 2Our study is the first to demonstrate an association between PIRCHE-II and DCGF in SRTR as well as the first attempt to identify TcEMM most predictive of DCGF. Nevertheless, we would like to acknowledge several limitations of the analyses and outline future research directions. First, while leveraging the analytical power enabled by the large SRTR dataset, which includes diverse populations of KTR, compensating for the sparsity of TcEMMs, it is vital to acknowledge that the TcEMM estimation is dependent on IMGT/HLA version considered and in the case of our analytic cohort relies on imputation . UnavailIn conclusion, we sought to assess the contribution of individual TcEMM as determinants of DCGF and were able to distinguish increasingly smaller numbers of TcEMM most predictive of this endpoint through various approaches. Further validation of these TcEMM as determinants of transplant outcomes in large independent cohorts with allele-level HLA genotypes is needed. Furthermore, investigation of the properties that may contribute to immune injury are also needed. While TcEMM is not ready for clinical application, our observations provide the foundation for future studies assessing whether these high risk TcEMM (or the TcEMM co-expressed with them) inform other hard clinical endpoints like biopsy proven rejection. Such verification would justify their avoidance during organ allocation or modifications of posttransplant management when mismatches cannot be avoided. Importantly, with a better differentiation of risk profiles of particular EMM and TcEMM, future research is needed to clarify how they interact and inform long-term transplant outcomes.https://www.srtr.org/requesting-srtr-data/data-requests/.The data analyzed in this study was obtained from the SRTR. To learn about the applicable licenses/restrictions and submit requests to access these datasets, please consult: The studies involving human participants were reviewed and approved by McGill University Health Center research ethics board. Written informed consent from the participants’ legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements.Study conception and design: WL, RS-P. Acquisition of data: RS-P. Analysis and interpretation of data: WL, DF, AY, and RS-P. Drafting of manuscript: WL and RS-P Critical revision: WL, AY, MN, KO, WK, LR, CP, RL, FC, HG, PK, AL, RS-P. All authors contributed to the article and approved the submitted version.https://www.calculquebec.ca) and Compute Canada (https://www.computecanada.ca) through a Resource Allocation for Research groups (RAC cna-921-ac), and a MITACS Accelerate grant. RS-P is supported by Fonds de recherche du Quebec—Santé chercheur boursier clinicien award (grant no. 254386).This research was enabled thanks to support provided by Genome Canada Large Scale Applied Research Program Award “Precision Medicine CanPREVENT AMR” funded by Genome Quebec, Genome British Columbia, Genome Alberta, and Canadian Institutes of Health Research, Calcul Québec  as the contractor for the Scientific Registry of Transplant Recipients (SRTR). The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy of or interpretation by the SRTR or the U.S. Government.


Chronic inflammation may promote the incidence and development of neoplasms. As a pro-inflammatory death pathway, pyroptosis could induce normal cells to transform into cancerous cells, but the potential effect of pyroptosis in head and neck squamous cell carcinoma (HNSCC) remains unclear. This study developed and evaluated a pyroptosis-related gene signature to predict the prognosis and immune status of patients with HNSCC. The gene expression, mutation information, and clinical characteristics of HNSCC were extracted from TCGA to establish a comprehensive genome database (GEO). Based on LASSO Cox regression model, nine pyroptosis-related genes  were used to construct a pyroptosis-related gene signature, which had good ability to predict the prognosis of HNSCC. Furthermore, the expression of nine pyroptosis-related genes in HNSCC and paracancerous tissues was detected by quantitative real-time PCR (qRT-PCR). The potential immunotherapeutic features and drug sensitivity prediction of this signature were also explored. Because pyroptosis regulators play an important role in HNSCC development and prognoses, further exploration might assist in identifying new biomarkers and predictors of prognosis to benefit clinical identification and management. Head and neck squamous cell carcinoma (HNSCC) is ranked the sixth most common cancer globally . It accoPyroptosis, referred to as cell inflammatory necrosis, is a procedural cell death . It mainThis study aimed to investigate the expression of apoptosis-related genes, prognosis, association with immune status, and the diversity of responses to immunotherapy in HNSCC.https://www.ncbi.nlm.nih.gov/geo/).Gene expression and clinical features of HNSCC samples were collected from the publicly available Cancer Genome Atlas (TCGA) and Gene Expression Omnibus . Finally, nine PRGs were identified to construct the signature for prognostic PRG model development. The risk score of each patient was calculated based on the gene expression level associated with pyroptosis and the regression coefficient. HNSCC patients in TCGA cohort were then classified as low- and high-risk groups based on their median risk score. R Survminer package for survival analysis was used to determine the different OS, and the survival and time ROC R package was used to assess the predictive accuracy. Correlation analysis of immune cells in different software and drug sensitivity differences in high and low-risk groups was also performed.First, the differentially expressed genes (DEGs) in normal and HNSCC tissues were identified, then gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analyses were conducted. Cox univariate analysis and LASSO Cox regression were then applied to identify the prognostic-related genes using “glnet” R package . All patients signed the informed consent form before surgery. The specimens were removed and rapidly frozen in liquid nitrogen and stored in a low-temperature refrigerator at −80°C for subsequent studies. Total RNA was extracted with a RNeasy mini kit  according to the manufacturer’s instructions. cDNA was reverse transcribed by a PrimeScript RT reagent kit with gDNA Eraser . The RNA and cDNA of each sample were analyzed by a GeneQuant pro RNA Calculator to assess the concentrations and purity. Quantitative real-time PCR was performed with real-time SYBR Green PCR reagents  and the 7300 Real-Time PCR System . The abundance of different transcripts was assessed in triplicates.−ΔΔCT) method, and Student’s t-test (two-tailed) was utilized to assess the significance of gene expression differences in GraphPad Prism (version 8.0).The data were analyzed using R (version 4.0.5) by Bioconductor packages. Derivation of prognostic signatures compared to different clinicopathological features of HNSCC was accessed using ROC curve analysis . The indThe expression of 52 PRGs in patients was clustered into two clusters using ConsensusClusterPlus package , then prepidermis cell differentiation, epidermis development, and collagen-containing   . Further= 0.002) . Conside= 0.002) . The dis= 0.002) . Nine ge= 0.002) .Different molecular HNSCC subtypes are characterized by distinctive gene expression profiles and have different features in tumor progress, therapy, and prognosis. Therefore, based on PRGs in these three subtypes, we selected nine genes  related to HNSCC prognosis and conducted a new prognostic feature for HNSCC using LASSO regression algorithm program and univariate Cox regression analysis. HNSCC patients were divided into low-risk and high-risk groups based on their median risk score. The risk status, age, gender, and stage were considered the final parameters in the nomogram . Based oSubsequently, a Kaplan-Meier analysis was performed of OS between the high-risk and low-risk teams with the training cohort, testing cohort, and all groups . The areThe information from database revealed that pyroptosis-related genes related to HNSCC prognosis. To verify the feasibility of the prognostic model, we measured the expression of genes in HNSCC tissues and paired normal paracancerous tissues by qRT-PCR. The primers utilized are presented in Pearson correlation analysis was conducted to analyze the correlation between the nine genes  associated with pyroptosis and twelve immune cell types . The comparison of high-risk and low-risk groups of the stromal, immune, ESTIMATE, and tumor purity scores in the Violin Plot indicated that only the immunescore was statistically significant .p = 0:047) (p = 0:12) (The highest 20 driver genes with the best mutation frequency of TP53 and TTN were considerably different between high  and low-= 0:047) . However = 0:12) . To dete = 0:12) .The incidence and mortality of HNSCC have recently increased, and HNSCC has become the foremost fatal malignancy in adults . HoweverThe present study investigated the potential prognostic significance of PRGs and investigated the expression of PRGs in 413 HNSCC patients. Such patients were classified as high or low-risk based on their median risk score, with the risk model considerably differentiating the clinical features of low and high-risk HNSCC patients; hence, it was a good independent prognostic indicator. Notably, GO, KEGG, GSEA, and ssGSEA analyses revealed the varied immune status of the high and low-risk groups. Nine genes associated with HNSCC prognosis  were used to construct a new prognostic signature for HNSCC by LASSO regression algorithm and univariate Cox regression.Based on human paired HNSCC tissues obtained by surgery, we validated the differential expression of six risk genes included in the risk model by qRT-PCR assays. The differential analysis revealed that DYNC1I1, SPINK5, TNFRSF18, and TTLL1 was significantly upregulated in HNSCC tissues, while GLDC and TRIML2 were downregulated in HNSCC tissues. One research shows that DYNC1I1 gene expression was up-regulated and further led to activation of the AKT/ERK signaling pathway to promote hepatocellular carcinoma (HCC) progression . Daniel λ (Age, stage, and risk score were considerably related to OS by Cox regression analysis. Actually, a lot of predictive models are widely established and reported in many studies by univariate Cox regression and Lasso Cox regression analysis. λ .Furthermore, high-risk patients determined based on this feature were confirmed to have a higher TMB. The TMB has become an important factor in disease progression and clinical relapse in HNSCC patients. A better understanding of the HNSCC biology, especially the interaction between cancer cells and their surrounding TME, may help identify new biomarkers, enabling patient stratification for clinical decision-making . Also, tThe combination of immunotherapy, chemotherapy, radiotherapy, and targeted medical help inhibit tumor progression through synergistic mechanisms and improve poor prognosis in cancer patients. Although tumor development is complex, the inflammatory response may be a relevant factor. Pyroptosis is a new type of cellular necrosis, and its characteristics are the release of many inflammatory factors. Chronic inflammatory reactions can result in native tissue damage and neoplastic lesions.in vivo and in vitro research is required to verify these results. Second, post-translational modifications play an important role in signal transduction and cellular function, but the translational modifications of these genes were not explored.This study has many advantages. First, the prognostic signature accurately predicts the OS for HNSCC patients. Additionally, it is considerably related to TMB and immune infiltration, indicating its biomarker potential in HNSCC. Non-etheless, this study has some limitations. First, all information for the analysis was retrieved from online databases, implying that future A nine pyroptosis-related gene signature was constructed to better predict the prognosis and immune status of patients with head and neck squamous cell carcinoma.


Drug-resistant cytomegalovirus (CMV) infection after hematopoietic stem cell transplantation (HSCT) often leads to morbidity and mortality. Several studies have shown that CMV-cytotoxic T lymphocytes (CTLs) can overcome drug-resistant CMV infection, but still many questions remain unanswered. Here, we present a case of refractory CMV infection after allogeneic HSCT . Donor-derived CMV-CTLs failed to eliminate the virus in unique peripheral blood on the first application, when 70 mg methylprednisolone (MP) was taken per day. After a second attempt with a combination of 8 mg MP with leflunomide, a complete and persisting clearance of all involved sites, including peripheral blood, urinary system, leptomeninges, and retina, was achieved. To summarize, intravenous infusion of CTLs can eliminate CMV in the oculi and central nervous system (CNS), and a low dosage of 8 mg MP has no interaction with CMV-CTLs. Cytomegalovirus (CMV) reactivation after hematopoietic stem cell transplantation (HSCT) is a common complication . SubsequIn this study, we presented a case with refractory CMV viremia, concurrent infections in both the urinary and CNS, and additional CMV retinitis after nearly 3-month application of foscarnet and anti-CMV immunoglobulin for CMV viremia. After two infusions of donor-derived CMV-CTLs and systemic administration of leflunomide, the patient reached a complete viral clearance in all involved organs and tissues, including the retina and CNS. The second CMV-CTLs infusion under the administration of 8 mg methylprednisolone (MP) per day proved the most effective. We proposed the application of CMV-CTLs as a treatment for resistant CMV disease even in the retina and CNS, better under the condition of a low dose of corticosteroid.We presented a case of 29-year-old man, diagnosed with acute myeloid leukemia and myelodysplasia-related changes (AML-MRCs) transformed from myelodysplastic syndrome (MDS). The patient (CMV-IgM-negative and CMV-IgG-positive) without hematological remission due to chemo-resistance underwent related 7/10 human leukocyte antigen (HLA) matched peripheral blood HSCT from his mother (CMV-IgM-negative and CMV-IgG-positive) after conditioning with modified BuCy2 in August 2020. In the process of HSCT, the patient was routinely immunosuppressed with rabbit anti-human thymoglobulin (ATG), cyclosporine (CSA), methotrexate (MTX), and mortimecofenate (MMF) for graft-versus-host disease (GVHD) prophylaxis  was diagnosed. Clinically poor response to standard therapy and occurrence of CMV retinitis indicated a condition refractory to foscarnet. Hence, the patient received weekly intravitreal injection with 2 mg/0.05 ml ganciclovir in addition to 0.6 mg/0.05 ml foscarnet, as well as systemic anti-CMV therapies. The latter included leflunomide, a medication against rheumatoid arthritis, chosen as a treatment option for resistant CMV infection together with the second infusion of CMV-CTLs. Leflunomide was taken orally at 100 mg/day for 3 days, hereafter reduced to 20 mg/day continuously. On day + 132, the patient received the second dose 5.00 × 109 of donor-derived CMV-CTLs; meanwhile, MP was taken at the dosage of 8 mg/day. Twelve days after the second infusion of CMV-CTLs, CMV copy numbers in the blood finally decreased, indicating CMV-CTLs and leflunomide went into effect. However, copy numbers of CMV DNA in aqueous humor remained unchanged; additionally, the eyesight did not improve, which led to the refusal of further intravitreal injections by the patient. Longer follow-up showed a continuous decrease of CMV DNA in the blood implying sufficient expansion of CMV CTLs and quick reconstitution of immunity against the virus. Meanwhile, a steady decline in retina inflammation indicated an improvement in retinitis.A resistance to foscarnet was suspected on day + 69, as the CMV DNAemia titer increased up to 8.94 × 10On day + 149, the patient was unable to urinate spontaneously without urine catheterization. Ultrasound and CT examination of the urinary system as well as the neuromagnetic resonance examination showed no abnormalities. Urine and cerebrospinal fluid were also tested for viruses and leukemia. The results showed positive CMV DNA in both body fluids, very high levels of protein, and no leukemia cells in cerebrospinal fluid. Hence, a CMV infection in the urinary system and leptomeninges were diagnosed. Since previous case reports demonstrated that CMV-CTLs can potentially completely eliminate CMV in the CNS, and valid reconstitution of antiviral immunity in the blood of our patient was confirmed, we continued with the leflunomide, CMV immunoglobulin, and supportive care. The clinical symptoms gradually abated and disappeared within a month. In addition, the CMV titer turned negative in cerebrospinal fluid on day + 200 (68 days after the second CTLs) and in urine on day + 273 (141 days after the second CTLs). In view of the significant clinical improvements, the patient agreed to an intravitreal puncture again on day + 276 (144 days after the second CTLs) to re-examine CMV DNA in aqueous humor, which was negative.Henceforth, the patient is in continuous hematological remission, and his blood, urine, cerebrospinal fluid, and aqueous fluid have all been continuously negative for CMV.Our patient showed severe refractory CMV infections under the treatment with a high dose of immunosuppression due to aGVHD after allo-HSCT. Initially, an increase of more than one log fold change of virus DNA copies in blood and a subsequent occurrence of CMVR under long-term therapy with foscarnet both indicated the resistance to the drug, even though no known defined mutation on UL54 and UL97 was found in the blood sample. Finally, additional resistant evidence showed that ganciclovir and foscarnet failed to decrease the copies of CMV in aqueous humor after weekly bilateral intraocular injections. The difficult question remained to choose a therapy in order to effectively treat the patient. As it was not feasible to run sequencing on a sample of aqueous humor, we could not select sensitive anti-CMV drugs, according to UL54 and UL97 gene mutations. In addition, neither systemic administration of ganciclovir nor maribavir and letermovir could be applied, due to a poor neutrophil level or unavailability.in vitro if the donor is ever infected by CMV. Fortunately, lymphocytes from the patient’s mother were appropriate for producing CMV-CTLs. We immediately tried the first dose of CMV-CTLs in our patient, when refractory status was suspected, which resulted in partial response in the blood, confirming CTLs’ effectiveness. These promising results lead us to the decision, which we also try CMV-CTLs again, when later a refractory CMVR was diagnosed.This is why we concluded CMV-CTLs would be the best option for our patient, as the mechanism of this kind of immune cells is completely different from those of traditional anti-CMV drugs . They atIn addition to CMV-CTLs, we simultaneously applied oral leflunomide. It can penetrate the BBB and inhibit virion assembly of CMV, overcoming drug resistance via a completely different mode as ganciclovir and foscarnet . Researcin vivo (It is well known that post-transplant patients exposed to corticosteroids are highly susceptible to CMV infection , 17. A hin vivo , 7. ThenIn conclusion, our case suggests that donor-derived CMV-CTLs, combined with leflunomide, can effectively and safely control the refractory CMV infection at multiple sites and can lead to persistent remission. Quick recovery of CMV-specific T cells by infusion of donor-derived CMV-CTLs dominantly controls infection and disease in the retina and CNS. Doses equal to or lower than 8 mg per day of MP do not prevent the proliferation of CTLs.The original contributions presented in this study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. Written informed consent was obtained from the individual for the publication of any potentially identifiable images or data included in this article.NS and DC guided the treatment of this case and analyzed the patient’s data regarding the hematological disease and the transplant. NS was a major contributor in writing the manuscript. NS and ZL reviewed all related literature. XY and DC critically revised the manuscript. PS and FG performed fundus examination, aqueous humor puncture, and intravitreal injection. All authors read and approved the final manuscript.


Background: Sexually transmitted infections (STIs) are a major global healthcare burden, disproportionately affecting women. Self-sampling interventions for diagnostic purposes have the potential to improve STI healthcare management and expand STI services. However, there is currently no published evidence of the global use of self-sampling interventions to diagnose STIs in women. The main aim of this scoping review was to map evidence on the use of self-sampling interventions to diagnose STIs in women. Methodology: The methodology of this scoping review was guided by Arksey and O’Malley and Levac. A comprehensive literature search was conducted in PubMed, Scopus, Web of Science, Medline (EBSCO), ProQuest, and Cochrane. For grey literature, a search was conducted in Open Grey, World Health Organization, Google, and conference proceedings and dissertations. All search results were screened and assessed for eligibility. Thereafter data from eligible studies was extracted and analysed. The quality of these studies was appraised using the Mixed Methods Appraisal Tool 2018 version. Results: A total of 770 articles were retrieved from databases and grey literature sources. A total of 44 studies were eligible for data extraction following title, abstract and full-text screening. Of the included studies, 63% presented evidence of research conducted in high-income countries and 37% presented evidence in low- and middle-income countries. Studies presented evidence on the following: feasibility of self-sampling in remote areas; acceptance and ease of use of self-sampling interventions; types of self-sampled specimens; pooled samples for diagnosing STIs; laboratory diagnostic assays for STI using self-sampled specimens; and self-testing of self-sampled specimens. Conclusions: Self-sampling interventions are feasible and easy to use and, therefore, can improve STI management and treatment in women across various age groups and various access levels to good-quality healthcare. Despite this, there is a lack of evidence of self-sampling interventions designed according to user preferences. We recommend studies to collaborate with women to co-develop user-friendly self-sampling interventions to diagnose STIs in women. Sexually transmitted infections (STIs) are a global health challenge, with one million new cases diagnosed every day . AlthougSelf-sampling to diagnose STIs is widely used in high-income countries (HIC) as an alternative to having healthcare workers collect samples . ThroughThe long-term effects of undiagnosed and untreated STIs, together with the difficulties associated with clinic-based management of STIs, contributes to the global challenges associated with STI management ,12. Selfhttps://osf.io/tnbx6 (accessed on 20 June 2022).This scoping review was part of a larger study aiming to develop a user-friendly self-sampling intervention to diagnose STIs among young women in poor urban communities in eThekwini District Municipality, in KwaZulu-Natal, in South Africa. The scoping review was guided by recommendations from Arksey and O’Malley , ColquhoWe asked the research question: What is the evidence on self-sampling interventions to diagnose STIs among women?We adopted the population, concept, and context (PCC) framework to effectively address the research question see .We conducted a systematic literature search of the following databases: PubMed, Scopus, Web of Science, Medline (EBSCO), ProQuest, and Cochrane. We used medical subject headings (MeSH) terms to define our searches with Boolean operators (AND/OR) between search terms. The search terms included (1) “self-sample” or “self-collect” or “self-administer” or “self-obtain”, (2) “sexually transmitted infections”, (3) “diagnostic specimens” or “diagnostic samples”, and (4) “women”. We searched the grey literature on the following websites: Open Grey, WHO, Google, and conference proceedings and dissertations. We adjusted keywords to suit different databases. We did not apply any time or language restrictions to ensure that we captured most of the literature. An experienced librarian conducted comprehensive database searches to ensure that the best search strategies were used for each database.Peer-reviewed journal articles;Studies presenting evidence on self-sampling interventions for STIs;Studies presenting evidence on self-sampling in women for STI diagnosis;Studies of all designs with relevant information; andStudies focussing on the type, acceptability, feasibility, and effectiveness of self-sampling.We included articles that fulfilled the following criteria:Articles were excluded if they:Focused on self-sampling interventions for HIV only; andOnly presented evidence of specimens collected by healthcare workers for STI diagnosis.Studies were selected in three stages. Firstly, article titles were screened according to their title in line with eligibility criteria. Eligible articles were exported to reference-manager software. In the second phase, two independent reviewers screened abstracts, using a screening tool that outlined the eligibility criteria. The screening tool was calibrated to ensure the accuracy and utility of screening questions. Calibration involved randomly selecting 21 (10%) articles from 211 articles, and then, pilot screening using the screening tool. The reviewers held extensive discussions to resolve any discrepancies and amend the screening tool accordingly. After the second stage of screening, eligible publications were exported to reference-manager software. The third stage included screening full texts using the screening tool. A third reviewer helped to resolve any discrepancies arising from full-text screening. Kappa statistics were used to determine the level of agreement between screeners.We developed a data charting tool with variables relevant to the research question. Two independent reviewers then piloted the data-extraction tool, using seven (10%) of the included studies. The reviewers discussed the results of the extraction tool and updated the tool accordingly. Data were extracted from each article and thematically organised in a spreadsheet. Extracted data included: author, aim, study design, country, study population and sample size, type of self-collected specimen, diagnostic test used, key findings and conclusions.Included articles were critically appraised using the Mixed Method Appraisal Tool (MMAT), version 2018 . IncludeThe included articles were thematically analysed to demonstrate how they related to the research question. The following themes emerged from the included articles: feasibility, acceptance and ease of self-sampling interventions; types of self-collected specimens; diagnostic accuracy of self-collected specimens; agreement between physician-collected specimens and self-sampled specimens; pooled specimens for STI diagnosis; and self-testing of self-collected specimens. Our research findings were narratively summarised.n = 20), they did not focus on STIs (n = 2), and they did not assess the accuracy or validity of results of self-collected specimens (n = 56). The remaining 64 studies were eligible for data extraction. During data extraction, we excluded 20 articles because they compared laboratory diagnostic assays (n = 16), compared uptake of internet-based services versus in-person services (n = 1), and did not focus on STIs (n = 1) or on self-sampling in women (n = 2). Ultimately, 44 studies were included for review.Our search and screening strategy is outlined in the PRISMA flow diagram . We retrp < 0.05). McNemar’s chi-square statistic suggested that reviewers had similar proportions of yes/no answers (p > 0.05).Reviewers showed moderate agreement following full-text screening  of studies [Chlamydia trachomatis/ Neisseria gonorrhoea (CT/NG) Test, PCR for CT , cobas® Amplicor CT/NG test, the Anyplex II Huma papillomavirus (HPV)28 Detection assay, Real-time PCR using CFX9, care HPV Assay, Ligase Chain Reaction (LCR), and Strand Displacement Amplification. One study used only conventional wet mount and culture techniques to diagnose STI [Nucleic acid amplification-based tests (NAATs) were used to diagnose STIs in 95% n =  of studi studies ,62,63,64 studies . The NAAnose STI . Only onnose STI .We reviewed studies that presented evidence on using self-sampled specimens for diagnosing STIs in women across the globe. The following themes emerged from the included studies: feasibility, acceptance and ease of self-sampling interventions; types of self-sampling specimens; diagnostic accuracy of self-sampled specimens; agreement between physician-collected specimens and self-sampled specimens; pooled samples for STI diagnosis; and self-testing of STIs using self-collected specimens.Nine studies reported on acceptance, ease of use, and feasibility of self-sampled specimens in settings where pelvic examinations were not routinely conducted and healthcare access was limited ,52,54,56Studies in the review investigated the use of different types of self-collected specimens to diagnose various STIs, including NG, CT, TV, HPV and genital mycoplasmas. Self-sampled specimens were collected using vaginal swabs, cervicovaginal swabs, rectal swabs, pharyngeal swabs, urine and tampons. Thirty-three studies used vaginal swabs ,59,60,61Two studies in the USA ,35 and oIn the USA, Fang et al.  demonstrSelf-sampling was also conducted using tampons. In the USA, tampons were highlighted as a sampling technique that could collect a bigger cell sample than vaginal swabs and, therefore, had the potential to rapidly diagnose women . ChandeyTwo Kenyan studies ,30, one Of the 44 included studies, 25 studies reported on the accuracy of laboratory diagnostic results ,58,60,61We reviewed 19 studies that compared physician-collected and self-sampled specimens ,56,57,59Two studies explored the use of pooled specimens to diagnose STIs ,65. In bOnly one USA study reported on the use of self-testing assays on self-collected samples . This stn = 42) of the included studies used NAAT to diagnose or detect STIs. We found few studies describing participant-tailored self-sampling interventions that could be used for routine STI management at local healthcare facilities. Most studies investigated the use of self-sampled vaginal swabs to diagnose STIs [This scoping review presents global evidence on self-sampling interventions used to diagnose STIs in women. Our findings show that 23% of included studies were conducted in the USA and 95% n =  of the iose STIs ,59,60,61ose STIs . We alsoose STIs  emphasizose STIs .Despite receiving verbal and/or written instructions for specimen self-collection, studies found that self-sampling interventions to diagnose STIs in women were feasible ,51,60,61Only two of the reviewed studies reported on the use of pooled samples to diagnose STIs and highlighted a gap in the use of pooled specimens. Pooling of specimens from the genital tract and extragenital tract has proven successful in detecting infections in individuals who practice oral and anal sex . The lacWe reviewed studies reporting on the accuracy of diagnostic results when using self-sampled specimens. We found that self-sampled specimens result in fairly accurate diagnoses ,68. SelfWhen considering high global STI statistics  and limiAlthough STIs have been of great interest among the medical population, the level of public knowledge of such is not well known. It has been proven that sufficient knowledge about STIs has an effect on minimizing the spread of infection . A studyWe conducted extensive searches on various databases and websites to retrieve all relevant studies. We used the PRISMA guidelines to guide the recording and reporting of our results thereby ensuring transparency. We did not have any language restrictions or study design limitations. We systematically identified relevant studies and charted and analysed data. Although we made every attempt to ensure a rigorous search strategy, we may have missed relevant studies. Our screening tool may not have been rigorous enough, resulting in the inclusion of 44 studies.Most of the studies included in this review were conducted in HICs where there is equitable access to good-quality healthcare services. In HICs, the use of advanced innovative healthcare practices is normal. Few studies on self-sampling interventions were conducted in LMICs where access to good-quality healthcare services still poses a challenge for ordinary citizens. In LMICs, healthcare systems are far behind in terms of the services they provide to their people. As such, LMICs continue to struggle with health issues that are no longer a burden in HICs. Our review highlights the ease and usefulness of self-sampled vaginal swabs, which may prove feasible and adaptable in LIMCs.The coronavirus disease of 2019 (COVID-19) pandemic has led to the minimization of human interaction and movement to reduce and prevent the spread of COVID-19.According to Pinto et al. , COVID-1Despite the potential benefit of self-sampling in LMICs, we found no evidence for self-sampling interventions that had been developed according to the needs and preferences of women. There is a need to develop self-sampling interventions for STI diagnosis which are tailored to the preferences of the user.We found that most of the research on self-sampling for STIs was conducted in HICs. We recommend that future studies be conducted in LMICs. Self-sampling seems to largely rely on self-collected vaginal swabs and there is opportunity to investigate different types of self-sampling including tampons, sanitary pads, and urine, which may promote the development of a self-sampling intervention tailored to the preferences of women. Since only two studies reported on the use of pooled samples for diagnosing STI, we recommend future research investigating the use of pooled specimens to diagnose STIs present in extragenital areas. We also found that self-sampling and POC testing was rare in primary healthcare practice. Future research should explore the use of POC tests and self-sampling to bring healthcare services closer to users who have limited access to healthcare.This scoping review shows that despite self-sampling interventions having the potential to improve STI management and treatment here is a need for self-sampling interventions tailored to the needs of users. Self-sampled vaginal swabs have the potential to increase access to healthcare. In LMIC settings, having women collect their own samples in private settings may save time and resources in primary care settings.