This transformation requires a shift from chemical safety assessment largely based on direct empirical observation of apical toxicity outcomes in whole organisms to predictive approaches in which outcomes and risks are inferred from accumulated mechanistic understanding. In the last decade, Adverse Outcome Pathways (AOPs)   have caps (AOPs) .e.g., endogenous ligand, xenobiotic) and a biomolecule) to an adverse outcome . The causal links between 2 KEs are referred to as key event relationships (KERs). AOPs provide a useful framework to connect mechanistic data to adverse effects on human health or wildlife populations as a basis for the identification of cell- or biochemical-based tests that could fit in Integrated Approaches to Testing and Assessment (IATAs), identifying KEs that could be targeted for the development of New Approach Methods (NAMs), as well as investigating similarities in mechanistic pathways between species.An AOP is a conceptual structured representation of existing toxicological knowledge describing the causally connected sequence of events, across different levels of biological organization, required to produce an adverse effect when an organism is exposed to a stressor. Specifically, AOPs depict a series of key events (KEs) linking a molecular initiating event . Indeed, both the World Health Organization (WHO) and the International Programme on Chemical Safety (IPCS) definition and the scientific criteria adopted by the European Union in 2017 are articulated around three key requirements, namely; evidence of an adverse effect, evidence of an endocrine-mediated (EM) mode-of-action, and the plausibility of the causal relationship between the mode-of-action and adverse effect. Both the European Chemical Agency (ECHA) and European Food Safety Authority (EFSA) recommend that more EM AOPs be developed for substantiation of chemicals’ ED properties . Of the Evidence-Based Methodologies (EBMs), including systematic maps and systematic reviews (SRs), aim to help assemble and assess the current knowledge on a topic in an objective, comprehensive and transparent manner. Although the AOP development process does not currently explicitly require use of EBMs , effortsThis perspective article draws on lessons learnt from the EURION cluster activities to review the circumstances in which EBMs approaches may be most usefully applied to EM AOP development and opportunities for further research and development of tools tailored to mechanistic evidence gathering and evaluation.EURION is a cluster of eight research projects, funded under the European Commission’s Horizon 2020 Research and Innovation Programme, focusing on developing new testing and screening methods identifying EDs and studying their effects on metabolism , female However, limited availability of test methods assessing EDs leave significant knowledge gaps in identification of EDs properties , that caAOP development within the EURION cluster is ongoing for different modalities, particularly, those related to androgen, thyroid hormone, and retinoid signalling. An AOP working group (WG) has been set up to support and facilitate AOP-related activities within the EURION projects and to bring together AOP-structured information and data across projects. This WG has identified potential synergies and areas for collaboration among projects for which EBMs may be relevant.i.e., SRs). A potential application of EBM in AOP development may therefore be as a series of KERs’ SRs , as well as the physiology and signalling pathways of endogenous ligands or well-characterised  agonists or antagonists especially relevant to the KE of interest. For instance, the Allan-Herndon-Dudley syndrome is caused by a rare defect in the gene encoding for monocarboxylate transporter 8 (MCT8) that leads to severe brain development deficits (impaired TH transport across brain cell membranes). Literature related to clinical presentation and putative pharmacological interventions ] often associated with liver steatosis and lipid accumulation  or similar statements used in EBMs. One single KER should avoid compounding events together and rather refer to one single measurable event . For insmulation ..g., taxonomy, sex, species, life stage). In theory, an AOP’s relevant biological domain of applicability is restricted to the narrowest domain of its components. For a specific KER, query terms should remain inclusive as long as the observed biological object  and its function are conserved across the domain category. However, restriction of the biological context becomes a must when equivalency of the structure or the function are not preserved. Typically, translational considerations should take into account the relevance of predicting AOs in humans from experimental animal models. For instance, certain female reproductive endpoints  in humans are absent or different in rodents, and vice versa   . This emystocia) . For exaystocia) , 2013. Li.e., their applicability should not be limited to a specific substance. However, search strategies employed in EBMs are typically articulated around search terms related to both the stressor (exposure) and the outcome (endpoint). The chemical agnosticism of AOPs raises questions over the validity of literature search strategies referring to specific substances. Nevertheless, the evidence used to support each KER is based on chemical-specific exposure data , they help search tools cover a larger spectrum. To our knowledge, this aspect has not yet been systematically investigated. One approach may be to develop search strategies for prototypical stressors or model compounds chosen from reliable resources like EURL ECVAM , for the methods/models validation , for hepatic steatosis , is a web server that has been developed to employ text-mining and graph theory approaches for identification of literature that links specific pesticides with AOP events.Another approach to support the development of adequate search strategies would be to evaluate agonists . Approacteatosis  and for teatosis . Similarteatosis . A notabFurther research is necessary to establish to what extent devising search strategies including terms related to specific chemical stressors would be suitable to retrieve negative evidence and whether they may compound publication bias or limit the applicability domain of an AOP. Such research should serve to develop a set of recommendations for literature search algorithms adapted to the retrieval of EM mechanistic data for AOP development.In addition, development of AOPs should be seen as an interdisciplinary framework, as it involves different and complementary expertise , in order to decipher the most complete picture of the biological complexity of systems.e.g., ToxRTool. ec.europa.eu/jrc/en/scientific-tool/toxrtool-toxicological-data-reliability-assessment-tool), and some have been adapted to cater for the appraisal like the SciRAP protocol  may be of help not only for critical appraisal but also for other aspects of the process, like PF . Their implementation for information retrieval ought to be validated and compared with manual methods for completeness to avoid introducing potential biases. It also is unclear whether automated methods would be compatible with the demands for transparently documented appraisal of the quality of individual pieces of evidence or the evaluation strength of the overall body of evidence. The development of MLT to support evidence-based AOP development is a promising field, that is complementary to already existing approaches, but that will nonetheless require a considerable validation effort before full implementation.A number of MLT that have been or are being developed can support the earlier stages of SR adapted to AOP development (


Elvin Hsing Geng and colleagues discuss mechanism mapping and its utility in conceptualizing and understanding how implementation strategies produce desired effects. PLOS Medicine illustrates this need [To advance as a science, implementation research must build an evidence base using, in part, experimental designs. But trials of implementation strategies—which are often complex health systems interventions—often do not demonstrate anticipated overall effects ,2. As a his need .Previous randomized trials and a meta-analysis provided evidence that weekend staffing with allied healthcare professionals  decreased length of stay in rehabilitation units, but such weekend staffing had no effects in general medical and surgical units . BecauseOne way to dissect how implementation strategies fail is through formal exploration of anticipated mechanisms. Several approaches in implementation science offer methods that can help conceptualize mechanisms systematically. The Intervention Mapping approach asks those planning health promotion activities to conceive of the multilevel, theory-based targets for behavior change that underlie a program and how they interact to produce desired effects . The TheFirst, decomposing the overall effects of an implementation strategy—in this case KB—into its hypothesized mechanistic component allows investigators to be more precise about where it may have broken down. Drawing from previous literature , we suggA visual mapping of the putative mechanism also highlights underlying assumptions and their uncertainties and therefore informs what to measure. The effect of conveying evidence (step b) assumed the evidence is perceived as credible. A mixed-methods manuscript  from theMechanism mapping also increases the rigor of a study through making explicit where and when particular elements of the context act on particular steps in the hypothesized chain of events. Several elements of context potentially differ between the study by Sarkies and colleagues and other settings using KB, differences that could inform external validity of null effects if better measured. For example, in this case, the nature of the evidence offers one important contextual element: It could be that evidence of a managerial practice in this study is perceived as fundamentally different from evidence of a clinical treatment and thereby attenuated the effect of brokered knowledge on target manager beliefs (step k). Additionally, the organizational relationship between the KB agency and the hospital may have a critical influence on the success of the social and affective link between the KB and the manager (step l) . Other pSarkies and colleagues’ new paper moves implementation science ahead in 2 ways. First, it suggests that KB depends on the status of the actor, the means of contact, the perceived applicability of evidence, the affective bond created by the KB, and the interactions between each of these factors. Future studies of KB must emphasize these elements. Second, and more broadly, the study reminds us that trials of complex health systems interventions must allow us to explain whether a strategy was used and, if not, why not ,2,17. In


Myriophyllum spicatum (Eurasian watermilfoil) to: (a) develop SDMs to predict invasion and impact from environmental variables based on presence–absence, presence‐only, and abundance data, and (b) compare evaluation metrics based on functional and discrimination accuracy for presence–absence and presence‐only SDMs.Availability of uniformly collected presence, absence, and abundance data remains a key challenge in species distribution modeling (SDM). For invasive species, abundance and impacts are highly variable across landscapes, and quality occurrence and abundance data are critical for predicting locations at high risk for invasion and impacts, respectively. We leverage a large aquatic vegetation dataset comprising point‐level survey data that includes information on the invasive plant Minnesota, USA.Eurasian watermilfoil presence–absence and abundance information were gathered from 468 surveyed lakes, and 801 unsurveyed lakes were leveraged as pseudoabsences for presence‐only models. A Random Forest algorithm was used to model the distribution and abundance of Eurasian watermilfoil as a function of lake‐specific predictors, both with and without a spatial autocovariate. Occurrence‐based SDMs were evaluated using conventional discrimination accuracy metrics and functional accuracy metrics assessing correlation between predicted suitability and observed abundance.Water temperature degree days and maximum lake depth were two leading predictors influencing both invasion risk and abundance, but they were relatively less important for predicting abundance than other water quality measures. Road density was a strong predictor of Eurasian watermilfoil invasion risk but not abundance. Model evaluations highlighted significant differences: Presence–absence models had high functional accuracy despite low discrimination accuracy, whereas presence‐only models showed the opposite pattern.Complementing presence–absence data with abundance information offers a richer understanding of invasive Eurasian watermilfoil's ecological niche and enables evaluation of the model's functional accuracy. Conventional discrimination accuracy measures were misleading when models were developed using pseudoabsences. We thus caution against the overuse of presence‐only models and suggest directing more effort toward systematic monitoring programs that yield high‐quality data. Multiple niche models for invasive Eurasian watermilfoil were developed and compared to evaluate the importance of response data and model accuracy metrics. Abundance data are crucial in gaining a fuller understanding of EWM invasion and improve model evaluation metrics. Thus, the study cautions against the overuse of simple presence–absence niche models. However, SDMs often do not involve true absence information, as confirmed absences are typically unavailable in most survey and monitoring databases. Given this difficulty to obtain absence information, several presence‐only SDM approaches have been developed in which false absences  are used in place of true absences. These pseudoabsences are locations where the species has not been documented, but in fact may not have been surveyed, and therefore, the true status of the species is unknown. The use of pseudoabsences involves many assumptions and needs careful planning  abundance  is yet another common technique employed in SDMs to account for spatial autocorrelation in environmental drivers and/or species distribution data  using response variables that differ in quality and definition. The goals of our study are to gain a comprehensive understanding of the environmental drivers of EWM invasion and simultaneously explore how data quality influences modeling results and interpretations. Specifically, we (a) develop multiple SDMs trained with EWM presence–absence, presence‐only, and abundance datasets with a focus on determining the relative importance of drivers for EWM occurrence versus abundance; (b) explore the effects of pseudoabsences and spatial lag terms on model results and performance; and (c) evaluate and compare presence–absence and presence‐only models based on discrimination accuracy and functional accuracy.Here, we make use of a rich long‐term aquatic plant monitoring dataset to build SDMs based on systematically collected presence, absence, and abundance data. We develop multiple SDMs for the invasive plant Eurasian watermilfoil (22.1https://www.dnr.state.mn.us/invasives/ais/infested.html). Among the characteristics that make EWM a successful invader are its efficient dispersal mechanisms and rapid growth early in the growing season . The presence‐only approach encompasses EWM‐invaded lakes together with unsurveyed lakes not known to have EWM, which are treated as pseudoabsences. Using three different spatial draws of pseudoabsences , the presence‐only data were further categorized into (a) random presence‐only data, where pseudoabsences were drawn randomly from the study area; (b) distant presence‐only data, where pseudoabsences were drawn from unsurveyed lakes outside a convex hull surrounding invaded lakes; and (c) proximal presence‐only data, with pseudoabsences drawn from unsurveyed lakes contained within the invaded‐lakes convex hull. These three different presence‐only datasets represent the commonly used pseudoabsence selection strategies . EWM spring growth is initiated when water temperature exceeds 10°C . Water chemistry measures for a lake were recorded as the average measure of all sampling events within a lake between the years 1995 and 2019. Lake connectivity variables comprised road density and stream density measures within 500 m from lake edges, which were sourced from the LAGOS database  from Olmanson et al.  algorithm . All model runs involved splitting the datasets into 70 percent training data and 30 percent test data for estimating model accuracy. Overall, the 10 distinct RF models provide a detailed comparison of EWM’s predicted niche in relation to multiple types of distribution measures, with and without accounting for spatial autocorrelation. We provide a detailed overview of all the steps involved in the RF species distribution modeling based on the ODMAP template developed recently  score when a variable was permuted  and abundance models, relative importance of variables was calculated as percent change in mean‐squared error , Kappa, and TSS (true skill statistic)—were calculated  were reported, one that included zero values for frequency of occurrence  and another that excluded zero values (nonzeror and nonzero⍴). Finally, linear quantile regression models were used to further explore the abundance–suitability relationship. For both SDMs, with and without spatial autocovariate quantile regressions were used to examine the relationship between predicted EWM invasion risk and upper limits of EWM frequency of occurrence .Functional accuracy for each occurrence‐based model was evaluated by quantifying the strength of the abundance–suitability relationship between EWM frequency of occurrence and predicted suitability for EWM invasion. For each occurrence‐based model, the Pearson and Spearman correlation coefficient estimate of the relationship between predictions of the model and frequency of occurrence was considered as the measure of its functional accuracy. Hence, high positive values of the correlation coefficient imply predicted EWM invasion risk was a strong predictor of EWM frequency of occurrence. Studies have generally shown that inclusion of zeros can potentially inflate correlation coefficient estimates as it entails predictions of low suitability for zero abundance values  and Spearman's correlation coefficients  showed a contrasting pattern, with presence–absence models recording the highest values compared to all other models. Overall, functional accuracy values showed the following ranking: presence–absence models > presence‐only with random pseudoabsences > presence‐only with proximal pseudoabsences > presence‐only with distant pseudoabsences. Inclusion of a spatial autocovariate generally improved discrimination accuracy and functional accuracy values with some exceptions. Specifically, inclusion of a spatial autocovariate reduced discrimination accuracy estimates under the quasi‐independent approach for presence‐only models with distant and proximal pseudoabsences, and it also reduced Pearson's r for presence‐only models with distant pseudoabsences. Averaging all the discrimination accuracy estimates provides a clearer picture, with only presence‐only models with proximal pseudoabsences continuing to show a slightly lower Kappa estimate when an autocovariate is included.Regardless of the evaluation approach, discrimination accuracy statistics  revealed a similar pattern, with presence‐only models with random pseudoabsences and presence‐only models with distant pseudoabsences always being better predictors of EWM invasion than presence–absence models Table . More spAbundance–suitability plots of EWM frequency of occurrence and predicted suitability for EWM invasion showed a wedge‐shaped relationship that varied among models with and without the spatial autocovariate Figure . Analysi44.1We developed multiple SDMs to gain a deeper understanding of the ecological drivers of EWM invasion, while also evaluating the importance of data quality and model assumptions. Results of the presence–absence, presence‐only, and abundance‐based SDMs showed considerable overlap; however, there were key differences with important implications for model interpretation. For instance, while growing degree days and lake depth consistently predicted EWM occurrence and abundance, road density around lakes mattered most for occurrence models of invasion risk. Similar effects of surrounding landscape conditions on EWM invasion risk have been reported previously, especially with respect to boating, vehicular traffic, and lake visitation rates, all of which facilitate overland spread of EWM , which is especially unlikely for invasive species. Invasive SDMs also assume that the data used for calibration capture the invasive species’ entire range of environmental conditions. While the multidecadal presence of EWM in Minnesota ensures the assumption of equilibrium is less of a problem than it would be for a newer invaded, it still cannot be completely discounted. Hence, future studies on EWM’s distribution and niche might benefit by taking a more exhaustive calibration data that include water temperature measures from EWM’s native range and by developing dynamic models that incorporate EWM’s dispersal potential.Species distribution models are an increasingly important tool in conservation decision making, and hence, their results and interpretations have tangible consequences. For invasive species, a practical application of SDMs might involve identifying environmental drivers of species distribution and abundance, leveraging this understanding to predict locations of high invasion risk. Here, we identify key ecological drivers of EWM distribution and abundance with a focus on better understanding the invasion processes. Prevention and management of EWM invasion may benefit by taking into consideration these key differences in the drivers of invasion risk versus abundance. Furthermore, through the evaluation of the abundance–suitability relationship, our study highlights the limitations of presence‐only models with pseudoabsences. It is apparent from our results that SDMs designed to maximize discrimination accuracy are not necessarily optimal when it comes to identifying models that accurately predict habitat suitability and species performance. This is especially true when models are based on presence‐only data with pseudoabsences. If presence‐only data are the only available option, random draws of pseudoabsence points are preferred for ensuring that the species–environment relationship is as accurate as possible. More importantly, high‐quality data in the form of systematically collected absence and abundance information are often not available, forcing researchers to rely excessively on presence‐only models. We thus caution against over‐reliance on presence‐only models in species distribution modeling and instead recommend that more resources be allocated to initiating and supporting monitoring programs that collect high‐quality data via systematic monitoring, rather than relying upon opportunistic reporting of presences.None declared.Shyam M. Thomas: Conceptualization (lead); Formal analysis (lead); Methodology ; Writing‐original draft (lead). Michael R. Verhoeven: Data curation (lead); Resources ; Writing‐review & editing . Jake R. Walsh: Funding acquisition ; Writing‐review & editing . Daniel J. Larkin: Resources ; Supervision ; Writing‐review & editing . Gretchen J. A. Hansen: Funding acquisition (lead); Methodology ; Project administration (lead); Supervision (lead); Writing‐review & editing .Table S1‐S2Click here for additional data file.


Patients undergoing bronchoscopy in spontaneous breathing are prone to hypoxaemia and hypercapnia. Sedation, airway obstruction, and lung diseases impair respiration and gas exchange. The restitution of normal respiration takes place in the recovery room. Nonetheless, there is no evidence on the necessary observation time. We systematically reviewed current guidelines on bronchoscopy regarding sedation, monitoring and recovery.This review was registered at the PROSPERO database (CRD42020197476). MEDLINE and awmf.org were double-searched for official guidelines, recommendation or consensus statements on bronchoscopy from 2010 to 2020. The PICO-process focussed on adults (Patients), bronchoscopy with maintained spontaneous breathing (Interventions), and recommendations regarding the intra- and postprocedural monitoring and sedation (O). The guideline quality was graded. A catalogue of 54 questions was answered. Strength of recommendation and evidence levels were recorded for each recommendation.Six guidelines on general bronchoscopy and three expert statements on special bronchoscopic procedures were identified. Four guidelines were evidence-based. Most guidelines recommend sedation to improve the patient’s tolerance. Midazolam combined with an opioid is preferred. The standard monitoring consists of non-invasive blood pressure, and pulse oximetry, furthermore electrocardiogram in cardiac patients. Only one guideline discusses hypercapnia and capnometry, but without consensus. Two guidelines discuss a recovery time of two hours, but a recommendation was not given because of lack of evidence.Evidence for most issues is low to moderate. Lung-diseased patients are not represented by current guidelines. Capnometry and recovery time lack evidence. More primary research in these fields is needed so that future guidelines may address these issues, too.The online version contains supplementary material available at 10.1186/s12890-021-01532-4. Flexible bronchoscopy (FB) can be performed with various regimes of monitoring and sedation –3. Non-iApnoea phases and resulting hypercapnia can therefore not adequately be detected. One third of the hypercapnic episodes appear delayed up to one hour after the end of FB . PatientThis adequate time also depends on the type and depth of sedation. Sedative regimes range from no sedation to general anaesthesia, although there is evidence that the patient’s comfort is higher if FB is performed in analgosedation . While rAlthough the depth of sedation impacts oxygen saturation, carbon dioxide tension, and recovery time, we hardly found any evidence or recommendations on the issues of monitoring, capnometry and observation time in a preliminary research. Thus, there is a need for elucidating the current evidence, so we conducted a systematic review of the current bronchoscopy guidelines on flexible bronchoscopy with focus on these topics.www.crd.york.ac.uk/prospero/CRD42020197476) and is performed following the PRISMA-P reporting guidelines . The coClinical questions were gathered in the PICO  format to define the scope of the guideline and inform the literature search: The population under review compasses adult subjects, the intervention is any bronchoscopic procedures with maintained spontaneous breathing, the comparators are guidelines, recommendations, or consensus statements. The main outcomes are the recommendations regarding the intra- and postprocedural monitoring and sedation.The systematic search is performed in the electronic databases Medline (using Pubmed) and awmf.de on July 06 2020. The AWMF  publishes official German guidelines of 175 scientific member societies and 3 associated societies from all medical specialties. The details of the systematic search are provided in the supplementary material.An article was considered eligible if it: (1) is an official guideline, recommendation or consensus statement of a national or international medical institution; (2) is evidence- or consensus-based; (3) recommends on the practice of bronchoscopy with maintained spontaneous breathing; (4) was published within the last ten years; (5) was presented in full-text form and in English or German language. Clinical trials, case series and reports, expert opinions, teaching literature, meta-analyses, and systematic reviews were excluded.Records were managed by electronic citation managers to screen the results of the database research. The search results were screened for eligibility based on title and abstract by two reviewers (DS and TG). Subsequently, full-text articles were evaluated on relevance by the same reviewers. Studies, which do not give practice recommendations on how sedation, monitoring, and observation should be performed, were excluded. The reasons for the exclusion of an article were documented. Disagreements were resolved through discussion and consensus; if an agreement could not be achieved, the decision was made by the senior researcher (ES).The following data were extracted from all included studies: main author’s last name; year of publication; publishing institution (stakeholder); type of guideline (consensus or evidence-based); patient characteristics; bronchoscopic intervention; practice recommendations on monitoring and sedation, the strength of recommendation; the level of evidence. Data are entered into a catalogue of 54 items Table , which aThe systems to rate the level of evidence and the strength of recommendation were gathered and re-assigned to three levels as shown in Tables scope and purpose (three items)stakeholder involvement (three items)rigor of development (eight items)clarity of presentation (four items)applicability (three items)editorial independence (two items)To assess the risk of bias, the AGREE II tool was used . The AGRItems are rated on a seven-point scale from 1 (strongly disagree) to 7 (strongly agree). A quality score is calculated for each of the six domains, presented as the percentage of the maximum possible score for each specific domain.We used a staged scoring process to assess the quality of the included guidelines as proposed by the 2017 AGREE-II-manual : First, Forty-four guidelines, recommendations and consensus paper were identified, of which 37 had to be excluded Fig. : Twenty-Nine guidelines, expert recommendations and consensus statements met the eligibility criteria and were included. They are listed in Table The six general guidelines were rated for the rigour of development with the AGREE-II-tool as follows: ITALF 31%, GRS 21%, ACCP 40%, BTS 100%, GS ORL HNS 31%, JICS 85%. The detailed rating of the BTS and JICS guidelines, which reached > 70% in the domain “rigour of development”, is presented in Fig. Four guidelines are evidence-, five are consensus-based. Three different systems to rate the levels of evidence are used Table . Most ev2) and electrocardiogram (ECG) were recommended by five studies, with a strength of recommendation ranging from weak to strong recommendations, with an overall low evidence level. The JICS guideline of 2019 strongly recommend NIBP and SpO2 with a low level of evidence. The use of an ECG during FB is only strongly recommended in patients with cardiac arrhythmias. Furthermore, the JICS endorse that the respiratory rate and the depth of sedation should be documented during FB. The ACCP assume adequate monitoring for FB and does not discuss it further.Non-invasive blood-pressure (NIBP) measurement, peripheral pulse oximetry  is recommended by 4 studies, with one strong, one moderate and two weak recommendations. According to the BTS, LA reduces cough, provides a better patient tolerance and may reduce the required doses of sedative agents (moderate evidence level). The GRS gives a moderate recommendation for the usage of a LA if oral intubation is performed. More recent guidelines find more evidence for the use of LA and give stronger recommendations than the older ones. Four studies recommend lidocaine for LA, two of which as preferred agent. The strengths of recommendation for lidocaine increase from 2010 to 2019.The use of sedation for FB is discussed by seven studies. Six studies recommend the use of sedation for FB with strength of recommendation ranging from weak to strong. The ILATF and BTS say that bronchoscopy without analgosedation can be performed as well, but patients’ preference should be sought. Evidence levels are low or moderate. Two guidelines recommend a moderate or conscious sedation, two propose to adapt the depth of sedation to the complexity of the procedure, ranging from minimal sedation to general anaesthesia.Four guidelines recommend Midazolam, two of which as the preferred sedative agent. Three guidelines recommend using the lowest possible dose. Lower dosage of midazolam in particular patient groups  were endorsed by two studies.The GRS 2011 recommends propofol either as mono-sedation or combined with midazolam. In contrast, the JICS and BTS endorse the combination of propofol with an opioid over propofol alone to improve the patient’s tolerance, supported by a high level of evidence. The lowest possible dose of propofol should be applied Propofol should only be given if the personnel are trained in the administration of propofol. According to the JICS, propofol must be cautiously administered in high-risk patient groups.According to the GRS, diazepam should not be used because of its long half-life. The other guidelines do not mention diazepam.The combination of midazolam and opioids is recommended by four guidelines, particularly to improve the patient’s tolerance during FB and to reduce the total dosage of sedative agents. Only the 2011 GRS guideline recommends against the use of opioids because of the risk of hypoventilation and they “have no advantages over the preferred substances [i.e. midazolam and propofol]”.Recommendations for pre-existing lung diseases were only covered by three papers regarding sedation. The BTS weakly recommends a cautious sedation of patients with COPD or respiratory failure. The GRS gives a moderate recommendation that a lower dosage of sedative agents should be used in pulmonary disease. The JICS gives a strong recommendation of cautious sedation for patients with COPD and Asthma. An extended monitoring or post-procedural observation time for patients with pre-existing lung diseases is not discussed by the guidelines.Four guidelines endorse the routine administration of oxygen during FB (low to moderate evidence), three guidelines limit oxygen to certain cases . An explicit statement for the stepwise escalating management for persistent hypoxemia was not given by the guidelines. Advanced airway equipment must be present according to the GRS.2 and ECG is given by five guidelines. The strengths of recommendation increase until 2019, but the level of evidence remains low. The GRS mentions SpO2 as the minimum monitoring. The UMCG mentions monitoring of NIBP, SpO2 and ECG, but gives no recommendation. The JICS endorses the monitoring of vigilance and respiratory rate after FB.Advice for post-procedural monitoring, particularly NIBP, SpORegarding the time patients are monitored in the recovery room, only the ILATF gives a specific recommendation of 2 h. One guideline mentions the recovery time of 2 h, but without a recommendation. Two guidelines propose, without going into detail, that patients be observed until they reach a level of pre-procedure consciousness and acceptable vital parameters.This systematic review is the first work to focus on the issues of monitoring and recovery in bronchoscopies.Insufficient monitoring combined with too deep sedation and undetected respiratory depression can lead to substantial complications in bronchoscopic procedures . Hence, Beside circulation, respiration is the main system to take care for during bronchoscopy. For instance, pulse oximetry is an adequate method to monitor hypoxemia during bronchoscopy , 36. NonHypercapnia is not only a predictor of apnoea, but leads to consciousness disorders and hypotension , particuHowever, the evidence which the bronchoscopy guidelines as well as the ASA and ESA (European Society of Anaesthesiology) guidelines on sedation rely on, mainly rises from studies on gastrointestinal endoscopies –48. In bParticularly in patients with pre-existing lung diseases or obstructive sleep apnea, transcutaneous capnometry is more precise in detecting hypercapnia during and after procedures with maintained spontaneous breathing than end-tidal capnometry . HoweverIn all the investigated guidelines of this review, no recommendation was given on the management of hypercapnia or a tolerable threshold of partial pressures of carbon dioxide during FB.Even though there is no evidence for tolerable thresholds of carbon dioxide during the procedure, after which the procedure should be immediately terminated, capnometry could help to identify patients at risk. Especially in long lasting procedures, such as EBUS or endoscopic lung volume reduction, capnometry can indicate a longer or more intensive postoperative observation , 53. In The type and depth of sedation influence the necessary recovery time, too , 42, 55.A trend could be identified regarding the sedative agents: While midazolam alone was preferred in the earlier guidelines, the combination of sedative agents with opioids is favoured now. The combination reduces cough, pain (due to the insertion of the endoscope), improves the patients’ tolerance, and reduces the total dose of sedative agents (high level of evidence). Furthermore the use of topical anaesthesia reduces cough and is beneficial for the patients tolerance . As explFour guidelines concern the issue of the appropriate recovery time, two of which recommend two hours of observation, and two recommend keeping the patient in the recovery room until the preprocedural level of consciousness and acceptable vital parameters are reached; these statements are not further specified. Neither the quantitative (“two hours”) nor the qualitative approach are supported by evidence. The ASA states that there is insufficient literature concerning the appropriate monitoring, as well as recovery time and discharge criteria during recovery care. A vague recommendation is given to monitor the patients’ oxygenation and circulation until a pre-procedure level of consciousness is re-attained, which aligns with the reviewed guidelines .None of the guidelines try to relate their recommendations on recovery time to patient-related factors , the type of bronchoscopy, or the type or depth of sedation. From our point of view, it is desirable to focus on these issues, because adequate recommendations could help to safely discharge of patients from the recovery unit and simultaneously limit the necessary resources to a sensible extent.The recommendations in the reviewed guidelines resemble in content but differ in the strength of recommendations. For most issues, the underlying evidence is low or moderate. The topics capnometry and recovery time are not sufficiently covered. There are only few recommendations adapted to patients with chronic lung diseases.Future guidelines for flexible bronchoscopy should include these issues in their scope and literature search. More primary studies on these topics are necessary.Additional file 1. PRISMA-P checklist.


The metabolism of bile acid by the gut microbiota is associated with host health. Bile salt hydrolases (BSHs) play a crucial role in controlling microbial bile acid metabolism. Herein, we conducted a comparative study to investigate the alterations in the abundance of BSHs using data from three human studies involving dietary interventions, which included a ketogenetic diet (KD) versus baseline diet (BD), overfeeding diet (OFD) versus underfeeding diet, and low-carbohydrate diet (LCD) versus BD. The KD increased BSH abundance compared to the BD, while the OFD and LCD did not change the total abundance of BSHs in the human gut. BSHs can be classified into seven clusters; Clusters 1 to 4 are relatively abundant in the gut. In the KD cohort, the levels of BSHs from Clusters 1, 3, and 4 increased significantly, whereas there was no notable change in the levels of BSHs from the clusters in the OFD and LCD cohorts. Taxonomic studies showed that members of the phyla Bacteroidetes, Firmicutes, and Actinobacteria predominantly produced BSHs. The KD altered the community structure of BSH-active bacteria, causing an increase in the abundance of Bacteroidetes and decrease in Actinobacteria. In contrast, the abundance of BSH-active Bacteroidetes decreased in the OFD cohort, and no significant change was observed in the LCD cohort. These results highlight that dietary patterns are associated with the abundance of BSHs and community structure of BSH-active bacteria and demonstrate the possibility of manipulating the composition of BSHs in the gut through dietary interventions to impact human health. Bile acids (BAs), which mainly include cholic acid (CA) and chenodeoxycholic acid (CDCA) in humans, are derived from cholesterol and are further conjugated with amino acids in hepatocytes. Conjugated BAs with both hydrophobic (lipid soluble) and polar (hydrophilic) faces are actively secreted into the small intestine to emulsify, solubilize, and transport lipids, such as fatty acids, cholesterol monoglycerides, and fat-soluble vitamins. The metabolism of BAs is associated with obesity, diabetes, gallbladder diseases, gastrointestinal diseases, liver diseases, and cardiovascular diseases . The conLactobacillus strains with BSH activity are a criterion for selecting probiotics with cholesterol-lowering and anti-obesity effects [Blautia obeum can shape the chemical environment of the gut through its BSH activity, which can degrade taurocholate and reduce colonization of the major human diarrheal pathogen Vibrio cholerae [In the ileum, most conjugated BAs are reabsorbed and transported via portal blood to the liver, while the remaining BAs <10%) are further metabolized by the gut microbiota to produce secondary BAs, including deoxycholic acid (DCA) and lithocholic acid (LCA) . Metabol% are fur effects . Blautiacholerae . Manipulcholerae .Studies regarding BSHs related to host health are primarily performed using mouse models. The effect of BSHs on human health is currently unclear. Recently, we demonstrated that gut BSH abundance is significantly related to human diseases, including obesity and T2D as well as cardiovascular, liver, gastrointestinal, and neurological diseases . Among tThe majority of studies regarding the effects of diet on the human gut microbiota have focused on the microbial community structure based on 16S rDNA analysis ,23. Compp value and fold-change (FC) at p < 0.05  (p = 0.89) (p = 0.02). In the 3 and 7 day study periods, the total abundance of BSHs did not show noticeable changes under LCD treatment (p = 0.11). Therefore, among the three dietary treatments tested in the study, only the KD significantly affected the abundance of BSHs.We used 44 previously characterized BSHs  to searcp < 0.05 . BSH abuC = 1.7) a. The ab = 0.89) b, despit = 0.89) c, and thThe protein sequence similarity network (SSN) of the gut BSHs was further generated with a criterion of >40% sequence identity, which separated the gut BSHs into seven clusters . The clap = 0.02, 1.5 × 10−5, and 0.0017, respectively; FC = 1.7, 2.3, and 2.9, respectively). In the OFD cohort, the BSH levels from the four clusters did not show a substantial difference. Finally, only the protein levels in Cluster 3 increased significantly at 3 days with the LCD (p = 0.027). There was no obvious trend of alteration in the abundance of BSH in other clusters in the LCD cohort. Overall, these results indicated that the relationship between the abundance of microbial BSHs in the gut and diet varies depending on different dietary patterns.Our previous study suggested that the abundance of BSHs from different clusters showed distinct relationships with human diseases . In thisAlistipes, Bacteroides, and Barnesiella. In the phylum Firmicutes, BSHs showed a wide distribution at the genus level, including Ruminococcus, Eubacterium, Lachnospira, Oscillibacter, Clostridium, Mediterraneibacte, Holdemanella, Roseburia, and Lactobacillus  (p = 0.11). The abundance of BSHs from Actinobacteria was significantly reduced under KD treatment . These results suggest that consuming a KD altered the community structure of BSH-active microbes significantly. For the UFD versus OFD, Bacteroidetes BSH levels decreased significantly . No significant difference in the abundance of BSHs from Firmicutes and Actinobacteria was observed (p > 0.05) (p = 0.037). After 14 days, no significant difference in the abundance of BSHs from Bacteroidetes, Firmicutes, and Actinobacteria was observed between LCD and BD subjects (p > 0.05). Taken together, these data suggest that the alteration of BSHs was limited to the KD cohort; the UFD and LCD did not change the community structure of BSH-active bacteria.BSHs in the gut are from 12 phyla but mainly belong to the two dominant gut phyla Bacteroidetes and Firmicutes . The BSHbacillus . The phyC = 2.0) b. The ab > 0.05) c. Althou > 0.05) d. Only tLactobacillus plantarum, marketed as a probiotic, has beneficial effects on host health [Dietary patterns and interventions affect the overall composition of the gut microbiome and exert direct effects on mammalian health. The effects of diet, including LFDs, HFDs, high protein diets, LCDs, very-low-calorie diets, and KDs, on the health and gut microbiota composition of animal models have been widely studied . Diet ist health , we propBacteroides thetaiotaomicron and Bacteroides ovatus [The BSHs from Clusters 1 and 3 were predominantly from the phylum Bacteroidetes. The abundance study based on taxonomic aspects further displayed a significant increase in the BSHs from Bacteroidetes but not Firmicutes in the KD cohort. However, this study of BSHs mainly focused on the enzymes from Firmicutes, as 39 were from Firmicutes out of the 44 experimentally characterized BSHs . Furthers ovatus ,38. Duris ovatus . As onlyThe present study indicated that only the KD altered the total abundance of BSHs, the abundance in different clusters, and community structure, while the OFD did not cause any changes. As the KD cohort had a low ratio of CHO and high ratio of fat—while the ratio of CHO, protein, and fat was the same for both the UFD and OFD—we propose that the dietary constituents, but not the food intake amounts, exerted a detrimental effect on the diversity of BSHs from Firmicutes and Bacteroidetes in the human gut. However, the abundance of BSHs in the LCD cohort did not show obvious changes despite the LCD and KD having a similar CHO, protein, and fat ratio. This may be because the LCD study recruited obese patients with NAFLD, where dysbiosis had occurred and confounded the quantification of BSHs .We separated BSH homologs from the UniProt database into seven clusters in a previous study . These sThe human diet can be influenced by many habitual, demographic, environmental, social, and individual factors . Rigorou−5, and the proteins from human gut microbiota were retained . The Kaiju program (version 1.7.3) was used to identify the taxonomic information of each read in the phylum rank [Whole-genome sequencing datasets of the human fecal metagenomes related to diet and generated on Illumina platforms were downloaded from the NCBI SRA database . Only dalum rank . The reaAll statistical analyses were performed using R. The Shapiro–Wilk test was used to assess the normality of the abundance of BSHs. The paired Wilcoxon signed-rank test was used to test the significance of differences in BSH abundance between test and control subjects, as the data were not normally distributed. The FC based on the RPM value was calculated by dividing the value from test diet-fed subjects by the value from the control subjects.In conclusion, we collected three datasets from human gut metagenomic sequencing studies related to diet. The abundance and community structure of the BSHs in the three cohorts were analyzed. The results showed that the KD significantly influenced the abundance and community structure of BSH-active bacteria, while overfeeding had no effect on BSH abundance. To our knowledge, this study is the first to demonstrate the relationship between diet and BSHs in the human gut, which may allow the manipulation of BA metabolism via diet for the benefit of human health.


GPS alarms aim to support users in independent activities. Previous systematic reviews have reported a lack of clear evidence of the effectiveness of GPS alarms for the health and welfare of users and their families and for social care provision. As GPS devices are currently being implemented in social care, it is important to investigate whether the evidence of their clinical effectiveness remains insufficient. Standardized evidence frameworks have been developed to ensure that new technologies are clinically effective and offer economic value. The frameworks for analyzing existing evidence of the clinical effectiveness of GPS devices can be used to identify the risks associated with their implementation and demonstrate key aspects of successful piloting or implementation.The principal aim of this study is to provide an up-to-date systematic review of evidence based on existing studies of the effects of GPS alarms on health, welfare, and social provision in the care of older adults compared with non–GPS-based standard care. In addition, the study findings were assessed by using the evidence standards framework for digital health technologies (DHTs) established by the National Institute for Health and Care Excellence (NICE) in the United Kingdom.active monitoring DHTs.This review was conducted according to the PRISMA  guidelines. Primary studies published in peer-reviewed journals and gray literature from January 2005 to August 2020 were identified through searches in 13 databases and several sources of gray literature. Included studies had individuals (aged ≥50 years) who were receiving social care for older adults or for persons with dementia; used GPS devices as an intervention; were performed in Canada, the United States, European Union, Singapore, Australia, New Zealand, Hong Kong, South Korea, or Japan; and addressed quantitative outcomes related to health, welfare, and social care. The study findings were analyzed by using the NICE framework requirements for Relevance to current pathways in health/social care system and Acceptability with users, and minimum evidence was identified for the tier 1 category Credibility with health, social care professionals. However, several evidence categories for tiers 1 and 2 could not be assessed, and no clear evidence demonstrating effectiveness could be identified. Thus, the evidence required for using DHTs to track patient location according to the NICE framework was insufficient.Of the screened records, 1.6% (16/986) were included. Following the standards of the NICE framework, practice evidence was identified for the tier 1 categories Evidence of the beneficial effects of GPS alarms on the health and welfare of older adults and social care provision remains insufficient. This review illustrated the application of the NICE framework in analyses of evidence, demonstrated successful piloting and acceptability with users of GPS devices, and identified implications for future research. This dechnology  and the l health , includil health . The glol health .GPS solutions enable the user to send an alarm to home care, family members, or both, either at home or outdoors. The user’s position can be localized through GPS coordinates when an alarm is sent. GPS alarms may also include a geofencing function that automatically generates an alarm if the user leaves a predefined geographical area. A European overview has identified ongoing implementation of GPS alarms in the municipal care of older adults in Sweden and Norway .Research on the implementation of welfare technology in Swedish municipalities has identified several barriers to its use, including lack of supporting evidence of the benefits and positive outcomes . Hence, active monitoring and thereby stratified into evidence tier 3b in the framework. Good levels of evidence for tier 3 DHTs include evidence of credibility with health and social care professionals, relevance to current care pathways in health care systems, acceptability with users, equalities considerations in provision and use, accurate and reliable measurements and transmission of data, reliable information content, ongoing and planned continuous data collection to follow up on the use and value of the DHT, quality and safeguarding, and demonstration of its effectiveness according to intended outcomes. The framework has been applied in examples of case studies that demonstrate evidence of effectiveness and economic value of a number of DHTs [When making implementation decisions, it is important to consider what kind of evidence is needed to make an informed decision. To date, there is no national Swedish evidence-based framework to support decision-making processes related to HWTs . However of DHTs . These sTwo previous scoping reviews of tracking technology in the care of older adults conducted by Røhne et al  and NeubThe aims of this review are to (1) systematically update evidence from existing studies of the effects of GPS alarms on the health, welfare, and social provision in receivers of care for older adults compared with non–GPS-based standard care and (2) review the findings using an established evidence framework for DHTs. Studies from both peer-reviewed journals and gray literature were included, and the findings were compared with the NICE evidence standards framework for DHTs . The goaThis systematic literature review was reported according to the PRISMA  guidelines .The elements of the review  were defined as shown in AimTo conduct a systematic review of existing evidence of the effects of GPS alarms on the health, welfare, and social provision in the care of older adults compared with standard non–GPS-based careInclusion criteriaOriginal, peer-reviewed publications published between January 2005 and August 2020 in the English languageStudies performed in Canada, the United States, European Union, Australia, New Zealand, Singapore, Hong Kong, South Korea, or JapanPopulation aged ≥50 yearsGPS-based alarm interventions enabled the users to initiate alarms, with or without localization and with or without geofencing functionsExclusion criteriaQualitative studies, technical validations, proof-of-concept studies, system descriptions, reviews, and editorialsOutcomesOutcomes related to the health and welfare of users and their informal caregivers, and outcomes related to provision in the care of older adultsA three-step search strategy was used: (1) an initial search of electronic peer-reviewed scientific publication databases; (2) a search of gray literature databases, trial registers, and Google Scholar; and (3) a search of gray literature from the Nordic countries in targeted websites set up by authorities and organizations, academic publication databases, and Google Scholar. All three steps used a snowballing approach ,15 in whA summary of information sources and retrieved records for all the search steps is presented in The literature search was completed on August 20, 2020, in the following electronic databases: Academic Search Elite, APA PsycINFO, Applied Social Sciences Index & Abstracts, CINAHL Plus, Cochrane Library, International Bibliography of the Social Sciences, IEEE Xplore, PubMed, Scopus, SocINDEX, Social Services Abstracts, Sociological Abstracts, and Web of Science Core Collection. The search strategy included both free-text and controlled vocabulary. The search was limited to articles published in 2005 or later.A primary search in gray literature databases was conducted on September 8 and 9, 2020. The databases searched included Base, OpenGrey, OAIster, DART-Europe, ProQuest Dissertations & Theses Global, WHO ICTRP, ClinicalTrials.gov, International HTA Database, and Google Scholar. The search strategy was simplified and adapted to the search interface of gray literature databases. Finally, a larger search for gray literature from the Nordic countries was conducted by searching the websites of government agencies and organizations working with health and welfare issues. Publication databases from universities in the Nordic countries were also searched including the databases and websites of associations of local authorities and regions in the Nordic countries and Google Scholar. The searches were conducted from September 22, 2020, to September 29, 2020, and involved searching for terms in Swedish, Norwegian, Danish, Finnish, and Icelandic.The relevant records were downloaded to the reference management software EndNote . In the search for Nordic gray literature, the retrieved records were screened to determine their relevance related to the aim of the review before downloading the publications to EndNote. In the other searches, all retrieved records were directly downloaded to EndNote. After the removal of duplicates, the records were transferred to the systematic review software Covidence . All four steps were performed by an information science specialist or librarian. The Covidence software, which automatically detected and removed any remaining duplicates, was used for title and abstract screening, full-text review, and data extraction. The screening of titles or abstracts, eligibility assessment of full-text articles, and full-text screening were performed independently by 2 reviewers; any conflicts were resolved by a third reviewer.Information on the included studies’ aims, design, conduct, population, intervention, and outcomes as well as the results for relevant outcomes were extracted from the publications by 2 reviewers independently using a predefined template. Any conflicts in eligibility assessment were resolved through discussion between the reviewers. Information regarding the included studies is presented in Publications that aimed to demonstrate evidence of effectiveness (for tier 3a) were assessed for risk of bias at the study level by 2 researchers independently. The criteria assessed for the randomized study followed the Cochrane Risk-of-Bias Tool 2.0 guidelines  and inclThe extracted data for relevant outcomes were categorized and summarized according to the tiers 1-3b evidence categories in the NICE evidence standards framework for DHTs described below. An overview of each study’s contribution to the respective evidence categories is presented in active monitoring and thereby stratified into evidence tier 3b. Moreover, the NICE guidelines state that “best practice evidence standards in each relevant evidence tier should be used for DHTs that present a potential high risk” [The framework classifies DHTs by function and thereby allows them to be stratified into evidence tiers based on the potential risk to users . Examplegh risk” . GPS alaGood levels of evidence for tier 3 DHTs are presented in The literature searches identified 1227 records. After the removal of 240  duplicates, the titles or abstracts of 80.36% (986/1227) of the publications were screened for relevance; 69.85%, (857/1227) of articles were excluded in the screening, and 10.51% (129/1227) full-text publications were assessed for eligibility according to the inclusion and exclusion criteria presented in The 16 included studies were published as original articles in scientific journals (n=6), conference papers (n=2), a master’s thesis (n=1), and project reports (n=7). A summary of the characteristics of each publication is presented in Of the 6 peer-reviewed journal studies, 1 was a randomized controlled trial (RCT), and the others were nonrandomized studies with either an experimental (n=4) or an observational design (n=1). The other 10 studies had the following study designs: observational design , pre- and postintervention design using mixed methods (n=2), economic evaluation (n=2), and within-subjects design using mixed methods (n=1). Of these 10 studies, 5 were part of larger innovation or pilot implementation projects.The study populations were older adults in general (n=4), older adults with dementia and their family CGs (n=11), and municipal employees working with GPS trackers for persons with dementia (n=1).Relevance to current pathways in health/social care system and Acceptability with users. In more than 60% of the included studies, GPS devices had been successfully piloted or implemented in social care systems. All these studies had been performed in Nordic countries as part of larger projects supporting the development of products, services, and decision-making processes. Most of these projects were part of national government programs that aimed to stimulate the use of welfare technology. Furthermore, best practice evidence showing that representatives from the intended user groups (older adults and persons with dementia) were involved in the testing of the GPS alarms and that the users were satisfied with them was identified in 38% (6/16) of the included studies. Credibility with health, social care professionals because relevant social care professionals had been involved in 75% (12/16) of the included studies.However, the evidence according to the standards for tier 2 evidence categories could not be assessed from the included studies. For example, because the alarm systems do not provide general information or advice to users concerning health, healthy living, lifestyle, diseases, illnesses, or conditions, the minimum and best practice standards were not relevant for this assessment. Nevertheless, the information that the alarm systems provides to formal and informal CGs and security service providers about user position and emergency situations must be accurate. None of the evaluated studies investigated the reliability of this information. However, one study elaborated on alarm testing and the timeliness of the transmission of information in case of an alarm during the development of test routines, and two studies investigated the CGs’ views on the accuracy of the information regarding the user position and the user-friendly aspects of the interfaces. The two latter studies identified that some situations  can limit the updating of user position and thereby reduce the reliability of the system’s information content.Furthermore, evidence of ongoing data collection to show use and value could not be identified from the included studies. Indeed, several studies demonstrated use and value on study follow-up occasions. Use was reported both for specific system functions and on a system level with varied levels of detail. Although some studies collected use data from system logs, reporting by CGs or users was more common. The measured values for users (persons with dementia or older adults) related to improved outdoor activity ; improved relationship with CGs (fewer conflicts with CGs and more freedom); increased security and safety (increased security in daily life and prolonged period living independently); and increased QoL. The measured values for CGs of persons with dementia related to improved well-being, QoL, enhanced possibility of giving more freedom to persons with dementia, and improved security and safety. Finally, examples of measures for safeguarding  in the use of GPS alarms were described in three of the included studies. However, evidence according to the standards could not be identified.P>.05) [Moreover, the included studies provide clear evidence of effectiveness in outcomes or improvements in outcomes relevant to tiers 3a and 3b. Of the 16 included studies, 10 ,33,36,37P>.05) . FurtherP>.05) . HoweverP>.05) , and anoP>.05) . In contP>.05) ,33,36. AThe summaries of the assessed risk of bias for individual studies that aimed to demonstrate evidence of effectiveness are presented in Relevance to current pathways in health/social care system and Acceptability with users) of the NICE evidence standards framework for DHTs [Credibility with health, social care professionals, although the minimum standard is insufficient for high-risk DHTs such as technologies that track patient location. More specifically, the studies in this review showed that social care professionals have been involved in the testing of alarm systems; that GPS trackers have been successfully piloted or implemented in the Swedish, Norwegian, and Danish social care systems; that representatives from the intended user groups (persons with dementia and older adults) have been involved in testing the alarm systems; and that users were satisfied with the alarm systems. Although a number of studies reported findings regarding use, value, and measures for safeguarding at specific time points, our review concluded that evidence categories for tier 2 could not be assessed from the included studies. Finally, this review identified a lack of clear evidence for effectiveness according to the standards of evidence categories in tiers 3a and 3b in the NICE framework, which is required for DHTs that track patient location [GPS alarms are implemented in social care with the aim of supporting users in independent activities of daily living, particularly outdoors. This systematic review included 16 studies investigating the effects of GPS alarms on health, welfare, and social provision in older adult care. The review demonstrates best practice evidence in peer-reviewed and gray literature for two of the tier 1 evidence categories , which identified limited evidence on the effectiveness of GPS tracker use on health-related outcomes, for example -12. The Moreover, the scoping review by Neubauer et al , which iThis review has identified a need for further research to provide the required evidence for the effects of the use of GPS-based mobile alarms on the health and welfare of older adults and social care provision. On the basis of the NICE evidence standards framework, examples of successful piloting of GPS alarms in social care systems and of testing that involved older adults and CGs have been identified.The results can be beneficial to the social care organizations that see the potential in GPS alarms to support older citizens’ independence in daily living activities. First, we demonstrated that there is a lack of evidence of the clinical effectiveness of GPS trackers in the care of older adults. Hence, the ongoing implementations of GPS trackers have not been based on evidence of their clinical effectiveness. Second, we clarified the risks of implementing patient-locating systems such as GPS with insufficient evidence based on the NICE evidence framework. On the basis of the framework, the types of potential risks associated with the use of HWTs with insufficient evidence  can be identified. Social care organizations can use this knowledge to make informed decisions on whether they should wait for, or demand, more evidence before they start using new HWTs. Hence, increased awareness of what can be gained from better evidence is important. Third, we presented experiences from successful piloting of GPS trackers in social care systems, for example, with regard to suitable user groups, usable and acceptable GPS solutions, customization and development of products and services, processes for decision-making, and implementation. The level of evidence regarding effectiveness and economic value needs to be considered in decision-making processes on the implementation of HWTs when potential benefits and risks need to be balanced. After all, money spent on improving the health of older adults needs to be spent wisely and efficiently.real-world implementation environment. Thus, the interventions to be evaluated should include user groups and service models that have been identified and developed in the previous implementation or pilot projects. In addition, generating real-world evidence during the implementation of GPS trackers in social care systems seems to be of great importance in addressing the evidence gaps.This review has identified critical knowledge gaps that need to be addressed in future research, most importantly with regard to clinical effectiveness. Open questions include the clinical effectiveness of specific GPS trackers for certain user groups with defined supporting services. The included studies can contribute with positive examples of implementation on which to base future research  and with challenges that have been experienced in previous research. Potential evolutions of this review are future studies on the clinical effectiveness of already implemented or piloted GPS trackers in their real world.There is insufficient evidence for the effects of the use of GPS-based mobile alarms on the health and welfare of older adults, as well as social care provision. Best practice evidence for two of the tier 1 evidence categories and evidence of minimum standard for the tier 1 category of the NICE evidence standards framework for DHTs  were ide


The raw EEG signal is always contaminated with many different artifacts, such as muscle movements (electromyographic artifacts), eye blinking (electrooculographic artifacts) or power line disturbances. All artifacts must be removed for correct data interpretation. However, various noise reduction methods significantly influence the final shape of the EEG signal and thus its characteristic values, latency and amplitude. There are several types of filters to eliminate noise early in the processing of EEG data. However, there is no gold standard for their use. This article aims to verify and compare the influence of four various filters  on the latency and amplitude of the EEG signal. By presenting a comparison of selected filters, the authors intend to raise awareness among researchers as regards the effects of known filters on latency and amplitude in a selected area—the sensorimotor area. The EEG-ERP has become very popular, especially in the last 20 years, due to its many advantages: The examination is inexpensive, safe and easy to carry out. The modern EEG is considered to be an excellent alternative to magnetic resonance imaging or computer tomography because of its outstanding high temporal resolution . The sigOwing to the growing popularity of the EEG over the past two decades, researchers have definitely been using more instruments. In turn, the development of new tools and software has made it possible to conduct more complex and methodologically advanced research. This is closely related to the demand for knowledge about data processing. There is growing pressure on developing more advanced statistical and signal processing methods. In addition, scientific practice is currently undergoing tremendous changes to improve the transparency of data collection, documentation and analysis, research reproducibility and manuscript review . Thus, aHowever, a review of the literature shows that this is not an evident approach. As summarized by Robbins et al. , to dateThe methods are available as built-in options in various toolboxes or as dedicated overlays which support the preprocessing phase. EEG signals recorded by a single electrode are a superposition of signals from multiple sources ; therefore, so-called spatial filters have come into use. There are also methods based on the principle of source signal estimation. An example of such a method is Blind Signal Separation (BSS) and, in particular, Independent Component Analysis (ICA) Delorme 2004). One of the more popular environments used for preprocessing is MATLAB software together with open packages, i.e., EEGLAB, ERPLAB 04. One o,22, IIR There is a recommendation for a package like EEGLAB that continuous EEG data should be filtered before being epoched or before the artifacts are removed. The process of filtering continuous data minimizes the need to filter artefacts at epoch boundaries  aged 20 to 35  without any neuromuscular or cerebral diseases took part in the study as volunteers. They were university students or alumni. All participants were right-handed, had normal color perception and normal visual acuity. All of the participants were healthy and had no neurological medical history. Information about their health and lifestyle was collected via a survey. The study was approved by the institutional ethics committee of the University of Silesia.Raw EEG signal data were taken from an experiment conducted in the laboratory. Participants were shown three Arabic numerals: 2, 3 and 4. Their task was to look at the center of the screen and respond to these numerals by pressing the appropriate keys on the keyboard with the index finger, middle finger and ring finger, respectively. A total of 450 right-hand and 300 left-hand trials were made. The stimulus interval was set at 800 ms. Each complete trial (stimulus + response + pause) lasted 2 s. Therefore, it took 15 min to complete the task for the right hand and 10 min for the left hand. Scenarios were created with Eevoke software (ANT Neuro running on PC desktop—MS Windows 7 OS). The experiment was carried out with a commercial ANT Neuro amplifier (AMP-TRF40AB model) in DC with 20,000 amplification gain and 256 Hz sampling rate, as well as ASA v.4.8 software. The stimuli included the Arabic numerals: 2, 3 and 4. The raw EEG signal and reaction times were recorded during the process for later analyses. The participants were seated in a comfortable chair, in front of a computer screen, at a distance of 1 m.Digits 2, 3 or 4 were shown in the center of the screen until a key was pressed, or until the digit automatically disappeared after 1200 ms. The subjects were required to respond by pressing the key with their index finger when “2” appeared, the middle finger when “3” appeared and the ring finger when “4” appeared. A new stimulus arrived 800 ms after the previous one. The order of all attempts was randomized. There were 150 attempts for each of these three arrangements for the right hand, and 100 attempts for the left hand. The order of these attempts was randomized.The EEG signal was recorded according to the standard 10–20 system, using an ANT Neuro amplifier and the ASA software, v.4.8. However, only eight electrodes were selected for the filtering process: Two frontocortical , two centrocephalic , two parietal  and two occipital . These channels were chosen because the visual perception and motor response had to be analyzed.The raw EEG signal from 450 measurements for the right hand and 300 measurements for the left hand was refined four times; a different filter was used each time. Subsequently, the ICA analysis was intended to remove the artifacts, divided into 450 and 300 epochs, respectively, and averaged. The maximum amplitude and latency were determined from the averaged signals. At the final stage, the amplitude and latency values of the raw signal and the signals purified by filters were compared. The raw signal was filtered with the use of four different filters  and NOTCH ) and processed. Two parameters are used to compare the effect of the filter on the EEG signal: Latency and amplitude. All analyses were performed in Python using the MNE toolkit on a PC. All analyses were performed using PC Dell Latitude E7270 with CPU Intel Core i5-6300U, Intel HD Graphics 520, 8 GB RAM and Windows 10 64 operating system. The data will be used to propose a model which uses machine learning ,40. Hz and Np < 0.05.A statistical analysis was performed with the Statistica 13.1 software. For all measures, descriptive statistics were calculated. The Shapiro–Wilk test was used to check the normality of distributions of the studied variables. The homogeneity of variances in the analyzed groups was verified by Levene’s test. If the data failed to fulfill the assumptions required for a parametric test, a nonparametric Friedman’s ANOVA test was applied. The level of significance was set at First, P100 and P300 refractions were located to verify the brain region in which the highest values were obtained. To present the results, we focused on selected electrodes/areas and the maximum and minimum values of both latency and amplitude. Several comparisons were made to show the differences between the selected approaches.Based on statistical analyses, there were no significant age-related differences for either latency or amplitude. By combining these topographical and temporal amplitude analyses, we confirmed the presence of differential responses to touch.EEG–ERP recordings were analyzed in order to identify the evoked potentials. On the basis of signal recordings obtained from seven subjects, tables were prepared with the values of amplitudes and latencies for the electrodes. It should be emphasized that among a considerable amount of data, only maximum and minimum values were chosen for the selected number of electrodes. In the first row, the highest amplitude value (for further consideration) is presented, which is associated with electrode C4 and exhibits the value of 250 ms. The latency was handled in the same way. Electrodes O1 and O2 were omitted in the presentation to narrow down the selected area to the sensorimotor area in the best possible way.Our analyses showed that the lowest latency obtained was 250 ms  and the highest latency value was 664 ms (F3). The highest latency value was observed in the signal row for electrode F3, for the test performed with the left hand. The lowest band pass latency obtained was 250 ms  and the highest was 664 ms (F3). The analysis for “notch” also showed the lowest latency value of 250 ms . In contrast, the highest value was 664 ms (F3) .The analysis was divided into a first paradigm analysis (for the right hand) and a second paradigm analysis (for the left hand), respectively.First paradigm. If analyzed sequentially, for one patient, the maximum value of latency changed/increased, the lowest was for raw, and the same for pass band and notch (648 ms). In patient 2, no difference was seen in the filters used; the latency value did not change. For the next one (3), the lowest latency value was 296 ms (C3) for raw, higher for pass band and even higher for notch, while the maximum latency value, interestingly, was the highest for raw (597 ms) and much lower for the other filters (382 ms). In case 4, the minimum latency value was the same for all. The maximum latency value for raw was obtained for C3 and was slightly higher for the other filters (664 ms) and in F3. In the analysis of patient 5, no difference was noticed in the filters used; the latency value did not change. In the analysis of patient 6, an increasing trend was observed, both for the minimum and maximum latency value. However, in the analysis of patient 7, the minimum value of latency  for three electrodes  was obtained, and it was exactly the same value, slightly bigger than for the applied filters. The maximum latency value for raw and filters was the same.Second paradigm. A detailed analysis for each individual is as follows: For patient 1 the minimum and maximum latency value for all analyses is the same. For patient 2, the minimum latency value is 312 ms (C3), while for the filters it is the same at 328 ms. Taking into account the maximum value of latency for raw, it is much higher at 542 ms (P4), and for the analysis using selected filters it is only 398 ms (F4). For patient 3, the minimum latency value for raw and filter is the same, while the maximum is the same for raw and notch at 648 ms (C4), and lower for band pass at 519 ms (F4). An analysis of patient 4 indicates that the minimum latency value for raw and filters is the same at 250 ms , while the maximum is the same for band pass and notch. The raw signal analysis is marginally higher. It can be seen in the case of patient 5 that the minimum latency value for raw and filter is the same, while the maximum latency value for pass band is slightly higher than the other values. For patient 6, the minimum and maximum latency value for raw signals is the highest. Patient 7 exhibited no difference in the values between the minimum latency values for the analyses, while the maximum was the highest for notch.Summary: Filters can affect the final latency time. They can change the latency values in comparison with the raw signal. In five out of seven patients, greater maximum latency values were observed for the first paradigm used compared to the second paradigm used for the left hand (filters). For raw signals: For four out of seven cases, higher maximum latency values were observed for the first paradigm used compared to the second paradigm used for the left hand.Next, a more detailed analysis was performed. For each of the eight electrodes, data concerning the amplitude and latency were gathered. The values concerned all fingers, 2, 3 and 4, focusing on the raw signal, FIR, IIR, FFT and NOTCH. The analysis was performed both for the right and left hand. As shown in The latency analysis in Comparisons of all selected filters were made. The graphs can be read twofold. Latency and amplitude values can be compared for each of the fingers, for the right and left hands for the selected electrodes. In addition, the values for the selected filters are presented. Consequently,  for the right hand, the largest scatter was noticed for finger 4. The difference between the filters used was negligible. For the left hand, the largest scatter was for finger 3. Interestingly, in this analysis there were differences in the filters used. For example, for FIR there was relatively little scatter for finger 2 compared to the IIR used.For the FIR filter, the amplitudes and latencies can be seen from the individual electrodes. In the case of O1 and O2 electrodes, the lowest latency values can be seen .The differences between the right and left hand are noticeable; for example, the FIR filter, both for finger 3 and finger 4. For finger 3 in the left hand, the scatter is significantly larger compared to the right hand; the same goes for finger 4.p < 0.05 and amounts to p = 0.00009 (for notch). For the analysis performed on the second finger p = 0.00006, third p = 0.00004 and fourth p = 0.00004. However, taking into account the amplitude , p = 0.03.For the right hand, the largest scatter can be seen for finger 4, while for the left hand, the largest scatter is discernible for finger 2. When considering the right hand, there is not much difference between the filters used. For the left hand there are noticeable differences between the filters used. In particular, a larger scatter can be observed for fingers 2 and 3 compared to the other filters. If we compare the latencies for the right hand  and the chosen electrodes, the selected significance level is less than There are more and more tools and possibilities for data analysis. The methods used can significantly affect the results and thus the subsequent diagnosis. Therefore, more papers should be published on different comparisons of software, methods and algorithms in use. This would make it much easier for young researchers at the beginning of their medical career to learn how to analyze and interpret the obtained results. There are over 150,000 publications on ERPs alone in the pub med database and over 17,000 on sensorimotor ERPs. This vast amount of information shows that it is often difficult to compare the results because they may depend on the methods used. The EEG itself is a relatively broad topic, yet new papers are published, related to the study of motor or speech areas, which are also key to understanding the motor planning of speech  or more It seems to the authors that far too few papers have been published with a focus on comparing several methods of analysis, or based on several different parameters. This seems to be a niche among the original papers. The impact of filters on data interpretation is not always fully appreciated. This paper reviews this issue and explains how a particular filter affects the ERP data if at all. The theoretical part related to the construction and description of filters, and to the problems that can be expected when using them, to the method of choosing the right filter and how to avoid filtering by using alternative tools has been elaborated on in the paper by Alain de Cheveigne and Israel Nelken .Filters are ubiquitous in brain data measurement and analysis. All data scientists involved in the analysis of both ERP and other signals deal with preprocessing and in particular with the choice of a filter for a specific analysis. It is important to improve the SNR, but it must also be remembered that filters affect the target signal. The authors have tried to point this out in this work.Obvious as this should be, most papers provide incomplete information about the filters used and the “methodology” in general due to journal restrictions. Another issue is the “arbitrariness” of the procedure and analysis, since the preprocessing alone can be done arbitrarily, with different parameters.The literature provides examples related to the use of filters, where it is indicated that their role is to suppress noise and enhance target activity. Yet, they can have detrimental effects that the researcher should be aware of.Considering the overall number of emerging publications related to image preprocessing (or based on image preprocessing) or even signals, relatively few papers present a comparison of results. By this we mean a comparison involving exactly the same data, but including a comparison of different types of analysis, or a change of one or more parameters. The results are more often presented using one of the adopted models of the preprocessing analysis.The question remains, can changes in amplitude or latency be crucial to the performance of EEG-based systems? Rhythms are divided primarily by their frequency range, but also by their amplitude, shape, duration and the location of the brain activity that accompanied their generation. Therefore, any change in amplitude or latency due to preprocessing or later postprocessing can have a significant impact on the medical expert’s assessment.The authors focus on presenting the results concerning the sensorimotor area, which is of great importance in the diagnosis related to neurodegenerative diseases, such as patients with multiple sclerosis ,48, ParkSome of the waveforms, particularly P50, N100, MMN, P300 and N400, are proposed as biomarkers of schizophrenia . A distiSomatosensory evoked potentials permit objectification and determination of the location of sensory disturbances. They can complement electronurography and electromyography  in the diagnosis of peripheral nervous system lesions . They are also used in the diagnosis of spinal cord injuries . Moreover, they play an important role in intraoperative monitoring of the integrity of sensory pathways  . SimilarFilters form an important part of any research methodology. They are designed to amplify the signal and suppress noise but, apart from their undeniable advantages, they can cause harmful effects. The user should be aware of the impact of filtering, particularly in the field of neuroscience. Based on seven research examples, it can be concluded that significant differences in both amplitude and latency values can occur due to the filter used and the preprocessing performed. It seems that there is a need to “standardize” preprocessing and filtering for individual disease entities in order to avoid erroneously prepared data, which, in turn, may result in a wrong medical diagnosis. The reader, researcher or expert should be aware of the potential effects, therefore more reports should be provided for different areas and selected potentials.In conclusion, it seems that each analysis should be performed at least twice to verify the results and to minimize the likelihood of misdiagnosis. To the best of our knowledge, the preprocessing of applied filters and other values is not structured yet, and there are simply some recommendations related to, e.g., the software used. Therefore, the literature exhibits quite a lot of freedom in the way that the selected methods are used. Each method has its supporters and opponents. Even an expert is unable to make a proper diagnosis without reliably prepared data. Hence, the influence of the filters on the amplitude and latency calls for a detailed analysis.