Neonatal sepsis (NS) continues to be a critical healthcare priority for the coming decades worldwide. The aim of this study was to critically appraise the quality of recent clinical practice guidelines (CPGs) for neonatal sepsis and to summarize and compare their recommendations.This study involves a systematic review of CPGs. We identified clinical questions and eligibility criteria and searched and screened for CPGs using bibliographic and CPG databases and professional societies. Each included CPG was assessed by four independent appraisers using the Appraisal of Guidelines for REsearch & Evaluation II (AGREE II) instrument. We summarized the recommendations in a comparison practical table. The systematic review was drafted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. Its protocol was registered in the PROSPERO International Prospective Register of Systematic Reviews (ID: CRD42021258732).Our search retrieved 4,432 citations; of which five CPGs were eligible and appraised: American Academy of Pediatrics (AAP 2018) (35 and 34 weeks); Canadian Pediatric Society (CPS 2017); National Institute for Health and Care Excellence (NICE 2021); and Queensland Maternity and Neonatal Services (QH 2020). Among these, the overall assessment of two evidence-based CPGs scored > 70% (NICE and QH), which was consistent with their higher scores in the six domains of the AGREE II instrument. In domain 3 (rigor of development), NICE and QH scored 99 and 60%, respectively. In domain 5 (applicability), they scored 96 and 74%, respectively, and in domain 6 , they scored 90 and 71%, respectively.The methodological quality of the NICE CPG was superior followed by the QH CPG with relevant recommendations for use in practice.https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021258732, PROSPERO (CRD42021258732). Neonatal sepsis (NS) continues to pose significant morbidity and mortality despite the continued advancement in neonatal care , 2. NeonThe global incidence of NS varies, with a population-level estimate of 2,202 per 100,000 live births, with mortality rates ranging from 11 to 19% in high- and middle-income countries  and 2.9 Identifying infants at risk for sepsis is crucial to reducing the complications of neonatal sepsis . Many orAt present, there is no unified national CPG in Saudi Arabia for the management of sepsis . FurtherIn 2021, the Saudi Neonatology Society (SNS) launched a number of projects to adapt national evidence-based CPGs for the management of high-priority health topics in neonatal healthcare, with the goal of providing evidence-based guidance and recommendations to neonatologists and pediatricians across the country. The “KSU-Modified-ADAPTE” as a formal CPG adaptation methodology consisting of three phases, namely, setup, adaptation, and finalization, has guided these projects .The Appraisal of Guidelines for REsearch and Evaluation (AGREE II) instrument is the gold standard for assessing the quality of CPGs. AGREE II is a CPG appraisal tool that has been cited and endorsed by a number of healthcare organizations –26. AGREhttp://www.guidelines-registry.org/ (Registration Number: IPGRP-2021CN383)  of neonatal sepsis , 27, 28.21CN383) .Both the PIPOH  and PICAR  models were used to guide the search strategy , 27.The protocol for this study was registered in PROSPERO  (Protocol ID: CRD42021258732).Our Guidelines Review Group (GRG) included seven expert consultant neonatologists: one of them with expertise in infectious diseases, one with expertise in systematic reviews, a consultant in Obstetrics and Gynecology, a clinical pharmacist with expertise in neonatal medication management, a specialized nurse with relevant expertise, a medical and healthcare librarian, and a CPG methodologist with a background in pediatrics.The librarian systematically searched MEDLINE, EMBASE, and CINAHL databases for relevant CPGs using the Ovid platform and hand-searched the relevant CPG databases and repositories for eligible CPGs (refer to search strategy in Two reviewers (LS and AH) independently screened the titles and abstracts of CPGs and articles that met the inclusion criteria. Three different reviewers checked the screening and full-text review . After retrieving and reviewing the full-text articles or full CPG documents, disagreements were resolved through focus group discussions.de novo development). (4) national or international scope, and (5) published by an organization or group authorship and accessible from a CPG database or peer-reviewed journal or relevant professional society website. Each source CPG was only appraised in its most recent version. Both organism-specific and nonspecific were considered in the search. CPGs that were published prior to 2016, were not in English or Arabic, were adapted from other CPGs, were presented as consensus or expert-based statements, or had a single author were excluded.The following were the NS CPGs eligibility requirements: (1) evidence-based, with a clear detailed record of the CPG development methodology. (2) English or Arabic language. (3) original source CPGs  has 23 items or questions divided into six domains, namely, scope and purpose, stakeholder involvement, rigor of development, clarity of presentation, applicability, and editorial independence. Using a 7-point Likert scale, each item was scored. The AGREE II evaluation was guided by its online version, “My AGREE PLUS,” which allows for the creation of a CPG appraisal group for each CPG and compiles and calculates the item ratings into domain ratings and comments. Each CPG was critically appraised by four AGREE II raters who were members of the GRG including four clinicians, and one of them was a methodologist  were resolved through discussion with the GRG. The standardized AGREE domain scores or ratings were calculated automatically by the online My AGREE PLUS. For each AGREE standardized domain score or rating, we agreed on a cutoff point of 70% since the AGREE II does not provide a specific cutoff point to define high- vs. low-quality CPGs, and several cutoff points have been proposed by different CPG appraisal groups. Following the appraisal, greater emphasis was placed on the scores of domains 3 and 5 in order to facilitate the filtration and final evaluation of the reporting quality of the included CPGs. Identical cutoff values have been reported , 30–32.Using the methods recommended by the AGREE II instrument, we calculated standardized scores ranging from 0 to 100% for each AGREE II domain. The key recommendations of the eligible CPGs were summarized in a comparative tabular format. The quality of CPGs was classified based on the rating of domain 3 (rigor of development), with a high-quality CPG receiving a standardized domain rating of more than or equal to 70%, a moderate-quality CPG receiving a domain rating of 40–69%, and a low-quality CPG receiving a domain rating of <40% .We used inter-rater reliability tests to determine the degree of agreement between raters (IRR) using a percent agreement inter-rater reliability assessment test for each question in each area of the five appraised CPGs to determine the level of agreement among the four raters. In addition to the percent agreement in the first overall assessment (OA1), we also investigated the consistency of ratings or the capacity for datasets that were gathered as clusters or sorted into clusters using intra-class correlation in the second overall assessment (OA2). Intra-class correlation is a popular IRR approach (ICC). We use this when there are more than two raters. A strong intra-class correlation coefficient (kappa) around 1 suggested that standards from the same set were quite comparable. A low kappa value around 0 indicated that standards from the same set were not similar. We used ANOVA “One-Way Random” on SPSS Statistics, version 21, since we had inconsistent raters/rates. We picked ICCC because of the wide range of numerical data from groups or clusters. This helped us determine the repeatability and how closely peers resembled one another in terms of certain features or attributes. We investigated how well two ordinal scale categories agreed with one another.K = 1 when there is no agreement larger than chance, and K is negative when there is agreement poorer than chance. K value might be interpreted . The weights are calculated as follows: Cohen's kappa notation is used. Because the difference between the first and second categories was comparable with the difference between the second and third categories, and so on, we chose linear weights. To quantify agreement, the kappa (K) statistic is used , 33: Wheerpreted .https://www.rayyan.ai/ . NICE presented its 13 health questions in the online full CPG document and appendices. The overall objective of the NICE CPG was clearly stated.The range of domain 2 was between 36 and 94%. The score of one CPG was > 70% (NICE = 94%) where the guideline development group was properly reported and included a multidisciplinary team representing all related disciplines to the health topic of neonatal sepsis.The range of domain 3 was between 9 and 99%. The score of one CPG was > 70% (NICE = 99%). The NICE CPG followed the NICE manual for CPG development that uses the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) method. It takes account of both clinical and economic evidence in the formulation of the recommendations. Full GRADE and GRADE-CERQual Evidence Tables were provided including the assessment of the five modified GRADE domains . The QH CPG reported an overall CPG development process. Both CPGs considered benefits and harms during the formulation of their recommendations.The range of domain 4 was between 65 and 100%. The score of three CPGs were > 70% . The three CPGs presented a clear summary of their key recommendations.The range of domain 5 was between 7 and 96%. Two CPGs scored > 70% . The NICE CPG reported a full package of CPG implementation tools including clinical pathways, quality standards, baseline assessment tool, visual summary versions of the CPG, a link to the online Kaiser Permanente neonatal sepsis calculator, patient health education information, and a shared learning experience from the United Kingdom. Furthermore, the QH CPG provided a variety of implementation tools like flowcharts, an implementation section, quality measures, safety and quality table, education, consumer information, a set of online learning resources, and audit items.The range of domain 6 was between 4 and 90%. The scores of two CPGs were > 70% in domain 6 . Documenting the funding body and the conflicts of interest were included in both CPGs.The AGREE II standardized domain scores for the first overall assessment ranged from 33 to 100%. Two CPGs scored > 70% (NICE and QH), which was consistent with the high scores in the six AGREE II domains. The second  assessment  revealed a consensus between the reviewers on recommending the use of two CPGs (NICE and QH).K = 0.0). No questions in any of the guidelines have a fair degree of agreement. There was very good agreement in 10 questions in CPS 2017 Canadian Pediatric Society, 12 questions in AAP 2018 American Academy of Pediatrics, 9 questions in AAP2 2018 American Academy of Pediatrics guideline, 14 questions in QH 2020 Queensland Maternity and Neonatal Clinical Guidelines, and 2 questions in NICE 2021. There was an excellent degree of agreement in 3 questions in CPS 2017 Canadian Pediatric Society, 8 questions in AAP 2018 American Academy of Pediatrics, 6 questions in AAP2 2018 American Academy of Pediatrics guideline, 1 question in QH 2020 Queensland Maternity and Neonatal Clinical Guidelines, and 18 questions in NICE 2021. Regarding the summation of scores, NICE 2021 showed the highest score of 786 and also 35 was the OA1 score. Overall assessment of NICE 2021 was “Excellent” (weighted kappa score = 1). The intraclass correlation coefficient  among raters of the four recommendations for the overall assessment  were ≥ 60% in domain 3 (rigor of development) that has been identified as the strongest indicator of the quality and evidence base of a CPG more than the other five domains . A compaThe Burden of Antibiotic Resistance in Neonates from Developing Societies (BARNARDS) Study conducted an international prospective observational cohort study across 12 clinical sites that highlighted the burden and high mortality of neonatal sepsis among facility-born neonates in low-income and middle-income countries . Based oOur study is the first systematic critical appraisal of CPGs with diagnostic and therapeutic recommendations for newborns with sepsis that we are aware of. Strengths of our study included using a comprehensive PRISMA-compliant systematic review methodology to identify potentially relevant CPGs and performed quality assessment using the AGREE II instrument by a multidisciplinary expert team of neonatology clinicians and methodologists.Nevertheless, some limitations were identified in our work. Earlier disadvantages of the AGREE II instrument have been addressed in the “AGREE-REX” (Recommendation EXcellence) tool, which addresses the clinical credibility of the CPG recommendations , 47. LanThe findings of this review can be further used to inform and support any relevant CPG development or adaptation project for neonatal sepsis.We recommend including the AGREE II criteria in the capacity building of clinicians to guide their decisions in selecting high-quality and evidence-based CPGs for use in their daily practice through evidence scouting and searching for similar published AGREE II assessments of CPGs in their needed neonatology health topic.Furthermore, we recommend building a recommendation map (or RecMap) for high-priority health topics or, if possible, for all published neonatology CPGs similar to RecMap initiative for COVID-19 CPGs and for tuberculosis CPGs to increase the accessibility of pre-appraised and living specialized CPGs by the professionals, parents, carers, and the public , 49.We recommend conducting research projects to further explore the impact of high or low quality of the NS CPGs on their implementability and implementation including facilitators and barriers in different healthcare contexts, especially in low-resource settings.The methodological quality of the NICE and QH CPGs was superior, followed by CPS and AAP CPGs. Recommendations included identification of risk factors, initial assessment, investigations, antibiotic therapy, and treatment of the two main types of neonatal sepsis .The original contributions presented in the study are included in the article/YA and JA conceptualized and designed the study. LH, YA, LS, AH, JA, and NA contributed to the search, screening, review, and critical appraisal of guidelines. YA, LS, and AE wrote the first draft of the manuscript. YA and AE analyzed and interpreted the data. YA and JA supervised the procedures in the study and reviewed the drafts and final version of this manuscript. All authors have made substantial contributions and provided final approval for the conception, drafting, and final version of this manuscript. All authors have read and approved the final version of the manuscript.This study was funded by the Saudi Neonatology Society (SNS).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Clearinghouses are influential repositories of information on the effectiveness of social interventions. To identify which interventions are “evidence-based,” clearinghouses review intervention evaluations using published standards of evidence that focus primarily on internal validity and causal inferences. Open science practices can improve trust in evidence from evaluations on the effectiveness of social interventions. Including open science practices in clearinghouse standards of evidence is one of many efforts that could increase confidence in designations of interventions as “evidence-based.” In this study, we examined the policies, procedures, and practices of 10 federal evidence clearinghouses that review preventive interventions—an important and influential subset of all evidence clearinghouses. We found that seven consider at least one open science practice when evaluating interventions: replication (6 of 10 clearinghouses), public availability of results (6), investigator conflicts of interest (3), design and analysis transparency (3), study registration (2), and protocol sharing (1). We did not identify any policies, procedures, or practices related to analysis plan registration, data sharing, code sharing, material sharing, and citation standards. We provide a framework with specific recommendations to help federal and other evidence clearinghouses implement the Transparency and Openness Promotion (TOP) Guidelines. Our proposed “TOP Guidelines for Clearinghouses” includes reporting whether evaluations used open science practices, incorporating open science practices in their standards for receiving “evidence-based” designations, and verifying that evaluations used open science practices. Doing so could increase the trustworthiness of evidence used for policy making and support improvements throughout the evidence ecosystem.The online version contains supplementary material available at 10.1007/s11121-021-01284-x. Clearinghouses uniquely sit at the intersection of prevention science and evidence-based policy by supporting work to implement evidence-based preventive interventions at scale , while others rate interventions according to several “tiers” of evidence , clearinghouses supported by the federal government are a subset of all clearinghouses that share several important characteristics. These clearinghouses are influential because investigators in prevention science and allied disciplines often design studies to meet federal clearinghouse standards of evidence. Federal recognition improves the visibility and perceived credibility of interventions, and it may increase the research funding and uptake of interventions. Journal editors, peer reviewers, and other research sponsors look to clearinghouses for guidance about which research to publish and which future research to support  to minimize risk of bias . However, studies using these methods often cannot be reproduced, which may be attributable to other limitations related to transparency and openness .Adapting the Donabedian “structure-process-outcome” model from health services research  funded by the Department of Justice, Office of Juvenile Justice and Delinquency Prevention, because it utilizes the same standards and database as CrimeSolutions, and was considered redundant. We also excluded the National Registry of Evidence-Based Programs and Practices (NREPP) funded by the Department of Health and Human Services, Substance Abuse, and Mental Health Services Administration because it permanently became publicly inaccessible prior to starting data collection.Overall, we found that seven federal clearinghouses (70%) consider at least one open science practice in at least one of their policies, procedures, or practices  consider adherence to standards for reporting research design and data analysis. WWC articulates design and analysis transparency standards in their author reporting guides, which provide checklists for reporting evaluations  address prospective inclusion of studies in a structured, web-based, publicly accessible registry. While not mentioned in its policies and procedures, HomVEE reports trial registration numbers (when they exist) as part of intervention entries on their website. When there are more than 15 eligible studies for an intervention, PSC assigns points in a manner that prioritizes studies that have been registered  addressed publicly sharing or publishing study protocols. PSC prioritizes studies with protocols as it prioritizes registered studies  address conflicts of interest of intervention evaluators. Both HomVEE and WWC report whether intervention developers were involved in the study  support the public availability of summary results. ESER, HomVEE, P2W, and PSC share outcome-level data using a standardized, tabular format for each intervention entry on their websites. TPP and WWC also provide access to a standardized, tabular database across interventions.Six federal clearinghouses (60%) consider replication of intervention effects in multiple, non-overlapping samples. TPP examines whether effects in subsequent studies are consistent with an initial study  registration policy as a model for supporting future implementation of transparency and openness standards without discarding the existing body of evidence. For example, ICMJE announced in 2004 that studies conducted after 2005 would have to be registered prospectively for publication Below is the link to the electronic supplementary material.


Bone is the second most common distant metastasis site in differentiated thyroid cancer (DTC) and is normally associated with the presence of other metastases, which are usually radioiodine‐resistant. The presence of bone metastasis (BM) determines low survival and greater morbidity due to the frequency of skeletal‐related events (SREs), which can be a serious complication of BM. There is evidence that antiresorptive therapy (AT) reduces SREs in other solid tumors, but not yet in DTC BM, for which data are scant. The same is true for systemic therapy with multikinase inhibitors (MKIs). In general, the results for MKI use are well known, although the effect on BM has rarely been evaluated. While MKIs are indicated in current clinical practice guidelines, studies evaluating the benefits and risks of concomitant treatment with MKIs and AT are lacking, and the available data come from small samples in retrospective studies. The objective of this article is to review the latest evidence for concomitant MKIs and AT. Bone is a common distant metastasis in differentiated thyroid cancer, that is associated with the presence of other metastases, low survival and high morbidity. There is evidence that antiresorptive therapy and multikinase inhibitors reduce skeletal‐related events in other solid tumors, but studies evaluating the benefits and risks of concomitant treatment are lacking in differentiated thyroid cancer. This article reviews the latest evidence. These SREs, occurring in between 55% and 78% of patients with DTC and BM,Provided both approaches have demonstrated improved morbidity and mortality of RR‐DTC patients as individual therapies, it is expected that their combination will result in even better overall disease control. However, to date, no evidence has been published on the use of this combination that could unequivocally support its use in RR‐DTC patients. Consequently, this paper reviews the currently available information on the use of each strategy for the management of BM from RR‐DTC and the potential benefits associated with their combined use.2Multiple MKIs have been studied in recent decades, although the only ones currently approved for the treatment of RR‐DTC are lenvatinib, sorafenib, and cabozantinib. The SELECT study of lenvatinib shows a median progression‐free survival (PFS) of 14.7 months longer than for placebo,AT blocks the increase in reabsorption and reduction in bone formation associated with BM whereby, if osteolysis is interrupted, the lesions can stabilize and the onset of SREs can be prevented and/or delayed. Two classes of antiresorptive drugs are currently approved for the treatment of BM, bisphosphonates  and denosumab. Bisphosphonates induce osteoclast apoptosis and reduce bone reabsorption, while denosumab is a monoclonal antibody that binds to the nuclear factor kappa‐B [RANK] ligand, and impairs its interaction with the RANK receptor, which inhibits osteoclast activity. Both drug classes have been approved for the treatment of BM from different types of tumors , since they reduce the incidence and delay the time to onset of the first SRE. These results have been extensively documented in randomized, controlled clinical trials.Denosumab is also used for the prevention of SREs in patients with bone metastases from solid tumors. Thus, denosumab is an alternative to bisphosphonate therapy in the management of thyroid cancer patients with BM. Although studies conducted in BM of solid tumors have shown the superiority of denosumab over zoledronate with regard to delaying or preventing SREs, no significant differences have been found in terms of overall survival or PFS.Additional benefit should be expected for combination therapy with MKIs and AT as most BM patients who have shown benefits have received concomitant systemic therapy, although the possible benefits for MKIs and AT in combination are unknown. In published studies in renal carcinoma, concomitant treatment improved median survival by 16 months in a few cases,The potential risks of concomitant therapy with MKIs and AT include ONJ, which occurs in 1.3%–1.8% of patients treated with AT, with no significant difference in risk between bisphosphonates and denosumab. 3Despite the absolute lack of published evidence to support this combination strategy in patients with RR‐DTC, extrapolated data from other tumor types have enabled the American Thyroid Association, European Thyroid Association, and National Comprehensive Cancer Network guidelinesIf concomitant therapy is initiated, caution must be exercised and prophylactic measures provided for possible adverse effects of these drugs, which may have synergistic effects. Evaluation of the oral cavity should be performed by a maxillofacial surgeon to assess the risk of ONJ. Dental examination should be performed and all dental treatments should be completed, particularly dentoalveolar surgery, before the therapy begins, as well as professional teeth cleaning and caries control. Effective oral hygiene is recommended and risk behaviors for oral health should be limited . If zoledronate is given, kidney function must be monitored as treatment with bisphosphonates may lead to kidney failure, although this is infrequent and reversible, and the dose should be titrated depending on renal function alterations.4The presence of BM in advanced RR‐DTC has a poor prognosis, with low survival and high morbidity. Although MKIs have demonstrated clinical results in RR‐DTC, their effects on BM control have barely been evaluated and would appear to be lower than those seen in metastases at other locations. Early use of AT may reduce and/or delay the onset of SREs and associated morbidity, although the available data in RR‐DTC are scarce, and their use is accepted in parallel with the outcomes obtained in other solid tumors.There are no data about the potential benefits of combined therapy or the risks of this treatment, although there is discrete evidence regarding the greater frequency of ONJ when certain drug classes are combined. There is an ongoing clinical trial to evaluate the outcomes from lenvatinib plus denosumab in patients with RR‐DTC BM, which will undoubtedly provide important information in the future. Until then, despite seeming feasible and currently recommended by guidelines, special caution should be exerted when combining these approaches in clinical practice.The author received an honorarium payment from Eisai Farmacéutica SA in line with ICMJE guidelines.Dr Elena Navarro‐Gonzalez has received research funding, honoraria, and non‐financial or other support from Eisai Farmacéutica SA.


Working from home (WfH) has public health implications including changes to physical activity (PA) and sedentary behavior (SB). We reviewed published and grey literature for interventions designed to support PA or reduce SB in WfH contexts. From 1355 published and grey literature documents since 2010, we screened 136 eligible documents and extracted ten intervention studies. Interventions designed specifically for WfH were limited and included structured exercise programs, infrastructure , online behavioral and educational programs, health professional advice and peer support, activity trackers and reminder prompts. Evidence of interventions to improve PA and reduce SB in WfH contexts is emergent but lacking in variety and in utilization of local environments to promote good health. Evidence is needed on the adaptation of existing workplace interventions for home environments and exploration of opportunities to support PA through alternative interventions, such as urban planning and recreational strategies. Work(ing)-from-home (WfH) is now more common, particularly in office-based professions [flexible work arrangements as an outcome of the conditions of the pandemic [The COVID-19 pandemic has changed the way people work. fessions . Similarfessions , while ifessions . Many orpandemic . Now as pandemic , they neWorkplace settings are important for the prevention of non-communicable disease (NCD) and to promote healthy lifestyles . WorkplaRecent research suggests positive health benefits associated with WfH, including reduced work-family conflict, lower absenteeism, better psychological health, and better physical health ,8,9. TheWorkplaces remain a key intervention setting for PA . InterveA scoping review design was deemed most appropriate for extracting information from new and unpublished sources, given the recent changes in the WfH context. We applied the Joanna Briggs Institute framework for scoping reviews, developing an a priori protocol for framing the research question, identification and selection of studies, search, extraction and analysis of evidence as outlined below . The priAfter removing duplicates, we screened titles and abstracts using the following criteria.Scientific studies, case studies, reports, book chapters, reviews that described an intervention aiming to improve PA or interrupt SB for office workers in a home-based setting. “Work” was defined as time spent in paid work from home for any number of days/hours over the working week.The intervention included any form of activity undertaken during work time, or to replace active commuting time that could contribute to a person achieving sufficient PA to meet recommended guidelines . This coPublished after 2010 in English.Conducted in a high or middle income country (HMIC) where WfH trends and occupations have concentrated .Inclusion criteria:Interventions developed for clinical use, institutionalized populations, elite athletes, older adults, children, students, or non-working populations.Conference abstracts with limited information.News articles, generic advice, or factsheets.Exclusion criteria:Screening was conducted using Covidence . For eacUsing an iterative approach, we extracted the following information from the included studies: country, date (pre/post COVID-19), WfH context, study population, descriptions of the intervention and outcomes, provider organization (including sector/discipline), level of scientific evidence (published or otherwise), and strength of evidence provided . The information was then summarized using thematic analysis in relation to the research question.n = 12). Other documents did not specifically refer to WfH (n = 34) or relevant working populations (n = 3). Of 136 full texts assessed for eligibility, we excluded 123. Many of the documents, particularly from targeted websites, provided only generic information or advice, encouraging workers to do PA and be aware of SB but offering no structured actions that constituted an intervention. We excluded other documents because they focused on interventions or outcomes  for which PA or SB may have had little direct or indirect impact .n = 6) used experimental or quasi-experimental evaluation designs. Of these, five included control groups. Primary outcomes reported included total minutes of PA, three also reporting SB. The exercise programs (of a set duration of PA) recorded their impact on SB other outcomes. These outcomes included musculoskeletal discomfort, psychological outcomes, work performance and overall health. None of these studies measured total PA to determine the contribution to overall PA levels. Two studies used objective measures to record PA  and the other four provided only self-reported outcomes. Study populations measuring efficacy were broadly samples selected for convenience during the COVID-19 pandemic, only one collected evidence on WfH during ‘business as usual’ and while this study did not compare with a control arm it did compare workers activity while working in home and office settings [Just over half of the included studies  for many organizations and for many employees. Multiple benefits have been enabled by working from home . At the While the COVID-19 pandemic catalyzed many changes for working populations globally, we found surprisingly few PA interventions reported in the WfH context. Virtual exercise programs were the most common intervention type. However, none of the identified exercise programs measured total levels of PA or SB time over the working day/week, providing little evidence of the overall effects of the interventions on overall PA levels. Organized group or individually guided virtual programs are very readily available, such as the three grey literature interventions identified here, but the efficacy of these interventions for implementation by workplaces appears to be limited. Many other organic PA programs may have been promoted during the pandemic by organizations for employees in virtual group or individual settings.The provision of sit-stand desks was effective, both in interrupting SB and in improving PA in one study but did not result in changes in cardiometabolic health . The exiFour interventions identified were behavioral type interventions offering health education, behavioral support, motivational counselling, goal setting, and peer support through virtual platforms. Activity trackers, emails or other prompts were also used to encourage PA or break SB. In general, multi-component workplace interventions have been the most effective in improving health behaviors in workplace settings .Only one intervention explored workers behavior both in the home and office environment and it appeared to be more effective in changing SB when workers attended the office than at home , suggestEvidence on effective interventions to support PA in the physical workplace setting is well established ,16,17,18Some recommendations during the initial phase of the pandemic promoted active work meetings, standing desks for home-based work, and incentives to encourage employees to exercise . These iImplementation research evidence is needed to improve understanding about the contextual factors influencing the successful uptake of these initiatives in the home environment. Implementation challenges in office settings include the workplace culture, job requirements and public perceptions . These mWfH will continue to grow and evolve into new labor markets and sectors including in lower income countries in the future. Supporting equity of access will require a suite of flexible interventions which can accommodate home-based, office-based and hybrid working. WHO recommends employers implement programs to promote healthy WfH, stating the importance of routine breaks and the need for achieving sufficient PA, but stops short on specifying how that could be achieved . The OECFinding ways to support PA within and beyond the working day is central to preventing chronic diseases in the adult population. Incidental PA accrued throughout the day by workers walking to a meeting or to food outlets as well as too and from work may be lost if home-based workers do not leave their homes (or do so by car). Alternative forms of PA are needed to replace these losses. Commuting to work by active or public transport five days per week can provide adults with sufficient PA for health . Active Changes to workplace policies and enhanced urban planning is needed, with policies fostering a culture and norms that prioritize health and wellbeing of employees. A combination of individual, organizational and environmental level strategies may be effective, particularly for reducing workplace SB . OrganizThe pandemic has highlighted the issue of equitable access to environments supportive of PA, including greenspace and walking/cycling infrastructure for recreational and active travel . The buiWhile this review has sought to comprehensively investigate PA interventions for WfH, we excluded interventions which did not explicitly refer to the WfH environment. Similarly, as we were interested in the working adult population, we excluded studies conducted to support PA in school and university populations. The paucity of research studies we found that focused on WfH adult contexts is a major evidence gap and limits any conclusive assessment of the types of interventions that should be implemented.Work culture has changed as a legacy of the COVID-19 pandemic with more people WfH. Few interventions have been developed and evaluated to support PA and interrupt SB for the WfH context, suggesting a need to adapt and test more interventions for PA promotion/ SB interruption in the WfH setting. The existing evidence is inadequate to determine the potential impact of PA interventions for WfH settings. Therefore, to reduce the risk of chronic diseases associated with physical inactivity there is a need to improve knowledge and practice-based interventions, and this should remain a focus of population health into the future as business models for WfH emerge and evolve.


There is agreement among researchers that no simple verbal cues to deception detectable by humans have been demonstrated. This paper examines the evidence for the most prominent current methods, critically considers the prevailing research strategy, proposes a taxonomy of lie detection methods and concludes that two common types of approach are unlikely to succeed. An approach to lie detection is advocated that derives both from psychological science and common sense: When an interviewee produces a statement that contradicts either a previous statement by the same person or other information the authorities have, it will in many cases be obvious to interviewer and interviewee that at least one of the statements is a lie and at the very least the credibility of the witness is reduced. The literature on Strategic Use of Evidence shows that features of interviews that foster such revelatory and self-trapping situations have been established to be a free account and the introduction of independent information late and gradually into the proceedings, and tactics based on these characteristics constitute the best current general advice for practitioners. If any other approach 1 day challenges this status quo, it is likely to be highly efficient automated systems. Researchers have tried to exploit this difference in cognitive demands on truth-tellers and liars with a variety of methods.There are many contexts in which the reliable detection of verbal lies would be useful: In everyday life, minor disagreements could be easily resolved if there were good cues to point out which party to a conflict was being deceptive. In situations where a crime is thought to have been committed, or about to be committed, even more is at stake, for instance for law enforcement determining whether a suspect or victim or witness is being truthful, or detecting who in a crowd or queue has malignant intent. The research effort over the past decades has moved from a search for general purpose lie detection tools that might be usable in a very wide range of contexts to those focussing more on the police interview situation, or as an aid to courts where decisions on who is being truthful have to be made. In this paper, we will look at the progress made in diverse branches of research aimed at verbal lie detection. Reflecting how the field has developed, these are methods that have mainly been aimed at contexts like the police interview or the courtroom where the question of interest will often be specific rather than general, ‘Is this person lying?’. We also include recent technological approaches that may provide a route to mass screening to spot those who intend to commit a crime. In this paper, our aim is to look at the progress made by these branches of research and evaluate whether there is empirical justification to adjust the recommendations of best practice.What would the current ‘gold standard’ advice from a balanced reading of the scientific literature on lie detection be? If instantaneous and reliable lie detection is beyond human capabilities, then the activity becomes less about seeing through deception with psychological X-ray sspecs and more about demonstrating possible lies through a clash with the established facts or documents of the case. Alternatively, and with a sensitivity to the limits of the precision of human autobiographical memory, simply documenting that the person has given contradictory accounts on different occasions would suggest that at least one is incorrect, inherently reducing the person’s credibility. These intuitive rules of thumb can be taken as the baseline of lie detection, and below we ask whether the post-DePaulo research has given practitioners any methods, strategies, tricks, or tips that are more useful and precise than these ground rules. Keep in mind that the task of the police interviewer is usually focused on the lie status of one person’s account about a single event, often from a single interview. One needs a relatively definitive answer to the question of whether this particular person is lying now, not a vague indication that s/he is lying.Some methods that have been used to investigate verbal cues operate without intervening in the information gathering process and without the need for extraneous information about the incident or even the person is talking about. This is analogous to much of the work on nonverbal cues. One records the verbal behaviour naturally produced by truth-tellers and liars and the methods are applied to the data to analyse whether there are reliable differences.Unexpected complications during the incident, Accurately reported details misunderstood, Admitting lack of memory and Pardoning the perpetrator.There are methods based on a general assumption that an account based on an actual experienced event will draw upon richer mental representations than an account based on a fictional event, and so the former type of account will be tend to be more marked by perceptual and affective features and richness of detail. These include Reality Monitoring and Criterion-Based Content Analysis (CBCA), which differ in detail only. CBCA is deemed to be the most widely used method to detect lies across the world and is admissible in many national jurisdictions. In it, a statement is evaluated using criteria, the presence of which is taken to indicate that the account is based on true experience rather than being made up. The types of criteria include specific details, peculiarities and motivation, and examples of criteria are Many studies have investigated to what degree the criteria distinguish between truth and lies, and One might think that such figures would suffice to show that the method should only be used with the greatest of caution and scepticism, even if used as only one of several sources of evidence to decide veracity. An additional problem for CBCA has been pointed out by We have focused on CBCA because it is the most widely used method of its type. It seems unlikely that there would be a more positive conclusion from, for example Reality Monitoring, largely because it rests on the same assumptions as CBCA, and the available evidence, for instance from non-verifiable statements than truth-tellers.A second important branch investigates lie detection in more convoluted and structured verbal situations. This appears to start addressing the issue of ecological validity for which the field has previously been criticised. These include settings such as the police interview that last over time, where one can take repeated measures from the same target person and compare the target’s behaviour under different conditions, for example while answering different types of questions.In the forensic context, lie detection becomes more a sophisticated investigation over time, where control conditions and repeated measures can be used but where the task difficulty increases due to the ample opportunity for the suspect to play complex psychological games, including convincing him- or herself of the truth of the lie, rendering detection more difficult, be it by psychological or physiological means. For this reason, the suggested methods are also necessarily more complex. This method is based on tried-and-tested, theory-based ways of eliciting information from an interviewee, the Cognitive Interview  and the There are some single studies that definitely warrant some optimism. For example, The generalizability and replicability of the finding will have to be probed, for instance, how long does the effect of training last and does the effect found in audio statements generalise to live interviews? On the basis of these data Assessment Criteria Indicative of Deception (ACID) is currently not close to being ready for the field. Another feature of the status of ACID is that a single laboratory is the source of much of the data; before implementing widely, it would be necessary to see positive results with the method from many other laboratories too. It also looks likely that it will be possible for reasonably sophisticated suspects to take countermeasures to ACID by learning what criteria the method relies on.Imposing cognitive load, Asking unexpected questions and Encouraging interviewees to say more. Of the three the latter appears to show most promise , an effect well known in visual psychophysics . In manyfirst decision in the test phase. This would give a truer (and perhaps lower) estimate of lie-catchers’ ability to detect lies with the method.In order to rule out this type of intra-experiment context effect, or indeed to determine how much it may have led to overestimates of methods’ discriminative ability, a study would need to train participants in the lie detection method under consideration and then collect one decision on a single statement per participant. Regarding the existing database of studies of lie detection training, one would need to reanalyse the data looking only at each participant’s A similar point has been made in the commentary by Taylor, Maroño and Warmelink in late in the interview, and gradually), SUE has been shown to lead to changes of substance in an interviewee’s statements thereby potentially trapping them in a lie or forcing them into changes of account that reduces their credibility; this seems by far the most promising human-based method, incorporating solid (and simple) psychological knowledge that can be applied in certain forensic contexts, but not others; and so it is not suited for mass checking of airport passengers for example, but for highly labour- and expertise-intensive investigations of low numbers of suspects, usually a single one (Strategic Use of Evidence (SUE) requires that the lie-catcher be in possession of reliable information about the event in question independent of, and prior to, the interview. In such cases, SUE is equivalent to an instantiation into a method of the sensible basic advice from the science outlined above. In concert with a free account, the judicious introduction of the other evidence the police possess  finesses the percentage question: SUE is set up to facilitate situations where an interviewee attempting to deceive will produce a demonstrable inconsistency with other evidence.The continued study of methods in the 70% range seems to us to be of primarily academic interest that may well facilitate the development of social psychological theory, but for which it is less clear what could be a navigable route to practical implementation. It is difficult to see how methods with hit rates or effect sizes between truth-teller and liars that are less than huge could be broadly useful, and, as shown, despite much research effort, these methods do not have success rates even close to what can be regarded as beyond reasonable doubt.The approaches likely to be successful are those that actively trap the person in a contradiction, not ones that give  differences between liars and truth-tellers. Late timing of confrontation of the witness with information the police have is apparently effective, and for obvious reasons. Thus, in our opinion, there are grounds to pursue research on the optimal use of methods constructed like SUE .Other than SUE, the methods that were deemed promising a decade ago have not delivered on that promise. The field needs to be careful to avoid what Generally, in our opinion, the literature on deception detection by verbal cues is characterised by the use of solid experimental psychology to tackle questions of high practical importance accompanied by an unwillingness fully to accept the results of said solid science. There is also a risk attached to the repeated pronouncement that there is legitimate hope that the field will soon document successful lie detection methods: Such optimism may provide succour to advocates of dubious or outright useless methods that the empirical database cannot lead one to recommend. If even researchers claim year after year, decade after decade, that some form of psychological strategy represents a promising avenue for reliably detecting lies (without the requisite evidence subsequently being forthcoming), then it is surely easier for disreputable actors also to push their clearly wrong-headed methods.When additional reliable evidence is available, cunning interviewing with late and gradual presentation of the evidence, as in the SUE technique, embodies a scientifically supported common sense approach. With carefully conducted science, there is considerable potential for automated methods to detect lies in verbal material, in the future. Until then, the best general advice from the psychological literature on verbal lie detection remains simply that a person is lying if what they say is inconsistent either with other things that they have said or with other evidence.From a joint idea, TB produced the first draft which SM revised and edited, and the manuscript was finalised together. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The review of reviews had three aims: (i) to synthesize the available evidence on interventions to improve college and university students’ mental health and wellbeing; (ii) to identify the effectiveness of interventions, and (iii) to highlight gaps in the evidence base for future study.Electronic database searches were conducted to identify reviews in English from high-income OECD countries published between 1999 and 2020. All review-level empirical studies involving post-secondary students attending colleges of further education or universities that examined interventions to improve general mental health and wellbeing were included. Articles were critically appraised using an amended version of the AMSTAR 2 tool. Evidence from the included reviews were narratively synthesized and organised by intervention types.Twenty-seven reviews met the review of reviews inclusion criteria. The quality of the included reviews varied considerably. Intervention types identified included: mindfulness-based interventions, psychological interventions, psychoeducation interventions, recreation programmes, relaxation interventions, setting-based interventions, and stress management/reduction interventions. There was evidence that mindfulness-based interventions, cognitive behavioural therapy (CBT), and interventions delivered via technology were effective when compared to a passive control. Some evidence suggested that the effects of CBT-related interventions are sustained over time. Psychoeducation interventions do not appear to be as effective as other forms of intervention, with its effects not enduring over time.The review of reviews located a sizeable body of evidence on specific interventions such as mindfulness and cognitive-behavioural interventions. The evidence suggests that these interventions can effectively reduce common mental health difficulties in the higher education student body. Gaps and limitations in the reviews and the underlying body of evidence have been identified. These include a notable gap in the existing body of review-level evidence on setting-based interventions, acceptance and commitment training, and interventions for students attending colleges in UK settings. Poor mental health of further and higher education students is a growing public policy concern , 2. ReceResearch suggests that young people’s mental health is poorer during university study than before entry. In a UK study, anxiety and depression were found to be higher at mid-course compared to one-month pre-entry into university . SimilarConcern around students’ mental health has prompted recent focus on mental health provision . ServiceGiven the increase in mental health problems among students and the surge in demand for formal support , 20, 21,What is the current evidence on interventions to improve the general mental health and wellbeing of college and university students?What does the evidence tell us about the effectiveness of current interventions and what interventions are likely to be the most effective?MEDLINE and MEDLINE In Process and other Non-Indexed Citations (via OVID); PsycINFO (via EBSCOhost); Social Science Citation Index (via Web of Science); and CINAHL Plus (via EBSCOhost), from 1999 (01/01/1999) to 2020 (31/12/2020), which reflects review-level evidence of interventions before the global COVID-19 pandemic. Reference lists of all eligible reviews were hand-searched in order to identify additional relevant reviews . Examples of each search strategy can be found in We conducted a search of English language peer-reviewed literature of We included all review-level empirical studies  involving post-secondary students attending colleges of further education or universities that examined interventions to improve general mental health and wellbeing. Both universal and indicated interventions aimed at improving mental health were included. Universal interventions are aimed at students without any pre-existing mental health problems, whilst indicated interventions are aimed at students who meet criteria for mild to moderate levels of mental health problems or have acknowledged an existing mental health problem, such as depression or anxiety. Thus, studies were included involving both general student populations and students with mental health problems. Studies were excluded if they examined interventions to address specific, pre-existing neurodevelopmental conditions  or focused on non-health or wellbeing outcomes . The search was limited to English language literature. Only peer-reviewed reviews published from year 1999 onwards from high-income countries of the Organisation for Economic Co-operation and Development (OECD) were included.Titles and abstracts of publications were independently screened by two reviewers (JW and AP). Full-text copies of relevant reviews were obtained and assessed independently for inclusion by two reviewers (JW and AP). Any queries or disagreements were resolved by discussion or by recourse to a third reviewer (RC).All reviews that met the inclusion criteria were critically appraised using an amended version of the AMSTAR 2 tool . The tooThe following data was extracted by the first author and checked for accuracy by the second author: aims, primary study design, setting/country, type of intervention, comparator (if any), population, outcomes reported, main findings in relation to the review questions, limitations, and conclusions specified by authors. Key findings from the reviews were tabulated and narratively synthesised . FindingThe search generated 4,006 records. Title and abstract screening resulted in 44 articles that met the study inclusion criteria. Full-text screening resulted in the inclusion of 27 reviews. Seventeen reviews were excluded as not meeting inclusion criteria see . A summaThe characteristics of included reviews are summarised within As shown in A systematic review and meta-analysis of RCTs  of different interventions for common mental health problems in 3396 university and college students found that MBIs were effective in reducing both depression and generalized anxiety disorder in the short term but were not durable . In theiAnother systematic review and meta-analysis of RCTs, which was graded as higher quality, examined the effectiveness of MBIs for mental health outcomes in 4211 post-secondary students . HalladaHalladay et al.  also anaStudies examining whether effects were sustained over time (follow-up studies) were split by type of intervention. Halladay et al.  found thA systematic review and meta-analysis of RCTs  of MBIs for mental and physical health in university students found that MBIs were effective in reducing distress, depression and state anxiety when compared to passive controls . In theiMa and colleagues conducted a meta-analytic review of RCTs  of MBIs . They foBamber and Morpeth’s  review, Fenton et al.  conducteConley et al.  conducteRegehr et al.  conducteConley et al.  reviewedBamber and Schneider  exploredHuang et al.  conducteCBT related interventions were associated with significant (pooled) reductions in anxiety . The pooled effect of other interventions  and mindfulness  for generalised anxiety disorder were associated with greater reductions in anxiety compared to CBT.Winzer et al.  conducteCuijpers et al.  carried In their review and meta-analysis  of the impact of universal mental health prevention programmes for higher education students, Conley et al.  found thIn their review and meta-analysis of evidence  on the effectiveness of preventative interventions in reducing mental health outcomes in university students, Regehr et al.  found thHowell and Passmore  conducteConley et al.  examinedOne review graded as lower quality reviewed evidence on the prevention and early intervention for mental health problems in higher education students found that CBT approaches are effective for prevention and early intervention . The autIn a literature review of studies of depression and treatment outcomes among US college students, graded as lower quality, brief individual cognitive therapy was found to be effective at reducing mild to moderate depressive symptoms . This fiIn their review of RCTs , Winzer et al.  exploredWhen Conley et al.  reviewedIn their 2013 review , Conley et al.  exploredIn their review  of prevention and early intervention for mental health issues in higher education students, Reavely and Jorm  reportedMiller and Chung  exploredIn their review of RCTs  on the effectiveness of interventions for common mental health difficulties, Huang et al.  found thWhen exploring the combined effects of yoga, meditation, and mindfulness on depression, anxiety, and stress in 1373 tertiary education students, Breedvelt et al.  found moA network of meta-analysis of RCTs  of exercise interventions for depression in 2010 college students found that exercise interventions were effective in reducing depression . When coFenton et al.  reviewedThe review of evidence  on the impact of universal mental health prevention programmes by Conley et al.  found thThe review  by Conley et al.  also exaIn their review of universal mental health prevention programmes for higher education students , Conley et al.  found reFernandez et al.  conducteA systematic review and meta-analysis  of stress management interventions for college students found that stress reduction interventions were effective in reducing distress . In theiYusufov et al.  conducteg = 0.18, 95% CI: 0.08 to 0.27), anxiety , and stress . There were, however, no significant effects on wellbeing. The effects were higher for interventions that were based on CBT principles.Different categories of interventions  can be delivered through different means. Harrer et al.  systematp<0.001), depression , and stress . The sensitivity analyses showed no significant effects for anxiety or depression, however, when compared to the active control group . Sensitivity analyses also showed no significant difference between the computer and web-based intervention for anxiety or depression when compared to comparison interventions that included a face-to-face version of the intervention, a web-based stress management intervention, another computer-based CBT program, and an online support group.Similarly, Davies et al.  reviewedLattie et al.  conducteConley et al.  conducteFarrer et al.  systematConley et al.  conducteRith-Najarian et al.  conducteThis review of reviews identified a range of interventions for student mental health and wellbeing, including mindfulness-based interventions (MBIs), psychological interventions , psychoeducation interventions, recreation programmes, relaxation interventions, and setting-based interventions . There was evidence that MBIs, CBT, and interventions delivered via technology were effective when compared to a passive control. There is some evidence to suggest that the effects of CBT-related interventions are sustained over time. The effects of interventions delivered via technology were found to be higher for interventions that were based on CBT principles in one higher quality review. Although technology-based CBT was effective in reducing depression and anxiety, traditional therapy with human contact was found to be more effective.Moving beyond CBT, recreation programmes were also found to be effective. In fact, while both CBT and MBIs were found to be effective, other interventions  were found to be more effective in one higher quality review. The review-level evidence suggests that psychoeducation interventions are not as effective as other interventions such as MBIs, cognitive-behavioural interventions, relaxation interventions, and meditation. The effects of psychoeducation interventions do not appear to sustain over time.The review of reviews only located single reviews of evidence on acceptance and commitment training interventions  and settThis is the first review of reviews to synthesise evidence on interventions to improve college and university students’ mental health and wellbeing. Despite every effort to gather the best evidence available, the review had several limitations. First, as our searches were limited to English language literature, we did not include evidence from studies reported in other languages. Identification and synthesis of evidence published in other languages is therefore desirable, although this would require sophisticated, technical, multilingual skills during study identification, appraisal and synthesis. Second, the searches were limited to a 21-year date range (1999 to 2020). Although this date range was deemed appropriate as we aimed to identify interventions that are most relevant to modern student populations and contexts, it should be noted that this review of review-level evidence reflects the time period before the global COVID-19 pandemic. Last, scarcity of high quality evidence syntheses on interventions to improve student mental health and wellbeing led to our decision to analyse data from all 27 reviews. This decision impacts on the quality of evidence synthesised. Despite limitations in the methodological strength of some evidence, the search identified a substantial group of higher methodological quality reviews and a large number of systematic reviews and meta-analyses. It should, therefore, be used to inform policies and practice alongside other considerations.Although there was a large body of evidence on specific interventions such as mindfulness and cognitive-behavioural interventions, review-level evidence was limited in relation to other interventions such as setting-based interventions and acceptance and commitment training. Therefore, further primary studies examining the efficacy of setting-based interventions and acceptance and commitment training for students are required. Also, as there was a notable gap in the existing body of review-level evidence on interventions for students attending colleges in UK settings, a systematic review should be conducted in this area to identify primary level studies.There are several limitations in the body of evidence. First, a number of the included reviews did not specify country and setting of the underlying evidence. It is likely that a substantial portion of the evidence is from US institutions, as this is typical for most evidence on health and wellbeing interventions. Another important limitation was that the included reviews only reported findings on beneficial effects of interventions. The underlying primary studies may have only attempted to assess efficacy and not the potential broader impacts of interventions. This is an important omission in the primary literature or the reviews. Interventions aiming for beneficial outcomes can often lead to unintended, adverse impacts for some participants. Primary and secondary research (including reviews) should attempt to identify adverse impacts so they can be eliminated or ameliorated, in accordance with the ‘first do no harm’ principle. A further limitation was that many of the included reviews did not consider the distribution of impacts from interventions across different population subgroups such as socio-economic status, age, gender, disability, and sexuality. As it is entirely possible that some interventions may work better for some students than for others, an evidence base that is more nuanced in terms of individual differences and differential impacts could underpin the tailoring of interventions to suit particular student characteristics leading, in time, to more suitable and effective interventions associated with nuanced, evidence-based delivery strategies. In addition to this, some of the included studies were lacking in detail on the nature of control groups. Greater detail on the nature of control groups should be provided in future studies. Last, few studies examined duration of effects over time. Future studies should routinely assess the duration of effects over time.In light of the above, future primary and review-level research should carefully consider the distribution of impacts of interventions by population sub-groups, including socioeconomic, gender, ethnic, age, sexuality, and disability groups . InterseThe review-of-reviews located a large body of evidence on specific interventions such as mindfulness and cognitive-behavioural interventions. The evidence suggests that these interventions can effectively reduce the common mental health difficulties of students. Evidence on other interventions was, however, limited. For example, although some work has begun developing curricula to support wellbeing, review-level evidence on organisational and structural interventions was limited. Thus, it is not currently possible to determine and rank which interventions work best, where and for whom, as this would require a larger body of evidence on certain intervention types, and comparative studies or reviews. Most of the included reviews did not consider the distribution of the intervention impacts  for population subgroups such as age, gender, ethnicity, and socio-economic status. Noting the gaps and limitations in the review-level evidence previously identified, universities should select interventions based on the best available evidence, taking into consideration: the methodological strength of the underlying evidence, and the evidence on effectiveness. A good quality primary evidence-base examining these areas needs to be developed and then systematically reviewed before confident conclusions can be drawn about what works best to sustain positive mental health and wellbeing in today’s diverse and growing post-secondary student population. The need for effective support in this area can only have grown following the global COVID-19 pandemic and the associated disruption to teaching, learning, and university and college life. Following the disruption to teaching and learning, together with other stressors placed on young people from the COVID-19 pandemic, there is an imperative need to support students’ mental health and wellbeing. Future research in this area should elucidate the unique challenges that COVID-19 has presented for students to inform and tailor interventions for this generation and future cohorts facing disruptions to their teaching and learning experience.S1 Checklist(DOCX)Click here for additional data file.S1 File(DOCX)Click here for additional data file.S2 File(DOCX)Click here for additional data file.S3 File(DOCX)Click here for additional data file.S4 File(DOCX)Click here for additional data file.


Dirofilaria immitis is a vector-borne disease that affects canids and felids, both domestic and wild, throughout the world. It is a chronic disease which causes vascular damage in pulmonary arteries, and in advanced stages, the presence of pulmonary hypertension and right-sided congestive heart failure can be evidenced. Moreover, pulmonary thromboembolism is caused by the death of the worms, which can be lethal for the infected animal. Furthermore, it is the causative agent of human pulmonary dirofilariosis, being a zoonotic disease. The aim of this review was to update the current epidemiological situation of heartworm in Europe in dogs, cats, wild animals, and vectors insects, and to analyse the factors that may have contributed to the continuous spread of the disease in the last decade (2012–2021). In Europe, the disease has extended to eastern countries, being currently endemic in countries where previously only isolated or imported cases were reported. Furthermore, its prevalence has continued to increase in southern countries, traditionally endemic. This distribution trends and changes are influenced by several factors which are discussed in this review, such as the climate changes, presence of vectors in new areas, the appearance of new competent vector species in the continent, increased movement of pets that travelled to or originated from endemic countries, the urbanisation of rural areas leading to the formation of so-called “heat islands”, or the creation of extensive areas of irrigated crops. The continuous expansion of D. immitis must be monitored, and measures adapted to the situation of each country must be carried out for adequate control.Heartworm disease caused by  Dirofilaria immitis is the causal agent of heartworm disease in domestic and wild carnivores, mainly dogs and cats. In addition, it is the causative agent of human pulmonary dirofilariosis, being a zoonotic disease. Its distribution is cosmopolitan, and currently, D. immitis can be found almost anywhere in the world, from tropical to cold climates. It is a vector-borne disease, in which the mosquitoes of genera Culex spp.; Aedes spp.; Anopheles spp.; Coquillettidia spp. act as vectors. When mosquitoes ingest blood with microfilariae, these moult to infective third stage larvae (L3) in approximately 14 days, depending on external temperature conditions: the higher the outside temperature, the shorter the moulting period. When the mosquitoes feed again, L3 are inoculated into the definitive host to continue their biological cycle [al cycle .D. immitis, and it is characterised by the development of pulmonary endarteritis that chronically can lead to the development of pulmonary hypertension and right congestive heart failure, being a severe and potentially mortal condition . In many cases, it is possible to find adult worms in the heart of infected dogs, and cases with >50 adult worms and microfilaremia in the blood in hyperendemic areas are a common finding [Heartworm infection is a vascular and pulmonary disease. The dog is considered the main host of  finding . However finding . For thi finding . Infecte finding . For theD. immitis can cause benign pulmonary nodules that can be mistaken for malignant lung tumours [As heartworm is a zoonotic disease, the presence of this parasite in canid and felid reservoirs poses a health risk to humans through the bite of infected mosquitoes.  tumours ,7,8.In Europe, the epidemiological situation in the two main hosts is markedly different. The number of studies addressing the epidemiological situation in dogs is significantly higher than in cats due to, among other factors, the difficulty in diagnosis and the number of cats compared to the number of dogs that can be accessed . From 20Currently, the epidemiological status has continued to change, as has the number of epidemiological reports. Europe is facing new climatic conditions caused by climate change, or the presence of new competent vectors that increase the time of exposure to the parasite  and that widen the risk zones . This, along with other factors, has contributed to the establishment of vectors in regions where they were not previously found. Therefore, the objective of this manuscript is to review and analyse the current epidemiological situation in Europe during the last decade in dogs, cats, wild animals, and vectors to assess changes in the distribution of animal heartworm through a retrospective analysis of published epidemiological studiesIn the last 10 years, canine heartworm disease has continued to spread to eastern and north-eastern European countries, some of which are considered as new endemic countries. In other non-endemic countries, isolated cases or cases imported from endemic areas have continued to appear .Moreover, in the traditionally endemic countries of southern Europe, prevalence in dogs has continued to increase, except for some territories where the control measures adopted have achieved a decrease in prevalence.Spain and Portugal have traditionally been considered endemic countries, although not all regions of those countries have been studied . In PortD. immitis, respectively [In Spain, the studies have not been carried out uniformly throughout all territories, with several studies conducted in different regions in the past . Recentlectively ,20. Ad hectively . The canectively  and in tectively ,24. FinaD. immitis was detected at 58.9% [In Italy, epidemiological studies throughout the country on dogs have continued to be published. Previously, epidemiological reports indicated that prevalence in the north of the country was decreasing while in the centre and south of the country, it was increasing, and even regions with autochthonous cases were appearing in previously non-endemic areas ,26,27,28at 58.9% . Finallyat 58.9%  between In France, while until 2011 no indication of expansion from the south, traditionally endemic, was published, there are recent data showing presence of canine heartworm in the centre of the country, with prevalence rates between 29.41–35.2% ,43. In aD. immitis in the country [D. immitis and three with co-infections with D. repens [D. immitis from 1998 to 2018, which reported that the number of infections and co-infections with D. repens had increased significantly, especially from 2015 onwards [D. immitis in Austria [In Austria, where previously only isolated cases were reported, there are already several studies reporting the solid presence of  country . On the . repens . On the  onwards , althoug Austria .D. immitis antigens detection by ELISA. Another study reported a prevalence of 0.2% in the federal state of Brandenburg, in the centre of the country [D. immitis which had travelled to endemic countries . Finally, Maerz [Germany faces a similar scenario, since it has been observed an increase in the number of infections in dogs that have travelled or came from endemic countries, but also in dogs that presumably have not travelled outside the country. Vrhovec et al. , after t country . In addi country  reportedy, Maerz  reportedy, Maerz , so the D. immitis as isolated cases. In Ireland, for the first time, a clinical case has been published in a dog imported from the Canary Islands (Spain) [In the United Kingdom and the Netherlands, Genchi et al. , based o (Spain) .D. immitis has been published recently, demonstrating prevalence of 0.8% of microfilaremic dogs in Cahul and Chişinău [In Russia, there is a study reporting a new endemic area, the Voronezh Natural Reserve, with prevalence ranging from 8.2 to 12.2% , which aChişinău .D. immitis infections were seen by veterinarians in the Baltic countries, whereas most cases seen by veterinarians in the Nordic countries appeared to be imported [Based on the answers to a questionnaire, autochthonous cases of imported . Moreoveimported .D. immitis were detected in 14.8% of the dogs tested [D. immitis in dogs in these countries before 2011 [D. immitis is reported for the first time, showing an overall prevalence of 1.89% in the region of the Bosnia-Podriuje canton (southern country), the prevalence being 0.93% for owned dogs and 2.86% for stray dogs [Serbia and Croatia are considered endemic countries. In the latter, there are not reported increases in the prevalence, ranging from 0.46–0.6% in the published studies ,67. Howes tested , being tray dogs .D. immitis and D. repens co-infections. In the western and south-western regions, Giubega et al. [D. immitis circulating antigens were found in 8.2% of the dogs; later, samples were heated and prevalence increased to 26.8% [Romania and Bulgaria are endemic countries as well, showing increased prevalence in the last decade. In Romania, reported prevalence has been increasing in correlation with increased interest and publications on canine heartworm. Mircean et al.  and Ionia et al.  reporteda et al. . The higa et al. . In anotto 26.8% .In Bulgaria, recent studies reported prevalence between 4.8–34.7%, being higher in the central, eastern, and southern regions and lower in the western and south-western regions ,81,82. ID. immitis was present as isolated or imported in cases in the past [In Albania, the past , but recthe past , while rthe past . In Greethe past . The repthe past ,93. Athathe past  carried the past .D. immitis of 6.7 and 2.7%, respectively [D. immitis infections in dogs in the country, reporting prevalence of 0.5 and 4.3% [Turkey showed a similar trend, studies with prevalence of 1.5% being reported in Erzurum, north-eastern Turkey , 0.6% inectively . Finallyectively . In Cyprand 4.3% ,102, resD. repens in Příbram, in the Central Bohemian region, being an imported case of Hungary [D. immitis were based on isolated or imported cases [D. immitis in the country [D. repens [D. repens was reported in the western region, higher than in the eastern region, with no positive cases detected in the centre of the country [D. immitis infection were diagnosed in the Košice region of the southeast [D. repens (3.2%) [The Czech Republic was considered endemic 10 years ago, with reports of autochthonous cases and infected dogs coming from neighbouring endemic countries ,9. Howev Hungary . Until 1ed cases ,4,9. How country . Two stu. repens ,105. In . repens  reported. repens . In anot. repens . Finally country . In addioutheast . In Hungoutheast , the numoutheast ,112,113 s (3.2%) , while as (3.2%) . Széll es (3.2%)  detecteds (3.2%) .D. immitis in cats in traditionally endemic countries, such as Spain, Portugal, Italy, and Greece, while the first reports of feline heartworm have been published in some new endemic countries as well (Germany and Austria).The number of publications in feline heartworm is still substantially lower than in dogs. Some studies have reported D. immitis antibodies) and a prevalence of 0.5% (antigens) [D. immitis had already been evidenced. It is the case of Zaragoza, where the seroprevalence reported was 24.4% and the prevalence was 3.6% [D. immitis antigens [In Spain, a recent nationwide study reported an overall seroprevalence of 9.4% (anti-ntigens) . This stntigens) . This stwas 3.6% . In Madrwas 3.6% . In Barcantigens . Moreoveantigens , so the antigens  and 22.9antigens  demonstrantigens . FurtherIn Portugal, feline prevalence studies are relatively recent, but demonstrate the important presence of this parasite in the cats living in the country. The seroprevalence of samples collected in the centre of Portugal in 2009 and 2010 was 15% , the higD. repens were reported in southern Italy [In Italy, studies are still scarce. If previously, prevalence in cats was heterogeneous being 6.06–27% in the north and centre of the country, in addition to reports of isolated cases ,123,124,rn Italy  and isolrn Italy ,127,128.rn Italy .D. immitis infection is published in 2012 [Ae. abstrusus [In Germany, a retrospective study from 2012 to 2020 identified heartworm in three cats in 2012 . In Aust in 2012 . In Bulgbstrusus ; in Romabstrusus .D. immitis in otters in areas near the Danube River in eastern regions of the country. References [D. immitis infection in a grey wolf and in a red fox. Penezić et al. [Although the studies focused on wild animals have increased substantially, they are still scarce. Between 2001 and 2011, a few studies were carried out in Italy, Spain, Portugal, and Bulgaria in foxes, otters, exotic felids, wolves, and jackals [ferences ,135,136 ć et al.  and Potkć et al.  showed pć et al.  showed pD. immitis infection was also published in a ferret [D. immitis was identified in two of ninety-three examined red foxes [D. immitis was found in foxes, jackals, and raccoon dogs with a global prevalence of 23.4% in Krasnodar Krai, being the highest prevalence on the European continent in the last 20 years [D. immitis antigens between 3–44.4% in red foxes, and 4.4–58.7% in golden jackals; furthermore, isolated cases of infected red foxes and golden jackals were detected by necropsy [In Hungary, a prevalence of 3.7% in red foxes and 7.4% in golden jackals was reported . Moreovea ferret . In souted foxes . In Ported foxes . In Romaed foxes ,141. In 20 years . In Ital20 years . In Bulg20 years  reportednecropsy ,89,144.Cx. theileri in Portugal, Cx. pipiens in peninsular Spain, and Cx. theileri in the Canary Islands (Spain), Cx. pipiens, Ae. albopictus, Ae. caspius, An. maculipennis, and Cq. richiardii in Italy, and Cx. pipiens and Ae. vexans in Turkey [D. immitis have been identified. Moreover, the number of countries that have detected competent mosquitoes has also increased notably , Santarém, and Setúbal (centre-southern) [Cx. pipiens quinquefasciatus was identified as a competent vector in Algarve [Cx. pipiens and Cx. theileri as potential vectors was reported in two endemic regions of the Iberian Peninsula [Dirofilaria in different regions of the country, such as Cx. pipiens in north-eastern Italy [Ae. albopictus, Cq. richiardii, Cs. annulate, Cx. pipiens, and Och. caspius in southern Italy [Ae. albopictus in Pelagie Archipelago [Ae. koreicus, which was identified in the Province of Belluno, north-eastern Italy, and in Chiasso, in the Swiss–Italian border region [In Portugal, the presence of outhern) ,146. Sim Algarve . In Spaieninsula ,149. In rn Italy , Ae. albrn Italy ,151, andhipelago . Moreover region ,153.Cx. pipiens and Och. caspius were identified as vectors for D. immitis [D. immitis larvae were detected in Cx. pipiens/torrentium, [Cx. modestus, Cx. pipiens, and Och. caspius were identified as heartworm vectors; furthermore, Cq. richiardii was also identified in the country [Mosquito species able to transmit the disease were reported for the first time in France, Belarus, Hungary, Germany, Moldova, Romania, Serbia, Slovakia, and Russia: in Corsica (France),  immitis . In Germrentium, . In the  country ,157.D. immitis in three species of mosquitoes; the highest prevalence was detected in An. maculipennis, followed by Cq. richiardii and An. hyrcanus. Other authors have reported the presence of heartworm larvae in the thorax/head of Cx. pipiens as well [An. maculipennis, Cx. pipiens/torrentium, Aedes behningi, and Anopheles pseudopictus were identified as vectors for the transmission of D. immitis [D. immitis in animals, Cx. pipiens/torrentium was identified as a vector of heartworm disease [D. immitis larvae in Ae. vexans mosquitoes in eastern Slovakia [Cq. richiardii, Cx. pipiens pipiens, and Och. sticus in western Slovakia [Cx. pipens, Cq. richiardii, and Och. caspius [In Romania, in the Danube Delta Biosphere Reserve, Tomazatos et al.  reported as well . In Mold immitis . In Bela disease . In SlovSlovakia  and Cq. Slovakia . In Serb caspius .D. immitis larvae were evident in the thorax were: Ae. cantans, Ae. cataphylla, Ae. communis, Ae. intrudens, Ae. geniculatus, Ae. albopictus Cq. richiardii, Cx. modestus, and Cx. pipiens; larvae were found in the abdomen of Ae. cexans, Ae. cinereus, Ae. excrucians, and An. messeae. In addition, in the Tula region near Moscow, Belarus, and Ukraine, the prevalence of D. immitis in infected mosquitoes was 1.5%, and larvae were found in Ae. geniculatus, Ae. vexans, Cx. pipiens, and Och. Cantans [In Russia, Shaikevich et al.  estimate Cantans .The presence and activity of vectors in a given region is directly related to climatic conditions. This is evident in the time needed for the larvae to develop to L3, which is temperature-dependent , while below 14 °C, larvae development stops . In thisThe increase in temperatures favours the transmission of the disease to animals and humans by allowing the annual periods of activity of the mosquitoes to be lengthened and the stages of development of the larvae to be shortened.D. immitis from the south to the north of the country [This has led to the creation of more optimal conditions that allow the spread of mosquitoes to other areas where previously the climatic conditions prevented their presence ,166,167. country . In addi country ,162,163.In relation to some species of culicid mosquitoes that have been reported as vectors of the disease in some countries in the last 10 years or the replacement by other species and/or the absence of other species, this may be due to the absence of studies in some countries in the last decade and the small number of studies that have been carried out on the subject, among other factors. More studies are needed to know whether environmental conditions have influenced or are influencing this change.D. immitis have increased in countries where the presence of this parasite was already known, while heartworm cases have been confirmed in regions and countries that to date remained free of its presence. Therefore, during the last decade, it has been shown that the disease continues to spread to countries in the centre and northeast of Europe.After analysing the epidemiological and sero-epidemiological data of dogs, cats, and wildlife, as well as the presence of culicid vectors, studies show that the number of infected animals and vectors continues to increase. Thus, reports of D. immitis. Several epidemiological reviews carried out in this regard [D. immitis. Moreover, as previously indicated, the introduction of new competent vectors that quickly adapt to the environmental conditions of the European countries  is of great concern. There are other factors of a more markedly anthropogenic nature, such as the urbanisation of rural areas, especially in areas close to irrigated crops or near rivers, marshes, or lakes. Buildings and asphalt retain the heat of the day, leading to the formation of so-called “heat islands”, which favour the creation of microclimates that support the development of D. immitis larvae in mosquitoes even during the colder months [In addition to climate change, mentioned above, there are other factors that could also be directly influencing changes in the distribution and expansion of s regard ,4,9,168 r months . The lacGeospatial analysis, geographical information systems, remote sensing, global positioning systems, and virtual globes have been a breakthrough in the study of vector-borne diseases, since they have made it possible to create maps that show the risk of infection. Currently, the use of these tools has grown in importance in the knowledge of zoonotic diseases because it allows for the evaluation of the risk of transmission to the human host ,171,172.D. immitis generations in mosquitoes and determined that transmission was limited to the summer months, mainly July and August.In Europe, until 2011, some studies on heartworm disease have been carried out by using geospatial analysis and Geographical Information Systems (GIS) in Italy; specifically in Naples, in Campania , and in regions located in the centre of the country ,173,174.D. immitis infection will spread to areas previously considered as free of infection [Moreover, considering that larval development does not occur below the threshold temperature of around 14 °C, the number of heartworm generations was determined and a high risk of infection was estimated in southern Spain and Portugal, some areas of southern France, Corsica, Bosnia and Herzegovina, Turkey, Cyprus, the coast of Albania, several regions of northern and southern Italy, Naples, Sardinia and Sicily, Greece, some areas of Bulgaria, south-eastern Ukraine, and the region of Rostov-na-Donu in Russia. Furthermore, a very high risk of infection was determined in localised areas of southern Spain, two coastal areas of Sicily, southern Calabria, southern Turkey, Cyprus, and in islands of southern Greece. The region with the longest risk of infection was in Murcia (southern Spain), which ranged from March 21 to November 11. It was also suggested that if the current trend of climate change continues, nfection ,175,176.D. immitis transmission in the country, based on data of temperature, rainfall, and the location of irrigated crops, concluding that the highest risk of transmission was located in several areas from the centre, east, and south of the Iberian Peninsula, where moderate/high temperatures concurred with the presence of extensive irrigated crops; similarly, high risk of transmission was also found in some places of the Canary Islands and the Balearic Islands. On the other hand, the lowest risk of infection was predicted in the north of the country and in dry non-irrigated regions of the southeast [In the last decade, several randomised studies were carried out in Spain, Romania, and Hungary that helped to understand the risk of infection in these countries. In Spain, a GIS model was developed to predict the risk of outheast . Anotheroutheast .A study of similar characteristics was carried out in Romania , where aD. immitis was evidenced, confirming the suitability of the climate in certain German regions for the establishment of natural cycles of heartworm transmission [In Germany, a study was carried out using data on average daily temperatures recorded by weather stations close to the locations where the presence of vectors infected with smission , which eD. immitis, where the highest prevalence of infected animals was also found [In Hungary, a study carried out between 1995 and 2018 reported a rapid spread of the disease, based on the geo-referencing of infected animals  and the detection of anomalous annual temperature data compared to the four previous years. The authors concluded that two main factors were favouring this spread: the increase in temperatures as well as the increase and expansion in the population of golden jackals, the most important reservoir of heartworm in the fauna of the Mediterranean Balkans. In addition, results showed that the climate of the Great Hungarian Plain was the most suitable for the establishment of so found .D. immitis. Similarly, necessary control measures are necessary to prevent further expansion and/or contribute to the decrease in prevalence in endemic areas, which is especially important given the zoonotic nature of the infection. To this aim, specific guidelines adapted to each country would be necessary, as recommended by the European Society of Dirofilariosis and Angyostrongilosis.In the last 10 years, considering the epidemiological data, the possible factors influencing transmission, and forecasting studies using GIS models in different European territories, it can be stated that animal heartworm has continued to spread to eastern and north-eastern European countries, some of which are currently considered new endemic countries. In other countries, isolated cases or cases imported from endemic areas have continued to appear and have even increased. Moreover, in the traditionally endemic countries of southern Europe, prevalence and seroprevalence in animals have continued to increase, except for some territories where the control measures adopted have achieved a decrease in prevalence. So, at present, most of the European continent could be considered endemic. Therefore, it is necessary to continue to conduct epidemiological and sero-epidemiological studies in animals and vectors, both in endemic and non-endemic countries, in order to monitor distribution trends of