Fragility fractures are a major public health concern owing to their worrying and growing burden and their onerous burden upon health systems. There is now a substantial body of evidence that individuals who have already suffered a fragility fracture are at a greater risk for further fractures, thus suggesting the potential for secondary prevention in this field.This guideline aims to provide evidence-based recommendations for recognizing, stratifying the risk, treating, and managing patients with fragility fracture. This is a summary version of the full Italian guideline.The Italian Fragility Fracture Team appointed by the Italian National Health Institute was employed from January 2020 to February 2021 to (i) identify previously published systematic reviews and guidelines on the field, (ii) formulate relevant clinical questions, (iii) systematically review literature and summarize evidence, (iv) draft the Evidence to Decision Framework, and (v) formulate recommendations.Overall, 351 original papers were included in our systematic review to answer six clinical questions. Recommendations were categorized into issues concerning (i) frailty recognition as the cause of bone fracture, (ii) (re)fracture risk assessment, for prioritizing interventions, and (iii) treatment and management of patients experiencing fragility fractures. Six recommendations were overall developed, of which one, four, and one were of high, moderate, and low quality, respectively.The current guidelines provide guidance to support individualized management of patients experiencing non-traumatic bone fracture to benefit from secondary prevention of (re)fracture. Although our recommendations are based on the best available evidence, questionable quality evidence is still available for some relevant clinical questions, so future research has the potential to reduce uncertainty about the effects of intervention and the reasons for doing so at a reasonable cost. Fragility fractures result from mechanical forces that would not ordinarily result in fracture, known as low-level (or “low energy”) trauma . The WorFragility fractures have garnered great attention as a public health concern. Worldwide, approximately 200 million women have osteoporosis and an increased risk of fragility fracture . It was The worrying burden of fragility fractures on individuals attributable to the high number of fracture-related annual losses of quality-adjusted (QALYs) and disability-adjusted life years –7, of siThere is now a substantial body of evidence that individuals who have already suffered a fragility fracture are at greater risk for further fractures –21, partGiven these premises, that is by considering that secondary prevention of fragility fracture is a huge concern for public health which needs to be addressed as a priority, the Italian National Health Institute, in accordance with the recently founded (2020) Italian Fragility Fracture Observatory , encouraged the establishment of a working group to draft guidelines in this field . The prThe current manuscript is a translated summary of the full version of the Italian Guidelines for “Diagnosis, risk stratification and continuity of care of fragility fractures” . We hopeThe Fragility Fracture Team (FFT) was made up of professionals appointed by speciality and primary care scientific societies and the National College of Nursing Professions, representatives of patients’ associations, in addition to a team of clinical epidemiologists and biostatisticians directly appointed by the Italian National Health Institute . The final document was signed by all FFT members, submitted for its endorsement to the National Centre for Clinical Excellence, Healthcare Quality and Safety, and approved by the Italian National Health Institute in October 2021.FFT took office in January 2020 for establishing the team arrangement by assigning each member to one or more panels including (i) the executive committee  for leading the FFT, and for convocation, and coordination of plenary meetings; (ii) the evidence review team  for defining the clinical questions, developing the literature search strategies, querying the bibliographic databases, and assessing the quality of the evidence; (iii) the skilled/stakeholder panel whose members  consulted the preliminary versions of the guidelines and expressed opinions, comments and viewpoints according to their own experience, and made recommendations for subsequent versions; and (iv) the quality assurance team  responsible for ensuring that the Guideline Development Process complied with methodological standards. FFT members met The GRADE-ADOLOPMENT approach (based on the GRADE EtD frameworks) was used to determine whether to develop a new guideline or adopt existing recommendations . ThroughTopics to be considered in the current guidelines were established in a plenary session by the entire FFT. They covered three clinical issues, namely, (i) recognition of frailty as the cause of bone fracture, (ii) the (re)fracture risk assessment for prioritizing interventions, and (iii) the treatment and management of patients experiencing a fragility fracture. Clinical Questions (CQ) covering the abovementioned clinical issues were organized according to the PICO model against which we issued the recommendations . PICO stFor each CQ, a literature search was conducted using PubMed/Medline, Embase, and the Cochrane Library –35, as wAfter making a final decision regarding the quality of evidence and conducting the corresponding meta-analytic syntheses, the SoF (summary of finding) table was developed for each combination of CQ and outcome. The GRADE evidence profile table was consistently built . The GRAThe process of moving from evidence to recommendations represents a cornerstone of guideline development , 52. AmoWhen a new systematic review was conducted, or when existing systematic reviews were evaluated and their results adapted, the FFT collaborated ahead of the recommendation decision according with the GRADE-EtD framework, developing drafts of the evidence for a decision table and recommendations’ text. Ratings for recommendation type and strength  together with GRADE quality assessment labels  were assigned. The balance of effects, values and acceptability, and feasibility were also considered. The manual from the Italian National System for Guidelines   was refeOverall, 351 original papers were included in our systematic review –74–389, Briefly, we recommend (i) recognizing bone fragility as the cause or contributing cause of the current fracture, (ii) measuring the individual (re)fracture risk using a validated tool, (iii) assessing the patient’s exposure to several factors associated with imminent (re)fracture risk, (iv) using a sequential pharmacologic scheme from anabolic to antiresorptive drugs, mainly in patients at higher/imminent risk of fracture, (v) avoiding treatment interruption, except for serious adverse events that occur, and (vi) implementing multidisciplinary care systems , for ensuring patients’ transition to hospital outpatient services. Of these six recommendations, one was of high quality, another one of low quality, the remaining four being of moderate quality.From now on, as current delivery of secondary fracture prevention globally is lamentably suboptimal and taking into account the availability of guideline-based recommendations, the key challenge facing us all is how to ensure that guidelines-based care becomes usual care. The promotion of widespread awareness of the new guidelines, must necessarily be accompanied by a robust evaluation plan aimed of (i) monitoring the quality of services for secondary fracture prevention ? and (ii) assessing their impact ?. In this regard, the combination of national clinical care standards and registries to enable benchmarking against such standards provides an opportunity to undertake so-called “real-world data” analyses for monitoring the changes and assessing the impact of usual care. There are currently 20 national hip fracture registries established worldwide, and the China National Hip Fracture Registry is at an advanced stage of development . FurtherThe current guidelines provide guidance to support individualized management of patients experiencing non-traumatic bone fracture aimed of secondary prevention of (re)fracture. Although our recommendations are based on the best available evidence, questionable quality evidence is still available for some relevant clinical questions, so future research has the potential to reduce uncertainty about the effects of intervention and the reasons for doing so at a reasonable cost.All authors contributed to the preparation of the guidelines, all participated in the data collection, drafting, writing and editing the manuscript. Concept and design: MLB, GC, SL, MR, UT. Acquisition, analysis, or interpretation of data: AB, LC, DG, SM, EP, GP, MP, RR. Statistical analysis: AB, GP, RR. MLB, GC, SL, MR, UT take responsibility for the integrity of the data and the data analysis. The external experts APC, BF peer reviewed the guidelines. All authors contributed to the article and approved the submitted version.


Physical literacy is a multidimensional construct that has been defined and interpreted in various ways, one of the most common being “the motivation, confidence, physical competence, knowledge and understanding to maintain physical activity throughout the life course”. Although its improvement can positively affect many behavioral, psychological, social, and physical variables, debate remains over an appropriate method of collecting empirical physical literacy data. This systematic review sought to identify and critically evaluate all primary studies  that assessed physical literacy in adults or have proposed measurement criteria. Relevant studies were identified by searching four databases , scanning reference lists of included articles, and manual cross-referencing of bibliographies cited in prior reviews. The final search was concluded on July 15, 2022. Thirty-one studies, published from 2016 to 2022, were analyzed. We found seven instruments measuring physical literacy in adults, of which six were questionnaires. The Perceived Physical Literacy Instrument was the first developed for adults and the most adopted. The included studies approached physical literacy definition in two ways: by pre-defining domains and assessing them discretely  and by defining domains as sub-scales after factorial analyses. We found a fair use of objective and subjective measures to assess different domains. The wide use of instruments developed for other purposes in combined assessments suggests the need for further instrument development and the potential oversimplification of the holistic concept, which may not result in a better understanding of physical literacy. Quality and usability characteristics of measurements were generally insufficiently reported. This lack of data makes it impossible to compare and make robust conclusions. We could not identify if any of the existing physical literacy assessments for adults is appropriate for large-scale/epidemiological studies. Physical literacy is a multidimensional construct that has been defined and interpreted in various ways, one of the most common being “the motivation, confidence, physical competence, knowledge and understanding to maintain physical activity throughout the life course” , 2. Its Despite its widely recognized value, uncertainty around the concept prevails . The lacPhysical literacy encompasses a cluster of domains conceptually linked together. Domains are defined differently within each distinct physical literacy interpretation, commonly including affective, physical, cognitive, behavioral, and social domains –12. MostPhysical literacy is philosophically founded on respecting the nature of the human being and considers every individual without concern of age group or living place, but practically all existing assessment instruments were developed against this contention , being fIn 2018, Edwards made the first and the most embracing effort so far to systematize physical literacy and related constructs assessments in different age groups . It seemTo systematize recent progress, we sought to identify all studies that measured physical literacy in adults or have proposed measurement criteria. To our knowledge, this is the first systematic review to consider published and non-published literature, without language restriction, concerning physical literacy assessment instruments and attempts in adults. Therefore, the purpose of the current paper is: 1) To systematically review and compare existing physical literacy assessment attempts in adults in relation to its: (a) alignment to the physical literacy concept; (b) measurement properties; and 2) To propose an appropriate instrument to evaluate physical literacy in adults that can contribute to public health promotion.This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) . We deveConsidering the scarcity of existing evidence, this systematic review sought to identify all studies  that measured physical literacy in adults age of 18 or older), using a physical literacy assessment method , or that have proposed measurement criteria. All primary studies, regardless of design, were considered eligible for inclusion to identify potentially relevant studies. Published (peer-reviewed) and unpublished literature, in the form of journal articles, dissertations/theses, pre-prints or conference papers, were examined. No language restrictions were applied to maintain the inclusive character of this systematic review and avoid language bias [ or olderRelevant studies were identified by searching four databases , scanning reference lists of included articles, and manual cross-referencing of bibliographies cited in prior reviews , 14, 15.Searches included combinations of three sets of terms following PICOS: (a) terms concerning the population of interest , (b) terms concerning type of “intervention”/exposure of interest, which in this case was related to measurement issues , and (c) terms concerning the outcomes of interest . All types of study design  were included, thus there were no restrictions on study design or comparator. A full search example can be seen in The study selection process is detailed in the PRISMA flow chart . FollowiA data extraction form was developed, informed by the PRISMA statement . Data exFollowing the example of Rockliffe, Google translate was initially used to assess the eligibility of non-English language abstracts and full texts . StudiesSelected studies were evaluated and analyzed. The retrieved data were organized into a table to facilitate the synthesis process. The full data sheet is available in To assess the quality of the available physical literacy assessment instruments, we retrieved psychometric properties and feasibility data from the studies. These data included measures of reliability, validity, and other relevant psychometric properties, such as factor structure, and item response characteristics. Feasibility data were also collected, including information on staff and equipment required, assessment time, and other available details.Two authors independently assessed the quality of each study using the Effective Public Health Practice Project Quality Assessment Tool (EPHPP) . First, The search strategy resulted in 1616 studies, and 102 were eligible for full-text screening. Characteristics of 31 studies included in the current review are summarized in We classified assessment approaches into five categories: 1) pre-validated physical literacy assessments; 2) combined assessments of pre-validated or self-constructed scales without a composite score; 3) combined assessments of pre-validated or self-constructed scales with a composite score; 4) adaptations of pre-validated physical literacy assessments; 5) original assessments. Original assessments included two survey-based instruments , a speech database for assessing physical competence under the concept of physical literacy, and a focus group to evaluate confidence, physical competence, sense of self, and knowledge in relation to physical literacy. Almost all studies utilized at least one questionnaire.Physical literacy was defined consistently within included studies, mostly using slightly different versions of Margaret Whitehead’s definitions. All adopted definitions and references—as provided by authors—are listed in Explicit physical literacy instruments—six questionaries and one objective measure—are summarized in The Perceived Physical Literacy Instrument (PPLI)  was the The College Student Physical Literacy Questionnaire (CSPLQ) was created specifically for young adults in 2022 . Apart fDotazníku sebehodnocení pohybové gramotnosti (DSPG) is a Czech instrument, created in 2019 and validated in young adults [g adults . It was g adults . DSPG waMa and colleagues introduced a novel method to measure physical competence . The stuA combined assessment approach was common in included studies. Four of them used a composite score, seven did not use it. Instruments and respective attributes are summarized in This study aimed to systematically review existing physical literacy assessment attempts in adults. We found 31 studies, published from 2016 to 2022 and seven—from which only three were original—explicit physical literacy assessment instruments. Measurement properties were reported to a limited extent. The lack of available instruments led to a repeated utilization of self-constructed combined assessments. Most research was concentrated in China and published in the English language.Since the completion of data collection for this review, additional physical literacy assessments have emerged, demonstrating the increasing research interest in this area. For instance, the Évaluation de la Littératie Physique —an assesIn “Physical literacy throughout the life course” Whitehead  describeWhile debate remains, studies included in the current review approached measurement in two different ways: by defining domains and assessing them discretely  and by defining domains as sub-scales after factorial analyses. The evolution of the Perceived Physical Literacy Instrument is a particularly interesting example of the latter. The original version of the instrument defined 3 domains: knowledge and understanding, self-expression and communication with others, sense of self and self-confidence ; the simStudies that pre-defined domains faced another limitation, as the instruments they adopted were developed for an entirely different purpose rather than to measure physical literacy. For instance, motivation for engaging in sports activities measured by the Sport Motivation Scale and motivation to take part in physical activity for life are two completely different entities. The test of Gross Motor Development is a robust assessment of fundamental movement skills for children between the ages of 3 to 10 years and 11 months , but canIn her work, Whitehead consistently discourages assessments that establish levels or comparisons with other individuals , 97, 98 We found a fair use of both objective and subjective measures to assess different physical literacy attributes.Objective measures, such as energy expenditure and step tracking, measure physical activity behavior and are easily obtained from wearable devices throughout the life course. In alignment with the physical literacy philosophical foundation, these measures embrace all movement and permit tracking individual’s progress. Ma  describePractical tasks, frequently adapted from instruments developed for children, were used to assess motor performance and physical fitness. Assessed skills may not reflect a diversity of movement requirements during different stages of life , nor accOne of the premises that underpin the concept of physical literacy is based on an appreciation of the different modes through which the embodied dimension is lived . The subWe found that assessments’ measurement and usability characteristics were generally insufficiently reported. This lack of data makes it impossible to provide a comparison and make conclusions about the instruments’ quality and feasibility. We call for researchers to include all relevant information when creating, validating or applying physical literacy instruments. Reporting the time required for completion is essential, especially for assessments combining different scales and instruments. Practical tasks and objective measures are more time-consuming, and often require special equipment and trained staff. Studies included in the current review reported equipment and staff prerequisites of practical tasks, but only one reported the time needed to complete the assessment.Poor measurement properties’ reporting can be partially explained by the common use of self-constructed scales. With a lack of invariance and temporal stability evidence even for validated instruments, it is unclear if those provide accurate results, especially over time.We believe there is an opportunity for physical literacy researchers to create new instruments that could be reused and provide solid data. A recent review of physical literacy concept implementation in Europe demonstrated that the development of standardized assessment instruments may constitute an important step in intensifying physical literacy activities . There iWe were not able to identify if any of the existing physical literacy assessments for adults is appropriate for large-scale/epidemiological studies. First, there is still no agreement between researchers on what constitutes the best way to capture such a complex multidimensional concept as physical literacy, or what attributes should be measured. Second, existing instruments lack validity and reliability data.The first instrument validated in adults, Perceived Physical Literacy Instrument , has alrThis systematic review on physical literacy assessments in adults provides valuable insights to the field. Firstly, the study offers a comprehensive review of existing assessment methods, providing an up-to-date and nuanced understanding of the available tools and their psychometric properties. This detailed analysis of assessment tools can help researchers, practitioners, and policy-makers make informed decisions about which tools are most appropriate for their specific contexts and purposes.Additionally, the study provides a useful discussion of the definition and conceptualization of physical literacy, highlighting the importance of a holistic and context-dependent understanding of the construct. This discussion helps to clarify the meaning of physical literacy, its relevance to adult populations and can inform the development of more comprehensive and effective assessments.Furthermore, the review contributes to the field by identifying gaps and limitations in current assessments of physical literacy in adults. For example, the study points out the need for further research on the psychometric properties and feasibility of different assessment instruments. Moreover, the study also identified a lack of progress in the understanding of how different types of assessments could provide better understanding of physical literacy. We suggest that a more comprehensive and integrated approach may be necessary. These insights can guide future research and development efforts to improve physical literacy assessments in adults.To our best knowledge this is the first physical literacy assessment review to include studies in a non-English language. Apart from avoiding a language bias , we beliWe adopted a holistic interpretation of physical literacy, which may have introduced a potential bias into our research. This bias stems from the fact that our analysis was grounded in a particular understanding of the concept of physical literacy, which may not be shared by all researchers in the field. Furthermore, our reliance on this holistic interpretation may have influenced our analysis of the data, potentially overlooking relevant aspects of physical literacy assessments that do not fit within this framework. We believe that in the importance of considering physical literacy as a multifaceted construct that goes beyond the simple measurement of different attributes and hope to inspire further research into the development of comprehensive and valid measures of physical literacy in adults.S1 File(DOCX)Click here for additional data file.S2 File(CSV)Click here for additional data file.S3 File(CSV)Click here for additional data file.S1 Checklist(DOCX)Click here for additional data file.


Challenging behavior, such as aggression, is highly prevalent in children and adolescents with autism and can have a devastating impact. Previous reviews of challenging behavior interventions did not include interventions targeting emotion dysregulation, a common cause of challenging behavior. We reviewed emotion dysregulation and challenging behavior interventions for preschoolers to adolescents to determine which evidence-based strategies have the most empirical support for reducing/preventing emotion dysregulation/challenging behavior. We reviewed 95 studies, including 29 group and 66 single-case designs. We excluded non-behavioral/psychosocial interventions and those targeting internalizing symptoms only. We applied a coding system to identify discrete strategies based on autism practice guidelines with the addition of strategies common in childhood mental health disorders, and an evidence grading system. Strategies with the highest quality evidence  were Parent-Implemented Intervention, Emotion Regulation Training, Reinforcement, Visual Supports, Cognitive Behavioral/Instructional Strategies and Antecedent-Based Interventions. Regarding outcomes, most studies included challenging behaviors measures while few included emotion dysregulation measures. This review highlights the importance of teaching emotion-regulation skills explicitly, positively reinforcing replacement/alternative behaviors, using visuals and metacognition, addressing stressors proactively, and involving parents. It also calls for more rigorously-designed studies and for including emotion dysregulation as an outcome/mediator in future trials. Challenging behavior – including aggression, self-injury, and property destruction – occur in as many as 80% of children and adolescents with autism spectrum disorder  Evidence-Based Practices for Children, Youth, and Young Adults with Autism Spectrum Disorder 2020 Report , and preWe used the criteria for “evidence-based” as set by the NCAEP and cross-referencing an evidence grading system as outlined in Harbour and Miller  that ratOur search strategy was registered with International Prospective Register of Systematic Reviews (PROSPERO): ID [to be added after review]. This review’s pre-registered protocol is available here: [to be added after review].Our team followed The PRISMA 2020 guidelines throughout this systematic review . We idenThe eligibility of each journal article was assessed for inclusion based on the following criteria: (1) the journal article was peer-reviewed; (2) it was written in (or translated into) English; (3) the study was specifically designed to target emotion regulation/dysregulation, externalizing behavior, or challenging behavior ; (4) the study included emotion dysregulation, emotion regulation, challenging behavior, and/or externalizing behavior as an outcome measure; (5) the children or adolescents were diagnosed with Autism Spectrum Disorder (ASD), Pervasive Developmental Disorder (PDD), or any subcategories of a PDD diagnosis; (6) the intervention evaluation design was either a group-based design  or a single case design ; and (7) the intervention was designed for school, home, clinic, or remote delivery. Exclusion criteria included: (1) medication only interventions; (2) interventions involving animals, massage, yoga, or physical therapy; (3) interventions only for adults; (4) interventions that targeted internalizing symptoms only; or (5) case reports/series. The role of emotion dysregulation in other psychopathology, such as internalizing behaviors, while recognized in the literature , was notκ = .6), and all disagreements were reviewed with the team to reach a consensus on final determination per article. This yielded a total of 186 articles that were then included in a full-text review by four raters. All articles were double coded to determine if they met eligibility criteria (100% overlap). Raters reached high reliability . Again, all disagreements were reviewed with the team to reach a 100% consensus on final determination per article. See Appendix A for the full list of included studies.Initially, six raters assessed eligibility of the articles based on a review of abstracts. Abstracts were reviewed with a 20% overlap to assess interrater reliability  author; (2) year; (3) country; (4) sample size; (5) sex; (6) age range; (7) IQ; (8) race/ethnicity; (9) delivery setting ; (10) intervention description; (11) delivery setting ; (12) teacher, therapist, parent, or research team mediated; (13) teacher/parent training methods; (14) control group description; (15) research design ; (16) evaluation design ; (17) for single-case designs, number of repetitions/phases of intervention sequences; (18) for group designs, baseline group matching; and (19) reliability of primary outcome measures .We based our evidence-based strategy coding system on the Evidence-Based Practices for Children, Youth, and Young Adults with Autism Report (2020) by the NCAEP Review Team based at the University of North Carolina. Additional discrete strategies were considered for inclusion based on the criteria for qualifying as an evidence-based strategy outlined by the NCAEP Review Team: (1) two or more group design studies conducted by at least two different researchers or research groups; (2) five or more single case design studies conducted by three different investigators or research groups and with a total of at least 20 participants across studies; or (3) a combination of one group design and at least three single case study designs conducted by at least two different investigators or research groups. Following the NCAEP Review Team’s methods, we focused on discrete intervention strategies rather than comprehensive treatment models or full intervention packages therefore comprehensive treatment models or full intervention packages were coded on the discrete intervention strategies included in the model or intervention package. We considered adding the following additional discrete strategies  by two coders (lead coder a PhD ASD research psychologist), and two additional coders , completed a random selection of 20% of articles for reliability . If studies referenced previously peer-reviewed manuscripts in describing intervention components, those manuscripts were also reviewed for evidence-based strategy coding purposes. All disagreements were reviewed by the team to reach an ultimate consensus per study.We used a coding scheme based on the evidence-based grading system outlined by Harbour & Miller 2001) [01 [20] tSecond, based on Harbour & Miller 2001),  All extracted studies were considered when determining descriptive statistics on outcome measures  but percFor the main analysis of evidence to support discrete strategies for reducing emotion dysregulation/challenging behavior, only the highest quality studies were included, including RCTs and high-quality single-subject design studies , and the strategies were further broken down as A grade (tested in RCTs) and B grade .After assessing eligibility, a total of 95 articles were included in our review, which incorporated data from 2,092 children and adolescents with ASD across four continents . These articles consisted of 29 group designs , and 66 were single-case designs . The number of studies per age of the individuals with ASD was as follows (mean or mode age used per study): 25 preschool (3–5 years), 56 elementary (6–11 years), 10 middle school (12–14 years), and 3 high school (15–18 years), 1 mixed (1 preschool student and 1 high school student). As would be expected for this population, most participants (82%) were male. Most studies did not include race/ethnicity (67%), but those that did showed 60% of participant were white, 18% Hispanic, 12% Black, 8% Asian, 2% multiracial, and 0.1% Native American. Likewise, most studies did not include an IQ score (74%), but across those that mentioned IQ or functional level, 55% of studies included children and adolescents with a below average IQ and/or who had significant support needs.Regarding setting, 46% of studies implemented the strategies primarily at school , 29% primarily at home, 18% primarily through university or community clinics, and 5% primarily remotely via tele-health platforms. The percentage of studies in which the main person who mediated the strategies were teachers or teaching staff was 24%, parents was 15%, therapists was 9%, researchers was 21%, and 27% were split across person type (4% not specified). Training was provided to the child’s/adolescent’s educational or therapeutic team including parents in 80% of studies (20% of studies did not report training). Eighty-five studies (89%) found a positive effect on challenging behavior or emotion dysregulation outcomes , and 10 studies (10%) found a null/negative effect on outcomes. In studies with a positive effect on outcomes, 49/92 (53%) performed a Functional Behavior Assessment (FBA) to inform strategy selection, as opposed to 2/12 (17%) of null/negative effect studies. See Appendices D and E for methods details for each of the 95 included studies.As shown in none were tested in RCTs in middle-school students. Although the total number of studies were conducted in the school > home > clinic setting (rank order), the level of evidence across these settings was largely similar across contexts when considering study design. Studies on challenging behavior/emotion dysregulation interventions delivered via telehealth are emerging, with the most recent one being conducted out of necessity due to the COVID-19 pandemic [The top ten evidence-based strategies rank ordered were Parent-Implemented Intervention, Emotion Regulation Training, Reinforcement, Visual Supports, Cognitive Behavioral/Instructional Strategies, Antecedent-Based Interventions, Role Play and Practice, Social Skills Training, Naturalistic Intervention and Functional Behavioral Assessment. Most (59%) of the evidence across all studies was for children with ASD in elementary school (6–11 years), few studies had a mean age in the middle (10%) or high school (3%) range. Only four strategies were tested in RCTs in high school students , and pandemic .This systematic review examined the evidence base on effective strategies to address emotional dysregulation and challenging behaviors in ASD. Unlike previous reviews, our focus encompasses both knowledge of evidence-based strategies to address challenging behaviors from the behavioral analytic field and knowledge on evidence-based strategies to support emotion dysregulation from the fields of psychology and psychiatry. We identified 30 evidence-based strategies that appear to have the most empirical support for addressing challenging behavior or/and emotion dysregulation, including 21 NCAEP identified strategies and nine ones that have been commonly used in the field childhood mental health but were unrecognized as part of the 2020 NCAEP report. Two of these previously unrecognized evidence-based strategies – Emotion Regulation Training, training to recognize one’s own bodily, cognitive, and behavioral signs of stress and employ proactive coping or emotion regulation skills to reduce one’s own stress, and Role Play and Practice, actively role playing with others to practice newly learned behavioral skills – were rated as a top 10 evidence-based strategy according to study design. This finding highlights the need to explicitly teach and actively engage children and adolescents with ASD in the recognition of their own emotional states and to help build their “toolbox” of emotion regulation strategies during times of distress, and to role play or practice other replacement behaviors.Many of the strategies designated as evidence-based in this review targeting challenging behavior or emotion dysregulation do so indirectly through teaching replacement skills and strategies to reduce stress. The focus on skill building rather than punishing challenging behavior represents a departure from previously accepted practices  and reflects the importance of framing challenging behavior in the context of lagging skills ,8. At scIndeed, fourth highest on the evidence-based strategy list  was FBA,Relatively few studies incorporated emotion dysregulation or emotion regulation outcome measures, and these tended to be more recent studies (since 2015), with two exemptions, ,26 markiThis review also highlights major gaps in the field in terms of studies covering certain developmental stages, contexts, and groups. Relatively few high-quality studies examined interventions targeting middle or high school students with ASD . Future research should aim to include more racial and ethnic diversity in samples to determine if results on evidence-based strategies and considerations around choosing target behaviors generalize across racial/ethnic groups. Overall, these findings suggest the knowledge gained to date about evidence-based strategies to support children and adolescents with ASD in reducing emotion dysregulation and challenging behavior is representative only of a sub-group of younger, less racially/ethnically diverse, mostly male with ASD, but not necessarily applicable to the wider ASD population. Further research is needed to fill each of these crucial gaps.Interestingly, we found that the proportion of null/negative effects was much lower in single-case design studies compared to group design studies, suggesting there may be publishing bias at play. Authors may choose to publish cases that have a higher rate of success in treatment, so attaining an accurate picture of null/negative effects using single-case design studies may be difficult . This poThis systematic review is not without limitations. First, although the evidence level across all evidence-based strategies within each study was given equal weight in our review, some evidence-based strategies may have been more important than others (the “active ingredients”) in producing positive intervention effects. However, no studies examined discrete evidence-based strategies within intervention packages separately. This, and the use of outcome measures that are not comparable across studies, precludes a fine-grained analysis of specific components within different intervention packages. Examining active ingredients of challenging behavior/emotion dysregulation interventions in children and adolescents with ASD is an important future direction for the field. Additionally, for consistency, we limited coding of the discrete strategies to the articles, or if studies referenced previously peer-reviewed manuscripts in describing intervention components, those manuscripts were also reviewed. However, for intervention packages, this may mean that we missed discrete strategies that are in intervention manuals but not described in the peer-reviewed publications. Finally, our search criteria may have presented biases as grey/unpublished literature and articles not translated to English were excluded. As such, our study is not exempt from publication bias or selection bias as relevant articles (with both positive and null/negative effects) may have been missed.This systematic review synthesizes knowledge of evidence-based strategies to address challenging behavior in ASD from the behavioral analytic field with the knowledge of evidence-based strategies to support emotion dysregulation from the fields of psychology and psychiatry. This review highlights the importance of teaching emotion-regulation skills to children and adolescents with ASD explicitly, positively reinforcing their replacement/alternative behaviors, using visuals and metacognition to teach them skills, addressing their stressors proactively, and involving their parents. Our hope is that the findings of the current systematic review will facilitate further development, demonstration, and dissemination of evidence-based practices to support children and adolescents with ASD who engage in challenging behaviors more equitably and effectively.


Primary and incisional ventral hernias are significant public health issues for their prevalence, variability of professional practices, and high costs associated with the treatment In 2019, the Board of Directors of the Italian Society for Endoscopic Surgery (SICE) promoted the development of new guidelines on the laparoscopic treatment of ventral hernias, according to the new national regulation. In 2022, the guideline was accepted by the government agency, and it was published, in Italian, on the SNLG website. Here, we report the adopted methodology and the guideline’s recommendations, as established in its diffusion policy. This guideline is produced according to the methodology indicated by the SNGL and applying the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) methodology. Fifteen recommendations were produced as a result of 4 PICO questions. The level of recommendation was conditional for 12 of them and conditional to moderate for one. This guideline's strengths include relying on an extensive systematic review of the literature and applying a rigorous GRADE method. It also has several limitations. The literature on the topic is continuously and rapidly evolving; our results are based on findings that need constant re-appraisal. It is focused only on minimally invasive techniques and cannot consider broader issues .The online version contains supplementary material available at 10.1007/s13304-023-01534-3. Primary and incisional ventral hernias are significant public health issues for their prevalence, variability of professional practices, and high costs associated with the treatment. Abdominal wall surgery for primary and incisional ventral hernia repair can also imply long and painful periods of illness, absence from work, and possible adverse outcomes. Surgery can be highly challenging due to the size of the hernia defect, prolonged operative time, extent of adhesions, and risk of iatrogenic bowel injuries. The complexity of the evidence available in the literature and its fragmentation make it difficult for a surgeon to determine the best possible treatment options.Different minimally invasive options  have been introduced along with several open techniques in an extreme variability that concerns not only the access for the defect repair but also the physio-pathological assumptions underlying it. A multi-institutional study analyzed the variability in the techniques used in different hospitals and demonstrated that the differences in the outcomes  among the different institutions were related to the techniques adopted . FurtherThe incidence of primary and incisional ventral hernias in Italy can be estimated at 17,000 cases per year. In 2019, there were 78,182 hospitalizations  with the primary diagnosis of ventral hernia; 68.9% were associated with a surgical operation, of which 79.5% were in elective and 20.5% in ambulatory settings. Currently, ventral hernias account for 64.9% of the series and umbilical for the remaining 35.1%. At least one-third of ventral hernias are operated on urgent/emergent settings, and 13.1% of the operations are performed laparoscopically. The average hospital stay for elective cases is 6.8 days, 5 for laparoscopic, and 7.1 days for open surgery .entified –28. The d trials –38. Our rials   [Confidence in effect estimates: low due to observational design of the studies]. Our meta-analysis showed an 82.9% reduction in the incidence of surgical site infections in favor of the laparoscopic approach . The sensitivity analyses performed after excluding the trials at high risk of bias and considering only those that excluded primary hernia confirmed the result  [Confidence in effect estimates: high].We showed a trend in favor of the laparoscopic approach for postoperative morbidity, with a 29% reduction in overall morbidity  [Confidence in effect estimates: low due to risk of bias and heterogeneity]  [Confidence in effect estimates: low due to risk of bias and imprecision]  [Confidence in effect estimates: moderate due to risk of bias]  [Confidence in effect estimates: low due to risk of bias and heterogeneity] . For mortality, overall morbidity, and length of hospitalization, the meta-analysis demonstrated only a trend in favor of the laparoscopic approach, with low evidence quality  confirming its advantage. For the other outcomes considered, it was impossible to demonstrate an advantage for one or the other technique. Therefore, the panel evaluated the balance between desirable and undesirable effects in favor of the laparoscopic approach to reduce postoperative infections.Equity, acceptability, feasibility. In the Italian health system context, the suggested approach has no equity and feasibility issues. However, regarding the acceptability by all stakeholders, there were concerns regarding a part of the surgical community that, based on their own experience, did not consider laparoscopic surgery acceptable or limited its implementation to more restricted indications.Note to the recommendation. The panel made a conditional recommendation in favor of the laparoscopic approach due to the very low certainty of the evidence and the size of the defect to be repaired. Therefore, the preoperative path must include the evaluation of the defect with imaging methods . The choice of intervention must also consider individual patient factors.PICO 1B. In elderly patients with a primary or incisional ventral hernia (P), is it preferable to choose laparoscopic (I) or open (C) surgery in terms of (O) mortality, morbidity, recurrence, quality of life, length of hospitalization, postoperative pain, and costs?RECOMMENDATION 1B. For the treatment of elderly patients (> 70 years) who require surgery for primary or incisional ventral hernia, the panel suggested that laparoscopic treatment be used as an alternative to open surgery.STRENGTH OF RECOMMENDATION. Conditional based on VERY LOW confidence in effect estimates, deriving from observational studies burdened by prognostic imbalance and imprecision.Evidence synthesis. There are no systematic reviews or randomized controlled trials assessing the role of laparoscopic ventral hernia repair in the elderly Two observational studies comparing the results of laparoscopic and open surgery in elderly patients  were analyzed. Both studies demonstrated an advantage for the laparoscopic approach in terms of reduction of the surgical site and systemic complications and length of hospital stay. Mortality was found to be lower in patients undergoing laparoscopic surgery in one of them , whereas the other showed no statistical difference between the two groups  [Confidence in effect estimates: very low due to risk of bias and imprecision] [ecision] , 45.vs. 11.7%; RR 0.77, 95%CI 0.59–1.01), the incidence of surgical site infections  and pulmonary complications  . In both studies, the length of hospitalization was shorter for patients in the laparoscopic group (3 ± 3.8 vs. 3.4 ± 6.2 days and 7.7 range 0–29 vs. 3.4 range 0–11 days) [Confidence in effect estimates: very low due to the risk of bias and imprecision]. The study by Spaniolas et al. did not investigate hernia recurrence, whereas, in the study by Neupane et al., fewer recurrences were found in the laparoscopic group  [Confidence in effect estimates: very low due to the risk of bias and imprecision].The second showed lower surgical site morbidity , laparoscopic surgery proved to be advantageous in terms of overall morbidity, both local  and systemic. The incidence of seromas was the only morbidity parameter disadvantageous for the laparoscopic technique in one observational study with a low sample size. The panel evaluated the balance between desirable and undesirable effects in favor of the laparoscopic approach.Equity, acceptability, and feasibility. The suggested approach has no equity, acceptability, or feasibility issues in the Italian health system context.Note to the recommendation. The panel issued a recommendation in favor of the laparoscopic approach conditioned not only by the very low certainty of the effects but also by the high variability in general conditions and operative risk in the elderly population. Therefore, the choice of intervention in each case must consider the patient's individual factors and local characteristics. The indication of the 70-year threshold for the recommendation was motivated by the demographic characteristics of the patients included in the published studies that supported the recommendation and cannot be regarded as a definite limit. The diameter of the defect already expressed for question 1A must also be considered in this subgroup of patients.PICO 1C. In people with obesity (body mass index ≥ 30 kg/m2) and primary or incisional ventral hernia (P), is it preferable to choose laparoscopic (I) or open (C) surgery in terms of (O) mortality, morbidity, recurrence, quality of life, length of hospitalization, postoperative pain, and costs?RECOMMENDATION 1C. The panel suggested that laparoscopic treatment be used as an alternative to open surgery for primary or incisional ventral hernias in patients with obesity.STRENGTH OF RECOMMENDATION. Conditional, based on LOW confidence in effect estimates, deriving from observational studies.Evidence synthesis. The literature search did not retrieve systematic reviews or randomized trials. However, several registry studies with large study groups compared the outcomes of open vs. laparoscopic repair for people with obesity and a primary or incisional ventral hernia. Between 2017 and 2019, Owei et al. .From the analysis by Owei et al. , 47, pat strokes , 47. A he et al.   [Confidence in effect estimates: low due to the observational design of the studies]. Fekkes et al. .angrene)  includedPatient values and preferences. No evidence was found in the literature. In the outcome prioritization phase, the patient representatives and patient advocate expressed their preferences in line with those of the rest of the panel. For this reason, the panel believed there was no variability or uncertainty about patients' values and preferences.Balance between desirable/undesirable effects. In an emergency setting, the overall lower morbidity and most of its components were desirable effects of laparoscopy. However, a higher incidence of accidental enterotomies was found after laparoscopic surgery, although no bowel resections were reported within 30 days following it. Therefore, the panel evaluated the balance between desirable and undesirable effects in favor of the laparoscopic approach.Equity, acceptability, and feasibility. The suggested approach has no equity, acceptability, or feasibility issues in the Italian health system context.Note to the recommendation. The panel formulated a recommendation in favor of the emergency laparoscopic approach conditioned not only by the very low certainty of the effects but also by the variability of the local and general conditions in this population group. Therefore, the choice of intervention in each case must consider the patient's individual factors, the general condition and the team's proficiency with emergency laparoscopy. The diameter of the defect already expressed for question 1A must also be considered in this subgroup of patients.PICO 1E. In treating patients with a border primary or incisional hernias (P), is it preferable to choose laparoscopic (I) or open (C) surgery in terms of (O) mortality, morbidity, recurrence, quality of life, length of hospitalization, postoperative pain, and costs?RECOMMENDATION 1E. The panel cannot issue a recommendation about the treatment of patients with a border primary or incisional hernia due to insufficient confidence in the effect estimates.STRENGTH OF RECOMMENDATION. No recommendation. The confidence in effect estimates was VERY LOW, as it derived from a single observational study with a small sample size (risk of imprecision) and a high risk of bias. It was impossible to balance desirable and undesirable effects, and the confidence in the estimates was too low to release a recommendation.Evidence synthesis. The literature that considered the laparoscopic treatment of border incisional hernias  included only case series that investigated the feasibility of laparoscopic surgery and compared its results with external controls of similar cases treated with an open technique. The only comparative, single-center, observational study included 55 patients with lumbar hernia operated on between 1995 and 2008 .and 2008 . This stPatient values and preferences. No evidence was found in the literature. In the outcome prioritization phase, the patient representatives and patient advocate expressed their preferences in line with those of the rest of the panel. For this reason, the panel believed there was no variability or uncertainty about patients' values and preferences.Balance between desirable/undesirable effects. It was impossible to balance desirable and undesirable effects since the evidence did not allow the panel to evaluate them sufficiently and were limited to a single type of border hernia. Therefore, the panel believed that the confidence in the estimates was too low, and a recommendation would have been too speculative.Equity, acceptability, and feasibility. The suggested approach has no equity, acceptability, or feasibility issues in the Italian health system context.PICO 1F. In patients with a parastomal hernia (P), is it preferable to choose laparoscopic (I) or open (C) surgery in terms of (O) mortality, morbidity, recurrence, quality of life, length of hospitalization, postoperative pain, and costs?RECOMMENDATION 1F. The panel suggested that laparoscopic surgery be used as an alternative to open treatment for patients with a parastomal hernia.STRENGTH OF RECOMMENDATION. Conditional, based on VERY LOW confidence in effect estimates, deriving from observational studies burdened with risk of bias, indirectness, and imprecision.Evidence synthesis. The literature search retrieved two systematic reviews of randomized and observational studies that compared the laparoscopic and open techniques in patients with parastomal hernias . In addition, Halabi et al. .Two additional observational studies directly compared the outcomes of the two techniques , 58. Hal.  examinedi et al.  demonstr. .Keller et al.  found a . [vs. 36% ± SE 15%) [Confidence in effect estimates: very low due to risk of bias and imprecision]. In both observational studies, the length of hospitalization was significantly shorter in the laparoscopic group [Confidence in effect estimates: very low due to risk of bias and imprecision].The 3-year recurrence rate, assessed with the Kaplan–Meier curves in the study by Keller et al. , was lowPatient values and preferences. No evidence was found in the literature. In the outcome prioritization phase, the patient representatives and patient advocate expressed their preferences in line with those of the rest of the panel. For this reason, the panel believes that there was no variability or uncertainty about patients' values and preferences.Balance between desirable/undesirable effects. Laparoscopic surgery in patients with parastomal hernia proved beneficial for all outcomes examined. The literature did not highlight any undesirable effects. The diameter of the defect already expressed for the PICO 1A must also be considered in this subgroup of patients.Equity, acceptability, feasibility. The suggested approach has no equity, acceptability, or feasibility issues in the Italian health system context.For Question 2, the panel considered the extreme variability of the single clinical conditions and of the different settings in which the intervention could be performed. Therefore, the panel did not intend to define each operative technical step but identified some aspects that appeared controversial or yet to be defined.The techniques whose relatively recent introduction has yet to allow the production of scientific literature sufficient for a comparison with the most common approaches were not considered .PICO 2A. In the laparoscopic treatment of patients with a primary or incisional ventral hernia (P), is it preferable to close the defect (IPOM plus) (I) or not (IPOM) (C) in terms of (O) mortality, morbidity, recurrence, quality of life, length of stay, postoperative pain, and costs?RECOMMENDATION 2A. The panel suggested that the hernia defect be sutured in the laparoscopic treatment of patients with a primary or incisional ventral hernia.STRENGTH OF RECOMMENDATION. Conditional, based on VERY LOW confidence in effect estimates. The analysis came from observational studies with a high risk of bias, heterogeneity, and imprecision of the estimates; and from randomized controlled trials with a low risk of bias but with severe imprecision and indirectness.Evidence synthesis. To date, four systematic reviews of randomized trials and observational studies have addressed the issue of hernia defect closure during laparoscopic primary or incisional hernia repair. Three of the four systematic reviews carried out a qualitative analysis only  and when analyzing seven observational studies    [Certainty of evidence: very low due to imprecision and heterogeneity]. Similarly, the pooled analysis of the observational studies showed no differences, although a trend in favor of IPOMplus was reported  [Certainty of evidence: very low due to high risk of bias and imprecision]  [Certainty of evidence: very low due to high risk of bias and imprecision]  [Certainty of evidence: low due to imprecision]. Also, the pooled analysis of the four observational studies did not show substantial differences, although a trend in favor of IPOMplus was reported  [Certainty of evidence: very low due to high risk of bias and imprecision]   and observational studies  showed no differences between the two techniques [Certainty of evidence: very low due to high risk of bias and imprecision]  and on the presence of chronic residual pain (9.3% vs. 11.4%) .The trend in overall morbidity was confirmed in the study by Henricksen et al.  (robotic. .Conversely, in the study by Altieri et al. , the univs. 9.2%; RR 0.62; 95%CI 0.23–1.68; I2 = 0%) [Certainty of evidence: low certainty due to high risk of bias]  , and matched analyses (MD 1 day) [Certainty of evidence: very low due to high risk of bias].Our meta-analysis included two studies investigating the difference in mean hospital stay between the laparoscopic and robotic approaches . A difference between the two techniques was not demonstrated  Fig.  . DeAsis et al. [. [Certainty of evidence: very low certainty of evidence due to risk of bias and indirectness].In the analysis of DeAsis et al. , the glo. .The three meta-analyses highlighted that the Sugarbaker technique was associated with a lower incidence of recurrence than the keyhole, suggesting that applying an intraperitoneal mesh with parietalization of the bowel reduced the risk of failure. In particular, Knaapen et al.  reporteds et al.  also desn et al.  who repoPatient values and preferences. No evidence was found in the literature. In the outcome prioritization phase, the patient representatives and patient advocate expressed their preferences in line with those of the rest of the panel. For this reason, the panel believed there was no variability or uncertainty about patients' values and preferences.Balance between desirable/undesirable effects. The Sugarbaker technique had a reduced recurrence rate compared to the keyhole technique. The literature did not compare mortality and morbidity outcomes between the two techniques. The panel evaluated the balance between effects desirable and undesirable in favor of the Sugarbaker technique.Equity, acceptability, and feasibility. The suggested approach has no equity, acceptability, or feasibility issues in the Italian health system context.PICO 2D. In the laparoscopic repair of patients with a primary or incisional hernia (P), is it preferable to fix the mesh with sutures (I) or mechanical tacks (C) in terms of (O) mortality, morbidity, recurrence, quality of life, length of stay, postoperative pain, and costs?RECOMMENDATION 2D. In the laparoscopic treatment of patients with a primary or incisional ventral hernia, the panel suggested that the mesh be fixed by mechanical tacks rather than transfixed sutures.STRENGTH OF RECOMMENDATION. Conditional, based on VERY LOW confidence in effect estimates, deriving from meta-analyses of randomized controlled trials, which, however, presented a high or uncertain risk of bias, imprecision, and indirectness. The risk of publication bias cannot be assessed.Evidence synthesis. Two meta-analyses of randomized trials .During the preparatory work for this guideline, Mathes et alchniques . There w. .The meta-analysis by Mathes et al. . also fo. [Certainty of evidence: very low due to high risk of bias and indirectness]. Similarly, Reynvoet et al. [Certainty of evidence: very low certainty of evidence due to risk of bias].The meta-analysis by Ahmed et al.  revealedt et al.  revealed. [Certainty of evidence: very low certainty of evidence due to risk of bias and indirectness]. The meta-analysis by Mathes et al. [Certainty of evidence: very low due to high risk of bias and imprecision].Regarding the duration of surgery, the meta-analysis by Ahmed et al.  reporteds et al.  also fou. [ I2 = 0%) and for the occurrence of seroma and hematoma  [Certainty of evidence: very low due to high risk of bias and indirectness].The meta-analysis by Ahmed et al.  revealedPatient values and preferences. No evidence was found in the literature. In the outcome prioritization phase, the patient representatives and patient advocate expressed their preferences in line with those of the rest of the panel. For this reason, the panel believed there was no variability or uncertainty about patients' values and preferences.Balance between desirable/undesirable effects. The use of mechanical tacks for the fixation of the mesh was beneficial for the reduction of the operative time. No other desirable effects were noted except for a tendency to have less seroma and hematoma formation. The panel evaluated the balance between desirable and undesirable effects in favor of fixing by mechanical means.Equity, acceptability, and feasibility. The suggested approach has no equity, acceptability, or feasibility issues in the Italian health system context.PICO 2E. For the laparoscopic treatment of patients with a ventral or incisional hernia (P), is it preferable to fix the mesh with absorbable (I) or non-absorbable (C) fixation devices in terms of (O) mortality, morbidity, recurrence, quality of life, length of stay, postoperative pain, and costs?RECOMMENDATION 2E. For the laparoscopic treatment of patients with a primary or incisional ventral hernia, the panel suggested that the mesh be fixed either with absorbable or permanent devices.STRENGTH OF RECOMMENDATION. Conditional, based on VERY LOW confidence in effect estimates, deriving from meta-analyses of randomized controlled trials, some of which presented a high or uncertain risk of bias and imprecision.Evidence synthesis. The use of absorbable tacks as a method of mesh fixation was introduced to reduce chronic postoperative pain. On the other hand, it was hypothesized that using absorbable tacks could favor recurrence. Two systematic reviews and meta-analyses considered the comparison between absorbable and permanent tacks. The first, published by Khan et al. in 2018 [. [. [. [Certainty of evidence: very low for high risk of bias and imprecision]. in 2018 , include in 2018 , 103 and in 2018 , 105 for in 2018 . For thi in 2018  and was  in 2018 . The stu18 [. [.  had a fo[. [. [.  demonstrPostoperative pain was analyzed separately for the two studies included in the meta-analysis .. [Certainty of evidence: very low for high risk of bias and imprecision]. Harslof et al. [vs. 43.5 ± 28.5 on a scale from 0 to 100) [Certainty of evidence: low certainty of evidence due to indirectness and high risk of bias].Colak et al.  evaluatef et al. , pain asPatient values and preferences. No evidence was found in the literature. In the outcome prioritization phase, the patient representatives and patient advocate expressed their preferences in line with those of the rest of the panel. For this reason, the panel believed there was no variability or uncertainty about patients' values and preferences.Balance between desirable/undesirable effects. From the direct comparison between the use of these two modes of fixation, no differences emerged for any of the outcomes examined, particularly the incidence of postoperative pain (acute or chronic) and recurrences.Equity, acceptability, feasibility. The suggested approach has no equity, acceptability, or feasibility issues in the Italian health system context.PICO 2F. For the laparoscopic treatment of patients with a ventral or incisional hernia (P) with the IPOM technique, what is the optimal overlap of the mesh on the abdominal wall surface (I) (C) in terms of (O) mortality, morbidity, recurrence, quality of life, length of stay, postoperative pain, and costs?RECOMMENDATION 2Fa. In treating patients with a primary or incisional ventral hernia with a defect diameter of 4 cm or larger, the panel suggested a minimum overlap of the mesh beyond the margins of the defect of 5 cm on each side.STRENGTH OF RECOMMENDATION. Conditional, based on VERY LOW confidence in effect estimates, deriving from observational studies with a high risk of bias.RECOMMENDATION 2Fb. In the treatment of patients with primary or incisional ventral hernia, with a defect less than 4 cm, the panel suggested a minimum overlap of the mesh beyond the margins of the defect of 3–5 cm on each side.STRENGTH OF RECOMMENDATION. Conditional based on VERY LOW confidence in effect estimates, deriving from observational studies with a high risk of bias.Evidence synthesis. A systematic review of the literature analyzed the amount of overlap between the mesh and the abdominal wall necessary to decrease the recurrence rate in laparoscopic IPOM [. [. [Certainty of evidence: very low due to indirectness and high risk of bias].pic IPOM . After t IPOM [.  publisheOM [. [.  included. [Certainty of evidence: very low certainty of evidence due to high risk of bias and indirectness].While keeping in mind its relevant limitations (high risk of bias and indirectness), the study by Hauters et al.  confirme. , 110 .ectness) . The outvs. 64 ± 31 min) and suturing of the defect (mean: 10 ± 9 min vs. 9 ± 7 min). The surgeon's assessment at the defect closure showed a difference in favor of the deep neuromuscular block (mean score 4.8 ± 0.4 vs. 4.0 ± 1.4).No difference was found between a deep and no neuromuscular block , and in the difference between the first and second phase . No difference was found in total operative time , the panel believed that the confidence in the estimates was too low, and a recommendation could have been speculative. Therefore, in clinical practice, it will be possible to refer to neuromuscular block guidelines not specific to the treatment of incisional and primary ventral hernias.Equity, acceptability, feasibility. The suggested approach has no equity, acceptability, or feasibility issues in the Italian health system context.Note to the recommendation. In the absence of a recommendation, it is desirable to monitor the neuromuscular block to administer a continuous infusion or multiple doses of muscle relaxant. Furthermore, monitoring is mandatory when surgery is conducted with a deep block  and in patients with severe liver or kidney insufficiency or neuromuscular pathology .Although with a small sample size  [Confidence in effect estimates: high] compared with administration of saline. Conversely, no difference was found in the intensity of pain measured at 24 h  [Confidence in effect estimates: moderate due to imprecision]. The randomized trial by Sinha et al. . The fourth study . There was also a difference in favor of the TAP block regarding the percentage of patients able to walk at 12 h (0% vs. 28%) and 24 h (28 vs. 65%) after the operation [Confidence in effect estimates: moderate due to imprecision]. The economic analysis showed that the model in which the TAP block was used turned out to be the "dominant" strategy because it simultaneously obtained better results (improvement of QALYs of 0.1) and lower costs (savings of $ 457) [Fields et al.  compareda et al.  includedth study , whose gf $ 457) .Patient values and preferences. No evidence was found in the literature. In the outcome prioritization phase, the patient representatives and patient advocate expressed their preferences in line with those of the rest of the panel. For this reason, the panel believed there was no variability or uncertainty about patients' values and preferences.Balance between desirable/undesirable effects. Along with the intervention's desirable effects, the studies examined did not describe procedural complications of loco-regional analgesia. Therefore, the balance was in favor of the desirable effects. However, it must be emphasized that all the studies assessed only one modality of loco-regional anesthesia (TAP block), which is not the only one available to manage pain in abdominal wall surgery.Equity, acceptability, feasibility. The suggested approach has no equity or acceptability issues in the Italian health system context. However, regarding feasibility, the panel believed there might be some variability among the stakeholders. In particular, the choice of one loco-regional technique rather than another may depend on the specific technical skills of the anesthesiologist and on the availability, in the operating room, of an ultrasonographer to allow the procedure.Note to the recommendation. The panel issued a recommendation conditioned, besides moderate certainty of the effects, on the characteristics of the patient, availability of the equipment to perform the procedure, and the specialist's skills . [ curve). –120.. A panel should issue a strong recommendation when it is likely that almost all informed people would make the recommended choice, with low variability. In contrast, a conditional recommendation implies a more significant impact of individual factors, preferences, and values on the decision.This is the first general surgery guideline published on the Italian national guideline database  held by the ISS . In 2017In our guidelines, all the recommendations are conditional. In fact, the panel agreed that the extreme variability of the possible clinical scenarios , and the generally low confidence in the effect estimates obtained by the literature, allowed broad discretion in patient and provider choices. It acknowledged that different choices are appropriate for different patients and situations, pointing out to a tailored approach in each case. Most people will still abide by the suggested course of action; however, the decision could be different but still sound in many cases.Many of the controversies about the role of minimally invasive techniques in the treatment of ventral hernias rely upon assumptions  with solid physio-pathological basis, but very difficult to prove in a clinical setting. One of the main challenges for the panel was to remain committed to the literature clinical evidence (or absence of evidence) about them without disregarding the legitimate worries of many surgeons. Once again, the GRADE methodology was appropriate for this purpose: its Evidence-to-Decision process insists that the recommendations, based on the literature evidence, take into account values, preferences, and acceptability by the concerned parties. The involvement of patient representatives and a patient advocate in the multidisciplinary and multi-professional panel proved functional in this process.The recommendations of any guideline do not directly relate to the statistical significance of the literature findings. The panel is committed to providing indications to be used in clinical practice even when the published series are not large enough to reach statistical significance. On the other side, the panel may decide to be cautious in the presence of statistically significant data, considering other aspects within the Evidence-to-Decision process. For recommendation 2A (IPOMplus vs. IPOM), the panel concluded that the balance between desirable and undesirable effects justified the decision. However, the meta-analysis did not show statistically significant results . On the contrary, the panel did not issue a recommendation in favor of the robotic repair (recommendation 2B—Robotic versus laparoscopic technique) despite the literature showing a statistically significant advantage for the robotic arm in more than one outcome because of equity and feasibility criteria (limited availability of the robotic technology). In the paper, we made every effort to clarify the reasons behind any decision.In two instances, the panel could not provide a recommendation for the scarcity of the literature on the subject (recommendations 1E and 3).This guideline's strengths include relying on an extensive systematic review of the literature and applying a rigorous GRADE method. It also has several limitations. The literature on the topic is continuously and rapidly evolving; our results are based on findings that need constant re-appraisal. The systematic review showed that high quality literature on the examined topics is scarce and the recommendations are mostly based on low certainty of evidence. This aspect must be considered in the decision-making process and has an impact on the practical application of the “conditional” recommendations. The guideline is focused only on minimally invasive techniques and did not consider broader issues . In addition, several recently introduced minimally invasive techniques could not be included because, at present, they are only anecdotally reported in the literature.Despite the described limitations and the limited evidence, the laparoscopic repair appears an alternative to open surgery within a tailored approach to each patient.Supplementary file1 (DOC 45 KB)Below is the link to the electronic supplementary material.


Drug‐associated delirium is a common but potentially preventable neuropsychiatric syndrome associated with detrimental outcomes. Empirical evidence for delirium‐associated medication is uncertain due to a lack of high‐quality studies. We aimed to further investigate the body of evidence for drugs suspected to trigger delirium.https://doi.org.10.17605/OSF.IO/4PUHY).A systematic update review and meta‐analyses of prospective studies presenting drug associations with incident delirium in adult study populations was conducted. Two authors independently searched MEDLINE, PsycINFO, Embase, and Google Scholar dated from October 1, 2009 to June 23, 2020, after screening a previous review published in 2011. The most reliable results on drug‐delirium associations were pooled in meta‐analyses using the random‐effects model. Quality of evidence was assessed using the GRADE‐approach. This study is preregistered with OSF , Olanzapine , Ketamine  or corticosteroids . Low‐level evidence suggests a three‐fold increased risk for anticholinergics . Opioids, benzodiazepines, HWe investigated the retrievable body of evidence for delirium‐associated medication. The results of this systematic review were then interpreted in conjunction with other evidence‐based works and guidelines providing conclusions for clinical decision‐making. Haloperidol, olanzapine, corticosteroids, and ketamine do not exhibit increased risk of delirium .There is insufficient evidence for the use of antipsychotics, corticosteroids, or ketamine as pharmacological prevention or treatment.1‐antihistamines , and polypharmacy might trigger delirium, but underlying evidence remains low.Anticholinergics, opioids , benzodiazepines, HMeta‐analysis results deriving from observational studies do not reach reliable evidence levels. Single study results should be interpreted with caution.Methodological differences in the studies included  limited the certainty of evidence.1Delirium is a serious and common neuropsychiatric disorder that is predominantly reported in elderly patients.1‐antihistamines) is inconsistent and conflicting.Narrative reviews suggest that benzodiazepines, (tricyclic) antidepressants, opioids, and anticholinergics are suspected to have deliriogenic potential.The aim of this systematic review is to update and comprehensively assess the certainty of evidence for drug‐delirium associations, and to conduct meta‐analyses for delirium with specific medication (classes). A systematic literature search is conducted to update a previous review from 2011.2This work is based upon the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions2.1The systematic search required RCTs and prospective observational studies (OS) (prospective cohort [PC] and nested case–control [CC]) with predefined eligibility criteria assessing medication associations with incident delirium in adult study populations. Retrospective study designs, case‐reports, and studies that failed to present exploratory statistics were considered to provide a very low level of evidence, and therefore excluded.2.2A search strategy using Medical Subject Headings (MeSH) and free text search terms was developed in order to systematically screen the MEDLINE (via PubMed), EMBASE, and PsycInfo databases. A complementary search on Google Scholar and screening of reference lists was conducted to extend the scope. The search strategy combined three search strings, reflecting (i) delirium as the dependent variable, (ii) medication exposure as the independent variable, and (iii) focus on elderly people (> 65 years old), by using the Boolean operator “AND.” Eligibility criteria required adult study populations (exclusion of <18 years old patients) with a focus on older patients. English‐, German‐ and French‐language journal articles were included if published between October 1, 2009–to update the previous systematic reviewThe literature search was initially conducted by screening the review by Clegg and Young2.3Data collection of included articles was undertaken by RM while DBJ checked for the accuracy of extracted data. We focused especially on delirium assessment, medication exposure, and statistical approach to ascertain reliable data and assess the possible risk of bias. Adjusted and unadjusted effect measures, as well as raw data, were collected.2.4age was defined as a primary confounder, and dementia and comorbidity/illness severity as joint secondary confounders. A score of ≥7 was regarded as indicative of sufficient bias control. There was a risk of bias, if more than one point in a single category was subtracted.RCTs were appraised using the Cochrane risk of bias tool (RoB).2.5Meta‐analyses were conducted if there were at least two studies investigating the same medication. These were pooled using the random‐effects model.p < 0.05) and the I2 statistic.Pooled odds ratios (ORs) with 95% confidence intervals (CI) were calculated for dichotomous outcomes (Cochran–Mantel–Haenszel test or generic inverse‐variance method). Statistical heterogeneity was calculated using the χ2 test . In full text screening, the eligibility criteria ,The RCTs included were based upon intention‐to‐treat (ITT) analyses with the following exception: two RCTs conducted per‐protocol (PP) analyses,3.3The RoB among the RCTs included was estimated to be low, and is presented in Figure 3.4Single medication associations (uni‐ and multivariable effect estimates and raw data) are presented in a comprehensive summary table in the Appendix 3.5We established a hierarchy of evidence, including meta‐analyses and single effect estimates on medication associations with delirium. Comprehensive meta‐analyses and sensitivity analyses are presented in the Appendix 3.5.12 of 44% (p = 0.13).There is high quality evidence from five pooled RCTsmoderate) due to insufficient optimal information size (OIS).The moderate quality evidence of one RCTmoderate because of insufficient OIS. Heterogeneity calculations showed a borderline result  but sensitivity analyses did not change results significantly . Borderline heterogeneity might be explained by different agents and dosages  was accepted because point estimates did not differ in direction. The GRADE‐rating had to be downgraded by one level to moderate due to serious imprecision.There is moderate quality of evidence from two RCTslow) due to very serious imprecision. Atropine (0.01 mg/kg i.m.) shows an insignificant result . PHC shows a strong association with delirium, but confidence intervals are very broad .There is low quality evidence from one RCT3.5.2very low quality of evidence: ACE‐inhibitors, antibiotics, oral anticoagulants, antidepressants, antiparkinsonian drugs, benzodiazepines, beta‐blockers, calcium‐channel blockers, digoxin, diuretics, H1‐ and H2‐antihistamines, heparin, Insulin, NSAIDs, paracetamol, opioids, propofol and polypharmacy (as a delirium‐associated drug entity). The results for selected medication that is commonly regarded as being delirium‐associatedAll other medication classes investigated in OS reached only very low due to serious imprecision.Antidepressants as a general drug class were investigated in one study (89 patients with negative dementia status undergoing spine surgery).very low due to serious inconsistency (I2 = 76%) and serious imprecision. AR estimates could not be calculated. Sensitivity analysis .Benzodiazepines did not significantly increase or decrease delirium rates in our meta‐analysis of four PCsvery low level because upgrading (dose–response gradient) was not possible due to prior downgrading (serious inconsistency and imprecision).A dose–response gradient is shown in four OSvery low due to serious imprecision.Among specific agents, lorazepam exhibited an increased risk for delirium and a dose–response gradient in 198 ICU‐patients (aOR of 1.24 [95% CI: 1.08–1.43]).2 of 85% which might be explained by heterogeneous clinical settings : aOR of 0.75, 95% CI: 0.14–4.16. AR resulted in 19 fewer cases per 1000 (95% CI: 70 fewer to 189 more). Evidence quality needed to be downgraded to very low due to serious inconsistency (I2 = 83%) and imprecision. Heterogeneity might be explained by the fact that H1‐antihistamines as a medication classMeta‐analysis of two CCs2 = 0%, p = 0.38).1‐antihistamines as a medication class (very low) because the same studies were included.Heterogeneity was low when results for diphenhydramine were pooled (I2 of 47% (p = 0.15). Confidence in evidence needed to be downgraded to very low due to serious imprecision. AR was not calculable due to a lack of raw data in one PC.Meta‐analysis of three PCsOpioids exhibited a dose–response gradient: a postoperative dose of >8 mg hydromorphone‐equivalent in comparison to <8 mg results in an adjusted OR of 2.60 (95% CI: 1.31–5.17)very low : the meta‐analysis .The specific agents morphine, fentanyl and meperidine showed higher possible risk than other opioid agents, although evidence levels are 2 = 0%). AR estimates could not be calculated. The GRADE‐rating for fentanyl and morphine was downgraded to very low due to serious imprecision.The same two studiesOne PCvery low due to insufficient OIS.In comparison, oxycodone and codeine did not show an association with delirium .2 = 67%), possibly due to heterogeneous definitions of polypharmacy  remains incomplete, and mostly of low quality, but some findings deserve attention, especially in the context of other evidence‐based works.The NICE‐guidelinesCholinergic deficiency and anticholinergic toxicity are considered the main pathophysiological correlates in delirium genesis.Only one PC investigated antidepressants as a group and presented an adjusted (insignificant) association with very low‐evidence certainity.not a significant risk factor.”Benzodiazepines are described as major pharmacological risk factors for inducing delirium due to paradoxical effects.1‐antihistamines  are usually considered deliriogenic.1‐antihistamines of “low to moderate quality.”1‐antihistamines as medication class). The NICE guidelines present “low quality evidence” for an increased risk from diphenhydramine and “very low evidence” not significantly altering delirium risk.1‐antihistamines in general and diphenhydramine in special), but relatively higher evidence suggests increased delirium risk.The anticholinergic properties of first generation Hnot to alter risk of delirium occurrence” in ICU settings.Opioid exposure is considered a well‐established independent risk factor for delirium, although empirical evidence (from OS) is inconsistent.Polypharmacy–especially the use of multiple psychoactive drugs ‐ was described as a major delirium risk factor  by Inouye et al.single triggers for delirium : ACE‐inhibitors; antibiotics, oral anticoagulants, antiparkinsonian drugs, beta‐blockers, calcium‐channel blockers, digoxin, diuretics , H2‐antihistamines, heparin, Insulin, NSAIDs, paracetamol and propofol. Notably, Clegg and Young describe dihydropyridines (nifedipine) as showing a “small to moderate” risk ,The GRADE quality of evidence ratings for all other investigated medication classes and agents were of a very low level. The following are therefore not regarded as playing a major role as 4.1This systematic review on delirium‐associated medication is the first work pooling individual studies and providing meta‐analyses according to medication classes and individual agents. Another strength lies in comprehensively grading the quality of evidence in a structured, transparent and standardized manner. We also compared our results to previous reviews and delirium guidelines.Although focusing on multivariable adjusted effect measures, there are limitations to evidence levels due to heterogeneous clinical settings, broad ranges of sample sizes and delirium rates, and lack of à priori power calculations, frequently resulting in insufficient OIS and imprecision estimation. The accounted covariates in multivariable regression analyses were inconsistent across studies and might affect comparability. The number of pooled studies included in meta‐analyses was too low to conduct funnel‐plots and estimate publication biases. Negative results were not reported systematically across the studies included.4.2This critical appraisal of current evidence on delirium‐associated medication has both clinical and research implications.Haloperidol (up to 6 mg/d) and olanzapine (10 mg) do not increase the risk of delirium . Nevertheless, there is insufficient evidence for the use of antipsychotics as pharmacologic prevention or treatment.Corticosteroids and ketamine (in subanesthetic dosage: up to 1 mg/kg) did not exhibit significantly increased delirium risk .Anticholinergics–whenever possible–should be de‐prescribed or avoided. There is low quality evidence for a three‐fold increased delirium risk.Opioids show a dose‐dependent increased delirium risk , and insufficiently treated acute pain seems to be a strong precipitating factor. We suggest avoiding meperidine. Oxycodone seems to have a favorable profile. Opioids do not seem to be a risk factor in the ICU‐setting.Exposure to benzodiazepines can dose‐dependently increase the risk of delirium, but evidence is of very low quality in non‐ICU‐settings. In ICU‐settings, there is strong evidence for increased risk . Lorazepam exhibited a higher risk compared to other agents , and showed a strong dose‐effect relationship, but quality of evidence is too low to draw clinical conclusions. We therefore suggest using non‐benzodiazepine sedatives 1‐antihistamines–especially diphenhydramine–seem to increase delirium risk, but evidence remains inconsistent and of very low quality.HPolypharmacy might strongly contribute to delirium but there is a lack of empirical evidence.continuous delirium assessment and adequate follow‐up time, sufficient statistical power calculations, predefined confounders , standardized dosages, and the sub‐categorization of delirium in the context of suspected drug‐induced pathophysiology .We recommend prospective study designs for future research, with Although the overall evidence is of low quality we suggest the following:51‐antihistamines, antidepressants) did not reach a reliable quality for drawing conclusions. Nevertheless, a synopsis including other evidence‐based works and guidelines shows that benzodiazepines are a strong dose‐dependent risk factor in the ICU. In non‐ICU‐settings, however, the evidence remains unclear. Opioids  can trigger delirium in a dose‐dependent manner, but insufficient analgesia in acute pain is a precipitating risk factor per se. In ICU‐settings, opioids do not seem to significantly contribute to delirium. H1‐antihistamines (diphenhydramine) seem to increase delirium risk although the evidence is very low. Polypharmacy might be a major condition, but empirical evidence is unclear. Medication reviews, avoiding and de‐prescribing possibly deliriogenic medication in people at risk is crucial in clinical practice. This review may help clinicians to prevent drug‐induced delirium.Meta‐analyses and GRADE certainty of evidence confirm the paucity of high‐quality studies. In summary, antipsychotics, corticosteroids and ketamine (in subanesthetic dosage) did not demonstrate increased delirium risk with moderate to high certainty evidence. Low quality evidence suggests a three‐fold increased risk with primary anticholinergics. Medication classes investigated in OS (e.g., opioids, benzodiazepines, HMichael Reisinger, Daniela Schoberer, and Eva Z. Reininghaus formulated the study design. Michael Reisinger pre‐registered the study protocol. Michael Reisinger and Johanna De Biasi conducted literature searches independently. Daniela Schoberer was consulted in case of disagreement on eligibility. Michael Reisinger extracted data, Johanna De Biasi checked for accuracy. Michael Reisinger and Daniela Schoberer contributed to data analysis, meta‐analyses and interpretation. Michael Reisinger wrote the first draft of the manuscript and prepared figures and tables. Daniela Schoberer, Eva Z. Reininghaus and Frederike T. Fellendorf edited the manuscript.This study did not receive financial or nonfinancial support from any funding agency in the public, commercial, or nonprofit sectors.We declare no competing interests.https://publons.com/publon/10.1111/acps.13505.The peer review history for this article is available at Appendix S1 Supporting Information.Click here for additional data file.Appendix S2 Supporting Information.Click here for additional data file.Appendix S3 Supporting Information.Click here for additional data file.Appendix S4 Supporting Information.Click here for additional data file.