Antiseizure medications are the cornerstone pharmacotherapy for epilepsy. They are not devoid of side effects. In search for better-tolerated antiseizure agents, cannabinoid compounds and other N-acylethanolamines not directly binding cannabinoid receptors have drawn significant attention. Among these, palmitoylethanolamide (PEA) has shown neuroprotective, anti-inflammatory, and analgesic properties. All studies examining PEA’s role in epilepsy and acute seizures were systematically reviewed. Preclinical studies indicated a systematically reduced PEA tone accompanied by alterations of endocannabinoid levels. PEA supplementation reduced seizure frequency and severity in animal models of epilepsy and acute seizures, in some cases, similarly to available antiseizure medications but with a better safety profile. The peripheral-brain immune system seemed to be more effectively modulated by subchronic pretreatment with PEA, with positive consequences in terms of better responding to subsequent epileptogenic insults. PEA treatment restored the endocannabinoid level changes that occur in a seizure episode, with potential preventive implications in terms of neural damage. Neurobiological mechanisms for PEA antiseizure effect seemed to include the activation of the endocannabinoid system and the modulation of neuroinflammation and excitotoxicity. Although no human study was identified, there is ground for testing the antiseizure potential of PEA and its safety profile in human studies of epilepsy. According to the International League Against Epilepsy (ILAE), seizures can be described as the “transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.” Epilepsy subsists when the patient’s brain shows an augmented tendency to the recurrence of seizures . It is oThe search is on for novel antiseizure agents with fewer adverse effects. Cannabinoid compounds as ASMs via the cannabinoid receptor type 1 (CB1) have already shown promising results ,7. The ePEA effects on glutamate signaling, ion channels and systemic inflammation, and/or peripheral immunity activation could represent promising mechanisms to reduce the likelihood for seizures’ occurrence and progression. This review aimed to bring together and discuss all available data generated by studies investigating the role of PEA in epilepsy by conducting a systematic literature search for all such data. All interventional and observational studies have been reviewed.In order to summarize previous research on the subject, inclusion criteria for studies were as follows: (1) human or animal studies; (2) studies assessing the effects of PEA administration in epilepsy and acute seizures; and (3) studies investigating PEA signaling-related molecular markers in epilepsy and acute seizures, including (a) blood serum levels, (b) brain tissue levels, (c) peripheral tissue levels, (d) enzyme activity, and (e) receptors. Exclusion criteria were (1) studies where PEA was not the intervention considered , (2) studies where PEA’s neuroprotective role was not evaluated with reference to epilepsy or acute seizures, and (3) studies in which PEA effects were not directly reported on.A literature search was conducted using electronic databases  for any published original study written in English, using a combination of search terms describing and/or concerning epilepsy  and PEA hexadecanamide)’, ‘(N-(2-hydroxyethyl)palmitate)’, ‘N-palmitoylethanolamine’), on 4 December 2021. No predefined duration of PEA exposure, default gender, stage of life/epilepsy, or therapeutic strategies for study search was adopted in order to be the most inclusive as possible. Reference lists of eligible studies were screened to identify additional eligible research. Publication data screening and extraction were performed following a 2-step selection process  conducted by 2 reviewers independently of each other (R.B. and M.C.).The methodological heterogeneity of the studies  includedIn summary, 52 records were retrieved. After excluding articles owing to article type (systematic and non-systematic reviews), by using a three-step screening approach, titles, abstracts, or full texts of all records were screened against the inclusion and exclusion criteria . A final50) comparable to that of the ASM phenytoin (PHT) and a higher protective index [Most studies identified in this review addressed the effects of PEA exposure in animal models of epilepsy and acute seizures using similar but not overlapping methodologies in terms of animal type  and their neurobiological underpinnings in seizures and epilepsy. All records identified consisted of animal studies, while no research conducted in humans was available. Previous reviews had mainly focused on the role of major phytocannabinoids, indicating that they may represent a complementary tool for the symptomatic management of refractory epilepsy . SpecifiPEA supplementation in animal models of epilepsy and acute seizures was found to reduce seizure frequency and severity ,18,19,20Another line of research identified lower brain levels of PEA and related alterations in the eCB levels in animal models of epilepsy and acute seizures ,21, depeThe findings of this systematic review must be seen considering some limitations. Research in the field is still in its infancy, and animal experiments often do not translate into replications in human trials . In the This review found a paucity of observational and experimental studies of PEA signaling in epilepsy. The eight investigations presented seemed to converge on the presence of PEA aberrancies in the brain and periphery, their role for the manifestations of different forms of seizures and epilepsy, and beneficial effects of PEA supplementation both in terms of antiseizure and antiepileptic effect. Subchronic pretreatment with PEA before the epileptogenic stimulus appeared to be a strategy to prevent its behavioral and neurobiological consequences, warranting investigation of PEA disease-modifying effect in epilepsy. It is time to test the antiseizure potential of PEA and its safety profile in human studies of epilepsy.


Introduction: The United States Centers for Disease Control and Prevention (CDC), through U.S. President's Emergency Plan for AIDS Relief (PEPFAR), supports a third of all people receiving HIV care globally. CDC works with local partners to improve methods to find, treat, and prevent HIV and tuberculosis. However, a shortage of trained medical professionals has impeded efforts to control the HIV epidemic in Sub-Saharan Africa and Asia. The Project Extension for Community Healthcare Outcomes (ECHOTM) model expands capacity to manage complex diseases, share knowledge, disseminate best practices, and build communities of practice. This manuscript describes a practical protocol for an evaluation framework and toolkit to assess ECHO implementation.Methods and Analysis: This mixed methods, developmental evaluation design uses an appreciative inquiry approach, and includes a survey, focus group discussion, semi-structured key informant interviews, and readiness assessments. In addition, ECHO session content will be objectively reviewed for accuracy, content validity, delivery, appropriateness, and consistency with current guidelines. Finally, we offer a mechanism to triangulate data sources to assess acceptability and feasibility of the evaluation framework and compendium of monitoring and evaluation tools.Expected impact of the study on public health: This protocol offers a unique approach to engage diverse group of stakeholders using an appreciative inquiry process to co-create a comprehensive evaluation framework and a compendium of assessment tools. This evaluation framework utilizes mixed methods , was pilot tested in Tanzania, and has the potential for contextualized use in other countries who plan to evaluate their Project ECHO implementation. TM) Project aims to address these gaps through a collaborative hub and spoke model to connect a multi-disciplinary team of health professionals and enable virtual communities of practice (The United States Centers for Disease Control and Prevention (CDC) partners with more than 50 countries to improve methods to find, treat, and prevent HIV and tuberculosis (TB) , 2. Howepractice .ECHO creates a global network of health workers at local, regional, and international medical centers to help disseminate best practices and improve health outcomes . The ECHThe importance of maintaining high-quality implementation was studied for education, technology, manufacturing, and service industry , 4, 11. The proposed evaluation framework and compendium of tools will be pilot tested in Tanzania. Tanzania is one of 13 PEPFAR high-priority countries with 1.6 million PLHIV and an estimated 5% prevalence of HIV in the adult general population . Among tTanzania has implemented an HIV ECHO clinic in an ‘all teach, all learn' interactive format. The University of Maryland, Baltimore (UMB) has facilitated more than 76 weekly ECHO sessions between November 2018 through July 2020 across the country.This is a multi-phased, mixed-methods , 18, devBox 11.1.) How do HIV ECHO participants and implementers  perceive high-quality implementation?1.2.) How do HIV ECHO participants and implementers perceive their level of engagement in the HIV ECHO program?1.3.) How do HIV ECHO participants and implementers perceive their level of satisfaction with HIV ECHO program?1.4.) How do HIV ECHO participants and implementers perceive their learning?1.5.) How do HIV ECHO participants and implementers perceive their self-confidence in managing complex HIV patients?1.6.) How do HIV ECHO participants and implementers perceive their level of competence?1.7.) What do HIV ECHO participants and implementers perceive are potential barriers to HIV ECHO participation?1.8.) To what degree has HIV ECHO sessions influenced behavior of the participants?1.9.) Was the content of previous HIV ECHO didactic presentations, accurate, clear, and valid?1.10.) Was the content of previous HIV ECHO case-based presentations, accurate, clear, and valid?1.11.) Were case-based recommendations made by the expert panel applicable to the case presented, appropriate, useful, and, relevant?1.) What are the current stakeholder perceptions of high-quality HIV ECHO implementation?2.) To what extent does the draft evaluation framework and compendium of tools describe, measure, and validate the described elements (constructs) to effectively monitor a high-quality HIV ECHO implementation routinely?3.) What are the recommendations for improving the proposed evaluation framework and the compendium of monitoring and evaluation tools?We will engage all stakeholders using a participatory approach using a modified appreciative inquiry methodology  that wilwww.qualtrics.com) platform. Email addresses will be obtained from participant registration forms and the iECHO database. All ECHO participants will be sent an email containing a link the web-based consent form and survey questionnaire. The survey will take approximately 30 min to complete.We will use an anonymous, on-line, standardized survey to better understand the perceptions and experiences of participants of the HIV ECHO program . QuestioWe plan to conduct an exploratory cross-case analysis between the themes that arise among the three different groups . Three focus group discussions (FGDs) will be conducted with each group comprising of ECHO participants who would have attended ECHO in at least the past year. Each FGD will consist of five to six participants. Each of the three groups will be comprised of participants who have similar backgrounds, job roles and experience to ensure that all participants are comfortable with participating and openly contribute to facilitated discussions . Guided,Participant names will not be recorded or retained to ensure confidentiality. The focus group facilitator will explain the evaluation objectives, procedures, risks, benefits, and the informed consent process. Individuals will be provided an opportunity to ask questions before consenting . The focA peer-reviewed concept shall be utilized to validate the educational content, improve standards of quality, and provide credibility in a transparent review process. Select HIV experts from low- and high-HIV prevalence countries will be invited to participate to maintain an impartial, fair, and objective assessment. Eligibility criteria for objective reviewers will include being familiar with the model, philosophy, and functioning of Project ECHO; Being a physician, nurse, or health care provider who knows the clinical guidelines of the relevant country and programmatic operations for HIV, TB, PEPFAR, or other relevant programming; Being fluent in the local language  in which ECHO sessions are conducted; Not being an employee or volunteer for the organization that implements the Project ECHO clinic(s) being evaluated; Not being affiliated with the organization that funds or competes with funding for the Project ECHO clinic(s) being evaluated; Not being a participant or subject matter expert (SME) of the Project ECHO clinic(s) being evaluated. The objective reviewer can, however, be a SME for a Project ECHO clinic not being evaluated.Each reviewer will assess three sessions each, and each session will have three reviewers. See Session recordings shall be randomly selected from previously conducted HIV ECHO session recordings for an objective review of the facilitation process using a standardized scorecard . An indeA random selection of previous ECHO session recordings shall undergo an objective review for didactic presentation accuracy, content validity, and delivery . An indeAn independent panel of reviewers will use a standard scorecard to assess case presentations from a random selection of ECHO sessions. Each selected session will be reviewed for the following: (1) extent to which the case-based presentation aligned with stated learning objectives; (2) presentation quality ; (3) appropriateness of the recommendations; (4) whether the recommendations were specific, measurable, achievable, reproducible, and time bound; (5) whether the recommendations were consistent with current national and international guidelines for standard practices of care . At the Secondary de-identified data  will be analyzed to identify trends and monitor performance over time . ApproprA trained evaluation team member from the project team will administer readiness assessment questionnaires of newly enrolled ECHO site coordinators through face-to-face interviews with ECHO program coordinators preparing to launch new ECHO hubs .Semi-structured interviews will be conducted with key-informants to obtain personal insights based on their experience and perspective . Key infBox 2Who needs what information?), (ii) feasibility , (iii) propriety , (iv) accuracy (What design will lead to accurate information being collected?).These interviews will assess the (i) utility  shall be invited to discuss the results from all the activities above. This interactive workshop-style meeting shall be organized at the completion of data analysis and triangulation to present evaluation findings. Facilitated discussion of feedback on usability and acceptability of the tools and framework adoption routinely shall be sought by key stakeholders, some of whom would be the same participants who attended the environmental scan workshop. Tools, POC, and frequency of data collection shall be recommended as the final deliverable.Online survey: All participants who have attended at least one Tanzania HIV ECHO session facilitated by UMB are eligible to participate.Focus group discussion: All participants who have attended at least one HIV ECHO session and completed the survey are eligible to participate. Twenty healthcare providers (HCP) and SMEs and/or implementers shall be randomly selected from the iECHO database and invited to participate in the FGD. Five to six participants shall be randomly selected from those who agree to participate. There will be three FGDs , each comprising of 5–6 people in each group. Implementers could be ECHO coordinators who are primarily responsible for coordinating and delivering the ECHO sessions routinely. Location of the interviews shall be pre-determined, and invitations shall be sent 1 month in advance.Readiness assessment: Two coordinators of new HIV ECHO hubs shall complete the readiness assessment checklist. These coordinators will be selected from those who have not started implementing their HIV ECHO hubs.Key-informant interviews: six purposively chosen opinion leaders or influencers  who can advocate for ECHO from public, private, academic, and Ministry of health (MOH) shall be invited for interview.Persons who have never attended a Tanzania HIV ECHO session shall be excluded from participation in any data collection efforts.Once the evaluation has been approved, the evaluation co-investigators will announce the opportunity to participate during an upcoming HIV ECHO session. Participant emails will be furnished by UMB, who routinely collect contact information at the start of ECHO sessions. Stakeholders who attended the stakeholder workshop (Activity 1) shall advocate and encourage participation in the online survey for all ECHO participants by announcements and reminders at monthly ECHO sessions. Gentle reminder emails once at the end of 1 month, and again 1 week before the 2-month deadline shall be sent to increase response rates for the online survey (Activity 1). All other activities shall include random selection of participants, or a purposeful invitation of expert faculty, ECHO participants, and implementers from the iECHO database.For the FGD (Activity 3), 5–6 participants will be selected for each group from among participants with similar roles and responsibilities; they will be selected only if they completed the above ECHO participant survey.For the key informant interviews (Activity 8), six key stakeholders (opinion leaders) will be selected amongst those engaged in ECHO implementation: two representatives from the two ECHO participant groups of HCP and SME, a representative from UMB and one from CDC-TZ, one from Tanzanian MOH and one UMB administrator be invited to review summaries of results of Activities 1–7, and all data collection tools.Since data collected is not intended to be generalizable, no formal sampling frame is required. Purposeful sampling  will be Descriptive statistics will be used to describe and summarize participant characteristics, perceptions, and self-efficacy measures of the HIV ECHO clinic. Chi-square statistics shall be used to assess potential relationships between select characteristics of the participants and outcomes of HIV ECHO based on satisfaction and knowledge gained. Descriptive statistics for ordinal ratings  for Activities 2, 4, and 6 shall be generated using simple frequencies or percentages, and medians or modes will be used as the measure of central tendency. Non-parametric statistical techniques will be employed . Based on the results, the 4-point scales may be recoded for simplicity of reporting. Stratified analysis between different groups (implementers and participants) will clarify relationships of the variety of perceptions on efficacy, satisfaction, and knowledge gain.a priori codes and recurring themes. Coding and thematic analysis shall be conducted for the qualitative data and compared and contrasted with the survey data. Auto coding using MAXQDA  will help with thematic analysis. Contextual or cross-case analysis for the significant codes shall be conducted between the various stakeholder roles. Understanding the alignment or discordance of the a priori codes among the different stakeholders will be key. Data-reduction efforts shall be undertaken to eliminate ancillary information that did not appear to be significant or relevant. Emergent codes identified will lead to revising the original code book  is stronger than one data source alone, further probing of main concepts of interest from survey during FGD, will help better understand the results . Since tAll evaluation and programmatic data will be owned by the Tanzania MOH or the implementing partner (UMB). No individual, personally identifiable information shall be collected, analyzed, or reported. All data will be kept in password protected computers, only accessible to co-investigators. Audio recordings of focus group discussions (Activity 3) shall be destroyed after data analysis and translation. Audio recordings and paper-based data will be stored under lock and key in cabinets with access limited to authorized evaluation personnel . Management of data shall be restricted to key personnel. All project information will be kept confidential and will be available only to authorized users involved in the evaluation project. Each evaluation personnel will sign a confidentiality agreement indicating that he/she has been instructed in confidentiality procedures under their MOH public health program jurisdiction/implementing partner protocols and will observe them . AggregaEthical approvals may require local and institutional approvals prior to implementation. This protocol was reviewed by National Institute of Medical Research in Dar es Salaam, Tanzania; the University of Illinois in Chicago, United States; and the University of Maryland, Baltimore, United States; and the Human Subjects Office within the Center for Global Health at the United States Centers for Disease Control and Prevention (CDC). For adoption in other countries or PEPFAR-funded programs, a protocol amendment may be sought from CDC, Atlanta to document any locally required changes.Project staff will obtain informed consent (Flesh-Kincaid Reading Level for Consent 7.5) for those individuals willing to participate in the evaluation activities. Consent forms will be in English and the local language, Kiswahili, describing the evaluation details, procedures, risks, and benefits. Forms will be translated from English to Kiswahili, then back to English to verify that nothing was lost or altered in a substantive manner during translation. The individuals will be asked to read and review the document. If the participant is not able to read the document or has low literacy skills, the consent form will be read aloud by the evaluation staff and individuals will be offered an opportunity to ask questions about the evaluation and the consent process.It will be emphasized that evaluation participation is voluntary and that either agreeing or declining to participate in the evaluation will not have an impact on the individual's access to future ECHO programs. Participants will be informed that their participation is voluntary and that responses will remain anonymous and confidential. No names shall be used in any publications or reports of evaluation findings. Project staff will store the signed consent forms in locked cabinets.The following considerations may be a prerequisite to implementing this evaluation: (1) garner political will and engage leadership early to affirm the value of monitoring performance and measuring impact; (2) integrate dedicated funding/resources for evaluation in the workplan and budget of ECHO programming; (3) dedicate personnel (ECHO Champion) who understand the value of evaluation to lead the adoption and implementation of this protocol and monitor performance and measure impact; (4) adapt, contextualize and utilize any or all parts of the comprehensive evaluation framework and tools within a local context; (5) ability to collect, analyze, and manage quantitative and qualitative data . Additional specialized skillsets and subject matter expertise may be needed in some settings. Without these prerequisites, we acknowledge that implementing some or all of this protocol may be challenging.Information and data gathered from this evaluation will identify essential elements for developing and implementing a high-quality ECHO program. These recommendations will be beneficial for program implementation and evaluation planners irrespective of disease, health condition, or geographic location. Because this evaluation framework is intended to be locally driven, the experience may facilitate the development of local capacity to engage in activities to better monitor, evaluate, and assess program performance beyond ECHO. Moreover, the process monitoring, and evaluation tools may be modified, contextualized, and utilized for other ECHO programs and programmatic activities. Thus, these evaluation activities may serve as a force multiplier  to strenFindings from this evaluation may be presented at scientific conferences and in peer-reviewed journals. A team consisting of evaluation investigators, including representatives from investigating or collaborating institutions, will be responsible for approving all presentations and publications developed from evaluation data.Many countries have been implementing Project ECHO for disseminating best practices to address a variety of disease topics, however evaluation activities have not been consistent or standardized. This protocol offers a comprehensive evaluation framework with a data collection toolkit with the potential to be contextualized and used immediately. This framework offers a unique process to engage a diverse group of stakeholders using an appreciative inquiry process to co-create a comprehensive evaluation framework and a compendium of data collection tools using a mixed methods developmental evaluation approach. Co-creation of data collection tools for an evaluation framework is designed to support action learning from implementation and dissemination, and thus may be worthy of wider use.SG, BBS, EP, and PKM conceived, designed, and drafted the initial manuscript. BMR, IM, EM, EP, and SS provided technical support to develop the toolkit. SG, BMR, IM, EM, JL, EP, SS, BBS, and PKM revised the initial draft and provided critically important intellectual content. SG, BMR, EP, and PKM integrated all feedback and resolved any questions from internal and required clearance at CDC prior to publication. SG and PKM responded to peer-reviewers and revised the manuscript for pre-publication. PKM provided overall leadership and oversight. All authors attest to the accuracy and integrity of final version.This project has been supported by the President's Emergency Plan for AIDS Relief (PEPFAR) through the Centers for Disease Control and Prevention (CDC) under the terms of Cooperative Agreement No: NU2GGH001950-00.The findings and conclusions in this publication are those of the authors and do not necessarily represent the official position of the funding agencies, US Centers for Disease Control and Prevention, or the US Government.BBS is Associate Director of Project ECHO, of the ECHO Institute, located in Albuquerque, University of New Mexico. The remaining 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.


Fragility fractures are fractures caused by mechanical forces, known as low-level or low-energy trauma that would not ordinarily lead to fractures. Such forces, quantified by the World Health Organization (WHO), are as forces equivalent to a fall from a standing height or less. As both a sign and a symptom of osteoporosis , fragiliAlthough great advances have been achieved in surgical techniques and instruments for the treatment of fragility fractures, current information of fragility fracture-related pain remains limited. Therefore, we organized this special issue, with the aim of conveying the updated knowledge in the field of evaluation and management of fragility fracture-associated pain.In this special issue, the readers will find six articles, including three focused on vertebral fractures, two on geriatric hip fractures, and one on foot fractures: “Effect of Preoperative Zoledronic Acid Administration on Pain Intensity after Percutaneous Vertebroplasty for Osteoporotic Vertebral Compression Fractures” by Hu et al.; “Percutaneous Vertebroplasty and Facet Blocking for Treating Back Pain Caused by Osteoporotic Vertebral Compression Fracture” by Cheng et al.; “Advances in Vertebral Augmentation Systems for Osteoporotic Vertebral Compression Fractures” by Long et al.; “Effects of Orem's Self-Care Model on the Life Quality of Elderly Patients with Hip Fractures” by Xu et al.; “Fascia Iliaca Compartment Block for Perioperative Pain Management of Geriatric Patients with Hip Fractures: A Systematic Review of Randomized Controlled Trials” by Wan et al.; and “Prophylaxis of Pain and Fractures within Feet in the Course of Osteoporosis: The Issue of Diagnosing” by Bitenc-Jasiejko et al.In the field of vertebral fractures, Hu et al. investigated the effects of preoperative administration of zoledronic acid (ZOL) on pain intensity after percutaneous vertebroplasty (PVP) for osteoporotic vertebral compression fractures (OVCFs). Based on a randomized controlled trial (RCT) of 242 patients, the authors concluded that intravenous infusion of ZOL before PVP can effectively decrease the postoperative pain intensity, reduce bone loss, increase bone density, reduce the risk of refracture, and improve the quality of life of the patient. However, the incidence of adverse events in the ZOL group was higher than in the controlled group.In a retrospective study, Cheng et al. compared the efficacy of PVP plus facet blocking (FB) with PVP alone in relieving postoperative back pain in patients with OVCFs. Based on an analysis of 204 patients, they concluded that PVP combined with FB could provide better pain relief than PVP alone in the short term (1 day and 3 months) after surgery, with similar outcomes at 1-year follow-up time. However, patients receiving the combination method had a longer operation time and more fluoroscopic exposure.In a review article, Long et al. introduced recent advances on vertebral augmentation systems for the management of OVCFs, including PVP, percutaneous kyphoplasty (PKP), the OsseoFix® system, the SpineJack® system, radiofrequency kyphoplasty (RFK), and the Kiva system. Each technique has advantages and disadvantages, and orthopedists should be familiar with the indications and contraindications of each technique.Regarding geriatric hip fractures, Xu et al. analyzed the effects of Orem's self-care program on the life quality of senile patients with hip fractures. Based on a RCT of 130 participants, the authors concluded that the self-care program based on Orem's model for geriatric patients with hip fractures could significantly improve life quality and reduce perioperative complications. Whether this nursing program can be routinely applied in this field requires more future studies.In a systema review, Wan et al. summarized the current evidence of fascia iliaca compartment block (FICB) for perioperative pain management of geriatric patients with hip fractures. Based on comprehensive analyses of 27 RCTs with 2478 cases, the authors concluded that FICB is a safe, reliable, and easy-to-conduct technique, which is able to provide adequate pain relief during perioperative management of geriatric patients with hip fractures. However, as indicated by the authors, due to the still existing flaws of the current RCTs , future RCTs are warranted.It is interesting that Bitenc-Jasiejko and colleagues explored the roles of examination of posture and pressure distribution during standing, postural balance, and gait in the prevention of foot fatigue fractures during osteoporosis. Based on the literature review and examples of their clinical patients, they indicated that detailed posture diagnostics and gait estimation, along with the analysis of pressure distribution within the feet, are an essential aspect for the prevention of structural degradation and fatigue fractures within the feet. In addition, they also provided helpful recommendations, which need to be testified in the future.In this issue, we did not receive submissions on distal radius fragility fractures, which never means the incidence of such a fracture is low. Actually, distal radius fragility fractures possess unique characteristics and treatment . Future


To present and assess evidence from Latin America and the Caribbean (LAC) on public policies and targeted programs which may have influenced variations in adolescent pregnancy or its proximate determinants, and to identify knowledge gaps that require further research.A systematic review was performed based on the 2015 PRISMA protocol. Five databases were searched for articles published between 2000 and 2019 that refer to at least one country in LAC. The outcomes of interest were adolescent pregnancy or its proximate determinants . Only studies exploring correlations between the outcomes of interest and public policies or targeted programs were included in the analysis.Thirty studies spanning 14 countries were selected for analysis. Twenty-three of these (77%) were not included in prior systematic reviews on adolescent pregnancy. Public policies related to conditional cash transfers and compulsory education have the strongest evidence of correlation with adolescent pregnancy prevention. Emerging research points to the potential positive impact of life-skills programs for adolescents. Evidence from public health policies and programs was limited.Further research which incorporates an intersectional analysis is needed to better understand which policies and programs could lead to steeper declines in adolescent pregnancy in the region. Evidence on effects of expanded family planning services and secondary school attainment upon adolescent pregnancy are particularly absent. In Latin America and the Caribbean (LAC), adolescents aged 15–19 account for 16.0 percent of total fertility among women of reproductive age 2015–2020), which represents the highest share of adolescent pregnancy of any region in the world 015–2020,,4. AdoleAs indicated by the 2013 Montevideo Consensus and periodic reviews of its implementation, governments in the region have been making continuous progress in addressing priorities around gender equality, sexual and reproductive health, and the specific needs of young people .To understand adolescent fertility, one must take into consideration that not all pregnancies come to term, due to both natural causes and voluntary interruptions. Moreover, not all sexual encounters result in pregnancy. However, sexual behaviors can provide some insight into the risk of adolescent pregnancy occurring. As a result, adolescent sexual behaviors, which include early sexual initiation, sexual activity, and contraceptive prevalence, serve as proxies to measure the risk of pregnancy exposure. The academic literature considers these behaviors to be proximate determinants of adolescent pregnancy and employs them to study and measure the effects of policies and programs .This systematic review addresses the knowledge gap in the intended and unintended effects that public policies in LAC countries have on adolescent pregnancy. It aims to present and assess key evidence from the region about what policies have been shown to correlate with variations in adolescent pregnancy through a thorough appraisal of peer-reviewed articles studying relationships between public policies or targeted programs and adolescent pregnancy. By presenting the collective evidence available from the region, this review also aims to identify areas that require further exploration, which ultimately will inform how public policies and programs can prevent unintended adolescent pregnancy.Global evidence suggests that reducing unintended adolescent pregnancy is best addressed through multidisciplinary approaches ,7. There1 which comprised: (i) descriptions of adolescents (e.g. (adolescent OR teenage); (adolescente)); (ii) descriptions of pregnancy and its related proximate determinants ] AND/OR [prevención OR reducción] AND/OR [((iniciación) OR (primera) OR (conducta) AND ) AND/OR (anticoncepción) AND/OR (planificación familiar) AND/OR (aborto)]; (iii) [(public polic*) AND/OR (program*)]; [(política* pública*) AND/OR programa*]; and (iv) references to LAC (e.g.Latin America and the Caribbean OR [country name list]).The database search included terms in both English and Spanish,The searches were conducted in EBSCO, The Cochrane Library, PubMed, LILACS, and The World Bank JOLIS. The final search was conducted in September 2019.A priori inclusion criteria were: (i) case study included a LAC country; (ii) outcome variables included behavioral effects or adolescent pregnancy; and (iii) effects were measured on adolescents (youth aged 10 to 19).2To focus on evidence from policies responding to the updated sexual and reproductive health paradigm contemplated in the ICPD Plan of Action and reflected in the Millennium Development Goals, articles were excluded if they presented only changes in knowledge and attitudes without assessing changes in behavior, or if they were published prior to 2000.To confirm exclusion/inclusion, the review manually screened article titles and, when these did not provide sufficient information, abstracts. The review identified articles through both search results and a snowballing exercise of references. A spreadsheet (Microsoft Office Excel v16.49) of all results tracked information on whether the article was included/excluded following review of the title, abstract, or full paper, with key words describing the rationale for exclusion. The search, identification, screening and eligibility analysis followed the 2015 PRISMA guidelines .The search and screening process, presented in Nine relevant studies explored the relationship between conditional cash transfer (CCT) policies and adolescent pregnancy or its proxy indicators.Progresa/Oportunidades, implemented in Mexico.3 This CCT entails the transfer of a monthly stipend to families, subject to conditions related to school attendance, health talks and check-ups, and nutrition. Research found effects vary across rural and urban populations, as well as during different stages of the program.Several studies in this category examined the policy Oportunidades on adolescent pregnancy or proximate determinants. One study focusing on urban populations across Mexico found delayed motherhood and age of sexual initiation as a result of exposure to CCT  and Nicaragua, where CCT programs did not adjust financial allocations for increased number of children, no increase in adolescent fertility was identified . HoweverThe review identified 14 papers exploring the effect of education-related policies on adolescent pregnancy. Three of them investigate educational reforms affecting the whole population, while 11 others explore the impact of specific curricula taught in controlled settings with the objective of changing knowledge, attitudes, and behaviors related to adolescent sexual and reproductive health.In the case of Chile and Peru, changes in education policies extended compulsory school hours ,28. EvidFive studies exploring the effect of sexual and reproductive health (SRH) sessions imparted in targeted high-schools in Brazil, Chile, Jamaica, and Mexico found no evidence of lasting behavioral changes on adolescents as a result of the interventions –34. In tAn additional study from Chile, using a random-control trial to explore the long-term effect of an abstinence-centered curriculum, found higher pregnancy rates among adolescents not exposed to the sex-education program . Two othA few studies explored the effect of larger sexuality education programs. Evidence indicates adolescents who had received sexuality education in Mexico had higher chances of using modern contraception at first intercourse . A studyFive studies explored the impact of health policies related to service delivery, access to abortion, and access to contraception and HIV prevention.A study on the impact of the Colombian SRH policy implemented from 2002 to 2006 found an uneven decrease in adolescent pregnancy rates across locations but could not confirm national policy as the driver . NotablyThree studies explored the effect of abortion legalization on adolescent pregnancy. They found legalization did not reduce childbearing among adolescents in the three years after its adoption in Mexico City , althougA final study from Paraguay seeked to identify the effect of expanded health coverage, through the introduction of outreach first-level clinics, on adolescent pregnancy . The stuJuventud y Empleo implemented in Dominican Republic, which targeted youth who were out of school and most at risk. The program combined classroom training and internship placements, and integrated socio-emotional skills building. An impact evaluation of the program found that Juventud y Empleo reduced the probability of teenage pregnancy in the treatment group, with a stronger effect on young and single women and those who were already mothers intended effects on adolescent pregnancy and its proximate determinants.The analysis supports evidence that CCTs have significant effects on decisions about motherhood. The majority of studies of CCTs find that financial transfers conditioned to health and education requirements have a positive effect on adolescent pregnancy prevention. While the studies cannot always attribute positive changes in behavior or reductions in adolescent pregnancy to these policies, there is no evidence that these policies are detrimental to positive changes in behavior or reductions in adolescent pregnancy, with one exception, Honduras, where the CCT benefits for higher fertility rates offset its opportunity cost.Research from LAC appears to confirm an incapacitation effect both of education, which reduces engagement in risky sexual behavior, and of the human capital effect, whereby education generates an increase in the opportunity cost of adolescent pregnancy versus investing in future opportunities . This ev. Predictably, then, the studies reviewed found behavioral effects in more innovative approaches, such as Haiti’s combination of SRH education with sports, or Chile’s health referrals. In addition, evidence from Brazil and Mexico supports the hypothesis that comprehensive sexuality-education does not accelerate sexual initiation.The studies reviewed show limited evidence for the effectiveness of behavior-centered interventions in modifying risky sexual behavior. This mirrors findings from other regions, which also present mixed and often inconclusive results . EvidencThe studies found on the relationships between health policies and adolescent pregnancy in LAC are limited in number and diverse in scope, ranging from assessments of national health policies to smaller, localized interventions, making it difficult to draw conclusions. Although results remain inconclusive and merit further research, the three studies on the effects of abortion legalization offer an important contribution to the global literature.Good health enables young people to attend school and increases academic performance, as well as labor market insertion. The evidence reviewed in this study on the effect of health sector policies on adolescent fertility is limited but promising. Investments in health are also associated with closer contact with health professionals, who may provide SRH information and services, expanding the fertility choices available to women and girls. This seems particularly relevant in LAC, where estimates indicate adolescent pregnancy would be reduced by 43% if the unmet need for family planning was satisfied .The original research on the youth livelihoods program in the Dominican Republic indicates that modifications in young people’s aspirations may affect fertility choices. The studies reviewed here, together with nascent literature on empowerment and livelihood for adolescents programs implemented in other regions, point to the potential of this type of policies . ResearcAs a whole, the evidence presented in this review largely echoes global guidance about the combination of policies and programs that may prevent adolescent pregnancy . These pThe analysis encountered two main limitations. The first is the vast heterogeneity of methodologies, interventions, sample sizes, and outcomes across studies, derived from the broad search conducted, which precluded the possibility of conducting a meta-analysis and of generalizing evidence. Important differences across LAC countries, given their varied population and geographical size, culture, ethnic and racial diversity, as well as state administrative organization, among other characteristics, also complicates generalizability. The second limitation of the evidence collected is its narrow disaggregation by sex and age, as well as by other intersectional characteristics. Consequently, there is little evidence on the differential effects of policies between younger and older adolescents, rural versus urban, and among indigenous populations. This is particularly relevant in a region where inequalities and poverty are closely linked to geographical area of residence and ethnicity/race, as is the incidence of adolescent pregnancy.Emerging evidence on the ability of life-skills policies to modify youth aspirations is promising and merits further investigation . EquallyGiven that adolescents’ unmet need for contraceptives has been highlighted as one of the key drivers of pregnancy among girls aged 15–19, especially in LAC, it is surprising that this review found no studies on this subject. Important gaps persist, with more studies needed on health policies targeting adolescents.Author hold sole responsibility for the views expressed in the manuscript, which may not necessarily reflect the opinion or policy of the RPSP/ PAJPH and/or PAHO.


Results were descriptively analyzed. This manuscript articulates policy proposals informed by the survey results. The study sample was 58% female, with median age of 51. A minority of the sample (17%) reported that all their practice was LM, while 56% reported that some of their practice was LM. A total of 55% of practitioners reported not being able to receive reimbursement for LM practice. Of those survey respondents who provided an answer to the question of what would make the practice of LM easier (n = 471), the following suggestions were offered: reimbursement overall (18%), reimbursement for more time spent with patients (17%), more support from leadership (16%), policy measures to incentivize health (13%), education in LM for practitioners (11%), LM-specific billing codes and billing knowledge along with better electronic medical record (EMR) capabilities and streamlined reporting/paperwork (11%), and reimbursement for the extended care team (10%). Proposed policy changes focus on three areas of focus: (1) support for the care process using a LM approach, (2) reimbursement emphasizing outcomes of health, patient experience, and delivering person-centered care, and (3) incentivizing treatment that produces disease remission/reversal. Rectifying reimbursement barriers to lifestyle medicine practice will require a sustained effort from health systems and policy makers. The urgency of this transition towards lifestyle medicine interventions to effectively address the epidemic of chronic diseases in a way that can significantly improve outcomes is being hindered by current reimbursement policies and models.Lifestyle medicine (LM) is a rapidly emerging clinical discipline that focuses on intensive therapeutic lifestyle changes to treat chronic disease, often producing dramatic health benefits. In spite of these well-documented benefits of LM approaches to provide evidence-based care that follows current clinical guidelines, LM practitioners have found reimbursement challenging. The objectives of this paper are to present the results of a cross-sectional survey of LM practitioners regarding lifestyle medicine reimbursement and to propose policy priorities related to the ability of practitioners to implement and achieve reimbursement for these necessary services. Results from a closed, online survey in 2019 were analyzed, with a total of  The majority of guidelines for treatment and management of chronic disease offer lifestyle changes  as a fir®); and (3) the payment is based on the resources-based relative value scale (RBRVS). Lifestyle medicine (LM) is currently not adequately supported by any of these three processes.Although education on nutrition and healthy lifestyle behaviors delivered during medical training is extremely limited , awareneIn terms of coded medical services, because LM is founded on health behavior education , some ofThe United States (US) healthcare system is predominantly founded on a fee-for-service model, which has incompatibility  with delThe objectives of this study were to (1) characterize challenges in reimbursement for clinicians who wish to practice LM, (2) present individual comments shared by clinicians in their own words describing their experiences with reimbursement and quality measures, and (3) propose policy changes to better support LM practice as a viable, financially rewarding path for clinicians.A closed, cross-sectional, survey hosted in the survey platform QuestionPro was administered to N = 3182 members of the American College of Lifestyle Medicine (ACLM) in the summer of 2019. Questions asked covered eight topics: respondent demographics, motivation and interest for practicing LM, medical practice and patient outcomes, reimbursement logistics, quality measures, follow-up on patient outcomes, behavior change and education, and practitioner quality of life. The survey included both multiple-choice and free-text questions. A sample of interest was restricted to consented individuals >18 years, self-identifying as a healthcare practitioner, and completing the survey within the US. The analysis for this paper, including descriptively summarizing quantitative data relating to practitioner demographics and reimbursement, was completed using SAS software, Version 9.4 of the SAS System for Windows, SAS Institute Inc., 2013, Cary, NC, USA. Free-text data were qualitatively coded in Excel by a single researcher (K.F.) and then double checked and collapsed for more parsimonious categories by a second researcher (M.K.). Key quotes were extracted to represent repeating themes. Policy priorities were developed through discussion with ACLM leadership, informed by survey results. This study was approved by the University of New England IRB.n = 1286 respondents began the survey, and after restricting the survey to those who answered yes to being a healthcare practitioner, and to being over the age of 18, provided informed consent, and responded to the survey from within the United States (based on an Internet Protocol (IP) address), a total sample of n = 857 was included in this analysis , the median number of years in practice was 17. A minority of the sample (17%) reported that all their practice was LM, while 56% reported that some of their practice was LM, and 9% reported that none of their practice was LM.Of this sample, 58% were female, with a median age of 51. Top reported clinical degrees were medical doctor (MD) or doctor of osteopathy (DO) (54%); registered nurse (RN) or registered dietician (RD) or occupational therapist (OT) or physical therapist (PT) (12%); and doctor of nursing practice (DNP) or advanced practice nurse/advanced practice registered nurse (APN/APRN) (4%); other clinical degree (9%); and not selected (22%). The top reported specialties were family medicine (23%) and internal medicine (17%). Of those with a complete answer  their employer or leadership were supportive (20%), (2) the owner of their practice is a LM practitioner (14%), or (3) that there was some or growing support for LM (25%). The single most frequently reported method of payment that did not involve billing insurance was out-of-pocket or direct pay (34%). However, 28% of respondents reported that they were not paid, not well-paid, or did not know how to get paid, and 11% were limited to incorporating LM into existing standard appointments. A total of 59% reported that robust income from shared medical appointments is restricted or a challenge and 33% reported that there are quality measures hindering their practice of LM. When asked what changes would be necessary to make the practice of LM easier, reimbursement overall (18%), reimbursement for more time spent with patients (17%), more support from leadership (16%), policy measures to incentivize health (13%), education in LM for practitioners (11%), LM-specific billing codes and billing knowledge along with better EMR capabilities and streamlined reporting/paperwork (11%), and reimbursement for the extended care team (10%) were among top-reported suggestions.Direct quotes captured by the free-text fields in the survey related to the themes of barriers to insurance reimbursement, challenges of the time limitations of appointments, perverse incentives for health outcomes improvement, LM made possible through grants or philanthropy, and alternative payment models are presented in Results of this cross-sectional survey describe logistical challenges faced by LM practitioners and those who want to practice in the field, particularly regarding payment and reimbursement. While a majority of survey respondents reported practicing LM for some part of their practice, and while a majority of respondents also reported having some degree of supportive leadership, over half of the respondents reported not being able to achieve reimbursement for the LM services. Support from leadership could occur in a number of ways, including budgetary planning, offering necessary space to practice, and flexing productivity expectations. This result is consistent with a previous survey of LM practitioners in which only 43% of the respondents reported receiving any form of compensation for their LM services. Of those receiving compensation in that survey, almost 44% identified cash payments from patients, philanthropic support, employer-funded programs, and “other” as the source of funding . AlthougAs previously described, LM practice involves multiple elements of care that fall outside the current fee-for-service model, including more time and follow-up with patients ,21,22, cRespondents described billing for LM practice as “prohibitive” and “no one knows how”, and described multiple constraints on time available to adequately educate patients in appointments, as well as time to develop materials and programs. These comments are indicative of the paradigm shift required to make healthy lifestyle change the foundation of healthcare. While patients are responsible for their own health behaviors, without adequate teaching time, support, accountability, and all the components of successful behavior change programs, uptake and adherence will be limited. The practitioners surveyed here report seeking creative ways to deliver these elements that will help patients be successful, but in many cases, this results in unpaid work, work that is not well-paid, or work that cannot be billed for because of the site of delivery such as a community location or teaching kitchen. A small segment reported seeking grant funding and philanthropic support to enable their LM practice . While admirable from the perspective of social responsibility, such methods of payments are not feasible for most practitioners, who also may have high rates of burnout and have usually entered the workforce with considerable personal debt from student loans ,37,38,39A minority of respondents reported working with an interdisciplinary team all of the time, and this has implications for the financial sustainability of delivering health behavior change interventions in the emerging context of value-based care. Coaching, counseling, or group education is best administered by professionals trained for those services, not necessarily physicians, because of the cost of service. At the same time, reimbursement for other healthcare professionals, such as RDs, educators, OTs/PTs, and group visits, group programs, and coaching/counseling, were among the top-suggested strategies for making the practice of LM feasible and sustainable. Practitioners also suggested policy changes to incentivize improved health outcomes and prioritize LM approaches; this is the foundation of value-based care. However, while value-based care holds great potential for intersecting with LM practice, mostly because of the superior outcomes made possible by sustained health behavior change, the success of the value-based care model lies in the details. Patient adherence is a critical limitation on the feasibility of paying practitioners based on outcomes, for both LM and conventional medical practice. Without an adequate support structure in the form of a healthcare team, thorough education, sufficient time with educators and practitioners, and referrals to group programs, LM interventions are handicapped from the outset and likely not to work. Intensive therapeutic lifestyle change cannot be effectively delivered in a portion of a 15 min appointment. Investment in staff resources, time with patients to support their health behavior change journey, and nurturing long-term relationships to maintain the desired changes are essential for success. These nurturing practitioner–patient relationships not only support effective behavior change but also improve practitioner satisfaction levels and well-being, with the potential to lower burnout rates.The authors report that physician residents and other healthcare professionals are hesitant to commit/plan to become certified in LM when there are no reimbursement/payments benefits. There is currently no reimbursement advantage for specialized LM care. While the residents acknowledge the education and training as beneficial, lack of financial gain due to inadequate reimbursement appears to be a hindrance.While many population-based and episode-based alternative payment models (APMs)  have beeOur survey results also highlight the reimbursement obstacles and perverse quality measure incentives  that encourage sick care and discourage genuine health care. Multiple survey respondents indicated that they had been reprimanded or penalized financially for not prescribing certain medications linked to quality measure payments. The results reported here are consistent with a review of more than 1100 National Quality Forum Quality Measures  related There are minimal quality measures that reward the time-intensive interventions necessary for successful LM approaches, such as assessing lifestyle behaviors proven to impact chronic disease progression and intensive therapeutic lifestyle change programs to support patients in sustaining beneficial change. Shared medical appointments (SMAs) can be a way to better utilize time by seeing patients in a group setting and having the opportunity to be reimbursed feasibly. However, the authors report that there are many hindrances to SMAs. It may be challenging to fill the appointment slots. Patients prefer to be seen during the evening or on a Saturday, which makes it difficult to count on filling daytime group visits with a targeted minimum number. The authors’ experience was consistent with the survey results, showing that most respondents found that SMA reimbursement was restricted or challenging. Location of service is also a barrier for SMAs, as the payor may deny a group visit claim if the location is lacking a National Provider Identifier (NPI) number. Thus, while these SMAs do have potential, more work needs to be done to ensure that the reimbursement is sustainable.Quality metrics that focus on care processes instead of outcomes inherently overlook patient choice, shared decision making, person-centered care ,44, and The current healthcare quality measures, performance measures, and incentive models are tied to a “disease management” model. Improvement in biometrics and resolution of symptoms to the point of no longer needing medication is not acknowledged as a primary goal, or even an option, within current reimbursement models. Misaligned quality measures in which the majority of measures focus on care processes instead of patient outcomes require re-examination.While much work remains to improve reimbursement for lifestyle interventions, a few models do exist. Some of the first lifestyle-based medical treatment programs to be reimbursed were the intensive cardiac rehabilitation programs (ICRPs) and the Medicare Diabetes Prevention Programs (MDPPs). These programs offer lifestyle change opportunities within a group setting with demonstrated effectiveness ,46,47,48care process using an LM approach, specifically the six pillars of LM: a whole-food, plant-predominant diet, physical activity, restorative sleep, stress management, positive social connection, and avoidance of risky substances;Support for the Reimbursement emphasizing outcomes of health, patient experience, and person-centered care;Incentivizing treatment that produces substantial outcome improvements vs. conventional care, such as outcomes of disease remission/reversal.Policy changes intended to facilitate sustainable LM practices that address both the barriers to LM practice and the limitations of current payment and reimbursement models e are proposed in Additionally, identifying policy improvements may not be enough; decision-makers need to truly understand the benefits of lifestyle medicine to impact care and payment. They may also need education about what LM is and what it looks like; understanding the needs and constraints of a different practice structure is necessary for effectively supporting a different reimbursement structure. This is a barrier to implementing practice and payment reform. In addition to these policy changes, effective communication strategies are needed to disseminate research results to a broad array of stakeholders. To successfully influence policies in reimbursement and payment models that support LM, the education of decision-makers is vital .A strength of this study is that it is one of the first surveys to describe logistical challenges with LM practice, using practitioners’ own words. A limitation of this study is that it is a cross-sectional survey only, and therefore, results should not be over-interpreted. Additionally, the sample was self-selected from within the closed list of ACLM members, and there was a high dropout rate. More research is needed to better characterize the demographics of LM practitioners, such as medical specialty, the extent to which individuals practice LM, and their associations with payment barriers and successes. Research on health outcomes comparing LM to standard medical care is required, along with better reimbursement, to enable benchmarking and comparisons of the value of LM care with conventional treatment. Additionally, further research on improving LM reimbursement is needed, such as case series that incorporate in-depth interviews, simulations of reimbursement, and randomized controlled trials comparing various payment models for health outcomes and effective use of resources. Beyond research, policy changes are necessary to implement the suggestions outlined here.LM promotes core values of public health in terms of supporting health behaviors, but it adds a novel dimension to clinical healthcare that has traditionally focused on symptom management. For LM to be effective in achieving meaningful health improvements, individuals need customized LM services delivered at the appropriate therapeutic dose , in the The results of this research have demonstrated the reimbursement barriers faced by healthcare practitioners who implement lifestyle medicine within their practices. While chronic disease management guidelines are all quite clear in recommending health behavior changes, the health systems and policies needed to support these interventions are lagging. If optimal health outcomes for chronic diseases truly are the goal, then significantly more resources need to be mobilized to best illuminate what types of lifestyle interventions are most impactful and how to successfully implement them in a sustainable manner. Benchmarking for best LM practices and quantification of benefits of LM will help to support further reimbursement. Now is the time to acknowledge that chronic diseases such as cardiovascular disease, diabetes, and obesity are reversible, that remission is possible, and that LM practitioners who efficiently address the mitigating factors of disease to achieve these outcomes should be paid for their services in a manner that is commensurate with the value they provide, thereby further promoting the growth and accessibility of LM interventions.


The Lancet Regional Health – Western Pacific, Jidong Jia and colleagues report on the improvements in linkage to care, disease monitoring and testing, and antiviral treatment among adults with chronic hepatitis B virus (HBV) infection in Beijing, China In Investigators from the Polaris Observatory Collaborators have previously highlighted the significant gaps in diagnosis and linkage to care and treatment among chronic HBV patients globally. Among the estimated 292 million individuals with chronic HBV, only 10% were diagnosed and linked to care, and among the estimated 94 million individuals with treatment-eligible chronic HBV, only 5% had received antiviral therapy A recent commission of international experts identified key recommendations that are needed to accelerate the global elimination of viral hepatitis Dr. Wong receives research grants (to his institution) and serves as a consultant and advisor to Gilead Sciences.


To provide an overview of quality indicators (QIs) for knee and hip osteoarthritis (KHOA) care and to highlight differences in healthcare settings. A database search was conducted in MEDLINE (PubMed), EMBASE, CINAHL, Web of Science, Cochrane CENTRAL and Google Scholar, OpenGrey and Prospective Trial Register, up to March 2020. Studies developing or adapting existing QI(s) for patients with osteoarthritis were eligible for inclusion. Included studies were categorised into healthcare settings. QIs from included studies were categorised into structure, process and outcome of care. Within these categories, QIs were grouped into themes . A narrative synthesis was used to describe differences and similarities between healthcare settings. We included 20 studies with a total of 196 QIs mostly related to the process of care in different healthcare settings. Few studies included patients’ perspectives. Rigorous methods for evidence synthesis to develop QIs were rarely used. Narrative analysis showed differences in QIs between healthcare settings with regard to exercise therapy, weight counselling, referral to laboratory tests and ‘do not do’ QIs. Differences within the same healthcare setting were identified on radiographic assessment. The heterogeneity in QIs emphasise the necessity to carefully select QIs for KHOA depending on the healthcare setting. This review provides an overview of QIs outlined to their healthcare settings to support healthcare providers and policy makers in selecting the contextually appropriate QIs to validly monitor the quality of KHOA care. We strongly recommend to review QIs against the most recent guidelines before implementing them into practice. Although the evidence-based recommendations for the management of knee and hip osteoarthritis (KHOA) are internationally similar, clinical practice is context-dependent and therefore varies between countries.Previous research has shown that quality indicators (QIs) cannot simply be transferred between countries, due to structural and cultural differences of healthcare systems.This review provides an overview of QIs for KHOA care showing considerable differences between QIs depending on their healthcare settings.This overview will support healthcare providers and policy makers in selecting the contextually appropriate QIs to validly monitor the quality of care, but we strongly recommend to review the QIs against the most recent guidelines before implementing them into practice.Osteoarthritis (OA) is one of the leading musculoskeletal causes of global disability, mainly affecting the knees and the hips.2–4Despite the presence of numerous consistent guidelines for the management of knee and hip OA (KHOA),13–15Although the evidence-based recommendations for the management of KHOA are internationally similar, clinical practice is context-dependent and therefore varies between countries. In the Netherlands, Scandinavian countries and the UK, the content of KHOA treatment depends on the healthcare setting. Non-surgical management of KHOA is largely provided in primary care. For patients who do not respond successfully to this approach, a referral to secondary care for surgical management is indicated.Several systematic reviews have focused on QIs for OA in primary care.Therefore, the aim of this systematic review was to provide an up-to-date overview of QIs for KHOA in which we outline the healthcare settings and countries for which the QIs have been developed or adapted.This systematic review was conducted and reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.An electronic database search was conducted by a trained medical librarian up to March 2020, using MEDLINE (PubMed), EMBASE, CINAHL, Web of Science, Cochrane CENTRAL and Google Scholar databases. For unpublished and ongoing studies, a similar search was conducted in OpenGrey and the Prospective Trial Register database. A range of search terms related to OA  combined with indicator terms  were used to identify studies. Full details of the search strategy are provided in 10.1136/rmdopen-2021-001590.supp1Supplementary dataStudies about the development of QI(s) and adaptation of existing QI(s) for another context were included . Reviews that contained QIs which were already included from other studies were excluded, as were conference abstracts and studies written in languages other than English, Scandinavian, Dutch, Turkish and German. Studies published before January 2000 were excluded, since they may contain QIs that are more likely to be outdated and may therefore include treatment modalities that are no longer recommended. Studies focusing on patients with OA and other diseases ) were included if QIs about OA were presented separately.QIs for OA care, either specifically in the knees and hips or OA not related to specific sites, were extracted from the studies. QIs that measure postsurgical healthcare  were excluded. Various types of individuals  could be involved in the adaptation or development process of the QIs, resulting in QIs from various perspectives of stakeholders.All titles and abstracts were double and independently screened for their relevance (IGA plus DS or RR). Full-texts of potentially eligible studies were gathered and screened again by double independent review to check for their relevance (IGA plus DS or RR). Data from the included studies were extracted into a pretested data extraction form by one reviewer (IGA) and checked by another reviewer (DS or RR). The following data were extracted: general information about the study, healthcare setting, country, target population, involved joints , perspective of QI(s), information of testing and implementation of the QI(s) if this was done in the study and the full QI(s). Furthermore, methods of evidence synthesis and consensus method were extracted. An evidence synthesis using a systematic review and consensus method using a RAND Appropriateness Method or a Delphi method were considered as the most rigorous methods.10.1136/rmdopen-2021-001590.supp2Supplementary dataThe search strategy identified 1966 studies, after removing duplicates . After s10.1136/rmdopen-2021-001590.supp3Supplementary dataThe characteristics of the studies included are summarised in 31–3310.1136/rmdopen-2021-001590.supp4Supplementary dataStudies were categorised into five healthcare settings: primary care (n=10), secondary care (n=3), the entire spectrum of disciplines (n=8) and centralised intake care (n=1) . Nine stA total of 196 QIs were derived from the included studies. See 10.1136/rmdopen-2021-001590.supp5Supplementary dataWith respect to the structure of care, one studyRegarding the process of care, we identified QIs on 10 different themes .QIs on assessment of functional status and level of pain were most common and focused on all healthcare settings, except for centralised intake care. QIs on assessment for assistive devices, appliances and aids, and radiographic assessment also focused on the entire spectrum of disciplines, except for centralised intake care. Differences were seen in the indication for radiographic assessment; from offering a radiography to patients with incident hip OA to only offering a radiograph to patients with worsening complaints or patients who seem resistant to conservative treatment. QIs on the diagnostic aspiration of the joint and examination of joint before drug use were less common and focused on the US only. QIs relating to history taking and health assessment to evaluate the given treatment were mainly described for (physiotherapy) primary care settings in Europe.QIs on this theme related to information on the pathology of OA, treatment options and self-management and were similar between countries. Most QIs on this theme were developed for primary care (physiotherapy) in the Netherlands, but least for secondary care and healthcare in the US.QIs regarding exercise therapy were mostly developed for primary care on recommending and prescribing physiotherapy or specific exercises and were similar between countries. Three QIs focusing on the entire spectrum of disciplines were found regarding the frequency and regular evaluations of exercise therapy sessions, and regarding tailoring exercise therapy to patients goals.2 vs >27 kg/m2, and at least once in 2 years vs annually).QIs for advice on weight loss were developed for primary care and the entire spectrum of disciplines. Body mass index (BMI) threshold and frequency for advising patients to lose weight differed between QIs for the entire spectrum of disciplines in the USA and QIs for family medicine in Mexico (>25 kg/mTwo QIs for primary care (physiotherapy) in the Netherlands focused on recommending against massage and physical modalities other than Transcutaneous Electrical Nerve Stimulation. One QI for the entire spectrum of disciplines focused on not prescribing a brace for people with knee OA, except for patients with unicompartmental knee OA with axial deviation.Most of the pharmacological treatment QIs were developed for primary care. These QIs were consistent in their content and covered: (1) the use of paracetamol as first-line pharmacological therapy, (2) prescribing a trial of maximum-dose paracetamol before changing to a different oral agent, (3) non-steroidal anti-inflammatory drugs (NSAIDs) prescription, (4) NSAID prescription concomitant with either misoprostol or proton-pump inhibitor and (5) informing/screening patients about the risks of medication use. One additional QIs for the entire spectrum of disciplines in Norway focused on the indication of injections.Four QIs were found regarding the referral of patients to exercise therapy/programmes/activities in all studies included in this study, except in studies focusing on Mexico and the USA. From the three QIs that focused on referral for weight loss services, only oneOnly two studies developed QIs on the indication for surgical treatment. One study for the entire spectrum of disciplinesSix QIs were found on documentation of information on measures from physical examination for the entire spectrum of disciplines in the USA43Although not all QIs on this theme defined a specific threshold, three QIs for primary care (physiotherapy) in the Netherlands and one for the entire spectrum of disciplines in the US healthcare specified a threshold for treatment frequency (<12 consultations), duration (<6 weeks) and follow-up (every 6 weeks). The study on primary care (physiotherapy) in the NetherlandsQIs at outcome level of care included experiences and satisfaction with healthcare (n=6), pain and functional capacity (n=3) and achievement of treatment goals (n=1) . The QIsThis systematic review provides an overview of 20 studies including a total number of 196 QIs for KHOA care for a variety of healthcare settings. Rigorous methods for evidence synthesis to develop QIs were rarely used in the included studies. Adequate reporting on the perspective of healthcare, the proposed method of measurement  and threshold of the QIs was lacking. QIs were mainly developed from the perspective of healthcare professionals and researchers, while a patient perspective is limited. Narrative analysis showed that most healthcare settings and countries contain QIs on the following themes with largely similar content: (1) examination of functional status and pain, (2) education and information, (3) exercise therapy, (4) referral to exercise therapy/programmes/activities (5) and pharmacological treatment regarding paracetamol, NSAID and risks of medication use. For example, regarding the use of paracetamol as first-line pharmacological therapy and prescribing a trial of maximum-dose paracetamol before changing to a different oral agent. Some differences in the content of QIs occur due to the healthcare system, that is, QIs about exercise therapy, weight counselling, referral to laboratory tests and ‘do not do’ QIs (mainly described for physiotherapy care in the Netherlands). Nevertheless, differences in the content of QIs occurred within the same healthcare setting with regard to indications for radiographic assessment of the joint.Studies in the current review included mostly QIs that were related to the process of care. An explanation therefore could be that the studies included developed QIs or adapted existing QIs for quality of care improvement purposes. Process measures offer a roadmap for improving care or list the actions required to eventually improve outcomes for quality improvement purposes. In contrast, outcome measures are mainly developed for public reporting and accountability purposes through feedback on quality of care in order to stimulate quality improvement rather than specific actions to improve the quality of care.This study identified differences within themes of QIs, which can be explained by differences between healthcare settings and countries. First, QIs for physiotherapy care in the Netherlands strongly focused on inventory of health-related problems, education and information, and exercise therapy. This is likely explained by the fact that the management of KHOA in physiotherapy care focuses on non-surgical and non-pharmacological management, containing the interventions these QIs include. Also, these QIs have been formulated in more detail, for example, regarding the specific content of self-management . This may be due to the great focus on informing, advising and self-management in the Dutch KHOA guidelines for physiotherapy where these QIs are derived from. Second, QIs for centralised intake care in CanadaThis systematic review did however identify differences which could not be fully explained by healthcare setting. These QIs concerned laboratory test in case of an NSAID prescription for ≥6 months to detect possible adverse events, a BMI threshold and frequency for advising patients to lose weight, and specific indications for radiographic assessment for KHOA. For example, two studies focusing on healthcare in the US described different indications, one describing that patients with incident hip OA should be offered an anteroposterior radiographOf some frequently used treatments for OA, very little is described in QIs. For example, only one of 196 identified QIs focused on the prescription of opioids. Furthermore, QIs regarding injections, not prescribing chondroitin and glucosamine-chondroitin and indications for surgical treatment for hip OA are scarce. Also, there is currently an overuse of imaging to diagnose KHOA, while guidelines recommend to diagnose KHOA clinically.This systematic review was restricted to studies that developed QIs or adapted existing QIs. A previously published reviewPreviously published reviewsThis review showed considerable differences between QIs depending on their healthcare settings. Furthermore, this review provides an overview of QIs outlined to their healthcare settings to support healthcare providers and policy makers in selecting the contextually appropriate QIs to validly monitor the quality of care for KHOA. However, we strongly recommend to review QIs against the most recent guidelines before implementing them into practice, especially QIs regarding pharmacological treatment. Furthermore, more adequate reporting of studies, rigorous methods of development of QIs and a greater variety of perspectives of stakeholders is needed. In addition, more uniformly formulated within the same healthcare settings and on several areas and up-to-date QIs are needed.


N-hydroxypipecolic acid (NHP) are two central plant immune signals involved in both resistance at local sites of pathogen infection  and at distal uninfected sites after primary infection (systemic acquired resistance). Major discoveries and advances have led to deeper understanding of their biosynthesis and signaling during plant defense responses. In addition to their well-defined roles in immunity, recent research is emerging on their direct mechanistic impacts on plant growth and development. In this review, we will first provide an overview of how SA and NHP regulate local and systemic immune responses in plants. We will emphasize how these two signals are mutually potentiated and are convergent on multiple aspects—from biosynthesis to homeostasis, and from signaling to gene expression and phenotypic responses. We will then highlight how SA and NHP are emerging to be crucial regulators of the growth-defense balance, showcasing recent multi-faceted studies on their metabolism, receptor signaling and direct growth/development-related host targets. Overall, this article reflects current advances and provides future outlooks on SA/NHP biology and their functional significance as central signals for plant immunity and growth. Because global climate change will increasingly influence plant health and resilience, it is paramount to fundamentally understand how these two tightly linked plant signals are at the nexus of the growth-defense balance.Salicylic acid (SA) and  In loca and SAR . The jmjse genes . AltogetICS1, EDS5, and PBS3) and SA production, as elegantly demonstrated by Because of common overlapping SA and NHP regulators, it is not surprising that SA/NHP cooperatively and synergistically influence each other to induce SAR . This muALD1 and FMO1 gene expression can be directly upregulated by SA , thereby increasing free auxin levels  constitute another major class of hormones mediating growth and development . During ynthesis . Complemvated SA .ugt76b1 mutant, while overexpression led to opposite phenotypes . Although crosstalk with hormones is relatively uncharacterized, the NHP precursor Pip has been described as an osmoprotectant in both bacteria and plants , and thiArabidopsis revealed that NHP-suppressed genes are associated with photosynthesis and primary metabolism, particularly those involved in fatty acid and amino acid biosynthesis (IAAs and AUXIN RESPONSE FACTORS/ARFs), BR (BRASSINOSTEROID INSENSITIVE 1/BRI1 and BRI1-EMS-SUPPRESSOR 1/BES1), and GA pathways . It is important to highlight that NHP-downregulation of these growth/development-related genes is less pronounced than in biologically induced SAR  overexpression enhances auxin signaling, resulting in lower SA levels and increased host susceptibility  kinase . TOR is These studies altogether suggest a model that growth and developmental processes mechanistically impact the SA pathway. It would be intriguing to investigate whether NHP biosynthesis and signaling are similarly impacted by major growth hormones and TOR, and whether this occurs dependently or independently of SA. It would not be surprising to discover direct functional linkage of growth/developmental processes on NHP biosynthesis and signaling, since growth suppression is associated with NHP over-accumulation  and the via the SA and NHP pathways remain low-hanging fruits, which can be facilitated by recent global datasets on microbiota assembly and hormone interactomes  Discovery Grant, Canada Foundation for Innovation, Ontario Research Fund, and the Faculty of Science at Wilfrid Laurier University (to CDMC). We also acknowledge funding from the Mitacs Research Training Award (to VS).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.


This paper presents data for the estimation of the life cycle carbon emission in Kenyan, Rwandan, and Tanzanian grid electricity generation and transmission systems. Data was collected and estimated using the developed life-cycle carbon emission inventory (LCCEI) algorithm implemented through Excel tabs (LCCEI Excel worksheets). The data acquired through the LCCEI modelled parameters . The presented dataset shows the results of the developed data collection model. The activity data were obtained from specialized data sources. Some information was obtained through meetings with relevant institutional actors and experts of national and regional power institutions as well as expert judgement. However, most of the data were also obtained from the reviewed published reputable sources, such as the scientifically indexed conference proceedings and journals. The obtained data are presented in this article and in a Mendeley data repository. The compiled data can also be customised and coded to commonly used evaluation software to enhance its open use by scientists, practitioners, and policymakers at national, regional and global levels. The obtained data can also be useful for evaluating the extent to which grid electricity generation and transmission system drivers are designed and operated in the context of environmental governance (EG) factors.•The compiled LCCEI data can also be customised and exported to commonly used evaluation software to enhance its use for scientists, practitioners, developers and policymakers at national, regional, and global scales.•The generated data can also enhance learnability and carbon emission monitoring of electrical power systems and sustainable sub-region and regional grid interconnections design.•Besides it is easy to replicate the collected (existing and new) data, collected data can also openly be used by anyone who has interest in conducting a life cycle assessment of electrical power systems.•The developed data can be openly-used for targeting and monitoring of local, regional, and global institutions for environmentally sustainable electrical power system development, and.•The data can also be openly-used to generate additional knowledge for guiding clean technologies and the design of environmentally sustainable electricity production and transmission systems.12019) of both the electrical product system capacity installed, operated, maintained, and surviving in a studied national grid for the base year 2019. The EFo, 2019 were calculated from different energy sources and presented in the dataset B1 (Cell K 8), B3. (Cell L 8) and B2 (Cell B 16). The dataset provides the carbon emission factor  of the electrical product system caused by the new installation, operation, and maintenance in the year 2049 product presented in dataset C1 (Cell H 10), C2. (Cell G 10), and C3 (Cell J 13). The EFm,2049 were calculated from different energy sources and transmission loss designed for different scenarios. The power transmission system loss capacity of 0.03% has been considered. The electrical power system capacity installed and survived  values of 1565.72 MW (Tanzania), 216.23 MW (Rwanda) and 2819 MW (Kenya) have been presented for the base year 2019.The quantitative data have been collected since the obtained pilot survey data showed the developed `gate to gate LCCEI' system boundaries is acceptable for the collection of both up and downstream inventory data for electrical power systems in the study area. The installed capacity and transmission loss data has been obtained from EAPP, SAPP, REG, EDCL, EUCL, TANESCO, TGDC, KenGen, GDC and KETRACO reports and/actor(s). The technology-specific carbon emission factors have been obtained from published scientific and technical papers. The electrical power system capacity in the year 2049 has been linearly adjusted from the last year of projection presented on the most recently updated national and regional power systems master plans. The dataset was compiled after modelled life-cycle carbon emission inventory (LCCEI) parameters administration from the studied national grids for, the base year 2019 and, the projected year 2049. The dataset files in the repository provide the carbon emission factors  in the year 2049 has been calculated in dataset D  in the year 2049, filling quantity of a carbon emission per unit of added electrical power system capacity  and the ratio of the carbon emission substituted remaining into the newly added electrical power system  in the year 2049. The dataset D also present the carbon emissions  data remaining from the retired and recycled electrical product systems in the year 2049, as a product of the quantity of carbon emitted in the newly added electrical power (generation and transmission) systems capacity  in the year 2048, retirement fraction of the newly added electrical power system  in the year 2048, and the ratio of a carbon emission remaining in the retired electrical power system  by the year 2049. Dataset D (Column H) presents the remaining data of the substituted recycling coefficient/the residual carbon emission fraction from the electrical power systems retired  in the year 2049. The higher the percentage of solar composition in the grid the lower the residual emission. The systems compose of long-lived hazardous wastes was also allocated (perceived to have) greater than 50% residue carbon emission. Dataset E presents the calculated LCCE,2049 (kg/MW) database of the studied grid electricity generation and transmission systems for the year 2049. Apart from the text data and Table provided by this article, the supplementary LCCEI data file  is also provided through the Mendeley data repository (https://data.mendeley.com/datasets/pcc8vhbvwz/2).The quantity of carbon emitted in the newly added electrical power (generation and transmission) systems capacity  in the sources of data identified by the researcher. The survey questions have been designed to validate the general inventory approach and assumptions. The survey has also ensured the developed research data is suitable for research question testing and avoid any potential bias. The obtained pilot survey data showed the developed `gate to gate LCCI' system boundaries is acceptable for the collection of both up and downstream inventory data for electrical power systems in the study area.The dataset format (spreadsheets) and structure were obtained from established system limits and algorithm. The assumptions regarding power systems coverage, representative year, technology/management level were described 2049 of a particular year using the parametric values  estimated based on the established mathematical algorithm, system boundary model, scenarios, and the key assumptions. The LCCE data have been computed from the available and assumed data using The use of national data has been preferred since sources are typically more up to date and provide better links to the originators of data. In some cases, directly applicable data was not available, therefore physically and statistically related alternative data that have a correlation with the missing data were applied to develop the LCCEI spreadsheet database. The Excel worksheets B1, B2, B3, C1, C2 and C3, of the LCCEI data file presented in a Mendeley data repository linked to this article, were applied to collect and/calculate grid electricity generations/consumptions data (for each fuel type for each end-use), transmission systems loss data (for each studied grid), and their respective life cycle carbon emission factor data. Excel worksheets D, of the presented LCCEI data file, has been used to calculate LCCE,•2049 calculated life cycle electrical power systems amount of carbon emission (kg/MW) in the year 2049,LCCE,•2049 represents the quantity of carbon emitted in the newly added electrical power (generation and transmission) systems capacity (kg/MW) in the year 2049,Qm,•2049 represents a carbon emission factor (kg/MW) of the electrical product system caused by the new installation, operation, and maintenance in the year 2049,EFm,•2019 is an electrical power system capacity (MW) installed and survived by the base year 2019,SP, •2019 represents a carbon emission factor (kg/MW) of the electrical power system capacity installed, operated, maintained, and survived by the base year 2019,EFo,•2049 represents the remaining quantity of carbon emissions (kg/MW) from retired and recycled electrical product systems in the year 2049, andRR,•2049 represents a remaining of the substituted recycling coefficient/the residual carbon emission fraction from the electrical power systems retired in the year 2049.RC,Where:2049 data have been computed from the available and assumed data using The Qm,•2049 represents the newly added electrical power system capacity (MW) in the year 2049,N,•2049 represents the filling quantity of a carbon emission per unit of added electrical power system capacity (kg/MW) in the year 2049, andA•2049 represents the ratio of the carbon emission substituted into the newly added electrical power system in the year 2049.SA,Where:2049 data have also been computed from the available and assumed data using •2049 represents the ratio of a carbon emission remaining in the retired electrical power system,PR,•2048 represents the quantity of carbon emitted in the newly added electrical power (generation and transmission) systems capacity (kg/MW) in the year 2048, andQm,•2048 is the retirement fraction of the newly added electrical power system in the year 2048.NR,The RR,The respective ethical operation guidelines, and procedures, were considered during the research and publication process This work was supported by the African Centre of Excellence in Energy for Sustainable Development through the World Bank's African Centre of Excellence II Project.Enock Chambile: Conceptualization, Methodology, Investigation, Formal analysis, Data curation, Funding acquisition, Writing – original draft. Nelson Ijumba: Supervision, Writing – review & editing, Validation. Burnet Mkandawire: Supervision, Writing – review & editing, Validation. Jean de Dieu Hakizimana: Supervision, Validation, Project administration.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.