Non-communicable diseases (NCDs) represent the leading cause of mortality and disability worldwide. Robust evidence has demonstrated that modifiable lifestyle factors such as unhealthy diet, smoking, alcohol consumption and physical inactivity are the primary causes of NCDs. Although a series of guidelines for the management of NCDs have been published in China, these guidelines mainly focus on clinical practice targeting clinicians rather than the general population, and the evidence for NCD prevention based on modifiable lifestyle factors has been disorganized. Therefore, comprehensive and evidence-based guidance for the risk management of major NCDs for the general Chinese population is urgently needed. To achieve this overarching aim, we plan to develop a series of expert consensuses covering 15 major NCDs on health risk management for the general Chinese population. The objectives of these consensuses are (1) to identify and recommend suitable risk assessment methods for the Chinese population; and (2) to make recommendations for the prevention of major NCDs by integrating the current best evidence and experts’ opinions.For each expert consensus, we will establish a consensus working group comprising 40–50 members. Consensus questions will be formulated by integrating literature reviews, expert opinions, and an online survey. Systematic reviews will be considered as the primary evidence sources. We will conduct new systematic reviews if there are no eligible systematic reviews, the methodological quality is low, or the existing systematic reviews have been published for more than 3 years. We will evaluate the quality of evidence and make recommendations according to the GRADE approach. The consensuses will be reported according to the Reporting Items for Practice Guidelines in Healthcare (RIGHT). In 2019, NCDs were responsible for 74% of all deaths and 63.8% of disability-adjusted life years (DALYs) worldwide  to identify and recommend suitable risk assessment methods for the Chinese population; and (2) to make recommendations for the prevention of major NCDs by integrating the current best evidence and experts’ opinions.2.This series of expert consensuses will be developed by the Chinese Health Risk Management Collaborative (CHRIMAC), which is an academic cooperative group of medical specialists with common interests in health risk assessment and prevention. CHRIMAC now includes over 80 members from epidemiology, healthcare management, clinical medicine, nutriology, and family medicine from 35 well-known medical institutions such as the affiliated hospitals of Sun Yat-sen University, Fudan University, The Chinese University of Hong Kong, Hong Kong University, Lanzhou University, etc. The inclusion of these medical institutions does not adopt a randomized approach, but is based on convenience – there is already a good foundation for cooperation among medical institutions. CHRIMAC will dynamically include experts from multiple disciplines in the future to develop the CHRIMAC expert consensus series. CHRIMAC is planning to develop consensuses covering major NCDs. In the first stage, we will focus on 15 diseases, including stroke, ischemic heart disease, diabetes mellitus, dementia, chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), osteoporosis, lung cancer, breast cancer, gastric cancer, colorectal cancer, oesophageal cancer, liver cancer, pancreatic cancer, and cholelithiasis. The selection of these 15 diseases is mainly based on expert discussion. Three aspects were considered during the expert discussion (1) whether the disease is common; (2) whether the disease is preventable; and (3) whether the included medical institutions have an advantage in preventing the disease. Because the methods for developing these consensuses are similar, we will not publish separate protocols for individual NCDs.The overall methodology and process of the expert consensuses will be guided by the WHO handbook for guideline development (2014 edition) and the Chinese Guidance for Development/Updating Clinical Practice Guidelines 2022 edition) , 22. Eac edition The consensuses will be applied to hospitals at all levels, community healthcare centers, health management centers , centers for disease control and prevention, and other healthcare institutions. The target audience of these consensuses is the general population in all regions of China, especially adults at high risk of major NCDs.2.1.The consensus working group will consist of the steering committee, consensus panel, evidence review team, external review group, and secretary group. All working group members will complete the conflict-of-interest disclosure form, update the conflict-of-interest situation promptly during the consensus development process, and release the disclosure form when the consensus is published.2.1.1.The steering committee will consist of 4–5 leading experts on the specific NCD and guideline methodologists. The primary responsibilities of the committee are to (1) determine the theme and scope of the consensuses; (2) establish other working groups and manage their conflicts of interest; (3) approve the consensus proposal; (4) supervise the consensus development process; (5) approve the recommendation statements and the full text of the consensuses; and (6) monitor and evaluate the implementation of the consensuses.2.1.2.The consensus panel will be comprised of 20–30 experts, with one chairman and 1–2 vice-chairman. The experts should be representative in terms of region and specialty . The panel will include 3–4 economists, patient representatives, and public representatives to balance cost-effectiveness and social justice. The primary responsibilities of the consensus panel are to (1) determine the final consensus questions; and (2) determine the strength of the recommendation statements.2.1.3.The evidence review team will include 10–15 master/PhD students or research assistants with systematic training in Evidence-Based Medicine. They will work collaboratively in coordination and management of consensus development, searching for evidence, evaluating and synthesizing evidence, and producing GRADE grids. The secretary group will be responsible for arranging and recording all work, liaising and communicating with consensus experts and addressing other matters which are not covered by other working groups. The leader of the evidence review team will also be the primary coordinator of this consensus.2.1.4.The external review group will include 5–8 experts in the related field who are not involved in the development of the consensuses. They will review and comment on the first draft of the consensuses. To increase the readability of the consensuses for the general population, we will invite 3–5 people with various occupation backgrounds and education levels to review the full text before publication.2.2.Consensus questions will be initially proposed by the steering committee based on their expertise, literature review, and 1–2 rounds of internal discussions. Then, an online questionnaire survey of 100–200 clinicians, healthcare managers and community health workers across China will be carried out to vote on the importance of consensus questions and collect additional consensus questions. Subsequently, the consensus panel will vote on the final questions through a consensus process of iterative discussions with all members of the consensus panel. For each candidate question, the importance will be graded from 1  to 7 points . A question will be included if >75% of the participants vote 6 or 7 points for importance.2.3.For consensus questions, the evidence review team will first search for relevant consensus guidelines and systematic reviews in PubMed, EMBASE, Cochrane Library, Wanfang, and CNKI. The search will not stop being updated until 6 months before the official publication of the consensuses. We will also search clinical guidelines websites, including Medlive, National Guideline Clearinghouse (NGC), Guideline International Network (GIN) and World Health Organization (WHO), for relevant guidelines/consensuses. Web search engines such as Google Scholar will be considered as additional sources of evidence.2.4.We will consider systematic reviews and meta-analyses as the primary evidence sources for each consensus question. The evidence review team will conduct new systematic reviews/meta-analyses if (1) there is no eligible systematic review or meta-analysis; (2) the methodological quality of existing systematic reviews or meta-analyses is low; and (3) the existing systematic reviews or meta-analyses have been published for more than 3 years.The evidence review team will carry out rapid systematic reviews according to the Cochrane Handbook for Systematic Reviews of Interventions . Briefly2.5.For each consensus question, the quality of evidence will be evaluated based on the combined effects of systematic reviews or meta-analyses. According to the GRADE approach , 26, the2.6.The steering committee, with assistance from the evidence review team, will discuss and make one or more preliminary recommendation statements for each consensus question. Then, the consensus panel will vote for the strength of the preliminary recommendation statements by Delphi methods. The preliminary recommendation statements, the evidence profile and other materials will be sent to the consensus group 1–2 weeks before the consensus meeting. The consensus experts will vote for the strength of the recommendations by considering four domains, namely estimates of effect for desirable and undesirable outcomes of interest, confidence in the estimates of effect, estimates of values and preferences, and resource use . The vot2.7.The consensus will be reported based on the Reporting Items for Practice Guidelines in Healthcare (RIGHT) . The ini2.8.The consensus will be updated and revised every 3 years in order to (1) address controversial content; (2) incorporate the latest evidence into the consensus; and (3) make adjustments to the recommendation statements based on the development of the specialty.2.9.This is a protocol for a series of expert consensuses, and patient and public involvement is not needed for the protocol.3.This is a protocol for the development of a series of expert consensuses, which will be used to establish comprehensive and evidence-based guidance for the risk management of 15 major NCDs in the Chinese population. Although China has already published several guidelines, these guidelines are mainly utilized in clinical settings and cannot satisfy the health demand of the general public. Additionally, the evidence for NCD prevention based on modifiable lifestyle factors in existing guidelines has still been disorganized. This series of expert consensuses can address the two problems.Considering methodological aspects, this series of expert consensuses will incorporate specialists from multiple disciplines, including epidemiology, healthcare management, clinical medicine, nutriology, and family medicine, etc. Three significant strengths of the expert consensuses can be highlighted. First, under the guidance of the methodologists, each expert consensus will apply a comprehensive search strategy covering five electronic databases, four clinical guidelines websites and Google Scholar. Second, the latest systematic reviews and meta-analyses will be considered as the primary source of evidence. Third, recommendations will be made by integrating the current best evidence and experts’ opinions using the GRADE approach. Unfortunately, it is expected that most recommendations will be made based on observational studies, which will be the main limitation of our expert consensuses.JY and KY conceived and initiated this study. DW and JY drafted and finalized the content of the protocol. KY, XW, and YH provided methodological support for consensus development. QH, BX, JZ, WC, SS, FH, JL, YZ, ZR, XL, XW, YH, YT, FW, HZ, HJ, JH, WM, and MB critically revised the manuscript for important intellectual content and will provide their opinions in specific consensus based on their area of expertise. All authors contributed to the article and approved the submitted version.


In 2021, the Adolescents 360 (A360) project pursued a human-centered design (HCD) process to layer complementary economic empowerment components on top of its existing sexual and reproductive health (SRH) interventions targeting adolescent girls aged 15 to 19. Given the volume of evidence informing successful approaches for improving economic and empowerment outcomes for adolescents, we pursued an intentionally evidence-informed and gender-intentional design process, while trying to also respond directly to user insights. In this open letter, we share how we utilized and validated the evidence-base while applying the core tenets of HCD (empathy and user insights) to design holistic, layered programming for girls. We describe three overarching categories which depict how we used the existing evidence and new user insights to strengthen our design process. Often the evidence base allowed us to expedite finding a solution that worked for our users. However, at times there was a disconnect between what we knew worked in the evidence base and what our users said they wanted. New insights also allowed us to build a greater understanding of our users’ lived experiences where there were existing evidence gaps. We were aided by the engagement of a technical partner, BRAC, who synthesized evidence for our design teams and functioned as an ‘on demand’ support mechanism as questions and challenges arose. Yet, the volume of information to absorb almost guaranteed that we would miss out on the opportunity to apply certain evidence-based practices. We encourage researchers to consider how to make evidence more easily digestible to practitioners and for the whole community of practice to work together to identify what questions need to be asked to effectively operationalize evidence in a local context. The views expressed in this article are those of the authors. Publication in Gates Open Research does not imply endorsement by the Gates Foundation.. Adolescence is a critical moment for intervention, as it is a period that establishes future behaviors and patterns and an important window before discriminatory gender norms are fully entrenched. Adolescents require age-appropriate information, opportunities to develop key life skills, and essential health services in a safe and supportive environment to grow, develop, and pursue healthy futures. Increasing access to tailored, adolescent-focused services and expanding opportunities for adolescents to engage in the design and delivery of interventions related to their own health are critical components of a rights-based approach to adolescent sexual and reproductive health (ASRH) programming. Yet, the specific needs of adolescent girls are often neglected or underemphasized in global, regional, and national-level priorities.Adolescent girls represent 16% of all women of reproductive age (15–49). Lack of sexual and reproductive health (SRH) knowledge and access to comprehensive SRH services, and cultural norms that promote early childbearing contribute to high rates of unplanned pregnancy among adolescents. Adolescents aged 15–19 have a low contraceptive prevalence rate (CPR), estimated to be around 10.2% and have double the unmet need of all women of reproductive age (43% vs. 24%). Simultaneously, discriminatory gender norms and patriarchal structures limit adolescent girls’ ability to achieve economic well-being. These barriers are built-in from an early age and constrain the extent to which girls can gain the skills and experiences necessary to pursue improved economic outcomes and economic autonomy. As adults, women are less likely to participate in the paid labor force compared to men and are more likely to be unemployed and over-represented in informal and vulnerable employment sectors.As girls transition into young women, they face many barriers including school dropout, child marriage, early pregnancy, physical and mental health problems, and gender-based violence. There is increasing interest from the broad community of practice  in addressing adolescent girls’ needs through programming that combines SRH with age-appropriate economic empowerment. For adult women, evidence suggests that reproductive health improvements can lead to improvements in economic empowerment. Yet, for adolescents, the evidence on the interplay between economic empowerment and SRH is more complex. There is some information, albeit limited, on successful programmatic approaches that integrate components of SRH into economic programming for adolescents. Some evidence also shows that interventions which have sought to prevent early and forced marriage, as well as early childbearing, have had significant impact on the economic empowerment of adolescent girls and young women (AGYW). Yet other research demonstrates diluted effects when combining SRH and economic empowerment components in programming for adolescent girls. Overall, there is a growing body of evidence on the types of interventions which demonstrate significant and meaningful impact on adolescent girls’ economic empowerment.There is a growing evidence base demonstrating adolescent girls’ need for a holistic package of services that can offer reproductive health information and services, build their agency, and establish a positive enabling environment for them to pursue their life goalsSmart Start in Ethiopia,Kuwa Mjanja in Tanzania,Matasa Matan Arewa (MMA) in northern Nigeria, and9ja Girls in southern Nigeria.In 2016, Population Services International (PSI) and its consortium of partners launched Adolescents 360 (A360) with funding from the Bill & Melinda Gates Foundation (BMGF) and the Children’s Investment Fund Foundation (CIFF). A360 was a 4.5-year project working directly with young people to design and deliver interventions that increase demand for, and voluntary uptake of, modern contraception among adolescent girls aged 15 to 19 years. A360 designed and implemented four interventions across three countries –In late 2020, A360 received funding to continue implementation for an additional five years under a follow-on project, A360 Amplify. The strategic priorities for this follow-on include 1) adaptation to strengthen our SRH interventions and to create proof of concept for holistic user-centered intervention components, 2) pursuit of sustainability for our ASRH interventions through institutionalization and scale within government systems, and 3) contribution to filling gaps in the local, regional, and global evidence base through high-quality research and learning activities.Our user insights indicate that resonance of our interventions in the initial project investment was dependent on offering more than contraceptive counseling and services. By including a life and/or vocational skills and livelihoods demonstration or training (VSLT) component in three out of four interventions , the project responded to what girls said they needed to secure a stable future for themselves. These components made the program feel relevant to girls, helped us to establish the relevance of contraception for girls’ lives, and fostered the approval of girls’ key influencers. However, girls had high expectations for these skills components and for some the reality fell short of their expectations, with girls stating that they needed the opportunity to learn more diverse, marketable skills and to receive additional support to apply these skills for improved income generation.“The mentor came to our compound to invite us, she told us that we will be learning about how to take care of our family, about nutrition, FP but what got me interested was that she said at the end, we will learn a skill.…Hearing that … I became so interested.” – Girl, Nasarawa State; A360 Process Evaluation Nigeria, 2019, Itad“They should be teaching us a variety of skills at a time because parents do stop their girls from participating once they discovered that they are only teaching them just one thing for a long time.” – Girl, Ogun State; A360 Participatory Action Research Nigeria, 2019, ItadThis learning clearly demonstrated the value of strengthening these program components to provide a more substantive economic empowerment offering to girls. As a result, in 2020 and 2021, we pursued a human-centered design (HCD) process to layer economic empowerment components onto our existing SRH interventions across all four program geographies. Given the volume of evidence informing successful approaches for improving economic outcomes for adolescents and increasing their empowerment more broadly, we pursued an intentionally evidence-informed and gender-intentional design process, while trying to also respond directly to user insights, maintaining our ‘girl-centered’ approach. In this open letter, we describe our experience cultivating this balance – how we utilized and validated the evidence-base while applying the core tenets of HCD (empathy and user insights) to design holistic, layered programming for girls.Across all geographies, the objective of the design process was to adapt the existing SRH interventions to offer participating girls the opportunity to further identify and progress towards their economic goals. As part of our intentional pursuit of gender transformative programming, we aimed to design age-appropriate program adaptations that not only supported girls to gain additional income, savings, and/or assets but did so in a way that built their self-efficacy and economic autonomy. Given the growing evidence around multi-component approaches that pursue both SRH and economic outcomes, we also wanted to understand how, if at all, these more intensive and intentional economic empowerment components would influence contraceptive uptake and continuation among participating adolescent girls.The HCD timeline and process was similar across geographies, with some notable differences. We followed the same three overarching design phases as we pursued in our formative design phase for A360’s SRH interventions in 2016 – insight gathering, rough prototyping, and live prototyping. Within each of these phases, potential program participants and other key stakeholders who might interact with the final intervention – such as mothers or husbands – were invited to participate in the testing and give feedback on the evolving concepts. To ensure we included youth perspectives and to help “bridge” the gap between adult researchers and adolescent girl participants, 18–24-year-olds were hired and trained as Youth Innovation Officers (Nigeria / Tanzania) or Young Designers (Ethiopia). These young people participated as full members of the design teams, leading research conversations and prototype testing in the field.Maverick Collective philanthropists. However, in Ethiopia we also had a more intentionally limited engagement from IDEO.org and as a result our design process converged with that of Nigeria and Tanzania in July 2021 during live prototyping. Across all design phases, we engaged 679 adolescent girls  along with 551 other stakeholders   . Quotes . Their participation in the HCD process was crucial, sharing best practices and evidence that responded to identified needs of adolescents and compiling literature to help guide inquiries that arose in the design process. As the design process evolved, the need for additions to existing A360 curricula content and follow-on support for economic empowerment outcomes became evident. BRAC then engaged in integrating selected ELA content into the A360 curriculum and training staff on its usage. BRAC continued to provide support to our teams as the pilot launched in 2022. In acknowledgment that economic empowerment programming is not one of PSI’s core technical competencies, throughout the design process, A360 collaborated with BRAC as a conduit to the global evidence base around girls’ economic empowerment. Their technical assistance role, beginning in 2021, included reviews of all design materials, rapid literature summaries, and development of skills or competency-based curriculum, drawing from their evidence-based Empowerment and Livelihoods for Adolescents (ELA) ModelKore Global provided technical assistance to pursue a gender-intentional design. With IDEO.org they co-developed a gender in design toolkit to guide the process and ensure the resulting program designs were gender responsive.The result of the design process is interventions that are informed by the evidence and directly responsive to our users’ lived experiences. While each program aims to achieve the same outcomes, namely increases in girls’ income, savings, and assets, and improved economic autonomy, the specific pathways differ by geography. All programs begin with their respective SRH intervention. Girls are then offered the chance to continue to participate in a more intensive economic empowerment program.Smart Steps  all members achieve 80% attendance in the initial period; b) the group has saved a minimum amount; and c) they have complied with their constitution and maintained proper bookkeeping. If the group meets these criteria, they are eligible to have their total savings matched at 150%. This money is transferred to the group as a whole and is then available as part of the loan pool.In Ethiopia, girls are brought into the economic empowerment program,t Steps , through couple . Girls aMMA+ and9ja Girls+ respectively, is a scaffolded package of soft, business, and vocational skills training combined with mentorship and coaching  or apprenticeships (southern Nigeria). Following the skills trainings, girls are then givenmentorship support to develop and execute a business plan. Their participation culminates in a large, public graduation that doubles as a marketplace for girls to display the products and services from their newly gained skills. This is a chance for the community to show public support for the program and for girls to show to their husbands or parents the value of what they have learned through their participation. The program models in southern and northern Nigeria, although serving different girls, are overall very similar.In both northern and southern Nigeria, the heart of the economic empowerment programs,oaching . Communi, Kishua Academy, provides a similar scaffolded skills-building experience as in Nigeria but incorporates additional elements of peer mentorship and partnership with TVET institutes  to apply for loans to grow their businesses through the local government-run youth development funding program. There is a moment post-graduation for thecommunity to gather to celebrate girls for their accomplishment and participation in the program.In Tanzania, the economic empowerment programtitutes . Girls aIn Nigeria and Ethiopia, work moved forward post-design into pilot, allowing for additional refinement, while work in Tanzania ended after live prototyping and no additional refinement was conducted.Across the design phases, we used the evidence base to inform and contextualize our design process and findings. In doing so we discovered nuance in how what we know from the evidence base corresponded with the insights we were drawing directly from our program users. We have described three overarching categories which depict how we used the existing evidence and new user insights to strengthen our design process. Though we describe these categories separately, in practice there was often overlap.1. The evidence base allowed us to expedite finding a solution that worked for our users. We prioritized practices that had specific evidence with adolescent populations to build prototypes that could be trialed within our geographies. In the early phases, we intentionally designed inquiry tools and rough prototypes to validate key elements of the evidence base. By speaking directly with adolescent girls and their influencers, we could confirm that they felt these elements were important and obtain additional details on how girls wanted to experience them in practice  group-based with opportunities to build solidarity and peer trust; b) mentor-led, particularly by mentors who understand the community context; c) combining vocational training, and business and soft skills development; d) introducing concepts around gender and power to shift girls’ critical consciousness; and e) inclusive of follow up after the initial training, such as through mentorship or coachingponents .Mining existing evidence-based practice provided value not just in insight gathering and initial prototype building, but also moving into the latter design phases  when we needed to build out detailed systems maps. When the design team identified a barrier that needed to be overcome to promote program effectiveness, we first consulted the evidence base to understand if there were existing practices that could be adopted to fill gaps in the proposed program design or strategy.. We recognized that, unlike our SRH interventions, there was not likely to be one partner or government ministry that would have the capacity to wholesale adopt these designs given the cross-sectoral nature of these interventions. Additionally, there are limited resources within ministries to take up these solutions as they are necessarily holistic and need to be delivered with integrity, making them time-intensive and requiring collaboration across multiple stakeholders. This informed our landscaping of potential pathways to scale during live prototyping and helped us focus on understanding which actors were best placed for what during the scale-up process.For example, in line with the broader project objectives to promote sustainability for our program interventions, we wanted to explore pathways to sustainable scale. We examined the evidence base on scaling economic empowerment programs for AGYW and identified key lessons. We learned that good practice required a locally grounded approach with more than one scale pathway, responding to local contexts and generating local ownership.As another example, in live prototyping in Ethiopia we noted that though girls showed interest in participating in savings and loans groups, they felt limited by their small savings pool, which constrained the amount of the loans available. This was affecting program attendance and meant girls were missing out on critical soft-skills training sessions. Working with BRAC, we learned about ways other organizations had managed similar challenges. After exploring the options and weighing them against our program priorities, we decided to institute group-level matching grants which groups were eligible to receive contingent on consistent savings and attendance. This was based on an approach successfully implemented by a BRAC partner in Rwanda2. At times there was a disconnect between what we knew worked in the evidence base and what our users said they wanted.Not all attempts to test existing promising practices with our users elicited positive reactions. This is to be expected – adolescent populations are not homogenous, and resonance of these program components is likely to vary across geographic contexts and specific adolescent sub-populations . However, a challenge in HCD can be that users may prioritize what is known or comfortable. If insight gathering and prototyping are not done well, this can lead to users reporting a preference for, at best, the status quo, and worst, harmful traditional practices, as they are the norm. In this instance, having the evidence-base in mind encouraged us to persist in pursuing promising practices and continue learning to understand the barriers that underlay resistance to what the evidence says works. In doing so, we better understood how to effectively apply the evidence base .3. New insights allowed us to build a greater understanding of our users’ lived experiences where there were existing gaps in the evidence baseThe evidence on promising practices for girls’ economic empowerment, though growing, is not exhaustive. In conducting our insight-gathering phase, we were able to uncover additional detail on the lived experiences of our program users that did not feature prominently in the evidence base. While the overall themes of the insights drawn from the design process are not new, the context-specific nuances were important for us in program development and can be valuable contributions to the existing body of evidence.Increasing resilience through a diversity of skillsIn the evidence base we saw that most programs focused on technical skills paired with some business or soft skills. Yet, our research demonstrated an enormous appetite by girls to learn a diverse set of skills that could provide them with a competitive advantage. Girls did not want one-dimensional training; they were eager for continuous upskilling that would allow them to weather shifts in the market and other situational factors, such as the impacts of climate shocks or conflict. They were eager to learn skills that could be layered together for greater profit, such as hairdressing and make-up or poultry rearing and fish farming. Best practice and research, in our exploration of the literature, did not address the need for young female entrepreneurs to have a set of skills that could allow them to adapt to seasons and trends to ensure continuous income throughout the year and in a longer-term time horizon. Designing a skills curriculum around this type of ‘resilience’ could also become even more critical as the impacts of climate change are felt more acutely within these communities.“I don’t want to learn about soap-making only.” – Girl, Tanzania“If we have a lot of businesses in our group…the clients will have a lot of choice to choose what they want.” – Girl, Tanzania“I want to own my own business in the future.I would like to own a hairdressing / mani-pedi business. Make-up will give me the most income…I’ll learn all the skills around make-up, pedicure, and manicure so I can have my own place.” – Girl, Ogun State, Nigeria (currently working as a make-up artist)Navigating business choices and market access for girls in conservative settingsIn certain geographies our design research uncovered greater specificity in the restrictions faced by married adolescent girls in conservative contexts that influence the ways in which they can enter and participate in the market. In northern Nigeria especially, where mixing between the sexes is restricted, girls were often severely limited in options for income-generating activities. In Ethiopia, although there is more interaction between the sexes, the result is much the same, as traditional gender roles mean that girls must be at home to take care of children. Yet, girls demonstrated incredible entrepreneurialism in the face of those restrictions. In Nigeria, girls participated in women-only markets on dedicated days or worked out of their home and relied on husbands or brothers to sell their products. In Ethiopia, girls focused on home-based income-generation activities (such as poultry rearing) or negotiated with extended family members to shift childcare responsibilities. These insights point to how adolescent girls, and women in general, can be successful in income generating activities in conservative settings. Nonetheless, the social practice of sex-based restrictions  has a significant impact on entrepreneurship opportunities and the ways these girls must navigate business. This uncovered a need for further research and best practices on how women can work within these existing restrictions even while systems and norm change are in process.“Women run their businesses at home and there is a market just for women (on Thursdays) where they trade and shop.” – Girl, Kaduna state, Nigeria"So far, we don't support each other. I work on the farm, she works at home. Maybe going forward we can help each other." – Husband of an adolescent girl, Ethiopia, “Most women are not into shoe making and in the whole of [LGA name] only two men are into shoe making…Yes, my husband would let me do it, but he won’t let me open a shop, so I would have to do it at home.” – Girl, Kaduna state, NigeriaLow trust in institutional support structuresWhile we expected to find some frustration or disappointment with prior financial inclusion initiatives that had ended or failed to provide the promised impact, the level of mistrust was greater than we anticipated. We were struck by the broad-based level of mistrust expressed by participants stemming from their interaction across non-governmental, governmental, and formal financial institutions. Users pointed to the failures of past NGO projects to promote lasting outcomes. Mistrust of government-run programs often stemmed from corruption, burdensome bureaucracy, or poor management that limited the funds available for community services. Some users, however, reported greater trust in government loan programs, as rates were generally considered favorable. This contrasts sharply with opinions about microfinance institutions. Across geographies, participants shared negative experiences about high interest rates that made loans difficult, if not impossible, to repay.These negative perceptions raise questions about how NGOs should be interacting with institutional structures to address persistent gaps and promote sustained change. Leveraging existing systems generally presents the greatest avenue for sustainability. However, given existing mistrust and structural deficiencies we question the feasibility of this without significant structural change. Our insights point to a need for the organizations promoting economic empowerment, especially for marginalized groups, to move beyond understanding these barriers to intentionally designing and implementing programming that pursues strengthening of financial institutions in a way which is sustainable and promotes community trust."LAPO [microfinance institution] are killers." – Mother of adolescent girl, Ogun state, Nigeria"I would not be interested [in government loans]. I do not have a reason, but the government are not useful, fair, and I would not want to use them." – Girl, Ogun state, NigeriaVariations in desired and required dosage for achieving economic empowermentAcross documented skill-building programming for adolescent girls, the topics covered, and time dedicated, differed, from a week to over a year long. The research on the appropriate dosage needed to achieve positive outcomes is limited. This leaves organizations to make their best guess about an appropriate timeline and to let budgetary limitations drive decision-making. Dosage is complicated by disparate needs across sub-populations of adolescents. We saw this across our own geographies in how insights led to differences in dosage – in northern Nigeria, our program provided 6–8 hours of SRH and soft skills sessions and 15–20 hours of economic empowerment training including soft and hard skills over the course of 12 weeks. While in Ethiopia, participants met for one and a half hours per week over the course of approximately 30 weeks. We struggled to balance the time girls needed to absorb skills and new information against the other demands on their time. Married girls were busy managing their household and caring for children. Younger unmarried girls were attending school and had a full load of chores at home, and older unmarried girls might already be involved in a basic income generation activity. In cases where girls were unable to leave home due to pregnancy or childbirth, we provided make up sessions to participants. Despite initial resistance mentioned previously to participate in soft skills training, attendance across geographies for these skills sessions was high, demonstrating that localized solutions with attention to the varying needs of different target populations are critical. These insights also point to the value in providing alternative learning pathways for individuals when they encounter challenges in attending regular group meetings for periods of time.Leveraging joint goal setting and crafting long term engagement plans for girls’ influencersWhile the evidence base is clear on the importance of engaging married girls’ husbands to support their participation in economic empowerment activities, there are fewer evidence-based strategies on how to do so effectively. In Ethiopia, where our SRH approach already targets couples, we used an extended goal-setting session to try and build this support. During the session, which included a facilitated conversation between the couple, they identified their long-term goals and how they would each contribute. Using a model couple, we demonstrated how goals could be reached sooner if both the husband and the wife participated in income generation. We took care to note the non-income-generating activities often falling on women (such as childcare or food preparation) that also contribute to the success of the household. At the end of the session, husbands were introduced to the economic empowerment program and asked to support their wife’s attendance. Both husbands and wives responded positively to these sessions, suggesting the value of harnessing shared goal setting and in making explicit the benefits of multiple earners. While this was a positive start, additional contact with husbands was needed. Some husbands required multiple visits from program facilitators to reinforce the importance of their wife’s attendance at weekly association meetings. In addition, it is essential to be clear what participants would and would not receive for participation. Some husbands expected that their wives would receive a cash transfer for participation and grew frustrated when that was not the case. Again, this required additional communication from program facilitators with husbands to resolve. On the other hand, we also saw some husbands who were very supportive of their wife’s participation, as demonstrated through attending sessions to contribute weekly savings if she was unable to attend.. The translation of evidence was exacerbated by the differences between the macro-economic contexts in which we are implementing. For example, a lack of vocational training centers or high levels of unemployment limit the opportunities available and what proven interventions may even be plausible. Additionally, as an organization focused on improving health and not economic outcomes, we were at a disadvantage. We know that girls need – and ask for – multi-sectoral solutions. In the absence of well-established collaboration across sectors, this may require organizations to pursue design and implementation of programs outside their existing wheelhouse.This open letter describes the complexity we encountered while trying to design with responsiveness to the existing evidence and to users’ desires and needs. A challenge we faced was that the evidence for economic empowerment among adolescent girls was not easily translatable to program design. First, the volume of evidence around economic empowerment programs for adolescents often seemed overwhelming. Second, the evidence base has significant gaps in research and practice around girls’ economic empowerment, particularly marginalized communitiesWe found that the HCD process helped us to translate the evidence and make it more easily usable to program designers. For example, as noted above, the insight gathering and prototyping processes allowed us to validate existing insights from the evidence base and hear more from girls about what they wanted to see in practice, for instance the need to help girls get more specific with their goal setting or help them to see the value of soft skills classes. The HCD process also allowed us to fill in gaps in the existing evidence base and supported us to adopt user-generated solutions, such as the need to offer multiple vocational skills to help girls stay competitive.Our economic strengthening technical partner also provided invaluable feedback and allowed our teams to rapidly expand their technical capacity in this new program area. We adopted two approaches to reduce the burden on teams to absorb too much information at once. The first was that the economic empowerment partner took on the role of synthesizing large volumes of information. Rather than share journal articles or large reviews, the partner developed presentations on key topics that lasted approximately an hour and allowed time for discussion. The second was to have an “on-demand” support mechanism as questions or challenges arose. Given the vast amount of information available, much of which might be irrelevant depending on the program model chosen, it did not feel efficient to try and proactively understand evidence around potential future challenges. It was important to provide design team members, especially those based in implementation geographies, the right information at the right time. In this way having a technical assistance approach which was demand-based allowed us to request detailed information on a specific challenge as it arose and focus our energies on understanding and applying the evidence. Nonetheless, we believe it would be better to have technical expertise fully embedded within the design team to support in the identification of gap areas as they arose, as a less experienced implementor may not always be able to recognize known gaps or program weaknesses.Though we instituted many ‘layers’ of technical support to promote translation and application of the evidence, we know that despite our best intentions there were pieces of evidence that we missed the opportunity to apply because we didn’t have the bandwidth to digest such a substantive body of knowledge. The volume of information to absorb almost guarantees that organizations will miss out on the opportunity to apply certain evidence-based practices. We encourage researchers to consider how to make evidence more easily digestible to practitioners and for the whole community of practice to work together to identify what questions need to be asked to effectively operationalize evidence in a local context. The letter explains clearly the importance of layering ASRH programs with economic empowerment opportunities. It also communicates well the complexity associated with this kind of programming and the challenges of applying both evidence-based practices and user-responsive strategies. The paper provides valuable information not only for ASRH and health program funders, designers and implementers, but also programs in other sectors that seek to address the intersectionality of social outcomes and economic opportunity and security. It delves deeper than most papers into specific and practical lessons of integrated program designs and the use of two best practices: being evidence-informed and generating and applying insights on program users’ lived experiences, especially among vulnerable and under-represented populations. The experiences/insights shared from this program will benefit ASRH programs seeking better and more sustained ASRH outcomes. The call for improving approaches to synthesizing evidence and making it accessible (and therefore useful) to program designers should be noted. An advantage of this paper beyond providing insights into programs that layer economic empowerment interventions into SRH is its focus on how the program design process took place. This paper offers practical insights into intervention design strategies that seek to optimize both human-centered and evidence-driven approaches without backing away from the challenge of working this way. Consultation with program users may be a standard practice. However, HCD introduces ways of working with people (youth in this case) that generates insights that may not be well reflected in published evidence. In the case of the four programs discussed, these user insights helped to tailor and refine evidence-driven health programs and strengthen intervention design. The layering of evidence, along with collaboration with economic empowerment experts, helped program designers find the right fit between interventions and a variety of youth program users across different countries, age groups, and life stages.    Tables 2 and 3 are particularly useful in illustrating how evidence and user insights can be complementary in program design. Where evidence provides a range of tested solutions , HCD helps to validate their relevance in specific program settings and populations, fill evidence gaps and streamline the prioritization of possible solutions. Where user insights did not line up fully with the published evidence, the HCD processes - user insights research and prototyping - helped to tailor interventions to the needs and desires of different users . The discord between evidence-based approaches and user insights was addressed through iteration and adaptation in the application of HCD. To further the application of this learning, it would be helpful if the authors could translate their learnings more explicitly for practitioners who are designing HCD-led interventions.Suggested minor revisions: While the focus on being evidence-informed is clear in the paper, the authors could explain more clearly how the design process was “gender-intentional.”It would help to reflect on the effectiveness of the balanced approach as well as its complexity. If there is any available evidence on the outcomes of any of the programs presented, it would be useful to mention it with the caveat that economic empowerment programs can take some time to produce results.Provide a brief explanation of what you mean by age-appropriate economic empowerment. Questions may arise around the a) legal age for employment in the three countries and b) legal and ethical considerations around work for 15 and 16-year-olds. It would be helpful to understand if this influenced project design or success.  Economic empowerment programs are gaining traction in ASRH programing. It would be valuable for this letter to recommend areas for further research to determine the influence of economic empowerment on ASRH programs.Using evidence during design phrases’ It should be ‘design phases’.P9 Header. There is a typo in ‘Does the article adequately reference differing views and opinions?YesAre all factual statements correct, and are statements and arguments made adequately supported by citations?YesIs the Open Letter written in accessible language?YesWhere applicable, are recommendations and next steps explained clearly for others to follow?PartlyIs the rationale for the Open Letter provided in sufficient detail?YesReviewer Expertise:NAWe confirm that we have read this submission and believe that we have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. This Open Letter describes Gates-funded project experience delivering SRH services to female adolescents in Sub-Saharan Africa (SSA) using gender transformative programming. The grantees used a human-centered design (HCD) process to solicit early feedback from stakeholders  on the participants' perceived needs and ideal modes of service delivery. Service providers incorporated this feedback into project design.Participants did not initially value SRH services and associated life skills training as much as the providers did based on international evidence. Participants wanted vocational skills training to help with income generation . They were more willing to participate in other trainings if they also got the vocational skills training.Participants mostly sought skills training in traditionally female fields, despite these not being the most lucrative.  Participants chose the "known and comfortable".  Engaging with stakeholders  at the outset was highly effective. In particular, engaging with husbands on joint goal setting proved effective. These insights are very valuable for practitioners, and clearly demonstrate the value of the HCD approach. While the cheapest design for an SRH project could be to simply provide the SRH services , if the target population does not demand these services and does not value them relative to vocational training, the cheapest design will be the least cost-effective. These findings help justify the use of more expensive but multi-faceted program design. They may also explain why many NGO- or donor-led programs for adolescent females do not scale into the public sector, where implementation silos dominate. Key findings included:   The practitioners' experience also highlighted the limits imposed by existing gender norms on the use of a gender transformative service provision model. The Letter also highlighted a known but undervalued result: that the success of life skills training is highly dependent on the quality of the mentor and the pedagogical methods.Statistics on female adolescents in SSA, not global statistics which are mostly meaningless in this context.A summary paragraph on what we know (evidence) about why adolescents in SSA have such a high rate of unmet contraception need compared with all women of reproductive age. This material would (i) set the scene for the program design, and (ii) help explain the findings. Ideally this discussion would go beyond the vague "discriminatory gender norms and patriarchal structures" since presumably these constrain all women, not just adolescents. Finally, although this Letter focused on practice, not causal evidence, some statistics on outcomes  would be helpful. Overall, the Letter is well written and presents the programming and results in clear writing and very helpful graphics. However, the introduction was less helpful and should be revised. A stronger introduction would include:Does the article adequately reference differing views and opinions?PartlyAre all factual statements correct, and are statements and arguments made adequately supported by citations?YesIs the Open Letter written in accessible language?YesWhere applicable, are recommendations and next steps explained clearly for others to follow?YesIs the rationale for the Open Letter provided in sufficient detail?YesReviewer Expertise:Youth Employment in Sub-Saharan Africa.I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. This is a very well researched and timely article and I congratulate the authors. Using HCD process to layer complementary economic empowerment components to existing SRH interventions is a very useful way to ensure sustainability of interventions and prevent high turnover of clients.  The manuscript would benefit further from additional insights/details on the following elements:  a) how does the layering of economic empowerment components to SRH interventions help navigate (positively or otherwise) the family/community dynamics and power relations associated with certain SRH interventions eg family planning; CSE etc;  b) do the retention rates improve for SRH components after the economic interventions stop;  c) Is there a "compromise" element to be factored in, i.e. do SRH interventions have to lowered in ambition for the package of SRH/economic empowerment to be accepted by clients and communities. For instance, does it preclude addressing certain SRH components over the others, e.g safe abortion; sexuality;  d) Did the study look into dimensions which should be factored in to ensure scale, i.e. how to you move this from boutique level to scale.  These are just some additional issues which would be useful for authors to address as they finalise the manuscript and develop next steps.Does the article adequately reference differing views and opinions?YesAre all factual statements correct, and are statements and arguments made adequately supported by citations?YesIs the Open Letter written in accessible language?YesWhere applicable, are recommendations and next steps explained clearly for others to follow?PartlyIs the rationale for the Open Letter provided in sufficient detail?YesReviewer Expertise:Gender equality, health eequity, SRHI confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.


Clinical Practice Guidelines (CPGs) development and implementation in the Kingdom of Saudi Arabia are suboptimal. The Kingdom’s Vision 2030 envisages a transformational change to achieve an effective, integrated, value-based ecosystem focused on patient health.This study aimed to develop a CPG appraisal tool that will support the realization of the Kingdom’s Vision 2030 through the development of high-quality and highly implementable CPGs. To maximize its impact, all vital healthcare paradigms, such as systems thinking, value-based healthcare, and information technology, will robustly be incorporated in the tool.The Saudi Health Council through its National Center of Evidence-Based Medicine (NCEBM) embarked on a program to develop this appraisal tool. A taskforce of experts was selected based on their experience in evidence-based practice and training. The task force, through a methodology of extensive literature review, deliberation, outside experts’ feedback, and Delphi and consensus voting, developed a prototype appraisal tool that was named the Holistic Appraisal Tool for CPGs (HAT-CPG).The HAT-CPG was developed comprising three sections: an initial basic information section, an internal validity section, and an external validity section with a total of 13 section items and 73 reporting elements.It is envisaged that the Holistic Appraisal Tool will support CPG developers and users in Saudi Arabia in realizing the objectives for which it was developed. Vision 2030, Saudi Arabia’s national growth and economic development strategy, calls for the country’s reliance on oil to be reduced, its economy to be diversified, and public service sectors such as health and education, as well as infrastructure, recreation, and tourism, to be strengthened. The Kingdom of Saudi Arabia’s (KSA) healthcare system is set to undergo major changes under Vision 2030. The healthcare transformation initiative seeks to “restructure the Saudi health sector in order to improve its status and capacities as an effective, integrated, value-based ecosystem focused on patient health.” These objectives will also be met by implementing new healthcare paradigms and promoting public health and disease prevention . To meetThe Kingdom’s current critical issues, including rising healthcare spending , an aginEvidence-based healthcare recommendations provided by well-developed clinical practice guidelines (CPGs) can benefit all stakeholders—from policymakers and healthcare workers to patients and healthy individuals. According to the Institute of Medicine, CPGs are statements that include recommendations based on a systematic review of evidence and an assessment of the benefits and drawbacks of alternative care options that are designed to optimize patient care . They coHealthcare practitioners in the United Kingdom follow CPGs developed and/or approved by the National Institute for Health and Care Excellence (NICE) or the Scottish Intercollegiate Guidelines Network (SIGN), while practitioners in Germany follow the Association of Scientific Medical Societies (AMWF), and those in Canada follow the International Centre for Evidence-Based Medicine Canada. No such national reference exists for health practitioners to follow in Saudi Arabia. Depending on where they were trained, healthcare practitioners in the KSA use a variety of CPGs. This variation in healthcare management has resulted in inconsistencies in the quality of healthcare for the country’s most prevalent and costly diseases such as diabetes, hypertension, and ischemic heart disease. Furthermore, due to factors such as lifestyle, culture, and religious values, these guidelines may not always address the appropriate care required for the Saudi community and residents.CPGs’ quality and implementation in the Gulf States and Saudi Arabia have been deficient . DespiteMore than 40 CPG appraisal tools have been developed to date to accelerate CPG development, credibility , and applicability  , 21. DesImplementation issues are caused by a variety of factors. Two factors contribute to this weakness in CPGs: trustworthiness (credibility) and implementation (applicability) –27. GuidThe Saudi Health Council (SHC) is a government organization authorized to coordinate all healthcare provider programs in Saudi Arabia. Its goal is to develop and implement healthcare service standards by managing and coordinating health communities’ programs. The SHC’s vision is to serve as a model for a world-class Saudi health system that improves the Saudi people’s health in a scalable, consistent, and responsible manner. The SHC has established the National Center for Evidence-Based Medicine (NCEBM), which is dedicated to developing evidence-based health practices. The center’s mission is to serve as the health system’s approved national reference center for knowledge and scientific evidence to support the development of more effective health practices.One of the NCEBM’s pioneering goals was to develop a CPG appraisal tool that outperformed current appraisal tools while being tailored to the needs of the Saudi population. More importantly, the new CPG appraisal tool was intended to advise and support CPG developers and users in the KSA by providing them with practical leverage tools critical to achieving the 2030 healthcare transformation initiative.Existing appraisal tools have been modified and reformed into the Holistic Appraisal Tool for Clinical Practice Guidelines (HAT-CPG), which examines the methodological rigor, transparency, and implementation actions required to develop a guideline.The HAT-CPG was created to increase the likelihood of CPGs being implemented successfully by drawing attention to issues that should be considered when appraising or developing guidelines. Two areas of focus were chosen. The first was a greater emphasis on implementation. The second was an innovative scoring system expected to improve the objectivity of this critical component. It is important to note that current CPG appraisal tool scoring systems and final scores, such as those obtained with the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool, have no bearing on the success or failure of a guideline and its implementation as they focus on the methodological quality of CPGs. The HAT-CPG’s internal and external validity sections include nine paradigms that characterize modern healthcare: evidence-based practice, quality-based practice (patient safety), competency-based training and certification, value-based healthcare, patient- and family-centeredness, high-reliability organization principles, health information technology, artificial intelligence, and sociocultural acceptance. Furthermore, the CPG appraisal assessment includes critical and appropriate dissemination, implementation, and monitoring tools relevant to these paradigms, which are intended to strategically enlighten and educate CPG developers and users about these tools, thereby promoting their incorporation and successful implementation in modern CPGs. Table The NCEBM is dedicated to developing evidence-based CPGs. To accomplish this, the newly developed HAT-CPG appraisal tool is expected to help advise and support CPG developers and users in the KSA. The HAT-CPG was created to draw attention to issues that should be considered when evaluating or developing CPGs. It aims to increase the likelihood of CPGs being implemented successfully. This will help standardize healthcare delivery and management across the KSA based on the Saudi population’s sociocultural needs. The launch of the NCEBM and the development of the HAT-CPG can help achieve three strategic goals: 1) establish a national standard for health practice by approving and implementing evidence-based CPGs; 2) improve the quality of health services and patient safety by strengthening evidence-based health practices; and 3) support digital transformation in the field of evidence-based medicine.


Sociology of quantification has spent relatively less energies investigating mathematical modelling than it has on other forms of quantification such as statistics, metrics, or algorithms based on artificial intelligence. Here we investigate whether concepts and approaches from mathematical modelling can provide sociology of quantification with nuanced tools to ensure the methodological soundness, normative adequacy and fairness of numbers. We suggest that methodological adequacy can be upheld by techniques in the field of sensitivity analysis, while normative adequacy and fairness are targeted by the different dimensions of sensitivity auditing. We also investigate in which ways modelling can inform other instances of quantification as to promote political agency. Historians, sociologists and politologists have studied how numbers are produced, used, trusted or feared in relation to different aspects of life, such as empowering systems of governance or control, promoting consumption or consensus, variously facilitating or complexifying human experience. Important contributions to this debate have also come from scholars of law and economics, expressing concern about risks from new numerical technologies and practices. This new attention to numbers, a true sociology of quantification, is an expanding field touching on many families where numbers are produced, from data science to algorithms, quantified self and indicators at various levels of aggregation Box .Some aspects less visited by these works are the science reproducibility crisis  and sensitivity auditing (SAUD), may be useful to other families of quantification. While SA complements an uncertainty analysis by identifying the inputs/structures that convey the most uncertainty to the model output  is an approach for the treatment of problems at the science-policy interface .Developing new measures, e.g., a new PPI in defence of the purchasing power of the poor.Identifying areas of exclusion and neglect of existing official statistics.Models embed the normative values and worldviews of their designers, and no model can serve all purposes and contexts. They need transparency and non-ritual forms participation  policies with preselected objectives. For Salais, this operates a reversal of the statistical pyramid, i.e., starting from the desired political objective to produce the desired system of measurement. In other words, it is a move from evidence-based policy to policy-based evidence aiming at demonstrating that the selected policies are successful.Sociologist of quantification Robert Salais  distinguQuantification thus plays an important role in the context of technocratic approaches to governance , as proposed by Amartya Sen . For SenModels for policy-making that retreat to being “theoretical” or “building blocks” when their unrealistic assumptions are criticised are known as “chameleon models”  is a valid starting point. It can be used via negativa, i.e., to demonstrate that there is simply not enough evidence to offer a measure, or that the measure is totally driven by untestable hypotheses rather than by available evidence.Due to the large use of mathematical models during the COVID-19 pandemic of 2020, problematic aspects of mathematical modelling have come to the fore. Models were praised by some for spurring action as well as vilified by others as promoters of ill-conceived policies.Results from models and other instances of quantification reflect the interests, disciplinary orientations and biases of their promoters, and this has become especially apparent with the pandemic. One cannot but take note of the “dramatic extent to which the people who did best during the pandemic resemble those who built the model”  literacy of citizens would solve our problems. Citizens are not the only subjects whose literacy needs to improve.Mathematical models, as statistical measures and indicators, can be an important tool of social discovery. Used instrumentally, i.e. to create an illusion of scientificity, models can make this discovery more arduousFollowing Dewey, the making of democracy is predicated on the existence of publics sharing commonly understood facts. Once the wall of numericized facts is built from above, citizens are cut out from meaningful and deliberative participation. Opposing such a trend needs bridges to be built across all sectors of society. If the “Informational basis of judgement in justice” is where the battle needs to be fought, meaning by this a focus on both the quality of numericized evidence and on its fairness, then an extended peer community involving both modellers and those interested in their use needs to be established. This process may not be entirely peaceful.


Biogenic amines (BAs) have been under study since the early 1970s ,3,4. ThiOne of the primary challenges with BAs is their analytical determination. The available and tested methods typically demand highly skilled personnel and sophisticated equipment. The European Food Safety Authority (EFSA) recommends an extraction technique coupled with high-performance liquid chromatography (HPLC) as the official method for quantifying BAs . HoweverIn recent years, high-resolution nuclear magnetic resonance (HR-NMR) has been employed to monitor changes during storage and is generally used as a predictive tool in various products . In addiBAs need to be thoroughly investigated, and despite the wealth of high-quality literature available, a cultural shift must occur, acknowledging that their presence in foods and beverages is inevitable. A stronger connection with health experts is encouraged to protect consumers or, at the very least, inform them of the potential effects of BAs. Even in this regard, we are at the forefront of exploration. Furthermore, innovative methods for evaluating BAs in food processing ,15,16,17All contributions are welcomed to support decision-making bodies and to encourage involved companies to prioritize BAs control as a quality assurance objective.


Background and Objectives: To assess the effects of fosfomycin compared with other antibiotics as a prophylaxis for urinary tract infections (UTIs) in men undergoing transrectal prostate biopsies. Materials and Methods: We searched multiple databases and trial registries without publication language or status restrictions until 4 January 2022. Parallel-group randomized controlled trials (RCTs) and non-randomized studies (NRS) were included. The primary outcomes were febrile UTI, afebrile UTI, and overall UTI. We used GRADE guidance to rate the certainty of evidence of RCTs and NRSs. The protocol was registered with PROSPERO (CRD42022302743). Results: We found data on five comparisons; however, this abstract focuses on the primary outcomes of the two most clinically relevant comparisons. Regarding fosfomycin versus fluoroquinolone, five RCTs and four NRSs with a one-month follow-up were included. Based on the RCT evidence, fosfomycin likely resulted in little to no difference in febrile UTIs compared with fluoroquinolone. This difference corresponded to four fewer febrile UTIs per 1000 patients. Fosfomycin likely resulted in little to no difference in afebrile UTIs compared with fluoroquinolone. This difference corresponded to 29 fewer afebrile UTIs per 1000 patients. Fosfomycin likely resulted in little to no difference in overall UTIs compared with fluoroquinolone. This difference corresponded to 35 fewer overall UTIs per 1000 patients. Regarding fosfomycin and fluoroquinolone combined versus fluoroquinolone, two NRSs with a one- to three-month follow-up were included. Based on the NRS evidence, fosfomycin and fluoroquinolone combined may result in little to no difference in febrile UTIs compared with fluoroquinolone. This difference corresponded to 16 fewer febrile UTIs per 1000 patients. Conclusions: Compared with fluoroquinolone, fosfomycin or fosfomycin and fluoroquinolone combined may have a similar prophylactic effect on UTIs after a transrectal prostate biopsy. Given the increasing fluoroquinolone resistance and its ease to use, fosfomycin may be a good option for antibiotic prophylaxis. A definitive diagnosis of prostate cancer depends on histopathological verification of adenocarcinoma in prostate biopsy cores. Therefore, a transrectal ultrasound-guided (TRUS) prostate biopsy has been the most common method for the past 30 years, although it can result in serious infections even in relatively healthy males. In addition, the hospitalization rate for sepsis after a TRUS prostate biopsy is about 3% ,2. Thus,Various methods have been used to reduce UTIs or infectious complications, including a pre-procedural enema, povidone iodine rectal preparation, rectal swab screening with targeted antibiotic prophylaxis ,4, switcEscherichia coli and extended-spectrum β-lactamase producing E. coli (ESBL) [Traditionally, fluoroquinolones (FQs) were recommended as the first choice for antibiotic prophylaxis. However, UTIs have been rising after prostate biopsies and are thought to be associated with the emergence of FQ-resistant i (ESBL) ,8,9,10.A spike in community FQ resistance of 20–30%, especially in Korea , has resRecent randomized controlled trials (RCTs) and non-randomized observational studies (NRSs) have shown the superior prophylactic effect of fosfomycin on UTIs after TRUS prostate biopsies compared with FQ or other antibiotics ,15,16,17This systematic review and meta-analysis was based on a priori registered protocol (PROSPERO: CRD42022302743). This study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and AMSTAR 2 Checklist.-Type of studies: RCTs, which provide a higher certainty of the evidence, and NRSs, which are similar to the relevant RCTs, as a source of complementary, sequential, or replacement evidence for the RCTs, were included regardless of their status, date, or language of publication.-Types of participants: Studies on males undergoing TRUS prostate biopsies who were suspected of prostate cancer by a prostate-specific antigen (PSA) and digital rectal exam (DRE) were included.-Types of interventions: Studies that used fosfomycin as a prophylactic antibiotic (versus FQ or other types of antibiotics) to prevent UTIs or infectious complications after TRUS prostate biopsies were considered, regardless of the use of other adjunctive therapies , provided these were consistent in both groups.The following inclusion criteria were used to identify relevant studies:The measurement of the outcomes assessed in this review was not used as an inclusion criterion. Primary outcomes were febrile UTI, afebrile UTI, and overall UTI. Secondary outcomes were adverse drug events, positive urine and blood cultures, and FQ resistance. All outcomes were measured within 30 days after the prostate biopsy. The clinically important differences were used to rate the overall certainty of the evidence in the ‘Summary of findings’ table . There iwww.covidence.org, accessed on 16 January 2022). Details of the search strategies are in A comprehensive literature search was performed up to 14 January 2022, using a range of established scientific databases  and trial registries  regardless of their publication status or the language of publication. The references of the full articles retrieved for our review were also searched to identify any additional studies. All steps were performed independently and in duplicate following the protocol using the Covidence software platform  independently extracted information on study design, study dates, setting, country, participant characteristics, intervention details, comparisons, outcomes, funding sources, and conflict of interest. No additional information was required beyond the published data. The risk of bias for RCTs was assessed using a recently developed version of the Cochrane ‘Risk of bias’ tool (RoB 2) . Modifie2 statistic. The I2 statistic was interpreted following the guidance of the Cochrane Handbook [The data were summarized using a random-effects model. The Review Manager 5.4.1 software  was used for the statistical analyses. Since the outcomes were all dichotomous, the risk ratio (RR) with a 95% confidence interval was calculated. Heterogeneity (inconsistency) was identified by visually inspecting the forest plots to assess the overlap of CIs and the IHandbook . When heHandbook . A sensiThe certainty of evidence (CoE) was rated on a per-outcome basis using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework, which considers five criteria related to the internal  and external (directness of results) validities . For eacEthical approval was waived due to the nature of this study.The search yielded 139 studies. After removing duplicates, the titles and abstracts of 116 studies were screened. After excluding 92 studies ; fosfomycin (intervention); other antibiotics (comparison)), 24 full-text articles were screened, of which ten studies were excluded that did not meet the inclusion criteria. In total, 14 studies Febrile UTIn = 784, FQ n = 727) reported febrile UTIs [2 = 0%; moderate-certainty evidence). We downgraded the certainty of the evidence due to serious study limitations (−1).Five RCTs with 1511 patients  reported febrile UTIs [2 = 73%; very low-certainty evidence). The certainty of the evidence was downgraded for inconsistency (−1) and imprecision (−1).Four NRSs with 2513 patients .(2)Afebrile UTIn = 784, FQ n = 727) reported afebrile UTIs [2 = 0%; moderate-certainty evidence). We downgraded the certainty of the evidence for serious study limitations (−1).Five RCTs with 1511 patients  reported afebrile UTIs [2 = 38%; very low-certainty evidence). We downgraded the certainty of the evidence for imprecision (−1).Three NRSs with 1926 patients .(3)Overall UTIn = 784, FQ n = 727) reported overall UTIs [2 = 25%; moderate-certainty evidence). We downgraded the certainty of the evidence for serious study limitations (−1).Five RCTs with 1511 patients  reported overall UTIs [2 = 79%; very low-certainty evidence). We downgraded the certainty of the evidence for inconsistency (−1) and imprecision (−1).Three NRSs with 1926 patients .(1)Adverse drug eventsn = 509, FQ n = 462) reported adverse drug events [2 = not applicable; moderate-certainty evidence). We downgraded the certainty of the evidence for serious study limitations (−1).Two RCTs with 971 patients  reported adverse drug events [2 = not applicable; low-certainty evidence).One NRS with 1109 patients .(2)Positive urine culturesn = 611, FQ n = 564) reported positive urine cultures [2 = 0%; low-certainty evidence). We downgraded the certainty of the evidence for serious study limitations (−1) and imprecision (−1).Three RCTs with 1175 patients  reported positive urine cultures [2 = 72%; very low-certainty evidence). We downgraded the certainty of the evidence for inconsistency (−1) and imprecision (−1).Three NRSs with 1926 patients .(3)Positive blood culturesn = 102, FQ n = 102) reported positive blood cultures [2 = not applicable; low-certainty evidence). We downgraded the certainty of the evidence for serious study limitations (−1) and imprecision (−1).One RCT with 204 patients  reported positive blood cultures [2 = 49%; very low-certainty evidence). We downgraded the certainty of the evidence for inconsistency (−1) and imprecision (−1).Three NRSs with 2316 patients .(4)FQ resistancen = 611, FQ n = 564) reported FQ resistance [2 = 0%; low-certainty evidence). We downgraded the certainty of the evidence for serious study limitations (−1) and imprecision (−1).Three RCTs with 1175 patients  reported FQ resistance [2 = 0%; low-certainty evidence).Three NRSs with 1926 patients .n = 1531, FQ n = 2324) were included in the analysis [Please refer to analysis ,39.(1)Febrile UTI2 = 0%; low-certainty evidence).Fosfomycin combined with FQ may result in little to no difference in febrile UTIs compared with FQ Afebrile UTI, (3) Overall UTIWe did not find any studies reporting these outcomes.(1)Adverse drug eventsWe did not find any studies reporting this outcome.(2)Positive urine cultures2 = 0%; low-certainty evidence).Fosfomycin combined with FQ may result in little to no difference in positive urine cultures compared with FQ Positive blood cultures2 = 0%; low-certainty evidence).Fosfomycin combined with FQ may result in little to no difference in positive blood cultures compared with FQ FQ resistance2 = 24%; low-certainty evidence).Fosfomycin combined with FQ may result in little to no difference in fluoroquinolone resistance compared with FQ , targeted prophylaxis with rectal cultures, and geographic locations. These potentially had significant implications on patient outcomes. A recent study confirmed the ability of fosfomycin to distribute to the prostate and seminal vesicles after one single dose and that a two-consecutive-dose regimen increases antibiotic availability inside these peripheral tissues . EstabliNevertheless, this study provides a more accurate analysis for physicians to assist them in better managing their patients. In particular, this is the first systematic review that registered fosfomycin alone and fosfomycin combined with FQ for the intervention group.The European Association of Urology guidelines on managing prostate biopsies to reduce infectious complications recommend that transperineal biopsies be the first choice. If not feasible, a transrectal biopsy should be considered as a second choice. If FQ is not licensed, alternative antibiotics such as fosfomycin (3 g before and 3 g 24–48 h after the biopsy) were considered with very low certainty . MoreoveConsidering the increase in FQ resistance of fecal flora and uropathogens ,11,44 anTransperineal prostate biopsies, magnetic resonance imaging fusion prostate biopsies , and tarCompared with FQ, fosfomycin or fosfomycin and FQ combined had a similar prophylactic effect on UTIs after a transrectal prostate biopsy. The certainty of the evidence for the primary outcomes of this review was moderate to low, which matches our confidence in the reported effect estimates, which are likely to be close to the true effect or are limited. Regardless of which regimen is adopted in clinical practice, the fosfomycin course was short (one or two doses only). Hence, it is likely to have good patient compliance, and decreased UTIs and admissions to the hospital may reduce overall costs. Given the increasing FQ resistance and its ease to use with a relatively safe profile, fosfomycin may be a good option for antibiotic prophylaxis.


Introduction: A person with diabetes is subject to developing micro and macrovascular complications and prevention requires an active role from the person. So, health literacy should have a preponderant role in the health of people with diabetes but this link is yet not fully understood. The objective of this study is to understand the relationship between health literacy and the prevalence of complications in people with diabetes mellitus type 2 (DM2).Methods: This is a multicentric transversal observational exploratory study. A survey was conducted with two health literacy instruments, the Medical Term Recognition Test (METER) and Newest Vital Sign (NVS), filled out by people with DM2 coming to consultation in primary health centers in three main regions of Portugal. Results: In this sample (n=141), 50.6% were male, 41 to 88 years old, and 56% earned more than the minimum wage. Using the METER tool, it was found that 57.4% of the diabetic patients had functional literacy. Adequate literacy was found in 24.1% with the NVS tool. Also with the NVS tool it was found that 36.2% of the sample subjects had s high probability of limited literacy. Utilizing the METER tool, a statistically significant decrease in health literacy was observed in individuals with diabetic complications (p=0.001). There was no significant relation between the presence of diabetic complications and present blood pressure values, low-density lipoprotein, and socioeconomic index.Conclusion: In this study, we found a significant relation between lower health literacy and the presence of diagnosed DM2 complications (p=0.001). Diabetes mellitus is considered one of the pandemics of the 21st century due to the constant increase in its incidence in recent years [Diabetes, as a chronic disease, requires complex management of concepts and materials and, consequently, an important understanding of the disease by the people affected by it, so that they can take better care of themselves on a daily basis .As a person with diabetes ages, there is an increased risk of developing complications: neuropathy, diabetic foot, retinopathy, nephropathy, and cardiovascular disease, these being the main causes of morbidity and mortality ,4. It isThus, good metabolic and cardiovascular control are two of the main goals of a person with diabetes, as it is essential to prevent or delay the onset of these complications .The emergence of complications is also related to relevant non-clinical factors, such as socioeconomic and psychosocial characteristics. Due consideration is also given to the important role of health literacy in the development of possible complications in people with diabetes, serving as a barrier to a better quality of life ,5.Health literacy has gained interest as a fundamental concept of the more active role of the person in their illness. It is known that there is a link between the level of literacy and the state of health of the person, probably because a low level of literacy is related to a more probable incomprehension of written and oral information provided by health professionals, inability to search services that may be necessary, or even following the indications of a prescription . People Several studies confirm that low health literacy is associated with a decrease in knowledge about diabetes ,11-14. TThis study aims to investigate the existence of a relationship between health literacy and complications of diabetes. Secondary objectives include understanding the relationship between complications of diabetes and sociodemographic variables and metabolic and cardiovascular control, in order to understand the influence of other associated factors.After receiving a favorable opinion from the Ethics Committees of the Northern Regional Health Administration (No. 130/2017), Central Regional Health Administration (No. 59/2017), and Lisbon and Tagus Valley Regional Health Administration (No. 10299/CES/2017), a cross-sectional observational study began in July 2017.The questionnaires were applied in a convenience sample in a primary care unit in 3 cities of Portugal  to people with DM2 who went to a medical consultation in the days when data was collected, after being informed and signed consent. All patients with diabetes who came to the medical consultation on the data collection days were identified in each unit by their physicians and were then approached by the local main investigator who questioned their interest in responding to the questionnaire. Complications diagnosed and recorded in the process  were also included. This data collection was done by inquiring users and checking the registrations in the clinical processes.The anonymous questionnaire was composed of the Medical Term Recognition Test (METER) which evaluates if literacy is associated or not with word recognition and the Newest Vital Sign (NVS) aimed at a more functional assessment of literacy, both validated for Portugal and containing a request for informed consent ,18. In awww.raosoft.com website, obtaining a minimum of 141 participants, with a confidence interval of 90% and a margin of error of 7%, defined for this exploratory study.The sample size was calculated through the tool on the For the descriptive statistical and inferential analysis, not having normality on the distribution of the variables, the mean, minimal, and maximal values were calculated, and the Mann-Whitney U and Kruskal-Wallis non-parametric tests (p<0.05) were used to relate the complications registered with literacy in health and other variables.Characterization of the sampleA total of 141 questionnaires were administered to people with DM2: 47 questionnaires in each unit. Table The sample, comprised of 141 respondents, encompassed people between 41 and 88 years of age (mean of 68 years), and 50.4% were men  of the respondents have a functional literacy. When using NVS, adequate literacy was verified in 24.1% (n=34) of respondents  presented diagnosed complications. Of this 27.7%, 6.4% (n=9) had retinopathy, 4.3% (n=6) had neuropathy; 1.4% (n=2) had diabetic foot and 12.1% (n=17) had nephropathy. Lastly, 6.4% (n=9) of respondents had already had an episode of stroke and 2.8% (n=4) of people had at least one acute myocardial infarction (AMI).Association between literacy and diagnosed complicationsUsing the METER instrument, there was a significant correlation between the presence of complications and a lower average of literacy (p=0.001). Through the NVS instrument, the same relationship was also observed, but without statistical significance p=0.283)  Table .In terms of trends with no statistical significance, the presence of complications was associated with a more advanced age and a socioeconomic index tending to be higher (lower socioeconomic level) and education lower, when compared with individuals without complications. There has also been a tendency for patients who do not present complications to be those with lower average systolic blood pressure values, but higher diastolic blood pressure, HbA1c, and LDL.This exploratory study, to our knowledge, was the first in Portugal to evaluate the correlation between literacy and the development of complications of DM2.A relationship between lower health literacy (METER) and the presence of complications (p=0.001) was found, but there was no significant association between the presence of complications and the socioeconomic level and education, nor with the values obtained in the variables of metabolic or cardiovascular control.Several factors may explain the association between verbal recognition literacy and the complications of diabetes. People with low health literacy are associated with decreased knowledge about their disease -8,14. DiA significant association was found between education and the presence of DM2 (p=0.019) complications, as confirmed by other literature about the correlation between high levels of education and high levels of health literacy .It is known that the disease progression time is related to a higher incidence of complications in people with DM2 [Several studies have also related reduced literacy with sociodemographic factors, as triggers for the appearance of complications . HoweverComparing this sample with the sociodemographic data regarding the Portuguese population with DM2, a similar degree of similarity was obtained since the mean age is 68 years [Regarding the clinical and laboratory parameters, it was observed that the average diastolic blood pressure was under better control than the systolic blood pressure, which has been observed in other studies . In thisAs for limitations, we utilized data derived from three distinct locales spanning diverse geographical regions. Although diversified, the sample was of convenience and limited in the number of respondents because it was an exploratory study, which limited the generalization to the Portuguese population and the analysis of some variables. Given the urban nature of the cities where the study was conducted, which inherently presume a higher literacy rate, the intrinsic potential for selection bias is evident, as this sampling does not adequately mirror the rural population.It is prudent to note further that the use of questionnaires to gauge behaviors raises the possibility of inaccuracies and biases. Furthermore, the willingness and motivation to respond to a questionnaire may in themselves be deemed indicators of health literacy, consequently potentially resulting in the exclusion of less proficient segments within the scope of our study.Another limitation of the study was due to the fact that the individual medical records of the respondents were not updated, nor were the complications properly recorded and coded.Given that there were two researchers in the data collection, this may have led to an inter-observer bias. Moreover, since it is a cross-sectional study, it is not possible to determine causality among these variables.Despite this, it must be underscored as a merit of this current work the adoption of a population-based sample, which facilitated the inclusion of individuals with diabetes across various stages of the condition. Also, the present study is made up of other points that reinforce its robustness: it encompasses three Portuguese cities in different regions, which diversifies the sample and, although it is of convenience, no selection was made when choosing the respondents that met the inclusion criteria of the study, except for the fact that they had a medical consultation on the days the data was collected; this study considers two assessment tools for health literacy validated in Portugal, which allow a more global assessment of the capacities of the respondents, also encompassing the most frequent complications in the Portuguese population, taking into account intermediate risk factors  and socioeconomic factors, in order to understand its possible influence in health literacy and complications of diabetes. Risk and socioeconomic factors have significant implications for health literacy, which pertains to an individual's capacity to access, comprehend, and effectively employ health-related information to make informed decisions about their well-being. The interplay between these factors impacts health literacy in several ways. For example, individuals with higher socioeconomic status tend to be more exposed to health-promoting environments, preventive care, and health risk awareness. Conversely, those with lower socioeconomic status may lack knowledge about health risks and the significance of health-promoting behaviors. Also, reduced education can impair reading, numeracy, and critical thinking skills necessary for comprehending intricate health information.Lastly, the study was not based on the complications reported by the people, but on the data collected in the respective clinical records, being more objective when compared with studies that were based on what the respondent reported .It is important to point out that this project is an exploratory study of a poorly explored subject, namely in a population with low health literacy, such as the Portuguese population. It seems important to continue its development, with larger samples, in order to be more representative of this population. It would also be important to try and understand how literacy is influencing the relation with complications and what factors are being conditioned by this low health literacy , to help determine the best way to intervene on this issue, as to improve the quality of life and reduce mortality in this population.Since the objective of this study was to understand if there is a relationship between health literacy and the presence of complications of diabetes mellitus type 2 (DM2), it was possible to conclude that in this sample there is a significant relationship between a more limited literacy and a higher incidence of complications associated with DM2 (p=0.001).It was also concluded that there is no significant relationship between the presence of complications with systolic and diastolic blood pressure, low-density lipoprotein, and the socioeconomic index, so that the relationship between literacy and complications may be independent of these variables. Future research should explore the development and effectiveness of health literacy educational programs, potentially mitigating the incidence of complications. It would be important to invest in longitudinal studies to explore the temporal relationship between changes in health literacy levels and the development of complications over time. Additionally, there is potential for conducting interventional studies to further validate the role of health literacy in complication prevention.