López-Alcalde et al. BMC Health Services Research (2019) 19:169 https://doi.org/10.1186/s12913-019-4001-9 RESEARCH ARTICLE Open Access Consideration of sex and gender in Cochrane reviews of interventions for preventing healthcare-associated infections: a methodology study Jesús López-Alcalde1,2,3,4* , Elena Stallings3, Sheila Cabir Nunes5, Abelardo Fernández Chávez6, Mathilde Daheron5, Xavier Bonfill Cosp7,8 and Javier Zamora3,8 Abstract Background: Healthcare-associated infections (HAIs) are common and increase morbidity, mortality, and healthcare costs. Their control continues to be an unresolved issue worldwide. HAIs epidemiology shows sex/gender differences. Thus the lack of consideration of sex/gender in Cochrane reviews will limit their applicability and capacity to support informed decisions. This study aims to describe the extent to which Cochrane reviews of interventions for preventing HAIs consider sex and gender. Methods: Methodology study appraising Cochrane reviews of interventions to prevent HAIs. Search methods: Cochrane Database of Systematic Reviews from 1995 (launch of the journal) to 31 December 2016. Two authors independently extracted data with EPPI-Reviewer 4 software, and independently appraised the sex/gender content of the reviews with the Sex and Gender Appraisal Tool for Systematic Reviews (SGAT-SR). Results: This study included 113 reviews assessing the effects of interventions for preventing HAIs. 100 reviews (88%) used at least one sex or gender-related term. The terminology used was heterogeneous, being “sex” the term used in more reviews (51%). No review defined neither sex nor gender. Thus we could not assess the definitions provided. Consideration of sex and gender was practically absent in the included reviews; in fact, no review met all the applicable items of the SGAT-SR, and 51 reviews (50%) fulfilled no item. No review provided a complete description of the sex and the gender of the samples of the included studies. Only ten reviews (10%) planned to perform sex- and gender-based analysis and only three (3%) could complete the analysis. The method chosen was always the subgroup analysis based on sex (one review) or gender (two reviews). Three reviews (3%) considered sex or gender-related findings in the conclusions. Conclusion: Consideration of sex and gender in Cochrane reviews of interventions for preventing HAIs was practically absent. This lack of attention to sex and gender reduces the quality of Cochrane reviews, and their applicability for all people: women and men, boys and girls, and people of diverse gender identities. Cochrane should attempt to address the shortfalls detected. Keywords: Systematic reviews, Data extraction, Sex, Gender, Sex/gender, Equity, Cochrane, Gender bias, Healthcare- associated infection * Correspondence: cochrane.madrid@ufv.es 1 Department of Paediatrics, Obstetrics & Gynaecology and Preventative Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain 2 Faculty of Health Sciences, Universidad Francisco de Vitoria (UFV)-Madrid, Madrid, Spain Full list of author information is available at the end of the article © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. López-Alcalde et al. BMC Health Services Research (2019) 19:169 Page 2 of 17 Background First, pharmacokinetics and pharmacodynamics of drugs Health inequality and health inequity differ between sexes, resulting in differential adverse event ‘Health inequality’ and ‘health inequity’ are commonly con- profiles and further affecting treatment outcomes [21–23]. fused terms, although they have different meanings. Health Secondly, sex and gender both affect environmental and inequalities refer to the differences in health status or in the occupational risks, risk-taking behaviours, access to health distribution of health determinants between different popu- care, health care-seeking behaviour, health care utilisation, lations (e.g., racial, ethnic, sex, gender, sexual orientation, or and perceived experience with health care, and thus, dis- socioeconomic groups) [1]. On the other hand, ‘health in- ease prevalence and treatment outcomes [16, 24]. equities’, also known as ‘health disparities’ [2], are avoidable and unfair differences in health across socioeconomic, Consideration of sex and gender in research demographic and geographic factors [1–6]. According to The consideration of sex and gender in research is relevant the World Health Organization (WHO) Commission on So- for many reasons, such as for warranting scientific rigour, for cial Determinants of Health, health inequity is caused by reducing and enhancing the effectiveness of healthcare inter- the following interacting factors: a) the socioeconomic and ventions, for promoting an informed-decision making, and political context, b) the social position, b) the material cir- for addressing inequities in health [17, 25–27]. The absence cumstances, and d) the health system [7]. of consideration of sex and gender in research limits the ex- To reduce health inequities both within and between ternal validity of research findings and their applicability for countries remains a priority on the agenda of international women, but also for men [16]. organisations, such as the WHO, and local, regional and na- Various stakeholders (e.g., journal editors, research fun- tional governments [8, 9]. The design and implementation of ders, policymakers) agree that sex and gender matter to health care interventions and health programmes should health outcomes [16]. As an example, the National Insti- apply an “equity lens” to ensure that benefits reach the most tutes of Health (NIH) Revitalization Act of 1993 in the hard-to-reach segments of the population and to avoid United States of America (USA) required NIH-funded clin- intervention-generated inequalities [10, 11]. See Add- ical trials to include women and minorities as participants itional file 1 for definitions of key terms. and to assess outcomes by sex and race or ethnicity [28]. Also, other relevant stakeholders are asking systematic re- The relevance of sex and gender in health views (SRs) to determine the evidence of differential effects Sex, gender, or sexual orientation are characteristics that across age, sex and socioeconomic status [29]; this is the may contribute to health inequalities and health inequities case of NICE (National Institute for Health and Care Excel- [5, 10, 12, 13]. The concepts of sex and gender are distinct lence) [30], or the PRISMA statement [31]. but interrelated [14]. According to the Canadian Institutes of However, research design, reporting, and implementa- Health Research, every cell is sexed, and every person is gen- tion, and general science communication often neglect dered [15]. Sex, usually defined as female or male, refers to a sex and gender differences [14, 16, 17, 25, 26, 32–35] and number of biological characteristics in humans and animals policies attempting to solve this problem, such as the NIH [16]. Sex is linked with physical and physiological features, policies cited above, have not resulted in significant in- such as chromosomes, gene expression, hormone function creases in reporting results by sex, race, or ethnicity [36]. and reproductive/sexual anatomy [16, 17]. On the other hand, gender refers to the social roles, be- Methods to consider sex and gender in systematic haviours, expressions and identities of girls, women, boys, reviews men, and gender diverse people [16, 17]. Consequently, A SR is a review that departs from a clear question and gender influences how people perceive themselves and follows rigorous and explicit methods in all its stages, each other, how they behave and interact, and how power that is, from the identification of the studies to the ana- and resources distribute in society [16, 17]. lysis of the data [37]. Sex and gender are usually conceptualised as binary fac- SRs are essential tools to transfer research knowledge tors. Thus, analyses often consider male/female for sex, as into evidence-informed policy and practice [29, 38, 39]. well as masculine/feminine for gender [16, 17]. However, Also, SRs are crucial in the promotion of health equity as this may not reflect the reality, as the attributes of gender they help to determine the effects of interventions across are multidimensional, dynamic, and interactive [18]. The studies conducted in a variety of settings and populations, term ‘sex/gender’ highlights this ‘entanglement’ of the bio- which allows for the exploration of both prognostic fac- logical and the social [17, 19, 20]. tors and treatment-covariate interactions [4, 29, 40–42]. Biological and gender-based differences result in differ- Decision-makers are interested in health equity as one of ential health risks, disease incidence, and health service the considerations for decision-making, as they need to needs [10]. Consequently, sex and gender interactions can know the effects of interventions in the overall population influence health and well-being in a variety of ways [16]. and across population groups [5, 43]. Considering sex and López-Alcalde et al. BMC Health Services Research (2019) 19:169 Page 3 of 17 gender in SRs is a significant step forward in determining identify to whom the research results apply and do not to whom the evidence applies, which is critical to make present adequate data and analyses about health equity sound clinical and policy decisions [33]. factors, including sex and gender [34, 40, 50–52]. A Sex- and gender-based analysis (SGBA) is the analytical proper SGBA framework can help in determining external approach that incoporates the sex and gender perspective validity—to whom a particular body of evidence applies into health research, policies, and programmes, and in health and to what degree there is sufficient evidence to general- planning and decision-making [16]. SGBA systemically in- ise results [14]. quiries about biological (sex-based) and socio-cultural (gen- The Sex/Gender Methods Group, a subgroup of the der-based) differences between women and men, and boys Campbell and Cochrane Equity Methods Group [53], and girls, without presuming that there are disparities [44]. was established in December 2005. One of its aims is to In the context of SRs, SGBA is any analytical framework develop methods and tools to integrate sex and gender aiming to promote the consideration of sex and gender in the development and reporting of research synthesis properly within SRs, so they have the potential to expand [54]. Cochrane Madrid is making this a priority, and this their findings for all people: women and men, boys, girls, article describes our first step to promote the application and people of diverse gender identities. of an “equity lens” to Cochrane reviews. There are several methodological approaches for address- ing factors related to equity (sex and gender among them) in Healthcare-associated infections: a public health problem SRs, such as performing subgroup analysis or performing Healthcare-associated infections (HAIs) are infections ac- targeted analyses of sex/gender populations [4]. quired as a result of the delivery of health care [55]. HAIs represent a public health problem worldwide, as about 6 Consideration of sex and gender in Cochrane reviews and 4% of the hospitalised patients in Europe and the U. Cochrane is an international organisation that prepares S, respectively, have at least one HAI [56, 57]. Rates of SRs to support people in making well-informed deci- HAIs seem to be even higher in low or middle-income sions about health care (36). Although the extent to countries [58]. HAIs increase morbidity (prolonged hos- which current Cochrane reviews consider sex and gen- pital stay and worse prognosis) [59], mortality [59, 60], der is not well known, some studies suggest that there is and healthcare costs [59, 61, 62]. Finally, there can be lim- much room for improvement. To our knowledge, only ited options for treating HAIs caused by certain the study by Doull et al. [14] has evaluated the consider- drug-resistant organisms, such as methicillin-resistant ation of sex and gender in Cochrane reviews. This study Staphylococcus aureus (MRSA) [56, 57, 63]. concluded that SGBA was generally absent in a random sample of 38 Cochrane reviews published before April Role of sex and gender in infectious diseases 2007 in cardiovascular health. transmission and outcomes Moreover, Cochrane reviews seem to rarely assess Traditionally, little attention has been paid to sex and whether interventions have intended or unintended effects gender differences in infectious diseases [24]. However, on health equity [29]; according to another study, only 1% both sex and gender can affect infectious diseases inci- of a random sample of Cochrane reviews assessed differ- dence, duration, severity, and mortality through several ences in the effectiveness of interventions across socioeco- pathways [24]. nomic or demographic factors [45]. This shortfall is also There are biological differences between sexes that present in non-Cochrane SRs. In fact, the analysis or re- affect infectious diseases. For example, pregnant and lac- port of equity issues, [38, 46–49], and sex/gender in par- tating women represent a high-risk group for many infec- ticular [17, 25, 26, 33, 35], is infrequent in SRs. tious diseases [24], or females have an increased risk of There are several obstacles to consider sex/gender in catheter-associated urinary tract infection (CAUTI) due to any type of SRs, such as how the included studies defined anatomy that facilitates the bacterial contamination of the sex and gender, the methodological difficulties in measur- catheter. On the other hand, the vulnerability to infections ing and analysing sex and gender, the availability of data differs between sexes due to differences in their immune to perform sex and gender analysis, and also the quality of systems; in this line, pre-menopausal females seem to have this data [33]. As an example, the studies included in SRs a natural advantage under septic conditions [64–69], usually do not report about the inclusion of specific popu- which may be explained by the role of sex steroids, that lations or, if they do, they may not assess variation in ef- change the host immune function, alter genes and modify fects across critical characteristics, such as sex, age, behaviours that influence susceptibility and resistance to ethnicity or socioeconomic status [5]. Moreover, sex and infection [69]. However, a recent SR concluded that the gender are highly interrelated, and it is sometimes difficult impact of sex on sepsis outcomes remains equivocal [70]. to attribute particular male-female differences to either Finally, males may present higher overall HAIs prevalence, sex or gender alone [24]. Consequently, SRs do not clearly thirty-day mortality, and one-year mortality [71]. López-Alcalde et al. BMC Health Services Research (2019) 19:169 Page 4 of 17 Gender differences in behaviours, activities, exposures, policies and programs which inadvertently increase health and access to resources and decision-making affect inequities [80, 81]. transmission and outcomes for different HAIs [24]. For example, women are less likely to receive antibiotics Study aims within 3 hours of the diagnostic of sepsis, as compared The general aim of this study was to describe the extent to men [72]. to which Cochrane reviews of interventions for prevent- ing HAIs consider sex and gender. The specific objec- Why this study is important tives were the following. Sex and gender are necessary to understand the trans- mission of infectious diseases. The integration of a sex/ Objective 1. To describe and assess the terminology gender perspective into SRs of interventions to control and definitions used for sex and gender. the transmission of HAIs is a new and challenging area Objective 2. To determine the content of the reviews but critical to defining successful infection control pro- about sex and gender. grammes [24]. Objective 3. To describe the SGBA of the reviews. Although we need more research to understand better Objective 4. To assess whether the review conclusions how sex and gender interact with HAIs, there is enough considered the sex- and gender-related findings. knowledge available to justify the inclusion of a sex/gender perspective in research and programmes for HAIs. How- Methods ever, infection control strategies in the healthcare setting Study design do not often consider sex and gender, and thus, they are Methodology study, that is, a study that assesses the generally the same for males or females [24, 73]. methods used in randomised trials, other healthcare To consider sex and gender in Cochrane reviews of in- evaluations or systematic reviews [82]. terventions to prevent HAIs is important. First, it will We did not register this study in PROSPERO database allow for the identification of the most effective and safest because it did not meet the inclusion criteria, mainly be- interventions for women and men. Second, it will contrib- cause this is not a systematic review [83]. Our research ute to the reduction of health inequities between men and does not adhere to any reporting statement as to our women, and thereby promote human rights [24]. Third, knowledge there is no guidance for reporting method- the consideration of sex and gender in Cochrane reviews ology studies. will help an informed-decision making for women and men. Fourth, the findings of our study will contribute to Criteria for considering reviews for this study promoting the incorporation of a sex/gender perspective Types of reviews that were eligible into Cochrane reviews of any topic. Cochrane reviews published from 1995 (launch of the We chose to focus our study on Cochrane reviews for journal) until 31st December 2016 that evaluated the ef- several reasons. First, we foresaw that a high number of fects of interventions for preventing HAIs. The review Cochrane reviews had evaluated infection control inter- had to be defined as a ‘published review’ (not at protocol ventions [74]. Second, a wide range of Cochrane Review nor title stage), an ‘active review’ (not withdrawn), and Groups publishes Cochrane reviews of infection control as an ‘intervention review’, that is, a review assessing the interventions, which gives an overview of the general ap- effects (benefits, harms or both) of health care or health proach of Cochrane as an organisation towards sex and policy interventions [84]. Thus, we excluded the gender. Third, Cochrane reviews are recognised as a reli- remaining types of Cochrane reviews: methodology re- able source of evidence worldwide and have a high impact views, diagnostic reviews, overviews of reviews, progno- on decision making, for example, through the consider- sis reviews, and qualitative reviews. ation of Cochrane reviews in clinical guidelines [75–77], Participants: the review must have considered any or in the medical policy documents of private health in- healthcare consumer in risk of healthcare-associated col- surers [78]. As an example, the percentage of Cochrane onisation or HAI, except for reviews focusing on neonates, reviews used in WHO guidelines have been steadily rising, pre-terms, low birth weight or immunocompromised pa- and so far for 2016, Cochrane reviews have been included tients, due to the epidemiological peculiarities of these in 90% of the WHO guidelines [77]. However, if Cochrane participants. We also excluded reviews focusing on the reviews do not consider sex and gender, they will not be prevention of infections in healthcare professionals. All able to generate evidence that applies to all the people that healthcare settings were eligible. can benefit from the research findings. Thus, Cochrane re- Interventions: any strategy, pharmacological or not, views may not be useful for policy-makers [29] who seek aimed at preventing any healthcare-associated colonisa- information on the distribution of effects in the popula- tion or infection. Additional file 2 details the eligible inter- tion [48, 79], or may even lead to the implementation of ventions. The review could consider any comparator, that López-Alcalde et al. BMC Health Services Research (2019) 19:169 Page 5 of 17 is, an inactive comparator (such as doing nothing, use of Data extraction placebo, or use of a sham intervention), or an active one We designed a data extraction template and piloted the (such as a pharmacological intervention, or a form on ten reviews. Two of the piloted reviews were non-pharmacological intervention, for example, an educa- not eligible for this study, but we used them because tional or organisational one). they had been defined by the Canadian Institutes of Outcomes: the review must have planned to assess at Health Research [87] as exemplar Cochrane reviews re- least one of the following outcomes: (a) occurrence of garding the consideration of sex and gender. The data HAIs; (b) occurrence of colonisations; (c) mortality due extraction template is available upon request. to HAI; (d) total mortality; (e) resistance to antimicro- We extracted data with the EPPI-Reviewer 4 software [85]. bials; or (f ) any surrogate measure of HAI, such as fever, At least two authors (JLA, ES, AF or SCN) extracted the positive culture, or antibiotic use. The review had to data for each item of the form. For critical items, two authors consider at least one of the previous outcomes in the extracted data independently. For other items, one author “Types of outcome measures” section (as a primary or extracted the data, and another author cross-checked the in- secondary outcome) or had to present results about any formation extracted. We resolved discrepancies by consen- of these outcomes (“Results” section). sus. In the case of no consensus, a third author intervened. We did not contact the review authors to obtain missing in- formation or clarification. Search methods for identification of reviews Next, we detail the methods used to complete each We searched the Cochrane Database of Systematic Re- specific objective. views (CDSR) looking for all the Cochrane interventions reviews active and published from 1995 (launch of the Analysis methods journal) until 31st December 2016. Additional file 3 de- Objective 1. To describe and assess the terminology and tails the full search strategy. We used EPPI-Reviewer 4 definitions used for sex and gender software [85] to create the database of reviews. We described the terms used for sex and gender and the sec- tions in which these terms appeared. Moreover, we assessed Selection of reviews the appropriateness of the terms and definitions used by Two authors (JLA and SCN or ES) screened each title comparing them with the proposals of the SAGER (Reporting and abstract independently to select potentially eligible of Sex and Gender Equity in Research) guidelines [16]. We reviews. If there was any uncertainty based on this infor- followed the classifications detailed in Tables 1 and 2. See mation, we obtained the full-text review for further as- also Additional file 1 for sex and gender definitions. sessment. Two authors (JLA and SCN or ES or AFC) independently assessed the eligibility of the retrieved full Objective 2. To determine the content of the reviews about texts and resolved disagreements by discussion. If there sex and gender was no consensus, we consulted a third author (JZ). We We determined the sex and gender content of each review used EPPI-Reviewer 4 software [85] to implement the se- according to the domains proposed by the Sex and Gen- lection process. We piloted the selection process with der Appraisal Tool for Systematic Reviews (SGAT-SR) [14]. 100 records. We created a PRISMA flowchart [86] de- This 21-item tool assesses how a Cochrane review has scribing the results of the selection process. considered sex and gender. It appraises seven review Table 1 Classification of the sex and gender terms Classification Correct Any of the following. 1. Male or female for sex and an adequate definition of sex (biological). 2. Men or women for gender and an adequate definition of gender (cultural and socially determined roles). Incorrect Any of the following. 1. Male or female for gender. 2. Men or women for sex. Unclear Any of the following. 1. Terms for sex or gender used without defining sex or gender. For example, if a review stated that the sex of the participants was male (56%) and female (64%), but there was no definition for sex, we judged the terminology as unclear because we could not know that the review was referring to sex or gender. 2. Terms inconsistently used in the review. For example, the review used the terms ‘male’ and ‘men’ for the same concept. 3. Abbreviations used without the full term provided. Not No mention to sex or gender applicable López-Alcalde et al. BMC Health Services Research (2019) 19:169 Page 6 of 17 Table 2 Classification of the sex and gender definitions Classification Correct Definitions like SAGER guidelines Incorrect Definitions different to SAGER guidelines Unclear Terms for sex or gender used without a definition for sex or gender Not applicable There was no mention of sex or gender in the review sections: (a) Background, (b) Objectives, (c) Criteria for in- et al. [90]). We will report the following key sex and clusion/exclusion, (d) Methods, (e) Results and analysis, gender characteristics. (f) Discussion and conclusions, and (g) Table of included • Sex measurement (ascertained by genotyping of studies. Each question of the tool has four answers: (a) blood sample) “Yes, review met criteria”; (b) “No, the review did not • Number of female and male participants meet criteria”; (c) “Item was not applicable to review”; or • Gender measurement (ascertained by self-report) (d) “Unable to determine”. The tool allows adding free • Number of women and men participants text comments to each response in case of need. We made We focused on the information that the review re- minor wording changes to the SGAT-SR. Additional file 4 ported in the table of included studies. We classified the shows the domains of the tool and the guidance on which review reporting of the sex and gender characteristics of we based our judgements. the study participants according to the following We tabulated the responses to the tool by simple categories. counts, and summarised the results numerically to pro- • Correct with a complete description: the review vide an indication of overall responses (as done by Doull attempted to describe all the key sex and gender charac- et al. [14] in a methodology study that used the teristics, and this information was available for all the in- SGAT-SR to examine the consideration of sex and gen- cluded studies. der in a sample of Cochrane reviews in the area of car- • Correct with an incomplete description: the review diovascular health). We calculated the percentage of attempted to describe all the key sex and gender charac- reviews meeting each item only when this was applicable teristics, but this information was not available for all (Number of reviews meeting item × 100/Total number the included studies, which was highlighted by the re- of included reviews in which the item was applicable); view authors. thus, when an item was not applicable for a review, that • Incorrect: the review did not attempt to describe all review was considered neither in the numerator nor in the key sex and gender characteristics for all the in- the denominator for that item. This omission applied to cluded studies. reviews focusing on females only, that is, those reviews addressing pregnancy and delivery. Breast cancer was Objective 3b. To describe the SGBA in the reviews not the case, as it can also affect males. First, we identified the SRs that had planned or used any Two authors (SCN, JLA, ES, or AFC) independently an- SGBA. Second, we described the SGBA methods swered each item of the tool not masked to the review de- planned and finally used. We considered Welch et al. [4] tails. We resolved disagreements through discussion and to describe the SGBA methods used: by consulting a third author if there was no consensus. • Subgroup analysis-pooled results: SRs that assessed We tabulated the judgements of the SGAT-SR and used impacts of health interventions on the outcome using Powerpoint 2016 [88] and Review Manager 5.3 [89] to subgroup analysis with pooling. summarise our judgements graphically. • Subgroup analysis-descriptive: SRs that described within-study differences without pooling. • Targeted analyses of sex or gender populations Objective 3. To describe the SGBA of the reviews • Other methods used for SGBA Objective 3a. To describe the reporting of the sex Objective 4. To assess whether the review conclusions and the gender characteristics of the study considered the sex- and gender-related findings participants We described if the review had attempted We calculated the percentage of reviews considering the to report the sex and gender characteristics of the partic- sex- and gender-related findings in the conclusions, in ipants recruited for each included study. For a review to particular: describe the study samples accurately, we agreed that it should have attempted to report at least the following  % of reviews considering sex or gender findings in information for each included study (based on Clayton the “Implications for clinical practice” section López-Alcalde et al. BMC Health Services Research (2019) 19:169 Page 7 of 17  % of reviews considering sex or gender findings in to prevent infections associated to vascular accesses (21/ the “Implications for research” section 113 [19%] reviews), and interventions based on patient  % of reviews performing SGBA that considered sex and healthcare personnel hygiene (14/113 [12%] reviews). or gender findings in the “Implications for clinical Other interventions evaluated were, for example, those to practice” section prevent urinary catheter-associated infection, education  % of reviews performing SGBA that considered sex and training to prevent HAIs, or interventions to prevent or gender findings in the “Implications for research” infection associated with dental procedures. section All the reviews planned to assess at least one of our study outcomes. HAI was defined as eligible in 105/113 Results (93%) reviews, followed by total mortality (66/113 re- Results of the search views [58%]), surrogate measures of HAI (31/113 re- The search strategy in CDSR generated 7156 records. views [27%]), colonisation (19/113 reviews [17%]), First, we screened their titles and abstracts, and we ex- mortality due to HAI (15/113 reviews [13%]), and resist- cluded 6836 records because they were not eligible. Sec- ance to antimicrobials (14/113 reviews [12%]). ond, we subsequently retrieved 320 full texts for further The most common study design was the randomised examination. We excluded 207 full texts (see reasons in controlled trial (RCT), which was eligible in all the in- Fig. 1), and we finally included 113 reviews. cluded reviews (100%). The RCT was the only study de- sign eligible in 57 reviews (50%), but another 55 reviews Description of the included reviews (49%) admitted the inclusion of at least one type of This study included 113 reviews (see Additional file 5, also non-randomised study (NRS) as well. For one review available in RIS format upon demand). The reviews were (1%), it was unclear if NRS were eligible. published between 2003 and 2016 within 23 different Cochrane Review Groups. The Cochrane Wounds Group Objective 1. To describe and assess the terminology and was the review group with the most reviews included in definitions used for sex and gender this study (35/113 reviews [31%]), followed by the Anaes- 100/113 reviews (88%) used at least one sex or thesia, Critical, and Emergency Care Group (13/113 re- gender-related term. The terms used varied, and no re- views [12%]), and the Incontinence Group (10/113 view made it explicit that sex and gender were different reviews [9%]). Each of the remaining Cochrane Review concepts. ‘Sex’ was the term used in the most reviews Groups published less than ten of the included reviews. (58/113 reviews, 51%), followed by ‘male’ (54/113 re- All the reviews evaluated the effects of interventions for views, 48%), ‘woman’ or ‘women’ (53/113 reviews, 47%), preventing HAIs. The interventions most frequently eval- ‘female’ (50/113 reviews, 44%), ‘gender’ (42/113 reviews, uated were those aiming to prevent HAIs associated to 37%), ‘men’ or ‘man’ (28/113 reviews, 25%), or other surgery (50/113 [44%] reviews), followed by interventions terms, in particular ‘boys’ and ‘girls’ (3/113 reviews, 3%). Fig. 1 Flow diagram of the selection process López-Alcalde et al. BMC Health Services Research (2019) 19:169 Page 8 of 17 13/113 reviews (12%) used no term related to sex nor our responses to the tool for each review, which can be gender. seen graphically in Fig. 3. The terms appeared mainly in the ‘Characteristics of No review met all the applicable items of the studies’ section (84/113 reviews, 74%). On the other SGAT-SR. In fact, 51/102 reviews (50%) fulfilled none of hand, only 10/113 (9%) reviews used these terms in the the applicable items. The remaining reviews fulfilled one conclusions section. Table 3 details the review sections (38/102 reviews [37%]), two (9/102 [9%]), three (3/102 that used these terms. [3%)], or four (1/102 [1%]) of the applicable items. The reviews defined neither sex nor gender. Thus we could not assess the definitions provided. Moreover, the Review section: background absence of definitions hindered our attempt to assess the 12/102 reviews (12%) used sex or gender-related terms appropriateness of the terms used. For thirteen reviews in the background. However, only 2/102 reviews (2%) it was not applicable to assess the terminology because defined the relevance of sex or gender to the review they did not use sex or gender terms. Another 11/100 question, and this was unclear for 8/102 reviews (8%). (11%) reviews used incorrect terms: ‘male’ or ‘female’ for No review (0/102) discussed in its background why sex gender (8 reviews), and ‘men’ or ‘women’ for sex (3 re- or gender differences might be expected. views). Also, 89/100 reviews (89%) used unclear termin- ology because there was no definition for sex or gender Review section: objectives (80 reviews), because both sex and gender terms were No review (0/102 reviews) used the terms sex, gender, used inconsistently apparently for the same concepts male, or female in the objectives. (eight reviews), or because the abbreviation “M” was used without detailing the full term (one review). Rea- Review section: criteria for inclusion/exclusion sons to judge the terms as unclear or incorrect are No review used sex or gender as criteria for deciding on shown in Fig. 2. study eligibility (0/102 reviews) or explained why to con- sider sex or gender differences for study eligibility (0/102 reviews). Objective 2. To determine the content of the reviews about sex and gender Review section: methods We did not determine the sex and gender content for No review (0/102 reviews) planned to examine or finally eleven reviews [91–101] as they included females only examined whether outcome measures were different for due to the topics addressed, that is, interventions to pre- males and females. No review planned to extract or ex- vent HAIs in caesarean section, operative vaginal deliv- tracted data by sex (0/102 reviews). No review extracted ery, abortion, amniotomy, or prelabour rupture of withdrawals and dropouts by sex (0/102 reviews). No re- membranes. Table 4 details the overall responses to the view used sex/gender as a proxy for other measures (0/ SGAT-SR questions, and Additional files 6 and 7 detail 102 reviews). Table 3 Percentage of reviews using sex and gender terms in each review section Review section Sex Gender Malea Femaleb Menc Womend Other Abstract 2% – – 1% 2% 8% – Background 3% 1% 4% 5% 3% 15% – Plain language summary 2% 1% 2% – 8% – Eligibility criteria 4% 8% 1% 1% 4% 13% – Search methods – – – – – 1% – Data collection and analysis 12% 12% 4% 4% 5% 9% – Results 9% 10% 12% 12% 7% 18% 1% Discussion 4% 2% 2% 1% 4% 15% – Authors’ conclusions 1% – – 1% 1% 7% – Characteristics of studies 31% 22% 42% 35% 13% 35% 2% Other sections 5% 3% – – – 3% – Not reported 49% 63% 52% 56% 75% 53% 97% a ‘Male’, ‘males’ or ‘m’ b ‘Female’, ‘females’ or ‘f c ‘Men’ or ‘man’ or ‘m’ d ‘Women’ or woman López-Alcalde et al. BMC Health Services Research (2019) 19:169 Page 9 of 17 Fig. 2 Appropriateness of the sex and gender terminology Table 4 Responses to the Sex and Gender Appraisal Tool for Systematic Reviews (SGAT-SR) Reviews meeting the Tool question Reviews meeting the criteria (n) criteria (n) Yes No Unable to Not determine applicable 1.Background 1.1. Are the terms sex and gender used in the background? 12 90 0 11 1.2. Are sex/gender identified as relevant or not to review question? 2 92 8 11 1.3. Does background discuss why sex/gender differences may be expected? 0 102 0 11 2. Objectives 2.1. Are the terms sex, gender, male, or female used in objectives? 0 102 0 11 3.Criteria for inclusion- 3.1. Do the review’s inclusion-exclusion criteria consider sex-gender 0 102 0 11 exclusion differences? 3.2. Was there justification or explanation for the exclusion of some groups? 0 102 0 11 4. Methods 4.1. Does the review examine whether outcome measures are different for 0 102 0 11 males and females? 4.2. Did the review extract data by sex? 0 102 0 11 4.3. Did the review extract data on sex of withdrawals and dropouts? 0 102 0 11 4.4. In cases where sex/gender is used as a proxy, is there an explanation? 0 0 0 113 4.5. Were any subgroup analyses completed? 41 61 0 11 4.6. Were subgroup analyses by sex completed? 3 99 0 11 5.Results and analysis 5.1. Do results distinguish between findings for males/females? 0 96 1 16 5.2. Does the review report conclusions that are different for men and 0 96 1 16 women? 5.3. If adverse effects are reported, is information sex-disaggregated? 0 60 0 53 5.4. Does review note that subgroup analyses by sex could not be done? 7 3 1 102 6. Discussion and 6.1. Does the review report that primary studies analysed or failed to analyse 0 97 0 16 conclusion results by sex? 6.2. Does the review address sex/gender implications for clinical practice? 1 101 0 11 6.3. Does the review address sex/gender implications for policy and 0 102 0 11 regulation? 6.4. Does the review address sex/gender implications for research? 2 100 0 11 7. Table of included 7.1. Detailed information on sex/gender of the study samples? 0 97 0 16 studies López-Alcalde et al. BMC Health Services Research (2019) 19:169 Page 10 of 17 Fig. 3 Sex and gender appraisal graph. Judgements across reviews for each item of the tool 86/102 reviews (84%) planned to perform subgroup analyse results by sex. This aspect was not applicable in analysis, but only 41/102 reviews (40%) could complete 16 reviews because they had no included studies (6 re- at least one subgroup analysis. 10/102 reviews (10%) views) or because they focused on one sex only (11 chose sex as the factor to analyse, but only three (3/102 reviews). [3%]) could complete the analysis. A total of 3/102 reviews (3%) considered sex/gender impli- cations in their conclusions: 1/102 review (1%) addressed the Review section: results and analysis implications for clinical practice, and the other 2/102 reviews No review in which it was applicable distinguished between (2%) considered the implications for research. However, no findings for males and females (0/97), or reported conclu- review addressed the implications of sex/gender for policy sions (of effectiveness, efficacy, safety) that were different for and regulation. men and women (0/97 reviews). For one review [102] we judged that these two items of the tool were unclear because the results and conclusions were reported separately only for Review section: table of included studies some review outcomes. For sixteen reviews it was not applic- No review (0/97 reviews [0%]) provided detailed in- able to assess these items because they focused on one sex formation on the sex and the gender of the samples only (11 reviews), or they included no study (6 reviews). of all the included studies. For sixteen reviews, this No review (0/60 reviews) reported adverse effects dis- was not applicable as they did not include any study aggregated by sex. For the remaining 53 reviews, it was (six reviews) or they focused on one sex only (eleven not applicable to assess this item of the tool due to the reviews). following reasons: the reviews focused on one sex only Regarding the sex of the participants recruited, 78/97 (11 reviews), they included no study (6 reviews), they did reviews (80%) provided no information at all. Another not plan to assess adverse effects (33 reviews), or al- 19/97 reviews (20%) provided unclear information. Re- though they planned to assess safety the included studies garding the gender, 87/97 reviews (90%) provided no in- did not report adverse effects (9 reviews). formation, and in the other 10/97 reviews (10%) the Seven out of the ten reviews (70%) that planned but information was unclear. We considered that the infor- could not perform subgroup analysis by sex explained mation about the sex or gender of the recruited samples why this analysis could not be completed. was unclear for several reasons: there was no definition for sex or gender, the authors used sex or gender terms Review section: discussion and conclusions but they did not state if they referred to sex or gender, No review in which it was applicable (0/97 reviews) re- or the authors misused the terms (men or women for ported if the included studies had analysed or failed to sex, or male or female for gender). López-Alcalde et al. BMC Health Services Research (2019) 19:169 Page 11 of 17 Objective 3. To describe the SGBA of the included reviews Discussion Summary of main results Objective 3a. To describe the reporting of the sex One hundred thirteen Cochrane reviews assessed the ef- and the gender characteristics of the study fects of interventions to prevent HAIs. Consideration of participants The review reporting of the sex and gender sex and gender in these reviews was practically absent. characteristics of the study participants was always in- Several reasons may explain this inattention. correct, as no review attempted to report the sex or the First, SRs may replicate limitations or gaps in primary gender of the participants of all the included studies. studies regarding their research question, their data ana- The method to ascertain the sex or gender of the re- lysis, and the interpretation of their results [14]. Primary cruited participants was never reported in the reviews. studies of hospital infection control interventions usually ignore sex, gender or having a gender identity that does not match one’s biological sex. Several reasons can ex- Objective 3b. Description of the SGBA in the plain this inattention. For example, researchers may con- included reviews Ten reviews (10/102 [10%]) planned sider that making conclusions about these factors is to perform SGBA, but only three (3/102 [3%]) could challenging because hospital-based studies are often complete the analysis. The method chosen for SGBA based on small sample sizes. Moreover, it is probably un- was always the use of subgroup analysis based on sex feasible for retrospective large primary studies, or those (one review) or gender (two reviews). Two reviews per- based on electronic records, to capture gender and sex formed subgroup analysis by pooling results of studies differences because they are based on data sources that to assess the effect of sex or gender on the outcome, and have not collected vital information, such as the assess- the other review performed a descriptive subgroup ana- ment of biological sex by genotyping or the gender lysis, that is, described within-study differences by gen- measurement by self-report. As a consequence, the in- der without pooling. cluded studies may not have reported the sex and gender distributions of the recruited samples. Alternatively, the authors may have just detailed that the study groups had Objective 4. To assess whether the review conclusions equal numbers of males and females at baseline as a proxy considered the sex- and gender-related findings for the randomisation success. Thus, sex was “controlled Only 3/102 reviews (3%) [102–104] considered the for” in the primary studies rather than considered to assess sex or gender-related findings in the conclusions. how the study outcomes vary across sex or gender groups One of them mentioned the sex/gender implications [5]. Our study did not assess the data provided by the pri- for clinical practice by stating that “Siliconised cath- mary studies, so we cannot confirm this. Nevertheless, eters may be less likely to cause urethral side effects other studies have highlighted that RCTs do not usually in men” [102]. The other two reviews considered the provide sex or gender disaggregated data [14, 36, 105–109], implications of sex/gender for research by stating and that sex/gender policies have not resulted in significant that “sub-group analysis would give valuable data as increases in reporting results by sex [36]. On the other to whether certain policies are more effective in hand, the SRs included in our study did not even plan to sub-groups such as females” [103], or “Future trials perform any SGBA, so we think the lack of data in the in- comparing suprapubic and intermittent urethral cluded studies cannot entirely explain their lack of attention catheterisation for short-term use in hospitalised to sex and gender. men should be conducted [...]” [104]. However, no Second, Cochrane launched the SGSR-AT [110] in review addressed the implications of sex/gender for 2011, that is, the Cochrane guidance to integrate sex and policy and regulation. Table 5 details how the re- gender in SRs is quite recent. Thus, the guidance was views considered sex or gender findings in their not available at the time of writing the protocols of the conclusions. included reviews. In fact, 31 included reviews (27%) were Table 5 Reviews considering sex or gender findings in the conclusions % reviews (n/total number of reviews) Reviews considering sex or gender findings in the “Implications for clinical practice” section 1% (1/102) Reviews considering sex or gender findings in the “Implications for research” section 2% (2/102) Reviews performing SGBA that considered sex or gender findings in the “Implications for clinical practice” 33% (1/3) section Reviews performing SGBA that considered sex or gender findings in the “Implications for research” section 33% (1/3) SGBA sex- and gender-based analysis López-Alcalde et al. BMC Health Services Research (2019) 19:169 Page 12 of 17 published in 2011 or before, and the 43 SRs published obtained (and not the inclusion criteria of the study). from 2012 to 2014 probably did not consider this guid- However, specific guidance to collect and report this in- ance at their protocol stage. formation in Cochrane reviews is still lacking. Third, the authors of the included SRs may have thought that sex/gender was not a relevant factor to Strengths and limitations of this study consider when evaluating the effects of interventions to Strengths prevent HAIs. Again, this is possible, but we cannot con- We made efforts to identify all the Cochrane reviews firm that this was the case as the review authors did not assessing the effects of interventions to prevent HAIs. We make this assumption explicit in the reviews. obtained all the Cochrane reviews published in CDSR Fourth, the review authors did not even consider the until December 31st, 2016 and screened all these records. role of sex/gender while planning the review. This situ- To minimise bias, at least two authors independently par- ation is, in our opinion, the most plausible explanation ticipated in the selection process, and, in case of disagree- and the most worrying one, as it denotes a knowledge ment, a third author was consulted. We also defined and gap about the potential relevance of sex and gender in applied explicit exclusion criteria which made the process these reviews. even more rigorous. We determined the sex/gender content of each review Overall completeness and applicability of evidence with the SGAT-SR. Again, to minimise bias, at least two This study aimed to describe the extent to which Cochrane reviewers (JLA and ES or SCN) independently partici- reviews of interventions for preventing HAIs consider sex pated in the assessment. In case of disagreement, a third and gender. We are quite confident that we have achieved reviewer (JZ) was consulted. Furthermore, to improve our goal. Firstly, we have identified all the Cochrane reviews the consistency we piloted the tool with several reviews, of interventions to prevent HAIs (we did not rely on a sam- and we prepared a user guide. ple of Cochrane reviews), and secondly, we have demon- The SGAT-SR helped us to assess how the different strated that SGBA is practically absent in these reviews. Cochrane review sections had considered sex and gender. Our study findings apply only to Cochrane reviews of in- We chose this tool because it is recommended by the Sex/ terventions to prevent HAIs. Thus, we cannot infer that our Gender Cochrane Working Group [54]. Moreover, we per- study findings can be applied to Cochrane reviews of other formed an extensive search up to April 2017 that revealed a health topics, or to non-Cochrane reviews. First, other lack of additional sex- and gender-specific appraisal tools Cochrane reviews may have incorporated the guidance of for SRs. As the tool had already been used to assess SRs on the Sex/Gender Methods Group [111]. Second, many inter- cardiovascular diseases, we were able to better understand ventions to prevent HAIs are non-pharmacological, for ex- the tool’s content by comparing our judgments with those ample, the use of gloves or hand washing. The methods used presented in the published article [14]. Independent subject to evaluate non-pharmacological interventions may differ experts had also reviewed the tool to ensure consistency from those applied to evaluate drugs, and this may imply a with common understandings of the concepts of sex and different approach to consider sex and gender. Third, there gender and to ensure compatibility with Cochrane review are other health areas where the consideration of the rele- format and style [14]. vance of sex and gender may be more common than in in- fection control research. Limitations The findings of this study are relevant and confirm This study aimed to assess how the reviews had been con- that the reviews did not consider the sex and the gender ducted, and not how they had been reported. However, we of the body of the evidence synthesised. Thus, these re- did not write to the review authors to obtain any missing, views do not provide critical information to judge the incomplete, or unclear information. Thus, we made as- applicability of the results to the target population [112]. sumptions for information that was not clear by reading Also, the sex and gender characteristics should have the review: we generally considered that the lack of report- been considered to judge the “indirectness” of the evi- ing of a particular aspect meant that this was not done. dence with the GRADE (Grading of Recommendations However, this may not represent what the reviewers did. Assessment, Development and Evaluation) system, and During the selection and data extraction processes, we therefore, to rate the quality of that evidence [113]; how- were not masked to the review team or institution. More- ever, we have demonstrated that this was not the case. over, JLA and SCN were the authors of this methodology The tables of characteristics of the included studies are study and three of the included reviews [114–116]. How- essential to describe the sex and the gender of the sub- ever, we prevented that this fact influenced the decisions, jects considered within each study. In our opinion, the as the selection and extraction processes were done by at relevant information is the sex and gender characteris- least two authors independently, and, in case of disagree- tics of the sample from which the study results were ment, we consulted a third author. López-Alcalde et al. BMC Health Services Research (2019) 19:169 Page 13 of 17 We did not measure the reliability of the SGAT-SR This gap does not only affect Cochrane reviews, as it is judgements (for example, by obtaining the kappa statistic), also present in non-Cochrane ones. In fact, SRs do not often so we cannot confirm that our decisions were reliable. analyse or report equity issues in general [38, 46–49], and We encountered some challenges with the use of the sex/gender in particular [17, 25, 26, 33, 35]. SGAT-SR. First, the tool needs to be more operative and manageable, that is, it should provide specific guidance Conclusions with examples taken from other reviews. Second, it is Main conclusions of this study not clear if some items of the tool refer to the planning Consideration of sex and gender in Cochrane reviews of of the review or to what the review finally did. Third, interventions for preventing HAIs was practically absent. the tool should suggest when an item is not applicable; This lack of attention to sex and gender reduces the for example, for reviews with no included studies, it is quality of Cochrane reviews, and the applicability of not clear if the items related to the results must be an- their results for all people: women and men, boys and swered as “not meeting the criteria” or as “not applic- girls, and people of diverse gender identities. able”. Fourth, the tool does not allow explicit assessment on the dimension of sex and the dimension of gender Recommendations derived from this study separately. It gathers both dimensions in the same ques- Cochrane should map the consideration of sex and gender tions. We think that each of these two domains warrants in all Cochrane reviews and, if necessary, plan how to ad- a focused appraisal. Fifth, the tool does not assess rele- dress the shortfalls detected efficiently. vant sections of a Cochrane review, such as the abstract, Cochrane should continue encouraging review authors the plain language summary, the discussion, or the sum- to consider sex and gender in their reviews. mary of findings tables. The SGAT-SR helps to assess how sex and gender As stated in the methods section, we considered that have been considered in a Cochrane review, although it was not applicable to use the SGAT-ST for reviews of this tool has some room for improvement. topics focused on one sex, such as pregnancy or delivery. Cochrane should provide review authors with more opera- We decided this because we felt that the SGAT-SR was tive guidance to consider sex and gender in Cochrane reviews. not developed to assess both features, sex and gender, Cochrane guidance to consider sex and gender in separately. However, although it did not apply to the as- Cochrane reviews should be updated, validated, and re- sessment of the sex content for these reviews, it was still quired to meet the Methodological Expectations of relevant to assess how the gender was addressed. Cochrane Intervention Reviews (MECIR) standards. Finally, it is noteworthy that although sex and gender are Primary studies should consider sex and gender differences important factors in clinical research [90], more work is in their research questions, data, analyses, interpretation and needed to standardise the way sex and gender are measured reporting of the study results. This approach will facilitate and reported, and the methods to determine how these fac- the consideration of sex and gender in systematic reviews tors influence health and health care [90]). There is no con- and meta-analyses. sensus on how to disaggregate demographic and outcome data by sex, gender, or both, or on how to report this infor- Additional files mation. Therefore, the report of crucial information on sex, gender, or both, is incomplete in primary studies and system- Additional file 1: Glossary of terms. (DOCX 28 kb) atic reviews. In the end, this lack of consensus moves away Additional file 2: Interventions defined as eligible. (DOCX 13 kb) from a personalised medicine approach. Additional file 3: Search strategy. (DOCX 15 kb) Additional file 4: SGAT-SR template and guidance. (DOCX 30 kb) Additional file 5: List of included reviews. (DOCX 21 kb) Agreements and disagreements with other studies or Additional file 6: Responses to the Sex and Gender Appraisal Tool for reviews Systematic Reviews (SGAT-SR). (DOCX 96 kb) Our results are consistent with another study describing Additional file 7: Sex and gender appraisal summary. (PDF 643 kb) the consideration of SGBA in Cochrane reviews in the area of cardiovascular health [14], which also concluded Abbreviations that SGBA was practically absent in this sample of CAUTI: Catheter-associated urinary tract infection; CDSR: Cochrane Database Cochrane reviews. In this line, our study supports the of Systematic Reviews; GRADE: Grading of Recommendations Assessment, Development and Evaluation; HAI: Healthcare-associated infection; idea that current Cochrane reviews do not consider sex MECIR: Methodological Expectations of Cochrane Intervention Reviews; and gender, and that there is much room for improve- MRSA: Meticillin- (or methicillin-) resistant Staphylococcus aureus; ment in this aspect. It is also noteworthy that, to our NICE: National Institute for Health and Care Excellence; NIH: National Institutes of Health (NIH); NRS: Non-randomised study; RCT: Randomised knowledge, only one study has appraised the SGBA done controlled trial; RevMan: Review Manager; SAGER: Sex and Gender Equity in in Cochrane reviews [14]. Research; SGAT-SR: Sex and gender appraisal tool for systematic reviews; López-Alcalde et al. BMC Health Services Research (2019) 19:169 Page 14 of 17 SGBA: Sex- and gender-based analysis; SR: Systematic review; UCL: University Ramón y Cajal (Madrid, Spain) and funded by the Institute of Health Carlos III College London; USA: United States of America; WHO: World Health (Ministry of Economy, Industry, and Competitiveness, Spain). SEXCOMPLEX aims Organization to assess the influence of sex/gender differences and sex hormones on the pathogenesis, clinical presentation, course and prognosis of chronic disorders Acknowledgements of complex multifactorial aetiology. This manuscript is the deliverable of one Rebeca Rees (EPPI Centre, Institute of Education, University of London) for of the work packages of the SEXCOMPLEX project. her methodological support and guidance. We published a prior abstract (less than 400 words) and poster presenting Purificación González Villanueva for her support in the data extraction. the preliminary results of this study as part of Global Evidence Summit, Cape EPPI reviewer technical support team for the technical support. Town, South Africa (2017) [117]. SEXCOMPLEX Working Group: Héctor F. Escobar-Morreale, Rosa del Campo, Agustín Albillos, Luisa María Villar, David Jiménez, Jesús López-Alcalde, Javier Ethics approval and consent to participate Zamora (Hospital Universitario Ramón y Cajal). Not applicable. The Ethics Committee of Hospital Universitario Ramón y Cajal (Madrid, Spain) did not require ethical approval for this study, as it does not Funding report on or involve the use of any animal or human data or tissue. This study is part of the SEXCOMPLEX project (“Influence of sex and sex hormones on human chronic disorders of complex etiology”), a two-year Consent for publication project (2017–2019) coordinated by Hospital Ramón y Cajal (Madrid, Spain). Not applicable. The manuscript does not contain data from any individual The SEXCOMPLEX project was supported by Instituto de Salud Carlos III (Plan person. Estatal de I + D + i 2013–2016) and co-financed by the European Development Regional Fund “A way to achieve Europe” (ERDF) grant number PIE16/00050. Competing interests These funding sources had no role in the design of this study, its execution, The authors declare that they have no competing interests. analyses, interpretation of the data, or decision to submit results. Availability of data and materials Publisher’s Note The datasets used and/or analysed during the current study are available Springer Nature remains neutral with regard to jurisdictional claims in from the corresponding author on reasonable request. published maps and institutional affiliations. Authors’ contributions Author details 1 JLA conceived, coordinated, designed, and conducted the study; designed Department of Paediatrics, Obstetrics & Gynaecology and Preventative and executed the search strategy; selected reviews for inclusion; designed Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain. 2Faculty of the data extraction template; piloted the data extraction; extracted data; Health Sciences, Universidad Francisco de Vitoria (UFV)-Madrid, Madrid, Spain. 3 checked the quality of data extraction; analysed and interpreted data and Clinical Biostatistics Unit, Hospital Universitario Ramón y Cajal (IRYCIS), wrote the conclusions; wrote and edited the manuscript; approved the final Madrid, Spain. 4Cochrane Associate Centre of Madrid, Madrid, Spain. 5 report prior to submission; and is the guarantor of the study. ES, SCN and Independent Researcher, Madrid, Spain. 6Preventive medicine Unit, Hospital AFC selected reviews for inclusion; designed the data extraction template; Universitario Ramón y Cajal, Madrid, Spain. 7Iberoamerican Cochrane Centre, piloted the data extraction; extracted data; checked the quality of data IIB Sant Pau, Universitat Autònoma de Barcelona, Madrid, Spain. 8CIBER extraction; analysed and interpreted data; edited the manuscript; revised the Epidemiology and Public Health (CIBERESP), Madrid, Spain. manuscript critically for important intellectual content; and approved the final report before submission. MD extracted data; checked the quality of Received: 14 August 2018 Accepted: 7 March 2019 data extraction; interpreted data; edited the manuscript; revised the manuscript critically for important intellectual content, and approved the final report before submission. XB interpreted data; edited the manuscript; References revised the manuscript critically for important intellectual content; and 1. Health Impact Assessment (HIA) - Glossary of terms used. Available from: approved the final report before submission. JZ conceived, coordinated, and http://www.who.int/hia/about/glos/en/index1.html. designed the study; interpreted data; edited the manuscript; revised the 2. Inequity and inequality in health. Available from: http://www. manuscript critically for important intellectual content, and approved the globalhealtheurope.org/index.php/resources/glossary/values/179-inequity- final report before submission. All authors have made substantive intellectual and-inequality-in-health.html. contributions to the study, and have read and given final approval of the 3. Whitehead M. The concepts and principles of equity and health. Int J manuscript. Health Serv. 1992;22:429–45. 4. Welch V, Petticrew M, Ueffing E, Benkhalti Jandu M, Brand K, Dhaliwal B, Authors’ informations Kristjansson E, Smylie J, Wells GA, Tugwell P. Does consideration and JLA is a PhD candidate in Methodology of Biomedical Research and Public assessment of effects on health equity affect the conclusions of systematic (Department of Paediatrics, Obstetrics & Gynaecology and Preventative reviews? A methodology study. PLoS One. 2012;7:e31360. Medicine at the Universitat Autònoma de Barcelona, Spain). This study is part 5. Petkovic J, Welch V, Jull J, Petticrew M, Kristjansson E, Rader T, Yoganathan of his PhD. M, McGowan J, Lyddiatt A, Grimshaw JM, et al. How health equity is SCN, as part of her dissertation for the MSc Research for Public Policy and reported and analyzed in randomized trials (Protocol). Cochrane Database Practice at the Institute of Education (IOE), University College London (UCL), Syst Rev. 2017:MR000046. https://doi.org/10.1002/14651858.MR000046. analysed a subgroup of the included reviews. The dissertation, presented 6. Nelson A. Unequal treatment: confronting racial and ethnic disparities in September 1st, 2017, was titled “Sex and gender analysis in Cochrane health care. J Natl Med Assoc. 2002;94:666–8. https://www.ncbi.nlm.nih.gov/ reviews of interventions for preventing methicillin-resistant Staphylococcus pubmed/25032386. aureus (MRSA)”, MSc, Institute of Education, University College London, 7. Kelly MP, Morgan A, Exworthy M, Popay J, Tugwell P, Robinson V, Simpson S, London UK. Thus, the dissertation had common elements with our study, in Narayan T, Myer L, Houweling T, et al. The social determinants of health: developing particular, the selection process of the reviews (screening for titles/abstracts an evidence base for political action. Geneva: Final report to the World Health and full texts assessment), and the development of the data extraction tem- Organization Commission on the social determinants of health; 2007. plates. From the total number of reviews included in the study, SCN identi- 8. Petticrew M, Roberts H. How to find the studies: the literature search. In: fied those reviews evaluating interventions to prevent MRSA transmission. Systematic reviews in the social sciences: a practical guide. Oxford: Moreover, the data extraction templates and processes used in the disserta- Blackwell; 2006. p. 79–124. tion represented a pilot of the whole study. 9. WHO Europe: Addressing the social determinants of health: the urban The SEXCOMPLEX Working Group leads the two-year project (2017–2019) ti- dimension and the role of local government. 2012. tled “Influence of sex and sex hormones on human chronic disorders of 10. O'Neill J, Tabish H, Welch V, Petticrew M, Pottie K, Clarke M, Evans T, Pardo complex etiology” (SEXCOMPLEX). The project is coordinated by Hospital Pardo J, Waters E, White H, Tugwell P. Applying an equity lens to López-Alcalde et al. BMC Health Services Research (2019) 19:169 Page 15 of 17 interventions: using PROGRESS ensures consideration of socially stratifying novel knowledge translation tool to aid the implementation of sex/gender factors to illuminate inequities in health. J Clin Epidemiol. 2014;67:56–64. analysis in systematic reviews: a pilot study. PLoS One. 2014;9:e110786. 11. Lorenc T, Petticrew M, Welch V, Tugwell P. What types of interventions 33. Runnels V, Tudiver S, Doull M, Boscoe M. The challenges of including sex/ generate inequalities? Evidence from systematic reviews. J Epidemiol gender analysis in systematic reviews: a qualitative survey. Syst Rev. 2014;3:33. Community Health. 2013;67:190–3. 34. Johnson SM, Karvonen CA, Phelps CL, Nader S, Sanborn BM. Assessment of 12. Evans T, Brown H. Road traffic crashes: operationalizing equity in the analysis by gender in the Cochrane reviews as related to treatment of context of health sector reform. Inj Control Saf Promot. 2003;10:11–2. cardiovascular disease. J Womens Health (Larchmt). 2003;12:449–57. 13. Oliver S. Health promotion, inequalities and young people’s health: a 35. Phillips SP, Hamberg K. Doubly blind: a systematic review of gender in systematic review of research. London: Evidence for Policy and Practice randomised controlled trials. Glob Health Action. 2016;9:29597. Information and Co-ordinating Centre; 2008. 36. Geller SE, Koch AR, Roesch P, Filut A, Hallgren E, Carnes M. The more things 14. Doull M, Runnels VE, Tudiver S, Boscoe M. Appraising the evidence: applying change, the more they stay the same: a study to evaluate compliance with sex- and gender-based analysis (SGBA) to Cochrane systematic reviews on inclusion and assessment of women and minorities in randomized cardiovascular diseases. J Womens Health (Larchmt). 2010;19:997–1003. controlled trials. Acad Med. 2017. https://doi.org/10.1097/ACM. 15. CIHR Institute of Gender and Health launches NEW Training Modules: 0000000000002027. Integrating Sex and Gender into Health Research | Canadian Association of 37. Glossary | Cochrane Community. http://community.cochrane.org/glossary. Research Ethics Boards (CAREB-ACCER). Available from: https://www.careb- 38. Lavis JN, Davies HT, Gruen RL, Walshe K, Farquhar CM. Working within and accer.org/newsroom/cihr-institute-gender-and-health-launches-new- beyond the Cochrane Collaboration to make systematic reviews more training-modules-integrating-sex-and-gender. useful to healthcare managers and policy makers. Healthc Policy. 2006;1:21– 16. Heidari S, Babor TF, Castro PD, Tort S, Curno M. Sex and Gender Equity in 33. https://www.ncbi.nlm.nih.gov/pubmed/19305650. Research: rationale for the SAGER guidelines and recommended use. Res 39. World Health Organization. World Health Assembly: Resolution 5834 on the Integr Peer Rev. 2016;1:2. ministerial summit on health research. 2005. 17. Canadian Institutes of Health Research Institute of Gender and Health: What 40. Mackenbach JP. Tackling inequalities in health: the need for building a a difference sex and gender make: a gender, sex and health research systematic evidence base. J Epidemiol Community Health. 2003;57:162. casebook - CIHR. Vancouver: British Columbia; 2012. 41. Thomas S, Fayter D, Misso K, Ogilvie D, Petticrew M, Sowden A, Whitehead 18. Doull M, Shea B, Puil L, Runnels V, Welch V, Tudiver S, Boscoe M. for the M, Worthy G. Population tobacco control interventions and their effects on Sex/Gender Methods Group: Addressing Sex/Gender in Systematic Reviews: social inequalities in smoking: systematic review. Tob Control. 2008;17:230– Cochrane HIV/AIDS Group Briefing Note. 2014-01. 7. 19. Springer KW, Mager Stellman J, Jordan-Young RM. Beyond a catalogue of 42. Chopra M, Munro S, Lavis JN, Vist G, Bennett S. Effects of policy options for human differences: a theoretical frame and good practice guidelines for resources for health: an analysis of systematic reviews. Lancet. 2008;371:668–74. researching sex/gender in human health. Soc Sci Med. 2012;74:1817–24. 43. Vogel JP, Oxman AD, Glenton C, Rosenbaum S, Lewin S, Gulmezoglu AM, Souza JP. 20. Kaiser A, Haller S, Schmitz S, Nitsch C. On sex/gender related similarities and Policymakers’ and other stakeholders’ perceptions of key considerations for health differences in fMRI language research. Brain Res Rev. 2009;61:49–59. system decisions and the presentation of evidence to inform those considerations: 21. Stangier J, Stähle H, Rathgen K, Fuhr R. Pharmacokinetics and an international survey. Health Res Policy Syst. 2013;11:19. pharmacodynamics of the direct oral thrombin inhibitor dabigatran in 44. Canadian Institutes of Health Research. Gender and sex-based analysis in health healthy elderly subjects. Clin Pharmacokinet. 2008;47:47–59. research: a guide for CIHR researchers and reviewers. Ottawa: CIHR; 2006. 22. Reilly PA, Lehr T, Haertter S, Connolly SJ, Yusuf S, Eikelboom JW, Ezekowitz 45. Tsikata S, Robinson V, Petticrew M, Kristjansson B, Moher D, McGowan J, MD, Nehmiz G, Wang S, Wallentin L, Investigators R-L. The effect of Shea B, Wells G, Tugwell P. Do cochrane systematic reviews contain useful dabigatran plasma concentrations and patient characteristics on the information about health equity? [abstract]. XI cochrane colloquium: frequency of ischemic stroke and major bleeding in atrial fibrillation evidence, health care and culture 2003. patients: the RE-LY Trial (Randomized Evaluation of Long-Term 46. Maden M. Consideration of health inequalities in systematic reviews: a Anticoagulation Therapy). J Am Coll Cardiol. 2014;63:321–8. mapping review of guidance. Syst Rev. 2016;5:202. 23. Soldin OP, Mattison DR. Sex differences in pharmacokinetics and 47. Tugwell P, Maxwell L, Welch V, Kristjansson E, Petticrew M, Wells G, pharmacodynamics. Clin Pharmacokinet. 2009;48:143–57. Buchbinder R, Suarez-Almazor ME, Nowlan MA, Ueffing E, et al. Is health 24. World Health Organization. Taking sex and gender into account in equity considered in systematic reviews of the Cochrane Musculoskeletal emerging infectious disease programmes: an analytical framework. Manila: Group? Arthritis Rheum. 2008;59:1603–10. WHO Regional Office for the Western Pacific; 2011. p. 85. 48. Petticrew M, Whitehead M, Macintyre SJ, Graham H, Egan M. Evidence for 25. Ovseiko PV, Greenhalgh T, Adam P, Grant J, Hinrichs-Krapels S, Graham KE, public health policy on inequalities: 1: the reality according to policymakers. Valentine PA, Sued O, Boukhris OF, Al Olaqi NM, et al. A global call for J Epidemiol Community Health. 2004;58:811–6. action to include gender in research impact assessment. Health Res Policy 49. Welch V, Tugwell P, Petticrew M, de Montigny J, Ueffing E, Kristjansson B, Syst. 2016;14:50. McGowan J, Benkhalti Jandu M, Wells GA, Brand K, Smylie J: How effects on 26. Day S, Mason R, Lagosky S, Rochon PA. Integrating and evaluating sex and health equity are assessed in systematic reviews of interventions. Cochrane gender in health research. Health Res Policy Syst. 2016;14:75. Database Syst Rev. 2010:Mr000028. https://doi.org/10.1002/14651858. 27. Doull M, Shea B, Puil L, Runnels V, Welch V, Tudiver S, Boscoe M, for the Sex MR000028.pub2. Gender Methods Group. Addressing Sex/Gender in Systematic Reviews: 50. Tugwell P, de Savigny D, Hawker G, Robinson V. Applying clinical Cochrane HIV/AIDS Group Briefing Note. Version 2014-01. 2014. epidemiological methods to health equity: the equity effectiveness loop. 28. National Institutes of Health. NIH Guidelines on the inclusion of women and BMJ. 2006;332:358–61. minorities as subjects in clinical research. Federal Register. 1994;59:14508– 51. Hankivsky O, Blackwood E, Hunt R, Pigg S, Morrow M, Reid C, Patton C. 13. https://grants.nih.gov/grants/funding/women_min/guidelines.htm. Gender, diversity and evidence-based decision-making. Health Law Can. 29. Welch V, Brand K, Kristjansson E, Smylie J, Wells G, Tugwell P. Systematic 2007;28:1-15. https://www.ncbi.nlm.nih.gov/pubmed/17982982. reviews need to consider applicability to disadvantaged populations: inter- 52. Rothwell PM. External validity of randomised controlled trials: “to whom do rater agreement for a health equity plausibility algorithm. BMC Med Res the results of this trial apply?”. Lancet. 2005;365:82–93. Methodol. 2012;12:187. 53. Cochrane Methods Equity. Available from: http://methods.cochrane.org/ 30. Methods for the development of NICE public health guidance (third equity/welcome. edition). Available from: https://www.nice.org.uk/process/pmg4/chapter/ 54. Sex/Gender Methods Group | Cochrane Equity. Available from: http:// reviewing-the-scientific-evidence. methods.cochrane.org/equity/sex-and-gender-analysis. 31. Welch V, Petticrew M, Tugwell P, Moher D, O'Neill J, Waters E, White H, group 55. Pratt RJ, Pellowe C, Loveday HP, Robinson N, Smith GW, Barrett S, et al. The P-EB. PRISMA-Equity 2012 extension: reporting guidelines for systematic epic project: developing national evidence-based guidelines for preventing reviews with a focus on health equity. PLoS Med. 2012;9:e1001333. healthcare associated infections. Phase I: Guidelines for preventing hospital- 32. Doull M, Welch V, Puil L, Runnels V, Coen SE, Shea B, O'Neill J, Borkhoff C, acquired infections. Department of Health (England). J Hospital Infect. 2001; Tudiver S, Boscoe M. Development and evaluation of 'briefing notes' as a (47 Suppl):S3-82. López-Alcalde et al. BMC Health Services Research (2019) 19:169 Page 16 of 17 56. European Centre for Disease Prevention and Control. Point prevalence 82. The Editorial Team: Cochrane Methodology Review Group. About The survey of healthcare associated infections and antimicrobial use in Cochrane Collaboration (Cochrane Review Groups (CRGs)). The Cochrane European acute care hospitals. Stockholm: ECDC; 2013. Library. 2012:Art. No.: METHOD. 57. Magill SS, Edwards JR, Bamberg W, Beldavs ZG, Dumyati G, Kainer MA, et al. 83. PROSPERO Inclusion criteria. Available from: http://www.crd.york.ac.uk/prospero/ Multistate point-prevalence survey of health care-associated infections. N #aboutregpage. Engl J Med. 2014;370:1198–208. 84. About Cochrane systematic reviews. Available from: http://www. 58. World Health Organization. Report on the burden of endemic health care- cochranelibrary.com/about/about-cochrane-systematic-reviews.html. associated Infection worldwide. A systematic review of the literature. 85. Thomas JBJ, Graziosi S. EPPI-Reviewer 4.0: software for research synthesis. Geneva: World Health Organisation; 2011. Version 4.0. London: Institute of Education; 2010. 59. World Health Organization. Antimicrobial resistance: global report on 86. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, Clarke M, surveillance, 2014. France; 2014. Devereaux PJ, Kleijnen J, Moher D. The PRISMA statement for reporting 60. Klevens RM, Edwards JR, Richards CL Jr, Horan TC, Gaynes RP, Pollock DA, et systematic reviews and meta-analyses of studies that evaluate health care al. Estimating health care-associated infections and deaths in U.S. hospitals, interventions: explanation and elaboration. Ann Intern Med. 2009;151:W65–94. 2002. Public Health Reports. 2007;122:160–6. 87. Featured Cochrane reviews. Available from: http://www.cihr-irsc.gc.ca/e/193.html. 61. Gould IM, Reilly J, Bunyan D, Walker A. Costs of healthcare-associated 88. Microsoft: Microsoft PowerPoint. 2016. methicillin-resistant Staphylococcus aureus and its control. Clin Microbiol 89. Review Manager (RevMan). Version 5.3. Copenhagen: The Nordic Cochrane Infect. 2010;16:1721–8. Centre, The Cochrane Collaboration; 2014. 62. Marchetti A, Rossiter R. Economic burden of healthcare-associated infection 90. Clayton JA, Tannenbaum C. Reporting sex, gender, or both in clinical in US acute care hospitals: societal perspective. J Med Econ. 2013;16:1399– research? JAMA. 2016;316:1863–4. 404. 91. Gyte Gillian M, Dou L, Vazquez Juan C. Different classes of antibiotics given 63. Siegel JD, Rhinehart E, Jackson M, Chiarello L, and the Healthcare Infection to women routinely for preventing infection at caesarean section. Cochrane Control Practices Advisory Committe: Management of multidrug-resistant Database Syst Rev. 2014. https://doi.org/10.1002/14651858.CD008726.pub2. organisms in healthcare settings. 2006. 92. Haas David M, Morgan S, Contreras K. Vaginal preparation with 64. Al-Hasan MN, Eckel-Passow JE, Baddour LM. Bacteremia complicating gram- antiseptic solution before cesarean section for preventing postoperative negative urinary tract infections: a population-based study. J Infect. 2010;60:278–85. infections. Cochrane Database Syst Rev. 2014;9:CD007892. https://doi. 65. Angele MK, Pratschke S, Hubbard WJ, Chaudry IH. Gender differences in org/10.1002/14651858.CD007892.pub4. sepsis: Cardiovascular and immunological aspects. Virulence. 2014;5:12–9. 93. Hadiati Diah R, Hakimi M, Nurdiati Detty S, Ota E. Skin preparation for 66. Fabbian F, De Giorgi A, Lopez-Soto PJ, Pala M, Tiseo R, Cultrera R, Gallerani preventing infection following caesarean section. Cochrane Database Syst M, Manfredini R. Is Female Gender as Harmful as Bacteria? Analysis of Rev. 2014;17(9):CD007462. https://doi.org/10.1002/14651858.CD007462.pub3. Hospital Admissions for Urinary Tract Infections in Elderly Patients. J 94. Liabsuetrakul T, Choobun T, Peeyananjarassri K, Islam QM. Antibiotic Womens Health. 2015;24:587–92. prophylaxis for operative vaginal delivery. Cochrane Database Syst Rev. 67. Cohen B, Choi YJ, Hyman S, Furuya EY, Neidell M, Larson E. Gender 2014;13(10):CD004455. https://doi.org/10.1002/14651858.CD004455.pub3. differences in risk of bloodstream and surgical site infections. J Gen Intern 95. Low N, Mueller M, Van Vliet HA, Kapp N. Perioperative antibiotics to prevent Med. 2013;28:1318–25. infection after first-trimester abortion. Cochrane Database Syst Rev. 2012; 68. Trentzsch H, Nienaber U, Behnke M, Lefering R, Piltz S. Female sex protects 14(3):CD005217. https://doi.org/10.1002/14651858.CD005217.pub2. from organ failure and sepsis after major trauma haemorrhage. Injury. 2014; 96. Mackeen AD, Packard Roger E, Ota E, Berghella V, Baxter Jason K. Timing of 45(Suppl 3):S20–8. intravenous prophylactic antibiotics for preventing postpartum infectious 69. Klein SL. The effects of hormones on sex differences in infection: from morbidity in women undergoing cesarean delivery. Cochrane Database Syst genes to behavior. Neurosci Biobehav Rev. 2000;24:627–38. Rev. 2014;5(12):CD009516. https://doi.org/10.1002/14651858.CD009516.pub2. 70. Papathanassoglou E, Middleton N, Benbenishty J, Williams G, Christofi MD, 97. May W, Gülmezoglu AM, Ba-Thike K. Antibiotics for incomplete abortion. Hegadoren K. Systematic review of gender- dependent outcomes in sepsis. Cochrane Database Syst Rev. 2007;17(4):CD001779. https://doi.org/10.1002/ Nurs Crit Care. 2017;22:284–92. 14651858.CD001779.pub2. 71. Koch AM, Nilsen RM, Eriksen HM, Cox RJ, Harthug S. Mortality related to 98. Nabhan Ashraf F, Allam Nahed E, Hamed Abdel-Aziz Salama M. Routes of hospital-associated infections in a tertiary hospital; repeated cross-sectional administration of antibiotic prophylaxis for preventing infection after studies between 2004-2011; 2015. caesarean section. Cochrane Database Syst Rev. 2016;17(6):CD011876. 72. Madsen TE, Simmons J, Choo EK, Portelli D, McGregor AJ, Napoli AM. The https://doi.org/10.1002/14651858.CD011876.pub2. DISPARITY Study: do gender differences exist in Surviving Sepsis Campaign 99. Ray A, Ray S: Antibiotics prior to amniotomy for reducing infectious morbidity resuscitation bundle completion, completion of individual bundle elements, in mother and infant. Cochrane Database Syst Rev. 2014;2014(10):CD010626. or sepsis mortality? J Crit Care. 2014;29:473.e477–11. https://doi.org/10.1002/14651858.CD010626.pub2. 73. World Health Organization: Addressing sex and gender in epidemic-prone 100. Smaill Fiona M, Grivell Rosalie M. Antibiotic prophylaxis versus no infectious diseases. Geneva; 2007. prophylaxis for preventing infection after cesarean section. Cochrane 74. Special Collection - Hospital acquired infections. Available from: https:// Database Syst Rev. 2014;10:CD007482. https://doi.org/10.1002/14651858. www.cochranelibrary.com/collections/doi/10.1002/14651858.SC000004/full. CD007482.pub3. 75. Tovey D. The role of The Cochrane Collaboration in support of the WHO 101. Wojcieszek Aleena M, Stock Owen M, Flenady V. Antibiotics for prelabour rupture of Nutrition Guidelines. Adv Nutr. 2014;5:35–9. membranes at or near term. Cochrane Database Syst Rev. 2014;29(10):CD001807. 76. Alderson PTT. The use of Cochrane Reviews in NICE clinical guidelines https://doi.org/10.1002/14651858.CD001807.pub2. [editorial]. Cochrane Database Syst Rev. 2011;8. https://doi.org/10.1002/ 102. Lam Thomas B, Omar Muhammad I, Fisher E, Gillies K, MacLennan S. Types 14651858.ED000032. of indwelling urethral catheters for short-term catheterisation in hospitalised 77. Use of Cochrane Reviews to inform WHO guidelines. Available from: http:// adults. Cochrane Database Syst Rev. 2014;23(9):CD004013. https://doi.org/10. www.cochrane.org/news/use-cochrane-reviews-inform-who-guidelines. 1002/14651858.CD004013.pub4. 78. Singh A, Hussain S, Najmi AK. Role of Cochrane Reviews in informing US 103. Cooper Fergus P, Alexander Cameron E, Sinha S, Omar Muhammad I. private payers' policies. J Evid Based Med. 2017;10:293–331. Policies for replacing long-term indwelling urinary catheters in adults. 79. Lavis J, Davies H, Oxman A, Denis JL, Golden-Biddle K, Ferlie E. Towards Cochrane Database Syst Rev. 2016;26(7):CD011115. https://doi.org/10. systematic reviews that inform health care management and policy-making. 1002/14651858.CD011115.pub2. J Health Serv Res Policy. 2005;10(Suppl 1):35–48. 104. Kidd Emily A, Stewart F, Kassis Nadine C, Hom E, Omar Muhammad I. 80. Tugwell P, Petticrew M, Robinson V, Kristjansson E, Maxwell L, Team CEFE. Urethral (indwelling or intermittent) or suprapubic routes for short-term Cochrane and Campbell Collaborations, and health equity. Lancet. 2006;367: catheterisation in hospitalised adults. Cochrane Database Syst Rev. 2015; 1128–30. 10(12):CD004203. https://doi.org/10.1002/14651858.CD004203.pub3. 81. Petticrew M, Tugwell P, Welch V, Ueffing E, Kristjansson E, Armstrong R, 105. Geller SE, Koch A, Pellettieri B, Carnes M. Inclusion, analysis, and reporting of Doyle J, Waters E. Better evidence about wicked issues in tackling health sex and race/ethnicity in clinical trials: have we made progress? J Womens inequities. J Public Health (Oxf). 2009;31:453–6. Health (Larchmt). 2011;20:315–20. López-Alcalde et al. BMC Health Services Research (2019) 19:169 Page 17 of 17 106. Geller SE, Adams MG, Carnes M. Adherence to federal guidelines for reporting of sex and race/ethnicity in clinical trials. J Womens Health (Larchmt). 2006;15:1123–31. 107. Gilmore-Bykovskyi A, Johnson R, Walljasper L, Block L, Werner N. Underreporting of gender and race/ethnicity differences in NIH-funded dementia caregiver support interventions. Am J Alzheimers Dis Other Demen. 2018;33(3):145-52. https://doi.org/10.1177/1533317517749465. Epub 2017 Dec 27. 108. Vidaver RM, Lafleur B, Tong C, Bradshaw R, Marts SA. Women subjects in NIH-funded clinical research literature: lack of progress in both representation and analysis by sex. J Womens Health Gend Based Med. 2000;9:495–504. 109. Grady D, Chaput L, Kristof M. Results of systematic review of research on diagnosis and treatment of coronary heart disease in women. Evid Rep Technol Assess (Summ). 2003:1–4. https://www.ncbi.nlm.nih.gov/pubmed/ 12827897. 110. Doull M, Runnels V, Tudiver S, Boscoe M. Sex and Gender in Systematic Reviews Planning Tool; 2011. 111. The Sex/Gender Methods Group: Guidance for reviews with the HIV/AIDS Review Group. Sex/Gender Methods Group Version 2014-01. 2014. 112. Britton A, McKee M, Black N, McPherson K, Sanderson C, Bain C. Threats to applicability of randomised trials: exclusions and selective participation. J Health Serv Res Policy. 1999;4:112–21. 113. Guyatt GH, Oxman AD, Kunz R, Woodcock J, Brozek J, Helfand M, Alonso- Coello P, Falck-Ytter Y, Jaeschke R, Vist G, et al. GRADE guidelines: 8. Rating the quality of evidence--indirectness. J Clin Epidemiol. 2011;64:1303–10. 114. Barajas-Nava Leticia A, López-Alcalde J, Roqué i Figuls M, Solà I, Bonfill Cosp X. Antibiotic prophylaxis for preventing burn wound infection. Cochrane Database Syst Rev. 2013;6(6):CD008738. https://doi.org/10.1002/14651858. CD008738.pub2. 115. Bravo Zuñiga Jessica I, Loza Munárriz C, López-Alcalde J. Isolation as a strategy for controlling the transmission of hepatitis C virus (HCV) infection in haemodialysis units. Cochrane Database Syst Rev. 2016;(8):CD006420. https://doi.org/10.1002/14651858.CD006420.pub2. 116. López-Alcalde J, Mateos-Mazón M, Guevara M, Conterno LO, Solà I, Cabir Nunes S, Bonfill Cosp X. Gloves, gowns and masks for reducing the transmission of meticillin-resistant Staphylococcus aureus (MRSA) in the hospital setting. Cochrane Database Syst Rev. 2015;7:CD007087. https://doi. org/10.1002/14651858.CD007087.pub2. 117. López-Alcalde J, Stallings E, Cabir S, Zamora J. Abstract 1052: Sex/gender analysis in Cochrane reviews of healthcare-associated infections is uncommon. Cochrane Database Syst Rev. 2017;9:160. https://doi.org/10. 1002/14651858.CD201702.