Reply to “Letter to the Editor, re: <scp>GRACE</scp>‐2: <scp>Low‐Risk</scp>, Recurrent Abdominal Pain in the Emergency Department”

In reply: Thank you for the interest in the Guidelines for Reasonable and Appropriate Care in the Emergency Department (GRACE) regarding low-risk, recurrent abdominal pain in the emergency department (ED).1 We hope that you and many others will take the time to read GRACE-2, to understand the complexity of the issues we considered over 18 months of careful and deliberate work. Many of the issues highlighted were thoroughly considered in the GRACE-2 document, accompanying reviews, and supplements, including items designed specifically for patient communication. The GRACE-2 writing group, with four female members including our patient representative, followed a comprehensive methodology process in an effort to achieve a guideline that is transparent and evidence-based and serves stakeholders, most importantly patients. GRACE exists for and because of Society for Academic Emergency Medicine (SAEM) members and we rely on members for active engagement by providing constructive feedback, for future topic ideas, and as content experts.2 Developing guidelines that we can trust has several challenges including funding, time commitment, expertise required, transparent methodological practices, reconciling conflicting guidelines, and managing conflicts of interest. The Institute of Medicine has called for trustworthy clinical guidelines for more than 30 years,3, 4 proposing standards that were followed by GRACE. In the context of better and transparent guidelines, the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was created,5 with specific guidance on how to interpret the evidence and facilitate the translation to the decisions and recommendations. Within each question proposed in the guidelines, there is a thorough evaluation of desirable and undesirable effects, certainty of the research evidence, values, balance of effects, resources required, cost-effectiveness, equity, acceptability, and feasibility. These assessments are based in both the research evidence and additional considerations that the GRACE-2 writing group (including the patient representative) discussed in each meeting during the development process. These evidence to decision frameworks are published as an accompanying appendix. The highlighted issues are very important, and we acknowledge the existence of sex and gender bias in medicine. Clinical guidelines rely heavily on published literature, and we performed a comprehensive review assisted by two librarians. We worked with direct and indirect evidence, extrapolating articles from both within and outside of emergency medicine.6 We did not find literature on recurrent low-risk abdominal pain presenting to the ED that included gender-informed or gender bias (or race, age, and sexual orientation)–specific topics7 and even less data on psychologizing chronic abdominal pain or dismissing symptoms in this scenario. GRADE calls for the strength of recommendations to be transparently communicated, and following this guidance, all of the GRACE-2 recommendations are designated as "no evidence" or "very low certainty"—allowing readers to understand the limited when deciding how to implement them. The GRACE-2 writing group considered the potential effects of sex and gender in each of the questions, not solely in relationship to imaging. Women are more likely to suffer abdominal pain, and biological sex is central for the differential diagnosis and management of these patients. GRACE-2 specifically mentioned how radiation and cancer risk differs by sex. We described how women are more likely to undergo repeat computed tomography (CT) (74%), and female gender is associated with higher CT positivity rate and repeated CTs. The importance of reducing radiation exposure in women of childbearing age was also mentioned. Furthermore, for the recommendation of ultrasound (US) after normal CT, we discussed pelvic US and gallbladder pathology, both more common in women. Transvaginal US was considered in the harm and burden section, discussing the discomfort of the procedure, the challenge for non–sexually active females and those with prior sexual trauma/abuse, and the need for additional resources such as a chaperone and private examination room. We discussed differences in management of abdominal pain, with women being less likely to receive any analgesia (60% vs. 67%) and opioids (45% vs. 56%), and women waiting longer than men for administration of analgesia (16-min difference) despite similar pain scores. These differences were also seen among racial minorities independent of biological sex, with patients who are Black and Latinx receiving less analgesia than those who are White.1, 8, 9 We strongly agree with the need for compassionate care and empathy for all patients, and we are surprised to hear that we might have given a different impression to readers. Our guidelines deliberately include patient representatives in the writing panels. Patients add their lived experiences and are key for the discussions and framing the recommendations. Specifically for GRACE-2, our patient representative was a woman who was included as a co-author. We strive for diverse writing groups including women, and all voices were heard in the nearly 50 h of group discussions over the year. Furthermore, women are represented throughout the entire GRACE process, including selecting topics, leading groups, and providing methodology expertise. We specifically discussed diversity characteristics (such as sex, gender, race, and ethnicity) as we reviewed the literature and created the guidelines. Regarding the authors' concern for screening for depression and anxiety in the ED, we agree that this is a sensitive topic and one that was discussed extensively during the GRACE-2 deliberation process. This topic was specifically supported by our patient representative. The inclusion of topics such as depression, anxiety, and opioids was an explicit attempt to look beyond more imaging/technology as the solution. The ED might be the only opportunity to engage a patient with an undiagnosed illness (which may include depression and/or anxiety) that has treatment (including nonpharmacological options). This is particularly important for patients who have limited access to health care services (e.g., undomiciled, uninsured, and underinsured patients). Recognition and early intervention of anxiety and depression are critical for better outcomes, with repeated presentations representing a unique opportunity to intervene. We highlighted that the presence of depression and/or anxiety does not exclude a coexisting serious cause of abdominal pain, and physicians should not use mental health screening as a method to determine the need for further evaluation of abdominal pain. We emphasized that the coexistence of depression and abdominal pain does not prove a causal relationship, and complex interactions are possible. We also discussed the importance of educating ED practitioners on nociplastic pain conditions, personality factors (of both practitioners and patients) that impact clinical outcomes, and the need for a compassionate approach to chronic pain conditions in the ED. Within the guideline, we extensively discuss the potential benefits, harms, and burdens of our recommendations, as guided by the GRADE process. We found no direct evidence on the harms of screening in our population of interest. We explicitly warn of the potential risks of stigma or mistakenly assuming that depression and/or anxiety are the cause of symptoms. We also include language guarding against this in documents written specifically for patient education, where we felt it was essential to address this issue. All GRACE clinical guidelines have a 45-day period open for comments before they are finalized and published. This process is critical to incorporate perspectives that might have been missed during the development process. Within this open period, we specifically invite all SAEM academies/groups and members to review the guideline and comment, so their feedback can be added to the evidence to decision framework and the recommendations can be reviewed prior to publication. We encourage readers and SAEM members to actively participate in this review process so that the resulting guidelines can have the greatest possible clinical value to all stakeholders. There are several ongoing as well as future GRACE clinical guidelines with an opportunity to continue to build up current research evidence. We invite the authors to consider how to further develop guidelines with a sex- and gender-based lens; directions on how, when, and in which scenarios the gender lens should be applied; and how to objectively measure whether a gender-based lens has or has not been attained.

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