Best Practice Recommendations for Conducting and Reporting Controlled Trials in Clinical Hypnosis Research.

There is an abundance of outcomes research for clinical hypnosis showing promising results. Nonetheless, hypnosis is still underutilized in clinical care. For a behavioral intervention to enter mainstream clinical care, efficacy needs to be demonstrated with exceptionally high quality of evidence, and its reporting needs to be complete and sufficiently clear to enable replication and clinical use. The present article provides best practice guidelines formulated by the Task Force for Establishing Efficacy Standards for Clinical Hypnosis for conducting and reporting clinical hypnosis research.The recommendations are presented in two tiers. Tier I recommendations include essential best practices, such as a call for the use of detailed research and intervention manuals, plans for and reporting of participant-education about hypnosis, the use of hypnotizability scales with good psychometric properties, and clear reporting of the hypnotizability measurement. Tier I also includes the sharing of intervention manuals, the reporting of the induction procedure, the labeling of the intervention for participants, and the definition of hypnosis used. Tier II includes preferred recommendations, calling for measurement of adherence to home practice, measurement of hypnotizability using scales with both subjective and behavioral measures of responsiveness, and the involvement of participants from the full hypnotizability spectrum. Tier II also includes the assessment of variables related to proposed mechanisms of action, the reporting of participants prior hypnosis experiences, and the relationship of expectancies and treatment outcomes.This list of recommendations will be useful for researchers, reviewers, and journal editors alike when conducting, reporting, or evaluating studies involving clinical hypnosis.

Diagnostic classification systems for disorders of gut-brain interaction should include psychological symptoms.

BACKGROUND AND AIMS: The group of disorders known as Disorders of Gut Brain Interaction (DGBI) were originally labeled functional GI disorders and were thought to be disorders of the gastrointestinal tract that had several psychological conditions as comorbidities. Despite mounting evidence that psychological morbidity plays an innate role in the etiology and maintenance of DGBI, none of the Rome IV criteria include any measure of psychological symptoms. This study tested the hypothesis that individuals would cluster differently if GI symptoms alone were considered versus GI symptoms combined with measures of psychological symptoms. METHODS: Data were obtained from the Rome Foundation Global Epidemiology Study measuring Rome IV GI symptoms, psychological measures and demographic characteristics. Latent profile models were used to cluster individuals based on (i) GI symptoms only (GI only) and then (ii) GI and psychological measures (GI + Psych). KEY RESULTS: Individuals clustering into the same group of individuals whether formed via GI only or GI + Psych, ranged from 96% for a 2-class solution (the most simplistic) to 76% with 6 classes (the parsimonious system) and 59% with twenty-two classes (mimicking Rome IV). The generalisability of this finding between six geographic regions was confirmed with agreement varying between 95%-97% for 2 clusters and 71-79% for 6 classes and 51%-63% for 22 classes. These findings were also consistent between DGBI (range 94% with 2 classes to 50% with 22 classes) and non-DGBI (range 97% with 2 clusters to 65% with 22 classes) groups. CONCLUSIONS & INFERENCES: Our data suggest that considering psychological as well as gastrointestinal symptoms would lead to a different clustering of individuals in more complex, and accurate, classification systems. For this reason, future work on DGBI classification should consider inclusion of psychological traits.

Symptom bothersomeness and life interference support Rome clinical criteria as clinically relevant indicators of DGBI.

BACKGROUND: Irritable bowel syndrome (IBS) and functional dyspepsia (FD) are common disorders of gut-brain interaction (DGBI). The Rome IV criteria are the gold standard for research when diagnosing DGBI. However, bothersomeness, or the degree to which symptoms are distressing or disruptive to a person's daily life, is a potential treatment-seeking motivator that is not assessed by the Rome criteria. The Rome Foundation developed and published diagnostic criteria for clinical practice that include bothersomeness. We aimed to evaluate these constructs via patient focus groups to determine what prompts healthcare-seeking as a means to assess its value in the Rome clinical criteria. METHODS: Adults meeting Rome IV criteria for IBS, FD, or both participated in focus groups in Australia and the United States. Semi-structured interview transcripts were analyzed using Template Thematic Analysis, with three a priori and other a posteriori themes refined iteratively through team discussion and consensus. KEY RESULTS: Participants confirmed the frequency and duration of symptoms was not sufficient to reflect illness experience. Four major themes emerged: (1) Bothersomeness should be included in assessments of IBS and FD; (2) Patients find many DGBI symptoms bothersome; (3) Bothersomeness traverses multiple domains of quality of life; (4) Patients may hesitate to seek medical advice due to past negative experiences. CONCLUSIONS AND INFERENCES: These findings support the value of the Rome Clinical Criteria. They emphasize the importance of expanding assessments of patients with DGBI to include how bothersome they perceive symptoms to be, how much symptoms interfere with their daily life, and what may moderate their decisions to seek treatment.

Worldwide Prevalence and Description of Cyclic Vomiting Syndrome According to the Results of the Rome Foundation Global Epidemiology Study.

INTRODUCTION: Cyclic vomiting syndrome (CVS) is a disorder of gut-brain interaction of unknown origin. The aim of this study was to evaluate the global prevalence of this disorder and its associated factors. METHODS: Data were collected from nationwide Internet surveys in 26 countries, with subjects evenly distributed by age, sex, and country. The survey included the Rome IV questionnaire and an extensive supplemental questionnaire to evaluate additional factors. RESULTS: A total of 54,127 participants completed the questionnaire (51% male, mean age 44.3 years). The pooled prevalence of CVS was 0.3% (95% confidence interval [CI] 0.3%-0.4%; n = 187), highest in Brazil (1%, 95% CI 0.6-1.5), and lowest in Japan and Germany (with no subject who fulfilled the criteria for CVS). The mean age of participants with CVS was 36.7 years (SD 13.5), and it was more common in women (56.7% vs 43.5%). Factors independently associated with this syndrome were female sex (odds ratio [OR] 1.52, 95% CI 1.13-2.03), young age (OR 2.57, 95% CI 1.34-4.94, for people between the ages of 18 and 39 years, compared with those older than 65 years), depression (OR 3.14, 95% CI 2.05-4.82, P < 0.001), and anxiety (OR 1.79, 95% CI 1.15-2.78, P < 0.001). Individuals with CVS had impaired quality of life (QoL) (Patient-Reported Outcomes Measurement and Information System 10-item score: physical QoL mean, 12.9 vs 15.5, P < 0.001; mental QoL mean 12.3 vs 14.4, P < 0.001) compared with others. DISCUSSION: CVS is a relatively common disorder that has a negative impact on QoL. It is important to raise awareness on this syndrome to avoid underdiagnosis and improve clinical practice.

Sex differences in patient-reported outcomes and the association with clinical factors in axial spondyloarthritis patients treated with tumour necrosis factor inhibitors.

OBJECTIVES: To investigate sex differences in patient-reported outcome measures (PROMs) among axSpA patients initiating their first TNFi and identify factors contributing to these disparities over the follow-up. METHODS: Data were included from 15 EuroSpA registries and consisted of axSpA patients initiating their first TNFi, with ≥2 measurements for each analysed PROM (BASDAI and BASFI, scale 0-100) taken at any time point. Linear mixed models were employed to analyse sex differences in PROMs over 24 months and to evaluate how baseline characteristics were related to the observed sex differences. RESULTS: We analysed 13 102 (38% women) in the BASDAI analyses and 10 623 (38% women) in the BASFI analyses. At follow-up, mean sex differences in BASDAI increased from 4.3 units at baseline (95% CI, 3.5-5.1)-8.0 (7.2-8.8) at 6 months, and in BASFI from 2.2 (1.4-3.1)-4.6 (3.6-5.5), with consistently worse scores in women. Baseline characteristics could not substantially account for the observed sex differences over time; however, the magnitude of the sex differences was reduced by HLA-B27 positivity, longer disease duration, and increased CRP levels, but increased by TNFi initiation in later years and peripheral arthritis. CONCLUSION: In axSpA patients initiating their first TNFi, baseline sex differences in BASDAI and BASFI increased two-fold after 6 months of treatment and persisted thereafter, with worse scores in women. Several baseline characteristics moderated the sex differences, though none could fully account for them. These findings improve our understanding of sex differences and underscore their importance in axSpA.

Pain is a cardinal symptom cutting across Rome IV anatomical categories in disorders of gut-brain interaction: A network-based approach.

INTRODUCTION: Disorders of gut-brain interaction (DGBI) are symptom-based disorders categorized by anatomic location but have high overlap and heterogeneity. Viewing DGBI symptoms on a spectrum (i.e. dimensionally) rather than categorically may better inform interventions to accommodate complex clinical presentations. We aimed to evaluate symptom networks to identify how DGBI symptoms interact. METHODS: We used the Rome IV Diagnostic Questionnaire continuously/ordinally scored items collected from the Rome Foundation Global Epidemiology Study. We excluded participants who reported ≥1 organic/structural gastrointestinal disorder(s). We sought to (1) identify core symptoms in the DGBI symptom networks, (2) identify bridge pathways between Rome IV diagnostic categories (esophageal, bowel, gastroduodenal, anorectal), and (3) explore how symptoms group together into communities. RESULTS: Of 54,127 adults, 20,229 met criteria for at least one DGBI (age mean = 42.2 ± 15.5; 57% female). General abdominal pain and epigastric pain were the core symptoms in the DGBI symptom network (i.e., had the strongest connections to other symptoms). Pain symptoms emerged as bridge pathways across existing DGBI diagnostic anatomic location (i.e., abdominal pain connected to chest pain, epigastric pain, rectal pain). Without a priori category definitions, exploratory network community analysis showed that symptoms grouped together into "pain," "gastroduodenal," and "constipation," rather than into groups by anatomic location. CONCLUSION: Our findings suggest pain symptoms are central and serve as a key connection to other symptoms, crosscutting anatomic location. Future longitudinal research is needed to test symptom network relations longitudinally and investigate whether targeting pain symptoms (rather than anatomic- or disorder-specific symptoms) has clinical impact.

Symptom profiles compatible with disorders of gut-brain interaction (DGBI) in organic gastrointestinal diseases: A global population-based study.

BACKGROUND: Patients with organic gastrointestinal (GI) diseases and diabetes mellitus (DM) can have concomitant disorders of gut-brain interaction (DGBI). OBJECTIVE: This study aimed to compare the global prevalence of DGBI-compatible symptom profiles in adults with and without self-reported organic GI diseases or DM. METHODS: Data were collected in a population-based internet survey in 26 countries, the Rome Foundation Global Epidemiology Study (n = 54,127). Individuals were asked if they had been diagnosed by a doctor with gastroesophageal reflux disease, peptic ulcer, coeliac disease, inflammatory bowel disease (IBD), diverticulitis, GI cancer or DM. Individuals not reporting the organic diagnosis of interest were included in the reference group. DGBI-compatible symptom profiles were based on Rome IV diagnostic questions. Odds ratios (ORs [95% confidence interval]) were calculated using mixed logistic regression models. RESULTS: Having one of the investigated organic GI diseases was linked to having any DGBI-compatible symptom profile ranging from OR 1.64 [1.33, 2.02] in GI cancer to OR 3.22 [2.80, 3.69] in IBD. Those associations were stronger than for DM, OR 1.26 [1.18, 1.35]. Strong links between organic GI diseases and DGBI-compatible symptom profiles were seen for corresponding (e.g., IBD and bowel DGBI) and non-corresponding (e.g., IBD and esophageal DGBI) anatomical regions. The strongest link was seen between fecal incontinence and coeliac disease, OR 6.94 [4.95, 9.73]. After adjusting for confounding factors, associations diminished, but persisted. CONCLUSION: DGBI-compatible symptom profiles are more common in individuals with self-reported organic GI diseases and DM compared to the general population. The presence of these concomitant DGBIs should be considered in the management of organic (GI) diseases.

Novel Irritable Bowel Syndrome Subgroups are Reproducible in the Global Adult Population.

BACKGROUND & AIMS: Current classification systems for irritable bowel syndrome (IBS) based on bowel habit do not consider psychological impact. We validated a classification model in a UK population with confirmed IBS, using latent class analysis, incorporating psychological factors. We applied this model in the Rome Foundation Global Epidemiological Survey (RFGES), assessing impact of IBS on the individual and the health care system, and examining reproducibility. METHODS: We applied our model to 2195 individuals in the RFGES with Rome IV-defined IBS. As described previously, we identified 7 clusters, based on gastrointestinal symptom severity and psychological burden. We assessed demographics, health care-seeking, symptom severity, and quality of life in each. We also used the RFGES to derive a new model, examining whether the broader concepts of our original model were replicated, in terms of breakdown and characteristics of identified clusters. RESULTS: All 7 clusters were identified. Those in clusters with highest psychological burden, and particularly cluster 6 with high overall gastrointestinal symptom severity, were more often female, exhibited higher levels of health care-seeking, were more likely to have undergone previous abdominal surgeries, and had higher symptom severity and lower quality of life (P < .001 for trend for all). When deriving a new model, the best solution consisted of 10 clusters, although at least 2 seemed to be duplicates, and almost all mapped on to the previous clusters. CONCLUSIONS: Even in the community, our original clusters derived from patients with physician-confirmed IBS identified groups of individuals with significantly higher rates of health care-seeking and abdominal surgery, more severe symptoms, and impairments in quality of life.

The aging gastrointestinal tract: Epidemiology and clinical significance of disorders of gut-brain interaction in the older general population.

BACKGROUND: Most previous reports on the prevalence of disorders of gut-brain interaction (DGBI) show higher rates in younger individuals. Exceptions are faecal incontinence and functional constipation. AIM: To compare prevalence rates for 22 DGBI and 24 primary symptoms, by age, using the Rome Foundation Global Epidemiology (RFGES) study dataset. METHODS: The RFGES dataset enables diagnosis of 22 DGBI among 54,127 participants (≥18 years) in 26 countries. Older age was defined as ≥65 years. We assessed differences between age groups by sex, geographic region, somatisation, abnormal anxiety and depression scores, quality of life (QoL), individual gastrointestinal symptoms and disease severity for irritable bowel syndrome (IBS). RESULTS: Rates for any DGBI were 41.9% and 31.9% in the <65 and ≥65 age groups, respectively. For all Rome IV diagnoses except faecal incontinence, rates were higher in the younger group. The older group had lower scores for any DGBI by geographic region, non-gastrointestinal somatic symptoms, abnormal anxiety and depression scores, and IBS severity, and better scores for QoL. The mean number of endorsed symptoms and their frequency were higher in the younger group. CONCLUSIONS: In this large general population study, the prevalence and impact of DGBI, apart from faecal incontinence, were higher in the younger group. Despite this, DGBI rates are still high in absolute terms in the ≥65 age group and necessitate clinical awareness and, perhaps, an age-specific treatment approach.

Acute and Long-Term Effects of App-Delivered Heartfulness Meditation on Psychological Outcomes and the Endocannabinoid Signaling System in Cyclic Vomiting Syndrome.

INTRODUCTION: Cyclic vomiting syndrome (CVS) is a disorder of gut-brain interaction often triggered by stress. Interventions such as meditation may improve psychological outcomes and health-related quality of life (HRQoL), but their efficacy and the underlying mechanism are unknown. METHODS: We conducted a 6-week single-arm pilot study to assess the effects of heartfulness meditation (HFM) in CVS using a custom-designed meditation app. Primary outcomes included state and trait anxiety and mood state changes pre vs post-meditation, and secondary outcomes were psychological distress, coping, sleep quality, and HRQoL at baseline and at weeks 3 and 6. Serum concentrations of endocannabinoids N -arachidonylethanolamine and 2-arachidonoylglycerol and related lipids were measured pre- and post-HFM at baseline and week 6. RESULTS: In 30 treatment completers, there was a significant improvement in state anxiety ( P < 0.001), total mood disturbance ( P < 0.001), and other mood states (all P values < 0.05) across the 3 time points. Trait anxiety was also improved at week 6. There was a significant improvement in psychological distress (Global Severity Index), sleep quality (daytime dysfunction), coping (using religion/spirituality), and HRQoL (mental and physical) across the 3 time points (all P < 0.05). Significant increases in N -arachidonylethanolamine and related lipids N -oleoylethanolamine and palmitoylethanolamide post vs pre-HFM were observed at week 6 ( P < 0.001, 0.002, 0.003, respectively). No adverse effects were noted. DISCUSSION: App-delivered HFM is feasible, safe, and effective and improves psychological outcomes and augments endocannabinoids. This provides insight into the mechanism underlying HFM and has potential for widespread use as a digital therapeutic in CVS and other disorder of gut-brain interaction.

Confirmatory validation of the patient health questionnaire - 4 (PHQ-4) for gastrointestinal disorders: A large-scale cross-sectional survey.

OBJECTIVE: Using the large Rome Foundation Global Epidemiology Survey dataset, the aim of this study was to evaluate the construct and convergent validity and internal consistency of the PHQ-4 across both gastrointestinal and non-gastrointestinal condition cohorts. Another aim was to provide descriptive information about the PHQ-4 including means, confidence intervals and percentage of caseness using a large representative sample. METHODS: A cross-sectional survey was conducted in 26 countries. Confirmatory factor and internal consistency analyses were conducted across subsamples of patients with gastrointestinal conditions (i.e., disorders of gut-brain interaction [DGBI; any DGBI, individual DGBI, and DGBI region], gastroesophageal reflux disease (GERD), coeliac disease, diverticulitis, inflammatory bowel disease (IBD), cancer anywhere in the gastrointestinal tract, peptic ulcer) and those without a gastrointestinal condition. Convergent validity was also assessed via a series of Pearson's correlation coefficients with PROMIS (physical and mental quality of life), and PHQ-12 (somatisation). RESULTS: Based on 54,127 participants (50.9% male; mean age 44.34 years) confirmatory factor analysis indicated acceptable to excellent model fits for the PHQ-4 across all subsamples and individual DGBI and DGBI region (Comparative Fit Index >0.950, Tucker-Lewis Index >0.950, Root Mean Squared Error of Approximation <0.05, and Standardised Root Mean Square Residual <0.05). The PHQ-4 was found to demonstrate convergent validity (Pearson's correlation coefficients >±0.4), and good internal consistency (Cronbach's α > 0.75). CONCLUSIONS: This study provides evidence that the PHQ-4 is a valid and reliable tool for assessing mental health symptomology in both gastrointestinal and non-gastrointestinal cohorts.

Worldwide population prevalence and impact of sub-diagnostic gastrointestinal symptoms.

BACKGROUND: The Rome Foundation Global Epidemiology Study (RFGES) found that 40.3% of adults in 26 internet-surveyed countries met Rome IV criteria for disorders of gut-brain interaction (DGBI). However, additional people not meeting DGBI criteria may also be burdened by frequent gastrointestinal symptoms. AIMS: To explore the prevalence and demographic distribution of sub-diagnostic gastrointestinal symptoms, and the hypothesised associated effects on quality of life (QoL), life functioning and healthcare needs. METHODS: We analysed data from the RFGES survey, which included the Rome IV diagnostic questionnaire and QoL, psychological, work productivity and healthcare questions. RESULTS: Of the 50,033 people without a history of organic gastrointestinal disorders, 25.3% classified in the sub-diagnostic group (no DGBI but one or more frequent gastrointestinal symptoms), 41.4% had DGBI and 33.4% had no frequent gastrointestinal symptoms (non-GI group). Sub-diagnostic prevalence in different world regions ranged from 22.2% (North America) to 30.5% (Middle East), was slightly higher among males than females and decreased with age. The sub-diagnostic group was intermediate between the non-GI and DGBI groups, and significantly different from both of them on QoL, anxiety, depression, somatisation, healthcare utilisation and life and work impairment. CONCLUSIONS: One in four adults without organic gastrointestinal disorders or DGBI report frequent gastrointestinal symptoms. This sub-diagnostic group has reduced QoL, greater psychological and non-GI bodily symptoms, impaired work productivity and life activities and greater healthcare use compared to non-GI individuals. This suggests that many in this sub-diagnostic group might benefit from healthcare services or symptom self-management advice.

Global Prevalence of Psychological Distress and Comorbidity With Disorders of Gut-Brain Interactions.

INTRODUCTION: This study focused on defining the global prevalence of clinically relevant levels of psychological distress and somatic symptoms and the prevalence of coexistence between these symptoms and disorders of gut-brain interaction (DGBI). We also analyzed how clinically relevant psychological distress and somatic symptoms and coexistent DGBI are associated with health-related outcomes. METHODS: We included a representative sample of 54,127 adult participants (49.1% women; mean age of 44.3 years) from 26 countries worldwide. Participants completed an Internet survey (the Rome Foundation Global Epidemiology Study) with validated self-report questionnaires. RESULTS: Clinically relevant psychological distress and/or somatic symptom severity was reported by 37.5% of the sample. These participants had 4.45 times higher odds to have at least one DGBI than individuals without psychological distress and/or somatic symptoms. Compared with participants with psychological distress and/or somatic symptoms with vs without DGBI, participants with a DGBI reported increased healthcare and medication utilization (with OR from 1.6 to 2.8). Coexistent DGBI in participants with psychological distress and/or somatic symptoms was the variable most strongly associated with reduced mental (ß = -0.77; confidence interval [-0.86 to -0.68]) and physical (ß = -1.17; confidence interval [-1.24 to -1.10]) quality of life. DISCUSSION: This global study shows that psychological distress, somatic symptoms, and DGBI are very common and frequently overlap. The coexistence between psychological distress/somatic symptoms and DGBI seems to be especially detrimental to quality of life and healthcare utilization. Individuals with psychological distress/somatic symptoms and DGBI coexistence seem to be a group vulnerable to psychosocial problems that should be studied further and would likely benefit from psychological/psychiatric interventions.

The aging gut: Symptoms compatible with disorders of gut-brain interaction (DGBI) in older adults in the general population.

BACKGROUND: Little is known about changes in gastrointestinal symptoms compatible with disorders of gut-brain interaction (DGBI) with increasing age at the population level. The objective of this study was to describe the patterns of DGBI in individuals 65 years of age and above and contrasting them with those of younger adults. METHODS: A community sample of 6300 individuals ages 18 and older in the US, UK, and Canada completed an online survey. Quota-based sampling was used to ensure equal proportion of sex and age groups (40% aged 18-39, 40% aged 40-64, 20% aged 65+) across countries, and to control education distributions. The survey included the Rome IV Diagnostic Questionnaire for DGBI, demographic questions, questionnaires measuring overall somatic symptom severity and quality of life, and questions on healthcare utilization, medications, and surgical history. RESULTS: We included 5926 individuals in our analyses; 4700 were 18-64 years of age and 1226 were ages 65+. Symptoms compatible with at least one DGBI were less prevalent in participants ages 65+ vs. ages 18-64 years (34.1% vs. 41.3%, p < 0.0001). For symptoms compatible with upper GI DGBI, lower prevalence for most disorders was noted in the 65+ group. For lower GI DGBI, a different pattern was seen. Prevalence was lower in ages 65+ for irritable bowel syndrome and anorectal pain, but no differences from younger participants for the disorders defined by abnormal bowel habits (constipation and/or diarrhea) were seen. Fecal incontinence was the only DGBI that was more common in ages 65+. Having a DGBI was associated with reduced quality of life, more severe non-GI somatic symptoms, and increased healthcare seeking, both in younger and older participants. CONCLUSION: Symptoms compatible with DGBI are common, but most of these decrease in older adults at the population level, with the exception of fecal incontinence which increases. This pattern needs to be taken into account when planning GI health care for the growing population of older adults.

[Eosinophilic small vessel vasculites (EGPA) a hidden severe asthma comorbitity].

A 72-year-old woman presented to the emergency department due to worsening dyspnea. She had been diagnosed with asthma a year earlier. At arrival, her oxygen saturation was only 84%. During lung auscultation, wheezing was noted over all lung fields. A blood test showed a significant increase in eosinophils in peripheral blood, highest value of 1.4 x 10E9/L. Further investigations in the respiratory ward showed a positive MPO-ANCA, which, together with clinical features of asthma, chronic rhinosinusitis with polyps, mononeuritis multiplex and eosinophilia, led to the diagnosis of eosinophilic granulomatosis with polyangiitis, or what used to be called Churg-Strauss syndrome. Corticosteroid treatment was initiated and subsequently tapered down when treatment with mepolizumab was started, which is an IL-5 inhibitor. Her symptoms quickly became much better. Frequent exacerbations and pulmonary symptoms became things of the past.

Dietary fatty acids improve perceived sleep quality, stress, and health in migraine: a secondary analysis of a randomized controlled trial.

Background: Migraine is a prevalent disabling condition often associated with comorbid physical and psychological symptoms that contribute to impaired quality of life and disability. Studies suggest that increasing dietary omega-3 fatty acid is associated with headache reduction, but less is known about the effects on quality of life in migraine. Methods: After a 4-week run-in, 182 adults with 5-20 migraine days per month were randomized to one of the 3 arms for sixteen weeks. Dietary arms included: H3L6 (a high omega-3, low omega-6 diet), H3 (a high omega-3, an average omega-6 diet), or a control diet (average intakes of omega-3 and omega-6 fatty acids). Prespecified secondary endpoints included daily diary measures (stress perception, sleep quality, and perceived health), Patient-Reported Outcome Measurement Information System Version 1.0 ([PROMIS©) measures and the Migraine Disability Assessment (MIDAS). Analyses used linear mixed effects models to control for repeated measures. Results: The H3L6 diet was associated with significant improvements in stress perception [adjusted mean difference (aMD): -1.5 (95% confidence interval: -1.7 to -1.2)], sleep quality [aMD: 0.2 (95% CI:0.1-0.2)], and perceived health [aMD: 0.2 (0.2-0.3)] compared to the control. Similarly, the H3 diet was associated with significant improvements in stress perception [aMD: -0.8 (-1.1 to -0.5)], sleep quality [aMD: 0.2 (0.1, 0.3)], and perceived health [aMD: 0.3 (0.2, 0.3)] compared to the control. MIDAS scores improved substantially in the intervention groups compared with the control (H3L6 aMD: -11.8 [-25.1, 1.5] and H3 aMD: -10.7 [-24.0, 2.7]). Among the PROMIS-29 assessments, the biggest impact was on pain interference [H3L6 MD: -1.8 (-4.4, 0.7) and H3 aMD: -3.2 (-5.9, -0.5)] and pain intensity [H3L6 MD: -0.6 (-1.3, 0.1) and H3 aMD: -0.6 (-1.4, 0.1)]. Discussion: The diary measures, with their increased power, supported our hypothesis that symptoms associated with migraine attacks could be responsive to specific dietary fatty acid manipulations. Changes in the PROMIS© measures reflected improvements in non-headache pain as well as physical and psychological function, largely in the expected directions. These findings suggest that increasing omega-3 with or without decreasing omega-6 in the diet may represent a reasonable adjunctive approach to reducing symptoms associated with migraine attacks. Trial Registration: ClinicalTrials.gov NCT02012790.