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.

Associations between Plasma Lipid Mediators and Chronic Daily Headache Outcomes in Patients Randomized to a Low Linoleic Acid Diet with or without Added Omega-3 Fatty Acids.

A previous report showed that 12-week lowering of dietary omega-6 linoleic acid (LA) coupled with increased omega-3 polyunsaturated fatty acid (PUFA) intake (H3-L6 diet) reduced headache frequency and improved quality of life in patients with chronic daily headaches (CDHs) compared to dietary LA reduction alone (L6 diet). The trial also showed that targeted dietary manipulation alters PUFA-derived lipid mediators and endocannabinoids. However, several additional classes of lipid mediators associated with pain in preclinical models were not measured. The current secondary analysis investigated whether the clinical benefits of the H3-L6 diet were related to changes in plasma unesterified PUFA-derived lipid mediators known to be involved in nociception, including prostanoids. Lipid mediators were measured by ultra-high-pressure liquid chromatography coupled with tandem mass-spectrometry. Compared to baseline, dietary LA lowering with or without added omega-3 fatty acids did not alter unesterified n-6 PUFA-derived lipid mediators, although several species derived from LA, di-homo-gamma-linolenic acid, and arachidonic acid were positively associated with headache frequency and intensity, as well as mental health burden. Alpha-linolenic acid (ALA)-derived metabolites were also associated with increased headache frequency and intensity, although they did not change from the baseline in either dietary group. Compared to baseline, docosahexaenoic acid (DHA)-derived epoxides were more elevated in the H3-L6 group compared to the L6 group. Diet-induced elevations in plasma DHA-epoxides were associated with reduced headache frequency, better physical and mental health, and improved quality of life (p < 0.05). Prostanoids were not detected, except for PGF2-alpha, which was not associated with any outcomes. This study demonstrates that diet-induced changes in DHA-epoxides were associated with pain reduction in patients with chronic headaches, whereas n-6 PUFA and ALA metabolites were associated with nociception. Lipid mediator associations with mental health and quality of life paralleled pain management outcomes in this population. The findings point to a network of multiple diet-modifiable lipid mediator targets for pain management in individuals with CDHs.

Targeted dietary interventions to reduce pain in persistent post-traumatic headache among service members: Protocol for a randomized, controlled parallel-group trial.

INTRODUCTION: Post-traumatic headache (PTH) is common after traumatic brain injury (TBI), especially among active-duty service members (SMs), affecting up to 35% of patients with chronic TBI. Persistent PTH is disabling and frequently unresponsive to treatment and is often migrainous. Here, we describe a trial assessing whether dietary modifications to increase n-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and reduce n-6 linoleic acid (LA), will alter nociceptive lipid mediators and result in clinical improvements in persistent PTH. METHODS: This prospective, randomized, controlled trial tests the efficacy, safety, and biochemical effects of targeted, controlled alterations in dietary n-3 and n-6 fatty acids in 122 adult SMs and military healthcare beneficiaries with diagnosed TBI associated with actively managed persistent frequent (>8 /month) PTH with migraine. Following a 4-week baseline, participants are randomized to one of two equally intensive dietary regimens for 12 additional weeks: 1) increased n-3 EPA + DHA with low n-6 LA (H3L6); 2) usual US dietary content of n-3 and n-6 fatty acids (Control). During the intervention, participants receive diet arm-specific study oils and foods sufficient for 75% of caloric needs and comprehensive dietary counseling. Participants complete daily headache diaries throughout the intervention. Clinical outcomes, including the Headache Impact Test (HIT-6), headache hours per day, circulating blood fatty acid levels, and bioactive metabolites, are measured pre-randomization and at 6 and 12 weeks. Planned primary analyses include pre-post comparisons of treatment groups on clinical measures using ANCOVA and mixed-effects models. Similar approaches to explore biochemical and exploratory clinical outcomes are planned. CLINICALTRIALS: gov registration: NCT03272399.

Dietary alteration of n-3 and n-6 fatty acids for headache reduction in adults with migraine: randomized controlled trial.

OBJECTIVE: To determine whether dietary interventions that increase n-3 fatty acids with and without reduction in n-6 linoleic acid can alter circulating lipid mediators implicated in headache pathogenesis, and decrease headache in adults with migraine. DESIGN: Three arm, parallel group, randomized, modified double blind, controlled trial. SETTING: Ambulatory, academic medical center in the United States over 16 weeks. PARTICIPANTS: 182 participants (88% women, mean age 38 years) with migraines on 5-20 days per month (67% met criteria for chronic migraine). INTERVENTIONS: Three diets designed with eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and linoleic acid altered as controlled variables: H3 diet (n=61)-increase EPA+DHA to 1.5 g/day and maintain linoleic acid at around 7% of energy; H3-L6 diet (n=61)-increase n-3 EPA+DHA to 1.5 g/day and decrease linoleic acid to ≤1.8% of energy; control diet (n=60)-maintain EPA+DHA at <150 mg/day and linoleic acid at around 7% of energy. All participants received foods accounting for two thirds of daily food energy and continued usual care. MAIN OUTCOME MEASURES: The primary endpoints (week 16) were the antinociceptive mediator 17-hydroxydocosahexaenoic acid (17-HDHA) in blood and the headache impact test (HIT-6), a six item questionnaire assessing headache impact on quality of life. Headache frequency was assessed daily with an electronic diary. RESULTS: In intention-to-treat analyses (n=182), the H3-L6 and H3 diets increased circulating 17-HDHA (log ng/mL) compared with the control diet (baseline-adjusted mean difference 0.6, 95% confidence interval 0.2 to 0.9; 0.7, 0.4 to 1.1, respectively). The observed improvement in HIT-6 scores in the H3-L6 and H3 groups was not statistically significant (-1.6, -4.2 to 1.0, and -1.5, -4.2 to 1.2, respectively). Compared with the control diet, the H3-L6 and H3 diets decreased total headache hours per day (-1.7, -2.5 to -0.9, and -1.3, -2.1 to -0.5, respectively), moderate to severe headache hours per day (-0.8, -1.2 to -0.4, and -0.7, -1.1 to -0.3, respectively), and headache days per month (-4.0, -5.2 to -2.7, and -2.0, -3.3 to -0.7, respectively). The H3-L6 diet decreased headache days per month more than the H3 diet (-2.0, -3.2 to -0.8), suggesting additional benefit from lowering dietary linoleic acid. The H3-L6 and H3 diets altered n-3 and n-6 fatty acids and several of their nociceptive oxylipin derivatives in plasma, serum, erythrocytes or immune cells, but did not alter classic headache mediators calcitonin gene related peptide and prostaglandin E2. CONCLUSIONS: The H3-L6 and H3 interventions altered bioactive mediators implicated in headache pathogenesis and decreased frequency and severity of headaches, but did not significantly improve quality of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT02012790.

Comparing prospective headache diary and retrospective four-week headache questionnaire over 20 weeks: Secondary data analysis from a randomized controlled trial.

BACKGROUND: Headache diaries and recall questionnaires are frequently used to assess headache frequency and severity in clinical and research settings. METHODS: Using 20 weeks of data from an intervention trial with 182 participants, we evaluated concordance between an electronic headache diary administered on a daily basis and designed to capture the presence and severity of headaches on an hourly basis (the headache diary) and a recall questionnaire, with retrospective estimation of the number of headache days assessed on a monthly basis. We further examined whether the duration or severity of headaches assessed by the electronic diary impacted concordance between these two measures. RESULTS: Over the course of four 28-day periods, people with migraine participating in a dietary intervention reported an average of 13.7 and 11.1 headache days in the headache diary and recall questionnaire, respectively. CONCLUSION: Over time, the concordance between headache days reported in these two measures tended to increase; however, the recall questionnaire headache estimates were lower than the diary measures in all four periods. When analysis was restricted to headaches lasting 8 hours or more, the number of headache days was more closely aligned with days reported in the recall questionnaire, indicating that the accuracy of recall estimates is likely to be influenced by headache duration. Restriction of analyses to moderate-to-severe headaches did not change results as much as headache duration. The findings indicate that recall questionnaires administered on a monthly basis may underestimate headache frequency and therefore should not be used interchangeably with headache diaries.Clinical Trials.gov Identifier: NCT02012790.

Identifying oxidized lipid mediators as prognostic biomarkers of chronic posttraumatic headache.

Chronic posttraumatic headache (PTH) is among the most common and disabling sequelae of traumatic brain injury (TBI). Current PTH treatments are often only partially effective and have problematic side effects. We previously showed in a small randomized trial of patients with chronic nontraumatic headaches that manipulation of dietary fatty acids decreased headache frequency, severity, and pain medication use. Pain reduction was associated with alterations in oxylipins derived from n-3 and n-6 fatty acids, suggesting that oxylipins could potentially mediate clinical pain reduction. The objective of this study was to investigate whether circulating oxylipins measured in the acute setting after TBI could serve as prognostic biomarkers for developing chronic PTH. Participants enrolled in the Traumatic Head Injury Neuroimaging Classification Protocol provided serum within 3 days of TBI and were followed up at 90 days postinjury with a neurobehavioral symptom inventory (NSI) and satisfaction with life survey. Liquid chromatography-tandem mass spectrometry methods profiled 39 oxylipins derived from n-3 docosahexaenoic acid (DHA), and n-6 arachidonic acid and linoleic acid. Statistical analyses assessed the association of oxylipins with headache severity (primary outcome, measured by headache question on NSI) as well as associations between oxylipins and total NSI or satisfaction with life survey scores. Among oxylipins, 4-hydroxy-DHA and 19,20-epoxy-docosapentaenoate (DHA derivatives) were inversely associated with headache severity, and 11-hydroxy-9-epoxy-octadecenoate (a linoleic acid derivative) was positively associated with headache severity. These findings support a potential for DHA-derived oxylipins as prognostic biomarkers for development of chronic PTH.

Diet-induced changes in n-3- and n-6-derived endocannabinoids and reductions in headache pain and psychological distress.

UNLABELLED: Omega-3 and omega-6 fatty acids are biosynthetic precursors of endocannabinoids with antinociceptive, anxiolytic, and neurogenic properties. We recently reported that targeted dietary manipulation-increasing omega-3 fatty acids while reducing omega-6 linoleic acid (the H3-L6 intervention)-reduced headache pain and psychological distress among chronic headache patients. It is not yet known whether these clinical improvements were due to changes in endocannabinoids and related mediators derived from omega-3 and omega-6 fatty acids. We therefore used data from this trial (N = 55) to investigate 1) whether the H3-L6 intervention altered omega-3- and omega-6-derived endocannabinoids in plasma and 2) whether diet-induced changes in these bioactive lipids were associated with clinical improvements. The H3-L6 intervention significantly increased the omega-3 docosahexaenoic acid derivatives 2-docosahexaenoylglycerol (+65%, P < .001) and docosahexaenoylethanolamine (+99%, P < .001) and reduced the omega-6 arachidonic acid derivative 2-arachidonoylglycerol (-25%, P = .001). Diet-induced changes in these endocannabinoid derivatives of omega-3 docosahexaenoic acid, but not omega-6 arachidonic acid, correlated with reductions in physical pain and psychological distress. These findings demonstrate that targeted dietary manipulation can alter endocannabinoids derived from omega-3 and omega-6 fatty acids in humans and suggest that 2-docosahexaenoylglycerol and docosahexaenoylethanolamine could have physical and/or psychological pain modulating properties. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01157208) PERSPECTIVE: This article demonstrates that targeted dietary manipulation can alter endocannabinoids derived from omega-3 and omega-6 fatty acids and that these changes are related to reductions in headache pain and psychological distress. These findings suggest that dietary interventions could provide an effective, complementary approach for managing chronic pain and related conditions.

Targeted alterations in dietary n-3 and n-6 fatty acids improve life functioning and reduce psychological distress among patients with chronic headache: a secondary analysis of a randomized trial.

Omega-3 and omega-6 fatty acids are precursors of bioactive lipid mediators posited to modulate both physical pain and psychological distress. In a randomized trial of 67 subjects with severe headaches, we recently demonstrated that targeted dietary manipulation-increasing omega-3 fatty acids with concurrent reduction in omega-6 linoleic acid (the H3-L6 intervention)-produced major reductions in headache compared with an omega-6 lowering (L6) intervention. Because chronic pain is often accompanied by psychological distress and impaired health-related quality of life (HRQOL), we used data from this trial to examine whether the H3-L6 intervention favorably impacted these domains. Additionally, we examined the effect of the interventions on the number of cases with substantial physical or mental impairments as defined by cutoff values in the Brief Symptom Inventory (BSI-18), Medical Outcomes Study Short Forms 12 (SF-12), Headache Impact Test (HIT-6), and the number of headache days per month. In the intention-to-treat analysis, participants in the H3-L6 group experienced statistically significant reductions in psychological distress (BSI-18 mean difference: -6.56; 95% confidence interval [CI]: -11.43 to -1.69) and improvements in SF-12 mental (mean difference: 6.01; 95% CI: 0.57 to 11.45) and physical (mean difference: 6.65; 95% CI: 2.14 to 11.16) health summary scores. At 12 weeks, the proportion of subjects experiencing substantial impairment according to cutoff values in the BSI-18, SF-12 physical, HIT-6, and headache days per month was significantly lower in the H3-L6 group. Dietary manipulation of n-3 and n-6 fatty acids, previously shown to produce major improvements in headache, was found to also reduce psychological distress and improve HRQOL and function.

Dietary omega-6 fatty acid lowering increases bioavailability of omega-3 polyunsaturated fatty acids in human plasma lipid pools.

BACKGROUND: Dietary linoleic acid (LA, 18:2n-6) lowering in rats reduces n-6 polyunsaturated fatty acid (PUFA) plasma concentrations and increases n-3 PUFA (eicosapentaenoic (EPA) and docosahexaenoic acid (DHA)) concentrations. OBJECTIVE: To evaluate the extent to which 12 weeks of dietary n-6 PUFA lowering, with or without increased dietary n-3 PUFAs, alters unesterified and esterified plasma n-6 and n-3 PUFA concentrations in subjects with chronic headache. DESIGN: Secondary analysis of a randomized trial. Subjects with chronic headache were randomized for 12 weeks to (1) average n-3, low n-6 (L6) diet; or (2) high n-3, low n-6 LA (H3-L6) diet. Esterified and unesterified plasma fatty acids were quantified at baseline (0 weeks) and after 12 weeks on a diet. RESULTS: Compared to baseline, the L6 diet reduced esterified plasma LA and increased esterified n-3 PUFA concentrations (nmol/ml), but did not significantly change plasma arachidonic acid (AA, 20:4n-6) concentration. In addition, unesterified EPA concentration was increased significantly among unesterified fatty acids. The H3-L6 diet decreased esterified LA and AA concentrations, and produced more marked increases in esterified and unesterified n-3 PUFA concentrations. CONCLUSION: Dietary n-6 PUFA lowering for 12 weeks significantly reduces LA and increases n-3 PUFA concentrations in plasma, without altering plasma AA concentration. A concurrent increase in dietary n-3 PUFAs for 12 weeks further increases n-3 PUFA plasma concentrations and reduces AA.

Dietary considerations in migraine management: does a consistent diet improve migraine?

The clinical expression of migraine is significantly impacted by dietary and gastrointestinal issues. This includes gut dysfunction during and between attacks, food triggers, increase in migraine with obesity, comorbid GI and systemic inflammation influenced by diet, and specific food allergies such as dairy and gluten. Practitioners often encourage migraineurs to seek consistency in their lifestyle behaviors, and environmental exposures, as a way of avoiding sudden changes that may precipitate attacks. However, rigorous evidence linking consistency of diet with improvement in migraine is very limited and is, at best, indirect, being based mainly on the consistency of avoiding suspected food triggers. A review of current data surrounding the issue of dietary consistency is presented from the perspective of migraine as an illness (vulnerable state), as a disease (symptom expression traits), and with a view toward the role of local and systemic inflammation in its genesis. Firm recommendations await further investigation.

Low-n-6 and low-n-6 plus high-n-3 diets for use in clinical research.

Few trials have evaluated the metabolic effects and health outcomes of lowering dietary n-6 PUFA. The objectives of the present paper were (1) to report the methods employed to lower dietary n-6 PUFA, while either increasing or maintaining n-3 PUFA intake and (2) to validate our methods with 24 h recalls and erythrocyte fatty acid analyses. A total of sixty-seven subjects were randomised to either (1) an average-n-3 PUFA, low-n-6 PUFA (L6) intervention designed to lower linoleic acid (LA; #2·5% of energy (en%)) and arachidonic acid (#60 mg/d), while maintaining an average US intake of n-3 PUFA or (2) a high-n-3 PUFA, low-n-6 PUFA (H3-L6) intervention designed to lower n-6 LA, while increasing the n-3 PUFA a-linolenic acid (ALA; $1·5 en%) and EPA þ DHA ($1000 mg/d). Pre- and intraintervention nutrient intakes were estimated with six 24 h dietary recalls per subject. Both groups achieved the targeted reductions in dietary LA to #2·5 en% (median LA 2·45 (2·1, 3·1); P,0·001). Intakes of n-3 PUFA did not change for the L6 group. Target increases in n-3 ALA (median 1·6 en%, (1·3, 2·0), P,0·001) and EPA þ DHA (1482 mg, (374, 2558), P,0·001) were achieved in the H3-L6 group. Dietary changes were validated by corresponding changes in erythrocyte n-6 and n-3 fatty acid composition. Dietary LA can be lowered to #2·5 en%, with or without concurrent increases in dietary n-3 PUFA, in an outpatient clinical trial setting using this integrated diet method.

Lowering dietary linoleic acid reduces bioactive oxidized linoleic acid metabolites in humans.

Linoleic acid (LA) is the most abundant polyunsaturated fatty acid in human diets, a major component of human tissues, and the direct precursor to the bioactive oxidized LA metabolites (OXLAMs), 9- and 13 hydroxy-octadecadienoic acid (9- and 13-HODE) and 9- and 13-oxo-octadecadienoic acid (9- and 13-oxoODE). These four OXLAMs have been mechanistically linked to pathological conditions ranging from cardiovascular disease to chronic pain. Plasma OXLAMs, which are elevated in Alzheimer's dementia and non-alcoholic steatohepatitis, have been proposed as biomarkers useful for indicating the presence and severity of both conditions. Because mammals lack the enzymatic machinery needed for de novo LA synthesis, the abundance of LA and OXLAMs in mammalian tissues may be modifiable via diet. To examine this issue in humans, we measured circulating LA and OXLAMs before and after a 12-week LA lowering dietary intervention in chronic headache patients. Lowering dietary LA significantly reduced the abundance of plasma OXLAMs, and reduced the LA content of multiple circulating lipid fractions that may serve as precursor pools for endogenous OXLAM synthesis. These results show that lowering dietary LA can reduce the synthesis and/or accumulation of oxidized LA derivatives that have been implicated in a variety of pathological conditions. Future studies evaluating the clinical implications of diet-induced OXLAM reductions are warranted.

Mind-body interventions for treatment of phantom limb pain in persons with amputation.

Phantom limb pain (PLP) is a significant source of chronic pain in most persons with amputation at some time in their clinical course. Pharmacologic therapies for this condition are often only moderately effective and may produce unwanted adverse effects. There is growing empirical evidence of the therapeutic effectiveness of mind-body therapies for the relief of chronic pain; therefore, an exploration of their role in relieving amputation-related chronic pain is warranted. We undertook a focused literature review on mind-body interventions for patients with amputation who experience PLP. Because of study heterogeneity, only descriptive presentations of the studies are presented. Only studies of hypnosis, imagery, and biofeedback, including visual mirror feedback, were found; studies on meditation, yoga, and tai chi/qigong were missing from the literature. Few studies of specific mind-body therapies were dedicated to management of PLP, with the exception of mirror visual therapy. Overall, studies were largely exploratory and reflect considerable variability in the application of mind-body techniques, making definitive conclusions inadvisable. Nevertheless, the weight of existing findings indicates that a mind-body approach to PLP pain management is promising and that specific methods may offer either temporary or long-term relief, either alone or in combination with conventional therapies. The authors discuss the potential for usefulness of specific mind-body therapies and the relevance of their mechanisms of action to those of PLP, including targeting cortical reorganization, autonomic nervous system deregulation, stress management, coping ability, and quality-of-life. The authors recommend more and better quality research exploring the efficacy and mechanisms of action.

Credibility of low-strength static magnet therapy as an attention control intervention for a randomized controlled study of CranioSacral therapy for migraine headaches.

BACKGROUND: Developing valid control groups that generate similar perceptions and expectations to experimental complementary and alternative (CAM) treatments can be challenging. The perceived credibility of treatment and outcome expectancy often contributes to positive clinical responses to CAM therapies, thereby confounding efficacy data. As part of a clinical feasibility study, credibility and expectancy data were obtained from subjects suffering from migraine who received either CranioSacral therapy (CST) or an attention-control, sham, and low-strength magnet (LSSM) intervention. OBJECTIVE: The objective of this study was to evaluate whether the LSSM intervention generated similar levels of subject credibility and expectancy compared to CST. DESIGN: This was a two-arm randomized controlled trial. SUBJECTS: Sixty-five (65) adults with moderate to severe migraine were the subjects of this study. INTERVENTIONS: After an 8-week baseline, subjects were randomized to eight weekly treatments of either CST (n=36) or LSSM (n=29). The latter involved the use of a magnet-treatment protocol using inactive and low-strength static magnets designed to mimic the CST protocol in terms of setting, visit timing, body positioning, and therapist-subject interaction. OUTCOME MEASURES: A four-item, self-administered credibility/expectancy questionnaire, based on a validated instrument, was completed after the first visit. RESULTS: Using a 0-9 rating scale, the mean score for perceived logicality of treatment was significantly less for LSSM (5.03, standard deviation [SD] 2.34) compared to CST (6.64, SD 2.19). Subject confidence that migraine would improve was greater for CST (5.94, SD 2.01) than for LSSM (4.9, SD 2.21), a difference that was not statistically significant. Significantly more subjects receiving CST (6.08, SD 2.27) would confidently recommend treatment to a friend than those receiving LSSM (4.69, SD 2.49). CONCLUSIONS: Although LSSM did not achieve a comparable level of credibility and expectancy to the CST, several design and implementation factors may have contributed to the disparity. Based on analysis of these factors, the design and implementation of a future study may be improved.

Mindfulness training reduces the severity of irritable bowel syndrome in women: results of a randomized controlled trial.

OBJECTIVES: This prospective, randomized controlled trial explored the feasibility and efficacy of a group program of mindfulness training, a cognitive-behavioral technique, for women with irritable bowel syndrome (IBS). The technique involves training in intentionally attending to present-moment experience and non-judgmental awareness of body sensations and emotions. METHODS: Seventy-five female IBS patients were randomly assigned to eight weekly and one half-day intensive sessions of either mindfulness group (MG) training or a support group (SG). Participants completed the IBS severity scale (primary outcome), IBS-quality of life, brief symptom inventory-18, visceral sensitivity index, treatment credibility scale, and five-facet mindfulness questionnaire before and after treatment and at 3-month follow-up. RESULTS: Women in the MG showed greater reductions in IBS symptom severity immediately after training (26.4% vs. 6.2% reduction; P=0.006) and at 3-month follow-up (38.2% vs. 11.8%; P=0.001) relative to SG. Changes in quality of life, psychological distress, and visceral anxiety were not significantly different between groups immediately after treatment, but evidenced significantly greater improvements in the MG than in the SG at the 3-month follow-up. Mindfulness scores increased significantly more in the MG after treatment, confirming effective learning of mindfulness skills. Participants' ratings of the credibility of their assigned interventions, measured after the first group session, were not different between groups. CONCLUSIONS: This randomized controlled trial demonstrated that mindfulness training has a substantial therapeutic effect on bowel symptom severity, improves health-related quality of life, and reduces distress. The beneficial effects persist for at least 3 months after group training.

Patient characteristics associated with frequent calls to a headache specialty clinic.

OBJECTIVE: To identify characteristics of patients who frequently initiate contact with a headache specialty clinic outside of scheduled appointments. MATERIALS AND METHODS: We scanned records of all telephone calls received during 1 calendar year at an academic headache clinic to identify frequent callers. High-frequency (HF) callers were defined as established patients who initiated calls on ≥20 days during the year. We compared these patients with a cohort of established low-frequency (LF) callers who initiated no telephone calls during the same year. Clinic records were analyzed for demographic characteristics, diagnoses, and medication use. Additionally, we administered a questionnaire to clinic physicians and administrative staff querying their perception of each patient's demands on clinic resources. RESULTS: High-frequency (n=26) and LF (n=18) callers did not differ significantly in marital status, ethnicity, diagnosis, or age. There was a trend toward female gender among HF callers and toward being outside of a body mass index range of 19 to 30 kg/m2. The groups were similar in their use of triptans and botulinum toxin treatments, but HF callers were more likely to be opioid users (96% vs 11.1%) and more likely to be taking multiple opioids in substantially higher potency, dosage, and quantity (154.4 mg vs 1.4 mg morphine equivalents/day). More than 80% of each group were migraineurs, but HF callers were more likely to have comorbid psychiatric disorders (P<0.05). High-frequency callers were also more likely to be rated by administrative staff and physicians as demanding and time-consuming. CONCLUSIONS: In this university-based headache specialty clinic, HF callers were more likely to be opioid users on high morphine-equivalent doses. Compared with LF callers, HF callers placed a greater burden on health care resources as perceived by staff and physicians.

Low omega-6 vs. low omega-6 plus high omega-3 dietary intervention for chronic daily headache: protocol for a randomized clinical trial.

BACKGROUND: Targeted analgesic dietary interventions are a promising strategy for alleviating pain and improving quality of life in patients with persistent pain syndromes, such as chronic daily headache (CDH). High intakes of the omega-6 (n-6) polyunsaturated fatty acids (PUFAs), linoleic acid (LA) and arachidonic acid (AA) may promote physical pain by increasing the abundance, and subsequent metabolism, of LA and AA in immune and nervous system tissues. Here we describe methodology for an ongoing randomized clinical trial comparing the metabolic and clinical effects of a low n-6, average n-3 PUFA diet, to the effects of a low n-6 plus high n-3 PUFA diet, in patients with CDH. Our primary aim is to determine if: A) both diets reduce n-6 PUFAs in plasma and erythrocyte lipid pools, compared to baseline; and B) the low n-6 plus high n-3 diet produces a greater decline in n-6 PUFAs, compared to the low n-6 diet alone. Secondary clinical outcomes include headache-specific quality-of-life, and headache frequency and intensity. METHODS: Adults meeting the International Classification of Headache Disorders criteria for CDH are included. After a 6-week baseline phase, participants are randomized to a low n-6 diet, or a low n-6 plus high n-3 diet, for 12 weeks. Foods meeting nutrient intake targets are provided for 2 meals and 2 snacks per day. A research dietitian provides intensive dietary counseling at 2-week intervals. Web-based intervention materials complement dietitian advice. Blood and clinical outcome data are collected every 4 weeks. RESULTS: Subject recruitment and retention has been excellent; 35 of 40 randomized participants completed the 12-week intervention. Preliminary blinded analysis of composite data from the first 20 participants found significant reductions in erythrocyte n-6 LA, AA and %n-6 in HUFA, and increases in n-3 EPA, DHA and the omega-3 index, indicating adherence. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01157208).

Rationales for CAM Education in Health Professions Training Programs.

The authors review the use of complementary and alternative medicine (CAM) in the United States. They then present and discuss the rationales used by the 15 National Center for Complementary and Alternative Medicine CAM educational grantees in their original proposals for incorporating CAM content into conventional health professions training programs. Fourteen of the grantees were from major U.S. medical and nursing schools, and one was from a medical student foundation. Awards were for five-year periods (with the exception of one three-year grant) from 2000 to 2008. Rationales for developing educational programs about CAM for conventional health professionals included (1) the prevalence and growth of CAM in the United States, (2) response to governmental, legislative, and other mandates, (3) need for enhanced communication between conventional providers and patients using CAM, (4) need to enhance safety of CAM use and interactions with conventional care, (5) CAM education's positive impact on broadening core competencies for conventional health care professionals, (6) positive impact on enhancing cultural competency, (7) need for better communication between conventional and CAM providers, (8) potential for improving health care coordination, (9) potential impact on increasing CAM research quality and capacity, and (10) potential for enhancing quality of care through informed CAM use. Integration of CAM with conventional health care requires educational venues that prepare conventionally trained caregivers with a sufficient knowledge base for assessing beneficial and detrimental interactions between CAM and conventional care approaches; development of criteria for making informed referrals to CAM practitioners; and enhanced research capacity.

The prevalence and spectrum of sleep problems in women with transformed migraine.

OBJECTIVES: It is our clinical observation that patients with transformed migraine (TM) almost invariably report nonrestorative sleep. In this study we sought first to validate that clinical observation, then to describe the prevalence and spectrum of factors that might contribute to nonrestorative sleep in a TM population. BACKGROUND: Although headaches have been linked with sleep problems for over a century, there is little information about the spectrum or prevalence of specific sleep problems associated with TM in adults. METHODS: We conducted a detailed sleep interview on 147 consecutive women with TM. Subjective sleep quality was assessed by asking patients to describe their state upon awakening as "refreshed" or "tired." RESULTS: None of the 147 patients reported awakening "refreshed," and 83.7% stated that they awakened "tired." Sleep complaints were prevalent and varied in this population. CONCLUSIONS: Although the relationship between pain and sleep is complex and ill understood, we found a very high prevalence of nonrestorative sleep and a similarly high prevalence of modifiable poor sleep habits in patients with TM. Since behavioral approaches have been found effective in improving sleep quality in patients with poor sleep hygiene, we propose that studies be undertaken to assess the impact of such treatment on TM.

Four methods of estimating the minimal important difference score were compared to establish a clinically significant change in Headache Impact Test.

OBJECTIVE: To estimate the smallest decrease in Headache Impact Test (HIT) scores that reflects meaningful clinical change among patients with chronic daily headache (CDH). STUDY DESIGN AND SETTING: We applied four methods of estimating the minimum important difference (MID) to data from 71 patients with CDH who participated in a clinical trial. The HIT was administered at baseline and at the 6-week follow-up assessment. Patients were considered to have experienced meaningful improvement if they reported that their headache condition was "somewhat better" or "much better" at the 6-week follow-up. RESULTS: Mean HIT scores at baseline and 6 weeks for all patients were 64.5 (standard deviation SD = 6.0) and 62.6 (SD = 5.7), respectively. HIT scores decreased 3.7 (SD = 4.4) and 1.4 (SD = 3.6) units, respectively, among patients who reported "somewhat better" change and those who reported no change at 6 weeks. Estimates of the MID of the HIT ranged from -2.7 to -2.3. CONCLUSIONS: The method that we judge to be most valid estimated the MID of the HIT at -2.3 units (95% confidence interval = -4.3, -0.3). This suggests that a between-group difference in HIT change scores of 2.3 units over time among patients with CDH reflects improvement in patients' headache condition that may be considered clinically significant.