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Objective We identified challenges and solutions to using electronic health record (EHR) systems for the design and conduct of pragmatic research. Materials and Methods Since 2012, the Health Care Systems Research Collaboratory has served as the resource coordinating center for 21 pragmatic clinical trial demonstration projects. The EHR Core working group invited these demonstration projects to complete a written semistructured survey and used an inductive approach to review responses and identify EHR-related challenges and suggested EHR enhancements. Results We received survey responses from 20 projects and identified 21 challenges that fell into 6 broad themes: (1) inadequate collection of patient-reported outcome data, (2) lack of structured data collection, (3) data standardization, (4) resources to support customization of EHRs, (5) difficulties aggregating data across sites, and (6) accessing EHR data. Discussion Based on these findings, we formulated 6 prerequisites for PCTs that would enable the conduct of pragmatic research: (1) integrate the collection of patient-centered data into EHR systems, (2) facilitate structured research data collection by leveraging standard EHR functions, usable interfaces, and standard workflows, (3) support the creation of high-quality research data by using standards, (4) ensure adequate IT staff to support embedded research, (5) create aggregate, multidata type resources for multisite trials, and (6) create re-usable and automated queries. Conclusion We are hopeful our collection of specific EHR challenges and research needs will drive health system leaders, policymakers, and EHR designers to support these suggestions to improve our national capacity for generating real-world evidence.

Objective The Mindfulness-Based Stress Reduction program is effective at improving chronic pain outcomes, but the time demand hinders participation. This preliminary study evaluated the feasibility, acceptability, and potential effects of providing an abbreviated mindfulness program for patients with chronic pain. Design A single-arm, mixed-methods, pre–post intervention study. Setting An outpatient rehabilitation clinic at an academic medical center. Subjects Participants were N = 23 adults with chronic pain who were new to mindfulness practice. Methods Mindfulness-based Stress Reduction was adapted to shorten the program to four weekly 90-minute sessions and to focus content on pain management. Three cohorts of six to nine participants completed baseline and post-treatment measures of 1) patient-reported outcomes, including pain intensity, pain interference, physical functioning, depressive/anxiety symptoms, positive affect and well-being, and sleep disturbance; 2) pain medication dosages; 3) psychosocial variables including pain acceptance, pain catastrophizing, and perceived stress; 4) dispositional mindfulness, as well as postintervention structured interviews about their experiences. Results Acceptable rates of retention and attendance and high ratings of satisfaction indicated that the intervention was feasible and acceptable. In interviews, participants found the program acceptable and beneficial and provided suggestions to improve it. From pre- to post-treatment, significant improvements were reported in all measures except physical functioning and anxiety. Conclusions In adults with chronic pain, a four-week mindfulness program is feasible and acceptable, addresses the barrier of a lengthy program, and may improve quality of life and psychological functioning. An appropriately powered randomized controlled trial with a comparison group is needed to assess the intervention’s effectiveness.

Local inflammation plays an important role in normal folliculogenesis and ovulation, and conditions of chronic systemic inflammation, such as obesity and polycystic ovarian syndrome, can disrupt normal follicular dynamics.This study aimed to determine the association between systemic inflammation, as measured by C-reactive protein levels, and menstrual cycle length.This study was a secondary analysis using data from Time to Conceive, a prospective time-to-pregnancy cohort study. The association between cycle length and C-reactive protein was analyzed using multivariable linear mixed and marginal models adjusted for age, race, education, body mass index, time since oral contraceptive use, alcohol, smoking, caffeine consumption, and exercise. Time to Conceive enrolled women aged 30 to 44 years with no history of infertility who were attempting to conceive for3 months. Serum C-reactive protein levels were measured on cycle day 2, 3, or 4. Participants recorded daily menstrual cycle data for ≤4 months.Main outcome measures included menstrual cycle length and follicular and luteal phase lengths. Multivariable analysis included 1409 cycles from 414 women. There was no linear association between C-reactive protein levels and menstrual cycle length. However, compared with1 mg/L, a C-reactive protein level10 mg/L was associated with3 times the odds (adjusted odds ratio, 3.7; 95% confidence interval, 1.67-8.11) of long cycles (defined as ≥35 days). When evaluating follicular phase length, a C-reactive protein level of10 mg/L was associated both with follicular phases that were 1.7 (95% confidence interval, 0.23-3.09) days longer and with2 times the odds of a long follicular phase (adjusted odds ratio, 2.2; 95% confidence interval, 1.05-4.74).There is a potential pathophysiological association between systemic inflammation and menstrual cycle changes. Further studies are needed to determine if systemic inflammation alters the menstrual cycle or if long menstrual cycles are a marker for elevated systemic inflammation.

396 Background: Frail cancer patients are more likely to die or experience treatment toxicity than non-frail patients. The Faurot frailty index (FFI) is a validated Medicare claims-based proxy that predicts frailty in individuals. Frailty is dynamic and can change over time. We assessed the distribution of the FFI and associations with 1-year mortality using varying durations of frailty ascertainment windows in breast cancer patients. Methods: We identified women (66+ yrs) with stage I-III breast cancer in the SEER-Medicare database who had ≥1 year of continuous enrollment in Medicare Parts A and B prior to diagnosis. The FFI-predicted probability of frailty was assessed using demographic and diagnostic and procedural billing information during varying pre-diagnosis ascertainment windows: 3, 6, 8, or 12 months or using all available pre-diagnosis claims. We described the distributions of the claims-based frailty measures using each of the five ascertainment windows and reported 1-year mortality for individuals with high (≥0.20), medium (0.05 - < 0.20), or low (< 0.05) claims-based frailty using Kaplan-Meier analysis. Follow-up began on the date of cancer diagnosis. Results: We identified 235,145 women with breast cancer. Using a 3-month ascertainment window, 76%, 20%, and 4% were classified as having low, medium, and high claims-based frailty. Although the distributions of claims-based frailty were similar using 3, 6, 8, and 12-month frailty ascertainment windows, the use of all available lookback led a wider interquartile range (IQR) for claims-based frailty (Table). Overall, 4% of women died within 1 year of diagnosis. Higher claims-based frailty was strongly associated with increased 1-year mortality risk, using each ascertainment window. Mortality associations were strongest with a 3-month ascertainment window: risk difference (RD) high vs. low frailty 20% (95% CI, 19-20%). Associations were weakest with an all available lookback window: RD high vs. low frailty 11% (95% CI, 11-12%). Conclusions: Varying frailty ascertainment window durations did not lead to substantial differences in the distribution of the FFI in women with stage I-III breast cancer. Associations between the FFI and 1-year mortality monotonically decreased with increasing ascertainment window durations. This may be due to claims in the distant past having less etiological relevance for predicting mortality during the year following cancer diagnosis.[Table: see text]

Background The Veterans Health Administration is undergoing a cultural transformation toward person-driven care referred to as the Whole Health System of Care. Objective This pilot study evaluated whether the Whole Health model resonates with patients of a large public university rehabilitation clinic. Methods Thirty participants completed the Veterans Health Administration’s Personal Health Inventory (PHI), and six attended the course “Taking Charge of My Life and Health.” Researchers analyzed PHI responses and post-course focus group transcripts. A short post-PHI survey and post-course evaluation were collected. Results Participants agreed the PHI is a simple, useful tool. The course, while well attended, did not meet participants’ expectations. Participants wanted access to integrative therapies and opportunities to contribute to healthcare transformation. Conclusion Rehabilitation patients resonated with the Whole Health vision. They expressed enthusiasm for the cultural transformation represented by the model along with frustration that standard healthcare experiences fall short of this vision.

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.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.gov registration: NCT03272399.

Objectives: Implementation science is key to translating complementary and integrative health intervention research into practice as it can increase accessibility and affordability while maximizing patient health outcomes. The authors describe using implementation mapping to (1) identify barriers and facilitators impacting the implementation of an Integrative Medical Group Visit (IMGV) intervention in an outpatient setting with a high burden of patients with chronic pain and (2) select and develop implementation strategies utilizing theory and stakeholder input to address those barriers and facilitators. Design: The authors selected a packaged, evidence-based, integrative pain management intervention, the IMGV, to implement in an outpatient clinic with a high burden of patients with chronic pain. The authors used implementation mapping to identify implementation strategies for IMGV, considering theory and stakeholder input. Stakeholder interviews with clinic staff, faculty, and administrators (n = 15) were guided by the Consolidated Framework for Implementation Research. Results: Based on interview data, the authors identified administrators, physicians, nursing staff, and scheduling staff as key stakeholders involved in implementation. Barriers and facilitators focused on knowledge, buy-in, and operational procedures needed to successfully implement IMGV. The implementation team identified three cognitive influences on behavior that would impact performance: knowledge, outcome expectations, and self-efficacy; and three theoretical change methods: cue to participate, communication, and mobilization. Implementation strategies identified included identifying and preparing champions, participation in ongoing training, developing and distributing educational materials, and organizing clinician implementation team meetings. Conclusions: This study provides an example of the application of implementation mapping to identify theory-driven implementation strategies for IMGV. Implementation mapping is a feasible method that may be useful in providing a guiding structure for implementation teams as they employ implementation frameworks and select implementation strategies for integrative health interventions.

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.

BACKGROUND & AIMS: Increasing dietary intake of n-3 EPA+DHA and lowering dietary n-6 LA is under investigation as a therapeutic diet for improving chronic pain syndromes as well as other health outcomes. Herein we describe the diet methodology used to modulate intake of n-3 and n-6 PUFA in a free living migraine headache population and report on nutrient intake, BMI and diet acceptability achieved at week 16 of the intensive diet intervention and week 22 follow-up time-point. METHODS: A total of 178 participants were randomized and began one of three diet interventions: 1) a high n-3 PUFA, average n-6 PUFA (H3) diet targeting 1500 mg EPA+DHA/day and 7% of energy (en%) from n-6 linoleic acid (LA), 2) a high-n-3 PUFA, low-n-6 PUFA (H3L6) targeting 1500 mg EPA+DHA/day and

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

Supplemental material, sj-pdf-1-cep-10.1177_0333102420949180 for Comparing prospective headache diary and retrospective four-week headache questionnaire over 20 weeks: Secondary data analysis from a randomized controlled trial by Vanessa E Miller, Keturah R Faurot, Olafur S Palssson, Beth A MacIntosh, Chirayath Suchindran, Gilson Honvoh, Susan Gaylord, Christopher E Ramsden and J Douglas Mann in Cephalalgia

Some of the biochemical abnormalities underlying schizophrenia, involve differences in methylation and methylating enzymes, as well as other related target genes. We present results of a study of differences in mRNA expression in peripheral blood lymphocytes (PBLs) and post-mortem brains of chronic schizophrenics (CSZ) and non-psychotic controls (NPC), emphasizing the differential effects of sex and antipsychotic drug treatment on mRNA findings. We studied mRNA expression in lymphocytes of 61 CSZ and 49 NPC subjects using qPCR assays with TaqMan probes to assess levels of DNMT, TET, GABAergic, NR3C1, BDNF mRNAs, and several additional targets identified in a recent RNA sequence analysis. In parallel we studied DNMT1 and GAD67 in samples of brain tissues from 19 CSZ, 26 NPC. In PBLs DNMT1 and DNMT3A mRNA levels were significantly higher in male CSZ vs NPC. No significant differences were detected in females. The GAD1, NR3C1 and CNTNAP2 mRNA levels were significantly higher in CSZ than NPC. In CSZ patients treated with clozapine, GAD-1 related, CNTNAP2, and IMPA2 mRNAs were significantly higher than in CSZ subjects not treated with clozapine. Differences between CSZ vs NPC in these mRNAs was primarily attributable to the clozapine treatment. In the brain samples, DNMT1 was significantly higher and GAD67 was significantly lower in CSZ than in NPC, but there were no significant sex differences in diagnostic effects. These findings highlight the importance of considering sex and drug treatment effects in assessing the substantive significance of differences in mRNAs between CSZ and NPC.

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 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

Importance Mind-body therapies (MBTs) are emerging as potential tools for addressing the opioid crisis. Knowing whether mind-body therapies may benefit patients treated with opioids for acute, procedural, and chronic pain conditions may be useful for prescribers, payers, policy makers, and patients. Objective To evaluate the association of MBTs with pain and opioid dose reduction in a diverse adult population with clinical pain. Data Sources For this systematic review and meta-analysis, the MEDLINE, Embase, Emcare, CINAHL, PsycINFO, and Cochrane Library databases were searched for English-language randomized clinical trials and systematic reviews from date of inception to March 2018. Search logic included (pain OR analgesia OR opioids) AND mind-body therapies. The gray literature, ClinicalTrials.gov, and relevant bibliographies were also searched. Study Selection Randomized clinical trials that evaluated the use of MBTs for symptom management in adults also prescribed opioids for clinical pain. Data Extraction and Synthesis Independent reviewers screened citations, extracted data, and assessed risk of bias. Meta-analyses were conducted using standardized mean differences in pain and opioid dose to obtain aggregate estimates of effect size with 95% CIs. Main Outcomes and Measures The primary outcome was pain intensity. The secondary outcomes were opioid dose, opioid misuse, opioid craving, disability, or function. Results Of 4212 citations reviewed, 60 reports with 6404 participants were included in the meta-analysis. Overall, MBTs were associated with pain reduction (Cohend = −0.51; 95% CI, −0.76 to −0.26) and reduced opioid dose (Cohend = −0.26; 95% CI, −0.44 to −0.08). Studies tested meditation (n = 5), hypnosis (n = 25), relaxation (n = 14), guided imagery (n = 7), therapeutic suggestion (n = 6), and cognitive behavioral therapy (n = 7) interventions. Moderate to large effect size improvements in pain outcomes were found for meditation (Cohend = −0.70), hypnosis (Cohend = −0.54), suggestion (Cohend = −0.68), and cognitive behavioral therapy (Cohend = −0.43) but not for other MBTs. Although most meditation (n = 4 [80%]), cognitive-behavioral therapy (n = 4 [57%]), and hypnosis (n = 12 [63%]) studies found improved opioid-related outcomes, fewer studies of suggestion, guided imagery, and relaxation reported such improvements. Most MBT studies used active or placebo controls and were judged to be at low risk of bias. Conclusions and Relevance The findings suggest that MBTs are associated with moderate improvements in pain and small reductions in opioid dose and may be associated with therapeutic benefits for opioid-related problems, such as opioid craving and misuse. Future studies should carefully quantify opioid dosing variables to determine the association of mind-body therapies with opioid-related outcomes.

Background Multiple claims-based proxy measures of poor function have been developed to address confounding in observational studies of drug effects in older adults. We evaluated agreement between these measures and their associations with treatment receipt and mortality in a cohort of older colon cancer patients. Methods Medicare beneficiaries age 66+ diagnosed with stage II-III colon cancer were identified in the Surveillance, Epidemiology, and End Results-Medicare database (2004-2011). Poor function was operationalized by: (1) summing the total poor function indicators for each model; and (2) estimating predicted probabilities of poor function at diagnosis. Agreement was evaluated using Fleiss' κ and Spearman's correlation. Associations between proxy measures and: (1) laparoscopic versus open surgery; (2) chemotherapy versus none; (3) 5-fluorouracil (5FU)+oxaliplatin (FOLFOX) versus 5FU monotherapy; and (4) 1-year mortality were estimated using log-binomial regression, controlling for age, sex, stage, and comorbidity. Survival estimates were stratified by functional group, age, and comorbidity. Results Among 29,687 eligible colon cancer patients, 67% were 75+ years and 45% had stage III disease. Concordance across the poor function indicator counts was moderate (κ: 0.64) and correlation of predicted probability measures varied (ρ: 0.21-0.74). Worse function was associated with lower chemotherapy and FOLFOX receipt, and higher 1-year mortality. Within age and comorbidity strata, poor function remained associated with mortality. Conclusions While agreement varied across the claims-based proxy measures, each demonstrated anticipated associations with treatment receipt and mortality independent of comorbidity. Claims-based comparative effectiveness studies in older populations should consider applying one of these models to improve confounding control.

African Americans have disproportionately high rates of stress-related conditions, including diabetes and diabetes-related morbidity. Psychological stress may negatively influence engagement in risk-reducing lifestyle changes (physical activity and healthy eating) and stress-related physiology that increase diabetes risk. This study examined the feasibility of conducting a randomized trial comparing a novel mindfulness-based stress management program combined with diabetes risk-reduction education versus a conventional diabetes risk-reduction education program among African American adults with prediabetes and self-reported life stress. Participants were recruited in collaboration with community partners and randomized to the mindfulness-based diabetes risk-reduction education program for prediabetes (MPD; n = 38) or the conventional diabetes risk-reduction education program for prediabetes (CPD; n = 30). The mindfulness components were adapted from the Mindfulness-based Stress Reduction Program. The diabetes risk-reduction components were adapted from the Power to Prevent Program and the Diabetes Prevention Program. Groups met for eight weeks for 2.5 hours, with a half-day retreat and six-monthly boosters. Mixed-methods strategies were used to assess feasibility. Psychological, behavioral, and metabolic data were collected before the intervention and at three and six months postintervention to examine within-group change and feasibility of collecting such data in future clinical efficacy research. Participants reported acceptability, credibility, and cultural relevance of the intervention components. Enrollment of eligible participants (79%), intervention session attendance (76.5%), retention (90%), and postintervention data collection attendance (83%, 82%, and 78%, respectively) demonstrated feasibility, and qualitative data provided information to further enhance feasibility in future studies. Both groups exhibited an A1C reduction. MPD participants had reductions in perceived stress, BMI, calorie, carbohydrate and fat intake, and increases in spiritual well-being. Considering the high prevalence of diabetes and diabetes-related complications in African Americans, these novel findings provide promising guidance to develop a larger trial powered to examine efficacy of a mindfulness-based stress management and diabetes risk-reduction education program for African Americans with prediabetes.

Mind-body therapies (MBTs), a subset of complementary and alternative medicine (CAM), are used by cancer survivors to manage symptoms related to their cancer experience. MBT use may differ by cancer survivorship stage (i.e., acute, short-term, long-term) because each stage presents varying intensities of medical activities, associated emotions, and treatment effects. We examined the relationship between MBT use and survivorship stage (acute1 year; short-term 1 to 5 years; long-term5 years since diagnosis) using the CAM supplement of the 2012 National Health Interview Survey. We also examined reported reasons for and outcomes of MBT use and frequency of MBT types.The sample included cancer survivors (N = 3076) and non-cancer controls (N = 31,387). Logistic regression tested the relationship of MBT use and survivorship stage. Weighted percentages were calculated by survivorship stage for reported reasons and outcomes of use and frequency of MBT types.MBT use varied by cancer survivorship stage (p = 0.02): acute (8.3 %), short-term (15.4 %), long-term (11.7 %) survivorship and non-cancer controls (13.2 %). In the adjusted model, short-term survivors had 35 % greater odds of MBT use than did controls (95 % CI 1.00, 1.83). Reasons for and outcomes of MBT use varied among the survivorship stages, with more acute survivors reporting medical-related reasons and more short-term survivors reporting to manage symptoms.MBT may fulfill different symptom management needs at varying stages of survivorship. These findings can help inform supportive care services of survivors' use of MBT for symptom burden at each stage and the allocation of these services.

The use of trial of labor after cesarean delivery calculators in the prediction of successful vaginal birth after cesarean delivery gives physicians an evidence-based tool to assist with patient counseling and risk stratification. Before deployment of prediction models for routine care at an institutional level, it is recommended to test their performance initially in the institution's target population. This allows the institution to understand not only the overall accuracy of the model for the intended population but also to comprehend where the accuracy of the model is most limited when predicting across the range of predictions (calibration).The purpose of this study was to compare 3 models that predict successful vaginal birth after cesarean delivery with the use of a single tertiary referral cohort before continuous model deployment in the electronic medical record.All cesarean births for failed trial of labor after cesarean delivery and successful vaginal birth after cesarean delivery at an academic health system between May 2013 and March 2016 were reviewed. Women with a history of 1 previous cesarean birth who underwent a trial of labor with a term (≥37 weeks gestation), cephalic, and singleton gestation were included. Women with antepartum intrauterine fetal death or fetal anomalies were excluded. The probability of successful vaginal birth after cesarean delivery was calculated with the use of 3 prediction models: Grobman 2007, Grobman 2009, and Metz 2013 and compared with actual vaginal birth after cesarean delivery success. Each model's performance was measured with the use of concordance indices, Brier scores, and calibration plots. Decision curve analysis identified the range of threshold probabilities for which the best prediction model would be of clinical value.Four hundred four women met the eligibility criteria. The observed rate of successful vaginal birth after cesarean delivery was 75% (305/404). Concordance indices were 0.717 (95% confidence interval, 0.659-0.778), 0.703 (95% confidence interval, 0.647-0.758), and 0.727 (95% confidence interval, 0.669-0.779), respectively. Brier scores were 0.172, 0.205, and 0.179, respectively. Calibration demonstrated that Grobman 2007 and Metz vaginal birth after cesarean delivery models were most accurate when predicted probabilities were60% and were beneficial for counseling women who did not desire to have vaginal birth after cesarean delivery but had a predicted success rates of 60-90%. The models underpredicted actual probabilities when predicting success at60%. The Grobman 2007 and Metz vaginal birth after cesarean delivery models provided greatest net benefit between threshold probabilities of 60-90% but did not provide a net benefit with lower predicted probabilities of success compared with a strategy of recommending vaginal birth after cesarean delivery for all women .When 3 commonly used vaginal birth after cesarean delivery prediction models are compared in the same population, there are differences in performance that may affect an institution's choice of which model to use.

BACKGROUND Frailty is a geriatric syndrome characterized by weakness and weight loss and is associated with adverse health outcomes. It is often an unmeasured confounder in pharmacoepidemiologic and comparative effectiveness studies using administrative claims data. METHODS Among the Atherosclerosis Risk in Communities (ARIC) Study Visit 5 participants (2011-2013; n = 3,146), we conducted a validation study to compare a Medicare claims-based algorithm of dependency in activities of daily living (or dependency) developed as a proxy for frailty with a reference standard measure of phenotypic frailty. We applied the algorithm to the ARIC participants' claims data to generate a predicted probability of dependency. Using the claims-based algorithm, we estimated the C-statistic for predicting phenotypic frailty. We further categorized participants by their predicted probability of dependency (

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.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.

Objectives Despite the enormous prevalence of autism spectrum disorder (ASD), its global impact has yet to be realized. Millions of families worldwide need effective treatments to help them get through everyday challenges like eating, sleeping, digestion, and social interaction. Qigong Sensory Training (QST) is a nonverbal, parent-delivered intervention recently shown to be effective at reducing these everyday challenges in children with ASD. This study tested the feasibility of a protocol for investigating QST’s neural mechanism. Methods During a single visit, 20 children, 4- to 7-year-old, with ASD viewed images of emotional faces before and after receiving QST or watching a video (controls). Heart rate variability was recorded throughout the visit, and power in the high frequency band (0.15–0.4 Hz) was calculated to estimate parasympathetic tone in 5-s nonoverlapping windows. Cerebral oximetry of prefrontal cortex was recorded during rest and while viewing emotional faces. Results 95% completion rate and 7.6% missing data met a priori standards confirming protocol feasibility for future studies. Preliminary data suggest: (1) during the intervention, parasympathetic tone increased more in children receiving massage (M = 2.9, SD = 0.3) versus controls (M = 2.5, SD = 0.5); (2) while viewing emotional faces post-intervention, parasympathetic tone was more affected (reduced) in the massage group ( p = 0.036); and (3) prefrontal cortex response to emotional faces was greater after massage compared to controls. These results did not reach statistical significance in this small study powered to test feasibility. Discussion/Conclusion This study demonstrates solid protocol feasibility. If replicated in a larger sample, these findings would provide important clues to the neural mechanism of action underlying QST’s efficacy for improving sensory, social, and communication difficulties in children with autism.

Medicare claims are increasingly used for epidemiologic studies in older adults. Claims capture longitudinal healthcare utilization (diagnoses, procedures, and medication dispensing), but lack clinical measures including frailty, which may confound or modify observed associations. Researchers previously developed a Medicare claims-based model (MCBM, 20 diagnoses, procedures, and durable medical equipment indicators) to predict severe dependence in activities of daily living as a proxy for frailty. Using Medicare claims linked with clinical data from Atherosclerosis Risk in Communities (ARIC) cohort participants (2011–2013), we assessed the validity of the MCBM to predict phenotypic frailty (PF), derived from cohort data. We described the prevalence of MCBM indicators (e.g., skin ulcer) among participants classified as frail, pre-frail, or robust and computed measures of model discrimination (c-statistic), calibration (Hosmer-Lemeshow test), and predictive validity (mortality using Cox proportional hazards models). Of 3,146 participants (median age: 75, 60% women, 22% Black), 7% were frail. The prevalence of MCBM indicators was highest among frail participants. The mean predicted probability of MCBM-derived frailty was 6.9% (range: 0.4%-78.4%). Model discrimination for prediction of PF was fair (c-statistic=0.744), while calibration was good (p-value=0.51). The crude hazard ratio (HR) for mortality (n=71, maximum follow-up=18 months) comparing older adults with high (>20%) versus low (

Purpose Estimating drug effectiveness and safety among older adults in population-based studies using administrative health care claims can be hampered by unmeasured confounding as a result of frailty. A claims-based algorithm that identifies patients likely to be dependent, a proxy for frailty, may improve confounding control. Our objective was to develop an algorithm to predict dependency in activities of daily living (ADL) in a sample of Medicare beneficiaries. Methods Community-dwelling respondents to the 2006 Medicare Current Beneficiary Survey, >65 years old, with Medicare Part A, B, home health, and hospice claims were included. ADL dependency was defined as needing help with bathing, eating, walking, dressing, toileting, or transferring. Potential predictors were demographics, International Classification of Diseases, Ninth Revision Clinical Modification diagnosis/procedure and durable medical equipment codes for frailty-associated conditions. Multivariable logistic regression was used to predict ADL dependency. Cox models estimated hazard ratios for death as a function of observed and predicted ADL dependency. Results Of 6391 respondents, 57% were female, 88% white, and 38% were ≥80. The prevalence of ADL dependency was 9.5%. Strong predictors of ADL dependency were charges for a home hospital bed (OR = 5.44, 95%CI = 3.28–9.03) and wheelchair (OR = 3.91, 95%CI = 2.78–5.51). The c-statistic of the final model was 0.845. Model-predicted ADL dependency of 20% or greater was associated with a hazard ratio for death of 3.19 (95%CI: 2.78, 3.68). Conclusions An algorithm for predicting ADL dependency using health care claims was developed to measure some aspects of frailty. Accounting for variation in frailty among older adults could lead to more valid conclusions about treatment use, safety, and effectiveness. Copyright © 2014 John Wiley & Sons, Ltd.

Objective To examine the traditional diet-heart hypothesis through recovery and analysis of previously unpublished data from the Minnesota Coronary Experiment (MCE) and to put findings in the context of existing diet-heart randomized controlled trials through a systematic review and meta-analysis. Design The MCE (1968-73) is a double blind randomized controlled trial designed to test whether replacement of saturated fat with vegetable oil rich in linoleic acid reduces coronary heart disease and death by lowering serum cholesterol. Recovered MCE unpublished documents and raw data were analyzed according to hypotheses prespecified by original investigators. Further, a systematic review and meta-analyses of randomized controlled trials that lowered serum cholesterol by providing vegetable oil rich in linoleic acid in place of saturated fat without confounding by concomitant interventions was conducted. Setting One nursing home and six state mental hospitals in Minnesota, United States. Participants Unpublished documents with completed analyses for the randomized cohort of 9423 women and men aged 20-97; longitudinal data on serum cholesterol for the 2355 participants exposed to the study diets for a year or more; 149 completed autopsy files. Interventions Serum cholesterol lowering diet that replaced saturated fat with linoleic acid (from corn oil and corn oil polyunsaturated margarine). Control diet was high in saturated fat from animal fats, common margarines, and shortenings. Main outcome measures Death from all causes; association between changes in serum cholesterol and death; and coronary atherosclerosis and myocardial infarcts detected at autopsy. Results The intervention group had significant reduction in serum cholesterol compared with controls (mean change from baseline −13.8% v −1.0%; P

Although dietary supplement use is common, its assessment is challenging, especially among ethnic minority populations such as Hispanics/Latinos. Using the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) (n = 16,415), this report compares two strategies for capturing dietary supplement use over a 30-day period: a medication-based inventory and a nutrition-based dietary supplement interview. Age-standardized prevalence was calculated across multiple dietary supplement definitions, adjusted with survey/nonresponse weights. The prevalence of dietary supplement use was substantially higher as measured in the dietary supplement interview, compared to the medication inventory: for total dietary supplements (39% vs 26%, respectively), for nonvitamin, nonmineral supplements (24% vs 12%), and for botanicals (9.2% vs 4.5%). Concordance between the two assessments was fair to moderate (Cohen's kappa: 0.31–0.52). Among women, inclusion of botanical teas increased the prevalence of botanical supplement use from 7% to 15%. Supplement assessment that includes queries about botanical teas yields more information about patient supplement use.

The aim of this study was to determine whether adolescents who were high in self-compassion self-reported different levels of emotional wellbeing than adolescents who were low in self-compassion, and to determine whether those high in self-compassion responded differently under a lab social stressor than those low in self-compassion. In a lab setting, participants (age 13–18; n = 28) completed the Trier Social Stress Test (TSST) and physiological stress was assessed via salivary cortisol, heart rate, blood pressure, and heart rate variability at baseline, during the TSST, and during recovery. After completing the lab protocol, an email was sent to participants that provided a link to an online survey which was composed of emotional wellbeing measures including perceived stress, life satisfaction, positive and negative affect. After conducting repeated measure ANOVAS to determine that the TSST induced a significant stress response, the sample was split at the median of self-compassion. T tests were conducted to determine meaningful differences (Hedges’ g > .20) between the groups. Findings indicated that those in the high self-compassion group (≥the median) self-reported greater emotional wellbeing than those in the low self-compassion group (

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.

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.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.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.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.

Early aggressive rehabilitation therapies maximize functional recovery. We examined patient-reported preferences for their initial rehabilitation therapy setting during their acute stroke hospitalization and whether there was an association between their preferences and their actual discharge destination.Eligible stroke patients were surveyed during their acute hospital stay at either a primary stroke center or a rural community hospital in North Carolina. Patients were questioned about their knowledge of inpatient rehabilitation, preferences for the initial rehabilitation therapy setting and intensity, and how far from home they were willing to travel to receive therapies. The primary outcome was their actual discharge destination. The exposure variable was their preference for initial rehabilitation therapy setting. Logistic regression models assessed the relationship between the outcome and exposure while controlling for other variables of interest.Among 53 patients surveyed in the study, 85% preferred to be discharged home. After controlling for other factors, discharge to the actual destination of home was associated with a preference for an initial rehabilitation therapy setting of home (OR, 7.19; 95% CI, 1.10-46.89).Patient preference for the initial rehabilitation therapy setting is home. Providers should inquire about patient preference and provide information about treatment options to help inform decision making.

Objectives. The study aims to compare the omega-6 (n-6) and omega-3 (n-3) highly unsaturated fatty acids (HUFA), and trans fatty acid (trans FA) status of Complex Regional Pain Syndrome (CRPS) patients to pain-free controls. Design. Case control study. Setting. The setting was at a multidisciplinary reha- bilitation center. Patients. Twenty patients that met the Budapest research diagnostic criteria for CRPS and 15 pain- free control subjects were included in this study. Outcome Measures. Fasting plasma fatty acids were collected from all participants. In CRPS patients, pain was assessed using the McGill Pain Questionnaire—Short Form. In addition, results from the perceived disability (Pain Disability Index), pain-related anxiety (Pain Anxiety Symptom Scale Short Form), depression (Center for Epidemio- logic Studies Depression Scale Short Form), and quality of life (Short Form-36 (SF-36)) were evaluated. Results. Compared with controls, CRPS patients demonstrated elevated concentrations of n-6 HUFA and trans FA. No differences in n-3 HUFA concentra- tions were observed. Plasma concentrations of the n-6 HUFA docosatetraenoic acid were inversely cor- related with the "vitality" section of the SF-36. Trans FA concentrations positively correlated with pain- related disability and anxiety. Conclusion. These pilot data suggest that elevated n-6 HUFA and trans FA may play a role in CRPS pathogenesis. These findings should be replicated, and more research is needed to explore the clinical significance of low n-6 and trans FA diets with or without concurrent n-3 HUFA supplementation, for the management of CRPS.

Use of dietary supplements (DS) is common in the United States; however little is known about the use of DS specifically in hospitalized patients.The goal of this study is to begin to characterize trends in DS use by hospitalized patients and to assess the degree of patient-physician communication about use of DS that occurs during hospitalization.This is a cross-sectional, observational pilot study.Participants were admitted to the general internal medicine or geriatrics service by house staff residents; thoseor= 18 years of age who were medically stable, cognitively intact and fluent in English and/or Spanish were invited to participate in the study.Nearly 80% of hospitalized patients reported use of DS, with 52% reporting use of non-vitamin/non-mineral DS. During the admission process, physicians documented inquiring about DS use only 20% of the time. While the majority of patients had no concern about temporarily discontinuing their DS during hospitalization, 13% of patients reported that they believed there was nothing wrong with continued use of DS while hospitalized regardless of the recommendations provided by their inpatient physicians.Use of DS in hospitalized patients is common, and communication between patients and physicians regarding their use is limited.

Increasingly, research is demonstrating the safety, efficacy, and patient satisfaction associated with use of nonpharmacological, complementary interventions for pain management in hospital settings. One such intervention, massage, has been found to be effective for pain and anxiety reduction in limited forms, such as described here, massage is relatively easy to learn and apply. The pilot project was designed to develop and assess a clinical intervention using hand and foot massage for management of pain and anxiety in inpatients on a rehabilitation unit. Methods included formal training of staff nurses in hand and foot massage and subsequently having them teach key family caregivers of the patient how to deliver hand or foot massage in response to reports of pain and anxiety. The report describes study rationale, project development, challenges to implementation in an academic, tertiary care, inpatient rehabilitation facility, and lessons learned for future project design and implementation. The need for a community-based participatory research perspective is addressed.

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.

Background: The prevalence of botanical supplement use among Hispanics/Latinos in the United States varies widely, thwarting efforts to understand patterns of use in these rapidly growing populations. In this systematic review of the literature, we present an analysis of patterns of botanical supplement use across available studies including Hispanics/Latinos in the United States, 1998-2011. Methods: Search strategies included CINAHL, EMBASE, Global Health, CAB Abstracts, AMED and Medline resulting in 33 studies reporting botanical supplement prevalence among Hispanic/Latino adults, limiting studies to those with similar outcomes and Hispanic/Latino sample ≥1%. Results: Median prevalence of botanical supplement use among Hispanics/Latinos varied from 12% for ≤30 days of use to 27% for 6-12 months of use and 45% for 2+ years of use. Variation in prevalence of botanical use among Hispanics/Latinos was largely dependent on study design factors, particularly sampling strategy and target population. Patterns associated with higher median prevalence included regional (42%, 95% CI: 35, 57%) vs. national (15%; 8, 22%) samples, convenience (45%; 35, 63%) vs. probability sampling (21%; 10, 42%), and majority Hispanic/Latino (45%; 32, 67%) vs. majority non-Hispanic/ Latino (21%; 15, 42%) samples. Studies targeting Hispanic/Latino populations with botanical assessments specific to these populations resulted in higher prevalence estimates (49% vs. 18%). The most common botanicals reported by Hispanics/ Latinos across studies were chamomile, aloe, and garlic. Conclusions: Although studies with probability sampling are less affected by selection bias, most target the general US population and exclude botanical supplements common among Hispanic/Latino populations. Improved estimates of botanical supplement use among Hispanics/Latinos require culturally-relevant assessment instruments and strategies. Assessments of botanical supplement use in other ethnic populations, e.g., among immigrants from Asian countries, are also likely to suffer from information bias.

Omega-3 and n-6 fatty acids are biosynthetic precursors to lipid mediators with antinociceptive and pronociceptive properties. We conducted a randomized, single-blinded, parallel-group clinical trial to assess clinical and biochemical effects of targeted alteration in dietary n-3 and n-6 fatty acids for treatment of chronic headaches. After a 4-week preintervention phase, ambulatory patients with chronic daily headache undergoing usual care were randomized to 1 of 2 intensive, food-based 12-week dietary interventions: a high n-3 plus low n-6 (H3-L6) intervention, or a low n-6 (L6) intervention. Clinical outcomes included the Headache Impact Test (HIT-6, primary clinical outcome), Headache Days per month, and Headache Hours per day. Biochemical outcomes included the erythrocyte n-6 in highly unsaturated fatty acids (HUFA) score (primary biochemical outcome) and bioactive n-3 and n-6 derivatives. Fifty-six of 67 patients completed the intervention. Both groups achieved targeted intakes of n-3 and n-6 fatty acids. In intention-to-treat analysis, the H3-L6 intervention produced significantly greater improvement in the HIT-6 score (-7.5 vs -2.1; P0.001) and the number of Headache Days per month (-8.8 vs -4.0; P=0.02), compared to the L6 group. The H3-L6 intervention also produced significantly greater reductions in Headache Hours per day (-4.6 vs -1.2; P=0.01) and the n-6 in HUFA score (-21.0 vs -4.0%; P0.001), and greater increases in antinociceptive n-3 pathway markers 18-hydroxy-eicosapentaenoic acid (+118.4 vs +61.1%; P0.001) and 17-hydroxy-docosahexaenoic acid (+170.2 vs +27.2; P0.001). A dietary intervention increasing n-3 and reducing n-6 fatty acids reduced headache pain, altered antinociceptive lipid mediators, and improved quality-of-life in this population.

Objective To evaluate the effectiveness of replacing dietary saturated fat with omega 6 linoleic acid, for the secondary prevention of coronary heart disease and death. Design Evaluation of recovered data from the Sydney Diet Heart Study, a single blinded, parallel group, randomized controlled trial conducted in 1966-73; and an updated meta-analysis including these previously missing data. Setting Ambulatory, coronary care clinic in Sydney, Australia. Participants 458 men aged 30-59 years with a recent coronary event. Interventions Replacement of dietary saturated fats (from animal fats, common margarines, and shortenings) with omega 6 linoleic acid (from safflower oil and safflower oil polyunsaturated margarine). Controls received no specific dietary instruction or study foods. All non-dietary aspects were designed to be equivalent in both groups. Outcome measures All cause mortality (primary outcome), cardiovascular mortality, and mortality from coronary heart disease (secondary outcomes). We used an intention to treat, survival analysis approach to compare mortality outcomes by group. Results The intervention group (n=221) had higher rates of death than controls (n=237) (all cause 17.6% v 11.8%, hazard ratio 1.62 (95% confidence interval 1.00 to 2.64), P=0.05; cardiovascular disease 17.2% v 11.0%, 1.70 (1.03 to 2.80), P=0.04; coronary heart disease 16.3% v 10.1%, 1.74 (1.04 to 2.92), P=0.04). Inclusion of these recovered data in an updated meta-analysis of linoleic acid intervention trials showed non-significant trends toward increased risks of death from coronary heart disease (hazard ratio 1.33 (0.99 to 1.79); P=0.06) and cardiovascular disease (1.27 (0.98 to 1.65); P=0.07). Conclusions Advice to substitute polyunsaturated fats for saturated fats is a key component of worldwide dietary guidelines for coronary heart disease risk reduction. However, clinical benefits of the most abundant polyunsaturated fatty acid, omega 6 linoleic acid, have not been established. In this cohort, substituting dietary linoleic acid in place of saturated fats increased the rates of death from all causes, coronary heart disease, and cardiovascular disease. An updated meta-analysis of linoleic acid intervention trials showed no evidence of cardiovascular benefit. These findings could have important implications for worldwide dietary advice to substitute omega 6 linoleic acid, or polyunsaturated fats in general, for saturated fats. Trial registration Clinical trials NCT01621087.

Few trials have evaluated the metabolic effects and health outcomes of lowering dietaryn-6 PUFA. The objectives of the present paper were (1) to report the methods employed to lower dietaryn-6 PUFA, while either increasing or maintainingn-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 ofn-3 PUFA or (2) a high-n-3 PUFA, low-n-6 PUFA (H3-L6) intervention designed to lowern-6 LA, while increasing then-3 PUFA α-linolenic acid (ALA; ≥ 1·5 en%) and EPA+DHA ( ≥ 1000 mg/d). Pre- and intra-intervention 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);Pn-3 PUFA did not change for the L6 group. Target increases inn-3 ALA (median 1·6 en%, (1·3, 2·0),PPn-6 andn-3 fatty acid composition. Dietary LA can be lowered to ≤ 2·5 en%, with or without concurrent increases in dietaryn-3 PUFA, in an outpatient clinical trial setting using this integrated diet method.

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.

Irritable bowel syndrome (IBS) is a prevalent functional disorder characterized by abdominal pain and hypervigilance to gastrointestinal sensations. We hypothesized that mindfulness training (MT), which promotes nonreactive awareness of emotional and sensory experience, may target underlying mechanisms of IBS including affective pain processing and catastrophic appraisals of gastrointestinal sensations. Seventy five female IBS patients were randomly assigned to participate in either 8 weeks of MT or a social support group. A theoretically grounded, multivariate path model tested therapeutic mediators of the effect of MT on IBS severity and quality of life. Results suggest that MT exerts significant therapeutic effects on IBS symptoms by promoting nonreactivity to gut-focused anxiety and catastrophic appraisals of the significance of abdominal sensations coupled with a refocusing of attention onto interoceptive data with less emotional interference. Hence, MT appears to target and ameliorate the underlying pathogenic mechanisms of IBS.

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)