Aerobic Exercise Improves Heart Rate Variability After an Implantable Cardioverter Defibrillator (ICD).

CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov: NCT00522340.

Age Differences in Core Symptoms and Symptom Relationships in Patients With Irritable Bowel Syndrome: A Network Analysis.

INTRODUCTION: Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction, characterized by symptoms of abdominal pain and changes in bowel habits. It often co-occurs with extraintestinal somatic and psychological symptoms. However, the nature of the interrelationships among these symptoms is unclear. Although previous studies have noted age differences in IBS prevalence and specific symptom severity, it remains unknown whether specific symptoms and symptom relationships may differ by age. METHODS: Symptom data were collected in 355 adults with IBS (mean age 41.4 years, 86.2% female). Network analysis was used to examine the interrelationships among 28 symptoms and to identify the core symptoms driving the symptom structure between young (≤45 years) vs older (>45 years) adults with IBS. We evaluated 3 network properties between the 2 age groups: network structure, edge (connection) strength, and global strength. RESULTS: In both age groups, fatigue was the top core symptom. Anxiety was a second core symptom in the younger age group, but not the older age group. Intestinal gas and/or bloating symptoms also exerted considerable influences in both age groups. The overall symptom structure and connectivity were found to be similar regardless of age. DISCUSSION: Network analysis suggests fatigue is a critical target for symptom management in adults with IBS, regardless of age. Comorbid anxiety is likely an important treatment focus for young adults with IBS. Rome V criteria update could consider the importance of intestinal gas and bloating symptoms. Additional replication with larger diverse IBS cohorts is warranted to verify our results.

Exploration of associations among dietary tryptophan, microbiome composition and function, and symptom severity in irritable bowel syndrome.

BACKGROUND: Imbalance of the tryptophan (TRP) pathway may influence symptoms among patients with irritable bowel syndrome (IBS). This study explored relationships among different components that contribute to TRP metabolism (dietary intake, stool metabolite levels, predicted microbiome metabolic capability) in females with IBS and healthy controls (HCs). Within the IBS group, we also investigated relationships between TRP metabolic determinants, Bifidobacterium abundance, and symptoms of IBS. METHODS: Participants with IBS (Rome III) and HCs completed a 28-day diary of gastrointestinal symptoms and a 3-day food record for TRP intake. They provided a stool sample for shotgun metagenomics, 16 S rRNA analyses, and quantitative measurement of TRP by mass spectrometry. RESULTS: Our cohort included 115 females, 69 with IBS and 46 HCs, with a mean age of 28.5 years (SD 7.4). TRP intake (p = 0.71) and stool TRP level (p = 0.27) did not differ between IBS and HC. Bifidobacterium abundance was lower in the IBS group than in HCs (p = 0.004). Predicted TRP metabolism gene content was higher in IBS than HCs (FDR-corrected q = 0.006), whereas predicted biosynthesis gene content was lower (q = 0.045). Within the IBS group, there was no association between symptom severity and TRP intake or stool TRP, but there was a significant interaction between Bifidobacterium abundance and TRP intake (q = 0.029) in predicting stool character. CONCLUSIONS: Dietary TRP intake, microbiome composition, and differences in TRP metabolism constitute a complex interplay of factors that could modulate IBS symptom severity.

Rest-Activity Rhythm Fragmentation and Weaker Circadian Strength Are Associated With Cognitive Impairment in Survivors of Acute Respiratory Failure.

Background: Survivors of acute respiratory failure (ARF) experience long-term cognitive impairment and circadian rhythm disturbance after hospital discharge. Although prior studies in aging and neurodegenerative diseases indicate actigraphy-estimated rest-activity circadian rhythm disturbances are risk factors for cognitive impairment, it is unclear if this applies to ARF survivors. This study explored the relationships of actigraphy-estimated rest-activity circadian rhythms with cognitive functioning in ARF survivors at 3 months after discharge. Methods: 13 ARF survivors (mean age 51 years and 69% males) completed actigraphy and sleep diaries for 9 days, followed by at-home neuropsychological assessment. Principal component factor analysis created global cognition and circadian rhythm variables, and these first components were used to examine the global relationships between circadian rhythm and cognitive measure scores. Results: Global circadian function was associated with global cognition function in ARF survivors (r = .70, p = .024) after adjusting for age, education, and premorbid cognition. Also, greater fragmented rest-activity circadian rhythm (estimated by intradaily variability, r = .85, p = .002), and weaker circadian strength (estimated by amplitude, r = .66, p = .039; relative strength, r = .70, p = .024; 24-h lag serial autocorrelation, r = .67, p = .035), were associated with global cognition and individual cognitive tests. Conclusions: These results suggest circadian rhythm disturbance is associated with poorer global cognition in ARF survivors. Future prospective research with larger samples is needed to confirm these results and increase understanding of the relationship between disrupted circadian rhythms and cognitive impairment among ARF survivors.

Physical function, psychological adjustment, and self-efficacy following sudden cardiac arrest and an initial implantable cardioverter defibrillator (ICD) in a social cognitive theory intervention: secondary analysis of a randomized control trial.

BACKGROUND: Sudden cardiac arrest (SCA) survivorship results in unique issues in return to physical and psychological function. The purpose of the study was to compare recovery across the first year between SCA survivors and other arrhythmia patients who received a first-time implantable cardioverter defibrillator (ICD) for secondary prevention, participating in a social cognitive theory (SCT) intervention. METHODS: 168 (129 males, 39 females) who received an ICD for secondary prevention (SCA N = 65; other arrhythmia N = 103) were randomized to one of two study conditions: SCT intervention (N = 85) or usual care (N = 83). Outcomes were measured at baseline hospital discharge, 1, 3, 6, & 12 months: (1) Physical Function: Patient Concerns Assessment (PCA), SF-36 (PCS); (2) Psychological Adjustment: State Trait Anxiety (STAI), CES-D depression, SF-36 (MCS); (3) Self-Efficacy: Self-Efficacy (SCA-SE), Self-management Behaviors (SMB), Outcome Expectations (OE). Outcomes were compared over 12 months for intervention condition x ICD indication using general estimating equations. RESULTS: Participants were Caucasian (89%), mean age 63.95 ± 12.3 years, EF% 33.95 ± 13.9, BMI 28.19 ± 6.2, and Charlson Index 4.27 ± 2.3. Physical symptoms (PCA) were higher over time for SCA survivors compared to the other arrhythmia group (p = 0.04), ICD shocks were lower in SCA survivors in the SCT intervention (p = 0.01); psychological adjustment (MCS) was significantly lower in SCA survivors in the SCT intervention over 6 months, which improved at 12 months (p = 0.05); outcome expectations (OE) were significantly lower for SCA survivors in the SCT intervention (p = 0.008). CONCLUSIONS: SCA survivors had greater number of physical symptoms, lower levels of mental health and outcome expectations over 12 months despite participation in a SCT intervention. Trial registration Clinicaltrials.gov: NCT04462887.

Cognitive Behavioral Therapy-Based Comprehensive Self-Management Program Improves Presenteeism in Persons with Irritable Bowel Syndrome: A Secondary Data Analysis.

Individuals with irritable bowel syndrome (IBS) are more likely to miss work (absenteeism), have reduced work effectiveness (presenteeism) and experience activity impairment. This study compared the effect of a comprehensive self-management (CSM) intervention program (incorporating cognitive behavioral therapy, diet education and relaxation) versus usual care on work- and activity-impairments in adults with IBS. This secondary data analysis used daily diaries and Work Productivity and Activity Impairment in Irritable Bowel Syndrome (WPAI-IBS) questionnaire data collected at baseline, 3, 6 and 12 months post-randomization from 160 adults with IBS. Mixed-effects modeling was used to compare the effect of CSM versus usual care on work- and activity-related outcomes. The effect of CSM was shown to be superior to usual care in improving WPAI-IBS and diary-measured presenteeism, overall work productivity loss and activity impairment with sustained effects up to 12 months post-randomization (all p < 0.05). Moreover, the CSM intervention was found to be particularly beneficial for IBS patients with greater baseline work and activity impairments (all p < 0.05). The CSM intervention may bring benefits to individuals and society through improving symptoms and reducing presenteeism associated with IBS.

Heart Rate Variability and Inflammatory Stress Response in Young African American Men: Implications for Cardiovascular Risk.

Background: African American men have a disproportionately higher incidence of and suffer greater severity and earlier death from cardiovascular disease (CVD). A common feature of many diseases, which disproportionately afflict disadvantaged African Americans, is inflammation. In particular, inflammation plays a decisive role in the pathogenesis of CVD in that persistent inflammation contributes to plaque evolution and destabilization. Adverse childhood experiences increase the risk for adult inflammatory based disease, particularly cardiovascular disease. This inflammatory burden becomes evident during stressful events and may be related to alterations in autonomic nervous system (ANS) activity. We previously reported that African American men who experienced childhood adversity exhibited a greater inflammatory (IL-6) response to acute stress challenge (Trier Social Stress Test - TSST). The purpose of this study was to determine whether altered ANS activity, as measured by heart rate variability (HRV), contributes to a greater proinflammatory response to stress in those exposed to childhood adversity. Methods: Thirty-four African American adult males underwent the TSST while instrumented with Holter monitors to record continuous heart rate for HRV determination. HRV was calculated as the low frequency (LF) to high frequency (HF) heart rate ratio (LF/HF), with higher LF/HF ratios corresponding to higher sympathetic vs. parasympathetic activity. Salivary samples were collected pre- and post-TSST to measure the proinflammatory cytokine IL-6. Childhood adversity was assessed by the Childhood Trauma Questionnaire. Results: Hierarchical linear modeling demonstrated that higher levels of physical abuse were related to a steeper rise in LF/HF ratio during the TSST. Further, a higher LF/HF ratio, in combination with greater exposure to emotional and physical abuse was associated with a greater IL-6 response to the TSST. Conclusions: These findings suggest that adverse childhood experiences associate with an adult phenotype characterized by an altered ANS response to stress as well as a greater proinflammatory (IL-6) response to an acute stressor. Elevations in salivary inflammatory markers have been associated with increased CVD risk. In conclusion, these findings suggest a role for the ANS in the underlying neuro-biological processes whereby childhood adversity predisposes to a more intense inflammatory response to stressful challenge during adulthood.

Associations between chronotype, social jetlag, and weekday sleep in women with irritable bowel syndrome.

Sleep deficiency is well-documented in individuals with irritable bowel syndrome (IBS). Sleep deficiency includes poor sleep quality and an inadequate amount of sleep, and is a modifiable risk factor for IBS symptom exacerbations. Prior studies in other populations have identified chronotype and social jetlag (SJL) as important determinants of sleep outcomes. However, chronotype and SJL have not been examined in women with IBS. We used multiple linear regression analyses to determine whether chronotype and SJL are associated with sleep outcomes during weekdays among women with IBS predominant constipation (IBS-C), IBS with predominant diarrhea (IBS-D), and healthy control (HC) women. This sample included 62 women with IBS (IBS-C = 29, IBS-D = 33) and 58 HC women who completed a 28-day daily diary from two study cohorts. The average age of the participants was 30.1 (SD 7.2) years. Chronotype was estimated from daily diary data with the average mid-sleep time on weekends (MSWwe). SJL was calculated by subtracting the average mid-sleep time on weekdays from MSWwe. Sleep outcomes included diary assessments of sleep quality, sleep need met, and restorative sleep during weekdays. In HCs, later chronotype was predictive of lower sleep quality (ß = -0.19, p < .01), a perception of sleep need not met (ß = -0.17, p < .001), and a less restorative sleep during weekdays (ß = -0.15, p = .073), whereas SJL was not associated with sleep outcomes. Similar to HCs, earlier chronotypes in women with IBS-C reported better sleep quality and more sufficient sleep need met and restorative sleep during weekdays than later chronotypes (all p > .05). Compared to HCs, the relationships of chronotype with weekday sleep outcomes in the women with IBS-D were in the opposite directions (all p < .05). This exploratory study suggests that chronotype expression may reflect the temporal associations of sleep outcomes within IBS bowel pattern predominance subgroups, particularly sleep quality and sleep need met. Additional investigations are warranted to examine whether specific temporal attributes of symptoms and/or symptom severity associated with IBS subgroups contribute to chronotype expression.

A Comprehensive Self-Management Program With Diet Education Does Not Alter Microbiome Characteristics in Women With Irritable Bowel Syndrome.

BACKGROUND AND PURPOSE: Changes in diet and lifestyle factors are frequently recommended for persons with irritable bowel syndrome (IBS). It is unknown whether these recommendations alter the gut microbiome and/or whether baseline microbiome predicts improvement in symptoms and quality of life following treatment. Therefore, the purpose of this study was to explore if baseline gut microbiome composition predicted response to a Comprehensive Self-Management (CSM) intervention and if the intervention resulted in a different gut microbiome composition compared to usual care. METHODS: Individuals aged 18-70 years with IBS symptoms ≥6 months were recruited using convenience sampling. Individuals were excluded if medication use or comorbidities would influence symptoms or microbiome. Participants completed a baseline assessment and were randomized into the eight-session CSM intervention which included dietary education and cognitive behavioral therapy versus usual care. Questionnaires included demographics, quality of life, and symptom diaries. Fecal samples were collected at baseline and 3-month post-randomization for 16S rRNA-based microbiome analysis. RESULTS: Within the CSM intervention group (n = 30), Shannon diversity, richness, and beta diversity measures at baseline did not predict benefit from the CSM intervention at 3 months, as measured by change in abdominal pain and quality of life. Based on both alpha and beta diversity, the change from baseline to follow-up microbiome bacterial taxa did not differ between CSM (n = 25) and usual care (n = 25). CONCLUSIONS AND INFERENCES: Baseline microbiome does not predict symptom improvement with CSM intervention. We do not find evidence that the CSM intervention influences gut microbiome diversity or composition over the course of 3 months.

Bile Acids and Microbiome Among Individuals With Irritable Bowel Syndrome and Healthy Volunteers.

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder. High bile acid (BA) profiles have been associated with abdominal pain symptoms, mucosal inflammation, and diarrhea in a subgroup of those with IBS. The purpose of this study was to compare: 1) fecal primary and secondary BAs in women with and without IBS; and 2) symptoms, gut microbiome, and diet between women with high and normal BAs (i.e., similar to healthy [HC] women). Women (ages 18-45) with IBS and HCs were recruited from healthcare providers or the community. Participants kept a 28-day symptom diary, completed a 3-day food journal, and collected a stool sample for microbiome analysis (16 S rRNA gene sequencing). Primary and secondary BA levels were determined by mass spectrometry. Primary BAs did not differ between IBS (n = 45) and HC (n = 28) groups; women with IBS had significantly increased conjugated secondary BAs (glycodeoxycholic acid [p = 0.006], taurodeoxycholic acid [p = 0.006], and glycolithocholic acid [p = 0.01]). Sixty percent of women with IBS had normal BAs whereas 40% had high BAs. Women with high fecal BAs were predominantly IBS-Diarrhea or IBS-Mixed and consumed less fiber and vegetable protein and more animal protein compared to women with IBS whose fecal BAs levels were comparable to HCs. Those with high conjugated secondary fecal BAs also had a greater Firmicutes/Bacteroidetes ratio, less abundance of phylum Bacteroidetes and genus Gemmiger, and more abundance of family Erysipelotrichaceae compared to IBS women with normal BAs. Determination of fecal BA levels provides additional insights into pathophysiological links between diet and microbiome in IBS.

Cytokine Levels and Symptoms Among Women with Irritable Bowel Syndrome: Considering the Role of Hormonal Contraceptive Use.

BACKGROUND: Young to middle-aged women are more likely than men to be diagnosed with irritable bowel syndrome (IBS). Immune dysfunction may be present in IBS, however, few studies have tested whether hormonal contraceptive use is linked to inflammatory markers. The purpose of this study was to compare cytokine levels between women (ages 18-45) with and without IBS and with and without hormonal contraceptive use and to examine the relationships of cytokine levels to IBS gastrointestinal (GI) and non-GI symptoms within those using and not using hormonal contraceptives. METHODS: Seventy-three women with IBS and 47 healthy control women completed questionnaires (demographics, hormonal contraceptive use) and kept a 28-day symptom diary. Fasting plasma and LPS-stimulated pro-inflammatory (IL-1ß, IL-6, IL-12p40, IL-12p70, IL-8, and TNF-α) and anti-inflammatory (IL-10) cytokines were assayed. RESULTS: No differences were found in plasma or stimulated cytokine levels between IBS and control women. Levels of IL-1ß (p = 0.04) and TNF-α (p = 0.02) were higher among women who did not use hormonal contraceptives compared to women who used hormonal contraceptives. Among women with IBS, significant correlations were found between daily psychological distress and plasma IL-10, IL-12p70, IL-1ß, IL-6, and IL-8 cytokine levels. CONCLUSIONS: These results suggest that hormonal contraceptive use might reduce IL-1ß and TNF-α cytokine levels in women with IBS. The impact of hormonal contraceptive use on innate immune activation among women with IBS requires further research.

Indirect effect of sleep on abdominal pain through daytime dysfunction in adults with irritable bowel syndrome.

STUDY OBJECTIVES: Sleep deficiency, psychological distress, daytime dysfunction, and abdominal pain are common in adults with irritable bowel syndrome. Prior research on individuals with chronic pain has identified the indirect effect of sleep on pain through psychological distress or daytime dysfunction; however, this effect is less clear in irritable bowel syndrome. The purpose of this study was to examine potential indirect effects of sleep on abdominal pain symptoms simultaneously through psychological distress and daytime dysfunction in adults with irritable bowel syndrome. METHODS: Daily symptoms of nighttime sleep complaints (sleep quality and refreshment), psychological distress, daytime dysfunction (fatigue, sleepiness, and difficulty concentrating), and abdominal pain were collected in baseline assessments from 2 randomized controlled trials of 332 adults (mean age 42 years and 85% female) with irritable bowel syndrome. Structural equation modeling was used to examine the global relationships among nighttime sleep complaints, psychological distress, daytime dysfunction, and abdominal pain. RESULTS: The structural equation modeling analyses found a strong indirect effect of poor sleep on abdominal pain via daytime dysfunction but not psychological distress. More than 95% of the total effect of nighttime sleep complaints on abdominal pain was indirect. CONCLUSIONS: These findings suggest that the primary impact of nighttime sleep complaints on abdominal pain is indirect. The indirect effect appears primarily through daytime dysfunction. Such understanding provides a potential avenue to optimize personalized and hybrid behavioral interventions for adults with irritable bowel syndrome through addressing daytime dysfunction and sleep behaviors. Additional study integrating symptoms with biological markers is warranted to explore the underlying mechanisms accounting for these symptoms. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov. Name: Nursing Management of Irritable Bowel Syndrome: Improving Outcomes, Nursing Management of IBS: Improving Outcomes. URLs: https://clinicaltrials.gov/ct2/show/NCT00167635, https://clinicaltrials.gov/ct2/show/NCT00907790. Identifiers: NCT00167635, NCT00907790.

Sleep and Circadian Rhythms in Survivors of Acute Respiratory Failure.

Background: Little is known about sleep and circadian rhythms in survivors of acute respiratory failure (ARF) after hospital discharge. Objectives: To examine sleep and rest-activity circadian rhythms in ARF survivors 3 months after hospital discharge, and to compare them with a community-dwelling population. Methods: Sleep diary, actigraphy data, and insomnia symptoms were collected in a pilot study of 14 ARF survivors. Rest-activity circadian rhythms were assessed with wrist actigraphy and sleep diary for 9 days, and were analyzed by cosinor and non-parametric circadian rhythm analysis. Results: All participants had remarkable actigraphic sleep fragmentation, 71.5% had subclinical or clinical insomnia symptoms. Compared to community-dwelling adults, this cohort had less stable rest-activity circadian rhythms (p < 0.001), and weaker circadian strength (p < 0.001). Conclusion: Insomnia and circadian disruption were common in ARF survivors. Sleep improvement and circadian rhythm regularity may be a promising approach to improve quality of life and daytime function after ARF.

Repetitive Transcranial Magnetic Stimulation in the Treatment of Bipolar Depression: Experience From a Clinical Setting.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive Food and Drug Administration (FDA)-approved treatment for unipolar treatment-resistant depression (TRD). rTMS has been utilized clinically to treat bipolar TRD; however, there remains a lack of evidence and support for effectively utilizing this intervention for bipolar TRD. We retrospectively analyzed data from a group of patients who were treated with rTMS for unipolar or bipolar TRD and describe a case example to further delineate management techniques for employing rTMS in the treatment of bipolar TRD. METHODS: Records of 71 patients treated with rTMS for unipolar (n=54) or bipolar (n=17) TRD between 2008 and 2017 were reviewed. The primary outcome of depression severity, the Quick Inventory of Depressive Symptomatology, was completed at baseline and after every 5 sessions throughout the course of 30 treatments. Secondary outcomes involved a comparison of outcomes and clinical characteristics within and between the bipolar and unipolar TRD groups. RESULTS: In the total sample, patients' depression improved significantly over the course of treatment. Patients with bipolar TRD showed greater response and remission rates over the course of treatment compared with patients with unipolar TRD, but this difference was not statistically significant. Both groups showed a similar pattern of depression response over treatment time. No manic or hypomanic episodes occurred during any patient's course of rTMS treatment. A case example is provided discussing the timing of rTMS in a patient with bipolar depression to decrease the likelihood of treatment-induced hypomania. LIMITATIONS: Limitations included the small overall sample size, the smaller size of the patient group with bipolar TRD compared with the group with unipolar TRD, and the naturalistic setting of this study. CONCLUSIONS: Our data suggest that rTMS may be equally effective and safe for patients with both unipolar and bipolar depression. Patients with bipolar TRD showed a similar response profile over treatment time compared with patients with unipolar TRD.

Aerobic Exercise Effects on Quality of Life and Psychological Distress After an Implantable Cardioverter Defibrillator.

PURPOSE: The purpose of this study was to evaluate quality of life (QOL), psychological function, and self-efficacy outcomes in the Anti-Arrhythmic Effects of Exercise After an ICD Trial. METHODS: In the Anti-Arrhythmic Effects of Exercise After an ICD Trial, 160 patients (124 men and 36 women) who had an implantable cardioverter defibrillator for primary (43%) or secondary (57%) prevention were randomized to exercise (EX, n = 84) or usual care (UC, n = 76). The EX consisted of 8 wk of home walking 1 hr/d 5 d/wk, followed by 16 wk of maintenance home walking for 150 min/wk. Adherence was determined from exercise logs, ambulatory HR recordings, and phone calls. Assessments were conducted at baseline, 8, and 24 wk for QOL: Patient Concerns Assessment and Short Form-36; anxiety: State Trait Anxiety Inventory; depression: Physician Health Questionnaire-Depression; and self-efficacy: Self-Efficacy for Walking Scale. RESULTS: Participants averaged 55 ± 12 yr of age with ejection fraction = 40.6 ± 15.7%. The EX significantly decreased depression severity (EX: 1.33 ± 0.64; UC: 1.51 ± 0.86, P = .05) and improved self-efficacy (EX: 7.65 ± 1.97; UC: 6.85 ± 2.40, P = .05) at 8 wk. There were no significant effects at 24 wk. Adherent exercisers had significant improvements in QOL, psychological, and self-efficacy outcomes at 8 and 24 wk compared with those who were nonadherent. There were no implantable cardioverter defibrillator shocks associated with exercise. CONCLUSIONS: The EX conferred significant effects on depression and self-efficacy at 8 wk, without effects on QOL. Adherent exercisers experienced significant improvements in outcomes over those who were nonadherent or received UC.

Relationships of Microbiome Markers With Extraintestinal, Psychological Distress and Gastrointestinal Symptoms, and Quality of Life in Women With Irritable Bowel Syndrome.

INTRODUCTION: Altered microbial diversity has been associated with gastrointestinal (GI) symptoms in persons with irritable bowel syndrome (IBS). Less is known about the relationship of microbiome with extraintestinal pain and psychological distress symptoms and quality of life (QOL) in persons with IBS. We aimed to evaluate the relationship of fecal microbiota to GI symptoms, stool consistency, psychological distress, extraintestinal pain, and QOL in participants meeting Rome III criteria for IBS. METHODS: Seventy-six women completed a 28-day diary that included GI, stool consistency, psychological distress, and extraintestinal pain ratings. Participants completed the IBS-Specific Quality of Life questionnaire. Stool samples were collected and analyzed by 16S rRNA gene sequencing. Principal component analysis was performed and the first 2 components (PC1, PC2) were used to test relationships among bacterial families and clinical measures. RESULTS: Participants were categorized as IBS constipation (n=22), IBS diarrhea (n=39), IBS mixed (n=13), and IBS unsubtyped (n=2). There was a significant group effect for the Firmicutes to Bacteroidetes ratio and PC1. Lower microbial diversity and richness were associated with increased urgency and extraintestinal pain, worse QOL, and looser stools. Lower extraintestinal pain was associated with increased Rikenellaceae, Christensenellaceae, Dehalobabacteriaceae, Oscillospiraceae, Mogibacteriaceae, Ruminococcaceae, Sutterellaceae, Desulfovibrionaceae, and Erysipelotrichaceae abundances. QOL was positively associated with many of these same bacterial families. Higher Firmicutes to Bacteroidetes ratio was positively associated with loose stools. There were no statistically significant relationships between daily psychological distress or abdominal pain and bacterial families. CONCLUSIONS: Stool microbial diversity and composition are linked to daily extraintestinal symptoms, stool consistency, and QOL in women with IBS.

Tryptophan Metabolites in Irritable Bowel Syndrome: An Overnight Time-course Study.

BACKGROUND/AIMS: Patients with irritable bowel syndrome (IBS) often report poor sleep quality. Whether poor sleep is associated with tryptophan (Trp) metabolites is unknown. We compared serum Trp metabolites in women with IBS and healthy controls (HCs) using targeted liquid chromatography mass spectrometry (LC-MS)-based profiling. In IBS only, we explored whether Trp metabolites are associated with IBS symptoms and subjective and objective sleep indices, serum cortisol, plasma adrenocorticotropic hormone (ACTH), and cortisol/ACTH levels. METHODS: Blood samples were obtained every 80 minutes in 21 HCs and 38 IBS subjects following an anticipation-of-public-speaking stressor during a sleep laboratory protocol. Subjects completed symptom diaries for 28 days. Adjacent values of metabolites were averaged to represent 4 time-periods: awake, early sleep, mid-sleep, and mid-to-late sleep. Thirteen of 20 targeted Trp metabolites were identified. RESULTS: Ten of 13 Trp metabolites decreased across the night, while nicotinamide increased in both groups. A MANOVA omnibus test performed after principal component analysis showed a significant difference in these 13 principal component (P = 0.014) between groups. Compared to HCs, nicotinamide levels were higher and indole-3-lactic acid levels lower in the IBS group. Melatonin and indole-3-acetic acid levels were associated with several subjective/objective sleep measures; decreased stool consistency/frequency and abdominal pain were positively associated with melatonin and serotonin in the IBS group. The kynurenine and kynurenic acid were associated with ACTH (positively) and cortisol/ACTH (negatively). CONCLUSION: Nighttime Trp metabolites may provide clues to poor sleep and stress with IBS. Further study of the mechanism of metabolite action is warranted.

Effects of a comprehensive self-management intervention on extraintestinal symptoms among patients with IBS.

OBJECTIVE: Adults with irritable bowel syndrome (IBS) often report extraintestinal pain, fatigue, and sleep disturbances in addition to abdominal pain. Few interventions have sought to reduce these extraintestinal symptoms within the IBS population. To address this, we compared the effects of a comprehensive self-management (CSM) intervention to a control intervention (usual care) on extraintestinal pain, fatigue, and sleep disturbances among patients with IBS. METHOD: Data were obtained from 243 IBS patients participating in two CSM intervention trials. Daily symptom diaries were collected at baseline, 3 and 6 months post-randomization. Daily symptoms of headache, backache, muscle pain, joint pain, fatigue, sleepiness during the day, sleep quality, and refreshed by sleep were analyzed. Analysis of covariance was used to determine the effects of the intervention on each symptom at 3 and 6 months controlling for 'study' and baseline symptom levels. RESULTS: Patients in the CSM intervention group reported decreased symptoms of fatigue, sleep disturbances, backache and headache compared to usual care at 3 and 6 months. The CSM group also reported significantly decreased joint pain at 3 months compared to usual care, but not 6 months. No significant difference was found for muscle pain. CONCLUSIONS: An existing CSM intervention is effective in reducing fatigue and sleep disturbances. However, mixed results for extraintestinal pain indicates a need to better differentiate between underlying mechanisms. Addressing such symptoms is important to decrease the overall burden of IBS, reduce health care expenditures, and improve patients' quality of life. TRIAL REGISTRATION: NCT00907790; NCT00167635.

A Feasibility Trial of Two Rehabilitation Models in Severe Cardiopulmonary Illness.

PURPOSE: The purpose of this study was to compare functional capacity and daily activity between two exercise rehabilitation interventions in severe chronic obstructive pulmonary disease (COPD) or heart failure with reduced ejection fraction (HFrEF) over 6 months. Secondarily, we compared intervention groups on symptoms, depression, quality of life, and cardiopulmonary function. DESIGN/METHODS: Ninety patients with severe COPD (n = 63) or HFrEF (n = 27) were randomized to either an exercise adherence intervention or standard cardiopulmonary rehabilitation. Patients were 65-year-old male veterans who had either severe COPD (FEV1 < 50% predicted) or HFrEF (EF% < 40%). RESULTS: There were no statistically significant differences between the intervention groups or COPD or HfrEF groups on functional capacity, daily activity, symptoms, depression, quality of life, or cardiopulmonary function at 6 months. CONCLUSION: In late-stage COPD and HFrEF, functional capacity is not improved with rehabilitation interventions. CLINICAL RELEVANCE: In severe COPD and heart failure, cardiopulmonary rehabilitation conducted at home or in the outpatient setting was not beneficial.

rTMS effects in patients with co-morbid somatic pain and depressive mood disorders.

BACKGROUND: Pain is a common co-morbidity among clinically depressed individuals. We investigated a group of patients who were treated with repetitive transcranial magnetic stimulation (rTMS) for treatment resistant depression (TRD) and who were assessed for severity of both depression and pain at baseline and throughout treatment. METHODS: Records of 71 patients treated for TRD with rTMS from 2008 to 2017 were reviewed. Primary outcome measures including depression severity using the Quick Inventory of Depressive Symptomatology (QIDS) and a 0-10 numeric pain rating scale were assessed at baseline and after every 5 sessions throughout the course of 30 treatments. RESULTS: In the total sample, pain improved significantly over the course of treatment. Changes within subjects in QIDS were associated with the changes in pain (p = 0.011). TRD patients with higher pain scores at baseline tended to be older, experienced a longer duration of illness, and showed significant differences in QIDS over treatment time as compared with the low baseline pain group. Patients who had failed a serotonin norepinephrine reuptake inhibitor (SNRI) (venlafaxine or duloxetine) trial in the past had less pain at baseline and showed a group difference in pain scores at all time points, which was significant at treatments 20, 25 and 30, compared to patient groups who had never taken these medications or were currently taking these medications. LIMITATIONS: Limitations include the potential impact of the discomfort over the treatment site on the scalp, as it is unclear whether patients' assessment of pain included this side effect, and the lack of a control group due to the naturalistic design of this study. CONCLUSION: Our data show that pain and depression respond well to rTMS in a TRD population. Pain and depression severity in rTMS patients may be associated over the course of rTMS treatment time-points in individuals with higher levels of baseline pain.