Management of Muscle Relaxation With Rocuronium and Reversal With Neostigmine or Sugammadex Guided by Quantitative Neuromuscular Monitoring.

BACKGROUND: The optimal pharmacological reversal strategy for neuromuscular blockade remains undefined even in the setting of strong recommendations for quantitative neuromuscular monitoring by several national and international anesthesiology societies. We evaluated a protocol for managing rocuronium blockade and reversal, using quantitative monitoring to guide choice of reversal agent and to confirm full reversal before extubation. METHODS: We conducted a prospective cohort study and enrolled 200 patients scheduled for elective surgery involving the intraoperative use of rocuronium. Providers were asked to adhere to a protocol that was similar to local practice recommendations for neuromusculalr block reversal that had been used for >2 years; the protocol added quantitative monitoring that had not previously been routinely used at our institution. In this study, providers used electromyography-based quantitative monitoring. Pharmacological reversal was accomplished with neostigmine if the train-of-four (TOF) ratio was 0.40 to 0.89 and with sugammadex for deeper levels of blockade. The primary end point was the incidence of postoperative residual neuromuscular blockade (PRNB), defined as TOF ratio <0.9 at time of extubation. We further evaluated the difference in pharmacy costs had all patients been treated with sugammadex. RESULTS: A total of 189 patients completed the study: 66 patients (35%) were reversed with neostigmine, 90 patients (48%) with sugammadex, and 33 (17%) patients recovered spontaneously without pharmacological reversal. The overall incidence of residual paralysis was 0% (95% CI, 0-1.9). The total acquisition cost for all reversal drugs was United States dollar (USD) 11,358 (USD 60 per patient) while the cost would have been USD 19,312 (USD 103 per patient, 70% higher) if sugammadex had been used in all patients. CONCLUSIONS: A protocol that includes quantitative monitoring to guide reversal with neostigmine or sugammadex and to confirm TOF ratio ≥0.9 before extubation resulted in the complete prevention of PRNB. With current pricing of drugs, the selective use of sugammadex reduced the total cost of reversal drugs compared to the projected cost associated with routine use of sugammadex for all patients.

Evaluation of a Protocol for the Management of Maintenance and Reversal of Rocuronium Block Using Neostigmine or Sugammadex.

BACKGROUND: Postoperative residual neuromuscular blockade (PRNB) is defined as an adductor pollicis train-of-four ratio (TOFR) <0.9. It is a common postoperative complication when nondepolarizing muscle relaxants are either not reversed or reversed with neostigmine. PRNB has been reported in 25% to 58% of patients who receive intermediate-acting nondepolarizing muscle relaxants, and it is associated with increased morbidity and decreased patient satisfaction. We conducted a prospective descriptive cohort study during the implementation of a practice guideline that included the selective use of sugammadex or neostigmine. The primary study aim of this pragmatic study was to estimate the incidence of PRNB at arrival to the postanesthesia care unit (PACU) when the practice guideline is followed. METHODS: We enrolled patients undergoing orthopedic or abdominal surgery requiring neuromuscular blockade. Rocuronium administration was guided by surgical requirements and based on ideal body weight, with dose reductions for women and/or age >55 years. Only qualitative monitoring was available to the anesthesia providers, and selection of sugammadex or neostigmine was guided by tactile assessments of the response to train-of-four (TOF) stimulation by a peripheral nerve stimulator. Neostigmine was administered if no fade was detected in the TOF response at the thumb. Deeper blocks were reversed with sugammadex. The prespecified primary and secondary end points were the incidence of PRNB at arrival to the PACU, defined as a normalized TOFR (nTOFR) < 0.9, and severe PRNB, defined as nTOFR <0.7 on arrival to the PACU. Anesthesia providers were blinded to all quantitative measurements made by research staff. RESULTS: Analysis included 163 patients, and 145 underwent orthopedic and 18 abdominal surgeries. Of the 163 patients, 92 (56%) were reversed with neostigmine and 71 (44%) with sugammadex. The overall incidence of PRNB at PACU arrival was 5 of 163 or 3% (95% confidence interval [CI], 1-7). The incidence of severe PRNB in PACU was 1% (95% CI, 0-4). Three of the 5 subjects with PRNB had TOFR <0.4 at time of reversal but were given neostigmine since anesthesia providers detected no fade by qualitative assessment. CONCLUSIONS: The use of a protocol that specifies rocuronium dosing and selective use of sugammadex versus neostigmine based on qualitative assessment of TOF count and fade allowed us to achieve an incidence of PRNB of 3% (95% CI, 1-7) at PACU arrival. Quantitative monitoring may be needed to further reduce this incidence.

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.

Exploring the Role of Vitamin D and the Gut Microbiome: A Cross-Sectional Study of Individuals with Irritable Bowel Syndrome and Healthy Controls.

Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction with multifaceted pathophysiology. Prior studies have demonstrated higher rates of vitamin D deficiency in individuals with IBS compared to healthy controls (HC), as well as associations of vitamin D concentration with IBS symptoms. A systematic review of 10 mouse and 14 human studies reported a positive association between vitamin D (serum levels and supplementation) and beta diversity of gut microbiome in a variety of conditions. The present retrospective case-control study aimed to compare vitamin D (25(OH)D) plasma concentrations and gut microbiome composition in adult women with IBS (n=99) and HC (n=62). Plasma concentrations of 25(OH)D were assessed using the Endocrine Society Guidelines definition of vitamin D deficiency (25(OH)D <20 ng/ml) and insufficiency (25(OH)D >20-<30 ng/ml). 16S rRNA microbiome gene sequencing data was available for 39 HC and 62 participants with IBS. Genus-level Bifidobacterium and Lactobacillus and phylum-level Firmicutes and Bacteroidetes relative abundances were extracted from microbiome profiles. Results showed vitamin D deficiency in 40.3% (n=25) vs. 41.4% (n=41), and insufficiency 33.9% (n=21) vs. 34.3% (n=34) in the HCs vs. IBS groups, respectively. The odds of IBS did not differ depending on 25(OH)D status (p=0.75 for deficient, p=0.78 for insufficient), and the average plasma vitamin D concentration did not differ between IBS (mean 24.8 ng/ml) and HCs (mean 25.1 ng/ml; p=0.57). We did not find evidence of an association between plasma 25(OH)D concentration and richness, Shannon index, Simpson index or specific bacterial abundances in either HCs or the IBS group.

The Association Between Hypophosphatemia and Lactic Acidosis After Cardiac Surgery With Cardiopulmonary Bypass: A Retrospective Cohort Study.

OBJECTIVES: The clinical significance of hypophosphatemia in cardiac surgery has not been investigated extensively. The aim of this study was to evaluate the association of postoperative hypophosphatemia and lactic acidosis in cardiac surgery patients at the time of intensive care unit (ICU) admission. DESIGN: A retrospective cohort study. SETTING: At a single academic center. PARTICIPANTS: Patients who underwent nontransplant cardiac surgery with cardiopulmonary bypass between August 2009 and December 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Serum phosphate and lactate levels were measured upon ICU admission in patients undergoing nontransplant cardiac surgery with cardiopulmonary bypass. There were 681 patients in the low-phosphate (<2.5 mg/dL) group and 2,579 patients in the normal phosphate group (2.5-4.5 mg/dL). A higher proportion of patients in the low phosphate group (26%; 179 of 681; 95% CI: 23-30) had severe lactic acidosis compared to patients in the normal phosphate group (16%; 417 of 2,579; 95% CI: 15-18). In an unadjusted logistic regression model, patients in the low phosphate group had 1.9-times the odds of having severe lactic acidosis (serum lactate ≥4.0 mmol/L) when compared to patients in the normal phosphate group (95% CI: 1.5-2.3), and still 1.4-times the odds (95% CI: 1.1-1.7) after adjusting for several possible confounders. CONCLUSIONS: Hypophosphatemia is associated with lactic acidosis in the immediate postoperative period in cardiac surgery patients. Future studies will need to investigate it as a potential treatment target for lactic acidosis.

Socioeconomic Status and Interest in Genetic Testing in a US-Based Sample.

Cancer is a significant burden, particularly to individuals of low socioeconomic status (SES). Genetic testing can provide information about an individual's risk of developing cancer and guide future screening and preventative services. However, there are significant financial barriers, particularly for individuals of low SES. This study used the Early Detection of Genetic Risk (EDGE) Study's patient baseline survey (n = 2329) to evaluate the relationship between socioeconomic status and interest in pursuing hereditary cancer genetic testing. Analysis was completed for two interest outcomes-overall interest in genetic testing and interest in genetic testing if the test were free or low cost. Many demographic and SES variables were predictors for interest in genetic testing, including education, income, and MacArthur Subjective Social Scale (SSS). After controlling for the healthcare system, age, and gender, having a higher education level and a higher household income were associated with greater general interest. Lower SSS was associated with greater interest in genetic testing if the test was free or low cost. If genetic testing is the future of preventative medicine, more work needs to be performed to make this option accessible to low-SES groups and to ensure that those services are used by the most underserved populations.

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.

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.

Neutrophil and lymphocyte counts are associated with different immunopathological mechanisms in systemic lupus erythematosus.

OBJECTIVE: Neutrophils contribute to the SLE pathogenesis. Neutrophil to lymphocyte ratio (NLR) is reported to correlate with disease activity in SLE. The aim of the study was to evaluate whether NLR reflects underlying immunopathogenic activity in SLE, as well as to determine the contribution of each component of NLR, neutrophil and lymphocyte count. METHODS: Data were obtained from a cohort of patients with SLE (n=141) recruited at Lund University, Sweden. NLR levels were compared between patients with SLE and healthy controls (n=79). The relationship between NLR and clinical and immunological markers was examined using Mann-Whitney U test and logistic regression analysis. High NLR was defined as above the 90th percentile of healthy individuals. RESULTS: Patients with SLE had elevated neutrophil count (p=0.04) and reduced lymphocyte count (p<0.0001), resulting in elevated NLR as compared with healthy controls (p<0.0001). Patients with high NLR had more active disease, and were more frequently on prednisone use and immunosuppressive medicines. High NLR was associated with immune complex (IC)-driven disease with presence of antidouble-stranded DNA antibodies (p=0.006), circulating ICs (p=0.02) and type I interferon (IFN) activity (p=0.009). Further, high NLR was associated with neutrophil abnormalities, including enrichment for low-density granulocytes (LDGs) (p=0.001), and increased levels of the serum neutrophil activation marker, calprotectin (p=0.02). Assessing the individual components within NLR, that is, neutrophil and lymphocyte count, high neutrophil count was associated with neutrophil activation markers (p<0.0001), whereas low lymphocyte count was associated with type I IFN activity and elevated numbers of LDGs (p=0.006 and p=0.001, respectively). CONCLUSIONS: NLR is elevated in patients with SLE as compared with healthy individuals, and is associated with key immunopathological events, including type I IFN activity and neutrophil activation. Neutrophil and lymphocyte count reflected different aspects of the pathogenesis of SLE. Further studies are needed to determine the causality of the associations.

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.

Aviation-Style Computerized Surgical Safety Checklist Displayed on a Large Screen and Operated by the Anesthesia Provider Improves Checklist Performance.

BACKGROUND: Many hospitals have implemented surgical safety checklists based on the World Health Organization surgical safety checklist, which was associated with improved outcomes. However, the execution of the checklists is frequently incomplete. We reasoned that aviation-style computerized checklist displayed onto large, centrally located screen and operated by the anesthesia provider would improve the performance of surgical safety checklist. METHODS: We performed a prospective before and after observational study to evaluate the effect of a computerized surgical safety checklist system on checklist performance. We created checklist software and translated our 4-part surgical safety checklist from wall poster into an aviation-style computerized format displayed onto a large, centrally located screen and operated by the anesthesia provider. Direct observers recorded performance of the first part of the surgical safety checklist that was initiated before anesthetic induction, including completion of each checklist item, provider participation and distraction level, resistance to use of the checklist, and the time required for checklist completion before and after checklist system implementation. We compared trends of the proportions of cases with 100% surgical safety checklist completion over time between pre- and postintervention periods and assessed for a jump at the start of intervention using segmented logistic regression model while controlling for potential confounding variables. RESULTS: A total of 671 cases were observed before and 547 cases were observed after implementation of the computerized surgical safety checklist system. The proportion of cases in which all of the items of the surgical safety checklist were completed significantly increased from 2.1% to 86.3% after the computerized checklist system implementation (P < .001). Before computerized checklist system implementation, 488 of 671 (72.7%) cases had <75% of checklist items completed, whereas after a computerized checklist system implementation, only 3 of 547 (0.5%) cases had <75% of checklist items completed. CONCLUSIONS: The implementation of a computerized surgical safety checklist system resulted in an improvement in checklist performance.

Hospitalized patients quantify verbal pain intensity descriptors: methodological issues and values for 26 descriptors.

Patients often tell others about their pain using their own verbal descriptors of pain intensity, but the meaning of this pain language is not universally evident, which could contribute to misinterpretation about pain severity. The study purpose was to discover the intensity values of verbal pain intensity descriptors. The 248 randomly selected inpatients used a visual analogue scale to assign a value to each of 26 pain intensity descriptors. Each participant completed 36 randomly ordered visual analogue scales, 10 of which were replications. Except for descriptors with medians close to 0 or 100 mm, there was large, across-person variability for the descriptors. For example, medians ± SD for some exemplar descriptors were no pain 0.7 ± 2.4; mild 16.2 ± 12.2; discomforting 31.3 ± 22.2; distressing 55.3 ± 24; horrible 87.8 ± 13.6; and excruciating 94.6 ± 9.3. Test-retest reliability indicated small within-person variability on scores assigned to each descriptor. Thirteen descriptors showed some statistically significant but rather small effects of presentation order. Findings contribute estimates for the magnitude of pain represented by each of the 26 descriptors. Clinicians, text data miners, and researchers should consider these values as they interpret the meaning of the descriptors that they hear in daily practice or research settings or that they find in electronic health records, email messages, or social media posts. Despite the wide variability in the magnitude of each descriptor, findings provide insights about the intensity of pain when individuals use verbal pain intensity descriptors in conversations, social media, or clinical encounters.

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.

Association of Fatigue With TPH2 Genetic Polymorphisms in Women With Irritable Bowel Syndrome.

Fatigue is the most common extraintestinal symptom in women with irritable bowel syndrome (IBS). Genetic polymorphisms of monoamines are associated with fatigue in many chronic diseases. In this pilot exploratory study, the primary aim was to determine whether genetic polymorphisms of tryptophan hydroxylase ( TPH1/TPH2), serotonin reuptake transporter ( SERT), or catechol-O-methyltransferase ( COMT) are associated with fatigue in women with IBS. Additionally, analysis explored whether these genetic associations with fatigue would be present when controlling for abdominal pain, psychological distress, feeling stressed, and sleepiness during the day. Secondary analysis of two randomized controlled trial baseline data sets in Caucasian women with IBS ( N = 185) was conducted. Participants kept a daily diary with one dimension (i.e., severity) for each of the 26 symptoms, including fatigue, for 28 days prior to randomization. DNA samples were tested for single-nucleotide polymorphisms (SNPs) of TPH1 (four SNPs) /TPH2 (one SNP), SERT (one SNP), and COMT (one SNP). Analysis of covariance was used to examine associations of percentage of diary days with moderate to very severe symptoms with genetic polymorphisms. Only one SNP, TPH2 rs4570625, was significantly associated with fatigue ( p = .005). T-allele (low functional) carriers of TPH2 (i.e., G/T or T/T genotypes) reported a greater percentage of days with moderate to very severe fatigue than G/G homozygotes ( p = .001). Reduced synthesis of tryptophan in the central nervous system may contribute to reports of fatigue in women with IBS. Understanding genetic risk factors for fatigue may elucidate preemptive strategies to reduce fatigue in individuals with IBS.

Randomized trial of telephone versus in-person delivery of a brief psychosocial intervention in post-stroke depression.

BACKGROUND: A psychosocial behavioral intervention delivered in-person by advanced practice nurses has been shown effective in substantially reducing post-stroke depression (PSD). This follow-up trial compared the effectiveness of a shortened intervention delivered by either telephone or in-person to usual care. To our knowledge, this is the first of current behavioral therapy trials to expand the protocol in a new clinical sample. 100 people with Geriatric Depression Scores ≥ 11 were randomized within 4 months of stroke to usual care (N = 28), telephone intervention (N = 37), or in-person intervention (N = 35). Primary outcome was response [percent reduction in the Hamilton Depression Rating Scale (HDRS)] and remission (HDRS score < 10) at 8 weeks and 12 months post treatment. RESULTS: Intervention groups were combined for the primary analysis (pre-planned). The mean response in HDRS scores was 39% reduction for the combined intervention group (40% in-person; 38% telephone groups) versus 33% for the usual care group at 8 weeks (p = 0.3). Remission occurred in 37% in the combined intervention groups at 8 weeks versus 27% in the control group (p = 0.3) and 44% intervention versus 36% control at 12 months (p = 0.5). While favouring the intervention, these differences were not statistically significant. CONCLUSIONS: A brief psychosocial intervention for PSD delivered by telephone or in-person did not reduce depression significantly more than usual care. However, the comparable effectiveness of telephone and in-person follow-up for treatment of depression found is important given greater accessibility by telephone and mandated post-hospital follow-up for comprehensive stroke centers. Clinical Trial Registration URL: https://register.clinicaltrials.gov , unique identifier: NCT01133106, Registered 5/26/2010.

Cosleeping, sleep disturbances, children's behavioral problems, and parenting self-efficacy among Korean American families.

The purpose of this study was to compare sleep disturbances of children and their mothers, children's behavioral problems, and parenting self-efficacy between Korean American families who coslept and those who did not cosleep. Forty-eight mothers of children between 3 and 8 years of age completed the following surveys: Children's Sleep Habits Questionnaire, Pediatric Symptom Checklist, Pittsburgh Sleep Quality Index, Parenting Self-Efficacy Questionnaire, and Acculturation Rating Scale for Mexican Americans II. Overall, 48% (n = 23) of families coslept, and families with younger children coslept more than families with older children (x2=12.48,p<.05). When the families were divided into non-cosleeping (i.e., rarely) and cosleeping (i.e., sometimes and usually) groups, 100% of the cosleeping children had sleep disturbances compared to 56% of the non-cosleeping children (x2=8.67,p<.01). For mothers, 28% (n = 7) of the non-cosleeping mothers reported sleep disturbances, compared to 52% (n = 12) of the cosleeping mothers (x2=2.93,p=.08). Children's behavioral problems were not different between the two groups (F = 1.78, p = NS). Cosleeping mothers reported lower parenting self-efficacy than non-cosleeping mothers (F = 6.26, p < .05). When providing care to Korean American families with young children, their cosleeping, sleep disturbances, and parenting self-efficacy need to be addressed.

Brain iron concentrations in regions of interest and relation with serum iron levels in Parkinson disease.

Brain iron has been previously found elevated in the substantia nigra pars compacta (SNpc), but not in other brain regions, of Parkinson's disease (PD) patients. However, iron in circulation has been recently observed to be lower than normal in PD patients. The regional selectivity of iron deposition in brain as well as the relationship between SNpc brain iron and serum iron within PD patients has not been completely elucidated. In this pilot study we measured brain iron in six regions of interest (ROIs) as well as serum iron and serum ferritin, in 24 PD patients and 27 age- gender-matched controls. Brain iron was measured on magnetic resonance imaging (MRI) with a T2 prime (T2') method. Difference in brain iron deposition between PD cases and controls for the six ROIs were calculated. SNpc/white matter brain iron ratios and SNpc/serum iron ratios were calculated for each study participant, and differences between PD patients and controls were tested. PD patients overall had higher brain iron than controls in the SNpc. PD patients had significantly higher SNpc/white matter brain iron ratios than controls, and significantly higher brain SNpc iron/serum iron ratios than controls. These results indicate that PD patients' iron metabolism is disrupted toward a higher partitioning of iron to the brain SNpc at the expenses of iron in the circulation.

COMT Val158Met Polymorphism and Symptom Improvement Following a Cognitively Focused Intervention for Irritable Bowel Syndrome.

BACKGROUND: Our nurse-delivered comprehensive self-management (CSM) program, a cognitive behavioral therapy intervention, is effective in reducing gastrointestinal and psychological distress symptoms in patients with irritable bowel syndrome (IBS). Findings from non-IBS studies indicate that the catechol-O-methyltransferase (COMT) Val158Met polymorphism may moderate the efficacy of cognitive behavioral therapy. It is unknown whether this COMT polymorphism is associated with symptom improvements in patients with IBS. OBJECTIVE: We tested whether this COMT Val158Met polymorphism influences the efficacy of our 2-month CSM intervention. METHODS: We analyzed data from two published randomized controlled trials of CSM. The combined European American sample included 149 women and 23 men with IBS (CSM, n = 111; usual care [UC], n = 61). The primary outcomes were daily reports of abdominal pain, depression, anxiety, and feeling stressed measured 3 and 6 months after randomization. Secondary outcomes were additional daily symptoms, retrospective psychological distress, IBS quality of life, and cognitive beliefs about IBS. The interaction between COMT Val158Met polymorphism and treatment group (CSM vs. UC) in a generalized estimating equation model tested the main objective. RESULTS: At 3 months, participants with at least one Val allele benefited more from CSM than did those with the Met/Met genotype (p = .01 for anxiety and feeling stressed, and p < .16 for abdominal pain and depression). The moderating effect of genotype was weaker at 6 months. DISCUSSION: Persons with at least one Val allele may benefit more from CSM than those homozygous for the Met allele. Future studies with larger and more racially diverse samples are needed to confirm these findings. RCT REGISTRATION: Parent studies were registered at ClinicalTrials.gov (NCT00167635 and NCT00907790).