"I wish I knew then what I know now" - pain science education concepts important for female persistent pelvic pain: a reflexive thematic analysis.

ABSTRACT: Pain science education (PSE) provides people with an understanding of "how pain works" grounded in the biopsychosocial model of pain; it has been demonstrated to improve outcomes in musculoskeletal pain conditions. Preliminary evidence suggests PSE may be effective for female individuals with persistent pelvic pain, but how the content of PSE needs to be modified for this group remains to be determined. A reflexive thematic analysis of qualitative data was performed to identify PSE concepts that female individuals with persistent pelvic pain consider important and why. Twenty individual, semistructured interviews were conducted with adult females who had engaged with PSE and had self-identified as having "improved" pelvic pain. Most participants had been diagnosed with endometriosis (n = 16). Four themes were generated capturing PSE concepts considered important by female individuals with "improved" pelvic pain: (1) "A sensitised nervous system leads to overprotective pain" validated their pelvic pain as being real; (2) "Pain does not have to mean the body is damaged (although sometimes it does)" provided reassurance that pelvic pain does not mean their condition is worsening; (3) "How I think, feel, and 'see' my pain can make it worse" enabled participants to find optimal ways to manage their pain; and (4) "I can change my pain… slowly" provided hope that pelvic pain can improve and empowered them to pursue pain improvement as a viable goal. This study generated 4 PSE learning concepts that were important to female individuals with improved pelvic pain and may be incorporated into PSE curricula for female individuals with pelvic pain.

Optimized Infliximab Induction Predicts Better Long-Term Clinical and Biomarker Outcomes Compared to Standard Induction Dosing.

OBJECTIVES: To evaluate the efficacy of standard and optimized infliximab induction dosing in attaining corticosteroid (CS) free clinical remission at week 52 and the effect that post-induction trough levels have on long-term outcome. METHODS: Inflammatory bowel disease (IBD) patients ≤18 years commenced on infliximab between August 1, 2016, and August 1, 2018, from Vancouver, Canada, and Glasgow, Scotland, were included. The Glasgow cohort followed standard induction while the Vancouver cohort undertook induction optimization based on clinical, biomarker, and proactive infliximab trough levels. Baseline characteristics and laboratory values were documented. RESULTS: In total, 140 children were included [median age 14.1 years (interquartile range (IQR) 12.0-16.0)]; 54% male. CS-free clinical remission at week 52 was higher in the optimized group compared to the standard cohort [65/78 (83%) vs. 32/62 (52%), P < 0.001]. Combined CS-free clinical and biomarker remission (CRP < 5 mg/L) was also higher in the optimized compared to the standard cohort [65/78 (83%) vs 25/62 (40%), P < 0.001]. The median post-induction trough level was higher in children who were in CS-free clinical remission at week 52 [3.6 mg/L (1.5-7.1)] vs. those who were not [2.0 mg/L (0.8-4.1), P = 0.04]. The odds of attaining a therapeutic post-induction trough level were almost 4-fold higher in the optimized group than the standard cohort (OR 3.97, 95% CI: 1.89-8.68, P < 0.001). CONCLUSIONS: Standard infliximab induction resulted in less favorable long-term outcomes for pediatric IBD patients. Optimizing induction using clinical, biomarker, and proactive trough levels resulted in higher post-induction trough levels and a greater odds of attaining long-term clinical remission.

Dietary triggers of gut inflammation following exclusive enteral nutrition in children with Crohn's disease: a pilot study.

BACKGROUND: The anti-inflammatory effect of exclusive enteral nutrition on the gut of children with Crohn's disease is rapidly lost after food reintroduction. This study assessed disease dietary triggers following successful treatment with exclusive enteral nutrition. METHODS: Nutrient intake, dietary patterns and dietary biomarkers in faeces (gluten immunogenic peptides, undigestible starch, short chain fatty acids) were assessed in 14 children with Crohn's disease during early food reintroduction, following exclusive enteral nutrition. Groups above (Group A) and below (Group B) the median levels of faecal calprotectin after food reintroduction were assigned for comparative analysis. RESULTS: Intakes of fibre, gluten-containing cereals and red and processed meat were significantly higher in Group A than Group B; (median [Q1, Q3], g/day; Fibre: 12.1 [11.2, 19.9] vs. 9.9 [7.6, 12.1], p = 0.03; Red and processed meat: 151 [66.7, 190] vs. 63.3 [21.7, 67], p = 0.02; gluten-containing cereals: 289 [207, 402] vs. 203 [61, 232], p = 0.035). A diet consisting of cereals and meat products was predictive (92% accuracy) of higher faecal calprotectin levels after food reintroduction. In faeces, butyrate levels, expressed as absolute concentration and relative abundance, were higher in Group A than Group B by 28.4 µmol/g (p = 0.015) and 6.4% (p = 0.008), respectively. Levels of gluten immunogenic peptide and starch in faeces did not differ between the two groups. CONCLUSIONS: This pilot study identified potential dietary triggers of gut inflammation in children with Crohn's disease after food reintroduction following treatment with exclusive enteral nutrition. TRIAL REGISTRATION: Clinical trials.gov registration number: NCT02341248; Clinical trials.gov URL: https://clinicaltrials.gov/ct2/show/NCT02341248 (retrospectively registered).

Epstein-Barr Virus Status and Subsequent Thiopurine Exposure Within a Paediatric Inflammatory Bowel Disease Population.

ABSTRACT: The use of thiopurine therapy in Epstein-Barr virus (EBV)-naïve inflammatory bowel disease (IBD) patients remains controversial due to a risk of EBV-associated complications. We evaluated EBV status and outcomes within our paediatric IBD population over an 8-year period; finding that 217 of 409 (53%) screened patients were seropositive for EBV at IBD diagnosis; that thiopurines were used in 189 of 217 (87%) seropositive and 159 of 192 (83%) seronegative patients (P = 0.22); and that 7 of 192 (4%) previously seronegative patients subsequently tested positive for EBV with 6 of 7 (86%) patients having concurrently recorded thiopurine use. All six patients continued thiopurine with/without a period of cessation; no EBV-associated lymphoproliferative disorders/serious complications were recorded within our cohort. A significant proportion of our patients would not receive thiopurine therapy should their use be avoided in EBV-negative patients (47%) or seronegative males (30%). The small but significant risks of thiopurine treatment must be balanced against the potential benefits of successful IBD management; further research into this is required.

Point-of-care faecal calprotectin testing in patients with paediatric inflammatory bowel disease during the COVID-19 pandemic.

OBJECTIVES: Following the disruption of normal paediatric inflammatory bowel disease (IBD) services during the peak of the COVID-19 pandemic, we prospectively audited the first-time use of home faecal calprotectin testing. We aimed to provide an alternative to laboratory tests and to assess the value of home testing as part of our regular services going forward. METHODS: Home test kits as well as accompanying user instructions were made available to our patients with paediatric IBD that required faecal calprotectin test between 17 April and 12 August 2020. Once the user completed the test, results were automatically uploaded to the result portal and clinical staff were alerted. A user feedback questionnaire was sent to users that had completed the home test. RESULTS: Of the 54 patients, 41 (76%) aged between 4.7 and 18.1 years used the home test. A total of 45 home tests were done, one of which produced an invalid result. The decision to modify management was made in 12 (29%) of the patients, while 14 (34%) had no changes made and 15 (37%) required further assessment. Twenty (48.8%) responded to the questionnaire and 85% stated that they preferred the home test to the laboratory testing method. CONCLUSIONS: Home calprotectin tests were useful in guiding clinical management during a time when laboratory testing was less available. They may offer benefits as part of routine paediatric IBD monitoring to help target appointments and reduce unnecessary hospital attendances in the future.

Ferric Carboxymaltose Across All Ages in Paediatric Gastroenterology Shows Efficacy Without Increased Safety Concerns.

OBJECTIVES: The aim of the study was to assess the efficacy, safety and side-effect profile of ferric carboxymaltose (FCM) for correcting IDA in children and adolescents in paediatric gastroenterology, hepatology, and nutrition. METHOD: This was a retrospective study of all gastroenterology patients <18 years who had FCM (October 2015 to October 2017). Haematological and biochemical parameters were recorded pre-infusion, at 4 weeks, 3 months, 6 months, and 1 year post-infusion. Recognised side-effects were documented. RESULTS: Sixty-six children received FCM during this period. Data was analysed on 61 children, 5 excluded because of inadequate data. The median age at administration was 14 years (IQR 7). Thirty-two (52%) were boys. Twenty-six (42%) were <14 years old. Seven (11.5%) were <5 years old. Seventeen (28%) were switched from oral iron supplements to FCM. The median dose of FCM delivered was 19 mg/kg. The median haemoglobin increased from 108 to 126 g/L at 1 month post-infusion (P value <0.00001). The mean cell volume also improved from 80 to 84 fL at 1 month post-infusion (P value = 0.0007). Forty-eight (94%) children corrected their anaemia after receiving FCM. Two patients (3%) reported side-effects with skin bruising and staining. CONCLUSIONS: FCM appears to be effective in correcting IDA in children across a wide range of gastroenterology indications and all ages. It is effective and generally well tolerated including in very young patients. Potential side-effects can be avoided by careful monitoring during infusions.

Using Natural Language Processing and Sentiment Analysis to Augment Traditional User-Centered Design: Development and Usability Study.

BACKGROUND: Sarcopenia, defined as the age-associated loss of muscle mass and strength, can be effectively mitigated through resistance-based physical activity. With compliance at approximately 40% for home-based exercise prescriptions, implementing a remote sensing system would help patients and clinicians to better understand treatment progress and increase compliance. The inclusion of end users in the development of mobile apps for remote-sensing systems can ensure that they are both user friendly and facilitate compliance. With advancements in natural language processing (NLP), there is potential for these methods to be used with data collected through the user-centered design process. OBJECTIVE: This study aims to develop a mobile app for a novel device through a user-centered design process with both older adults and clinicians while exploring whether data collected through this process can be used in NLP and sentiment analysis. METHODS: Through a user-centered design process, we conducted semistructured interviews during the development of a geriatric-friendly Bluetooth-connected resistance exercise band app. We interviewed patients and clinicians at weeks 0, 5, and 10 of the app development. Each semistructured interview consisted of heuristic evaluations, cognitive walkthroughs, and observations. We used the Bing sentiment library for a sentiment analysis of interview transcripts and then applied NLP-based latent Dirichlet allocation (LDA) topic modeling to identify differences and similarities in patient and clinician participant interviews. Sentiment was defined as the sum of positive and negative words (each word with a +1 or -1 value). To assess utility, we used quantitative assessment questionnaires-System Usability Scale (SUS) and Usefulness, Satisfaction, and Ease of use (USE). Finally, we used multivariate linear models-adjusting for age, sex, subject group (clinician vs patient), and development-to explore the association between sentiment analysis and SUS and USE outcomes. RESULTS: The mean age of the 22 participants was 68 (SD 14) years, and 17 (77%) were female. The overall mean SUS and USE scores were 66.4 (SD 13.6) and 41.3 (SD 15.2), respectively. Both patients and clinicians provided valuable insights into the needs of older adults when designing and building an app. The mean positive-negative sentiment per sentence was 0.19 (SD 0.21) and 0.47 (SD 0.21) for patient and clinician interviews, respectively. We found a positive association with positive sentiment in an interview and SUS score (ß=1.38; 95% CI 0.37 to 2.39; P=.01). There was no significant association between sentiment and the USE score. The LDA analysis found no overlap between patients and clinicians in the 8 identified topics. CONCLUSIONS: Involving patients and clinicians allowed us to design and build an app that is user friendly for older adults while supporting compliance. This is the first analysis using NLP and usability questionnaires in the quantification of user-centered design of technology for older adults.

Severe hypophosphataemia following ferric carboxymaltose infusion in paediatric patients with inflammatory bowel disease.

This case series describes the cases of three adolescent patients with established inflammatory bowel disease (IBD) who experienced significant hypophosphataemia following intravenous infusion of ferric carboxymaltose as treatment for iron deficiency anaemia. Hypophosphataemia may cause a diverse range of symptoms and may be difficult to diagnose clinically due to their non-specific nature. Checking a baseline phosphate (PO4) prior to intravenous iron infusion may identify patients at higher risk for significant hypophosphataemia and perhaps allow the selection of an alternative iron preparation. The routine monitoring of PO4 levels postinfusion presents a greater challenge; with cases of asymptomatic hypophosphataemia likely to be uncovered, as in case 3. Clinicians, patients and families should be aware of the symptoms of hypophosphataemia, and symptomatic patients should have bloods checked to allow prompt identification and correction of abnormalities where required. Review of guidelines surrounding intravenous iron infusion and management of hypophosphataemia in paediatric patients is now required.

Dissecting the Contemporary Clerkship: Theory-based Educational Trial of Videos Versus Lectures in Medical Student Education.

BACKGROUND: Despite increasing use of the flipped classroom (FC) technique in undergraduate medical education, the benefit in learning outcomes over lectures is inconsistent. Best practices in preclass video design principles are rarely used, and it is unclear if videos can replace lectures in contemporary medical education. METHODS: We conducted a prospective quasi-experimental controlled educational study comparing theory-based videos to traditional lectures in a medical student curriculum. Medical students enrolled in an emergency medicine clerkship were randomly assigned to either a lecture group (LG) or a video group (VG). The slide content was identical, and the videos aligned with cognitive load theory-based multimedia design principles. Students underwent baseline (pretest), week 1 (posttest), and end-of-rotation (retention) written knowledge tests and an observed structured clinical examination (OSCE) assessment. We compared scores between both groups and surveyed student attitudes and satisfaction with respect to the two learning methods. RESULTS: There were 104 students who participated in OSCE assessments (49 LG, 55 VG) and 101 students who participated in knowledge tests (48 LG, 53 VG). The difference in OSCE scores was statistically significant 1.29 (95% confidence interval = 0.23 to 2.35, t(102) = 2.43, p = 0.017), but the actual score difference was small from an educational standpoint (12.61 for LG, 11.32 for VG). All three knowledge test scores for both groups were not significantly different. CONCLUSIONS: Videos based on cognitive load theory produced similar results and could replace traditional lectures for medical students. Educators contemplating a FC approach should devote their valuable classroom time to active learning methods.

A Decade of Varicella Screening Within a Paediatric Inflammatory Bowel Disease Population.

INTRODUCTION: Increased risk of opportunistic infection-e.g., varicella zoster infection-secondary to therapies is a cause of morbidity in inflammatory bowel disease [IBD] patients. The UK vaccination schedule does not include varicella immunisation. We aimed to evaluate the varicella screening and immunisation programme in a paediatric IBD population. METHODS: Data regarding IBD diagnosis, varicella status, and consequent immunisations/treatment interventions were collected retrospectively from the records of patients diagnosed with IBD over a 10-year period [2009-2018]. RESULTS: In all, 520 IBD patients were diagnosed; 505/520 [97%] had varicella testing; 46/505 [9%] were naïve. Of 501 patients, 391[78%] were tested before or within 7 days of diagnosis; this increased in the second 5-year period compared with the first (229/268 [85%] versus 162/233 [70%]; p <0.00001). Median diagnosis age of naïve patients was lower [8.3 years versus 12.8 years; p <0.00001]. Where vaccination was feasible, 21/31 [68%] had two and 7/31 [23%] one immunisation. Prednisolone induction led to lower rates of vaccination (5/13 [39%] versus 23/33 [70%] for other induction therapies; p =0.02). Of 28 vaccinated patients, 5 [18%] had suspected breakthrough varicella; and 6/18 [33%] unimmunised patients required post-exposure prophylaxis or treatment for varicella. Immunisation was associated with a decrease in patients requiring post-exposure prophylaxis (0/28 [0%] versus 5/18 [28%]; p =0.0006) and varicella-related hospital admission (1/28 [4%] versus 4/18 [22%]; p =0.01). CONCLUSIONS: High rates of varicella screening and immunisation within a PIBD population are possible, resulting in a reduction in hospital admissions for varicella treatment. Varicella immunisation may be of increasing importance within the PIBD population with the emergence of novel therapeutic strategies.

Prehabilitation: The Impact of Preoperative Exclusive Enteral Nutrition on Paediatric Patients With Crohn Disease.

Exclusive enteral nutrition (EEN) is effective in inducing remission in paediatric Crohn Disease (CD) and has been shown to reduce inflammation and improve outcomes in adult CD patients when used before resectional surgery. This retrospective study demonstrates that preoperative EEN is achievable in paediatric CD patients undergoing right hemicolectomy and is associated with positive peri-operative outcomes. Seventeen patients (8 who received preoperative EEN and 9 who did not) were included in the study. Six of 8 (75.0%) managed EEN orally; 1 via nasogastric tube and another via a previously sited gastrostomy. Use of preoperative EEN was associated with a decreased rate of moderate/severe disease on resection pathology (5/8 [62.5%] vs 9/9 [100%]; P = 0.04). Larger studies are required to determine the wider potential benefits of preoperative EEN on postoperative outcomes within paediatric practice.

Using a Steroid-sparing Tool in Paediatric Inflammatory Bowel Disease to Evaluate Steroid Use and Dependency.

OBJECTIVES: The aim of the study was to evaluate the use of steroids within the paediatric inflammatory bowel disease (PIBD) population at a tertiary paediatric centre over a year; to identify cases of steroid dependency; and assess factors associated with steroid excess. METHODS: The prevalent PIBD population (May 1, 2017-April 30, 2018) were reviewed. Data were collected retrospectively from patient records and entered into an online steroid assessment tool (modified for paediatrics). RESULTS: A total of 229 patients (181 Crohn disease, 31 ulcerative colitis [UC], and 17 inflammatory bowel disease-unclassified) were included. Of the 229 patients 38 (16.6%) received oral steroids; 12 of 38 (31.6%) receiving >3-month course. Eleven of 38 (28.9%) received >1 steroid course (maximum 2). Of the 229 patients 37 (16.2%) had exclusive enteral nutrition, with 26 of 37 (11.4% total cohort) avoiding steroid use during the study period.Quiescent disease activity had a negative correlation with steroid use (11/127 [8.7%] vs 27/102 [26.5%] P < 0.01), and steroid dependency (3/127 [2.4%] vs 12/102 [11.8%] P < 0.01). Patients with UC were more likely to be steroid dependent (5/31 [16.1%] UC vs 10/198 [5.1%]; P = 0.02); as were network-managed patients (8/11 [72.7%] vs 7/27 [25.9%]; P = 0.01). Fourteen of 15 (93.3%) of steroid-dependent patients had active steroid sparing strategies in place (eg, commencement, switching, or optimization of therapies). CONCLUSIONS: We have described rates of steroid use and dependency within our PIBD population. Exclusive enteral nutrition served as a steroid sparing tool in 11.4% of the total cohort. Replication of this study in other paediatric centres would allow comparative analysis.

The reduction of faecal calprotectin during exclusive enteral nutrition is lost rapidly after food re-introduction.

BACKGROUND: Faecal calprotectin decreases during exclusive enteral nutrition in children with active Crohn's disease. It is unknown how faecal calprotectin changes during food re-introduction and the influence of maintenance enteral nutrition. AIMS: To study changes to faecal calprotectin during exclusive enteral nutrition and at food reintroduction, and explore associations with maintenance enteral nutrition. METHODS: Children with Crohn's disease were followed during exclusive enteral nutrition and during food-reintroduction. Faecal calprotectin was measured before, at 33 and 54 days of exclusive enteral nutrition, and at 17, 52 and 72 days after food-reintroduction. Maintenance enteral nutrition use was recorded with estimated weight food diaries. Data are presented with medians and Q1:Q3. RESULTS: Sixty-six patients started exclusive enteral nutrition and 41 (62%) achieved clinical remission (weighted paediatric Crohn's disease activity index <12.5). Baseline faecal calprotectin (mg/kg) decreased after 4 and 8 weeks of exclusive enteral nutrition (Start: 1433 [Q1: 946, Q3: 1820] vs 33 days: 844 [314, 1438] vs 54 days: 453 [165, 1100]; P < .001). Within 17 days of food reintroduction, faecal calprotectin increased to 953 [Q1: 519, Q3: 1611] and by 52 days to 1094 [660, 1625] (both P < .02). Fifteen of 41 (37%) children in remission used maintenance enteral nutrition (333 kcal or 18% of energy intake). At 17 days of food reintroduction, faecal calprotectin was lower in maintenance enteral nutrition users than non-users (651 [Q1: 271, Q3: 1781] vs 1238 [749, 2102], P = .049) and correlated inversely with maintenance enteral nutrition volume (rho: -0.573, P = .041), kcals (rho: -0.584, P = .036) and % energy intake (rho: -0.649, P = .016). Maintenance enteral nutrition use was not associated with longer periods of remission (P = .7). Faecal calprotectin at the end of exclusive enteral nutrition did not predict length of remission. CONCLUSIONS: The effect of exclusive enteral nutrition on faecal calprotectin is diminished early during food reintroduction. Maintenance enteral nutrition at ~18% of energy intake is associated with a lower faecal calprotectin at the early phase of food reintroduction but is ineffective in maintaining longer term remission.

Responses of Plasma Catecholamine, Serotonin, and the Platelet Serotonin Transporter to Cigarette Smoking.

Cigarette smoking is one of the major causes of coronary heart disease with a thirty percent mortality rate in the United States. Cigarette smoking acting on the central nervous system (CNS) to stimulate the sympathetic nervous system (SNS) through, which facilitates the secretion of serotonin (5-HT) and catecholamines to supraphysiological levels in blood. The enhanced levels of 5-HT and catecholamines in smokers' blood are associated with increases in G protein-coupled receptor signaling and serotonylation of small GTPases, which in turn lead to remodeling of cytoskeletal elements to enhance granule secretion and promote unique expression of sialylated N-glycan structures on smokers' platelets. These mechanisms enhance aggregation and adhesion of smokers' platelets relative to those of non-smokers. This review focuses on the known mechanisms by which 5-HT and SERT, in coordinated signaling with catecholamines, impacts cigarette smokers' platelet biology.

Switching From Originator to Biosimilar Infliximab in Paediatric Inflammatory Bowel Disease Is Feasible and Uneventful.

The safety, clinical efficacy, and cost-effectiveness of biosimilar infliximab in adult inflammatory bowel disease (IBD) have now been extensively shown. Limited data have been collected in the paediatric setting. We report nationwide, prospective, clinical safety and effectiveness data for patients from all 3 Scottish paediatric inflammatory bowel disease networks switching from originator to biosimilar infliximab. Prospective clinical data were collected for 33 patients. Information was collected from electronic patient records, laboratory reports, and patient case notes. There were no clinically significant changes to disease activity, biomarkers, antidrug antibodies, or trough drug levels (P > 0.1) within a 12-month follow-up period; in addition, there were no significant adverse events reported. No infusion reactions were seen in the 264 infusions delivered. Switching from originator infliximab to the biosimilar (CT-P13) appears to be associated with neither an increase in infusion reactions nor significant loss of effectiveness in the short term.

Biosimilar infliximab use in paediatric IBD.

BACKGROUND: Biosimilar infliximab became available in the UK in 2015. Paediatric experience to date on its use is limited. We prospectively evaluated the safety and efficacy of biosimilar infliximab (Remsima) in two paediatric gastroenterology networks in patients with inflammatory bowel disease. METHODS: Prospective clinical data were collected from laboratory reports, electronic patient records and case notes of 40 patients starting Remsima for the first time. Disease activity scores together with blood and stool biomarkers were used to assess response. RESULTS: Our data set highlights that Remsima was associated with a significant clinical and biochemical improvement (p<0.01 or less for all parameters assessed) in Crohn's disease post induction. There were no significant safety issues noted. The total cost saving was £47 800, representing a 38% reduction from originator. CONCLUSION: We found that biosimilar infliximab is as effective as originator infliximab and its use is associated with significant cost savings.

Ambulation of patients who are mechanically ventilated: nurses' views.

Aims Equipment and skills in intensive care have advanced dramatically, and early rehabilitation and ambulation for patients in intensive care units (ICUs) are part of their journey to recovery. The aim of this study is to understand better nurses' perspectives on ambulating mechanically ventilated patients, and to determine why this is not a routine part of ICU patient care. Method Interpretative phenomenological analysis was used to extract data from semi-structured interviews. The questions were piloted twice before being used in the main study. Results Two overarching themes, staff anxiety and organisational culture, were identified, within which there are several subthemes. The study also found that education and training programmes could increase staff confidence and consequently result in routine ambulation of mechanically ventilated patients. Conclusion The study identified that nursing staff are aware of the benefits of ambulation for patients in ICUs, but the personal satisfaction gained from undertaking this activity does not outweigh the anxiety it causes. This is compounded by the organisational culture of ICUs; for example, the hierarchical pyramid of leadership, which dictates that consultants decide when patients are ready to ambulate.

Cigarette Smoking-Associated Alterations in Serotonin/Adrenalin Signaling Pathways of Platelets.

BACKGROUND: Cigarette smoking plays a major role in cardiovascular diseases. The acute effects of cigarette smoking produce central nervous system-mediated activation of the sympathetic nervous system. The overactive sympathetic nervous system stimulates the secretion of serotonin (5-HT) and catecholamine into blood at supraphysiological levels. The correlation between these pathological conditions induced by smoking and the increased risk of thrombosis has not been thoroughly investigated. The goal of our study was to explore cigarette smoking-associated changes in platelet biology mediated by elevated 5-HT and catecholamine levels in blood plasma. METHODS AND RESULTS: Using blood samples collected from healthy nonsmokers and smokers (15 minutes after smoking), we determined that cigarette smoking increased the plasma 5-HT/catecholamine concentration by several fold and the percent aggregation of platelets 2-fold. Liquid chromatography-tandem mass spectrometry analysis of proteins eluted from platelet plasma membranes of smokers and nonsmokers demonstrated that GTPase-activating proteins and proteins participating in the actin cytoskeletal network were differentially and significantly elevated in smokers' platelet membranes compared with those of nonsmokers. Interestingly, Matrix-assisted laser desorption/ionization-mass spectrometry analyses of the glycans eluted from platelet plasma membranes of the smokers demonstrated that the level and structures of glycans are different from the nonsmokers' platelet surface glycans. Pharmacological blockade of 5-HT or catecholamine receptors counteracted the 5-HT/catecholamine-mediated aggregation and altered the level and composition of glycan on platelet surfaces. CONCLUSIONS: Based on our findings, we propose that smoking-associated 5-HT/catecholamine signaling accelerates the trafficking dynamics of platelets, and this remodels the surface proteins and glycans and predisposes platelets to hyperactive levels. Smokers' platelets also had correspondingly higher resting concentrations of intracellular calcium and transglutaminase activity. These findings suggest a link among smoking, platelet 5-HT, catecholamine signaling, and their downstream effectors-including phospholipase C and inositol-1,4,5-triphosphate pathways-resulting in an increased tonic level of platelet activation in smokers.

Dietary treatment of Crohn's disease: perceptions of families with children treated by exclusive enteral nutrition, a questionnaire survey.

BACKGROUND: Diet is strongly associated with the aetiology of Crohn's Disease (CD) and exclusive enteral nutrition (EEN) is the primary induction treatment in paediatric CD. This study explored opinions around the use of EEN and alternative novel, solid food-based diets (SFDs) expressed by paediatric patients with CD, previously treated with EEN and their parents. METHODS: This anonymous questionnaire surveyed families of CD patients treated with EEN over 1 year. Two questionnaire forms were completed; one asking the patients' opinions and another referring to their main carer. This questionnaire explored participants' demographic characteristics; acceptability of a repeat EEN course to treat a future flare (EEN repeat); their opinion on how difficult EEN would be compared to an example SFD; and their intention to participate in a future clinical trial assessing the therapeutic efficacy of an SFD in CD. RESULTS: Forty-one families of CD patients were approached with 29 sending replies (71%). Most of our participants were positive on completing another EEN course, however the majority would choose an SFD alternative (Patients:66, Parents:72%). Both patients and their parents rated EEN to be more difficult to adhere to compared to an example SFD (p < 0.05), and their ratings were strongly correlated (EEN:r = 0.83, SFD:r = 0.75, p < 0.001). The majority of our respondents would agree to participate in a clinical trial assessing an SFD's effectiveness (Patients:79, Parents:72%) for the management of active CD. CONCLUSIONS: While patients with CD and their families would accept an EEN repeat, the majority would prefer an SFD alternative. CD families surveyed are supportive of the development of solid food-based dietary treatments.