Twitter debate: Controversies in functional gastrointestinal disorders

The new ‘Controversies In…’ series for the Frontline Gastroenterology Twitter debates addressed the difficult area of functional gastrointestinal disorders, facilitated by the former editor-in-chief Anton Emmanuel. Key topics discussed included distinguishing functional dyspepsia from genuine gastroparesis, when we should investigate for bile acid malabsorption, the current treatments for constipation-predominant irritable bowel syndrome and, importantly, how to manage consultations with complex patients presenting with functional bowel disease. The debate generated over a million impressions on twitter and this article aims to summarise the key educational points from the event

Evaluation and treatment of neurogenic bowel dysfunction – a review

Neurogenic bowel dysfunction is a severely troubling entity for patients with neurological disease or injury. The complex symptom cluster presents a challenge, not only for the patients but also for the treating clinician. Without intervention, patients are bound to have a reduced quality of life, and experience social impacts and secondary complications that come along with it. A careful initial assessment provides an idea of symptom severity and is crucial for successful rehabilitation. The mainstay of treatment remains a conservative approach of managing faecal incontinence or optimising the mechanics of defecation to improve patient’s quality of life. This article attempts to provide a comprehensive review of existing literature on pathophysiology, assessment and management of neurogenic bowel dysfunction

The patient burden of opioid-induced constipation: New insights from a large, multinational survey in five European countries

BACKGROUND: Despite its high prevalence, opioid-induced constipation (OIC) remains under-recognised and undertreated, and its true impact on wellbeing and quality of life (QoL) may be underestimated. METHODS: A quantitative, questionnaire-based international survey was conducted. RESULTS: Weak-opioid users appeared as bothered by constipation as strong-opioid users (38% vs 40%, respectively; p = 0.40), despite it causing less-severe physical symptoms and impact on QoL. Strong-opioid users meeting Rome IV OIC criteria appeared to experience greater symptomatic and biopsychosocial burden from constipation than those not satisfying these criteria. Almost one-fifth of respondents were dissatisfied with their current constipation treatment and around one-third found balancing the need for adequate pain relief with constipation side effects challenging. Consequently, more than half failed to adhere to their prescribed treatment regimens, or resorted to suboptimal strategies, e.g. 40% reduced their opioid intake, to relieve constipation. Almost 60% of healthcare professionals did not adequately counsel patients about constipation as a common side effect of opioid use. CONCLUSIONS: Findings suggest that both weak- and strong-opioid users suffer comparable bother and decreased QoL, Rome IV criteria can identify patients with more-severe OIC, but may underdiagnose patients showing fewer symptoms, and increased education is needed to manage patients’ expectations and enable improved OIC self-management

Joint Hypermobility Syndrome Affects Response to a Low Fermentable Oligosaccharide, Disaccharide, Monosaccharide and Polyol Diet in Irritable Bowel Syndrome Patients: A Retrospective Study

Background: The low fermentable oligosaccharide, disaccharide, monosaccharide and polyol (FODMAP) diet causes significant clinical improvement in patients with irritable bowel syndrome (IBS). Joint hypermobility syndrome (JHS), defined as musculoskeletal symptoms in a hypermobile individual in the absence of systemic rheumatological disease, may be associated with functional gastrointestinal symptoms, including IBS. The aim of this study is to examine whether JHS can affect the response to the low FODMAP diet in patients with IBS. Methods: In this retrospective study, we included patients with IBS according to Rome III criteria who had followed a low FODMAP diet. Symptoms scores were measured before and after the low FODMAP diet. Results: A total of 165 patients (130 females, age 44 ± 14 years) were included. Diarrhea predominant IBS (IBS-D) was present in 40.6% of our patients while JHS was present in 21.2%. The score for abdominal pain was higher for JHS compared to non-JHS prior to intervention (P = 0.011). Symptoms improved in both groups of patients after a low FODMAP diet (P < 0.0001). The largest effects were shown with significant decreases of the average score and bloating. When broken down by JHS and IBS type, a low FODMAP diet significantly improved pain, bloating, diarrhea, constipation, and the average score with the largest effect in JHS/constipation predominant IBS (IBS-C), JHS/mixed IBS and unclassified IBS (IBS-M), JHS/IBS-D, non-JHS/IBS-C and JHS/IBS-M, respectively. Conclusions: Our study suggests that a low FODMAP diet has a greater effect on IBS symptoms in JHS than non-JHS patients

Efficacy and Safety of Prucalopride in Patients with Chronic Noncancer Pain Suffering from Opioid-Induced Constipation

Opioid-induced constipation (OIC) has negative effects on quality of life (QOL). Prucalopride is a new, selective 5-HT4 agonist and enterokinetic with strong clinical data in chronic constipation. This study investigated the efficacy, safety, and tolerability of prucalopride in patients with noncancer pain and OIC. A phase II, double-blind, placebo-controlled study of 196 patients randomized to placebo (n = 66), prucalopride 2 mg (n = 66) or 4 mg (n = 64), for 4 weeks, was carried out. The primary endpoint was the proportion of patients with increase from baseline of a parts per thousand yen1 spontaneous complete bowel movement (SCBM)/week. Secondary endpoints [proportion of patients with a parts per thousand yen3 SCBM/week, weekly frequency of (SC)BM, severity of constipation, and efficacy of treatment], adverse events (AEs), and safety parameters were also monitored. More patients had an increase from baseline of a parts per thousand yen1 SCBM per week (weeks 1-4) in the prucalopride groups [35.9% (2 mg) and 40.3% (4 mg)] versus placebo (23.4%), reaching statistical significance in week 1. Over weeks 1-4, more patients in the prucalopride groups achieved an average of a parts per thousand yen3 SBM per week versus placebo (60.7% and 69.0% versus 43.3%), reaching significance at week 1. Prucalopride 4 mg significantly improved patient-rated severity of constipation and effectiveness of treatment versus placebo. Patient Assessment of Constipation-Symptom (PAC-SYM) total scores and Patient Assessment of Constipation-Quality of Life (PAC-QOL) total and satisfaction subscale scores were improved. The most common AEs were abdominal pain and nausea. There were no clinically relevant differences between groups in vital signs, laboratory measures or electrocardiogram parameters. In this population with OIC, prucalopride improved bowel function and was safe and well tolerated

Complex Precipitation Pathways in Multi-Component Alloys

One usual way to strengthen a metal is to add alloying elements and to control the size and the density of the precipitates obtained. However, precipitation in multicomponent alloys can take complex pathways depending on the relative diffusivity of solute atoms and on the relative driving forces involved. In Al-Zr-Sc alloys, atomic simulations based on first-principle calculations combined with various complementary experimental approaches working at different scales reveal a strongly inhomogeneous structure of the precipitates: owing to the much faster diffusivity of Sc compared with Zr in the solid solution, and to the absence of Zr and Sc diffusion inside the precipitates, the precipitate core is mostly Sc-rich, whereas the external shell is Zr-rich. This explains previous observations of an enhanced nucleation rate in Al-Zr-Sc alloys compared with binary Al-Sc alloys, along with much higher resistance to Ostwald ripening, two features of the utmost importance in the field of light high-strength materials

The use of Open Reading frame ESTs (ORESTES) for analysis of the honey bee transcriptome

BACKGROUND: The ongoing efforts to sequence the honey bee genome require additional initiatives to define its transcriptome. Towards this end, we employed the Open Reading frame ESTs (ORESTES) strategy to generate profiles for the life cycle of Apis mellifera workers. RESULTS: Of the 5,021 ORESTES, 35.2% matched with previously deposited Apis ESTs. The analysis of the remaining sequences defined a set of putative orthologs whose majority had their best-match hits with Anopheles and Drosophila genes. CAP3 assembly of the Apis ORESTES with the already existing 15,500 Apis ESTs generated 3,408 contigs. BLASTX comparison of these contigs with protein sets of organisms representing distinct phylogenetic clades revealed a total of 1,629 contigs that Apis mellifera shares with different taxa. Most (41%) represent genes that are in common to all taxa, another 21% are shared between metazoans (Bilateria), and 16% are shared only within the Insecta clade. A set of 23 putative genes presented a best match with human genes, many of which encode factors related to cell signaling/signal transduction. 1,779 contigs (52%) did not match any known sequence. Applying a correction factor deduced from a parallel analysis performed with Drosophila melanogaster ORESTES, we estimate that approximately half of these no-match ESTs contigs (22%) should represent Apis-specific genes. CONCLUSIONS: The versatile and cost-efficient ORESTES approach produced minilibraries for honey bee life cycle stages. Such information on central gene regions contributes to genome annotation and also lends itself to cross-transcriptome comparisons to reveal evolutionary trends in insect genomes

Vitamin D Levels in Asymptomatic Adults-A Population Survey in Karachi, Pakistan

Background: It is well established that low levels of 25(OH) Vitamin D (/dL) are a common finding world over, affecting over a billion of the global population. Our primary objective was to determine the prevalence of vitamin D deficiency and insufficiency in the asymptomatic adult population of Karachi, Pakistan and the demographic, nutritional and co-morbidity characteristics associated with serum vitamin D levels. Methods: A cross-sectional population survey was conducted at two spaced out densely populated areas of the city. Serum levels of 25OH vitamin D were measured and GFR as renal function was assessed by using 4 variable MDRD formula. Results: Our sample of 300 had a median age of 48(interquartile range 38-55) years. The median level of serum vitamin D was 18.8 (IQ range 12.65-24.62) ng/dL. A total of 253 (84.3%) respondents had low levels (/dL) of 25OH vitamin D. Serum PTH and vitamin D were negatively correlated (r = -0.176, p = 0.001). The median PTH in the vitamin D sufficiency group was 38.4 (IQ range28.0-48.8)pg/mL compared with 44.4 (IQ range 34.3-56.8) pg/mL in the deficiency group (p = 0.011).The median serum calcium level in the sample was 9.46(IQ range 9.18-9.68) ng/dL. Low serum levels of vitamin D were not associated with hypertension (p = 0.771) or with an elevated spot blood pressure (p = 0.164).In our sample 75(26%) respondents had an eGFR corresponding to stage 2 and stage 3 CKD. There was no significant correlation between levels of vitamin D and eGFR (r = -0.127, p-value = 0.277). Respondents using daily vitamin D supplements had higher 25 OH vitamin D levels (p-value = 0.021). Conclusion: We observed a high proportion of the asymptomatic adult population having low levels of vitamin D and subclinical deterioration of eGFR. The specific cause(s) for this observed high prevalence of low 25OH vitamin D levels are not clear and need to be investigated further upon

Haematological and Biochemical Reference Values for Healthy Adults in the Middle Belt of Ghana

BACKGROUND: Reference values are very important in clinical management of patients, screening participants for enrollment into clinical trials and for monitoring the onset of adverse events during these trials. The aim of this was to establish gender-specific haematological and biochemical reference values for healthy adults in the central part of Ghana. METHODS: A total of 691 adults between 18 and 59 years resident in the Kintampo North Municipality and South District in the central part of Ghana were randomly selected using the Kintampo Health and Demographic Surveillance System and enrolled in this cross-sectional survey. Out of these, 625 adults made up of 316 males and 309 females were assessed by a clinician to be healthy. Median values and nonparametric 95% reference values for 16 haematology and 22 biochemistry parameters were determined for this population based on the Clinical Laboratory and Standards Institute guidelines. Values established in this study were compared with the Caucasian values being used currently by our laboratory as reference values and also with data from other African and western countries. RESULTS: REFERENCE VALUES ESTABLISHED INCLUDE: haemoglobin 113-164 g/L for males and 88-144 g/L for females; total white blood cell count 3.4-9.2 × 10(9)/L; platelet count 88-352 × 10(9)/L for males and 89-403 × 10(9)/L for females; alanine aminotransferase 8-54 U/L for males and 6-51 U/L for females; creatinine 56-119 µmol/L for males and 53-106 µmol/L for females. Using the haematological reference values based on the package inserts would have screened out up to 53% of potential trial participants and up to 25% of the population using the biochemical parameters. CONCLUSION: We have established a panel of locally relevant reference parameters for commonly used haematological and biochemical tests. This is important as it will help in the interpretation of laboratory results both for clinical management of patients and safety monitoring during a trial