DOMINO trial post hoc analysis: evaluation of the diet effects on symptoms in IBS subtypes.

Background: Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction characterized by recurrent abdominal pain related to defecation and/or associated to a change in bowel habits. According to the stool type, four different IBS subtypes can be recognized, constipation predominant (IBS-C), diarrhea predominant (IBS-D), mixed (IBS-M), and undefined (IBS-U). Patients report that their IBS symptoms are exacerbated by food. Thus, it is important to find a nutritional approach that could be effective in reducing IBS symptoms. Objective: The present work is a post hoc analysis of the previously published DOMINO trial. It aimed to evaluate the effects of a self-instructed FODMAP-lowering diet smartphone application on symptoms and psychosocial aspects in primary care IBS stratifying the results for each IBS subtypes. Design: Post hoc analysis. Methods: Two hundred twenty-two primary care IBS patients followed a FODMAP-lowering diet for 8 weeks with the support of a smartphone application. Two follow-up visits were scheduled after 16 and 24 weeks. IBS-Symptoms Severity Score (IBS-SSS), quality of life (QoL), and adherence and dietary satisfaction were evaluated. Results: After 8 weeks, IBS-SSS improved in all IBS subtypes (p < 0.0001). Physician Health Questiionnaire (PHQ-15) improved only in IBS-D (p = 0.0006), whereas QoL improved both in IBS-D (p = 0.01) and IBS-M (p = 0.005). Conclusion: This post hoc analysis showed that the app is useful in all IBS subtypes; thus, it could be used as an effective tool by both general practitioners and patients to manage symptoms in primary care. Trial registration: Ethical Commission University Hospital of Leuven reference number: S59482. Clinicaltrial.gov reference number: NCT04270487.

What is already known about this subject? The low FODMAP (fermentable oligo-, di-, and monosaccharides and polyols) diet has shown efficacy for controlling IBS (irritable bowel syndrome) symptoms in small controlled trials in tertiary care patients. As this approach requires several visits with an experienced dietitian, it seems less suitable for primary care. What are the new findings? The benefit of the FODMAP lowering app was already present at 4 weeks and persisted during follow-up until 24 weeks. How might it impact on clinical practice in the foreseeable future? Given its superiority to standard first-line pharmacotherapy, and its ease of use, a FODMAP lowering app has the potential to become the preferred first-line treatment for primary care IBS.

Diet or medication in primary care patients with IBS: the DOMINO study - a randomised trial supported by the Belgian Health Care Knowledge Centre (KCE Trials Programme) and the Rome Foundation Research Institute.

BACKGROUND: In Europe, IBS is commonly treated with musculotropic spasmolytics (eg, otilonium bromide, OB). In tertiary care, a low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet provides significant improvement. Yet, dietary treatment remains to be explored in primary care. We evaluated the effect of a smartphone FODMAP-lowering diet application versus OB on symptoms in primary care IBS. METHODS: IBS patients, recruited by primary care physicians, were randomised to 8 weeks of OB (40 mg three times a day) or diet and followed for 24 weeks. We compared IBS Symptom Severity Score and the proportion of responders (improvement ≥50 points) in all patients and the subgroup fulfilling Rome IV criteria (Rome+). We also evaluated treatment efficacy, quality of life, anxiety, depression, somatic symptom severity (Patient Health Questionnaire (PHQ15, PHQ9)) and treatment adherence and analysed predictors of response. RESULTS: 459 primary care IBS patients (41±15 years, 76% female, 70% Rome+) were randomised. The responder rate after 8 weeks was significantly higher with diet compared with OB (71% (155/218) vs 61% (133/217), p=0.03) and more pronounced in Rome+ (77% (118/153) vs 62% (98/158), p=0.004). Patients allocated to diet (199/212) were 94% adherent compared with 73% with OB (148/202) (p<0.001). The significantly higher response rate with diet was already observed after 4 weeks (62% (132/213) vs 51% (110/215), p=0.02) and a high symptom response persisted during follow-up. Predictors of response were female gender (OR=2.08, p=0.04) for diet and PHQ15 (OR=1.10, p=0.02) for OB. CONCLUSION: In primary care IBS patients, a FODMAP-lowering diet application was superior to a spasmolytic agent in improving IBS symptoms. A FODMAP-lowering diet should be considered the first-line treatment for IBS in primary care. TRIAL REGISTRATION NUMBER: NCT04270487.

Attacks against health care in Syria, 2015-16: results from a real-time reporting tool.

BACKGROUND: Collecting credible data on violence against health services, health workers, and patients in war zones is a massive challenge, but crucial to understanding the extent to which international humanitarian law is being breached. We describe a new system used mainly in areas of Syria with a substantial presence of armed opposition groups since November, 2015, to detect and verify attacks on health-care services and describe their effect. METHODS: All Turkey health cluster organisations with a physical presence in Syria, either through deployed and locally employed staff, were asked to participate in the Monitoring Violence against Health Care (MVH) alert network. The Turkey hub of the health cluster, a UN-activated humanitarian health coordination body, received alerts from health cluster partners via WhatsApp and an anonymised online data-entry tool. Field staff were asked to seek further information by interviewing victims and other witnesses when possible. The MVH data team triangulated alerts to identify individual events and distributed a preliminary flash update of key information (location, type of service, modality of attack, deaths, and casualties) to partners, WHO, United Nations Office for the Coordination of Humanitarian Affairs, and donors. The team also received and entered alerts from several large non-health cluster organisations (known as external partners, who do their own information-gathering and verification processes before sharing their information). Each incident was then assessed in a stringent process of information-matching. Attacks were deemed to be verified if they were reported by a minimum of one health cluster partner and one external partner, and the majority of the key datapoints matched. Alerts that did not meet this standard were deemed to be unverified. Results were tabulated to describe attack occurrence and impact, disaggregated where possible by age, sex, and location. FINDINGS: Between early November, 2015, and Dec 31 2016, 938 people were directly harmed in 402 incidents of violence against health care: 677 (72%) were wounded and 261 (28%) were killed. Most of the dead were adult males (68%), but the highest case fatality (39%) was seen in children aged younger than 5 years. 24% of attack victims were health workers. Around 44% of hospitals and 5% of all primary care clinics in mainly areas with a substantial presence of armed opposition groups experienced attacks. Aerial bombardment was the main form of attack. A third of health-care services were hit more than once. Services providing trauma care were attacked more than other services. INTERPRETATION: The data system used in this study addressed double-counting, reduced the effect of potentially biased self-reports, and produced credible data from anonymous information. The MVH tool could be feasibly deployed in many conflict areas. Reliable data are essential to show how far warring parties have strayed from international law protecting health care in conflict and to effectively harness legal mechanisms to discourage future perpetrators. FUNDING: None.

Estimating the number of women with female genital mutilation in Belgium.

OBJECTIVE: To estimate the number of women with female genital mutilation (FGM) living in Belgium, the number of girls at risk, and the target population of medical and social services (MSSs) concerned. METHODS: Data about prevalence of FGM from the most recently published Demographic and Health Surveys and Multiple Indicator Cluster Surveys were applied to females living in Belgium who migrated from countries where excision or infibulation are being practised, and to their daughters. RESULTS: Amongst the 22,840 women and girls living in Belgium who are from a country concerned, 6,260 have 'most probably already undergone a FGM' (women born in the country of origin), and 1,975 are 'at risk' (second generation born in Belgium). The target population of MSSs comprises 1,190 girls less than five years old attending well-baby clinics, 1,690 girls aged 5-19 years attending preventive school health centres, 4,905 women 20-49 years old and 450 women over 50 years of age attending reproductive health services. The population of women concerned is unequally dispersed in Belgium and reflects the distribution of migrant settlement in the different provinces. CONCLUSION: FGM in Belgium requires a more concerted approach in terms of prevention, and medical and social care. Accurate information about the distribution of women concerned should permit better planning of competent services.

Monitoring of all-cause mortality in Belgium (Be-MOMO): a new and automated system for the early detection and quantification of the mortality impact of public health events.

OBJECTIVES: Be-MOMO is the monitoring of all-cause death registry data in Belgium. The new methods are described and the detection and quantification of outbreaks is presented for the period April 2006-March 2007. Sensitivity, specificity and timeliness are illustrated by means of a temporal comparison with known health events. METHODS: Relevant events are identified from important mortality risks: climate, air pollution and influenza. Baselines and thresholds for deaths by gender, age group, day and week are estimated by the method of Farrington et al. (J R Stat Soc Ser A, 159:547-563, 1996). By adding seasonal terms to the basic model, a complete 5-year reference period can be used, while a reduction of noise allows the application to daily counts. RESULTS: Ignoring two false positives, all flags could be classified into five distinct outbreaks, coinciding with four heat periods and an influenza epidemic. Negative deviations from expected mortality in autumn and winter might reflect a displacement of mortality by the heat waves. Still, significant positive excess was found during five influenza weeks. Correcting for the delay in registration of deaths, outbreaks could be detected as soon as 1-2 weeks after the event. CONCLUSION: The sensitivity of Be-MOMO to different health threats suggests its potential usefulness in early warning: mortality thresholds and baselines might serve as rapid tools for detecting and quantifying outbreaks, crucial for public health decision-making and evaluation of measures.

Modified poly(propylene imine) dendrimers as effective transfection agents for catalytic DNA enzymes (DNAzymes).

The major bottleneck in gene therapy remains the issue of delivery. In this work, various modified poly(propylene imine) (PPI) dendrimers are introduced as gene transfection agents. Commercially available PPI-dendrimers have been modified (i) at the exterior primary amines with acetyl groups or glycol gallate (PEG-like) groups, and (ii) at the interior tertiary amines with methyl iodide (MeI) or MeCl to produce multiple quaternized cationic sites in the core of the dendrimer. The prepared materials have been tested with respect to their binding capabilities to DNA, their toxicity in cell cultures, their in vitro transfection efficiency and their in vivo delivery possibilities. In all cases, a 33-mer oligonucleotide (DNAzyme) was used. Polyacrylamide gel electrophoresis (PAGE) studies have demonstrated strong but reversible binding, where the quarternized and higher generation dendrimer species have shown more potent binding. Typically, for the modified fourth PPI-dendrimers, binding is observed at a concentration of about 4 microM DNA and a dendrimer-DNA charge ratio of around 2:1-1:1. All the tested PPI-dendrimers display a low cellular toxicity, especially when higher serum contents are used in the culture medium. For example, most of the prepared fourth generation PPI-dendrimers are not or hardly toxic up to at least 20 microM in 20% serum. An in vitro characterization has revealed a high dendrimer-mediated intracellular uptake of the DNAzyme: all the tested fourth generation PPI-dendrimers display transfection efficiencies close to or exceeding 80%, even when the concentration of serum in the medium is increased from 10 to 40%. Finally, the potential of using modified PPI-dendrimers for in vivo gene therapy experiments is demonstrated. Injecting a G4-PEG(MeI)-ssDNA complex intravenously into Nude mice has resulted in a high nuclear uptake as confirmed by co-localization studies.