RESUMO
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.
Assuntos
Síndrome do Intestino Irritável , Academias e Institutos , Bélgica , Atenção à Saúde , Dieta , Dissacarídeos/uso terapêutico , Feminino , Fermentação , Humanos , Síndrome do Intestino Irritável/terapia , Masculino , Monossacarídeos/uso terapêutico , Oligossacarídeos , Parassimpatolíticos , Atenção Primária à Saúde , Qualidade de Vida , Cidade de RomaRESUMO
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.
RESUMO
Bombus terrestris bumblebees are important pollinators of wild flowers, and in modern agriculture they are used to guarantee pollination of vegetables and fruits. In the field it is likely that worker bees are exposed to pesticides during foraging. To date, several tests exist to assess lethal and sublethal side-effects of pesticides on bee survival, growth/development and reproduction. Within the context of ecotoxicology and insect physiology, we report the development of a new bioassay to assess the impact of sublethal concentrations on the bumblebee foraging behavior under laboratory conditions. In brief, the experimental setup of this behavior test consists of two artificial nests connected with a tube of about 20 cm and use of queenless micro-colonies of 5 workers. In one nest the worker bees constructed brood, and in the other food (sugar and pollen) was provided. Before exposure, the worker bees were allowed a training to forage for untreated food; afterwards this was replaced by treated food. Using this setup we investigated the effects of sublethal concentrations of the neonicotinoid insecticide imidacloprid, known to negatively affect the foraging behavior of bees. For comparison within the family of neonicotinoid insecticides, we also tested different concentrations of two other neonicotinoids: thiamethoxam and thiacloprid, in the laboratory with the new bioassay. Finally to evaluate the new bioassay, we also tested sublethal concentrations of imidacloprid in the greenhouse with use of queenright colonies of B. terrestris, and here worker bees needed to forage/fly for food that was placed at a distance of 3 m from their hives. In general, the experiments showed that concentrations that may be considered safe for bumblebees can have a negative influence on their foraging behavior. Therefore it is recommended that behavior tests should be included in risk assessment tests for highly toxic pesticides because impairment of the foraging behavior can result in a decreased pollination, lower reproduction and finally in colony mortality due to a lack of food.
Assuntos
Anabasina/toxicidade , Comportamento Apetitivo/efeitos dos fármacos , Abelhas/efeitos dos fármacos , Inseticidas/toxicidade , Polinização/efeitos dos fármacos , Análise de Variância , Animais , Bioensaio/métodos , Imidazóis/toxicidade , Neonicotinoides , Nitrocompostos/toxicidade , Oxazinas/toxicidade , Piridinas/toxicidade , Medição de Risco , Tiametoxam , Tiazinas/toxicidade , Tiazóis/toxicidade , Testes de Toxicidade Crônica/métodosRESUMO
BACKGROUND: This study was undertaken to identify the potential side effects of the novel naturalyte insecticide spinetoram in comparison with spinosad on the bumblebee Bombus terrestris L. The potential lethal effects together with the ecologically relevant sublethal effects on aspects of bumblebee reproduction and foraging behaviour were evaluated. Bumblebee workers were exposed via direct contact with wet and dry residues under laboratory conditions to spinetoram at different concentrations, starting from the maximum field recommended concentration (MFRC) and then different dilutions (1/10, 1/100, 1/1000 and 1/10 000 of the MFRC), and compared with spinosad. In addition, the side effects via oral exposure in supplemented sugar water were assessed. RESULTS: Direct contact of B. terrestris workers with wet residues of spinosad and spinetoram showed spinetoram to be approximately 52 times less toxic than spinosad, while exposure to dry residues of spinetoram was about 8 times less toxic than exposure to those of spinosad. Oral treatment for 72 h (acute) indicated that spinetoram is about 4 times less toxic to B. terrestris workers compared with spinosad, while exposure for a longer period (i.e. 11 weeks) showed spinetoram to be 24 times less toxic. In addition, oral exposure to the two spinosyns resulted in detrimental sublethal effects on bumblebee reproduction. The no observed effect concentration (NOEC) for spinosad was 1/1000 of the MFRC, and 1/100 of the MFRC for spinetoram. Comparison between the chronic exposure bioassays assessing the sublethal effects on nest reproduction, with and without allowing for foraging behaviour, showed that the respective NOEC values for spinosad and spinetoram were similar over the two bioassays, indicating that there were no adverse effects by either spinosyn on the foraging of B. terrestris workers. CONCLUSION: Overall, the present results indicate that the use of spinetoram is safer for bumblebees by direct contact and oral exposure than the use of spinosad, and therefore it can be applied safely in combination with B. terrestris. Another important conclusion is that the present data provide strong evidence that neither spinosyn has a negative effect on the foraging behaviour of these beneficial insects. However, before drawing final conclusions, spinetoram and spinosad should also be evaluated in more realistic field-related situations for the assessment of potentially deleterious effects on foraging behaviour with the use of queenright colonies of B. terrestris.
Assuntos
Abelhas/efeitos dos fármacos , Controle de Insetos/métodos , Inseticidas/toxicidade , Macrolídeos/toxicidade , Animais , Abelhas/fisiologia , Combinação de Medicamentos , Masculino , Reprodução/efeitos dos fármacosRESUMO
BACKGROUND: This project assessed the potential hazards of different classical and novel acaricides against an important non-target and beneficial insect for the pollination of wild flowers and cultivated crops, the bumblebee Bombus terrestris (L). Twenty-three acaricides used commercially in the control of phytophagous mites (Acari) were tested in greenhouses and/or the open field. Side effects included acute mortality and also sublethal effects on nest reproduction. The different compounds were administered in the laboratory via three different worst-case field scenario routes of exposure: dermal contact and orally via the drinking of treated sugar water and via treated pollen. The compounds were tested at their respective maximum field recommended concentration (MFRC), and, when strong lethal effects were observed, a dose-response assay with a dilution series of the MFRC was undertaken to calculate LC(50) values. RESULTS: From the different acaricide classes, several chemistries caused high levels of acute toxicity in bumblebee workers, especially bifenthrin and abamectin which resulted in 100% mortality by contact. In addition, several acaricides tested were found to have a detrimental effect on drone production. For oral exposures via treated sugar water, the dose-response assay showed the LC(50) values for abamectin, bifenazate, bifenthrin and etoxazole to be 1/15 MFRC (1.17 mg AI L(-1)), 1/10 MFRC (9.6 mg AI L(-1)), 1/83 MFRC (0.36 mg AI L(-1)) and 1/13 MFRC (4.4 mg AI L(-1)) respectively, indicating that their use should be carefully evaluated. CONCLUSION: Overall, the results suggest that most of the acaricides tested are compatible with bumblebees, with the exceptions of abamectin, bifenazate, bifenthrin and etoxazole. However, the risks also depended on the type of treatment. As a result, the sugar water treatment seems to present the worst-case situation of exposure, indicating that this approach is suitable for determining the hazards of pesticides against bumblebees. Finally, it is suggested that future tier testing under more field-related conditions is required for a final decision of their risks.