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Abstract: Background: The Rome criteria for irritable bowel syndrome (IBS) have been revised and are expected to apply only to the subset of Rome III IBS subjects with abdominal pain as predominant symptom, occurring at least once a week. The aim of this study was to determine the percentage of Rome III IBS subjects that fulfills Rome IV criteria and to evaluate differences between Rome IV‐positive and Rome IV‐negative subjects. Methods: Four hundred and four Rome III IBS subjects completed a 14‐day end‐of‐day symptom diary, the Gastrointestinal Symptom Rating Scale (GSRS), Hospital Anxiety and Depression Scale, and RAND 36‐item Short‐Form Health Survey (SF‐36). Diary‐based surrogate Rome IV criteria were defined as occurrence of abdominal pain at least 1 day each week with a severity of ≥2 (mild; definition 1) or ≥3 (considerable; definition 2). Key Results: Using surrogate Rome IV criteria, 353 (87.4%, definition 1) and 249 (61.6%, definition 2) subjects were defined as Rome IV positive. These patients were more often female, younger, and recruited from secondary/tertiary care compared with Rome IV‐negative subjects. They also presented with higher abdominal pain scores and gastrointestinal (GI) symptom severity on both end‐of‐day diary and GSRS, higher psychological symptom scores, and lower quality of life compared with Rome IV‐negative subjects. Conclusions and Inferences: The Rome IV IBS population likely reflects a subgroup of Rome III IBS patients with more severe GI symptomatology, psychological comorbidities, and lower quality of life. This implies that results from Rome III IBS studies may not be directly comparable to those from Rome IV IBS populations. [ABSTRACT FROM AUTHOR]

Background Although irritable bowel syndrome ( IBS) is a symptom-based diagnosis, clinicians' management of and communication about the disorder is often hampered by an unclear conceptual understanding of the nature of the problem. We aimed to elucidate an integrated explanatory model ( EM) for IBS from the existing literature for pragmatic use in the clinical setting. Methods Systematic and exploratory literature searches were performed in PubMed to identify publications on IBS and EMs. Key Results The searches did not identify a single, integrated EM for IBS. However, three main hypotheses were elucidated that could provide components with which to develop an IBS EM: (i) altered peripheral regulation of gut function (including sensory and secretory mechanisms); (ii) altered brain-gut signaling (including visceral hypersensitivity); and (iii) psychological distress. Genetic polymorphisms and epigenetic changes may, to some degree, underlie the etiology and pathophysiology of IBS and could increase the susceptibility to developing the disorder. The three model components also fit into one integrated explanation for abdominal symptoms and changes in stool habit. Additionally, IBS may share a common pathophysiological mechanism with other associated functional syndromes. Conclusions & Inferences It was possible to elucidate an integrated, three-component EM as a basis for clinicians to conceptualize the nature of IBS, with the potential to contribute to better diagnosis and management, and dialog with sufferers. [ABSTRACT FROM AUTHOR]

Objective To review studies on the perceptions, diagnosis and management of irritable bowel syndrome ( IBS) in primary care. Methods Systematic searches of PubMed and Embase. Results Of 746 initial search hits, 29 studies were included. Relatively few primary care physicians were aware of (2-36%; nine studies) or used (0-21%; six studies) formal diagnostic criteria for IBS. Nevertheless, most could recognise the key IBS symptoms of abdominal pain, bloating and disturbed defaecation. A minority of primary care physicians [7-32%; one study (six European countries)] preferred to refer patients to a specialist before making an IBS diagnosis, and few patients [4-23%; three studies (two European, one US)] were referred to a gastroenterologist by their primary care physician. Most PCPs were unsure about IBS causes and treatment effectiveness, leading to varied therapeutic approaches and broad but frequent use of diagnostic tests. Diagnostic tests, including colon investigations, were more common in older patients (>45 years) than in younger patients [<45 years; five studies (four European, one US)]. Conclusions There has been much emphasis about the desirability of an initial positive diagnosis of IBS. While it appears most primary care physicians do make a tentative IBS diagnosis from the start, they still tend to use additional testing to confirm it. Although an early, positive diagnosis has advantages in avoiding unnecessary investigations and costs, until formal diagnostic criteria are conclusively shown to sufficiently exclude organic disease, bowel investigations, such as colonoscopy, will continue to be important to primary care physicians. [ABSTRACT FROM AUTHOR]

Background The most effective initial treatment strategy of dyspepsia is still under debate. Individual biological characteristics, such as condition of gastric mucosa, might contribute to selection of the most appropriate acid suppression treatment strategy. Aim To assess whether pre-treatment testing of gastric mucosal status is relevant for treatment success in an RCT comparing step-up and step-down therapies in newly diagnosed dyspepsia patients. Methods Baseline serum samples were collected to assess gastric mucosal status using serum levels of pepsinogens-I&II, gastrin-17, and Helicobacter pylori IgA/IgG-antibodies. The 6-month treatment success was compared between step-up and step-down for patients with serum diagnoses: normal; gastritis; corpus atrophy or antrum atrophy. Results In all, 519 patients (M/F: 249/270, age: 47 (18–85) years, 29% H. pylori+) were randomized to step-up ( n = 293) or step-down ( n = 226). Normal mucosa, gastritis and corpus atrophy were diagnosed serologically in 70%, 28% and 2% of the patients, evenly distributed between the strategies ( P = 0.65). Treatment success was achieved in respectively, 69%, 70% and 70% for the serum diagnosis groups, and did not differ between the strategies. Conclusions Dyspepsia treatment success could not be predicted by gastric mucosal status. Therefore, serum diagnosis of gastric mucosal status is no useful tool for patient allocation to acid suppressive treatment strategies. [ABSTRACT FROM AUTHOR]

Purpose: Update of a clinical practice guideline for the physiotherapy management of patients with chronic obstructive pulmonary disease supporting the clinical decision-making process. Methods: A systematic computerized literature search was performed on different modalities for improving physical exercise capacity, reducing exertional dyspnoea, improving airway clearance and encouraging changes in physical activity behaviour. Methodological quality was scored with the PEDro Scale. Scientific conclusions were graded according to the criteria of the 'Dutch Evidence Based Guideline Development Platform'. These, together with practical considerations, were used to formulate recommendations for clinical practice. Results: A total of 103 studies were included in the systematic review, consisting of five meta-analyses of randomized controlled trials, 84 randomized controlled trials and 14 uncontrolled studies. Twenty scientific conclusions supported six recommendations on physical exercise training. Nineteen scientific conclusions supported eight recommendations on interventions for reducing dyspnoea. Five scientific conclusions supported seven recommendations concerning treatment modalities to improve mucus clearance, and two scientific conclusions supported two recommendations on strategies for encouraging permanent changes in physical activity behaviour. Conclusions: Strong recommendations support the use of physical exercise training to improve health-related quality of life and functional exercise capacity. Future research should investigate whether additional interventions for reducing exertional dyspnoea have a place as adjuncts to physical exercise training in selected patients. In addition, treatment of impaired mucus clearance, especially during acute exacerbations, requires further research. With the advance of new technologies for objective measurements of physical activities in daily life more research is needed concerning interventions to initiate and maintain physical activity behaviour change during and after supervised physical exercise training programmes. [ABSTRACT FROM AUTHOR]

INTRODUCTION: In the context of international collaboration for the development of practice guidelines, the Royal Dutch Society for Physical Therapy (Koninklijk Nederlands Genootschap voor Fysiotherapie, KNGF) has developed guidelines for the clinical practice of physical therapy in patients with Chronic Obstructive Pulmonary Disease (COPD). It has also stimulated its translation into other languages to make it accessible to international audiences. OBJECTIVES: The present document brings the Portuguese version of the KNGF Clinical Practice Guidelines for physical therapy in COPD patients. Its purpose was to describe evidence-based physical therapy for COPD patients with impairments in pulmonary function, peripheral and respiratory muscle function, exercise capacity, mucus clearance and quality of life, in addition to limitations in physical activity in daily life due to dyspnea and/or exercise intolerance. CONCLUSION: The guideline provides practical and therapeutic recommendations based on currently available scientific evidence to help the physical therapist provide the best possible treatment to COPD patients. [ABSTRACT FROM AUTHOR]

Background Personality and psychiatric disorders are reported to be more common in dyspeptic patients with severe complaints, but it remains unclear whether this association exists for patients with mild and moderate dyspepsia. Aim To study the association between dyspeptic symptom severity and psychopathology, major life events and coping ability in patients with a new episode of dyspepsia. Methods Dyspeptic symptom severity was measured using the validated eight symptom Veldhuyzen van Zanten questionnaire. Psychopathology was measured using the Symptom Check List-90 (SCL 90). Major life events were measured with a modified version of the Social Readjustment Rating Scale (SRRS). Coping styles were measured by a short version of the Utrecht Coping Questionnaire, distinguishing six coping styles. Linear regression was used to assess the relationship between dyspepsia symptom severity and psychological factors. Results In all, 664 patients with a new episode of uninvestigated dyspepsia, aged >18 years were included. Dyspeptic symptom severity was positively correlated with the presence of depression ( P < 0.01), somatization symptoms ( P < 0.01), use of an active coping style ( P < 0.01) and negatively correlated with age ( P < 0.01). Conclusions Primary care patients consulting with dyspepsia have higher levels of depression and somatization especially at younger age. An active coping style is associated with dyspepsia symptom severity. [ABSTRACT FROM AUTHOR]

Background Exposure to a high level of house dust mite allergens (HDMAs) is considered as a risk factor for HDM sensitization and development of asthma in genetically disposed people. Mattresses are one of the most important sources of HDMA in people's living environment. Objective The aim of this study was to evaluate the association between mattress characteristics and HDMA concentrations on mattresses. Methods Dust samples of mattress surfaces were taken to evaluate the level of Der p 1 allergen. All participants filled in a questionnaire about the type of mattress, the type of covering (upper layer) of the mattress, dwelling characteristics and cleaning habits. Humidity and temperature of the bedroom were measured at the time of dust sampling. Results One hundred and sixty-eight questionnaires were filled in. Synthetic upper layer of the mattress was associated with a higher level of Der p 1 compared with cotton upper layer (2.6 vs. 0.8 μg/g Der p 1). Moreover, higher relative humidity (RH) was associated with significant higher concentrations and density of Der p 1. Conclusions Two factors were associated with lower levels of Der p 1 found on mattresses, namely: a cotton upper layer of the mattress compared with a layer of synthetic material and lower RH at the time of sampling. As far as we know, the association between type of upper layer and concentration of Der p 1 has not been described before and could lead to the formulation of practical advices in order to reduce HDMA concentrations on mattresses. [ABSTRACT FROM AUTHOR]

: The percentage of patients receiving long-term treatment with acid suppressive drugs, mainly proton pump inhibitors, is higher than the prevalence of diseases that are commonly accepted as the proper indication for long-term proton pump inhibitor use. : To evaluate whether a patient-directed intervention (direct mail) reduced the prescription of antisecretory medication for dyspepsia in general practice. : A cluster-randomized trial was performed. One hundred and thirteen chronic users of proton pump inhibitors were recruited by 20 general practitioners. An unsolicited information leaflet was sent to patients that suggested stopping or reducing the use of proton pump inhibitors. The number of patients who stopped or reduced proton pump inhibitor use was measured at 12 and 20 weeks after the intervention. Secondary outcome measures were dyspepsia symptom severity and perceived quality of life measured at 12 weeks after the intervention. : Fourteen of the 59 (24%) intervention group patients stopped or reduced their use of proton pump inhibitors, compared with three of the 45 (7%) control group patients (relative risk ratio 3.56; CI 95%: 1.088–11.642). Dyspepsia symptom severity and quality of life did not change. : A simple patient-directed intervention reduced the volume of long-term prescriptions of proton pump inhibitors in patients with dyspepsia. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To assess the efficacy of roxithromycin relative to amoxicillin. STUDY DESIGN: We conducted a double-blind randomized controlled trial of oral 500 mg amoxicillin 3 times per day vs oral 300 mg roxithromycin once a day for 10 days. POPULATION: We included 196 adults who had presented to a general practitioner with lower respiratory tract infection (LRTI) and, in the physician's opinion, needed antibiotic treatment. OUTCOMES MEASURED: We measured clinical response after 10 and 28 days, defined in 4 ways: (1) decrease in LRTI symptoms; (2) complete absence of symptoms; (3) decrease in signs; and (4) complete absence of signs. Self-reported response included the decrease in symptoms and the time until resumption of impaired or abandoned daily activities on days 1 through 10, 21, and 27. RESULTS: Clinical cure rates after the completion of antibiotic treatment (10 days) were not significantly different for the 2 groups. After 28 days, the roxithromycin group showed no increase in cure rate as evidenced by the decrease in symptoms, indicating a significantly lower cure rate. However, this difference did not alter physicians' overall conclusion after complete follow-up that 90% of patients, regardless of age, had been effectively treated with either amoxicillin or roxithromycin. CONCLUSIONS: The surplus value of roxithromycin was not confirmed. Amoxicillin remains a reliable first-choice antibiotic in the treatment of LRTI in general practice. [ABSTRACT FROM AUTHOR]

Background and Aims: Patient health literacy (HL), illness perception and awareness are key factors driving health behaviour. This observational study aims to assess the level of HL, illness perception and awareness about non-alcoholic fatty liver disease (NAFLD)/ steatohepatitis (NASH) in high-risk primary care (PC) patients in Greece, Spain and the Netherlands. Methods: Eligibility criteria included: 1) aged ≥ 50 years, and 2) obesity, and/or metabolic syndrome, and/or diabetes. Patients consecutively visiting PC practices completed a questionnaire assessing socio-demographic characteristics and health habits. HL, illness perception and NAFLD/NASH awareness were assessed using the European Health Literacy Survey Questionnaire, the Brief Illness Perception Questionnaire and the Public Awareness of NAFLD Questionnaire respectively. Results: Data are available at this moment from the Greek setting. Among the Greek participants (N = 141, 53.2% females, mean age 66 years) 66.7% had diabetes, 78% obesity and 71.6% metabolic syndrome, with 22.7% reporting active smoking. Most (71.6%) had heard about NAFLD by their personal physician. Obesity (78%), excess alcohol intake (45.8%), lack of exercise (38.7%) and diabetes (32.4%) were recognized as the commonest determinants of fatty liver disease, while 78% were aware of ultrasound as the main diagnostic modality and 47% did not know whether there is an available treatment. Only 39% of the participants find information of their treatments easily. Conclusions: Our preliminary results show that the majority of patients seem to be aware about NAFLD/NASH and their determinants. It’s alarming that a lot do not know about treatment, although they are high-risk.Key messages: Our preliminary results show that the majority of patients seem to be aware about NAFLD/NASH and their determinants. It’s alarming that a lot of patients do not know about their treatment, although they are high-risk. [ABSTRACT FROM AUTHOR]

The article describes a case of allergic contact dermatitis without accompanying oral symptoms caused by a metal-based orthodontic retainer wires in a 35-year-old woman with Von Willebrand's disease. The patient complains of excessive peri-oral and peri-orbital itchy eczema lesions and her lymphocyte proliferation test showed a significant sensitization to nickel.

BACKGROUND: Activation of the PI3K/MAPK pathways results in anti-estrogen resistance in vitro, however a biomarker that can predict clinical resistance has not yet been identified. Common drivers of these pathways are PIK3CA mutations, loss of PTEN and over-expression of HER2 and IGF-1R. We aimed to test the prognostic and predictive value of PI3K/MAPK pathway drivers as well as downstream activated proteins in postmenopausal breast cancer patients. METHODS: We collected primary tumor tissue from 563 ERα positive breast cancer patients who were randomized between tamoxifen (1-3 years) versus no adjuvant systemic therapy. PIK3CA hotspot mutations were assessed by Sequenom Mass Spectrometry. Immunohistochemistry was performed for expression of PTEN, IGF-1R and the downstream markers p-AKT(Thr308), p-AKT(Ser473), p-mTOR, p-p706SK and p-ERK1/2. Cox proportional hazard models for recurrence free interval were used to assess hazard ratios and interaction between these markers and treatment. RESULTS: No significant interaction between any of the tested PI3K/MAPK pathways drivers and tamoxifen was found. [/bold]However, interactions were identified between tamoxifen and the downstream activated proteins (p-AKT(Thr308), p- mTOR, p-p70S6K and p-ERK1/2). After correcting for multiple testing, p-p70S6K remained significantly associated with tamoxifen resistance. Patients whose tumor did not express p-p70S6K did derive significant benefit from tamoxifen (HR 0.24, 95 % CI= 0.12-0.47, p < 0.0001), while patients whose tumor did express p-p70S6K did not (multivariate HR=1.02, 95% CI=0.48-2.21, p = 0.95), p for interaction 0.003. CONCLUSION: We conclude that the downstream marker of PI3K/MAPK activation p-p70S6K predicts tamoxifen resistance in ERα positive postmenopausal breast cancer patients. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to assess the impact of on-demand versus continuous prescribing of proton pump inhibitors (PPIs) on symptom burden and health-related quality of life in patients with gastroesophageal reflux disease (GERD) presenting to primary care., Methods: Thirty-six primary care centres across Europe enrolled adult GERD patients from electronic health records. Participants were randomised to on-demand or continuous PPI prescriptions and were followed for 8 weeks. PPI intake, symptom burden, and quality of life were compared between the two groups using mixed-effect regression analyses. Spearman's correlation was used to assess the association between changes in PPI dose and patient-reported outcomes., Results: A total of 488 patients (median age 51 years, 58% women) completed the initial visit, with 360 attending the follow-up visit. There was no significant difference in PPI use between the continuous and on-demand prescription groups ( b =.57, 95%CI:0.40-1.53), although PPI use increased in both groups ( b  = 1.33, 95%CI:0.65 - 2.01). Advice on prescribing strategy did not significantly affect patient-reported outcomes. Both symptom burden (Reflux Disease Questionnaire, b=-0.61, 95%CI:-0.73 - -0.49) and quality of life (12-item Short Form Survey physical score b  = 3.31, 95%CI:2.17 - 4.45) improved from baseline to follow-up in both groups. Increased PPI intake correlated with reduced reflux symptoms ( n  = 347, ρ=-0.12, p  = 0.02) and improved quality of life ( n  = 217, ρ = 0.16, p  = 0.02)., Conclusion: In real-world settings, both continuous and on-demand PPI prescriptions resulted in similar increases in PPI consumption with no difference in treatment effects. Achieving an adequate PPI dose to alleviate reflux symptom burden improves quality of life in GERD patients. EudraCT number 2014-001314-25.