Effectiveness of a symptom-clinic intervention delivered by general practitioners with an extended role for people with multiple and persistent physical symptoms in England: the Multiple Symptoms Study 3 pragmatic, multicentre, parallel-group, individually randomised controlled trial.

BACKGROUND: People with multiple and persistent physical symptoms have impaired quality of life and poor experiences of health care. We aimed to evaluate the effectiveness of a community-based symptom-clinic intervention in people with multiple and persistent physical symptoms, hypothesising that this symptoms clinic plus usual care would be superior to usual care only. METHODS: The Multiple Symptoms Study 3 was a pragmatic, multicentre, parallel-group, individually randomised controlled trial conducted in 108 general practices in the UK National Health Service in four regions of England between Dec 6, 2018, and June 30, 2023. Participants were individually randomised (1:1) to the symptom-clinic intervention plus usual care or to usual care only via a computer-generated, pseudo-random list stratified by trial centre. Allocation was done by the trial statistician and concealed with a centralised, web-based randomisation system; masking participants was not possible due to the nature of the intervention. The symptom-clinic intervention was a sequence of up to four medical consultations that aimed to elicit a detailed clinical history, fully hear and validate the participant, offer rational explanations for symptoms, and assist the participant to develop ways of managing their symptoms; it was delivered by general practitioners with an extended role. The primary outcome was Patient Health Questionnaire-15 (PHQ-15) score 52 weeks after randomisation, analysed by intention to treat. The trial is registered on the ISRCTN registry (ISRCTN57050216). FINDINGS: 354 participants were randomly assigned; 178 (50%) were assigned to receive the community-based symptoms clinic plus usual care and 176 (50%) were assigned to receive usual care only. At the primary-outcome point of 52 weeks, PHQ-15 scores were 14·1 (SD 3·7) in the group receiving usual care and 12·2 (4·5) in the group receiving the intervention. The adjusted between-group difference of -1·82 (95% CI -2·67 to -0·97) was statistically significantly in favour of the intervention group (p<0·0001). There were 39 adverse events in the group receiving usual care and 36 adverse events in the group receiving the intervention. There were no statistically significant between-group differences in the proportion of participants who had non-serious adverse events (-0·03, 95% CI -0·11 to 0·05) or serious adverse events (0·02, -0·02 to 0·07). No serious adverse event was deemed to be related to the trial intervention. INTERPRETATION: Our symptom-clinic intervention, which focused on explaining persistent symptoms to participants in order to support self-management, led to sustained improvement in multiple and persistent physical symptoms. FUNDING: UK National Institute for Health and Care Research.

The IL-33/IL-31 Axis in Allergic and Immune-Mediated Diseases.

Interleukin 31 (IL-31) belongs to the IL-6 superfamily [...].

A rare hepatic mass in an Italian resident.

BACKGROUND: Amebiasis is a rare condition in developed countries but epidemiologically growing. Clinical manifestation may range from asymptomatic to invasive disease, amoebic liver abscess being the most common manifestation. We report a peculiar case of left hepatic amoebic liver abscess in a patient without a well-known source of infection and presenting with left portal vein thrombosis. CASE PRESENTATION: Patient, working as longshoreman, presented with complaints of remittent-intermittent fever lasting from 2 weeks. Physical examination was normal. Blood tests showed mild anemia, neutrophilic leukocytosis and elevated inflammation markers. Chest x-rays was normal. Abdominal ultrasound showed multiple hypoechoic liver masses. CT-scan of abdomen showed enlarged left liver lobe due to the presence of large abscess cavity along with thrombosis of left portal vein. The indirect hemagglutination test for the detection of antibodies to Entamoeba histolytica (Eh) was positive. Ultrasound-guided percutaneous drainage revealed "anchovy sauce" pus. Metronidazole and a follow up imaging at 3 months showed resolution of abscess cavity. CONCLUSION: This case shows that amoebic liver abscess is possible even in first world country patients without travel history. Left sided abscess and portal vein thrombosis are rare and hence reported.

Tranexamic acid adverse reactions: a brief summary for internists and emergency doctors.

Tranexamic acid (TXA) is a synthetic lysine analogue that is well known as antifibrinolytic agent. It can reduce blood loss in clinical use, especially in conditions where fibrinolysis or hyperfibrinolysis are involved, such as trauma or surgery. Moreover, TXA has been approved as second-line prophylactic therapy for hereditary angioedema and further data have been published about a possible use of TXA as maintenance treatment for nonhistaminergic angioedema and treatment for episodes of bradykinin-mediated angioedema induced by ACE inhibitors. TXA can be administered through several routes: orally, topically, or intravenously. Although, it is a drug with a very high safety profile, in few cases hypersensitivity reactions have been described occurring with different clinical manifestations. Ethamsylate can be an alternative in TXA sensitized patients. In this brief article we describe TXA adverse reactions and current protocols which have been proposed to help clinicians to diagnose TXA hypersensitivity.

IL-33/IL-31 Axis in Immune-Mediated and Allergic Diseases.

Several allergic and immunologic diseases including asthma, food allergy (FA), chronic spontaneous urticaria (CSU), atopic dermatitis (AD), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), and Behçet's disease (BD) are characterized by the involvement of Th2 immunity. Several mediators lead to immunoglobulin (Ig)E production, thus including key cytokines such as interleukin (IL)-4, IL-5, and IL-13. Among them, IL-31 and IL-33 have been recently studied as novel biomarkers and future therapeutic targets for allergic and immunological disorders. IL-31 is a proinflammatory cytokine-it regulates cell proliferation and is involved in tissue remodeling. IL-33, acting through its receptor suppression of tumorigenity (ST2L), is an alarmin cytokine from the IL-1 family, whose expression is mediated by tissue damage. The latter has a pleiotropic effect, as it may modulate specific and innate immune cells functions. To date, several researchers have investigated the involvement of IL-31 and IL-33 in several allergic and immune-mediated diseases. Further studies are needed to understand the future applications of these molecules as novel therapeutic agents. This paper aims to give the readers a complete and updated review of IL-31 and IL-33 involvement among the most common autoimmune and allergic disorders.

Effects of AntagomiRs on Different Lung Diseases in Human, Cellular, and Animal Models.

INTRODUCTION: MiRNAs have been shown to play a crucial role among lung cancer, pulmonary fibrosis, tuberculosis (TBC) infection, and bronchial hypersensitivity, thus including chronic obstructive pulmonary disease (COPD) and asthma. The oncogenic effect of several miRNAs has been recently ruled out. In order to act on miRNAs turnover, antagomiRs have been developed. MATERIALS AND METHODS: The systematic review was conducted under the PRISMA guidelines (registration number is: CRD42019134173). The PubMed database was searched between 1 January 2000 and 30 April 2019 under the following search strategy: (((antagomiR) OR (mirna antagonists) OR (mirna antagonist)) AND ((lung[MeSH Terms]) OR ("lung diseases"[MeSH Terms]))). We included original articles, published in English, whereas exclusion criteria included reviews, meta-analyses, single case reports, and studies published in a language other than English. RESULTS AND CONCLUSIONS: A total of 68 articles matching the inclusion criteria were retrieved. Overall, the use of antagomiR was seen to be efficient in downregulating the specific miRNA they are conceived for. The usefulness of antagomiRs was demonstrated in humans, animal models, and cell lines. To our best knowledge, this is the first article to encompass evidence regarding miRNAs and their respective antagomiRs in the lung, in order to provide readers a comprehensive review upon major lung disorders.

On illness and value: biopolitics, psychosomatics, participating bodies.

In its heyday, around the mid-twentieth century, psychosomatic medicine was promoted as heralding a new science of body/mind relations that held the promise of transforming medicine as a whole. Sixty years on, the field appears to have achieved no more than a respectable position as a research specialism within the medical status quo. This paper articulates the problematic of psychosomatics through a number of propositions that reconnect its promise of novelty to the present and to contemporary concerns. In contrast to classic approaches to 'psychosomatic problems', which typically set out by denouncing the conceptual inadequacy of mind/body dualism, the focus proposed is on the resilience of dualism as an empirical datum deserving closer analysis. The paper thus asks: what is the character of dualism considered under the aspect of what it achieves, and thus as an expression of value? Drawing on the thought of A N Whitehead, Michel Foucault and Viktor von Weizsäcker, the argument formulates a set of 'psychosomatic problems' informed by the concept of biopolitics and introduces their relevance in relation to the politics of participatory medicine.

Chronic fatigue syndrome and an illness-focused approach to care: controversy, morality and paradox.

Contemporary medicine distinguishes between illness and disease. Illness refers to a person's subjective experience of symptoms; disease refers to objective bodily pathology. For many illnesses, medicine has made great progress in finding and treating associated disease. However, not all illnesses are successfully relieved by treating the disease. In some such cases, the patient's suffering can only be reduced by treatment that is focused on the illness itself. Chronic disabling fatigue is a common symptom of illness, for which disease-focused treatment is often not effective, but for which illness-focused treatments (psychological or behavioural) often are. In this article, we explore a controversy surrounding illness-focused treatments for fatigue. We do this by contrasting their acceptance by people whose fatigue is associated with a disease (using the example of cancer-related fatigue) with their controversial rejection by some people whose fatigue is not associated with an established disease (chronic fatigue syndrome or CFS, sometimes called ME (myalgic encephalomyelitis)). In order to understand this difference in acceptability we consider the differing moral connotations of illness and disease and then go on to examine the limitations of the concepts of illness and disease themselves. We conclude that a general acceptance of illness-focused treatments by all who might benefit from them will require a major long-term change in thinking about illness, but that improvements to the care of individual patients can be made today.

Late-Life Depression versus Amnestic Mild Cognitive Impairment: Alzheimer's Disease Incidence in 4 Years of Follow-Up.

BACKGROUND/AIM: The aim of the study was to evaluate the prognostic power of late-life depression (LLD) compared with amnestic mild cognitive impairment (aMCI) for the onset of Alzheimer's disease (AD) within 4 years of follow-up. METHODS: We estimated the incidence of AD in 60 patients presenting with aMCI, 115 patients suffering of LLD treated with antidepressants with good compliance, and 66 healthy control (HC) patients, followed for 4 years. RESULTS: The risk to develop AD, within 4 years, was 68.33% for aMCI and 49.57% for LLD. In AD patients 5.60% deteriorated without depression, and 72.20% deteriorated with depression after 4 years of follow-up (p < 0.0001). No HC patients deteriorated to AD or any other dementia type. CONCLUSION: In our results, aMCI was the first predictive condition that increased the risk to develop AD. Depression is a potentially preventable medical condition across the lifespan and may be a modifiable risk factor.

Matrix effect on baked egg tolerance in children with IgE-mediated hen's egg allergy.

BACKGROUND: Children with IgE-mediated hen's egg allergy (IgE-HEA) often tolerate baked egg within a wheat matrix. OBJECTIVE: To evaluate the influence of wheat matrix and the effects of little standardized cooking procedures on baked egg tolerance. METHODS: Fifty-four children with IgE-HEA were enrolled. They underwent prick-by-prick (PbP) tests and open oral food challenges (OFC) performed with baked HE within a wheat matrix (a home-made cake, locally called ciambellone), baked HE without a wheat matrix (in the form of an omelet, locally named frittata) and boiled HE. Three months after passing ciambellone OFC, parents were asked to answer a survey. RESULTS: About 88% of children tolerated ciambellone, 74% frittata, and 56% boiled HE. Negative predictive value of PbP performed with ciambellone, frittata, and boiled HE was 100%. No IgE-mediated adverse reactions were detected at follow-up carried out by the survey. CONCLUSIONS: Wheat matrix seemed to be relevant only in few cases. If our results will be confirmed by larger studies, a negative PbP with ciambellone, frittata, or boiled HE will allow patients with IgE-HEA to eat these foods without undergoing OFC. Moreover, our study showed that very strict standardized cooking procedures do not seem to be essential, to guarantee tolerance toward baked HE.

Grass pollen sublingual immunotherapy and paediatric allergic rhinitis: A patient-oriented decision.

Guidelines and systematic review report that allergen immunotherapy (AIT) is, in general, effective in the treatment of allergic rhinitis. However, experts suggest not generalising the results of different clinical studies: for example, it would not be advisable to translate the results found in an adult population to a paediatric population or the results on the efficacy of AIT against a specific allergen to the AIT against a different allergen. Moreover, according to Evidence Based Medicine (EBM), clinical decisions are individualised and should derive from the "integration of best research evidence with clinical expertise and patient values". Taking into account the high specificity of the AIT and EBM principles, we tried to answer the question on how advisable it is to prescribe the AIT for the management of grass allergic rhinitis in children. To do this, we revised the scientific literature in order to solve a specific case scenario.

The Politics of Attachment: Lines of Flight with Bowlby, Deleuze and Guattari.

Research on attachment is widely regarded in sociology and feminist scholarship as politically conservative - oriented by a concern to police families, pathologize mothers and emphasize psychological at the expense of socio-economic factors. These critiques have presented attachment theory as constructing biological imperatives to naturalize contingent, social demands. We propose that a more effective critique of the politically conservative uses of attachment theory is offered by engaging with the 'attachment system' at the level of ontology. In developing this argument we draw on Deleuze and Guattari, making use of the common language of ethology which links their ideas to that of attachment theory. The attachment system can and has been reified into an image of the infant returning to their caregiver as an image of familial sufficiency. This has offered ammunition for discourses and institutions which isolate women from health, social and political resources. Yet Deleuze and Guattari can help attachment theory and research to be recognized as a powerful ally for progressive politics, for reflection on the movement of human individuation, and for arguing for the meaningful resourcing of those who care for someone else.

Chronic food protein-induced enterocolitis syndrome caused by cow's milk proteins passed through breast milk.

We describe 2 cases of food protein-induced enterocolitis syndrome (FPIES) caused by cow's milk (CM) passed through breast milk. The onset in both cases was characterized by chronic symptoms (regurgitation, colic, diarrhea, failure to thrive); in one patient, two acute episodes due to the direct consumption of CM formula by the infant were also reported. The diagnosis of FPIES through breast milk can be easily overlooked, especially in milder cases. We also discuss some important issues concerning the general management of the disease. In conclusion, (1) the diagnosis of chronic FPIES should be taken into account even in exclusively breast-fed infants who present suggestive symptoms such as persistent regurgitation, small amounts of vomiting, lethargy, failure to thrive, dehydration, diarrhea (sometimes bloody) and abdominal distention. A 2-week maternal elimination diet should be considered even in apparently mild cases. (2) CM seems to be the most frequently reported culprit food. (3) In those cases in which acute FPIES is elicited by the direct consumption of the culprit food in breast-fed infants, maternal diet may be unrestricted.

Ondansetron for food protein-induced enterocolitis syndrome.

Recently, a study on 5 patients [Holbrook et al.: J Allergy Clin Immunol 2013;132:1219-1220] documented the efficacy of the intravenous administration of ondansetron in children with acute symptoms due to food protein-induced enterocolitis syndrome (FPIES). We report on the experience at our institution using ondansetron during oral food challenge (OFC) in 5 children affected by FPIES. In all 5 cases, the use of intramuscular ondansetron led to a complete and rapid resolution of symptoms within 15 min. Intramuscular administration, without the need for intravenous access for an infusion or steroid administration, enables this therapy to be easily performed, even at home (i.e. out of a hospital setting). A home treatment with ondansetron cannot be considered as an alternative to a medical examination with eventual treatment in hospital, which is advised after any acute episode of FPIES. We consider ondansetron to be very useful in the management of acute FPIES. Further study is required to confirm its efficacy.

Constipation and cow's milk allergy: a review of the literature.

The causal association between cow's milk allergy (CMA) and constipation is not well established. Some guidelines describe constipation as a possible symptom of CMA, while others do not mention it. We conducted a literature review and found 10 prospective clinical trials. In all of them, an oral food challenge was performed, and 2 of them were randomized. These studies reported that a cow's milk (CM) protein-free diet has a beneficial effect on constipation, with a rate of successful outcomes ranging from 28 to 78%. The hypothetic pathogenic mechanism lies in increased anal pressure at rest, probably caused by allergic inflammation of the internal sphincter area due to mucosal eosinophil and mast cell infiltration. Eighty percent of patients reach tolerance within 1 year after the diagnosis of CMA-related constipation. We believe that a CM-free diet for 2-4 weeks should be proposed for children with chronic functional constipation, even if it is not severe or resistant to laxatives.

Explanation for symptoms and biographical repair in a clinic for persistent physical symptoms.

Introduction: Biographical disruption describes the process by which illness impacts not just on a person's body and their participation in activities, but also on their sense of self. Biographical disruption is often followed by a process of biographical repair in which identity is reconstructed and a new normality is restored. People with persistent physical symptoms (sometimes referred to as medically unexplained symptoms) experience biographical disruption. This can be complicated by lack of explanation and the implication that if the problem is not medical, then it might be the person/psychological. We aimed to examine this tension in people attending a novel "Symptoms Clinic" for people with persistent physical symptoms. Methods: This study reports an embedded qualitative study in a UK based randomised controlled trial. Data were collected by audio recordings of consultations and semi-structured interviews with patients. We used theoretically informed thematic analysis with regular coding and discussion meetings of the analysis team. This analysis explores the role of intervention components in facilitating biographical repair. Results: The lack of acceptable explanation for persistent symptoms acted as a block to biographical repair. In the clinic, multi-layered explanations were offered and negotiated that viewed persistent symptoms as understandable entities rather than as indicators of something still hidden. These explanations allowed study participants to make sense of their symptoms and in turn opened new opportunities for self-management. The result was that participants were able to reframe their symptoms in a way that enabled them to see themselves differently. Even if symptoms had not yet improved, there was a sense of being better. This can be understood as a process of biographical repair. Conclusion: Explaining persistent physical symptoms enables biographical repair.

Recognition, explanation, action, learning: Teaching and delivery of a consultation model for persistent physical symptoms.

OBJECTIVE: To describe the teaching and delivery of an extended consultation model designed for clinicians to use with patients with persistent physical symptoms and functional disorders. The model is underpinned by current scientific knowledge about persistent physical symptoms and the communication problems that arise in dealing with them. METHODS: Process evaluation of training and delivery of the Recognition, Explanation, Action, Learning (REAL) model within the Multiple Symptoms Study 3: a randomised controlled trial of an extended-role GP "Symptoms Clinic". Evaluation used clinician and patient interviews and consultation transcripts. RESULTS: 7 GPs were trained in the intervention and 6 of them went on to deliver the REAL model in Symptoms Clinics either face-to-face or online. The Symptoms Clinic provided a set of 4 extended consultations to approximately 170 patients. Evaluation of training indicated that there was a considerable load in terms of new knowledge and skills. Evaluation of delivery found clinicians could adapt the model to individual patients while maintaining a high level of fidelity to its core components. CONCLUSION: REAL is a teachable consultation model addressing specific clinical communication issues for people with persistent physical symptoms. PRACTICE IMPLICATIONS: REAL enables clinicians to explain persistent physical symptoms in a beneficial way.

Sjögren's syndrome: a systemic autoimmune disease.

Sjögren's syndrome is a chronic autoimmune disease characterized by ocular and oral dryness resulting from lacrimal and salivary gland dysfunction. Besides, a variety of systemic manifestations may occur, involving virtually any organ system. As a result, the disease is characterized by pleomorphic clinical manifestations whose characteristics and severity may vary greatly from one patient to another. Sjögren's syndrome can be defined as primary or secondary, depending on whether it occurs alone or in association with other systemic autoimmune diseases, respectively. The pathogenesis of Sjögren's syndrome is still elusive, nevertheless, different, not mutually exclusive, models involving genetic and environmental factors have been proposed to explain its development. Anyhow, the emergence of aberrant autoreactive B-lymphocytes, conducting to autoantibody production and immune complex formation, seems to be crucial in the development of the disease. The diagnosis of Sjögren's syndrome is based on characteristic clinical signs and symptoms, as well as on specific tests including salivary gland histopathology and autoantibodies. Recently, new classification criteria and disease activity scores have been developed primarily for research purposes and they can also be useful tools in everyday clinical practice. Treatment of Sjögren's syndrome ranges from local and symptomatic therapies aimed to control dryness to systemic medications, including disease-modifying agents and biological drugs. The objective of this review paper is to summarize the recent literature on Sjögren's syndrome, starting from its pathogenesis to current therapeutic options.

Involvement of Il-33 in the Pathogenesis and Prognosis of Major Respiratory Viral Infections: Future Perspectives for Personalized Therapy.

Interleukin (IL)-33 is a key cytokine involved in type-2 immunity and allergic airway disease. At the level of lung epithelial cells, where it is clearly expressed, IL-33 plays an important role in both innate and adaptive immune responses in mucosal organs. It has been widely demonstrated that in the course of respiratory virus infections, the release of IL-33 increases, with consequent pro-inflammatory effects and consequent exacerbation of the clinical symptoms of chronic respiratory diseases. In our work, we analyzed the pathogenetic and prognostic involvement of IL-33 during the main respiratory viral infections, with particular interest in the recent SARS-CoV-2virus pandemic and the aim of determining a possible connection point on which to act with a targeted therapy that is able to improve the clinical outcome of patients.