Enabling usable science takes a community: Using our roles as funders to catalyze change.

Calls to support co-designed and usable science to inform management of natural resources are growing. Making the shift will require diverse collaborations between those who hold, share, and use knowledge.

When trust is lost: the impact of interpersonal trauma on social interactions.

BACKGROUND: Trauma due to deliberate harm by others is known to increase the likelihood of developing Post-Traumatic Stress Disorder (PTSD). This is the first study investigating basic and dynamic trust in 'interpersonal' PTSD. METHODS: Thirty-two participants with PTSD and 22 healthy controls played a novel multi-round version of a monetary investment protocol, the so-called 'Trust Game', a task from the behavioural economics literature, which is considered to involve trust and reciprocity. We used two 'Trust Games' including cooperative and unfair partners. RESULTS: Findings showed an effect for lower basic investment in PTSD compared to healthy controls, that trended towards significance (p = 0.09). All participants showed behavioural flexibility and modified their trust based on behavioural cues from their cooperative and unfair game partners. However, participants with PTSD made significantly lower investments towards the cooperative partner than controls. Investments towards the unfair partner did not differ between groups. Higher trauma scores were associated with lower levels of trust-related investments towards the cooperative but not the unfair game partner. CONCLUSION: The association between reduced trust towards cooperative others in individuals who experienced interpersonal trauma could indicate acquired insensitivity to social rewards or inflexible negative beliefs about others as a sequel of the traumatic experience, which increases in a dose response relationship with the severity of the trauma. A specific focus on cooperation and trusting behaviour could provide a treatment target for future cognitive and pharmacological interventions.

Regulation, circulation and distribution of penicillin in Portugal (1944-1954).

Portugal did not participate in World War II but was one of the first countries in the world to receive penicillin for civilian use. The Portuguese Red Cross began to import the antibiotic from the United States of America in 1944 and appointed a controlling committee to oversee its distribution, due to the small amount available. In 1945, as world production increased, penicillin began to be distributed through the normal channels. An important role in its regulation was played by the official department responsible for controlling pharmaceutical and chemical products in Portugal, the Comissão Reguladora dos Produtos Químicos e Farmacêuticos (Regulatory Committee for Chemical and Pharmaceutical Products). Penicillin was imported as a raw material from 1947 and the first medicaments containing penicillin, prepared in Portugal, were released into the commercial circuit in 1948. A laboratory had been established in 1942 by the Comissão Reguladora for the analytical verification of medicaments and medicinal products with the aim of certifying their quality and minimizing the number of products with no attested therapeutic efficacy. The number of medicaments analysed by this laboratory increased substantially from 72 in the year of its foundation (1942) to 2478 in 1954, including, after 1948, medicaments containing penicillin. The aim of the present paper was to elucidate the role of the Comissão Reguladora dos Produtos Químicos e Farmacêuticos in regulating and controlling the distribution of penicillin in Portugal during the 1940s and 1950s.

[The history of Pharmacy in Portugal (1900-1950) : pharmaceutical industry and community pharmacy ].

The aim of this article is to present the history of pharmacy in Portugal during the first half of the twentieth century, considering two contemporary issues : the industrialization of medicines in Portugal, with regard to law and regulation of medicines and professional activity (emphasizing community pharmacy) and other relevant issues concerning pharmacy and public health.

The imprecision of micronutrient requirement values: the example of vitamin D.

Food, not nutrients, is the fundamental unit in nutrition. Nutrient requirement values and recommended daily intakes have long been determined and organized in tables by several regulators. These figures, however, overlook the complexity of mixing different foods in a diet and the mediation by human gut microbiota on digestion, metabolism, and health. The microbiome molecular mechanisms and its potential influence on nutrient requirements are far from clear. Guidelines should depend on the sort of intake, along with the dietary habits, rather than focusing on single nutrients. Despite many decades of attempts to investigate the proximate nutrient composition of foods consumed by different world populations, there are still neither standardization of food composition databases nor harmonized dietary intake methods of assessment of nutrients. No all-inclusive attempt was yet made to emphasize the requirements of the various micronutrients, phytonutrients, and non-nutrients on gut microbiota and vice versa, and thereafter reflected into dietary guidelines. New multifaceted methods have been advanced to reevaluate the way nutrients and nutrient requirements are assessed within the intricate biological systems. Our main goal here was to enhance the fact that existing food guidelines hold inherent strengths and limitations but fail, in many aspects, namely, in not taking into account essential geographical, ethnic and cultural differences, and the different stages of life, infant nutrition, and the microbiota impact on several micronutrient requirements. Vitamin D is given as an illustration on present inaccuracy of its requirements. Defining dietary reference intakes is therefore an ongoing process specific for each population.

Sickle Cell Disease Update: New Treatments and Challenging Nutritional Interventions.

Sickle cell disease (SCD), a distinctive and often overlooked illness in the 21st century, is a congenital blood disorder characterized by considerable phenotypic diversity. It comprises a group of disorders, with sickle cell anemia (SCA) being the most prevalent and serious genotype. Although there have been some systematic reviews of global data, worldwide statistics regarding SCD prevalence, morbidity, and mortality remain scarce. In developed countries with a lower number of sickle cell patients, cutting-edge technologies have led to the development of new treatments. However, in developing settings where sickle cell disease (SCD) is more prevalent, medical management, rather than a cure, still relies on the use of hydroxyurea, blood transfusions, and analgesics. This is a disease that affects red blood cells, consequently affecting most organs in diverse manners. We discuss its etiology and the advent of new technologies, but the aim of this study is to understand the various types of nutrition-related studies involving individuals suffering from SCD, particularly in Africa. The interplay of the environment, food, gut microbiota, along with their respective genomes collectively known as the gut microbiome, and host metabolism is responsible for mediating host metabolic phenotypes and modulating gut microbiota. In addition, it serves the purpose of providing essential nutrients. Moreover, it engages in direct interactions with host homeostasis and the immune system, as well as indirect interactions via metabolites. Nutrition interventions and nutritional care are mechanisms for addressing increased nutrient expenditures and are important aspects of supportive management for patients with SCD. Underprivileged areas in Sub-Saharan Africa should be accompanied by efforts to define and promote of the nutritional aspects of SCD. Their importance is key to maintaining well-being and quality of life, especially because new technologies and products remain limited, while the use of native medicinal plant resources is acknowledged.

Modelling terrigenous DOC across the north west European Shelf: Fate of riverine input and impact on air-sea CO2 fluxes.

Terrigenous carbon in aquatic systems is increasingly recognised as an important part of the global carbon cycle. Despite this, the fate and distribution of terrigenous dissolved organic carbon (tDOC) in coastal and oceanic systems is poorly understood. We have implemented a theoretical framework for the degradation of tDOC across the land to ocean continuum in a 3D hydrodynamical-biogeochemical model on the North West European Shelf. A key feature of this model is that both photochemical and bacterial tDOC degradation rates are age dependant constituting an advance in our ability to describe carbon cycling in the marine environment. Over the time period 1986-2015, 182±17 Gmol yr-1 of riverine tDOC is input to the shelf. Results indicate that bacterial degradation is by far the most important process in removing tDOC on the shelf, contributing to 73±6 % (132±11 Gmol yr-1) of the total removal flux, while 21±3 % (39±6 Gmol yr-1) of riverine tDOC was advected away from the shelf and photochemical degradation removing 5±0.5 % of the riverine flux. Explicitly including tDOC in the model decreased the air-sea carbon dioxide (CO2) flux by 112±8 Gmol yr-1 (4±0.4 %), an amount approximately equivalent to the CO2 released by the UK chemical industry in 2020. The reduction is equivalent to 62 % of the riverine tDOC input to the shelf while approximately 17 % of riverine input is incorporated into the foodweb. This work can improve the assumptions of the fate of tDOC by Earth System Models and demonstrates that the inclusion of tDOC in models can impact ecosystem dynamics and change predicted global carbon budgets for the ocean.

An Overview of Biosimilars-Development, Quality, Regulatory Issues, and Management in Healthcare.

Biological therapies have transformed high-burden treatments. As the patent and exclusivity period for biological medicines draws to a close, there is a possibility for the development and authorization of biosimilars. These products boast comparable levels of safety, quality, and effectiveness to their precursor reference products. Biosimilars, although similar to reference products, are not identical copies and should not be considered generic substitutes for the original. Their development and evaluation involve a rigorous step-by-step process that includes analytical, functional, and nonclinical evaluations and clinical trials. Clinical studies conducted for biosimilars aim to establish similar efficacy, safety, and immunogenicity, rather than demonstrating a clinical benefit, as with the reference product. However, although the current knowledge regarding biosimilars has significantly increased, several controversies and misconceptions still exist regarding their immunogenicity, extrapolation, interchangeability, substitution, and nomenclature. The development of biosimilars stimulates market competition, contributes toward healthcare sustainability, and allows for greater patient access. However, maximizing the benefits of biosimilars requires cooperation between regulators and developers to ensure that patients can benefit quickly from access to these new therapeutic alternatives while maintaining high standards of quality, safety, and efficacy. Recognizing the inherent complexities of comprehending biosimilars fully, it is essential to focus on realistic approaches, such as fostering open communication between healthcare providers and patients, encouraging informed decision-making, and minimizing risks. This review addresses the regulatory and manufacturing requirements for biosimilars and provides clinicians with relevant insights for informed prescribing.

Laparoscopic cholecystectomy versus conservative management for adults with uncomplicated symptomatic gallstones: the C-GALL RCT.

Background: Gallstone disease is a common gastrointestinal disorder in industrialised societies. The prevalence of gallstones in the adult population is estimated to be approximately 10-15%, and around 80% remain asymptomatic. At present, cholecystectomy is the default option for people with symptomatic gallstone disease. Objectives: To assess the clinical and cost-effectiveness of observation/conservative management compared with laparoscopic cholecystectomy for preventing recurrent symptoms and complications in adults presenting with uncomplicated symptomatic gallstones in secondary care. Design: Parallel group, multicentre patient randomised superiority pragmatic trial with up to 24 months follow-up and embedded qualitative research. Within-trial cost-utility and 10-year Markov model analyses. Development of a core outcome set for uncomplicated symptomatic gallstone disease. Setting: Secondary care elective settings. Participants: Adults with symptomatic uncomplicated gallstone disease referred to a secondary care setting were considered for inclusion. Interventions: Participants were randomised 1: 1 at clinic to receive either laparoscopic cholecystectomy or observation/conservative management. Main outcome measures: The primary outcome was quality of life measured by area under the curve over 18 months using the Short Form-36 bodily pain domain. Secondary outcomes included the Otago gallstones' condition-specific questionnaire, Short Form-36 domains (excluding bodily pain), area under the curve over 24 months for Short Form-36 bodily pain domain, persistent symptoms, complications and need for further treatment. No outcomes were blinded to allocation. Results: Between August 2016 and November 2019, 434 participants were randomised (217 in each group) from 20 United Kingdom centres. By 24 months, 64 (29.5%) in the observation/conservative management group and 153 (70.5%) in the laparoscopic cholecystectomy group had received surgery, median time to surgery of 9.0 months (interquartile range, 5.6-15.0) and 4.7 months (interquartile range 2.6-7.9), respectively. At 18 months, the mean Short Form-36 norm-based bodily pain score was 49.4 (standard deviation 11.7) in the observation/conservative management group and 50.4 (standard deviation 11.6) in the laparoscopic cholecystectomy group. The mean area under the curve over 18 months was 46.8 for both groups with no difference: mean difference -0.0, 95% confidence interval (-1.7 to 1.7); p-value 0.996; n = 203 observation/conservative, n = 205 cholecystectomy. There was no evidence of differences in quality of life, complications or need for further treatment at up to 24 months follow-up. Condition-specific quality of life at 24 months favoured cholecystectomy: mean difference 9.0, 95% confidence interval (4.1 to 14.0), p < 0.001 with a similar pattern for the persistent symptoms score. Within-trial cost-utility analysis found observation/conservative management over 24 months was less costly than cholecystectomy (mean difference -£1033). A non-significant quality-adjusted life-year difference of -0.019 favouring cholecystectomy resulted in an incremental cost-effectiveness ratio of £55,235. The Markov model continued to favour observation/conservative management, but some scenarios reversed the findings due to uncertainties in longer-term quality of life. The core outcome set included 11 critically important outcomes from both patients and healthcare professionals. Conclusions: The results suggested that in the short term (up to 24 months) observation/conservative management may be a cost-effective use of National Health Service resources in selected patients, but subsequent surgeries in the randomised groups and differences in quality of life beyond 24 months could reverse this finding. Future research should focus on longer-term follow-up data and identification of the cohort of patients that should be routinely offered surgery. Trial registration: This trial is registered as ISRCTN55215960. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/192/71) and is published in full in Health Technology Assessment; Vol. 28, No. 26. See the NIHR Funding and Awards website for further award information.

The C-GALL study assessed the benefits, in terms of symptoms, quality of life and costs, of cholecystectomy versus observation (conservative management: by the patient and general practitioner that might include dietary advice and pain management and surgery if needed). Four hundred and thirty-four patients with symptomatic gallstones were randomly allocated surgery or conservative management. The main symptom of ongoing bodily pain and some other quality-of-life measures were assessed over the next 2 years using postal questionnaires. After 2 years, 70% of those allocated to surgery had been operated on and 37% of the observation group either had an operation or were waiting for one. There was no difference in bodily pain or overall quality of life between the groups. However, participants in the surgery group reported fewer ongoing problems related to their gallstone disease or after surgery than those in the conservative management group. Surgery was, however, more costly than conservative management. The C-GALL study has shown that for some patients, a conservative management approach may be a sufficient and less costly way of managing their gallstone symptoms rather than going straight on the waiting list for surgery. More research is needed to identify which patients benefit most from surgery.

Refugee and Asylum Seeker Communities and Access to Mental Health Support: A Local Case Study.

The complex mental health needs of refugee and asylum seeker (RAS) communities, often resulting from past trauma, are not met by overburdened and inadequate service provision. Pre-displacement, in-transit, and post-settlement traumas create a specific set of mental health needs which underfunded mental health services often cannot meet, despite the illusion of access to a range of services. This paper aims to explore how a range of stakeholders responded to inadequate provision at the local level. Interviews and focus groups with regional stakeholders, charities and RAS community groups, which were conducted as part of wider mixed-methods project on international migration in Northern England, revealed several gaps in provision. Findings indicate that charities and community groups are often left to fill the gap and provide signposting and liaison with local authorities. However, these groups are often ill-equipped to provide sufficient support but the absence of commissioned services leaves limited options. We conclude by suggesting that further research is necessary on trauma, RAS communities, and the pathways to mental health support.

Do loneliness and social exclusion breed paranoia? An experience sampling investigation across the psychosis continuum.

Background: The role of loneliness and social exclusion in the development of paranoia is largely unexplored. Negative affect may mediate potential associations between these factors. We investigated the temporal relationships of daily-life loneliness, felt social exclusion, negative affect, and paranoia across the psychosis continuum. Method: Seventy-five participants, including 29 individuals with a diagnosis of non-affective psychosis, 20 first-degree relatives, and 26 controls used an Experience Sampling Method (ESM) app to capture the fluctuations in loneliness, feelings of social exclusion, paranoia, and negative affect across a 1-week period. Data were analysed with multilevel regression analyses. Results: In all groups, loneliness and feelings of social exclusion were independent predictors of paranoia over time (b = 0.05, p < .001 and b = 0.04, p < .05, respectively). Negative affect predicted paranoia (b = 0.17, p < .001) and partially mediated the associations between loneliness, social exclusion, and paranoia. It also predicted loneliness (b = 0.15, p < .0001), but not social exclusion (b = 0.04, p = .21) over time. Paranoia predicted social exclusion over time, with more pronounced effects in controls (b = 0.43) than patients (b = 0.19; relatives: b = 0.17); but not loneliness (b = 0.08, p = .16). Conclusion: Paranoia and negative affect worsen in all groups following feelings of loneliness and social exclusion. This highlights the importance of a sense of belonging and being included for mental well-being. Loneliness, feeling socially excluded, and negative affect were independent predictors of paranoid thinking, suggesting they represent useful targets in its treatment.

An Update on Drug-Nutrient Interactions and Dental Decay in Older Adults.

In recent decades, the global demographic landscape has undergone a discernible shift that has been characterised by a progressive increase in the proportion of elderly individuals, indicative of an enduring global inclination toward extended lifespans. The aging process, accompanied by physiological changes and dietary patterns, contributes to detrimental deviations in micronutrient consumption. This vulnerable aging population faces heightened risks, including dental caries, due to structural and functional modifications resulting from insufficient nutritional sustenance. Factors such as physiological changes, inadequate nutrition, and the prevalence of multiple chronic pathologies leading to polypharmacy contribute to the challenge of maintaining an optimal nutritional status. This scenario increases the likelihood of drug interactions, both between medications and with nutrients and the microbiome, triggering complications such as dental decay and other pathologies. Since the drug industry is evolving and new types of food, supplements, and nutrients are being designed, there is a need for further research on the mechanisms by which drugs interfere with certain nutrients that affect homeostasis, exemplified by the prevalence of caries in the mouths of older adults. Infectious diseases, among them dental caries, exert serious impacts on the health and overall quality of life of the elderly demographic. This comprehensive review endeavours to elucidate the intricate interplay among drugs, nutrients, the microbiome, and the oral cavity environment, with the overarching objective of mitigating the potential hazards posed to both the general health and dental well-being of older adults. By scrutinising and optimising these multifaceted interactions, this examination aims to proactively minimise the susceptibility of the elderly population to a spectrum of health-related issues and the consequences associated with dental decay.

Effectiveness of conservative management versus laparoscopic cholecystectomy in the prevention of recurrent symptoms and complications in adults with uncomplicated symptomatic gallstone disease (C-GALL trial): pragmatic, multicentre randomised controlled trial.

OBJECTIVE: To assess the clinical and cost effectiveness of conservative management compared with laparoscopic cholecystectomy for the prevention of symptoms and complications in adults with uncomplicated symptomatic gallstone disease. DESIGN: Parallel group, pragmatic randomised, superiority trial. SETTING: 20 secondary care centres in the UK. PARTICIPANTS: 434 adults (>18 years) with uncomplicated symptomatic gallstone disease referred to secondary care, assessed for eligibility between August 2016 and November 2019, and randomly assigned (1:1) to receive conservative management or laparoscopic cholecystectomy. INTERVENTIONS: Conservative management or surgical removal of the gallbladder. MAIN OUTCOME MEASURES: The primary patient outcome was quality of life, measured by area under the curve, over 18 months using the short form 36 (SF-36) bodily pain domain, with higher scores (range 0-100) indicating better quality of life. Other outcomes included costs to the NHS, quality adjusted life years (QALYs), and incremental cost effectiveness ratio. RESULTS: Of 2667 patients assessed for eligibility, 434 were randomised: 217 to the conservative management group and 217 to the laparoscopic cholecystectomy group. By 18 months, 54 (25%) participants in the conservative management arm and 146 (67%) in the cholecystectomy arm had received surgery. The mean SF-36 norm based bodily pain score was 49.4 (standard deviation 11.7) in the conservative management arm and 50.4 (11.6) in the cholecystectomy arm. The SF-36 bodily pain area under the curve up to 18 months did not differ (mean difference 0.0, 95% confidence interval -1.7 to 1.7; P=1.00). Conservative management was less costly (mean difference -£1033, (-$1334; -€1205), 95% credible interval -£1413 to -£632) and QALYs did not differ (mean difference -0.019, 95% credible interval -0.06 to 0.02). CONCLUSIONS: In the short term (≤18 months), laparoscopic surgery is no more effective than conservative management for adults with uncomplicated symptomatic gallstone disease, and as such conservative management should be considered as an alternative to surgery. From an NHS perspective, conservative management may be cost effective for uncomplicated symptomatic gallstone disease. As costs, complications, and benefits will continue to be incurred in both groups beyond 18 months, future research should focus on longer term follow-up to establish effectiveness and lifetime cost effectiveness and to identify the cohort of patients who should be routinely offered surgery. TRIAL REGISTRATION: ISRCTN registry ISRCTN55215960.

Pharmacist Intervention in Portuguese Older Adult Care.

Healthy ageing has become one of the most significant challenges in a society with an increasing life expectancy. Older adults have a greater prevalence of chronic disease, with the need for multiple medications to appropriately control these issues. In addition to their health concerns, ageing individuals are prone to loneliness, dependence, and economic issues, which may affect their quality of life. Governments and health professionals worldwide have developed various strategies to promote active and healthy ageing to improve the quality of life of older adults. Pharmacists are highly qualified health professionals, easily accessible to the population, thus playing a pivotal role in medication management. Their proximity to the patient puts them in a unique position to provide education and training to improve therapeutic adherence and identify medication-related problems. This paper aims to address the importance of Portuguese community pharmacists in the medication management of older adults, emphasising their intervention in health promotion, patient education, medication-related problems, deprescription, dose administration aids, and medication review and reconciliation. We also discuss home delivery services and medication management in long-term care facilities.

Characterisation of institutionalised Portuguese older adult fallers: is there a place for pharmacist intervention? A preliminary study.

Background: Falls are a major public health issue, given their prevalence and social impact. Older adults living in long-term care facilities (LTCF) are at greater risk of injury resulting from a fall due to multiple factors, such as nutritional, functional/cognitive impairment, postural instability, polypharmacy, and the presence of potentially inappropriate medications (PIMs). Medication management in LTCF is complex and often sub-optimal and might be crucial for falls. Pharmacist intervention is important, since they have a unique knowledge of medication. However, studies mapping the impact of pharmaceutical activities in Portuguese LTC settings are scarce. Objective: This study aims to assess the characteristics of older adult fallers living in LTFCs and examine the relationship between falling and several factors in this population. We also intend to explore the prevalence of PIMs and their relationship with the occurrence of falls. Methods: The study was conducted in two long-term care facilities for elderly people, in the central region of Portugal. We included patients aged 65 and older with no reduced mobility or physical weakness and with the ability to understand spoken and written Portuguese. The following information was assessed: sociodemographic characteristics, comorbidities, polypharmacy, fear of falling, functional, nutritional and cognitive status. PIMs were evaluated according to the Beers criteria (2019). Results: A total of 69 institutionalised older adults, 45 women and 24 men, with a mean age of 83.14 ± 8.87 years were included. The prevalence of falls was 21.74% Out of these, 46.67% (n=7) fell once, 13.33% (n=2) fell twice, and 40% (n=6) fell 3 or more times. Fallers were mainly women, had lower levels of education, were well nourished, had moderate to severe levels of dependence, and displayed moderate cognitive impairment. All adult fallers had a fear of falling. The main comorbidities of this population were related to the cardiovascular system. Polypharmacy was present in every patient, and at least one PIM was identified in 88.41% of the subjects. Fear of falling (FOF) and cognitive impairment (in subjects with 1 to 11 years of education) showed statistically significant associations with the occurrence of falls (p=0.005 and p=0.05, respectively). No significant differences were found between fallers and non-fallers for any other factors. Conclusions: This present study is a preliminary contribution to characterise a group of older adult fallers living in Portuguese LTCFs and demonstrated that fear of falling and cognitive impairment are associated with the occurrence of falls in this population. The high prevalence of polypharmacy and PIMs emphasises the need for tailored interventions featuring the collaboration of a pharmacist to optimise medication management in this population.

Application of nanotechnology in management and treatment of diabetic wounds.

Diabetic wounds are one of the most common health problems worldwide, enhancing the demand for new management strategies. Nanotechnology, as a developing subject in diabetic wound healing, is proving to be a promising and effective tool in treatment and care. It is, therefore, necessary to ascertain the available and distinct nanosystems and evaluate their performance when topically applied to the injury site, especially in diabetic wound healing. Several active ingredients, including bioactive ingredients, growth factors, mesenchymal stem cells, nucleic acids, and drugs, benefit from improved properties when loaded into nanosystems. Given the risk of problems associated with systemic administration, the topical application should be considered, provided stability and efficacy are assured. After nanoencapsulation, active ingredients-loaded nanosystems have been showing remarkable features of biocompatibility, healing process hastening, angiogenesis, and extracellular matrix compounds synthesis stimulation, contributing to a decrease in wound inflammation. Despite limitations, nanotechnology has attracted widespread attention in the scientific community and seems to be a valuable technological ally in the treatment and dressing of diabetic wounds. The use of nanotechnology in topical applications enables efficient delivery of the active ingredients to the specific skin site, increasing their bioavailability, stability, and half-life time, without compromising their safety.

Reducing asthma attacks in children using exhaled nitric oxide (RAACENO) as a biomarker to inform treatment strategy: a multicentre, parallel, randomised, controlled, phase 3 trial.

BACKGROUND: The benefit of fractional exhaled nitric oxide (FeNO) in guiding asthma treatment is uncertain. We evaluated the efficacy of adding FeNO to symptom-guided treatment in children with asthma versus only symptom-guided treatment. METHODS: RAACENO was a multicentre, parallel, randomised, controlled, phase 3 trial done in 35 secondary care centres and 17 primary care recruitment sites (only seven primary care sites managed to recruit patients) in the UK. Patients with a confirmed asthma diagnosis, aged 6-15 years, prescribed inhaled corticosteroids, and who received a course of oral corticosteroids for at least one asthma exacerbation during the 12 months before recruitment were included. Participants were randomly assigned to either FeNO plus symptom-guided treatment (intervention) or symptom-guided treatment alone (standard care) using a 24 h in-house, web-based randomisation system. Participants and the clinical and research teams were not masked to the group allocation. A web-based algorithm gave treatment recommendations based on the Asthma Control Test (ACT) or Childhood ACT (CACT) score; current asthma treatment; adherence to study treatment in the past 3 months; and use of FeNO (in the intervention group). Follow-up occurred at 3-month intervals for 12 months. The primary outcome was any asthma exacerbation treated with oral corticosteroids in the 12 months after randomisation, assessed in the intention-to-treat population. This study is registered with the International Standard Randomised Controlled Trial Registry, ISRCTN67875351. FINDINGS: Between June 22, 2017, and Aug 8, 2019, 535 children were assessed for eligibility, 20 were ineligible and six were excluded post-randomisation. 509 children were recruited and at baseline, the mean age of participants was 10·1 years (SD 2·6), and 308 (60·5%) were male. The median FeNO was 21 ppb (IQR 10-48), mean predicted FEV1 was 89·6% (SD 18·0), and median daily dose of inhaled corticosteroids was 400 µg budesonide equivalent (IQR 400-1000). Asthma was partly or fully controlled in 256 (50·3%) of 509 participants. The primary outcome, which was available for 506 (99%) of 509 participants, occurred in 123 (48·2%) of 255 participants in the intervention group and 129 (51·4%) of 251 in the standard care group, the intention-to-treat adjusted odds ratio (OR) was 0·88 (95% CI 0·61 to 1·27; p=0·49). The adjusted difference in the percentage of participants who received the intervention in whom the primary outcome occurred compared with those who received standard care was -3·1% (-11·9% to 5·6%). In 377 (21·3%) of 1771 assessments, the algorithm recommendation was not followed. Adverse events were reported by 27 (5·3%) of 509 participants (15 in the standard care group and 12 in the intervention group). The most common adverse event was itch after skin prick testing (reported by eight participants in each group). INTERPRETATION: We found that the addition of FeNO to symptom-guided asthma treatment did not lead to reduced exacerbations among children prone to asthma exacerbation. Asthma symptoms remain the only tool for guiding treatment decisions. FUNDING: National Institute for Health Research.

In the eye of the beholder? Oxytocin effects on eye movements in schizophrenia.

BACKGROUND: Individuals with schizophrenia have difficulty in extracting salient information from faces. Eye-tracking studies have reported that these individuals demonstrate reduced exploratory viewing behaviour (i.e. reduced number of fixations and shorter scan paths) compared to healthy controls. Oxytocin has previously been demonstrated to exert pro-social effects and modulate eye gaze during face exploration. In this study, we tested whether oxytocin has an effect on visual attention in patients with schizophrenia. METHODS: Nineteen male participants with schizophrenia received intranasal oxytocin 40UI or placebo in a double-blind, placebo-controlled, crossover fashion during two visits separated by seven days. They engaged in a free-viewing eye-tracking task, exploring images of Caucasian men displaying angry, happy, and neutral emotional expressions; and control images of animate and inanimate stimuli. Eye-tracking parameters included: total number of fixations, mean duration of fixations, dispersion, and saccade amplitudes. RESULTS: We found a main effect of treatment, whereby oxytocin increased the total number of fixations, dispersion, and saccade amplitudes, while decreasing the duration of fixations compared to placebo. This effect, however, was non-specific to facial stimuli. When restricting the analysis to facial images only, we found the same effect. In addition, oxytocin modulated fixation rates in the eye and nasion regions. DISCUSSION: This is the first study to explore the effects of oxytocin on eye gaze in schizophrenia. Oxytocin had enhanced exploratory viewing behaviour in response to both facial and inanimate control stimuli. We suggest that the acute administration of intranasal oxytocin may have the potential to enhance visual attention in schizophrenia.

One Health, Fermented Foods, and Gut Microbiota.

Changes in present-day society such as diets with more sugar, salt, and saturated fat, bad habits and unhealthy lifestyles contribute to the likelihood of the involvement of the microbiota in inflammatory diseases, which contribute to global epidemics of obesity, depression, and mental health concerns. The microbiota is presently one of the hottest areas of scientific and medical research, and exerts a marked influence on the host during homeostasis and disease. Fermented foods and beverages are generally defined as products made by microbial organisms and enzymatic conversions of major and minor food components. Further to the commonly-recognized effects of nutrition on the digestive health (e.g., dysbiosis) and well-being, there is now strong evidence for the impact of fermented foods and beverages (e.g., yoghurt, pickles, bread, kefir, beers, wines, mead), produced or preserved by the action of microorganisms, on general health, namely their significance on the gut microbiota balance and brain functionality. Fermented products require microorganisms, i.e., Saccharomyces yeasts and lactic acid bacteria, yielding alcohol and lactic acid. Ingestion of vibrant probiotics, especially those contained in fermented foods, is found to cause significant positive improvements in balancing intestinal permeability and barrier function. Our guts control and deal with every aspect of our health. How we digest our food and even the food sensitivities we have is linked with our mood, behavior, energy, weight, food cravings, hormone balance, immunity, and overall wellness. We highlight some impacts in this domain and debate calls for the convergence of interdisciplinary research fields from the United Nations' initiative. Worldwide human and animal medicine are practiced separately; veterinary science and animal health are generally neither considered nor inserted within national or international Health discussions. The absence of a clear definition and subsequent vision for the future of One Health may act as a barrier to transdisciplinary collaboration. The point of this mini review is to highlight the role of fermented foods and beverages on gut microbiota and debate if the need for confluence of transdisciplinary fields of One Health is feasible and achievable, since they are managed by separate sectors with limited communication.

A symptom-based approach to treatment of psychosis in autism spectrum disorder [corrected].

The optimal management of autism with psychosis remains unclear. This report describes a 22-year-old man with autism and psychosis who was referred to a tertiary-level specialist psychosis service, following a 6-year history of deterioration in mental health starting around the time of sitting GCSE examinations and an episode of bullying at school. We describe the individualised symptom-based approach that was effective in his treatment. Declaration of interest The authors declare no conflict of interest.