The Feasibility and Efficacy of Warrior Health and Fitness: A 3-Month Fitness and Nutrition Program for Veterans.

INTRODUCTION: Veterans are at risk for mental and physical health problems but may not seek traditional health care services. Wellness-based interventions, including exercise and nutrition, have been associated with improvements in physical and mental health among this population. This study explores the acceptability, feasibility, and efficacy of a 3-month health and fitness program for veterans. MATERIALS AND METHODS: Participants in 2 time-based cohorts from 2019 to 2023 (cohort 1: n = 261; cohort 2: n = 256) were cleared by a physician to participate. Participants then completed a fitness test and self-reported surveys (e.g., quality of life, sleep, and pain) before and after the 3-month program. Participants were recruited to participate at one of three sites: Boston, MA Fort Myers, FL, or Tampa, FL. The 3-month program consisted of weekly, supervised group fitness and one-on-one sessions, nutritional consultations, yoga, and other wellness activities. Primary program outcomes were measured by fitness assessments, self-report surveys, program completion, and program satisfaction. Fitness assessments included measures of weight, body mass index, grip strength, waist to hip ratio, body fat, lean mass, fat mass, heart rate, and blood pressure (BP). Self-report measures included quality of life, depression, loneliness, sleep quality, pain intensity, and pain interference. RESULTS: In cohort 1, significant improvements were found for measures of weight (P = .01), left-handed grip strength (P < .01), body fat percent (P < .01), and quality of life (P < .01). In cohort 2, significant improvements were found for measures of waist:hip ratio (P = .02), right and left-handed grip strength (P < .01), body mass index (P = .02), body fat percent (P < .01), and quality of life (P = .02). For both cohorts, pain intensity (cohort 1: P = .01, cohort 2: P < .001) and pain interference (cohort 1: P = .02, cohort 2: P < .001) increased significantly. CONCLUSIONS: These data suggest that a 3-month health and fitness program for veterans is acceptable and feasible and may improve physical and mental health outcomes. Considerations for program retention and assessment completion are discussed.

Surgery and Anesthesia in Patients with Pulmonary Hypertension.

Pulmonary hypertension is characterized by right ventricular impairment and a reduced ability to compensate for hemodynamic insults. Consequently, surgery can be challenging but is increasingly considered in view of available specific therapies and improved longer term survival. Optimal management requires a multidisciplinary patient-centered approach involving surgeons, anesthetists, pulmonary hypertension clinicians, and intensivists. The optimal pathway involves risk:benefit assessment for the proposed operation, optimization of pulmonary hypertension and any comorbidities, the appropriate anesthetic approach for the specific procedure and patient, and careful monitoring and management in the postoperative period. Where patients are carefully selected and meticulously managed, good outcomes can be achieved.

Factors Predicting Long-term Outcome and the Need for Surgery in Graves Orbitopathy: Extended Follow-up From the CIRTED Trial.

Graves orbitopathy is both disabling and disfiguring. Medical therapies to reduce inflammation are widely used, but there is limited trial data beyond 18 months of follow-up. METHODS: Three-year follow-up of a subset of the CIRTED trial (N = 68), which randomized patients to receive high-dose oral steroid with azathioprine/placebo and radiotherapy/sham radiotherapy. RESULTS: Data were available at 3 years from 68 of 126 randomized subjects (54%). No additional benefit was seen at 3 years for patients randomized to azathioprine or radiotherapy with regard to a binary clinical composite outcome measure (BCCOM), modified European Group on Graves' Orbitopathy score, or Ophthalmopathy Index.Clinical Activity Score (CAS), Ophthalmopathy Index, and Total Eye Score improved over 3 years (P < .001). However, quality of life at 3 years remained poor. Of 64 individuals with available surgical outcome data, 24 of 64 (37.5%) required surgical intervention. Disease duration of greater than 6 months before treatment was associated with increased need for surgery [odds ratio (OR) 16.8; 95% CI 2.95, 95.0; P = .001]. Higher baseline levels of CAS, Ophthalmopathy Index, and Total Eye Score but not early improvement in CAS were associated with increased requirement for surgery. CONCLUSION: In this long-term follow-up from a clinical trial, 3-year outcomes remained suboptimal with ongoing poor quality of life and high numbers requiring surgery. Importantly, reduction in CAS in the first year, a commonly used surrogate outcome measure, was not associated with improved long-term outcomes.

Feeding thermally processed spray-dried egg whites, singly or in combination with 15-acetyldeoxynivalenol or peroxidized soybean oil on growth performance, digestibility, intestinal morphology, and oxidative status in nursery pigs.

Two experiments (EXP) determined the susceptibility of spray-dried egg white (SDEW) to oxidation (heating at 100 °C for 72 h; thermally processed, TP) and whether feeding TP-SDEW, 15-acetyldeoxynivalenol (15-ADON), or peroxidized soybean oil (PSO), singularly or in combination, would affect pig performance, intestinal morphology, digestibility, and markers of oxidative stress in nursery pigs. In EXP 1, 32 pigs (7.14 kg body weight, BW) were placed individually into pens and fed diets containing either 12% SDEW, 6% TP-SDEW plus 6% SDEW, or 12% TP-SDEW. Performance was measured at the end of the 24-d feeding period with biological samples harvested following euthanasia. In EXP 2, 64 pigs (10.6 kg BW) were placed individually into pens and fed diets containing 7.5% soybean oil or PSO, 10% SDEW or TP-SDEW, and diets without or with 3 mg 15-ADON/kg diet in a 2 × 2 × 2 factorial arrangement. Performance was measured at the end of the 28-d feeding period with biological samples harvested following euthanasia. In EXP 1, dietary treatment did not affect pig performance, apparent ileal digestibility of amino acids (AAs), apparent total tract digestibility (ATTD) of gross energy (GE) or nitrogen (N), ileal crypt depth, or villi height:crypt depth ratio (P > 0.05). The effects of feeding TP-SDEW on protein damage in the plasma and liver (P < 0.05) were variable. In EXP 2, there were no three-way interactions and only one two-way interactions among dietary treatments on parameters evaluated. There was no effect of feeding TP-SDEW on ATTD of GE or N, intestinal morphology, or on oxidative markers in the plasma, liver, or ileum (P > 0.05). There was no effect of feeding diets containing added 15-ADON on ATTD of GE, ileal AA digestibility, intestinal morphology, oxidative markers in the plasma, liver, or ileum, or pig performance (P > 0.05). Feeding pigs diets containing PSO resulted in reduced ATTD of GE and N, plasma vitamin E concentration, and pig performance (P < 0.01) but did not affect intestinal morphology or oxidative markers in the liver or ileum (P > 0.05). In conclusion, it was difficult to induce protein oxidation in SDEW and when achieved there were limited effects on performance, digestibility, intestinal morphology, and oxidative status. Furthermore, singly adding 15-A-DON to a diet had no effect on the animal. At last, adding PSO reduces animal performance, but has limited effect on digestibility, intestinal morphology, and oxidative status in nursery pigs.

Swine can be exposed to a variety of nutritional stressors that can affect their well-being and productivity. Three stressors of concern include grains with naturally occurring mycotoxins, oxidized proteins in feedstuffs due to overheating during processing, or lipids that have been damaged by excessive heating. Experiments were conducted to determine how susceptible a previously processed feedstuff was to protein oxidation and whether feeding mycotoxins, oxidized protein, or peroxidized soybean oil would affect growth performance, intestinal morphology, digestibility, and markers of oxidative stress in nursery pigs. Results indicate it was difficult to induce protein oxidation in previously processed protein by heating in a forced air oven, and if some protein oxidation did occur, there is limited effects on growth performance, digestibility, intestinal morphology, and oxidative status in nursery pigs. The data also indicated that adding an isolated mycotoxin was difficult to ensure proper mixing from which to analyze the complete diet from which to conduct animal research. At last, the data show that adding soybean oil that has been thermally processed to contain high concentrations of aldehydes will result in a dramatic reduction in animal performance, but has limited effects on digestibility, intestinal morphology, and oxidative status in nursery pigs.

Effects of feeding variable levels of mycotoxins with or without a mitigation strategy on growth performance, gut permeability, and oxidative biomarkers in nursery pigs.

The objectives were to determine how high levels (> 2.5 mg/kg diet) of deoxynivalenol (DON), in conjunction with other naturally occurring mycotoxins (MTX) would impact growth, intestinal integrity, and oxidative status, with or without a mitigation strategy, in nursery pigs. One-hundred and five pigs (5.5 ± 0.52 kg) were randomly allotted to 35 pens and fed dietary treatments for 45 d. Treatments were factorially arranged with the inclusion of MTX being low (L-MTX; < 1 mg/kg diet) or high (H-MTX; > 2.5 mg/kg diet) in combination with no mitigation strategy or the inclusion of a mitigation strategy (Biofix® Plus, BPL; 1.5 mg/kg diet). There was no interaction between MTX level and BPL inclusion on average daily gain (ADG) or gain to feed ratio (GF), (P > 0.10). Compared to pigs fed diets containing L-MTX, feeding pigs diets containing H-MTX decreased ADG and GF (P < 0.05). The addition of BPL had no effect on ADG (P > 0.10), but improved GF (P = 0.09). There was an interaction between MTX and BPL on average daily feed intake (ADFI), where the addition of BPL had no effect on ADFI of pigs fed L-MTX diets but improved ADFI of pigs fed H-MTX diets (P = 0.09). An interaction was detected between MTX and BPL on protein oxidation as measured by plasma protein carbonyls (PC, P = 0.01), where the inclusion of BPL decreased plasma PC in pigs fed H-MTX diets to a greater extent than pigs fed the L-MTX diets. There was no interaction between MTX and BPL, or an effect of MTX or BPL on DNA damage as measured by 8-hydroxy-2'dexoxyguanosine (P > 0.10). There was no interaction between MTX and BPL, or a BPL effect on lipid damage as measured by thiobarbituic acid reactive substances (TBARS, P > 0.10), but pigs fed diets containing H-MTX exhibited lower concentrations of plasma TBARS (P = 0.07) compared to pigs fed L-MTX diets. There was no interaction between MTX and BPL, or an effect of MTX or BPL on plasma lactulose and mannitol ratio as a measure of intestinal permeability (P > 0.10). In conclusion, feeding H-MTX decreased ADG and GF, decreased plasma TBARS, but did not affect plasma 8-hydroxy-2'dexoxyguanosine or plasma LM ratio. The inclusion of a mitigation strategy improved ADFI when pigs were fed H-MTX diets and improved GF regardless of MTX level. Addition of a mitigation strategy also reduced plasma protein damage but did not affect indicators of DNA or lipid damage or affect gastrointestinal integrity.

The person-based development and realist evaluation of a summary report for GP consultations [version 1; peer review: 2 approved].

Background: Use of telephone, video and e-consultations is increasing. These can make consultations more transactional. This study aimed to develop a complex intervention to address patients' concerns more comprehensively in general practice and test the feasibility of this in a cluster-randomised framework.The complex intervention used two technologies: a patient-completed pre-consultation form used at consultation opening and a doctor-provided summary report provided at consultation closure. This paper reports on the development and realist evaluation of the summary report. Methods: A person-based approach was used to develop the summary report. An electronic protocol was designed to automatically generate the report after GPs complete a clinical template in the patient record. This was tested with 45 patients in 3 rounds each, with iterative adjustments made based on feedback after each round. Subsequently, an intervention incorporating the pre-consultation form with the summary report was then tested in a cluster-randomised framework with 30 patients per practice in six practices: four randomised to intervention, and two to control. An embedded realist evaluation was carried out. The main feasibility study results are reported elsewhere. Results: Intervention Development: 15 patients were recruited per practice. Eight patients and six GPs were interviewed and 18 changes made. The summary report improved substantially; GPs and patients in the final practice were more satisfied with the report than the first practice.Realist evaluation: The summary was most useful for consultations when safety-netting advice was important or with multiple complex follow-up steps in patients who have difficulty remembering or communicating. It generated greater clarity on the follow-up and greater patient empowerment and reassurance. Conclusions: The person-based approach was successful. The summary report creates clarity, empowerment and reassurance in certain consultations and patients. As it takes a few minutes per patient, GPs prefer to select patients who will benefit most.

Extended Tourniquet Times and the Impact on Wound Healing in Foot Surgery.

OBJECTIVE: The aim of this study was to compare the effect of tourniquet time less than or in excess of 120 minutes on foot surgery wound healing. NULL HYPOTHESIS: A tourniquet time of over 120 minutes will not affect wound healing in foot surgery. DESIGN, SETTING, PARTICIPANTS AND METHOD: A retrospective comparative cohort analysis was performed on 96 patients undergoing complex hindfoot surgery in a large central teaching hospital. Fifty-five patients receiving tourniquet pressure for >120 minutes and 41 receiving <120 minutes of tourniquet pressure were identified from electronic case records. The primary outcome was surgical wound healing. Secondary outcomes were discharge date and complication rate. RESULTS: There was no significant difference in reported time for wounds to heal in the <120-minute or >120-minute cohort. There were no other significant differences in secondary clinical outcomes and no significant variations in patient demographics. CONCLUSION: This study suggests that tourniquet times from 2 to 3 hours in foot and ankle surgery with pressures up to 300 mmHg are not associated with a significant effect on wound healing.

'Sometimes I can't look in the mirror': Recognising the importance of the sociocultural context in patient experiences of sexuality, relationships and body image after ovarian cancer.

OBJECTIVE: Ovarian cancer (OC) can significantly change the way women feel about their body. However, personal accounts regarding these changes are lacking in the literature. Therefore, the aim of this study was to gain an understanding of the ways in which OC can affect relationships, sexuality, womanhood and body image. METHODS: Ninety-eight Australian women aged 18 and over diagnosed with OC completed an online survey that invited narrative responses to open-ended questions about relationships, sexuality, body image and womanhood following OC treatment. Responses were analysed thematically while applying a sociocultural lens. RESULTS: Three themes and two subthemes were identified: Failure and Loss of Femininity and Womanhood, Internalising Public Perception of Body and Illness and Altered Relationships which comprised two subthemes, Loss of the Sexual Self and Relationship Burden. These themes suggest women view themselves and their relationships in comparison with sociocultural understandings of body normalcy. Women often questioned their self-worth, their relationships and place within society due to changes in fertility, sexuality and bodily functioning. CONCLUSION: These results highlight a need for health care professionals to open dialogue with women about sexuality and ensure information and support is given to reduce stigma and positively influence self-perception and increase body acceptance.

Involvement of ischemia-driven 5-lipoxygenase-resolvin-E1-chemokine like receptor-1 axis in the resolution of post-coronary artery bypass graft inflammation in coronary arteries.

AIMS: Expression status of pro-resolvin lipid mediators (PLM) and receptors in the post-Coronary artery bypass grafting (CABG) coronary arteries are largely unknown. Here, we aim to investigate the expression of the enzymes involved in PLM synthesis and their receptors in the atherosclerotic post-CABG swine (AS) left anterior descending (LAD) compared to without CABG (LAD-AS), and in isolated coronary artery smooth muscle cells (CASMCs) cultured under ischemia. METHODOLOGY: The arteries of interest were harvested from post-CABG atherosclerotic swine and the histomorphology and the expression status of key PLM mediators were quantified using immunostaining. Smooth muscle cells (SMCs) were cultured under ischemia and confirmed the expression on PLM mediators at transcript and protein level. RESULTS: The histomorphometric analysis revealed considerable alterations in the tissue architecture in LAD-CABG and LAD-AS arteries compared to control. PLM synthetic enzyme 5-lipoxygenases (5LO) was significantly upregulated in LAD-CABG and LAD-AS whereas the other enzymes including 12LO, 15LO, and cyclooxygenase-2, and the receptors including Chemokine like receptor 1 (ChemR23), 7-transmembrane G-protein coupled receptor-18 (GPCR18), GPCR120 were decreased in LAD-CABG than control. LO enzymes and PLM receptors were upregulated in ischemic CASMCs with respect to control. Western blot showed the upregulation of 5LO, and ChemR23. Additionally, higher level of resolvin-E1 (RvE1) was observed in ischemic control CASMCs which was decreased following reperfusion. CONCLUSION: These findings suggest that the CASMCs withstand the ischemia-triggered proinflammatory episodes by increasing the secretion of RvE1 mediated through 5LO and ChemR23 signaling.

Sexual functioning after ovarian cancer: are women receiving the information and support they need?

Ovarian cancer (OC) can significantly impact sexual functioning beyond initial treatment and into survivorship. However, research suggests that the information and advice women want on this topic may not be readily provided by health professionals (HPs). We explored the psychological and sexual wellbeing of a sample of Australian women diagnosed with OC, to inform the development of effective, targeted sexuality resources. This paper presents a subset of our findings. Participants were recruited nationwide via social media, print advertisement and the database of a support organisation, Ovarian Cancer Australia. Self-reported demographic and clinical survey data were collected including perceptions of the availability and adequacy of sexuality support post-OC. Participants (n = 98) were on average 52.8 years old and 5.5 years post-diagnosis. A minority (22%) reported that the impact of OC on their sexuality was discussed by HPs; and 46% were satisfied with that discussion. Approximately half (52%) had wanted to discuss sexuality concerns with a HP during treatment and 43% still felt the need for this discussion. Open-ended responses revealed the need for more information that was detailed and specified what to expect post-diagnosis. Shortcomings of HPs in addressing sexuality were also revealed. This research provides further evidence that sexual health remains inadequately addressed in OC care across the trajectory for the majority of women, and is an area of unmet need.

Post-oral sensing of fat increases food intake and attenuates body weight defense.

In mammals, changes in weight elicit responses that favor a return to one's previous weight and promote weight stability. It has been hypothesized that palatable sweet and high-fat foods disturb the defense of body weight, leading to weight gain. We find that increasing sweetness or percent calories from fat increases diet palatability but that only increases in nutritive fat content increase caloric intake and body weight. In a mouse model of overfeeding that activates weight defense, high-fat diets, but not sweetened diets, attenuate the defense of body weight, leading to weight gain. The ability of a palatable, high-fat diet to increase food intake does not require tasting or smelling the food. Instead, the direct infusion of a high-fat diet into the stomach increases the ad libitum intake of less palatable, low-fat food. Post-oral sensing of percent calories from fat modulates feeding behavior to alter weight stability.

Antibiotic-induced changes in the human gut microbiota for the most commonly prescribed antibiotics in primary care in the UK: a systematic review.

OBJECTIVE: The gut microbiota influences many aspects of human health. We investigated the magnitude and duration of changes in gut microbiota in response to antibiotics commonly prescribed in UK primary care. METHODS: We searched MEDLINE, EMBASE and AMED, all years up to May 2020 including all study designs, collecting and analysing data on the effect of antibiotics prescribed for respiratory and urinary tract infections. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Cochrane standard methods. Risk of bias was evaluated using the Critical Appraisal Skills Programme. Narrative synthesis was used to report the themes emerging from the data. MAIN OUTCOME MEASURES: Primary outcomes were antibiotic-induced changes in the composition and/or diversity of the gut microbiota. Secondary outcome was the time for the microbiota to return to baseline. RESULTS: Thirty-one articles with low or unclear risk of bias showed that antibiotics impact the gut microbiota by causing rapid and diminished levels of bacterial diversity and changes in relative abundances. After cessation of treatment, gut bacteria recover, in most individuals, to their baseline state within a few weeks. Some studies suggested longer term effects from 2 to 6 months. Considerable heterogeneity in methodology makes the studies prone to biases and other confounding factors. Doxycycline was associated with a marked short-term decrease in Bifidobacterium diversity. Clarithromycin decreased the populations of Enterobacteria, and the anaerobic bacteria Bifidobacterium sp and Lactobacillus sp in numbers and diversity for up to 5 weeks. Phenoxymethylpenicillin, nitrofurantoin and amoxicillin had very little effect on the gut microbiome. CONCLUSIONS: Despite substantial heterogeneity of the studies and small sample sizes, there is evidence that antibiotics commonly used in primary care influence the composition of the gastrointestinal microbiota. Larger population-based studies are needed to fully understand how antibiotics modulate the microbiota, and to determine if these are associated with (longer term) health consequences. PROSPERO REGISTRATION NUMBER: CRD42017073750.

Anaesthetic-analgesic ear drops to reduce antibiotic consumption in children with acute otitis media: the CEDAR RCT.

BACKGROUND: Acute otitis media (AOM) is a common reason for primary care consultations and antibiotic prescribing in children. Options for improved pain control may influence antibiotic prescribing and consumption. OBJECTIVE: The Children's Ear Pain Study (CEDAR) investigated whether or not providing anaesthetic-analgesic ear drops reduced antibiotic consumption in children with AOM. Secondary objectives included pain control and cost-effectiveness. DESIGN: A multicentre, randomised, parallel-group (two-group initially, then three-group) trial. SETTING: Primary care practices in England and Wales. PARTICIPANTS: 1- to 10-year-old children presenting within 1 week of suspected AOM onset with ear pain during the preceding 24 hours and not requiring immediate antibiotics. Participating children were logged into the study and allocated using a remote randomisation service. INTERVENTIONS: Two-group trial - unblinded comparison of anaesthetic-analgesic ear drops versus usual care. Three-group trial - blinded comparison of anaesthetic-analgesic ear drops versus placebo ear drops and unblinded comparison with usual care. MAIN OUTCOME MEASURES: The primary outcome measure was parent-reported antibiotic use by the child over 8 days following enrolment. Secondary measures included ear pain at day 2 and NHS and societal costs over 8 days. RESULTS: Owing to a delay in provision of the placebo drops, the recruitment period was shortened and most participants were randomly allocated to the two-group study (n = 74) rather than the three-group study (n = 32). Comparing active drops with usual care in the combined two-group and three-group studies, 1 out of 39 (3%) children allocated to the active drops group and 11 out of 38 (29%) children allocated to the usual-care group consumed antibiotics in the 8 days following enrolment [unadjusted odds ratio 0.09, 95% confidence interval (CI) 0.02 to 0.55; p = 0.009; adjusted for delayed prescribing odds ratio 0.15, 95% CI 0.03 to 0.87; p = 0.035]. A total of 43% (3/7) of patients in the placebo drops group consumed antibiotics by day 8, compared with 0% (0/10) of the three-group study active drops groups (p = 0.051). The economic analysis of NHS costs (£12.66 for active drops and £11.36 for usual care) leads to an estimated cost of £5.19 per antibiotic prescription avoided, but with a high degree of uncertainty. A reduction in ear pain at day 2 in the placebo group (n = 7) compared with the active drops group (n = 10) (adjusted difference in means 0.67, 95% CI -1.44 to 2.79; p = 0.51) is consistent with chance. No adverse events were reported in children receiving active drops. LIMITATIONS: Estimated treatment effects are imprecise because the sample size target was not met. It is not clear if delayed prescriptions of an antibiotic were written prior to randomisation. Few children received placebo drops, which hindered the investigation of ear pain. CONCLUSIONS: This study suggests that reduced antibiotic use can be achieved in children with AOM by combining a no or delayed antibiotic prescribing strategy with anaesthetic-analgesic ear drops. Whether or not the active drops relieved ear pain was not established. FUTURE WORK: The observed reduction in antibiotic consumption following the prescription of ear drops requires replication in a larger study. Future work should establish if the effect of ear drops is due to pain relief. TRIAL REGISTRATION: Current Controlled Trials ISRCTN09599764. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 34. See the NIHR Journals Library website for further project information. Alastair D Hay was funded by a NIHR Research Professorship (funding identifier NIHR-RP-02-12-012).

Ear infections are common in children < 10 years of age, with 40% of these children suffering from an ear infection at least once per year. During the infection, germs multiply in the confined space of the middle ear, resulting in a build-up of pressure that pushes on and stretches the ear drum. This causes severe pain and distress to the child, which in turn leads to disrupted family life. Although there is world-class evidence showing that antibiotics do not help, and the National Institute for Health and Care Excellence advises against their use, > 85% of UK children with middle ear infections (acute otitis media) are prescribed an antibiotic, which is a higher percentage than for any other childhood infection. Antibiotics do not treat the child's pain and, in most cases, they do not help to treat the infection (because many ear infections are caused by viruses that do not respond to antibiotics), but they can cause side effects (such as diarrhoea) and increase the problem of antibiotic resistance, which is a major public health concern. The Children's Ear Pain Study (CEDAR) wanted to find out whether or not painkilling ear drops [benzocaine­phenazone otic solution (Auralgan^®) currently manufactured by Pfizer Consumer Healthcare(Pfizer Inc., New York, NY USA)] can, by treating children's ear pain, reduce the number of parents giving their children antibiotics for acute otitis media. Children were given the painkilling drops, placebo (dummy) drops or usual care. The study found that, if the children were given the painkilling drops, significantly fewer of them were given antibiotics. Unfortunately, there were not enough children who took part in the study to change advice on how doctors treat ear infections. However, these results suggest that ear drops help reduce unnecessary antibiotic use and should be investigated in a further larger study.

Syringe disposal among people who inject drugs before and after the implementation of a syringe services program.

INTRODUCTION: Due to the increase in people who use opioids in the US, there has been a steady increase in injection drug use. Without access to safe syringe disposal locations, people who inject drugs (PWID) have few options other than improper disposal, including in public places. In 2016, Florida's first legal Syringe Services Program (SSP) was established in Miami. This study aims to compare syringe disposal practices among PWID before and after the implementation of an SSP. METHODS: Visual inspection walkthroughs of randomly selected census blocks in the neighborhoods in the top quartile of narcotics-related arrests were conducted to assess improperly discarded syringes. Syringe location was geocoded in ArcGIS. Adult PWID pre-SSP (n = 448) and post-SSP (n = 482) implementation were recruited for a survey using respondent-driven sampling in Miami. A Poisson regression model was used to determine the adjusted relative risk (aRR) of improper syringe disposal pre- and post-SSP. RESULTS: A total of 191 syringes/1000 blocks were found post-implementation versus 371/1000 blocks pre-implementation, representing a 49% decrease after SSP implementation. In the surveys, 70% reported any improper syringe disposal post-SSP implementation versus 97% pre-SSP implementation. PWID in the post-implementation survey had 39% lower adjusted relative risk (aRR = 0.613; 95% CI = 0.546, 0.689) of improper syringe disposal as compared to pre-implementation. CONCLUSIONS: There was a significant decrease in the number of improperly discarded syringes in public in Miami after the implementation of an SSP. Providing PWID with proper disposal venues such as an SSP could decrease public disposal in other communities.

Immunopathological and molecular basis of functional dyspepsia and current therapeutic approaches.

INTRODUCTION: Functional dyspepsia (FD) is widespread with 20% prevalence worldwide and a significant economic burden due to health care cost and constraints on daily activities of patients. Despite extensive investigation, the underlying causes of dyspepsia in a majority of patients remain unknown. Common complaints include abdominal discomfort, pain, burning, nausea, early satiety, and bloating. Motor dysfunction of the gut was long considered a major cause, but recent investigations suggest immune-based pathophysiological and molecular events in the duodenum are more probable contributing factors. Areas Covered: Inflammatory mediators and immune cells including duodenal eosinophils, intraepithelial lymphocytes, and T-cells have been implicated in the underlying cause of disease process, as have genetic factors. In this article, we critically reviewed findings, identified gaps in knowledge and suggested future directions for further investigation to identify targets and develop better therapeutic approaches. Expert commentary: Impaired gastric accommodation, slow gastric emptying, and increased visceral sensitivity have long been thought of as main causal factors of FD. However, more recent identification of eosinophilic degranulation and recruitment of T cells that induce mild duodenal inflammation are giving rise to new insights into immune-mediated pathophysiology. These insights offer promising avenues to explore for immune-mediated therapy in the future.

Establishing the usefulness of the GO-QOL in a UK hospital-treated population with thyroid eye disease in the CIRTED trial.

Thyroid eye disease (TED) is a potentially sight-threatening and cosmetically disfiguring condition arising in 25-50% of patients with Graves' hyperthyroidism. CIRTED is the first study to evaluate the long-term role of radiotherapy and prolonged immunosuppression with azathioprine in treating TED, one aim of which was to validate the use of the English version of GO-QOL in an UK population with TED. In a three stage design over a 48 week period, the GO-QOL was tested and compared to a general measure of quality of life (WHOQOL-Bref). In stage 1 utilising a standard 14 day test-retest design both GO-QOL subscales achieved Cronbach's alphas demonstrating excellent validity and internal reliability (Visual Function 0.929 and 0.931; Appearance 0.888 and 0.906). In stage 2, Repeated Measures ANOVA demonstrated longitudinal validity, with both subscales of the GO-QOL showing significant change over time (Visual Function, η2 = 0.114, p < .001; Appearance, η2 = 0.069, p < .002). In stage 3 the GO-QOL showed discriminant validity at the week 48 time point, with the visual function subscale being able to detect changes in groups identified by clinicians (using BCCOM ratings of improvement or deterioration), while both subscales could detect group differences when based on participants' subjective ratings of TED noticeability and severity. The results of this project provide support for the English translation of the GO-QOL as an outcome measure for patients with moderately severe active Graves' orbitopathy/TED.

Combined immunosuppression and radiotherapy in thyroid eye disease (CIRTED): a multicentre, 2 × 2 factorial, double-blind, randomised controlled trial.

BACKGROUND: Standard treatment for thyroid eye disease is with systemic corticosteroids. We aimed to establish whether orbital radiotherapy or antiproliferative immunosuppression would confer any additional benefit. METHODS: CIRTED was a multicentre, double-blind, randomised controlled trial with a 2 × 2 factorial design done at six centres in the UK. Adults with active moderate-to-severe thyroid eye disease associated with proptosis or ocular motility restriction were recruited to the trial. Patients all received a 24 week course of oral prednisolone (80 mg per day, reduced to 20 mg per day by 6 weeks, 10 mg per day by 15 weeks, and 5 mg per day by 21 weeks) and were randomly assigned via remote computerised randomisation to receive either radiotherapy or sham radiotherapy and azathioprine or placebo in a 2 × 2 factorial design. Randomisation included minimisation to reduce baseline disparities in potential confounding variables between trial interventions. Patients and data analysts were masked to assignment, whereas trial coordinators (who monitored blood results), pharmacists, and radiographers were not. The radiotherapy dose was 20 Gy administered to the retrobulbar orbit in ten to 12 fractions over 2 to 3 weeks. Azathioprine treatment was provided for 48 weeks at 100-200 mg per day (dispensed as 50 mg tablets), depending on bodyweight (100 mg for <50 kg, 150 mg 50-79 kg, 200 mg for ≥80 kg). The primary outcomes were a binary composite clinical outcome score and an ophthalmopathy index at 48 weeks, and a clinical activity score at 12 weeks. The primary analysis was based on the intention-to-treat allocation and safety was assessed in all participants. This study is registered with ISRCTN, number 22471573. FINDINGS: Between Feb 15, 2006, and Oct 3, 2013, 126 patients were recruited and randomly assigned to groups: 31 patients to radiotherapy plus azathioprine, 31 to sham radiotherapy and azathioprine, 32 to radiotherapy and placebo, and 32 to sham radiotherapy and placebo. Outcome data were available for 103 patients (54 for sham radiotherapy vs 49 for radiotherapy and 53 for placebo vs 50 for azathioprine), of whom 84 completed their allocated treatment of radiotherapy or sham radiotherapy and 57 continued to take azathioprine or placebo up to 48 weeks. There was no interaction betweeen azathioprine and radiotherapy (pinteraction=0·86). The adjusted odds ratio (ORadj) for improvement in the binary clinical composite outcome measure was 2·56 (95% CI 0·98-6·66, p=0·054) for azathioprine and 0·89 (0·36-2·23, p=0·80) for radiotherapy. In a post-hoc analysis of patients who completed their allocated therapy the ORadj for improvement was 6·83 (1·66-28·1, p=0·008) for azathioprine and 1·32 (0·30-4·84, p=0·67) for radiotherapy. The ophthalmopathy index, clinical activity score, and numbers of adverse events (161 with azathioprine and 156 with radiotherapy) did not differ between treatment groups. In both groups, the most common adverse events were mild infections. No patients died during the study. INTERPRETATION: In patients receiving oral prednisolone for 24 weeks, radiotherapy did not have added benefit. We also did not find added benefit for addition of azathioprine in the primary analysis; however, our conclusions are limited by the high number of patients who withdrew from treatment. Results of post-hoc analysis of those who completed the assigned treatment suggest improved clinical outcome at 48 weeks with azathioprine treatment. FUNDING: National Eye Research Centre, Above and Beyond, and Moorfields Eye Charity.

Nanopore Sequencing as a Surveillance Tool for Plant Pathogens in Plant and Insect Tissues.

Plant pathogens are constantly emerging and spreading into new areas and there are often limited postdiagnosis treatment options for infection, making surveillance key to their control. Here we present results from a study testing the efficacy of a portable nanopore-based massively parallel sequencing (MPS) technology for use in the detection of diverse plant pathogens in selected samples. The Oxford MinION device was coupled with whole transcriptome amplification (WTA) to sequence the metatranscriptome of plant and insect tissues infected with either Candidatus Liberibacter asiaticus or plum pox virus. Results showed that this methodology is useful for detecting unsuspected viral and bacterial pathogens in plant and insect tissues. The percentage of generated reads assigned to plum pox virus was 95% from infected tissue and 3% from the viruliferous insect, Myzus persicae. Diaphorina citri sequencing led to 22% of the reads mapping as Ca. L. asiaticus. Plum pox virus and Ca. L. asiaticus were detected in both tissue and insect samples near the beginning of each sequencing run, demonstrating the capability of this methodology to obtain results rapidly. This approach also proved the capability of this system to determine the major components of the insect vector's microbiome and the specific strain of small-genome, high-titer pathogens.

Enhancement of microbial density and methane production in advanced anaerobic digestion of secondary sewage sludge by continuous removal of ammonia.

Ammonia inhibition mitigation in anaerobic digestion of high solids content of thermally hydrolysed secondary sewage sludge by the NH4+ affinitive clinoptilolite and a strong acid type ion-exchange resin S957 was investigated. Continuous NH4+-N removal was achieved through ion-exchanging at both temperatures with average removals of 50 and 70% for the clinoptilolite and resin dosed reactors, respectively. Approximate 0.2-0.5unit of pH reduction was also observed in the dosed reactors. The synergy of NH4+-N removal and pH reduction exponentially decreased free NH3 concentration, from 600 to 90mg/L at 43°C, which mitigated ammonia inhibition and improved methane yields by approximately 54%. Microbial community profiling suggested that facilitated by ammonia removal, the improvement in methane production was mainly achieved through the doubling in bacterial density and a 6-fold increase in population of the Methanosarcinaceae family, which in turn improved the degradation of residual volatile fatty acids, proteins and carbohydrates.

Choice of Moisturiser for Eczema Treatment (COMET): feasibility study of a randomised controlled parallel group trial in children recruited from primary care.

OBJECTIVES: To determine the feasibility of a randomised controlled trial of 'leave on' emollients for children with eczema. DESIGN: Single-centre, pragmatic, 4-arm, observer-blinded, parallel, randomised feasibility trial. SETTING: General practices in the UK. PARTICIPANTS: Children with eczema aged 1 month to <5 years. OUTCOME MEASURES: Primary outcome-proportion of parents who reported use of the allocated study emollient every day for the duration of follow-up (12 weeks). Other feasibility outcomes-participant recruitment and retention, data collection and completeness and blinding of observers to allocation. INTERVENTIONS: Aveeno lotion, Diprobase cream, Doublebase gel, Hydromol ointment. RESULTS: 197 children were recruited-107 by self-referral (mainly via practice mail-outs) and 90 by inconsultation (clinician consenting and randomising) pathways. Participants recruited inconsultation were younger, had more severe Patient-Oriented Eczema Measure scores and were more likely to withdraw than self-referrals. Parents of 20 (10%) of all the randomised participants reported using the allocated emollient daily for 84 days. The use of other non-study emollients was common. Completeness of data collected by parent-held daily diaries and at monthly study visits was good. Daily diaries were liked (81%) but mainly completed on paper rather than via electronic ('app') form. Major costs drivers were general practitioner consultations and eczema-related prescriptions. Observer unblinding was infrequent, and occurred at the baseline or first follow-up visit through accidental disclosure. CONCLUSIONS: It is feasible in a primary care setting to recruit and randomise young children with eczema to emollients, follow them up and collect relevant trial data, while keeping observers blinded to their allocation. However, reported use of emollients (study and others) has design implications for future trials. TRIAL REGISTRATION NUMBER: ISRCTN21828118/EudraCT2013-003001-26.