Breath biomarkers in idiopathic pulmonary fibrosis:A systematic review 11 Medical and Health Sciences

Background: Exhaled biomarkers may be related to disease processes in idiopathic pulmonary fibrosis (IPF) however their clinical role remains unclear. We performed a systematic review to investigate whether breath biomarkers discriminate between patients with IPF and healthy controls. We also assessed correlation with lung function, ability to distinguish diagnostic subgroups and change in response to treatment. Methods: MEDLINE, EMBASE and Web of Science databases were searched. Study selection was limited to adults with a diagnosis of IPF as per international guidelines. Results: Of 1014 studies screened, fourteen fulfilled selection criteria and included 257 IPF patients. Twenty individual biomarkers discriminated between IPF and controls and four showed correlation with lung function. Meta-analysis of three studies indicated mean (± SD) alveolar nitric oxide (CalvNO) levels were significantly higher in IPF (8.5 ± 5.5 ppb) than controls (4.4 ± 2.2 ppb). Markers of oxidative stress in exhaled breath condensate, such as hydrogen peroxide and 8-isoprostane, were also discriminatory. Two breathomic studies have isolated discriminative compounds using mass spectrometry. There was a lack of studies assessing relevant treatment and none assessed differences in diagnostic subgroups. Conclusions: Evidence suggests CalvNO is higher in IPF, although studies were limited by small sample size. Further breathomic work may identify biomarkers with diagnostic and prognostic potential

Urogenital pathogens, associated with Trichomonas vaginalis, among pregnant women in Kilifi, Kenya : a nested case-control study

Background: Screening of curable sexually transmitted infections is frequently oriented towards the diagnosis of chlamydia, gonorrhea, syphilis and trichomoniasis, whereas other pathogens, sometimes associated with similar urogenital syndromes, remain undiagnosed and/or untreated. Some of these pathogens are associated with adverse pregnancy outcomes. Methods: In a nested case-control study, vaginal swabs from 79 pregnant women, i.e., 28T. vaginalis-positive (cases) and 51T. vaginalis-negative (controls), were screened by quantitative PCR for Adenovirus 1 and 2, Cytomegalovirus, Herpes Simplex Virus 1 and 2, Chlamydia trachomatis, Escherichia coli, Haemophilus ducreyi, Mycoplasma genitalium, M. hominis, candidatus M. girerdii, Neisseria gonorrhoeae, Streptococcus agalactiae, Treponema pallidum, Ureaplasma parvum, U. urealyticum, and Candida albicans. Additionally, we determined whether women with pathogens highly associated with T. vaginalis had distinct clinical signs and symptoms compared to women with T. vaginalis mono-infection. Results: M. hominis was independently associated with T. vaginalis (adjusted odds ratio=6.8, 95% CI: 2.3-19.8). Moreover, M. genitalium and Ca M. girerdii were exclusively detected in women with T. vaginalis (P=0.002 and P=0.001), respectively. Four of the six women co-infected with T. vaginalis and Ca M. girerdii complained of vaginal itching, compared to only 4 out of the 22 women infected with T. vaginalis without Ca M. girerdii (P=0.020). Conclusion: We confirm M. hominis as a correlate of T. vaginalis in our population, and the exclusive association of both M. genitalium and Ca. M. girerdii with T. vaginalis. Screening and treatment of these pathogens should be considered

Protocol, rationale and design of SELPHI: A randomised controlled trial assessing whether offering free HIV self-testing kits via the internet increases the rate of HIV diagnosis 11 Medical and Health Sciences 1117 Public Health and Health Services 11 Medical and Health Sciences 1103 Clinical Sciences

BACKGROUND: Among men who have sex with men (MSM) in the UK, an estimated 28% have never tested for HIV and only 27% of those at higher risk test at least every 6 months. HIV self-testing (HIVST), where the person takes their own blood/saliva sample and processes it themselves, offers the opportunity to remove many structural and social barriers to testing. Although several randomised controlled trials are assessing the impact of providing HIVST on rates of HIV testing, none are addressing whether this results in increased rates of HIV diagnoses that link to clinical care. Linking to care is the critical outcome because it is the only way to access antiretroviral treatment (ART). We describe here the design of a large, internet-based randomised controlled trial of HIVST, called SELPHI, which aims to inform this key question. METHODS/DESIGN: The SELPHI study, which is ongoing is promoted via social networking website and app advertising, and aims to enroll HIV negative men, trans men and trans women, aged over 16 years, who are living in England and Wales. Apart from the physical delivery of the test kits, all trial processes, including recruitment, take place online. In a two-stage randomisation, participants are first randomised (3:2) to receive a free baseline HIVST or no free baseline HIVST. At 3 months, participants allocated to receive a baseline HIVST (and meeting further eligibility criteria) are subsequently randomised (1:1) to receive the offer of regular (every 3 months) free HIVST, with testing reminders, versus no such offer. The primary outcome from both randomisations is a laboratory-confirmed HIV diagnosis, ascertained via linkage to a national HIV surveillance database. DISCUSSION: SELPHI will provide the first reliable evidence on whether offering free HIVST via the internet increases rates of confirmed HIV diagnoses and linkage to clinical care. The two randomisations reflect the dual objectives of detecting prevalent infections (possibly long-standing) and the more rapid diagnosis of incident HIV infections. It is anticipated that the results of SELPHI will inform future access to HIV self-testing provision in the UK. TRIAL REGISTRATION: DOI 10.1186/ISRCTN20312003 registered 24/10/2016

Association of screen time and physical activity with health-related quality of life in Iranian children and adolescents 11 Medical and Health Sciences 1117 Public Health and Health Services

Background: Health-related quality of life (HRQoL) is a multidimensional concept with significant effects and children and adolescence; while physical activity (PA) and screen time (ST) have been suggested as its probable predictors. Present study aims to investigate the association of PA, ST and their combination, with HRQoL in a nationally-representative sample of Iranian children and adolescents. Methods: As for the estimated sample size, 25,000 students aged 6-18 years were selected via multi-stage cluster sampling from 30 provinces of Iran. Sociodemographic data was obtained by using the questionnaire of the World Health Organization-Global school based student health survey (GSHS). Persian Pediatric Quality of Life inventory (PedsQL) and Physical Activity Questionnaire for the pediatric age group (PAQ-A) were applied for evaluating HRQoL and PA, respectively. PA scores 1-1.9 and 2-5 were respectively considered as low and high PA. The average duration of time spent on watching TV and leisure time computer use were considered as ST behaviors. ST of less than 2 h was considered low. Results: Out of 25,000 invited individuals, 23,043 students (mean age: 12.5) completed the study (response rate: 92.17). In linear regression models, ST duration had significant inverse association with total QoL (β:-0.49, p < 0.05). PA showed positive significant associations with HRQoL total score (β: 1.8, p < 0.05). Joint association of PA and ST revealed the strongest association of "high PA-low ST" category with total HRQoL (β: 2.2, p < 0.05); while "high PA-high ST" showed better total HRQoL score (β: 1.3) compared to "low PA-low ST" subgroup. Conclusion: Both PA and ST are significantly and independently associated with HRQoL in Iranian children and adolescents; while the adverse effect of prolonged ST could be diminished by a high PA. © 2019 The Author(s)

Pain coping skills training for African Americans with osteoarthritis study: Baseline participant characteristics and comparison to prior studies 11 Medical and Health Sciences 1103 Clinical Sciences 11 Medical and Health Sciences 1117 Public Health and Health Services

Background: The Pain Coping Skills Training for African Americans with OsteoaRTthritis (STAART) trial is examining the effectiveness of a culturally enhanced pain coping skills training (CST) program for African Americans with osteoarthritis (OA). This disparities-focused trial aimed to reach a population with greater symptom severity and risk factors for poor pain-related outcomes than previous studies. This paper compares characteristics of STAART participants with prior studies of CST or cognitive behavioral therapy (CBT)-informed training in pain coping strategies for OA. Methods: A literature search identified 10 prior trials of pain CST or CBT-informed pain coping training among individuals with OA. We descriptively compared characteristics of STAART participants with other studies, in 3 domains of the National Institutes of Minority Health and Health Disparities' Research Framework: Sociocultural Environment (e.g., age, education, marital status), Biological Vulnerability and Mechanisms (e.g, pain and function, body mass index), and Health Behaviors and Coping (e.g., pain catastrophizing). Means and standard deviations (SDs) or proportions were calculated for STAART participants and extracted from published manuscripts for comparator studies. Results: The mean age of STAART participants, 59 years (SD = 10.3), was lower than 9 of 10 comparator studies; the proportion of individuals with some education beyond high school, 75%, was comparable to comparator studies (61-86%); and the proportion of individuals who are married or living with a partner, 42%, was lower than comparator studies (62-66%). Comparator studies had less than about 1/3 African American participants. Mean scores on the Western Ontario and McMaster Universities Osteoarthritis Index pain and function scales were higher (worse) for STAART participants than for other studies, and mean body mass index of STAART participants, 35.2 kg/m2 (SD = 8.2), was higher than all other studies (30-34 kg/m2). STAART participants' mean score on the Pain Catastrophizing scale, 19.8 (SD = 12.3), was higher (worse) than other studies reporting this measure (7-17). Conclusions: Compared with prior studies with predominantly white samples, STAART participants have worse pain and function and more risk factors for negative pain-related outcomes across several domains. Given STAART participants' high mean pain catastrophizing scores, this sample may particularly benefit from the CST intervention approach. Trial registration: NCT02560922

Physical activity and sedentary time among preschoolers in centre-based childcare: A systematic review 11 Medical and Health Sciences 1117 Public Health and Health Services

Background: Many preschoolers spend a substantial portion of their day enrolled in centre-based childcare; the amounts of physical activity and sedentary time accumulated in this environment are critical to preschoolers\u27 ability to meet movement guidelines. The purpose of this systematic review was to provide a comprehensive overview of the objectively assessed physical activity and sedentary time of preschoolers in centre-based childcare (registration no. CRD42016033502). Methods: Eight online databases were searched using terms related to physical activity, sedentary time, preschoolers and centre-based childcare. Published, peer-reviewed primary studies written in English that objectively assessed (via accelerometry) the physical activity and sedentary time of preschoolers (2-5 years) in centre-based childcare were included. Results: Fifty-five studies (published 2004-2017) from 11 countries, representing 13,956 participants were included. Studies reported light physical activity (n=38) ranging from 2.94 to 29.96 mins/hr, moderate-to-vigorous physical activity (n=46) which ranged from 1.29 to 22.66 mins/hr, and total physical activity (n=42) ranging from 4.23 to 47.17 mins/hr. Sedentary time (n=47) ranged from 12.38 to 55.77 mins/hr. Conclusion: Physical activity and sedentary time were highly varied and inconsistent between studies; therefore, it is difficult to determine preschoolers\u27 true amount of physical activity and sedentary time during childcare hours. Despite this variability, preschoolers were noted to participate in high rates of sedentary time in this setting. The lack of homogeneity is an important finding in and of itself as it highlights the lack of consistency in measuring, processing, and reporting paediatric physical activity data

Markers of MEK inhibitor resistance in low-grade serous ovarian cancer: EGFR is a potential therapeutic target 11 Medical and Health Sciences 1112 Oncology and Carcinogenesis

Background: Although low-grade serous ovarian cancer (LGSC) is rare, case-fatality rates are high as most patients present with advanced disease and current cytotoxic therapies are not overly effective. Recognizing that these cancers may be driven by MAPK pathway activation, MEK inhibitors (MEKi) are being tested in clinical trials. LGSC respond to MEKi only in a subgroup of patients, so predictive biomarkers and better therapies will be needed. Methods: We evaluated a number of patient-derived LGSC cell lines, previously classified according to their MEKi sensitivity. Two cell lines were genomically compared against their matching tumors samples. MEKi-sensitive and MEKi-resistant lines were compared using whole exome sequencing and reverse phase protein array. Two treatment combinations targeting MEKi resistance markers were also evaluated using cell proliferation, cell viability, cell signaling, and drug synergism assays. Results: Low-grade serous ovarian cancer cell lines recapitulated the genomic aberrations from their matching tumor samples. We identified three potential predictive biomarkers that distinguish MEKi sensitive and resistant lines: KRAS mutation status, and EGFR and PKC-alpha protein expression. The biomarkers were validated in three newly developed LGSC cell lines. Sub-lethal combination of MEK and EGFR inhibition showed drug synergy and caused complete cell death in two of four MEKi-resistant cell lines tested. Conclusions: KRAS mutations and the protein expression of EGFR and PKC-alpha should be evaluated as predictive biomarkers in patients with LGSC treated with MEKi. Combination therapy using a MEKi with EGFR inhibition may represent a promising new therapy for patients with MEKi-resistant LGSC

2017 WSES and SICG guidelines on acute calcolous cholecystitis in elderly population 11 Medical and Health Sciences 1103 Clinical Sciences

Background: Gallstone disease is very common afflicting 20 million people in the USA. In Europe, the overall incidence of gallstone disease is 18.8% in women and 9.5% in men. The frequency of gallstones related disease increases by age. The elderly population is increasing worldwide. Aim: The present guidelines aims to report the results of the World Society of Emergency Surgery (WSES) and Italian Surgical Society for Elderly (SICG) consensus conference on acute calcolous cholecystitis (ACC) focused on elderly population. Material and methods: The 2016 WSES guidelines on ACC were used as baseline; six questions have been used to investigate the particularities in elderly population; the answers have been developed in terms of differences compared to the general population and to statements of the 2016 WSES Guidelines. The Consensus Conference discusses, voted, and modified the statements. International experts contributed in the elaboration of final statements and evaluation of the level of scientific evidences. Results: The quality of the studies available decreases when we approach ACC in elderly. Same admission laparoscopic cholecystectomy should be suggested for elderly people with ACC; frailty scores as well as clinical and surgical risk scores could be adopted but no general consensus exist. The role of cholecystostomy is uncertain. Discussion and conclusions: The evaluation of pro and cons for surgery or for alternative treatments in elderly suffering of ACC is more complex than in young people; also, the oldest old age is not a contraindication for surgery; however, a larger use of frailty and surgical risk scores could contribute to reach the best clinical judgment by the surgeon. The present guidelines offer the opportunity to share with the scientific community a baseline for future researches and discussion

E-learning for self-management support: Introducing blended learning for graduate students - A cohort study 13 Education 1303 Specialist Studies in Education 11 Medical and Health Sciences 1117 Public Health and Health Services

Background: E-learning allows delivery of education in many diverse settings and researchers have demonstrated it can be as effective as learning conducted in traditional face-to-face settings. However, there are particular practices and skills needed in the area of providing patient self-management support (SMS), that may not be achievable online. The aim of this study was to compare three approaches in the training of university students regarding the preparation of a Chronic Condition Self-Management Care Plan: 1) traditional face-to-face delivery of SMS training, 2) an e-learning approach and 3) a blended approach (combining e-learning and face-to-face teaching). Methods: Graduate entry physiotherapy students and medical students at Flinders University were recruited. Depending on the cohort, students were either exposed to traditional face-to-face training, e-learning or a blended model. Outcomes were compared between the three groups. We measured adherence to care plan processes in the preparation of an assessment piece using the Flinders Program Chronic Care Self Management tools. A total of 183 care plans were included (102 traditional, 52 blended, 29 e-learning,). All students submitted the Flinders Program Chronic Care Plan for university assessment and these were later assessed for quality by researchers. The submission was also assigned a consumer engagement score and a global competence score as these are integral to successful delivery of SMS and represent the patient perspective. Results: The blended group performed significantly better than the traditional group in quality use of the Flinders Program tools: Problem and Goals (P < 0.0001). They also performed significantly better in the total care plan score (P < 0.0001) and engagement score (P < 0.0001). There was no significant difference between the groups for the Partners in Health tool. Conclusions: In this pilot study, the blended learning model was a more effective method for teaching self-management skills than the traditional group, as assessed in the development of a chronic condition self-management care plan. We anticipate that future research with identical groups of students would yield similar results but in the meantime, academics can have confidence that blended learning is at least as effective as traditional learning methods