Objective To evaluate evidence from randomised controlled trials and non-randomised controlled trials on the effectiveness of hospital clowns for a range of symptom clusters in children and adolescents admitted to hospital with acute and chronic conditions. Design Systematic review of randomised and non-randomised controlled trials. Data sources Medline, ISI of Knowledge, Cochrane Central Register of Controlled Trials, Science Direct, Scopus, American Psychological Association PsycINFO, Cumulative Index to Nursing and Allied Health Literature, and Latin American and Caribbean Health Sciences Literature. Study selection Randomised and non-randomised controlled trials were peer reviewed using the following eligibility criteria: children and adolescents who were admitted to hospital for acute conditions or chronic disorders, studies comparing use of hospital clowns with standard care, and studies evaluating the effect of hospital clowns on symptom management of inpatient children and adolescents as a primary outcome. Data extraction and synthesis Two investigators independently screened studies, extracted data, and appraised the risk of bias. Methodological appraisal was assessed by two investigators independently using the Jadad scale, the revised Cochrane risk-of-bias tool for randomised controlled trials (RoB 2), and the risk of bias in non-randomised studies (ROBINS-I) tool for non-randomised controlled trials. Results 24 studies (n=1612) met the inclusion criteria for data extraction and analysis. Most studies were randomised controlled trials (n=13). Anxiety was the most frequently analysed symptom (n=13), followed by pain (n=9), psychological and emotional responses and perceived wellbeing (n=4), stress (n=4), cancer related fatigue (n=3), and crying (n=2). Five studies used biomarkers, mainly cortisol, to assess stress or fatigue outcome following hospital clowns. Most of the randomised controlled trials (n=11; 85%) were rated as showing some concerns, and two trials were rated with a high risk of bias. Most non-randomised controlled trials (n=6; 55%) were rated with a moderate risk of bias according to ROBINS-I tool. Studies showed that children and adolescents who were in the presence of hospital clowns, either with or without a parent present, reported significantly less anxiety during a range of medical procedures, as well as improved psychological adjustment (P<0.05). Three studies that evaluated chronic conditions showed favourable results for the intervention of hospital clowns with significant reduction in stress, fatigue, pain, and distress (P<0.05). Conclusions These findings suggest that the presence of hospital clowns during medical procedures, induction of anaesthesia in the preoperative room, and as part of routine care for chronic conditions might be a beneficial strategy to manage some symptom clusters. Furthermore, hospital clowns might help improve psychological wellbeing in admitted children and adolescents with acute and chronic disorders, compared with those who received only standard care. Systematic review registration PROSPERO CRD42018107099.

Background Clown intervention has been shown to enhance emotional and behavioral processes, but few studies have comprehensively examined the effectiveness of this practice using biomarkers. Objective The aim of this study was to evaluate the effect of a clown intervention on the levels of psychological stress and cancer-related fatigue in pediatric patients with cancer undergoing chemotherapy. Methods Sixteen patients who met all criteria from a pediatric oncology inpatient unit in a Brazilian comprehensive cancer care hospital participated in this quasi-experimental study. Eight saliva samples were collected, comprising 4 at baseline and 4 after clown intervention (+1, +4, +9, and +13 hours after awakening). Salivary cortisol and α-amylase levels were determined using high-sensitivity enzyme-linked immunosorbent assay kits. Stress and fatigue were measured by the Child Stress Scale-ESI and the PedsQL Multidimensional Fatigue Scale, respectively. Relationships among stress, fatigue, and biomarker levels were investigated using nonparametric statistics. Results In comparison with baseline measurements, the total psychological stress and fatigue levels improved after the clown intervention at the collection time point +4 hours (P = .003 and P = .04, respectively). Salivary cortisol showed a significant decrease after clown intervention at the collection time points +1, +9, and +13 hours (P < .05); however, α-amylase levels remained unchanged. Conclusion These findings provide preliminary evidence that clown intervention merits further study as a way to reduce stress and fatigue in pediatric cancer inpatients, and that self-report and biomarker measures are feasible to collect in this patient group. Implications for Practice Clown intervention as a nonpharmacological intervention may improve stress and fatigue levels in pediatric inpatients with cancer undergoing chemotherapy.

The present study aimed to evaluate the effects of two serine proteases from Bothrops pirajai snake venom, named BpirSP27 and BpirSP41, on the complement system and the inflammatory response. The effects of these enzymes on the human complement system were assessed by kinetic hemolytic assays, evaluating the hemolysis promoted by the classical/lectin (CP/LP) and alternative (AP) pathways after incubation of normal human serum with the serine proteases. The results suggested that these enzymes were able to induce modulation of CP/LP and AP at different levels: BpirSP41 showed higher inhibitory effects on the hemolytic activity of CP/LP than BpirSP27, with inhibition values close to 40% and 20%, respectively, for the highest concentration assayed. Regarding AP, both enzymes showed percentages of inhibition of the hemolytic activity around 20% for the highest concentrations tested, indicating similar effects on this complement pathway. The proinflammatory effects of B. pirajai serine proteases were evaluated regarding their ability to induce paw edema, variations in the pain threshold and leukocyte recruitment at the site of injection. Both showed mild effects on these inflammatory processes, leading to low levels of increase of paw volumes and decrease in pain thresholds in rats up to 6 h after injection, and inducing neutrophil recruitment without significant increases in the total number of leukocytes in the inflammatory exudates after 6 and 24 h of administration into mice peritoneal cavity. These results suggest that serine proteases must present a minor role in the inflammation caused by B. pirajai snake venom.

IntroductionSince March 2020, when the COVID-19 outbreak has been deemed a pandemic by the WHO, the SARS-CoV-2 spreading has been the focus of attention of scientists, authorities, public health agencies and communities around the world. One of the great concerns and challenges, mainly in low-income and middle-income countries, is the identification and monitoring of COVID-19 cases. The large-scale availability of testing is a fundamental aspect of COVID-19 control, but it is currently the biggest challenge faced by many countries around the world. We aimed to synthesise and critically evaluate the scientific evidence on the influence of the testing capacity for symptomatic individuals in the control of COVID-19.Methods and analysisA systematic review will be conducted in eight databases, such as Medical Literature Analysis and Retrieval System Online, ISI-of-Knowledge, Cochrane Central Register of Controlled Trials, Embase, SCOPUS, Latin American and Caribbean Health Sciences Literature, PsycINFO and Chinese National Knowledge Infrastructure, from inception to 30 July 2020. No restriction regarding the language, publication date or setting will be employed. Primary outcomes will include the sensitivity as well as the specificity of the tests for COVID-19. Study selection will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Methodological assessment of the studies will be evaluated by the Cochrane Risk-of-Bias tool for randomised controlled trials, the MINORS for non-randomised studies and the Newcastle-Ottawa Scale for cohort or case–control studies. Findings will be structured according to the test type and target population characteristics and focused on the primary outcomes (sensitivity and specificity). Moreover, if sufficient data are available, a meta-analysis will be performed. Pooled standardised mean differences and 95% CIs will be calculated. Heterogeneity between the studies will be determined by I2 statistics. Subgroup analyses will also be conducted. Publication bias will be assessed with funnel plots and Egger’s test. Heterogeneity will be explored by random effects analysis.Ethics and disseminationEthical approval is not required. The results will be disseminated widely via peer-reviewed publication and presentations at conferences related to this field.PROSPERO registration numberCRD42020182724.

Background: Pediatric cancer patients experience different psychological processes during hospitalization that may regulate the immune response and affect recovery and response to cancer treatment. In this study, we aimed to examine the feasibility of longitudinal testing of psychophysiological parameters of stress and fatigue in pediatric osteosarcoma patients hospitalized for chemotherapy submitted to clown intervention; and to investigate whether changes in the levels of biomarkers are associated with psychological stress and fatigue levels in these patients after the clown intervention. Methods: A pretest-posttest quasi-experimental pilot study was conducted at the pediatric oncology inpatient unit in a comprehensive cancer care center in Brazil including children and adolescents with osteosarcoma hospitalized for chemotherapy. Eight saliva samples were collected, comprising 4 at baseline (pre-intervention) and 4 after the clown intervention (+1, +4, +9, and +13 hours post-awakening). Salivary cortisol, α-amylase (sAA), cytokines, and matrix metalloproteinase-9 (MMP-9) levels were determined using high-sensitivity enzyme-linked immunosorbent assay (ELISA) kits. Stress and fatigue were measured by Child Stress Scale–ESI and PedsQL Multidimensional Fatigue Scale respectively. Bivariate association analysis between stress and fatigue scores and biomarker levels were investigated using nonparametric statistics. Effect sizes were calculated for each outcome variable. Results: Six pediatric osteosarcoma patients were enrolled with no missing data. No significant effects sizes were observed for psychophysiological outcomes. Effect sizes ranged from 0.54 (cortisol) to 0 (interleukin-1β [IL-1β]). Decreasing overall trends were observed for cortisol levels for all 6 pediatric osteosarcoma patients over time. In addition, a similar pattern of tumor necrosis factor–α (TNF-α) levels over time was found for all 6 patients. Patients with metastatic osteosarcoma showed a linear trend for a decrease in MMP-9 levels between 1 and 9 hours after the clown intervention and restoration to basal levels after 13 hours. Conclusions: The results of this pilot study suggest that it is feasible longitudinally measure psychophysiological outcomes in the pediatric osteosarcoma inpatients for chemotherapy. Clown intervention merits further study as a way to reduce stress as well as fatigue, since that the stress and cytokines measurements are feasible based on our work.

BACKGROUND Colitis-associated cancer (CAC) accounts for 2%-3% of colorectal cancer (CRC) cases preceded by inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis. Intestinal microbiota has been reported to play a central role in the pathogenesis of IBD and CAC. Recently, numerous prebiotics and probiotics have being investigated as antitumor agents due to their capacity to modulate inflammatory responses. Previous studies have indicated that lactic acid bacteria could be successfully used in managing sporadic CRC, however little is known about their role in CAC. AIM To investigate the effect of the probiotic Lactobacillus bulgaricus ( L. bulgaricus ) during the development of an experimental model of colitis associated colon cancer (CAC). METHODS C57BL/6 mice received an intraperitoneal injection of azoxymethane (10 mg/kg), followed by three cycles of sodium dextran sulphate diluted in water (5% w/v). Probiotic group received daily L. bulgaricus . Intestinal inflammation was determined by scoring clinical signs. Cytokines levels were determined from colon and/or tumor samples by ELISA BD OptEIATM kits. The level of significance was set at P < 0.05. Graphs were generated and statistical analysis performed using the software GraphPad Prism 6.0. RESULTS L. bulgaricus treatment inhibited of total tumor volume and mean size of tumors. In addition, the probiotic also attenuated the clinical signs of intestinal inflammation inducing a decrease in intestinal and tumor levels of IL-6, TNF-α, IL-17, IL-23 and IL-1β. CONCLUSION Our results suggest a potential chemopreventive effect of probiotic on CAC. L. bulgaricus regulates the inflammatory response and preventing CAC.

The results demonstrate that HYAL inhibited cellular recruitment, edema formation and pro-inflammatory mediators production, resulting in decreased adherence of leukocytes to blood vessels and tissue infiltration. Our data suggest that HYAL may be considered an effective candidate to ameliorate acute inflammation.

IntroductionClown intervention may playing an important complementary role in paediatric care and recovery. However, data on its utility for symptom cluster management of hospitalised children and adolescents in acute and chronic disorders are yet to be critically evaluated. As clinicians strive to minimise the psychological burden during hospitalisation, it is important that they are aware of the scientific evidences available regarding clown intervention for symptom management. We aim to provide quality evidence for the effectiveness of clown intervention on symptom cluster management in paediatric inpatients, both in acute and chronic conditions.Methods and analysisA systematic review of randomised controlled trials (RCTs) and non-randomised controlled trials (NRCTs) will be conducted. MEDLINE, Web of Science, Cochrane Library, Science Direct, PsycINFO, CINAHL, LILACS and SciELO databases will be searched from January 2000 to December 2018. Primary outcomes will include measures related with the effect of clown intervention on symptom cluster of paediatric inpatients (anxiety, depression, pain, fatigue, stress and psychological, emotional responses and perceived well-being). Study selection will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and the methodological appraisal of the studies will be assessed by the Jadad Scale as well as Cochrane Risk-of-Bias Tool for RCTs, and Risk-of-Bias In Non-Randomized Studies Tool for NRCTs. A narrative synthesis will be conducted for all included studies. Also, if sufficient data are available, a meta-analysis will be conducted. The effect sizes will be generated using Hedges’ g score for both fixed and random effect models. I 2 statistics will be used to assess heterogeneity and identify their potential sources.Ethics and disseminationAs it will be a systematic review, without human beings involvement, there will be no requirement for ethical approval. Findings will be disseminated widely through peer-reviewed publication and in various media, for example, conferences, congresses or symposia.Trial registration numberCRD42018107099.