Powder diet exacerbates oropharyngeal candidiasis in a mouse model.

This study reports on the influence of a powder diet in a mouse model of oropharyngeal candidiasis (OPC), a significant health concern caused primarily by Candida albicans. Despite identical nutritional composition, we found that a powdered diet significantly increased Candida burdens and oral lesions, and aggravated weight loss compared to a standard pelleted diet. High fungal burdens and severe oral lesions were accomplished within 48 hours after infection with only one dose of cortisone. Moreover, mice on a powder diet recovered a week after infection. Using a powder diet, we thus modified the cortisone OPC murine model in a way that simplifies the infection process, enhances reproducibility, and facilitates studies investigating both pathogenesis and recovery processes. Our findings also underscore the pivotal role of the physical form of the diet in the progression and severity of oral Candida infection in this model. Future research should investigate this relationship further to broaden our understanding of the underlying mechanisms, potentially leading to novel prevention strategies and improved disease management.IMPORTANCEOropharyngeal candidiasis (OPC) is a multifactorial disease and a significant health concern. We found that the physical form of the diet plays a critical role in the severity and progression of OPC. We developed a modified cortisone OPC murine model that facilitates studies investigating pathogenesis and recovery processes.

Maternal and Perinatal Outcomes Associated With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection During Pregnancy, Florida, 2020-2021: A Retrospective Cohort Study.

BACKGROUND: The objective was to estimate risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy and assess adverse maternal and perinatal outcomes. METHODS: We used a population-based, retrospective cohort of all pregnancies with a live birth or fetal death in Florida from 1 March 2020 to 30 April 2021. Coronavirus disease 2019 (COVID-19) case reports were matched to vital registries. Outcomes assessed were risk of infection in pregnancy, preterm birth, maternal or neonatal admission to an intensive care unit (ICU), perinatal or fetal death, and maternal death. Modified Poisson and multinomial logistic regression models were used to derive relative risk estimates. RESULTS: Of 234 492 women with a live birth or fetal death during the study period, 12 976 (5.5%) were identified with COVID-19 during pregnancy. Risk factors for COVID-19 in pregnancy included Hispanic ethnicity (relative risk [RR] = 1.89), Black race (RR = 1.34), being unmarried (RR = 1.04), and being overweight or obese pre-pregnancy (RR = 1.08-1.32). COVID-19 during pregnancy was associated with preterm birth (RR = 1.31), Cesarean delivery (RR = 1.04), and neonatal (RR = 1.17) and maternal (RR = 3.10) ICU admission; no association was found with increased risk of perinatal (RR = 0.72) or fetal death (RR = 0.86). Women infected during any trimester showed increased risk of preterm birth. Fourteen maternal deaths were identified among COVID-19 cases; of those who died, 12 were obese. The death rate per 10 000 was 22.09 among obese and 1.22 among non-obese gravida with COVID-19 during pregnancy (RR = 18.99, P = .001). CONCLUSIONS: Obesity is a risk factor for SARS-CoV-2 infection in pregnancy and for more severe COVID-19 illness among pregnant women. SARS-CoV-2 infection is associated with preterm birth.

Optimizing Post-Cesarean Opioid Prescription Practices at Mayo Clinic: A Quality Improvement Initiative.

OBJECTIVE: Optimal prescriptions practices of opioids in the post-cesarean period remain controversial. The primary aim of this initiative was to minimize unused prescription narcotic medication, with a goal of ≤4 leftover pills of 5-mg oxycodone at postoperative day (POD) 14 without affecting pain or satisfaction measures. STUDY DESIGN: This was a prospective longitudinal quality improvement (QI) initiative starting in 2017 utilizing the DMAIC methodology. The measurement phase consisted of validated surveys over 3 months, along with chart review to determine current institutional prescription practices and predictors of outpatient opioid use. Resulting recommendations were adopted, and 1 year later, all patients undergoing cesarean were surveyed for 3 months to determine the effectiveness of the intervention. The study was approved by the Department's QI Committee. RESULTS: The response rate was 48%, with 50 of 101 patients completing surveys pre-intervention and 52 of 111 post-intervention. Pre-intervention, surplus medication was predicted (p <0.05) only by the quantity of the opioid prescription. In addition, patients who required ≤37.5 morphine milligram equivalents (MMEs) during the inpatient postoperative stay did not require outpatient narcotic prescriptions. Thereafter, a strategy of matching inpatient use to outpatient prescription 1:1 in a linear regression model (p <0.001, R 2 0.55) optimally matched patient needs up to 200 MME. In the post-intervention survey, mean (SD) prescription decreased from 17.6 (13.7) MME to 8.4 (8.3) MME (p <0.01); 39% compared with 16% of women were discharged without a prescription (p <0.01); and amongst all patients 82.7% compared with 59.6% (p <0.01) had ≤4 pills remaining without differences in patient satisfaction or pain perception. CONCLUSION: This initiative highlights a practical approach to QI utilizing industry techniques in health care. This approach resulted in significant reductions in over-prescription and unused medication, without impacting pain or satisfaction scores. KEY POINTS: · 20% of patients may manage pain at home without opioids.. · In-hospital opioid use is reflective of outpatient need.. · Customize prescriptions to reduce leftover narcotics..

Femur morphology in healthy infants and young children.

The objective of this study was to characterize femur morphology in healthy infants and young children. Anterior-posterior (AP) radiographs of the femur from children age 0-3 years with no history of bone disease were obtained from two children's hospitals and one medical examiner's office. Femur morphological measures (bone length, minimum diaphysis diameter, growth plate width, and femur radius of curvature) and sectional structural measures were determined. Measures were described and compared based on subject age and mass. Relationships between measures and age and mass were evaluated. The 169 AP femur radiographs were obtained from 99 children (59.6% males, median age = 12.0 months, IQR = 0-27.5 months, median body weight = 10.0 kg, IQR = 4.4-15.6 kg). Femur length (rs  = 0.97, p < 0.001; rs  = 0.89, p < 0.001), trochanter width (rs  = 0.86, p < 0.001; rs  = 0.85, p < 0.001), minimum diaphysis diameter (rs  = 0.91, p < 0.001; rs  = 0.87, p < 0.001), and growth plate width (rs  = 0.91, p < 0.001; rs  = 0.84, p < 0.001) increased with age and weight, respectively. Cross-sectional area (rs  = 0.87; rs  = 0.86; p < 0.01), polar moment of inertia (rs  = 0.91; rs  = 0.87; p < 0.001), moment of inertia (rs  = 0.91; rs  = 0.87; p < 0.001), polar modulus (rs  = 0.91; rs  = 0.87; p < 0.001) and medullary canal diameter (rs  = 0.83, p < 0.001; rs  = 0.73, p < 0.001) at the minimum diaphysis also increased with age and weight, respectively. Changes during rapid bone growth are important to understanding fracture risk in infants and young children as they transition to independent walking. Femur length, trochanter width, minimum diaphysis diameter and growth plate width increased with age and weight. Structural properties associated with fracture resistance also increased with age and weight.

Candida albicans induces mucosal bacterial dysbiosis that promotes invasive infection.

Infectious complications are a common cause of morbidity and mortality in cancer patients undergoing chemotherapy due to increased risk of oral and gastrointestinal candidiasis, candidemia and septicemia. Interactions between C. albicans and endogenous mucosal bacteria are important in understanding the mechanisms of invasive infection. We published a mouse intravenous chemotherapy model that recapitulates oral and intestinal mucositis, and myelosuppression in patients receiving 5-fluorouracil. We used this model to study the influence of C. albicans on the mucosal bacterial microbiome and compared global community changes in the oral and intestinal mucosa of the same mice. We validated 16S rRNA gene sequencing data by qPCR, in situ hybridization and culture approaches. Mice receiving both 5Fu and C. albicans had an endogenous bacterial overgrowth on the oral but not the small intestinal mucosa. C. albicans infection was associated with loss of mucosal bacterial diversity in both sites with indigenous Stenotrophomonas, Alphaproteobacteria and Enterococcus species dominating the small intestinal, and Enterococcus species dominating the oral mucosa. Both immunosuppression and Candida infection contributed to changes in the oral microbiota. Enterococci isolated from mice with oropharyngeal candidiasis were implicated in degrading the epithelial junction protein E-cadherin and increasing the permeability of the oral epithelial barrier in vitro. Importantly, depletion of these organisms with antibiotics in vivo attenuated oral mucosal E-cadherin degradation and C. albicans invasion without affecting fungal burdens, indicating that bacterial community changes represent overt dysbiosis. Our studies demonstrate a complex interaction between C. albicans, the resident mucosal bacterial microbiota and the host environment in pathogenesis. We shed significant new light on the role of C. albicans in shaping resident bacterial communities and driving mucosal dysbiosis.

Biofilm Interactions of Candida albicans and Mitis Group Streptococci in a Titanium-Mucosal Interface Model.

Streptococci from the mitis group (represented mainly by Streptococcus mitis, Streptococcus oralis, Streptococcus sanguinis, and Streptococcus gordonii) form robust biofilms with Candida albicans in different experimental models. These microorganisms have been found in polymicrobial biofilms forming on titanium biomaterial surfaces in humans with peri-implant disease. The purpose of this work was to study mutualistic interactions in biofilms forming on titanium and their effect on the adjacent mucosa, using a relevant infection model. Single and mixed biofilms of C. albicans and each Streptococcus species were grown on titanium disks. Bacterial and fungal biovolume and biomass were quantified in these biofilms. Organotypic mucosal constructs were exposed to preformed titanium surface biofilms to test their effect on secretion of proinflammatory cytokines and cell damage. C. albicans promoted bacterial biofilms of all mitis Streptococcus species on titanium surfaces. This relationship was mutualistic since all bacterial species upregulated the efg1 hypha-associated gene in C. albicans Mixed biofilms caused increased tissue damage but did not increase proinflammatory cytokine responses compared to biofilms comprising Candida alone. Interestingly, spent culture medium from tissues exposed to titanium biofilms suppressed Candida growth on titanium surfaces.IMPORTANCE Our findings provide new insights into the cross-kingdom interaction between C. albicans and Streptococcus species representative of the mitis group. These microorganisms colonize titanium-based dental implant materials, but little is known about their ability to cause inflammation and damage of the adjacent mucosal tissues. Using an in vitro biomaterial-mucosal interface infection model, we showed that mixed biofilms of each species with C. albicans enhance tissue damage. One possible mechanism for this effect is the increased fungal hypha-associated virulence gene expression we observed in mixed biofilms with these species. Interestingly, we also found that the interaction of multispecies biofilms with organotypic mucosal surfaces led to the release of growth-suppressing mediators of Candida, which may represent a homeostatic defense mechanism of the oral mucosa against fungal overgrowth. Thus, our findings provide novel insights into biofilms on biomaterials that may play an important role in the pathogenesis of mucosal infections around titanium implants.

Characteristics of rib fractures in young abused children.

BACKGROUND: The presumed mechanism of rib fractures in abuse is violent grasping of the torso causing anterior-posterior chest compression. We hypothesized an asymmetrical distribution of rib fractures in abused infants given the greater incidence of right-hand dominance within the general population. OBJECTIVE: The objective of this study was to characterize rib fractures in abused children, particularly sidedness; additionally, we evaluated the sidedness of other abusive skeletal fractures. MATERIALS AND METHODS: We reviewed medical records from abused children (0-18 months old) with rib fractures. We also retrospectively reviewed their radiographs to determine characteristics of rib fractures (number, side, rib region, level, acuity) and other skeletal fractures (number, side, location), as well as differences in the distribution of rib and other skeletal fractures. RESULTS: A total of 360 rib fractures were identified on 273 individual ribs involving 78 abused children. Sixty-three children (81%) had multiple rib fractures. There was a significantly greater number of left-side rib fractures (67%) than right-side fractures (P<0.001). Fractures were most often identified in the posterior and lateral regions and mid level of the ribcage (Ribs 5 through 8). Fifty-four percent of subjects had other skeletal fractures; these non-rib fractures were also predominantly on the left side (P=0.006). CONCLUSION: In our study of abused children, there was a higher incidence of rib fractures in the posterior, lateral and mid-level locations. Additionally, we found a predominance of left-side rib and other skeletal fractures. Further research is needed to understand whether factors such as perpetrator handedness are associated with these unequal distributions of fractures in abused children.

Retraction Note to: Radiographic characteristics that delineate abusive from accidental skull fractures, including the significance of fracture extension to sutures.

The authors have retracted the abstract #029 "Radiographic characteristics that delineate abusive from accidental skull fractures, including the significance of fracture extension to sutures".

Treatment patterns and related clinical consequences in adults with asthma.

OBJECTIVE: A stepwise therapeutic management is recommended for asthma patients by the Global Initiative for Asthma (GINA). Little is known about the recommendations applied in real world settings. This study aims to associate Treatment step with clinical events in patients with mild or severe asthma. METHODS: A retrospective claims database analysis included adult patients with mild (GINA step 1) or severe asthma (GINA step 4). Maximum Treatment Step was measured within the first and second 90-day period after index date (the first date of asthma diagnosis during the inclusion period). Step-down was defined as a Treatment Step change from a higher to lower step, while Step-up was defined as a Treatment Step change from a lower to higher step. The primary outcome was a composite endpoint of asthma-related clinical events, measured at the third 90-day period. RESULTS AND CONCLUSIONS: A total of 6,354 mild-asthma patients and 5,695 severe-asthma patients were included. In mild-asthma, when compared with No Change in Treatment Step, Step-down was associated with a lower risk of future clinical events [adjusted odds ratio (OR) 0.80, 95% confidence interval (95% CI); 0.69-0.94], while Step-up was not associated with a change in clinical events [OR 0.98, 95% CI: 0.77-1.27]. In severe-asthma patients, Step-down was not associated with a change in clinical events [OR 0.94, 95% CI: 0.81-1.10], while Step-up was associated with a higher risk of future clinical events [OR 2.07, 95% CI: 1.29-3.33]. Our findings reassure the appropriateness of stepping-down treatment in mild-asthma patients. Clinicians should closely monitor and/or provide detailed asthma action plans for severe-asthma patients who are stepping-up treatment.

Factors influencing the acceptance of referrals for clinical pharmacist managed disease states in primary care.

OBJECTIVE: Clinical pharmacists use population health methods to generate chronic disease management referrals for patients with uncontrolled chronic conditions. The purpose of this study was to compare primary care providers' (PCPs) referral responses for 4 pharmacist-managed indications and to identify provider and patient characteristics that are predictive of PCP response. DESIGN: Retrospective cohort study. SETTING: This study occurred in an academic internal medicine clinic. PARTICIPANTS: Clinical pharmacy referrals generated through a population health approach between 2012 and 2016 for hypertension, chronic pain, depression, and benzodiazepine management were included. MAIN OUTCOME MEASURES: Proportion of referrals accepted, left pending, or rejected and influencing provider and patient characteristics. RESULTS: Of 1769 referrals generated, PCPs accepted 869 (49%), left pending 300 (17%), and rejected 600 (34%). Compared with referrals for hypertension, benzodiazepine management, and depression, chronic pain referrals had the lowest likelihood of rejection (odds ratio [OR] 0.31; 95% CI 0.19-0.49). Depression referrals had an equal likelihood of being accepted or rejected (OR 1.04; 95% CI 0.66-1.64). Provider characteristics were not significantly associated with referral response, but residents were more likely to accept referrals. Patient characteristics associated with lower referral rejection included black race (OR 0.39; 95% CI 0.18-0.87), higher systolic blood pressure (OR 0.98; 95% CI 0.97-0.99), and missed visits (OR 0.24; 95% CI 0.07-0.81). CONCLUSION: The majority of referrals for clinical pharmacists in primary care settings were responded to, varying mostly between acceptance and rejection. There was variability in referral acceptance across indications, and some patient characteristics were associated with increased referral acceptance.

"Reasonable adjustments" under the UK's Equality Act 2010: An enquiry into the care and treatment to patients with intellectual disabilities in acute hospital settings.

OBJECTIVES: To understand the views of qualified medical practitioners regarding "reasonable adjustments" and the quality of the care and treatment provided to adults with intellectual disabilities when admitted to acute hospitals as inpatients. METHODS: Semi-structured interviews took place with 14 medical practitioners, seven from each of two acute hospitals, with a thematic analysis of the resulting data. RESULTS: All 14 medical practitioners reported problems in the diagnosis and treatment of patients with intellectual disabilities. Most participants attributed these difficulties to communication problems and/or behaviours that, in the context of a hospital ward, were non-conforming. However, a minority reported that, because they were likely to have multiple comorbid health conditions, patients with intellectual disabilities were more complex. In addition, half of all these respondents reported making little use of "reasonable adjustments" introduced to improve the quality of the care received by this group of patients. CONCLUSIONS: Medical practitioners should make better use of the "reasonable adjustments" introduced in the UK to address inequities in care and treatment received by patients with intellectual disabilities. However, training should also focus on the biomedical complexities often presented by these men and women.

Semaglutide: The Newest Once-Weekly GLP-1 RA for Type 2 Diabetes.

OBJECTIVE: To review efficacy and safety of the glucagon-like peptide-1 receptor agonist (GLP-1 RA) semaglutide for type 2 diabetes (T2D). DATA SOURCES: A literature search of PubMed/MEDLINE and EMBASE using the term semaglutide was completed through April 2018. A search of clinicaltrials.gov was also conducted. STUDY SELECTION AND DATA EXTRACTION: English-language studies assessing the efficacy and/or safety of semaglutide were evaluated. DATA SYNTHESIS: Semaglutide is a newly approved GLP-1 RA for the treatment of T2D. Administered once weekly at a dose of 0.5 or 1 mg, it has been compared with placebo, sitagliptin, insulin glargine, a combination of oral antidiabetic therapies, and 2 GLP-1 RAs, exenatide ER and dulaglutide, and demonstrated greater efficacy compared with these therapies. Published data from studies ranging from 30 to 104 weeks duration demonstrate efficacy with decreases in hemoglobin A1C (A1C) ranging from 1.1% to 2.2%. Studies show reductions in weight from 1.4 to 6.5 kg. Semaglutide demonstrated a reduction in the composite outcome of cardiovascular (CV) death, nonfatal myocardial infarction, or nonfatal stroke compared with placebo in patients at high risk of CV events (hazard ratio = 0.74; P = 0.02). Common adverse effects include nausea, vomiting, and diarrhea as seen with other GLP-1 RAs. Relevance to Patient Care and Clinical Practice: Semaglutide represents an attractive GLP-1 RA considering its A1C and weight reduction. It provides patient convenience and high patient satisfaction. CONCLUSIONS: Semaglutide is an appealing option for the treatment of T2D as a once-weekly GLP-1 RA with established glycemic, CV, and weight benefits.

Developing a caseload classification tool for community nursing.

Acuity and dependency in the community nursing caseload in combination with safe staffing levels are a national issue of concern. Current evidence suggests that there are no clear approaches to determining staff capacity and skill mix in these community settings. As community nursing caseloads are large with differing complexities, there is a need to allocate community nursing with the best skill mix to achieve the best patient outcomes. A city-wide service improvement initiative developed a tool to classify and categorise patient demand and this was linked to an electronic patient record system. The aim was to formulate an effective management response to different levels of acuity and dependency within community nursing teams and a consensus approach was used to allow the definition of complexity for twelve packages of care. The tool was piloted by a group of community nurses to assess the validity as a method to achieve a caseload classification. Seventy nurses were trained and applied the tool to 3000 patient referrals. Based on this, standards of care were agreed including expectations of assessment, intervention, visit length and frequency. Community nursing caseloads can now be organised according to acuity and complexity of patient need, which determines allocation of staff and skill mix.

Streptococcus oralis and Candida albicans Synergistically Activate µ-Calpain to Degrade E-cadherin From Oral Epithelial Junctions.

Streptococcus oralis forms robust mucosal biofilms with Candida albicans that have increased pathogenic potential. In this study, using oral epithelial cultures, organotypic oral mucosal constructs, and a mouse model of oral infection, we demonstrated that S. oralis augmented C. albicans invasion through epithelial junctions. C. albicans and S. oralis decreased epithelial E-cadherin levels by synergistically increasing µ-calpain, a proteolytic enzyme that targets E-cadherin. In the mouse coinfection model this was accompanied by increased fungal kidney dissemination. Coinfection with a secreted aspartyl protease (sap) mutant sap2456 and S. oralis increased µ-calpain and triggered mucosal invasion and systemic dissemination, suggesting that fungal protease activity is not required for invasion during coinfection. We conclude that C. albicans and S. oralis synergize to activate host enzymes that cleave epithelial junction proteins and increase fungal invasion.

Biomechanical investigation of the classic metaphyseal lesion using an immature porcine model.

OBJECTIVE: The classic metaphyseal lesion is highly associated with abuse in infants. Classic metaphyseal lesions, also referred to as corner or bucket-handle fractures, are fractures through the metaphyseal region of the long bones near the growth plate. Knowledge of the biomechanics and mechanisms necessary to produce a classic metaphyseal lesion may provide insight into the injury causation associated with this unique fracture type. Thus, the purpose of this study was to investigate loading conditions necessary to create a classic metaphyseal lesion using an immature porcine model. MATERIALS AND METHODS: Twenty-four pelvic limb specimens from 7-day-old and 3-day-old piglets were tested in lateral bending (varus and valgus) using an electromechanical testing machine. All specimens were loaded dynamically in four-point bending at a rate of 100 inches/min. Microcomputed tomography was performed on specimens before and after testing. Pre- and posttest CT images were compared to assess whether fracture had occurred. RESULTS: Fractures resembling classic metaphyseal lesions were identified in 12 of the 24 specimens. Microcomputed tomography images revealed trabecular disruptions visually similar to classic metaphyseal lesions in children. CONCLUSION: Metaphyseal fractures, consistent with clinical classic metaphyseal lesions, resulted from a single loading event delivering varus or valgus bending to the stifle (knee). A classic metaphyseal lesion is a unique type of fracture with specific morphologic characteristics. Therefore, we suggest using the term "classic metaphyseal fracture" in lieu of classic metaphyseal lesion to improve precision of terminology.

Dulaglutide: the newest GLP-1 receptor agonist for the management of type 2 diabetes.

OBJECTIVE: To review the pharmacology, pharmacokinetics, safety, and efficacy of the glucagon-like peptide-1 receptor agonist (GLP-1 RA), dulaglutide, in the treatment of type 2 diabetes mellitus (T2D). DATA SOURCES: A PubMed search was completed to identify publications from 1947 to October 2014 using the search terms dulaglutide and LY2189265. References were reviewed to identify additional resources. STUDY SELECTION AND DATA EXTRACTION: Articles were included if they evaluated the pharmacology, pharmacokinetics, safety, or efficacy of dulaglutide. DATA SYNTHESIS: Dulaglutide reduces both glycosylated hemoglobin (A1C) and weight by stimulating insulin secretion and suppressing glucagon in a glucose-dependent manner, delaying gastric emptying, and promoting satiety. Dulaglutide consists of 2 GLP-1 analogues that have been modified to make it a long-acting, once-weekly agent. Dulaglutide has been studied as monotherapy and in combination with metformin, glimepiride, pioglitazone, and insulin lispro. It has demonstrated superior A1C reduction compared with placebo, metformin, insulin glargine, sitagliptin, and twice-daily exenatide. It demonstrated noninferiority in A1C reduction to liraglutide. Dulaglutide changed A1C by -0.78% to -1.51%, and it changed weight by -0.35 kg to -3.03 kg. The most common adverse effects in clinical studies were nausea, vomiting, and diarrhea. CONCLUSIONS: Dulaglutide is the fifth GLP-1 RA approved for T2D in the United States. It is an attractive option because it is dosed once-weekly, provides A1C lowering similar to liraglutide, weight reduction similar to exenatide, and has an adverse effect profile similar to exenatide and liraglutide.

Noise at night in hospital general wards: a mapping of the literature.

English NHS inpatient surveys consistently identify that noise at night in hospitals and its impact on patients' sleep is a persisting problem that needs addressing. To identify how noise at night in hospital affects patients on general wards and the range of interventions aimed at reducing the problem, a systematic mapping of the literature was undertaken. All primary studies and relevant literature published January 2003-July 2013 were included. Key issues identified in the literature included noise levels and causes, impact on patient experience, and lack of staff awareness. Interventions to reduce noise were targeted at staff education, behaviour modification, care organisation and environmental solutions. The scoping suggested that when compared with specialist units, there is little evidence on effective interventions reducing disturbance from night-time noise on general wards. The available evidence suggests a whole systems approach should be adopted to aid quality sleep and promote recovery.

Prognostic indicators for children and young people at the end of life: A Delphi study.

BACKGROUND: Recognizing transitions in end of life care for children is difficult and hinders communication and care planning. AIM: To identify the signs and symptoms that are most useful in signalling which children may have end of life care needs. METHODS: A Delphi study was undertaken with palliative care professionals who rated the extent to which 75 symptoms alerted them that a child/young person may have moved into his or her last (a) weeks/days, (b) 6-12 months of life using a 7-point response scale. Level of support for items was indicated by the median, and consensus was shown by the mean absolute deviation from the median. The impact of the Delphi on final agreement and consensus was also assessed. RESULTS: Second-round questionnaires were completed by 49 (89%) individuals. It was easier to identify prognostic items in the last weeks/days than earlier in the end of life trajectory. Items most indicative included failure of physiological systems, deteriorating level of consciousness, loss of autonomic control (e.g. breathing and peripheral circulation), together with a feeling of the professional that life is ending and an agreement that resuscitation would be futile. Items most indicative of last 6/12 months suggest a progressive decline in disease trajectory, increased chest infections or other complications from which the child has difficulty in making a full recovery and which may require high dependency or critical care. CONCLUSION: This study provides important insight into which signs and symptoms are considered most valuable in identifying children approaching the end of the life.

Sport and exercise as contributors to the health of nations.

Self-reported rates of participation in sport vary by country. In the UK, about 40% of men and women aged 16 years or older participate in at least one sport every week. Although few data exist to assess trends for participation in sport, there is little evidence of change in the past decade among adults. Large cohort studies suggest that such participation in sport is associated with a 20-40% reduction in all-cause mortality compared with non-participation. Randomised trials and crossover clinical studies suggest that playing sport is associated with specific health benefits. Some sports have relatively high injury risk although neuromuscular training programmes can prevent various lower extremity injuries. Clinicians can influence a large number of patients through brief interventions that promote physical activity, and encouragement toward participation in sport for some physically inactive patients qualifies as evidence-based therapy. Exercise might also be considered as a fifth vital sign and should be recorded in patients' electronic medical records and routine histories.