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Determine the effectiveness and acceptability of a text message intervention (DTEXT) on HbA1c and self-management behaviors for Australian adults with type 2 diabetes.Using intention to treat analysis and generalized estimating equations, this randomized controlled trial of 395 adults determined change in HbA1c at 3 and 6 months between the intervention and control group. Secondary outcomes included change in nutrition, physical activity, blood lipid profile, body mass index, quality of life, self-efficacy, medication taking and program acceptability.No significant difference was observed between the intervention or control group for HbA1c at 3 months (P = 0.23) or 6 months (P = 0.22). Significant improvements were seen in consumption of vegetables at 3 months (P0.001) and 6 months (P = 0.04); fruit at 3 months (P = 0.046) and discretionary sweet foods at 3 months (P = 0.02). No other significant effects seen. The intervention demonstrated high rates of acceptability (94.0%) and minimal withdrawal (1.5%).DTEXT was an acceptable text message intervention that improved some nutritional behaviors in people with type 2 diabetes, but did not significantly improve HbA1c or other outcomes. Further research is required to optimize DTEXT.DTEXT provides an acceptable, feasible form of self-management support that may complement existing diabetes care.

Objective This study examined hospitalisations and associated in-patient costs for babies during the first year of life following spontaneous labour, compared with labour induction or prelabour Caesarean section, at each gestational age. Methods Birth data for singleton liveborn babies from 33 weeks gestation in New South Wales from 2005 to 2014 were linked to hospital and death data. Generalised linear models were used to examine the association between the type of labour and the length of hospitalisations and hospital costs. Results From 2005 to 2014, 598 640 women gave birth to 1 187 451 liveborn singleton babies. The mean total length of hospitalisations and costs of hospitalisations for babies in the first year of life decreased significantly as week of gestational age increased to 39 weeks, then plateaued. Overall, the total length of hospitalisations and hospital costs were significantly (P

Background: The UK Biobank (UKB) has been used widely to examine associations between lifestyle risk factors and mortality outcomes. It is unknown whether the extremely low UKB response rate (5.5%) and lack of representativeness materially affects the magnitude and direction of effect estimates. Methods: We used poststratification to match the UKB sample to the target population in terms of sociodemographic characteristics and prevalence of lifestyle risk factors (physical inactivity, alcohol intake, smoking, and poor diet). We compared unweighted and poststratified associations between each lifestyle risk factor and a lifestyle index score with all-cause, cardiovascular disease (CVD), and cancer mortality. We also calculated the unweighted to poststratified ratio of HR (RHR) and 95% confidence interval as a marker of effect-size difference. Results: Of 371,974 UKB participants with no missing data, 302,009 had no history of CVD or cancer, corresponding to 3,298,958 person years of follow-up. Protective associations between alcohol use and CVD mortality observed in the unweighted UKB were substantially altered after poststratification, for example, from a hazard ratio (HR) of 0.63 (0.45–0.87) unweighted to 0.99 (0.65–1.50) poststratified for drinking ≥5 times/week versus never drinking. The magnitude of the poststratified all-cause mortality hazard ratio comparing least healthy with healthiest tertile of lifestyle risk factor index was 9% higher (95% confidence interval: 4%, 14%) than the unweighted estimates. Conclusions: Lack of representativeness may distort the associations of alcohol with CVD mortality, and may underestimate health hazards among those with cumulatively the least healthy lifestyles.

Background There is an urgent need for scaled-up effective interventions which overcome barriers to health-enhancing physical activity for children and adolescents. In New South Wales (NSW), Australia, the state government implemented a universal voucher program, ‘Active Kids’ to support the cost of structured physical activity registration for school-enrolled children aged 4.5–18 years old. The objective of this study was to understand the effects a financial incentive intervention delivered in a real-world setting has on children and adolescent’s physical activity participation. Method In 2018, all children and adolescents registered for an Active Kids voucher provided sociodemographic characteristics, physical activity and research consent. This prospective cohort study used an online survey with validated items to measure physical activity and other personal and social factors in children and adolescents who used an Active Kids voucher. Generalized linear mixed models were used to examine changes from registration to after voucher use at ≤8 weeks, 9–26 weeks and ≥ 6 months. Results Study participants reported increasing their days achieving physical activity guidelines from 4.0 days per week (95%CI 3.8, 4.2) at registration (n = 37,626 children) to 4.9 days per week (95%CI 4.7, 5.1) after 6 months (n = 14,118 children). Increased physical activity was observed for all sociodemographic population groups. The voucher-specific activity contributed 42.4% (95%CI 39.3, 45.5) to the total time children participated in structured physical activities outside of school. Children and adolescents who increased to, or maintained, high levels of activity were socially supported to be active, had active parent/caregivers, had better concentration and were overall happier than their low-active counterparts. Conclusion The Active Kids program significantly increased children’s physical activity levels and these increases continued over a six-month period. The Active Kids voucher program shows promise as a scaled-up intervention to increase children and adolescents’ physical activity participation. Trial registration Australian New Zealand Clinical Trial Registry ACTRN12618000897268, approved May 29th, 2018 - Retrospectively registered.

OBJECTIVES Noninvasive ventilation is widely used to avoid tracheal intubation in critically ill children. The objective of this study was to assess whether noninvasive ventilation failure was associated with severe tracheal intubation-associated events and severe oxygen desaturation during tracheal intubation. DESIGN Prospective multicenter cohort study of consecutive intubated patients using the National Emergency Airway Registry for Children registry. SETTING Thirteen PICUs (in 12 institutions) in the United States and Canada. PATIENTS All patients undergoing tracheal intubation in participating sites were included. Noninvasive ventilation failure group included children with any use of high-flow nasal cannula, continuous positive airway pressure, or bilevel noninvasive ventilation in the 6 hours prior to tracheal intubation. Primary tracheal intubation group included children without exposure to noninvasive ventilation within 6 hours before tracheal intubation. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Severe tracheal intubation-associated events (cardiac arrest, esophageal intubation with delayed recognition, emesis with aspiration, hypotension requiring intervention, laryngospasm, pneumothorax, pneumomediastinum) and severe oxygen desaturation (< 70%) were recorded prospectively. The study included 956 tracheal intubation encounters; 424 tracheal intubations (44%) occurred after noninvasive ventilation failure, with a median of 13 hours (interquartile range, 4-38 hr) of noninvasive ventilation. Noninvasive ventilation failure group included more infants (47% vs 33%; p < 0.001) and patients with a respiratory diagnosis (56% vs 30%; p < 0.001). Noninvasive ventilation failure was not associated with severe tracheal intubation-associated events (5% vs 5% without noninvasive ventilation; p = 0.96) but was associated with severe desaturation (15% vs 9% without noninvasive ventilation; p = 0.005). After controlling for baseline differences, noninvasive ventilation failure was not independently associated with severe tracheal intubation-associated events (p = 0.35) or severe desaturation (p = 0.08). In the noninvasive ventilation failure group, higher FIO2 before tracheal intubation (≥ 70%) was associated with severe tracheal intubation-associated events. CONCLUSIONS Critically ill children are frequently exposed to noninvasive ventilation before intubation. Noninvasive ventilation failure was not independently associated with severe tracheal intubation-associated events or severe oxygen desaturation compared to primary tracheal intubation.

Background A multi-disciplinary led, charity-funded initiative was implemented to deliver an Activity Promotion Project (APP) on the older adult wards of a large teaching hospital, providing acute medical management for adults over 65 with complex needs. Introduction Previous local studies show that our patients are inactive, lonely and their activity is inhibited by ward culture. Cognitively impaired patients experiencing long delays for placement are often agitated and restless. Staff feel disheartened by their inability to spare time for non-medical needs. To respond to the Social Prescribing directive the APP aims to create a sustainable volunteer team to provide patients with company, stimulation and opportunities to be active. Methods A Volunteer and Activity Coordinator (VAC) was appointed to recruit, train and coordinate applicants for the volunteer role on the unit which is advertised on the trust website. Analysis of volunteer team impact has been through patient, carer and staff surveys. Observational studies recorded patients’ physical position, activity and company as well as use of the dayrooms before and during the project. Interventions Patients of all functional abilities can be referred by any staff member. Individual and group activities include conversation, games, reminiscence quizzes, lunch and tea parties, musical bingo, walking tours, trips to hospital facilities and gardens and visits from therapy dogs and musicians. Before discharge participating patients are given information about local social and exercise opportunities. Results All staff surveyed would recommend the project to colleagues, 97% thought it improved patient mood. One noted: ‘volunteers have created a new energy on the ward, the patients appear to be much more engaged and occupied, and the dayroom is being used as it is intended to be’. Observational data showed a change in the percentage of patients resting in bed from 59% before the intervention to 49% during and a decrease in patients who were alone from 83% to 60%. Conclusions The volunteer team has had a positive effect on ward culture and patient well-being and could be replicated in other ward settings. The programme’s impact is contingent on the consistency and reliability of volunteers, which makes the role of the VAC essential for careful management and communication of clear expectations. The VAC role will be proposed in business planning for next financial year.

Patient safety efforts have largely focused on reduction of events collectively called hospital-acquired conditions (HACs). These events include device-related events such as central line–associated bloodstream infections and catheter-associated urinary tract infections, immobility and pressure injuries, other hospital acquired infections, falls, and readmissions. This review will discuss causes of harm beyond traditional HACs. The authors hope to raise awareness that to achieve further reductions in patient harm events, physicians must play an increasingly active role in improvement efforts. Diagnostic error is a significant source of patient harm for all ages and healthcare settings. Hospital-acquired kidney injury occurs in children, may lead to chronic renal dysfunction, and can be mitigated by limiting the use of nephrotoxic medications and monitoring of creatinine in exposed patients. Adoption of restrictive red blood cell transfusion practices decreases transfusion-related harm by decreasing the number of exposures. Further reductions in patient harm will require active engagement of physicians and other providers to understand how practice habits and the systems in which we practice contribute to harm and implement strategies that will bring about changes in how we function as individuals, within teams and within systems. It is unlikely that continuing to focus on improvement project by project (HACs) will significantly reduce harm events.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To evaluate the impact of interventions to improve inhaler technique on performance and clinical outcomes in people with COPD.

Design This study is a monocentre cohort study with a primary aim to assess the five-year survival of alumina-toughened zirconia (ATZ) implants (Metoxit AG, Thayngen, Switzerland). Secondary aims were to evaluate peri-implant marginal bone loss (MBL), soft tissue health and patient-reported outcome measures (PROMs). The implants were placed into healed ridges and, following a period of temporisation, were restored with either IPS e.max CAD LT or IPS e.max ZirCAD veneered with IPS e.max ZirPress (Ivoclar Vivadent, Schaan, Liechtenstein). Patients were followed up at prosthetic delivery, one-year and five-years post-implant placement. The clinical parameters recorded were clinical attachment levels (CAL), probing depth (PD), gingival recession (GR), modified bleeding index (mBI) and modified plaque index (mPI). MBL was evaluated using standardised radiographs. PROMs were used to assess patients' satisfaction utilising a visual analogue scale (VAS) to rate function, aesthetics, sense, speech and self-esteem. The null hypothesis assumed there was no difference in implant survival between one and five years post-operatively. This study was approved by the ethics committee at the University of Freigburg, Germany (No. 354/07).Cohort selection Forty patients from the Department of Prosthetic Dentistry requiring either an implant supported single crown or a three-unit implant-supported bridge were included in the study. Patients ranged from age 18 to 70 and were selected on a 'convenience basis'. Inclusion criteria stipulated patients must have good oral hygiene, compliance and be systemically healthy. Additionally, they were to have a stable occlusion, no signs of significant bruxism and sufficient bone volume to allow implant placement without the need for larger augmentative procedures.Data analysis Implant success was defined by three main criteria: (1) no local or systemic reactions; (2) no signs of radiolucency on an intraoral radiograph; and (3) provides support to a functional restoration. The MBL was classified as successful when at a one-year follow-up, implants demonstrating no clinical or radiographic signs of pathology are assigned a grade I success with

Background Sports should endeavour to provide inclusive opportunities for all people to participate. More evidence is required to understand who joins sports clubs and what keeps participants engaged throughout their lifetime. Little is known about who plays netball or what drives participation and retention of players in netball. This study aimed to identify the sociodemographic characteristics of Netball New South Wales (NSW) members, their odds of re-registering in the sport, and explore their motivations to play, experiences during participation and the perceived benefits of playing netball. Methods We used longitudinal sport registration data from all Netball NSW members in 2018 and 2019. A cross-sectional online survey was sent to all players registered during the two-year study period (n = 157,152). We used logistic regression to determine the odds of individuals returning to netball in 2019 after playing in 2018 and linked the sports registration data with the survey responses, calculating frequencies and proportions. Results Netball NSW members were mostly female (98 %) and aged less than 18 years old (69 %). Netball NSW retained 68 % of members in 2019 who played the previous year. Members who were male, aged 18–44 years old, lived in low SES areas, lived in regional/remote locations, identified as Aboriginal or Torres Strait Islander, spoke a language other than English at home or were born outside Australia had lower odds of returning to play from 2018 to 2019. Survey participants (n = 10,795) rated their experience playing netball highly and reported that playing netball improved their health and wellbeing. The main reason to play netball reported was ‘fun and enjoyment’ while the main reason to consider quitting was the ‘skill/experience of umpires and officials’. Conclusions This study highlights the strengths of netball in engaging and retaining females, who often participate in less sport than males. The positive experiences reported by netball participants should be fostered to retain current participants throughout the lifecourse. The data provided by members should be inform strategic actions to enhance netball participation for sociodemographic groups who had greatest odds of dropout. Routine surveillance using linked registration and player feedback should be utilised by sports to enhance sport delivery and increase participation.

Issue addressed Support for broad policies to prevent childhood obesity is not clear. This study aimed to investigate the level of support for state government health promotion policies among mothers with infants and its associated factors. Methods This secondary analysis of data from 1155 mothers in NSW assessed approval for six policy options derived from public health approaches to obesity. Descriptive statistics were used to show the extent of policy approval across the cohort. Logistic regression models tested associations between perceived susceptibility and perceived severity of childhood obesity and approval of each policy option. Results The proportion of mothers who felt these policy options were 'about the right amount' (56%-68%) or 'not going far enough' (24%-36%), collectively represented 89%-95% approval of government intervention. In comparison, 5%-11% felt that these policies were 'going too far'. Factors associated with their levels of support varied between each policy option, based on mothers' characteristics and perceptions of childhood obesity. Conclusion These findings indicate high support for government intervention to prevent obesity among mothers in NSW and support health promotion advocacy in this area. SO WHAT?: Governments should give due consideration to implementing each of the six policy options and prioritise the implementation of restrictions on fast food advertising in publicly owned or controlled areas.

Background: A combination of walking, other moderate physical activity, and vigorous physical activity is recommended for achieving good health. Vigorous activity has unique health benefits but may be less accessible to disadvantaged people. To reduce health inequity, we need to understand the differences in physical activity participation among socioeconomic subgroups and whether this is changing over time. Methods: Data from the 2002 to 2015 Adult New South Wales Population Health Surveys (164,652 responses) were analyzed to investigate trends in walking, moderate and vigorous physical activity participation by socioeconomic status as measured by educational attainment. Analysis used age- and sex-adjusted multivariable linear models that accounted for complex survey design. Results: In 2002, the highest socioeconomic group spent 18.5 (95% confidence interval, 8.2–28.8) minutes per week more than the lowest socioeconomic group being vigorously active. By 2015, this gap had steadily increased to 41.4 (95% confidence interval, 27.6–55.1) minutes per week. Inequity between groups was also found for duration of moderate activity but not for time spent walking. Conclusions: Low participation in vigorous activity in the lowest socioeconomic group is likely driving increasing inequities in physical activity and widening participation gaps over time. Barriers preventing the most disadvantaged people in New South Wales from engaging in vigorous activity should be addressed urgently.

Cricoid pressure is often used to prevent regurgitation during induction and mask ventilation prior to high-risk tracheal intubation in critically ill children. Clinical data in children showing benefit are limited. Our objective was to evaluate the association between cricoid pressure use and the occurrence of regurgitation during tracheal intubation for critically ill children in PICU.A retrospective cohort study of a multicenter pediatric airway quality improvement registry.Thirty-five PICUs within general and children's hospitals (29 in the United States, three in Canada, one in Japan, one in Singapore, and one in New Zealand).Children (18 yr) with initial tracheal intubation using direct laryngoscopy in PICUs between July 2010 and December 2015.None.Multivariable logistic regression analysis was used to evaluate the association between cricoid pressure use and the occurrence of regurgitation while adjusting for underlying differences in patient and clinical care factors. Of 7,825 events, cricoid pressure was used in 1,819 (23%). Regurgitation was reported in 106 of 7,825 (1.4%) and clinical aspiration in 51 of 7,825 (0.7%). Regurgitation was reported in 35 of 1,819 (1.9%) with cricoid pressure, and 71 of 6,006 (1.2%) without cricoid pressure (unadjusted odds ratio, 1.64; 95% CI, 1.09-2.47; p = 0.018). On multivariable analysis, cricoid pressure was not associated with the occurrence of regurgitation after adjusting for patient, practice, and known regurgitation risk factors (adjusted odds ratio, 1.57; 95% CI, 0.99-2.47; p = 0.054). A sensitivity analysis in propensity score-matched cohorts showed cricoid pressure was associated with a higher regurgitation rate (adjusted odds ratio, 1.01; 95% CI, 1.00-1.02; p = 0.036).Cricoid pressure during induction and mask ventilation before tracheal intubation in the current ICU practice was not associated with a lower regurgitation rate after adjusting for previously reported confounders. Further studies are needed to determine whether cricoid pressure for specific indication with proper maneuver would be effective in reducing regurgitation events.

OBJECTIVES Evaluate differences in tracheal intubation-associated events and process variances (i.e., multiple intubation attempts and oxygen desaturation) between pediatric cardiac ICUs and noncardiac PICUs in children with underlying cardiac disease. DESIGN Retrospective cohort study using a multicenter tracheal intubation quality improvement database (National Emergency Airway Registry for Children). SETTING Thirty-six PICUs (five cardiac ICUs, 31 noncardiac ICUs) from July 2012 to March 2016. PATIENTS Children with medical or surgical cardiac disease who underwent intubation in an ICU. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Our primary outcome was the rate of any adverse tracheal intubation-associated event. Secondary outcomes were severe tracheal intubation-associated events, multiple tracheal intubation attempt rates, and oxygen desaturation. There were 1,502 tracheal intubations in children with underlying cardiac disease (751 in cardiac ICUs, 751 in noncardiac ICUs) reported. Cardiac ICUs and noncardiac ICUs had similar proportions of patients with surgical cardiac disease. Patients undergoing intubation in cardiac ICUs were younger (median age, 1 mo [interquartile range, 0-6 mo]) compared with noncardiac ICUs (median 3 mo [interquartile range, 1-11 mo]; p < 0.001). Tracheal intubation-associated event rates were not different between cardiac ICUs and noncardiac ICUs (16% vs 19%; adjusted odds ratio, 0.74; 95% CI, 0.54-1.02; p = 0.069). However, in a sensitivity analysis comparing cardiac ICUs with mixed ICUs (i.e., ICUs caring for children with either general pediatric or cardiac diseases), cardiac ICUs had decreased odds of adverse events (adjusted odds ratio, 0.71; 95% CI, 0.52-0.97; p = 0.033). Rates of severe tracheal intubation-associated events and multiple attempts were similar. Desaturations occurred more often during intubation in cardiac ICUs (adjusted odds ratio, 1.61; 95% CI, 1.04-1.15; p = 0.002). CONCLUSIONS In children with underlying cardiac disease, rates of adverse tracheal intubation-associated events were not lower in cardiac ICUs as compared to noncardiac ICUs, even after adjusting for differences in patient characteristics and care models.

Waveform capnography use has been incorporated into guidelines for the confirmation of tracheal intubation. We aim to describe the trend in waveform capnography use in emergency departments and PICUs and assess the association between waveform capnography use and adverse tracheal intubation-associated events.A multicenter retrospective cohort study.Thirty-four hospitals (34 ICUs and nine emergency departments) in the National Emergency Airway Registry for Children quality improvement initiative.Primary tracheal intubation in children younger than 18 years.None.Patient, provider, and practice data for tracheal intubation procedure including a type of end-tidal carbon dioxide measurement, as well as the procedural safety outcomes, were prospectively collected. The use of waveform capnography versus colorimetry was evaluated in association with esophageal intubation with delayed recognition, cardiac arrest, and oxygen desaturation less than 80%. During January 2011 and December 2015, 9,639 tracheal intubations were reported. Waveform capnography use increased over time (39% in 2010 to 53% in 2015; p0.001), whereas colorimetry use decreased (0.001). There was significant variability in waveform capnography use across institutions (median 49%; interquartile range, 25-85%; p0.001). Capnography was used more often in emergency departments as compared with ICUs (66% vs. 49%; p0.001). The rate of esophageal intubation with delayed recognition was similar with waveform capnography versus colorimetry (0.39% vs. 0.46%; p = 0.62). The rate of cardiac arrest was also similar (p = 0.49). Oxygen desaturation occurred less frequently when capnography was used (17% vs. 19%; p = 0.03); however, this was not significant after adjusting for patient and provider characteristics.Significant variations existed in capnography use across institutions, with the use increasing over time in both emergency departments and ICUs. The use of capnography during intubation was not associated with esophageal intubation with delayed recognition or the occurrence of cardiac arrest.

Physical activity (PA) decreases during the transition from childhood to adolescence, with larger declines observed in girls. School-based interventions are considered the most promising approach for increasing adolescents’ PA levels although, it is unclear which types of school-based interventions have the greatest impact. The objective of this systematic review is to assess the impact and design of school-based PA interventions targeting adolescent girls. A systematic search was conducted using four electronic databases (PubMed, Web of Science, SPORTDiscus and PsychInfo). This systematic review was registered with PROSPERO (Registration number: CRD42016037428) and PRISMA guidelines (2009) were followed throughout. Twenty studies were identified as meeting the inclusion criteria and were included in a narrative synthesis. Seventeen studies were eligible for inclusion in a meta-analysis. There was a significant small positive treatment effect for school-based PA interventions for adolescent girls (k=17, g= 0.37, p

Background Tetralogy of Fallot (ToF) and coarctation of the aorta (CoA) each constitute approximately 7% of congenital heart disease (CHD) births worldwide. Compared to developed countries, developing countries have a disparate level of access to prompt diagnosis and treatment for these diseases. Computational fluid dynamics (CFD) approaches implemented on routinely available non-invasive imaging data may yield low-cost improvements to the management of these patients. Purpose The purpose of this research is to develop a patient-specific computational pipeline that allows the modelling of blood flow in diseased arteries of patients suffering from ToF and CoA. The project aims to prove the feasible use of broadly available imaging techniques - CT angiograms (CTA) and echocardiographs (echo) - for achieving this in low-to-middle income countries. The capability of the pipeline will be demonstrated through a qualitative study of the effects of different systemic to pulmonary shunt configurations used in the palliative treatment of ToF. In addition, the effects of idealised stent configurations on the blood flow through the aorta of a patient with CoA will be studied. Methods A retrospective search through the hospital database was conducted to select suitable CTA data for a CoA and ToF case. Data for patient A, a five-month-old child with typical CoA, and patient B, a twelve-month-old child with typical ToF who had a central shunt in place, was found. Echo data was obtained for patient A through an investigation protocol which focused on CFD application whereas there was no echo data available for patient B. As a result, idealised volume flow rate data was implemented for patient B. Geometries for patient A and patient B were extracted and volume discretisation was implemented for grid independence testing. The Navier-Stokes governing equations for fluid flow were solved using the open source software, OpenFOAM, for the transient case where inlet volume flow rate was defined for four cardiac cycles. Figure 1 shows key features of the flow in the shunt and pulmonary branches (A), the aortic arch (B), the inlet at the ascending aorta (C) and the descending aorta (D) for the geometry extracted from the data set of patient B. Figure 1. Key flow features of patient B Results and discussion We have implemented CFD models which are able to qualitatively assess the favourable or unfavourable impact of different approaches to ToF and CoA repairs on the characteristics of blood flow in the aorta and pulmonary arteries. An echo investigation protocol has been developed and successfully applied. CTA studies have been shown as feasible sources of geometry data in spite of the restriction on quality by the important requirement for low doses of radiation in paediatric patients. This project represents progress towards an advanced tool that may be broadly implemented in both well-resourced and minimally-resourced hospitals. Acknowledgement/Funding National Research Fund, British Heart Foundation, Newton Fund (UK MRC, South African Medical Research Council), University of Cape Town

Contains fulltext : 167701.pdf (Publisher’s version ) (Open Access) The overall understanding of the molecular etiologies of intellectual disability (ID) and developmental delay (DD) is increasing as next-generation sequencing technologies identify genetic variants in individuals with such disorders. However, detailed analyses conclusively confirming these variants, as well as the underlying molecular mechanisms explaining the diseases, are often lacking. Here, we report on an ID syndrome caused by de novo heterozygous loss-of-function (LoF) mutations in SON. The syndrome is characterized by ID and/or DD, malformations of the cerebral cortex, epilepsy, vision problems, musculoskeletal abnormalities, and congenital malformations. Knockdown of son in zebrafish resulted in severe malformation of the spine, brain, and eyes. Importantly, analyses of RNA from affected individuals revealed that genes critical for neuronal migration and cortex organization (TUBG1, FLNA, PNKP, WDR62, PSMD3, and HDAC6) and metabolism (PCK2, PFKL, IDH2, ACY1, and ADA) are significantly downregulated because of the accumulation of mis-spliced transcripts resulting from erroneous SON-mediated RNA splicing. Our data highlight SON as a master regulator governing neurodevelopment and demonstrate the importance of SON-mediated RNA splicing in human development.

Cybersickness is an affliction common to users of virtual environments. Similar in symptoms to motion sickness, cybersickness can result in nausea, headaches, and dizziness. With these systems becoming readily available to the general public, reports of cybersickness have increased and there is a growing concern about the safety of these systems. This review presents the current state of research methods, theories, and known aspects associated with cybersickness. Current measurements of incidence of cybersickness are questionnaires, postural sway, and physiological state. Varying effects due to display and rendering modes, such as visual display type and stereoscopic or monoscopic rendering, are compared. The known and suspected application aspects that induce cybersickness are discussed. There are numerous potential contributing application design aspects, many of which have had limited study, but field of view and navigation are strongly correlated with cybersickness. The effect of visual displays is not well understood, and application design may be of greater importance.

BACKGROUND Endotracheal tube suctioning is necessary for patients receiving mechanical ventilation. Studies examining saline instillation before suctioning have demonstrated mixed results. METHODS A prospective study to evaluate whether saline instillation is associated with an increased risk of suctioning-related adverse events in patients 18 years old or younger requiring mechanical ventilation through an endotracheal tube for at least 48 hours when suctioned per protocol using a bedside decision tree. RESULTS A total of 1986 suctioning episodes (1003 with saline) were recorded in 69 patients. The most common indication for use of saline was thick secretions (87% of episodes). In 586 suctioning episodes, at least 1 adverse event occurred with increased frequency in the saline group (P < .001). Normal saline was more likely to be associated with hemodynamic instability (P = .04), bronchospasm (P < .001), and oxygen desaturation (P < .001). Patient factors associated with adverse events include younger age (P < .001), a cuffed endotracheal tube (P = .001), endotracheal tube diameter of 4.0 mm or less (P < .001), respiratory or hemodynamic indication for intubation (P < .001), underlying respiratory disease (P < .001), and longer duration of mechanical ventilation (P < .001). Saline instillation (P < .001), endotracheal tube size of 4.0 mm or less (P = .03), and comorbid respiratory diseases (P = .03) were associated with an increased risk of adverse events. CONCLUSIONS Saline instillation before endotracheal tube suctioning is associated with hemodynamic instability, bronchospasm, and transient hypoxemia. Saline should be used cautiously, especially in children with a small endotracheal tube and comorbid respiratory disease.

To determine the extent to which initial therapy for nonmetastatic prostate cancer was concordant with nationally recognized guidelines using supplemented cancer registry data and what factors were associated with receipt of nonguideline-concordant care.Initial therapy for 8229 nonmetastatic prostate cancer cases diagnosed in 2004 from cancer registries in 7 states was abstracted as part of the Centers for Disease Control's Patterns of Care Breast and Prostate Cancer study conducted during 2007 to 2009. The National Comprehensive Cancer Network clinical practice guidelines version 1.2002 was used as the standard of care based on recurrence risk group and life expectancy (LE). A multivariable model was used to determine risk factors associated with receipt of nonguideline-concordant care.Nearly 80% with nonmetastatic prostate cancer received guideline-concordant care for initial therapy. Receipt of nonguideline-concordant care (including receiving either less aggressive therapy or more aggressive therapy than indicated) was related to older age, African American race/ethnicity, being unmarried, rural residence, and especially to being in the high recurrence risk group where receiving less aggressive therapy than indicated occurred more often than receiving more aggressive therapy (adjusted OR=4.2; 95% CL, 3.5-5.2 vs. low-risk group). Compared with life table estimates adjusted for comorbidity, physicians tended to underestimate LE.Receipt of less aggressive therapy than indicated among high-risk group men with5-year LE based on life table estimates adjusted for comorbidity was a concern. Physicians may tend to underestimate 5-year survival among this group and should be alerted to the importance of recommending aggressive therapy when warranted. However, based on more recent guidelines, among those with low-risk disease, the proportion considered to be receiving less aggressive therapy than indicated may now be lower because active surveillance is now considered appropriate.

Background: Schools have been identified as key environments to promote child physical activity (PA). Implementation of multi-component PA interventions within schools is advocated but research has showed that they may not always be effective at increasing child PA. Results of the Active Schools: Skelmersdale (AS:Sk) multi-component pilot intervention indicated no significant positive change to child PA levels. Process evaluations can provide information on which aspects of an intervention were delivered and how. Therefore, the purpose of this study was to use a combination of methods to elicit child and teacher perceptions regarding the feasibility and acceptability of the\ud AS:Sk intervention, alongside systematic researcher observations. The overarching study aim was to understand how schools implemented the AS:Sk intervention, with a specific focus on the frequency of intervention component implementation, and how the components were incorporated into the school day.\ud Methods: The study generated five data sets. Data elicited from 18 participating children via a write draw, show and tell task included, frequency counts of most enjoyable intervention components, drawings, and verbatim data. Teacher verbatim data was collected from 3 interviews, and 18 researcher observations were recorded using field notes. The data sources were pooled to produce the themes presented in the results section.\ud Results: The combination of data sources revealed four themes and 16 sub-themes. Implementation methods: how and when the components were implemented in schools. Child engagement: enjoyment and positive behaviour. Facilitators: peer influence, teacher influence, staggered implementation, incentives, rewards, challenges and competition, flexibility and adaptability, child ownership, routine. Barriers: time within an intense curriculum, space, sustaining child interest, parental support, school policies.\ud Conclusions: This study revealed that teachers believed classroom based activities were most feasible and acceptable due to the reduced implementation barriers of sufficient time and space. In contrast, children reported that the activities outside of the classroom were preferred. Future school-based PA interventions should aim to achieve a balance between routine PA at a set time and PA that is flexible and adaptable. Further process evaluations of multicomponent school-based PA interventions are warranted to develop the limited evidence base.

IntroductionChildren with CHD and acquired heart disease have unique, high-risk physiology. They may have a higher risk of adverse tracheal-intubation-associated events, as compared with children with non-cardiac disease.Materials and methodsWe sought to evaluate the occurrence of adverse tracheal-intubation-associated events in children with cardiac disease compared to children with non-cardiac disease. A retrospective analysis of tracheal intubations from 38 international paediatric ICUs was performed using the National Emergency Airway Registry for Children (NEAR4KIDS) quality improvement registry. The primary outcome was the occurrence of any tracheal-intubation-associated event. Secondary outcomes included the occurrence of severe tracheal-intubation-associated events, multiple intubation attempts, and oxygen desaturation.ResultsA total of 8851 intubations were reported between July, 2012 and March, 2016. Cardiac patients were younger, more likely to have haemodynamic instability, and less likely to have respiratory failure as an indication. The overall frequency of tracheal-intubation-associated events was not different (cardiac: 17% versus non-cardiac: 16%, p=0.13), nor was the rate of severe tracheal-intubation-associated events (cardiac: 7% versus non-cardiac: 6%, p=0.11). Tracheal-intubation-associated cardiac arrest occurred more often in cardiac patients (2.80 versus 1.28%; pConclusionsThe overall incidence of adverse tracheal-intubation-associated events in cardiac patients was not different from that in non-cardiac patients. However, the presence of a cardiac diagnosis was associated with a higher occurrence of both tracheal-intubation-associated cardiac arrest and oxygen desaturation.

Cancer stem cells (CSC) are a distinct subpopulation within a tumor shown to drive tumor progression, metastasis, and recurrence. A review of the literature reveals poor consensus, with the use of a wide variety of surface markers and functional assays to identify and isolate cancer stem cells. Utilizing a novel technology that enables live-cell mRNA quantitation, we have demonstrated the ability to identify and sort viable CSC based on markers associated with stemness in pluripotent cells. Fresh tumor samples from a variety of cancer types were examined by flow cytometry for Nanog expression. Levels of CSC detected ranged from 6% to 19%. This method of CSC detection was cross-validated with other commonly used surface markers with good correlation. Matrigel invasion assays confirmed that CSC isolated using this method are both highly motile and invasive. This approach simplifies the process of identifying viable CSC from fresh tumor tissue, providing a level of accuracy not previously available. This method may also provide a valuable tool for screening and validating new CSC biomarkers.

Objective. To examine the attitudes toward breastfeeding in public and perceptions toward appropriate durations. Methods. A total of 1036 adults completed an online survey on comfort levels toward themselves/partner or others breastfeeding in various locations, and perceived appropriate durations of breastfeeding from 3 months to over 2 years. We used multivariable ordered logistic regression to examine the association between demographic characteristics and comfort levels of one’s breastfeeding and appropriate duration. Results. The sample was 68% female, 87% non-Hispanic white, 84% with college degree or higher, and 68% residing in the northeastern United States. After adjusting for demographic factors, men had significantly lower odds of being comfortable with having their partner (odds ratio [OR] range = 0.58-0.69, P < .05) or other women (OR range = 0.49-0.60, P < .05) breastfeed in malls, parks, restaurants, health clubs, and open spaces in general. Men had half the odds than women toward comfort with 2 or more years of breastfeeding (OR = 0.50, 95% confidence interval = 0.32-0.77). Ethnicity, residential setting, age, and education were not independently associated with comfort in breastfeeding in public or breastfeeding duration. Conclusions. In this mostly white, well-educated sample, women were significantly more comfortable with others and themselves/partner breastfeeding in public than males. The same was true regarding approval of longer durations of breastfeeding.

// Kaushlendra Tripathi 1, * , Usama K. Hussein 1, 2, * , Roja Anupalli 1, 3, * , Reagan Barnett 1 , Lavanya Bachaboina 1 , Jennifer Scalici 1 , Rodney P. Rocconi 1 , Laurie B. Owen 1 , Gary A. Piazza 1 , Komaraiah Palle 1, * 1 Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, Mobile, Alabama, USA 2 Faculty of Science, Beni Suef University, Beni Suef, Egypt 3 Department of Genetics, Osmania University, Hyderabad, India * These authors have contributed equally to this work Correspondence to: Komaraiah Palle, e-mail: kpalle@health.southalabama.edu Keywords: Dietary isothiocyanates, replication stress, DNA damage response, radiosensitization, non-small cell lung cancer Received: November 21, 2014 Accepted: January 01, 2015 Published: January 27, 2015 ABSTRACT Allyl isothiocyanate (AITC), a constituent of many cruciferous vegetables exhibits significant anticancer activities in many cancer models. Our studies provide novel insights into AITC-induced anticancer mechanisms in human A549 and H1299 non-small cell lung cancer (NSCLC) cells. AITC exposure induced replication stress in NSCLC cells as evidenced by γH2AX and FANCD2 foci, ATM/ATR-mediated checkpoint responses and S and G2/M cell cycle arrest. Furthermore, AITC-induced FANCD2 foci displayed co-localization with BrdU foci, indicating stalled or collapsed replication forks in these cells. Although PITC (phenyl isothiocyanate) exhibited concentration-dependent cytotoxic effects, treatment was less effective compared to AITC. Previously, agents that induce cell cycle arrest in S and G2/M phases were shown to sensitize tumor cells to radiation. Similar to these observations, combination therapy involving AITC followed by radiation treatment exhibited increased DDR and cell killing in NSCLC cells compared to single agent treatment. Combination index (CI) analysis revealed synergistic effects at multiple doses of AITC and radiation, resulting in CI values of less than 0.7 at Fa of 0.5 (50% reduction in survival). Collectively, these studies identify an important anticancer mechanism displayed by AITC, and suggest that the combination of AITC and radiation could be an effective therapy for NSCLC.

External laryngeal manipulation is a commonly used maneuver to improve visualization of the glottis during tracheal intubation in children. However, the effectiveness to improve tracheal intubation attempt success rate in the nonanesthesia setting is not clear. The study objective was to evaluate the association between external laryngeal manipulation use and initial tracheal intubation attempt success in PICUs.A retrospective observational study using a multicenter emergency airway quality improvement registry.Thirty-five PICUs within general and children's hospitals (29 in the United States, three in Canada, one in Japan, one in Singapore, and one in New Zealand).Critically ill children (18 years) undergoing initial tracheal intubation with direct laryngoscopy in PICUs between July 1, 2010, and December 31, 2015.Propensity score-matched analysis was performed to evaluate the association between external laryngeal manipulation and initial attempt success while adjusting for underlying differences in patient and clinical care factors: age, obesity, tracheal intubation indications, difficult airway features, provider training level, and neuromuscular blockade use. External laryngeal manipulation was defined as any external force to the neck during laryngoscopy. Of the 7,825 tracheal intubations, the initial tracheal intubation attempt was successful in 1,935/3,274 intubations (59%) with external laryngeal manipulation and 3,086/4,551 (68%) without external laryngeal manipulation (unadjusted odds ratio, 0.69; 95% CI, 0.62-0.75; p0.001). In propensity score-matched analysis, external laryngeal manipulation remained associated with lower initial tracheal intubation attempt success (adjusted odds ratio, 0.93; 95% CI, 0.90-0.95; p0.001).External laryngeal manipulation during direct laryngoscopy was associated with lower initial tracheal intubation attempt success in critically ill children, even after adjusting for underlying differences in patient factors and provider levels. The indiscriminate use of external laryngeal manipulation cannot be recommended.

ObjectiveQuality physical education (PE) is the cornerstone of comprehensive school physical activity (PA) promotion programmes. We tested the efficacy of a teacher professional learning intervention, delivered partially via the internet, designed to maximise opportunities for students to be active during PE lessons and enhance adolescents’ motivation towards PE and PA.MethodsA two-arm cluster randomised controlled trial with teachers and Grade 8 students from secondary schools in low socioeconomic areas of Western Sydney, Australia. The Activity and Motivation in Physical Education (AMPED) intervention for secondary school PE teachers included workshops, online learning, implementation tasks and mentoring sessions. The primary outcome was the proportion of PE lesson time that students spent in moderate-to-vigorous physical activity (MVPA), measured by accelerometers at baseline, postintervention (7–8 months after baseline) and maintenance (14–15 months). Secondary outcomes included observed PE teachers’ behaviour during lessons, students’ leisure-time PA and students’ motivation.ResultsStudents (n=1421) from 14 schools completed baseline assessments and were included in linear mixed model analyses. The intervention had positive effects on students’ MVPA during lessons. At postintervention, the adjusted mean difference in the proportion of lesson time spent in MVPA was 5.58% (pConclusionsAMPED produced modest improvements in MVPA and compares favourably with previous interventions delivered exclusively face-to-face. Online teacher training could help facilitate widespread dissemination of professional learning interventions.Trial registration numberACTRN12614000184673.

Tracheal intubation in PICUs is a common procedure often associated with adverse events. The aim of this study is to evaluate the association between immediate events such as tracheal intubation associated events or desaturation and ICU outcomes: length of stay, duration of mechanical ventilation, and mortality.Prospective cohort study with 35 PICUs using a multicenter tracheal intubation quality improvement database (National Emergency Airway Registry for Children: NEAR4KIDS) from January 2013 to June 2015. Desaturation defined as Spo2 less than 80%.PICUs participating in NEAR4KIDS.All patients less than18 years of age undergoing primary tracheal intubations with ICU outcome data were analyzed.Five thousand five hundred four tracheal intubation encounters with median 108 (interquartile range, 58-229) tracheal intubations per site. At least one tracheal intubation associated event was reported in 892 (16%), with 364 (6.6%) severe tracheal intubation associated events. Infants had a higher frequency of tracheal intubation associated event or desaturation than older patients (48% infants vs 34% for 1-7 yr and 18% for 8-17 yr). In univariate analysis, the occurrence of tracheal intubation associated event or desaturation was associated with a longer mechanical ventilation (5 vs 3 d; p0.001) and longer PICU stay (14 vs 11 d; p0.001) but not with PICU mortality. The occurrence of severe tracheal intubation associated events was associated with longer mechanical ventilation (5 vs 4 d; p0.003), longer PICU stay (15 vs 12 d; p0.035), and PICU mortality (19.9% vs 9.6%; p0.0001). In multivariable analyses, the occurrence of tracheal intubation associated event or desaturation was significantly associated with longer mechanical ventilation (+12%; 95% CI, 4-21%; p = 0.004), and severe tracheal intubation associated events were independently associated with increased PICU mortality (OR = 1.80; 95% CI, 1.24-2.60; p = 0.002), after adjusted for patient confounders.Adverse tracheal intubation associated events and desaturations are common and associated with longer mechanical ventilation in critically ill children. Severe tracheal intubation associated events are associated with higher ICU mortality. Potential interventions to decrease tracheal intubation associated events and oxygen desaturation, such as tracheal intubation checklist, use of apneic oxygenation, and video laryngoscopy, may need to be considered to improve ICU outcomes.

Ethylene glycol (EG), commonly found in antifreeze and deicing solutions, continues to be a cause of morbidity and mortality in the pediatric population. EG metabolism produces toxins that cause metabolic acidosis and calcium oxalate deposition throughout the body. Deposition in the central nervous system is associated with significant neurologic sequelae, including altered mental status, seizures, and cerebral edema. We present a case of intentional EG poisoning in a 17-year-old male with resulting cerebral edema and coma. Neuroimaging studies were initially normal but eventually demonstrated diffuse abnormalities on both cranial computed tomography and magnetic resonance imaging (MRI). The patient ultimately made a complete recovery with resolution of the MRI abnormalities noted at the peak of illness. While neuroimaging is often incorporated into the management of EG poisoning, this is the first case report to show the evolution of EG-related MRI changes before, during, and after the resolution of EG-induced intracranial hypertension.

Patient comorbidities may affect the applicability of performance measures that are inherent in multidisciplinary cancer treatment guidelines. This article describes the distribution of common comorbid conditions by disease site and by patient and facility characteristics in patients who received radiation therapy as part of treatment for cancer of the breast, cervix, lung, prostate, and stomach, and investigates the association of comorbidities with treatment decisions.Stratified two-stage cluster sampling provided a random sample of radiation oncology facilities. Eligible patients were randomly sampled from each participating facility for each disease site, and data were abstracted from medical records. The Adult Comorbidity Evaluation Index (ACE-27) was used to measure comorbid conditions and their severity. National estimates were calculated using SUDAAN statistical software.Multivariable logistic regression models predicted the dependent variable "treatment changed or contraindicated due to comorbidities." The final model showed that ACE-27 was highly associated with change in treatment for patients with severe or moderate index values compared to those with none or mild (P.001). Two other covariates, age and medical coverage, had no (age) or little (medical coverage) significant contribution to predicting treatment change in the multivariable model. Disease site was associated with treatment change after adjusting for other covariates in the model.ACE-27 is highly predictive of treatment modifications for patients treated for these cancers who receive radiation as part of their care. A standardized tool identifying patients who should be excluded from clinical performance measures allows more accurate use of these measures.

We sampled soil and water at two mineral springs (salt licks) in Baxter State Park, ME, and describe chemical characteristics of each. One site (Wadleigh) is a small spring-fed pond and the other site (Hudson) is a spring with water emerging at the base of a bedrock outcrop; both drain into nearby streams. These sites are frequently visited by Odocoileus virginianus (White-tailed Deer) and by Alces americanus (Moose). Potassium (K) and sodium (Na) concentrations in water were substantially higher at licks than at upstream control sites—Wadleigh Lick: K = 2.33 vs. 0.31 mg/L, Na = 15.7 vs. 1.9 mg/L; Hudson Lick: K = 0.95 vs. 0.19 mg/L, Na = 9.4 vs. 0.9 mg/L. Chloride at the Hudson Lick was 120 vs. 10.7 µeq/L in water upstream. Exchangeable calcium (Ca), K, and magnesium (Mg) in soil at the Wadleigh site were typical of Maine soils but Na was greatly elevated. The elevated concentrations of K and Na in the water are typical of groundwater that has circulated through bedrock, instead of overlying till.

Background There is growing concern that residents are not receiving the necessary experience to become proficient with medical procedures. We created a structured curriculum to improve resident comprehension, experience and confidence with pediatric procedures. Methods A two-week procedure curriculum commenced with a three-day training course to review 26 pediatric procedures using lectures, videos, demonstrations and simulations. Residents spent the remainder of the rotation as the hospital's on-call procedure resident. Pre- and post-rotation surveys, knowledge testing and procedure logging were used to evaluate course effectiveness, along with follow up metrics a year after completing the rotation. Results were compared to a control group of residents completing their second year of residency who did not participate in the curriculum. Results Participants (N = 35) averaged 67.2 procedures over the 2 weeks, compared to 41.3 procedures for controls (N = 20) during their first 2 years of residency. Participants had a higher confidence than controls (3.0 vs. 2.5 on a five-point scale) and better knowledge (65% vs. 47% correct on testing), both statistically significant. Compared to their own individual pre-rotation scores, participants showed improved knowledge (49% vs. 65%) and confidence (2.0 vs. 3.0), both statistically significant. Long-term follow up showed that these improvements were mostly sustained a year later. Conclusions Overall, interns completing the rotation demonstrated procedure counts, knowledge levels, and confidence greater than rising third year residents. Participants were inclined to have superior confidence in procedures where higher procedure counts were achieved. Most results were sustained over the course of one year.

Habitat features associated with nest locations can affect survival and reproductive success of individuals living at particular nest sites. In this study we analyzed vegetation associated with nests of prairie voles (Microtus ochrogaster), living in 0.1 ha outdoor enclosures, and found they differed from plants at randomly selected locations. Although vegetation changed during the 15 wk study, vegetation at nests tended to provide cover (taller plants) or impede predators (thornier plants). Vegetation close to nests as well as in the habitat patch (enclosure) where the nest was located predicted female survival, pup survival, and female reproductive success. The number of pups produced per nest was not related to vegetation near nests but increased with increasing thorny vegetation within enclosures. Pup survival was greater when there was more woody vegetation near nests and more dicots within enclosures. Female survival was negatively associated with plant height at nests and woody vegetation within enclosures but positively related to preferred food plants within enclosures. Our results suggest fitness consequences resulting from vegetation near nests and on a larger spatial scale surrounding the nest could influence nest site selection in prairie voles.

Supplemental Digital Content is available in the text., Introduction: Despite evidence that red blood cell (RBC) transfusions may be associated with more harm than benefit, current transfusion practices vary significantly. This multicenter, quality improvement study aimed to sustainably decrease the rate of RBC transfusions in pediatric intensive care units (PICUs). Methods: This 16-month prospective study included 5 PICUs. We implemented a standardized project plan including education, bedside tools, real-time reminders, and email feedback. We collected data from consecutive transfusions during pre-implementation (Phase I), postimplementation (Phase II), and post-stabilization phases (Phase III). Results: Of the 2,064 RBC transfusions, we excluded 35% (N = 729) from analysis in patients undergoing extracorporeal membrane oxygenation. Transfusion/1,000 admissions improved throughout the study periods from a baseline 209.6 -199.8 in Phase II and 195.8 in Phase III (P value < 0.05). There were fewer transfusions outside of the hemoglobin threshold guideline, decreasing from 81% of transfusions outside of guidelines in Phase I to 74% in Phases II and III, P < 0.05. Study phase, site, co-management status, service of requesting provider, admit reason, previous transfusion status, and age were associated with transfusion above guideline threshold. Conclusions: Multicenter collaboration can successfully deploy a standardized plan that adheres to implementation science principles to sustainably decrease the rate of RBC transfusion outside of guideline thresholds. However, we did not decrease the total number of transfusions in our study. The complexity of multiple specialties co-managing patients is common in the contemporary PICU. Educational initiatives aimed at one specialty may have limited effectiveness in a multifaceted system of care.

Recently, we have shown that CXCL12/CXCR4 signaling plays an important role in gemcitabine resistance of pancreatic cancer (PC) cells. Here, we explored the effect of gemcitabine on this resistance mechanism. Our data demonstrate that gemcitabine induces CXCR4 expression in two PC cell lines (MiaPaCa and Colo357) in a dose- and time-dependent manner. Gemcitabine-induced CXCR4 expression is dependent on reactive oxygen species (ROS) generation because it is abrogated by pretreatment of PC cells with the free radical scavenger N-acetyl-L-cysteine. CXCR4 up-regulation by gemcitabine correlates with time-dependent accumulation of NF-κB and HIF-1α in the nucleus. Enhanced binding of NF-κB and HIF-1α to the CXCR4 promoter is observed in gemcitabine-treated PC cells, whereas their silencing by RNA interference causes suppression of gemcitabine-induced CXCR4 expression. ROS induction upon gemcitabine treatment precedes the nuclear accumulation of NF-κB and HIF-1α, and suppression of ROS diminishes these effects. The effect of ROS on NF-κB and HIF-1α is mediated through activation of ERK1/2 and Akt, and their pharmacological inhibition also suppresses gemcitabine-induced CXCR4 up-regulation. Interestingly, our data demonstrate that nuclear accumulation of NF-κB results from phosphorylation-induced degradation of IκBα, whereas HIF-1α up-regulation is NF-κB-dependent. Lastly, our data demonstrate that gemcitabine-treated PC cells are more motile and exhibit significantly greater invasiveness against a CXCL12 gradient. Together, these findings reinforce the role of CXCL12/CXCR4 signaling in gemcitabine resistance and point toward an unintended and undesired effect of chemotherapy.

Objective To determine whether rural residents were at a disadvantage compared with urban residents with regard to the receipt of curative therapy for prostate cancer. Materials and Methods Using the Breast and Prostate Cancer Data Quality and Patterns of Care Study II, patients with prostate cancer who were diagnosed in 2004 were identified. Registrars reviewed the medical records of randomly selected patients with incident prostate cancer (n = 1906). The patients' residential address was geocoded and linked to the census tract from the 2000 U.S. Census. The place of residence was defined as rural or nonrural according to the census tract and rural-urban commuting area categorization. The distance from the residence to the nearest radiation oncology facility was calculated. The odds ratio and 95% confidence intervals associated with receipt of noncurative treatment was calculated from logistic regression models and adjusted for several potential confounders. Results Of the incident patients, 39.1% lived in urban census tracts, 41.5% lived in mixed tracts, and 19.4% lived in rural tracts. Hormone-only or active surveillance was received by 15.4% of the patients. Relative to the urban patients, the odds ratio for noncurative treatment was 1.01 (95% confidence interval 0.59-1.74) for those living in mixed tracts and 0.96 (95% confidence interval 0.52-1.77) for those living in rural tracts. No association was found for noncurative treatment according to the Rural-Urban Commuting Area categorization. The linear trend was null between noncurative treatment and the distance to nearest radiation oncology facility (P = .92). Conclusion The choice of curative treatment did not significantly depend on the patient's place of residence, suggesting a lack of geographic disparity for the primary treatment of prostate cancer.

Objective To assess the effect of an intervention designed to enhance physiotherapists' communication skills on patients' adherence to recommendations regarding home-based rehabilitation for chronic low back pain. Design Cluster randomized controlled trial. Setting Publicly funded physiotherapy clinics. Participants A sample (N=308) of physiotherapists (n=53) and patients with chronic low back pain (n=255; 54% female patients; mean age, 45.3y). Interventions Patients received publicly funded individual physiotherapy care. In the control arm, care was delivered by a physiotherapist who had completed a 1-hour workshop on evidence-based chronic low back pain management. Patients in the experimental arm received care from physiotherapists who had also completed 8 hours of communication skills training. Main Outcome Measures (1) Patient-reported adherence to their physiotherapists' recommendations regarding home-based rehabilitation measured at 1, 4, 12, and 24 weeks after the initial treatment session. (2) Pain and pain-related function measured at baseline and at 4, 12, and 24 weeks. Results A linear mixed model analysis revealed that the experimental arm patients' ratings of adherence were higher than those of controls (overall mean difference, .41; 95% confidence interval, .10–.72; d =.28; P =.01). Moderation analyses revealed that men, regardless of the intervention, showed improvements in pain-related function over time. Only women in the experimental arm showed functional improvements; female controls showed little change in function over time. The Communication Style and Exercise Compliance in Physiotherapy intervention did not influence patients' pain, regardless of their sex. Conclusions Communication skills training for physiotherapists had short-term positive effects on patient adherence. This training may provide a motivational basis for behavior change and could be a useful component in complex interventions to promote adherence. Communication skills training may also improve some clinical outcomes for women, but not for men.

Purpose The purpose of this survey was to test the feasibility of using proposed quality indicators to assess radiotherapy quality in prostate cancer management based on a 2007 stratified random survey of treating academic and nonacademic US institutions. Methods and Materials A total of 414 patients with clinically localized prostate cancer treated with external beam radiotherapy (EBRT) or brachytherapy were selected from 45 institutions. Indicators used as specific measurable clinical performance measures to represent surrogates for quality of radiotherapy delivery included established measures such as the use of prescription doses ≥ 75 Gy for intermediate- and high-risk EBRT patients and androgen-deprivation therapy (ADT) in conjunction with EBRT for patients with high-risk disease, and emerging measures, including daily target localization (image-guidance) to correct for organ motion for EBRT patients. Results Among the 354 patients treated with EBRT, the beam energy was recorded in 353 patients. One hundred sixty-seven patients (47%) were treated with 6 MV photons, 31 (9%) were treated with 10 MV, 65 (18%) received 15 MV, and the remaining 90 (26%) 16-23 MV. For intermediate- plus high-risk patients (n = 181), 78% were treated to ≥75 Gy. Among favorable-risk patients, 72% were treated to ≥75 Gy. Among high-risk EBRT patients, 60 (87%) were treated with ADT in conjunction with EBRT and 13% (n = 9) with radiotherapy alone. Among low- and intermediate-risk patients, 10% and 42%, respectively, were treated with ADT plus EBRT. For 24% of EBRT patients (85 of 354), weekly electronic portal imaging was obtained as verification films without daily target localization, and the remaining 76% were treated with daily localization of the target using various methods. Conclusions Adherence to defined quality indicators was observed in a majority of patients. Approximately 90% of high-risk patients were treated with ADT plus EBRT and ≈80% of intermediate- and high-risk patients received prescription doses ≥75 Gy, consistent with the published results of randomized trials.

Purpose We report on quality of dose delivery to target and normal tissues from low-dose-rate prostate brachytherapy using postimplantation dosimetric evaluations from a random sample of U.S. patients. Methods and Materials Nonmetastatic prostate cancer patients treated with external beam radiotherapy or brachytherapy in 2007 were randomly sampled from radiation oncology facilities nationwide. Of 414 prostate cancer cases from 45 institutions, 86 received low-dose-rate brachytherapy. We collected the 30-day postimplantation CT images of these patients and 10 test cases from two other institutions. Scans were downloaded into a treatment planning system and prostate/rectal contours were redrawn. Dosimetric outcomes were reanalyzed and compared with calculated outcomes from treating institutions. Results Median prostate volume was 33.4 cm3. Reevaluated median V100, D90, and V150 were 91.1% (range, 45.5–99.8%), 101.7% (range, 59.6–145.9%), and 53.9% (range, 15.7–88.4%), respectively. Low gland coverage included 27 patients (39%) with a D90 lower than 100% of the prescription dose (PD), 12 of whom (17% of the entire group) had a D90 lower than 80% of PD. There was no correlation between D90 coverage and prostate volume, number of seeds, or implanted activity. The median V100 for the rectum was 0.3 cm3 (range, 0–4.3 cm3). No outcome differences were observed according to the institutional strata. Concordance between reported and reevaluated D90 values (defined as within ±10%) was observed in 44 of 69 cases. Conclusions Central review of postimplantation CT scans to assess the quality of prostate brachytherapy is feasible. Most patients achieved excellent dosimetric outcomes, yet 17% had less than optimal target coverage by the PD. There was concordance between submitted target-coverage parameters and central dosimetric review in 64% of implants. These findings will require further validation in a larger cohort of patients.

peer-reviewed Background: PE lessons are the formal opportunity in schools for promotion of physical activity and fitness. This study aimed to evaluate the effectiveness of a pilot PE intervention on physical activity, fitness, and psychosocial outcomes. Methods: Participants were 139 children aged 10–11 years from four schools. For six weeks children in two schools received a twice-weekly pilot ‘Born to Move’ (BTM) physical activity (PA) and fitness intervention alongside one regular PE lesson. Children in the two comparison (COM) schools received their regular twice weekly PE lessons. Outcomes were lesson time and whole-day light (LPA), moderate (MPA), vigorous (VPA), and MVPA, and sedentary time, muscular fitness, cardiorespiratory fitness (CRF), and lesson-specific perceived exertion, enjoyment, and perceived competence. Outcomes were assessed at baseline (T0), midway through the intervention (T1), and at the end (T2) using ANOVAs and ANCOVAs. Intervention fidelity was measured using child and teacher surveys at T2 and analysed using Chi-square tests. Results: The BTM group engaged in moderate PA for significantly more lesson time (29.4 %) than the COM group (25.8 %; p = .009, d = .53). The amount of moderate-to-vigorous PA (MVPA) during the T1 BTM lesson contributed 14.0 % to total MVPA, which was significantly more than the COM group’s T1 PE lesson (11.4 %; p < .001, d = .47). The BTM group were significantly more active during the whole-day (p < .05) and the school-day (p < .01). In both groups push-up test performance increased (p < .001) and CRF test performance decreased (p < .01). Perceived exertion, enjoyment, and perceived competence increased in both groups (p < .05), but the BTM group rated their enjoyment of the T1 BTM lesson higher than the COM group rated their PE lesson (p = .02, d = .56). The children’s and teachers’ responses to the intervention indicated that the delivery aims of enjoyment, engagement, inclusivity, and challenge were satisfied. Conclusions: The BTM pilot programme has potential to positively impact on physical activity, fitness, and psychosocial outcomes. Further, BTM was enjoyed by the children, and valued by the teachers. This study can inform the design of a modified larger-scale cluster RCT evaluation.

Data on initial treatment of 8232 cases of localized prostate cancer diagnosed in 2004 were obtained by medical record abstraction (including hospital and outpatient locations) from seven state cancer registries participating in the Centers for Disease Control and Prevention's Breast and Prostate Cancer Data Quality and Patterns of Care Study. Distinction was made between men receiving no therapy with no monitoring plan (no therapy/no plan [NT/NP]) and those receiving active surveillance (AS). Overall, 8.6% received NT/NP and 4.7% received AS. Older age at diagnosis, lower clinical risk group, and certain registry locations were significant predictors of use of both AS and NT/NP. AS was also related to having more severe comorbidities, whereas nonwhite race was predicted receiving NT/NP. Men receiving AS lived in areas with a higher number of urologists per 100 000 men than those receiving NT/NP. In summary, physician and clinical factors were stronger predictors of AS, whereas demographic and regional factors were related to receiving NT/NP. Physicians appear reluctant to recommend AS for younger patients with no comorbidities.