A consensus exercise identifying priorities for research into clinical effectiveness among children's orthopaedic surgeons in the United Kingdom

Aims: High-quality clinical research in children’s orthopaedic surgery has lagged behind other surgical subspecialties. This study used a consensus-based approach to identify research priorities for clinical trials in children’s orthopaedics. / Methods: A modified Delphi technique was used, which involved an initial scoping survey, a two-round Delphi process and an expert panel formed of members of the British Society of Children’s Orthopaedic Surgery. The survey was conducted amongst orthopaedic surgeons treating children in the United Kingdom and Ireland. / Results: A total of 86 clinicians contributed to both rounds of the Delphi process, scoring priorities from one (low priority) to five (high priority). Elective topics were ranked higher than those relating to trauma, with the top ten elective research questions scoring higher than the top question for trauma. Ten elective, and five trauma research priorities were identified, with the three highest ranked questions relating to the treatment of slipped capital femoral epiphysis (mean score 4.6/ 5), Perthes’ disease (4.5) and bone infection (4.5). / Conclusion: This consensus-based research agenda will guide surgeons, academics and funders to improve the evidence in children’s orthopaedic surgery and encourage the development of multicentre clinical trials

Detection of known haemophilia B mutations and carrier testing by microarray

The molecular basis of haemophilia B is heterogeneous and many mutations of the Factor IX (FIX) gene have been characterised. Using the allele-specific arrayed primer extension (AS-APEX) technology, we have designed a FIX array to simultaneously analyse 69 mutations found in British, Thai and Chinese patients. This technology overcomes the problem of multiple reverse dot-blot analysis and has a 100% accuracy in the detection of both affected subjects and carriers in families with known mutations. In seven unknown mutations from Thailand, the array could detect the specific mutation in five and in the remainders the normal primer at specific spots failed to extend due to a mutation a few nucleotides upstream, thus allowing their identification. Hence this FIX array can detect 53% of the 2891 mutation entries in the FIX database. Each of the microarray slide can be used for three different test samples and would be useful for carrier testing for common mutations and prenatal diagnosis. It is simpler and more cost effective than genome sequencing and would be particularly useful in laboratories with limited technical capabilities. © 2005 Schattauer GmbH, Stuttgart.published_or_final_versio

Aspiration of parenteral nutrition – a previously unreported complication of central venous access in an infant: a case report

Introduction: The insertion of percutaneous central venous catheters is a common procedure in neonatal intensive care nurseries. Placement of the catheter tip in a large central vein is most desirable. Occasionally, due to difficult venous access, catheter tips are left in places that are less than ideal. Case presentation: A female infant with a complicated gastroschisis developed signs of short bowel syndrome post surgery. She was treated with a combination of parenteral nutrition and enteral feeds. A central venous line was inserted through a scalp vein. The tip was noted to be in a vessel at the level of the mandible. She subsequently became unwell with large milky pharyngeal aspirates and episodes of bradycardia. Chest radiography revealed aspiration. The central venous line was removed because of presumed extravasation. This is the first reported case of parenteral nutrition extravasation into the pharynx causing aspiration in an infant. Conclusion: This complication may have been prevented by recognising that the tip of the catheter was not correctly placed. When catheters are in unusual positions it may be useful to obtain a second radiograph from a different angle or an ultrasound scan to confirm the positioning of the catheter tip

Aspiration of parenteral nutrition – a previously unreported complication of central venous access in an infant: a case report

Introduction: The insertion of percutaneous central venous catheters is a common procedure in neonatal intensive care nurseries. Placement of the catheter tip in a large central vein is most desirable. Occasionally, due to difficult venous access, catheter tips are left in places that are less than ideal. Case presentation: A female infant with a complicated gastroschisis developed signs of short bowel syndrome post surgery. She was treated with a combination of parenteral nutrition and enteral feeds. A central venous line was inserted through a scalp vein. The tip was noted to be in a vessel at the level of the mandible. She subsequently became unwell with large milky pharyngeal aspirates and episodes of bradycardia. Chest radiography revealed aspiration. The central venous line was removed because of presumed extravasation. This is the first reported case of parenteral nutrition extravasation into the pharynx causing aspiration in an infant. Conclusion: This complication may have been prevented by recognising that the tip of the catheter was not correctly placed. When catheters are in unusual positions it may be useful to obtain a second radiograph from a different angle or an ultrasound scan to confirm the positioning of the catheter tip

Encouraging brisk walking with the free Active10 app in postnatal women who had a hypertensive pregnancy: "Just Walk It" feasibility study.

OBJECTIVE: To explore the feasibility of a future trial to investigate whether encouraging use of the free NHS smartphone app Active10 increases brisk walking and reduces blood pressure (BP) in postnatal mothers who had hypertensive disorders of pregnancy (HDP). DESIGN: 3-month feasibility study. SETTING: London maternity unit. POPULATION: 21 women with HDP. METHODS: At recruitment we recorded initial (booking) clinic BP and asked participants to complete a questionnaire. Two months after delivery all participants were sent (by post/email/WhatsApp) a "Just Walk It" leaflet encouraging them to download the Active10 app and walk briskly for at least 10 minutes/day. This was backed by a telephone call after 2-weeks. Assessments were repeated 3-months later, and included telephone interviews about the acceptability and use of Active10. MAIN OUTCOME MEASURES: Were recruitment rate, follow-up rate and acceptability/use of Active10. RESULTS: Of 28 women approached, 21 (75%, 95% CI 55.1-89.3%) agreed to participate. Age range was 21-46 years and five (24%) self-identified as black ethnicity. One woman dropped out of the study, and one became ill. The remaining participants (90%, 19/21, 95% CI 69.6-98.8%) were followed up after 3-months. Ninety-five percent (18/19) downloaded the Active10 app and 74% (14/19) continued using it at 3-months, averaging 27-minutes brisk walking/day according to Active10 weekly screenshots. Comments included: "Brilliant app", "Really motivates me". Mean BP was 130/81mmHg at booking and 124/80mmHg at 3-months follow-up. CONCLUSIONS: The Active10 app was acceptable to postnatal women after HDP and may have increased minutes of brisk walking. A future trial could explore whether this simple, low-cost intervention could reduce long-term BP in this vulnerable group

The Prevalence and Characteristics of Performance-Enhancing Drug Use Among Bodybuilding Athletes in the South of Iran, Bushehr

Background: Several reports have implied progressive increase of performance-enhancing drug (PED) use among Iranian athletes. More importantly, most of the previous research in the Iranian population had mainly focused on the anabolic steroid abuse, and ignored other agents. Objectives: The aim of this study was to investigate the prevalence and characteristics of PED use among bodybuilding athletes in Bushehr, south of Iran. Methods: Four hundred and fifty three male bodybuilding athletes were recruited from Bushehr gyms between February and May of 2015. Men were eligible to participate in the survey if they had regularly participated in the strength-training exercise (minimum of 1 year and 4 hour/week). Data were collected via a face-to-face interview. The survey consisted of three separate parts including demographic data, exercise pattern and PED use. Results: According to this study, 234 (51.7%) of bodybuilding athletes had used PEDs. The PED users reported an average of 3.80 � 4.52 agents’ use in their programs and they had used PEDs for the average of 3.24 � 3.99 years. The most prevalent agents which had been abused by the athletes were anabolic steroids (used by 185 athletes (79.4% of athletes). Furthermore, 110 (47%) of athletes reported stimulant agents’ use during their routines. The most prevalent motivation for using PEDs was increasing muscle mass that was reported by 164 (70.1%) of PED users. In addition, sexual and dermatologic effects were the most prevalent adverse effects reported by the PED user athletes (114 (49.4%) and 103 (44.2%), respectively). Conclusions: This study showed the high rate of PED use among recreational and professional Iranian bodybuilding athletes that can expose them to the serious side effects of these agents

Improving Early Antibiotic Administration for Treatment of Sepsis at Children’s Hospital of Richmond at VCU: 2012-2019

Background: The Surviving Sepsis Campaign recommends initiating IV antibiotic administration within one hour of recognition of severe sepsis. Several studies have shown that prompt blood culture collection, administration of broad-spectrum antibiotics, and fluid resuscitation following recognition improves child survival. Objective: Our goal was to evaluate effectiveness of sepsis initiatives and institutional changes in the timing of early antibiotic administration at Children’s Hospital of Richmond at VCU. Methods: We formed a Pediatric Sepsis Committee with representatives from each unit in 2013. In 2016, the committee began tracking time from the order of a first stat dose IV antibiotic to administration as a marker of early treatment and reviewed data on a monthly basis with run charts for overall and unit-specific data. Other interventions included improved availability of antibiotics in automated dispensing machines, sepsis screening and alert systems, sepsis huddles, and auto-generated pages to charge nurses upon order of stat IV antibiotics. We included percent of stat antibiotics administered in less than one hour from order across all pediatric units since 2012. Results: Across all units, the centerline of first dose stat antibiotics delivered within one hour improved from a baseline of 34% in 2012 to 76% in 2019. The NICU and PICU centerlines improved by 53% and 48%, respectively since 2012. The Pediatric ED improved from 66% in 2012 to 84% in 2016. The Acute Care Pediatrics (ACP) Unit centerline improved from 24% in 2012 to 50% in 2017. Conclusion: Time from order to stat antibiotic administration has improved in all units receiving quality improvement initiatives. These improvements have been made possible by widespread emphasis on the dangers of untreated sepsis, multidisciplinary collaboration between nursing and physician staff, structural pharmacy changes and electronic alerts. Further studies are needed to determine impact on patient outcomes

'The Drug Survey App': a protocol for developing and validating an interactive population survey tool for drug use among Aboriginal and Torres Strait Islander Australians.

BACKGROUND: Disadvantage and transgenerational trauma contribute to Aboriginal and Torres Strait Islander (Indigenous) Australians being more likely to experience adverse health consequences from alcohol and other drug use than non-Indigenous peoples. Addressing these health inequities requires local monitoring of alcohol and other drug use. While culturally appropriate methods for measuring drinking patterns among Indigenous Australians have been established, no similar methods are available for measuring other drug use patterns (amount and frequency of consumption). This paper describes a protocol for creating and validating a tablet-based survey for alcohol and other drugs ("The Drug Survey App"). METHODS: The Drug Survey App will be co-designed with stakeholders including Indigenous Australian health professionals, addiction specialists, community leaders, and researchers. The App will allow participants to describe their drug use flexibly with an interactive, visual interface. The validity of estimated consumption patterns, and risk assessments will be tested against those made in clinical interviews conducted by Indigenous Australian health professionals. We will then trial the App as a population survey tool by using the App to determine the prevalence of substance use in two Indigenous communities. DISCUSSION: The App could empower Indigenous Australian communities to conduct independent research that informs local prevention and treatment efforts

Effects of beta-alanine supplementation on brain homocarnosine/carnosine signal and cognitive function: an exploratory study

Objectives: Two independent studies were conducted to examine the effects of 28 d of beta-alanine supplementation at 6.4 g d-1 on brain homocarnosine/carnosine signal in omnivores and vegetarians (Study 1) and on cognitive function before and after exercise in trained cyclists (Study 2). Methods: In Study 1, seven healthy vegetarians (3 women and 4 men) and seven age- and sex-matched omnivores undertook a brain 1H-MRS exam at baseline and after beta-alanine supplementation. In study 2, nineteen trained male cyclists completed four 20-Km cycling time trials (two pre supplementation and two post supplementation), with a battery of cognitive function tests (Stroop test, Sternberg paradigm, Rapid Visual Information Processing task) being performed before and after exercise on each occasion. Results: In Study 1, there were no within-group effects of beta-alanine supplementation on brain homocarnosine/carnosine signal in either vegetarians (p = 0.99) or omnivores (p = 0.27); nor was there any effect when data from both groups were pooled (p = 0.19). Similarly, there was no group by time interaction for brain homocarnosine/carnosine signal (p = 0.27). In study 2, exercise improved cognitive function across all tests (P0.05) of beta-alanine supplementation on response times or accuracy for the Stroop test, Sternberg paradigm or RVIP task at rest or after exercise. Conclusion: 28 d of beta-alanine supplementation at 6.4g d-1 appeared not to influence brain homocarnosine/ carnosine signal in either omnivores or vegetarians; nor did it influence cognitive function before or after exercise in trained cyclists

The Ecm11-Gmc2 complex promotes synaptonemal complex formation through assembly of transverse filaments in budding yeast

During meiosis, homologous chromosomes pair at close proximity to form the synaptonemal complex (SC). This association is mediated by transverse filament proteins that hold the axes of homologous chromosomes together along their entire length. Transverse filament proteins are highly aggregative and can form an aberrant aggregate called the polycomplex that is unassociated with chromosomes. Here, we show that the Ecm11-Gmc2 complex is a novel SC component, functioning to facilitate assembly of the yeast transverse filament protein, Zip1. Ecm11 and Gmc2 initially localize to the synapsis initiation sites, then throughout the synapsed regions of paired homologous chromosomes. The absence of either Ecm11 or Gmc2 substantially compromises the chromosomal assembly of Zip1 as well as polycomplex formation, indicating that the complex is required for extensive Zip1 polymerization. We also show that Ecm11 is SUMOylated in a Gmc2-dependent manner. Remarkably, in the unSUMOylatable ecm11 mutant, assembly of chromosomal Zip1 remained compromised while polycomplex formation became frequent. We propose that the Ecm11-Gmc2 complex facilitates the assembly of Zip1 and that SUMOylation of Ecm11 is critical for ensuring chromosomal assembly of Zip1, thus suppressing polycomplex formation