The effect of high-flow nasal oxygen flow rate on gas exchange in apnoeic patients: a randomised controlled trial.

High-flow nasal oxygen can be administered at induction of anaesthesia for the purposes of pre-oxygenation and apnoeic oxygenation. This intervention is claimed to enhance carbon dioxide elimination during apnoea, but the extent to which this occurs remains poorly quantified. The optimal nasal oxygen flow rate for gas exchange is also unknown. In this study, 114 patients received pre-oxygenation with high-flow nasal oxygen at 50 l.min-1. At the onset of apnoea, patients were allocated randomly to receive one of three nasal oxygen flow rates: 0 l.min-1; 70 l.min-1; or 120 l.min-1. After 4 minutes of apnoea, all oxygen delivery was ceased, tracheal intubation was performed, and oxygen delivery was recommenced when SpO2 was 92%. Mean (SD) PaCO2 rise during the first minute of apnoea was 1.39 (0.39) kPa, 1.41 (0.29) kPa, and 1.26 (0.38) kPa in the 0 l.min-1, 70 l.min-1 and 120 l.min-1 groups, respectively; p = 0.16. During the second, third and fourth minutes of apnoea, mean (SD) rates of rise in PaCO2 were 0.34 (0.08) kPa.min-1, 0.36 (0.06) kPa.min-1 and 0.37 (0.07) kPa.min-1 in the 0 l.min-1, 70 l.min-1 and 120 l.min-1 groups, respectively; p = 0.17. After 4 minutes of apnoea, median (IQR [range]) arterial oxygen partial pressures in the 0 l.min-1, 70 l.min-1 and 120 l.min-1 groups were 24.5 (18.6-31.4 [12.3-48.3]) kPa; 36.6 (28.1-43.8 [9.8-56.9]) kPa; and 37.6 (26.5-45.4 [11.0-56.6]) kPa, respectively; p < 0.001. Median (IQR [range]) times to desaturate to 92% after the onset of apnoea in the 0 l.min-1, 70 l.min-1 and 120 l.min-1 groups, were 412 (347-509 [190-796]) s; 533 (467-641 [192-958]) s; and 531 (462-681 [326-1007]) s, respectively; p < 0.001. In conclusion, the rate of carbon dioxide accumulation in arterial blood did not differ significantly between apnoeic patients who received high-flow nasal oxygen and those who did not.

The approach to extracorporeal cardiopulmonary resuscitation (ECPR) in children. A narrative review by the paediatric ECPR working group of EuroELSO.

Extracorporeal Cardiopulmonary Resuscitation (ECPR) has potential benefits compared to conventional Cardiopulmonary Resuscitation (CCPR) in children. Although no randomised trials for paediatric ECPR have been conducted, there is extensive literature on survival, neurological outcome and risk factors for survival. Based on current literature and guidelines, we suggest recommendations for deployment of paediatric ECPR emphasising the requirement for protocols, training, and timely intervention to enhance patient outcomes. Factors related to outcomes of paediatric ECPR include initial underlying rhythm, CCPR duration, quality of CCPR, medications during CCPR, cannulation site, acidosis and renal dysfunction. Based on current evidence and experience, we provide an approach to patient selection, ECMO initiation and management in ECPR regarding blood and sweep flow settings, unloading of the left ventricle, diagnostics whilst on ECMO, temperature targets, neuromonitoring as well as suggested weaning and decannulation strategies.

Pre-oxygenation with facemask oxygen vs high-flow nasal oxygen vs high-flow nasal oxygen plus mouthpiece: a randomised controlled trial.

High-flow nasal oxygen used before and during apnoea prolongs time to desaturation at induction of anaesthesia. It is unclear how much oxygenation before apnoea prolongs this time. We randomly allocated 84 participants to 3 minutes of pre-oxygenation by one of three methods: 15 l.min-1 by facemask; 50 l.min-1 by high-flow nasal cannulae only; or 50 l.min-1 by high-flow nasal cannulae plus 15 l.min-1 by mouthpiece. We then anaesthetised and intubated the trachea of 79 participants and waited for oxygen saturation to fall to 92%. Median (IQR [range]) times to desaturate to 92% after pre-oxygenation with facemask oxygen, high-flow nasal oxygen only and high-flow nasal oxygen with mouthpiece, were: 309 (208-417 [107-544]) s; 344 (250-393 [194-585]) s; and 386 (328-498 [182-852]) s, respectively, p = 0.014. Time to desaturation after facemask pre-oxygenation was shorter than after combined nasal and mouthpiece pre-oxygenation, p = 0.006. We could not statistically distinguish high-flow nasal oxygen without mouthpiece from the other two groups for this outcome. Median (IQR [range]) arterial oxygen partial pressure after 3 minutes of pre-oxygenation by facemask, nasal cannulae and nasal cannulae plus mouthpiece, was: 49 (36-61 [24-66]) kPa; 57 (48-62 [30-69]) kPa; and 61 (55-64 [36-72]) kPa, respectively, p = 0.003. Oxygen partial pressure after 3 minutes of pre-oxygenation with nasal and mouthpiece combination was greater than after facemask pre-oxygenation, p = 0.002, and after high-flow nasal oxygen alone, p = 0.016. We did not reject the null hypothesis for the pairwise comparison of facemask pre-oxygenation and high-flow nasal pre-oxygenation, p = 0.14.

Exercise Compared to Mindfulness for Physical and Mental Wellbeing in Medical Students.

Aim Physical Activity (PA) and Mindfulness-Based Stress Reduction (MBSR) both have positive effects on medical student well-being. The 'MED-WELL' programme is a curricular intervention that combines PA and education on exercise as medicine. This trial evaluates whether there is a mean difference in outcomes of participants of an exercise intervention, the 'MED-WELL' programme, versus a control group which engages in a MBSR programme. Methods All second-year medical students were voluntarily allocated into the intervention or control group. Data on overall health and well-being, sleep quality, loneliness, current level of PA, and confidence in prescribing exercise as medicine was analysed from both groups at baseline and after eight weeks. Results Within groups the intervention and control groups showed statistically significant improvements in overall well-being (p=0.010, p=0.005 respectively) and in sleep quality (p<0.001, p=0.007 respectively). The intervention group had statistically significant improvements in levels of PA (p=0.003) and confidence in prescribing exercise (p<0.001). However, there were no statistically significant differences in changes in outcome measures between groups. Conclusion This study has shown that participants in an exercise intervention, the 'MED-WELL' programme, had similar improvements in overall wellbeing and sleep quality to those in a control group who participated in a MBSR programme of the same duration.

Apnoeic oxygenation in paediatric anaesthesia: a narrative review.

Apnoeic oxygenation refers to oxygenation in the absence of any patient or ventilator effort to move the lungs. This phenomenon was first described in humans in the mid-20th century but has seen renewed interest in the last decade following the demonstration of apnoeic oxygenation with low-flow, and subsequently high-flow, nasal oxygen. This narrative review summarises our understanding of apnoeic oxygenation in the paediatric population. We examine the evidence supporting oxygenation via tracheal tube, modified laryngoscopes and nasal cannulae. The evidence for prolongation of safe apnoea time at induction of anaesthesia is also appraised. We explore the capacity for carbon dioxide clearance, flow rate selection with high-flow nasal oxygen and complications associated with the technique. It remains uncertain whether apnoeic oxygenation in paediatric patients results in a meaningful clinical benefit compared with standard care for outcomes such as the number of tracheal intubation attempts or the incidence of hypoxaemia. In particular, the role of apnoeic oxygenation in paediatric difficult airway management is unclear as this has not been the targeted focus of any published research to date.

Uses and mechanisms of apnoeic oxygenation: a narrative review.

Apnoeic oxygenation refers to oxygenation in the absence of spontaneous respiration or mechanical ventilation. It has been described in humans for over half a century and has seen a resurgence in interest given its potential to delay oxygen desaturation during airway management, especially with the advent of high-flow nasal cannulae. This narrative review summarises our current understanding of the mechanisms of gas exchange during apnoeic oxygenation and its diverse range of clinical applications, including its use at induction of anaesthesia and for the facilitation of 'tubeless anaesthesia'. Additional discussion covers use in critical care, obese, obstetric and paediatric sub-populations. The article also highlights current research efforts aiming to enhance the evidence base for the use of this technique.

Food environments in and around post-primary schools in Ireland: Associations with youth dietary habits.

BACKGROUND: The food environment within and surrounding schools may influence children's diets. This study explored if the internal and external school food environments were associated with intake of specific food groups among adolescents. METHODS: Participants were a subset of 5344 post-primary school students that took part in the Health Behaviour in School-aged Children (HBSC) survey. Four school-level variables were created: urban/rural, disadvantaged status, percentage fast food premises within one kilometer of the school and food sold in the school. Logistic regression models were used to examine school-level influences on daily food consumption controlling for individual and family food environmental factors. RESULTS: For students in disadvantaged schools, the odds of having soft drinks (OR 1.79, 95% CI 1.30-2.47) or chips (OR 1.82, 95% CI 1.17-2.83) daily were larger and the odds of consuming fruits (OR 0.79, 95% CI 0.62-0.99) or vegetables (OR 0.73, 95% CI 0.60-0.88) daily were smaller than for students at other schools. Girls and those from higher socioeconomic classes also had healthier eating habits. Attending a school where more than 10% of the food premises within one kilometer of the school were fast food outlets was associated with a 0.78 (95% CI 0.64 to 0.94) and a 0.79 (95% CI 0.66 to 0.93) decreased odds of daily fruit and vegetable intake, respectively. CONCLUSIONS: Fast food environments around post-primary schools are associated with less fruit and vegetable intake. Children in disadvantaged schools and from lower social classes are more likely to report poorer dietary habits than children in other schools or from higher social classes, respectively. Multiple contexts influence diet, and children at an economic or social disadvantage are at most risk of poor dietary habits.

Genetic Landscape of Rett Syndrome Spectrum: Improvements and Challenges.

Rett syndrome (RTT) is an early-onset neurodevelopmental disorder that primarily affects females, resulting in severe cognitive and physical disabilities, and is one of the most prevalent causes of intellectual disability in females. More than fifty years after the first publication on Rett syndrome, and almost two decades since the first report linking RTT to the MECP2 gene, the research community's effort is focused on obtaining a better understanding of the genetics and the complex biology of RTT and Rett-like phenotypes without MECP2 mutations. Herein, we review the current molecular genetic studies, which investigate the genetic causes of RTT or Rett-like phenotypes which overlap with other genetic disorders and document the swift evolution of the techniques and methodologies employed. This review also underlines the clinical and genetic heterogeneity of the Rett syndrome spectrum and provides an overview of the RTT-related genes described to date, many of which are involved in epigenetic gene regulation, neurotransmitter action or RNA transcription/translation. Finally, it discusses the importance of including both phenotypic and genetic diagnosis to provide proper genetic counselling from a patient's perspective and the appropriate treatment.

Peri-conception and first trimester diet modifies reproductive development in bulls.

Nutritional perturbation during gestation alters male reproductive development in rodents and sheep. In cattle both the developmental trajectory of the feto-placental unit and its response to dietary perturbations is dissimilar to that of these species. This study examined the effects of dietary protein perturbation during the peri-conception and first trimester periods upon reproductive development in bulls. Nulliparous heifers (n=360) were individually fed a high- or low-protein diet (HPeri and LPeri) from 60 days before conception. From 24 until 98 days post conception, half of each treatment group changed to the alternative post-conception high- or low-protein diet (HPost and LPost) yielding four treatment groups in a 2×2 factorial design. A subset of male fetuses (n=25) was excised at 98 days post conception and fetal testis development was assessed. Reproductive development of singleton male progeny (n=40) was assessed until slaughter at 598 days of age, when adult testicular cytology was evaluated. Low peri-conception diet delayed reproductive development: sperm quality was lowered during pubertal development with a concomitant delay in reaching puberty. These effects were subsequent to lower FSH concentrations at 330 and 438 days of age. In the fetus, the low peri-conception diet increased the proportion of seminiferous tubules and decreased blood vessel area in the testis, whereas low first trimester diet increased blood vessel number in the adult testis. We conclude that maternal dietary protein perturbation during conception and early gestation may alter male testis development and delay puberty in bulls.

A Cross-Sectional Study of Antibiotic Prescribing for Childhood Upper Respiratory Tract Infections in Irish General Practice

Introduction This study aimed to analyse antibiotic prescribing in cases of upper respiratory tract infection (URTI) in children under 6 years attending Irish daytime and out-of-hours General Practice (GP) services. There have been large scale changes in entitlements for free GP care for this group in recent years. Methods A cross-sectional study of children under 6 years with URTI presentations was performed, over a two-week period for three years from 2015 to 2017. Factors associated with antibiotic prescription and preferred antibiotic compliance were examined using multivariate logistic regression. Results 1,007 Under-6 patients presented with an URTI in our sample over the study period. Following introduction of free GP care, patients were 50% less likely to receive an antibiotic prescription. Overall antibiotic prescribing fell from 70% to 50% in daytime services and from 72% to 60% in the out-of-hours setting. Patients presenting to out-of-hours services were more likely to receive an antibiotic (OR: 1.42) and less likely to receive a deferred antibiotic (OR: 0.53). One quarter to one third of all prescriptions were for deferred antibiotics. Year-on-year trends showed a 13% decrease in prescriptions and 13% increase in preferred antibiotic use. Conclusion The introduction of free GP care led to significant reductions in antibiotic prescribing, which may be due to changes in health seeking behaviour by parents or other reasons. Antibiotic prescribing was more commonplace in the out-of-hours setting, and rates remains high by international standards. This study underlines the importance of ongoing work around GP antimicrobial stewardship, particularly in the out-of-hours setting.

Oncological outcomes in an Australian cohort according to the new prostate cancer grading groupings.

BACKGROUND: A new 5-tiered grading grouping system has recently been endorsed for reporting of prostate cancer (PCa) grade to better reflect escalating risk of progression and cancer death. While several validations of the new grade groupings have been undertaken, most have involved centralised pathological review by specialist urological pathologists. METHODS: Participants included 4268 men with non-metastatic PCa diagnosed between 2006 and 2013 from the multi-institutional South Australia Prostate Cancer Clinical Outcomes Collaborative registry. PCa-specific survival and biochemical recurrence-free survival were compared across the five grade groups using multivariable competing risk regression. RESULTS: For the entire cohort, risk of PCa death increased with increasing grade groups (at biopsy) Adjusted subdistribution-hazard ratios [sHR] and 95% confidence intervals [95%CI] were: 2.2 (1.5-3.6); 2.5 (1.6-4.2); 4.1 (2.6-6.7) and 8.7 (4.5-14.0) for grade groups II (pattern 3 + 4), III (pattern 4 + 3), IV (total score 8) and V (total score 9-10) respectively, relative to grade group I (total score < =6). Clear gradients in risk of PCa death were observed for radical prostatectomy (RP), but were less clear for those who had radiotherapy (RT) with curative intent and those who were managed conservatively. Likewise, risk of biochemical recurrence increased across grade groups, with a strong and clear gradient for men undergoing RP [sHR (95%CI): 2.0 (1.4-2.8); 3.8 (2.9-5.9); 5.3 (3.5-8.0); 11.2 (6.5-19.2) for grade groups II, III, IV and V respectively, relative to grade group I], and a less clear gradient for men undergoing RT. CONCLUSION: In general, the new five-tiered grade groupings distinguished PCa survival and recurrence outcomes for men with PCa. The absence of a clear gradient for RT may be due to heterogeneity in this patient group.

Apnoeic oxygenation with high-flow nasal oxygen for laryngeal surgery: a case series.

Surgery under apnoeic conditions with the use of high-flow nasal oxygen is novel. Between November 2016 and May 2017, 28 patients underwent tubeless laryngeal or tracheal surgery under apnoeic conditions with high-flow nasal oxygen as the sole method of gas exchange. Patients received total intravenous anaesthesia and neuromuscular blocking agents for the duration of their surgery. The median (IQR [range]) apnoea time was 19 (15-24 [9-37]) min. Four patients experienced an episode of oxygen desaturation to a value between 85% and 90%, lasting less than 2 min in each case. Median (IQR [range]) end-tidal carbon dioxide (ETCO2 ) level following apnoea was 8.2 (7.2-9.4 [5.8-11.8]) kPa. The mean (SD) rate of ETCO2 increase was 0.17 (0.07) kPa.min-1 from an approximated baseline value of 5.00 kPa. Venous blood sampling from 19 patients demonstrated a mean (SD) partial pressure of carbon dioxide (PV CO2 ) of 6.29 (0.71) kPa at baseline and 9.44 (1.12) kPa after 15 min of apnoea. This equates to a mean (SD) PV CO2 rise of 0.21 (0.08) kPa.min-1 during this period. Mean (SD) pH was 7.40 (0.03) at baseline and 7.23 (0.04) after 15 min of apnoea. Mean (SD) standard bicarbonate was 26.7 (1.8) mmol.l-1 at baseline and 25.4 (1.8) mmol.l-1 at 15 min. We conclude that high-flow nasal oxygen under apnoeic conditions can provide satisfactory gas exchange in order to allow tubeless anaesthesia for laryngeal surgery.

Prognostic factors for musculoskeletal injury identified through medical screening and training load monitoring in professional football (soccer): a systematic review.

OBJECTIVES: To identify prognostic factors and models for spinal and lower extremity injuries in adult professional/elite football players from medical screening and training load monitoring processes. METHODS: The MEDLINE, AMED, EMBASE, CINAHL Plus, SPORTDiscus electronic bibliographic databases and the Cochrane Database of Systematic Reviews were searched from inception to July 2016. Searches were limited to original research, published in peer reviewed journals of any language. The Quality in Prognostic Studies (QUIPS) tool was used for appraisal and the modified GRADE approach was used for synthesis. Prospective and retrospective cohort study designs of spinal and lower extremity injury incidence were found from populations of adult professional/elite football players, between 16 and 40 years. Non-football or mixed sports were excluded. RESULTS: 858 manuscripts were identified. Removing duplications left 551 studies, which were screened for eligibility by title and abstract. Of these, 531 studies were not eligible and were excluded. The full text of the remaining 20 studies were obtained; a further 10 studies were excluded. 10 studies were included for appraisal and analysis, for 3344 participants. CONCLUSIONS: Due to the paucity and heterogeneity of the literature, and shortcomings in methodology and reporting, the evidence is of very low or low quality and therefore cannot be deemed robust enough to suggest conclusive prognostic factors for all lower limb musculoskeletal injury outcomes identified. No studies were identified that examined spinal injury outcomes or prognostic models.

The short-lived neon damsel Pomacentrus coelestis: implications for population dynamics.

Daily increments of Pomacentrus coelestis, an abundant and well-studied fish, were validated for the life of the fish and depending on the location, age-maxima were estimated to be 127-160 days on reefs separated by tens to hundreds of kilometres on the Great Barrier Reef. This contrasts with congeners and other damselfishes that live for 5 years or more. Otoliths of P. coelestis were thinner and had different patterns of banding when compared with relatively long-lived congeners. It is suggested that banding patterns in P. coelestis may be related to patterns of maturation and spawning. The consequences of a short life would have a great influence on the population dynamics of this widespread species. Further, the demographics and habitat preferences of this species suggest rapid colonization and establishment of breeding populations that would quickly change the relative abundance of sympatric fishes.

A knee brace alters patella position in patellofemoral osteoarthritis: a study using weight bearing magnetic resonance imaging.

OBJECTIVE: To assess using weight bearing magnetic resonance imaging (MRIs), whether a patellar brace altered patellar position and alignment in patellofemoral joint (PFJ) osteoarthritis (OA). DESIGN: Subjects age 40-70 years old with symptomatic and a radiographic Kellgren-Lawrence (K-L) evidence of PFJOA. Weight bearing knee MRIs with and without a patellar brace were obtained using an upright open 0.25 T scanner (G-Scan, Easote Biomedica, Italy). Five aspects of patellar position were measured: mediolateral alignment by the bisect offset index, angulation by patellar tilt, patellar height by patellar height ratio (patellar length/patellar tendon length), lateral patellofemoral (PF) contact area and finally a measurement of PF bony separation of the lateral patellar facet and the adjacent surface on the femoral trochlea (Fig. 1). RESULTS: Thirty participants were recruited (mean age 57 SD 27.8; body mass index (BMI) 27.8 SD 4.2); 17 were females. Four patients had non-usable data. Main analysis used paired t tests comparing within subject patellar position with and without brace. For bisect offset index, patellar tilt and patellar height ratio there were no significant differences between the brace and no brace conditions. However, the brace increased lateral facet contact area (P = .04) and decreased lateral PF separation (P = .03). CONCLUSION: A patellar brace alters patellar position and increases contact area between the patella and femoral trochlea. These changes would lower contact stress at the PFJ. Such changes in patella position in weight bearing provide a possible biomechanical explanation for the success of the PFJ brace in clinical trials on PFJOA.

Whole-exome sequencing points to considerable genetic heterogeneity of cerebral palsy.

Cerebral palsy (CP) is a common, clinically heterogeneous group of disorders affecting movement and posture. Its prevalence has changed little in 50 years and the causes remain largely unknown. The genetic contribution to CP causation has been predicted to be ~2%. We performed whole-exome sequencing of 183 cases with CP including both parents (98 cases) or one parent (67 cases) and 18 singleton cases (no parental DNA). We identified and validated 61 de novo protein-altering variants in 43 out of 98 (44%) case-parent trios. Initial prioritization of variants for causality was by mutation type, whether they were known or predicted to be deleterious and whether they occurred in known disease genes whose clinical spectrum overlaps CP. Further, prioritization used two multidimensional frameworks-the Residual Variation Intolerance Score and the Combined Annotation-dependent Depletion score. Ten de novo mutations in three previously identified disease genes (TUBA1A (n=2), SCN8A (n=1) and KDM5C (n=1)) and in six novel candidate CP genes (AGAP1, JHDM1D, MAST1, NAA35, RFX2 and WIPI2) were predicted to be potentially pathogenic for CP. In addition, we identified four predicted pathogenic, hemizygous variants on chromosome X in two known disease genes, L1CAM and PAK3, and in two novel candidate CP genes, CD99L2 and TENM1. In total, 14% of CP cases, by strict criteria, had a potentially disease-causing gene variant. Half were in novel genes. The genetic heterogeneity highlights the complexity of the genetic contribution to CP. Function and pathway studies are required to establish the causative role of these putative pathogenic CP genes.

Prostate cancer in men aged less than 50 years at diagnosis.

PURPOSE: Prostate cancer (CaP) in younger men (age ≤50 years) appears to present differently compared with older men. This study describes CaP characteristics and outcomes in Australian young men. METHODS: The South Australian Prostate Cancer Clinical Outcomes Collaborative database was used to identify men diagnosed with CaP 1998-2012. Men were stratified by age at diagnosis into groups ≤50, 50-70 and ≥70 years. Primary outcomes of cumulative biochemical recurrence (BCR) and cumulative prostate cancer-specific mortality (PCSM) were assessed at 5 and 10 years. RESULTS: In total, 7018 men were included. At time of diagnosis, 182 (2.6 %) were aged ≤50 years. Median follow-up exceeded 4 years. Younger men had a greater proportion of T stage <2 disease, lower median PSA and higher rates of Gleason score <7 (all p < 0.001). They were more likely to experience active surveillance (AS) (4.9, 3.1, 1.5 %) or radical prostatectomy (RP) (70, 55, 8 %) and less likely radiotherapy (13, 24, 29 %) as their principal modality (all p < 0.001). Although only 4.9 % underwent AS, 48 % of men ≤50 years were eligible for AS. Men ≤50 years had both the lowest unadjusted cumulative BCR and PCSM at 10 years. After multivariate analysis, BCR was not significantly different. Sample size limited multivariate analysis of PCSM. CONCLUSIONS: In our cohort, men ≤50 years with CaP had less aggressive clinical characteristics, but were more likely to undergo RP. They appear to experience lower unadjusted PCSM, but similar rates of adjusted BCR. Further studies are needed to assess whether AS is appropriately utilised in these men.