Adaptive school grounds design in response to COVID-19: Findings from six primary schools in South East England.

The purpose of this research is to look at how primary schools in England have adapted their outdoor spaces in the context of COVID-19 rules and guidelines to meet the needs of students returning from school closures and national lockdown of Spring/Summer 2020, how that impacted play and learning value of their grounds, and to consider how these findings might inform future school grounds design. Thus, we used a mixed-method approach that included qualitative interviews with representatives from six primary schools (three in rural and three in urban areas), quantitative desk research, and in-person site surveys. We used literature-based scoring criteria to quantify changes in the playground before and after the implementation of COVID-19 measures. The research reveals that the zoning of play areas and other aspects of the school grounds may negatively affected the value of play and learning. We also found a substantial disparity in the amount of outside space per pupil (OSPP) available across schools. Those with the lowest OSPP also had the lowest outdoor and environmental learning provision, lacking the flexibility to accommodate this alongside other requirements of staggered play breaks and PE. The amount of outdoor space that a school has available per pupil averaged at 32 m2 for urban schools and 43 m2 for rural schools. Finally, we have explored how spatial layout and design elements may have supported or inhibited schools' abilities to respond to children's needs, and how this might inform adaptive school grounds design considerations for the future.

Effect of CYP2C9 *11/*11 genotype on initial and long-term warfarin dose requirement and therapeutic response.

The warfarin dose requirement and therapeutic response of a 42-year-old African-American male with genotype CYP2C9 *11/*11, VKORC1 -1639GG and CYP4F2 433Val/Val anticoagulated for ischemic stroke is described herein. Warfarin was dosed according to the institution's personalized medicine program recommendations of a 10 mg mini-load dose, followed by dose decreases to 4-6 mg/day through discharge. Stable international normalized ratio was achieved after eight doses, with good overall long-term maintenance of therapeutic international normalized ratio over several years with warfarin doses of 3.1-4.3 mg/day. This case report sheds further light on the clinical impact of CYP2C9 *11/*11 on warfarin dose requirements, short- and long-term treatment response and practical considerations for warfarin management in suspected carriers of rare variant CYP2C9 alleles.

Vaccination against pertussis and influenza in pregnancy: a qualitative study of barriers and facilitators.

OBJECTIVES: Influenza and pertussis vaccination programmes have been in place for pregnant women in the UK since 2009 and 2012, respectively. In 2015, vaccine uptake rates were 55% for influenza and 63% for pertussis in Northern Ireland. We conducted a qualitative study with the aim of learning about the views of pregnant women and identifying potential barriers to vaccination in pregnancy. STUDY DESIGN: Qualitative study using focus groups and in-depth interviews. METHODS: We conducted focus group discussions and interviews on vaccination in pregnancy using a discussion guide developed in consultation with stakeholders and service users. Pregnant women were recruited on-street. We performed inductive coding of transcripts and thematic analysis, using a phenomenological approach. RESULTS: Sixteen pregnant women participated. We identified six key themes. Information and knowledge: Vaccinated and unvaccinated women demonstrated similar levels of knowledge and desire for information, preferring direct communication with healthcare professionals. The influence of others: Some vaccinated participants reported firm endorsements of vaccination by healthcare professionals including midwives, while some unvaccinated women recalled neutral or reticent staff. Acceptance and trust: Most women expressed trust of health professionals. Fear and distrust: Vaccinated individuals expressed concerns about side-effects more than unvaccinated women. A few unvaccinated women expressed distrust of vaccines and healthcare systems. Responsibility for the baby: Both groups prioritised protecting the baby but unvaccinated participants were concerned about vaccine-related harm. Accessing vaccination: Multiple appointments, lack of childcare, time off work and having responsibility to organise vaccination hindered some participants from getting immunised. Some women were willing to be vaccinated but did not recall being offered vaccination or were not sufficiently motivated to make arrangements themselves. CONCLUSION: Healthcare professionals appear to have a vital influential role in pregnant women's decisions about vaccination. Involving midwives and improving convenience of vaccination access may increase uptake. Strategies to develop interventions should address the aforementioned barriers to meet the pregnant women's needs.

Multisite Investigation of Outcomes With Implementation of CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention.

OBJECTIVES: This multicenter pragmatic investigation assessed outcomes following clinical implementation of CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary intervention (PCI). BACKGROUND: CYP2C19 loss-of-function alleles impair clopidogrel effectiveness after PCI. METHODS: After clinical genotyping, each institution recommended alternative antiplatelet therapy (prasugrel, ticagrelor) in PCI patients with a loss-of-function allele. Major adverse cardiovascular events (defined as myocardial infarction, stroke, or death) within 12 months of PCI were compared between patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy. Risk was also compared between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy. Cox regression was performed, adjusting for group differences with inverse probability of treatment weights. RESULTS: Among 1,815 patients, 572 (31.5%) had a loss-of-function allele. The risk for major adverse cardiovascular events was significantly higher in patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy (23.4 vs. 8.7 per 100 patient-years; adjusted hazard ratio: 2.26; 95% confidence interval: 1.18 to 4.32; p = 0.013). Similar results were observed among 1,210 patients with acute coronary syndromes at the time of PCI (adjusted hazard ratio: 2.87; 95% confidence interval: 1.35 to 6.09; p = 0.013). There was no difference in major adverse cardiovascular events between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy (adjusted hazard ratio: 1.14; 95% confidence interval: 0.69 to 1.88; p = 0.60). CONCLUSIONS: These data from real-world observations demonstrate a higher risk for cardiovascular events in patients with a CYP2C19 loss-of-function allele if clopidogrel versus alternative therapy is prescribed. A future randomized study of genotype-guided antiplatelet therapy may be of value.

Clinical effect of CYP2C9*5/*6 genotype on a patient's warfarin dose requirement.

We describe a 38-year-old African-American female treated with warfarin for acute bilateral pulmonary emboli who is a carrier of two rare CYP2C9 variant alleles, *5 and *6, along with VKORC1 -1639GG and CYP4F2 433Val/Val genotypes. Warfarin was dosed according to the hospital's Personalized Medicine Program recommendations of 5-6 mg/day for the first 6 days, and reduced to 2.5 mg/day starting on day 8 and continued for the following 3 weeks. This case sheds further light on the cumulative clinical impact of the CYP2C9 variant alleles, *5 and *6, on warfarin dose requirements and practical considerations for warfarin genotyping in a racially and ethnically diverse population.

The aetiologies of Failed Back Surgery Syndrome: A systematic review.

PURPOSE: Four to fifty percent of patients will develop Failed Back Surgery Syndrome (FBSS) following lumbar spine surgery. Repeated surgeries lead to escalating costs and subsequent decreases in success rate. Much of the research to date has focused on the psychosocial factors associated with FBSS. All factors including physical and pathological aetiologies should be examined. These factors may be independent, co-exist with or predispose patients to the psychological factors associated with FBSS. Previous reviews on the topic have been limited by a lack of systematic overview. The aim of this review is to identify the physical, physiological and pathological aetiologies of FBSS. METHODS: This review was done in accordance with the PRISMA guidelines. A computer-aided search of the electronic databases from inception to December 2014 was performed. Outcome measures of interest included pain, functional and radiological assessments. Two reviewers independently selected studies for inclusion. Methodological quality was assessed using the Newcastle Ottawa Scale. RESULTS: Six studies met the inclusion criteria and included a total of 663 patients. A total of twenty two aetiologies were identified. Only three studies reviewed non-surgical aetiologies. Many of the studies relied on medical imaging to identify the aetiologies. A meta-analysis was not undertaken due to the heterogeneity of studies. CONCLUSIONS: The causes of FBSS can be attributed to patho-anatomical, peripheral pain generators, physical/ mechanical, neurophysiological, surgical and `other' aetiologies. Three of the studies only examined surgical causes of FBSS. Further research, that examines surgical and non-surgical aetiologies, is required to draw firm conclusions. With nineteen aetiologies identified, FBSS remains an unclear diagnosis for a complex heterogeneous group of patients.

In-vitro characterisation of a novel celecoxib microbead formulation for the treatment and prevention of colorectal cancer.

OBJECTIVES: Colorectal cancer (CRC) is a life-threatening disease that can develop as a consequence of a sustained chronic inflammatory pathology of the colon. Although not devoid of side effects, the anti-inflammatory drug celecoxib (CLX) has been shown to exert protective effects in CRC therapy. The purpose of this study was to develop and characterise a novel CLX microbead formulation suitable for use in the treatment and prevention of CRC, which has the potential to minimise the side effects associated with CLX. METHODS: The study involved the assessment of the effectiveness of CLX formulations in an in-vitro cell model (HT29 cells) and a comparison of these effects to that of the marketed CLX product, Celebrex. Liquid CLX formulations were developed as precursors to microbead formulations. The effect of liquid CLX formulations on HT29 cell viability (MTT and flow cytometry apoptotic assays) and motility (scratch wound assay) were assessed and compared with the effect of Celebrex. A correlation between the in-vitro dissolution performance of the formulations and the effect in the cell model was also explored. Liquid CLX formulations were translated into an optimised CLX microbead formulation, and a colonic targeted sustained release coat (Surelease) was applied to the beads with the aim of producing a formulation for a future in-vivo study to compare the effect of the coated CLX microbeads versus Celebrex in the attenuation of CRC tumours and inflammation in a CRC murine model. The production of CLX microbeads was scaled-up using vibrating-jet encapsulation technology to allow for the development of an optimised dissolution profile to enable colonic release. KEY FINDINGS: In-vitro cell viability and motility were shown to be significantly reduced after treatment with CLX liquid formulations relative to the control, whereas the results for treatment with Celebrex were comparable with the control. Dissolution experiments and correlation analysis demonstrated that the formulations that showed a greater extent of drug release had reduced cell viability and motility. The CLX liquid formulations were translated into colon-targeted CLX microbeads suitable for use in a future in-vivo mouse study. CONCLUSIONS: These results represent a significant step forward in the chemopreventative treatment of CRC using CLX, as the microbead formulation developed suggests the possibility of presenting CLX in a format that has the potential to minimise gastrointestinal and cardiovascular side effects.

Effect of prehabilitation on the outcome of anterior cruciate ligament reconstruction.

BACKGROUND: Prehabilitation is defined as preparing an individual to withstand a stressful event through enhancement of functional capacity. HYPOTHESIS: We hypothesized that a preoperative exercise program would enhance postoperative outcomes after anterior cruciate ligament reconstruction (ACLR). STUDY DESIGN: Randomized controlled clinical trial; Level of evidence, 1. METHODS: Twenty volunteers awaiting ACLR were randomly assigned to a control or exercise intervention group. The exercise group completed a 6-week gym- and home-based exercise program. Assessments include single-legged hop test; quadriceps and hamstring peak torque and magnetic resonance imaging cross-sectional area (CSA); Modified Cincinnati Knee Rating System score; and muscle biopsy of the vastus lateralis muscle completed at baseline, preoperatively, and 12 weeks postoperatively. Myosin heavy chain (MHC) isoforms protein and messenger RNA (mRNA) expression were determined with SDS-PAGE (sodium dodecyl sulfate polyacrylamide gel electrophoresis) and RT-PCR (real-time polymerase chain reaction), respectively; IGF-1 (insulin-like growth factor 1), MuRF-1 (muscle RING-finger protein-1), and MAFbx (muscle atrophy f-box) mRNA expression were determined with quantitative RT-PCR. RESULTS: Following 6 weeks of exercise intervention, the single-legged hop test results improved significantly in the exercise-injured limb compared with baseline (P = .001). Quadriceps peak torque in the injured limb improved with similar gains in CSA compared with baseline (P = .001). However, this was not significantly increased compared with the control group. Quadriceps and vastus medialis CSA were also larger in the exercise group than in controls (P = .0024 and P = .015, respectively). The modified Cincinnati score was better in the exercise-injured limb compared with baseline. At 12 weeks postoperatively, the rate of decline in the single-legged hop test was reduced in the exercise group compared with controls (P = .001). Similar trends were not seen for quadriceps peak torque and CSA. The vastus medialis CSA had regressed to similar levels as the control group (P = .008). The modified Cincinnati score continued to increase in the exercise group compared with controls (P = .004). The expression of the hypertrophic IGF-1 gene was significantly increased after the exercise intervention (P = .028), with a decrease back to baseline 12 weeks postoperatively (P = .012). Atrophic MuRF-1 gene expression was decreased after intervention compared with baseline (P = .05) but increased again at 12 weeks postoperatively (P = .03). The MAFbx levels did not change significantly in either group and within each time point. On the mRNA level, there was a shift from MHC-IIx isoform to MHC-IIa after exercise, with significant changes compared with control preoperatively (P = .028). Protein testing was able to reproduce this increase for MHC-IIa isoform expression only. CONCLUSION: The 6-week progressive prehabilitation program for subjects undergoing ACLR led to improved knee function based on the single-legged hop test and self-reported assessment using the modified Cincinnati score. These effects were sustained at 12 weeks postoperatively. This study supports prehabilitation as a consideration for patients awaiting ACLR; however, further studies are warranted.

Screening for EGFR and KRAS mutations in endobronchial ultrasound derived transbronchial needle aspirates in non-small cell lung cancer using COLD-PCR.

EGFR mutations correlate with improved clinical outcome whereas KRAS mutations are associated with lack of response to tyrosine kinase inhibitors in patients with non-small cell lung cancer (NSCLC). Endobronchial ultrasound (EBUS)-transbronchial needle aspiration (TBNA) is being increasingly used in the management of NSCLC. Co-amplification at lower denaturation temperature (COLD)-polymerase chain reaction (PCR) (COLD-PCR) is a sensitive assay for the detection of genetic mutations in solid tumours. This study assessed the feasibility of using COLD-PCR to screen for EGFR and KRAS mutations in cytology samples obtained by EBUS-TBNA in routine clinical practice. Samples obtained from NSCLC patients undergoing EBUS-TBNA were evaluated according to our standard clinical protocols. DNA extracted from these samples was subjected to COLD-PCR to amplify exons 18-21 of EGFR and exons two and three of KRAS followed by direct sequencing. Mutation analysis was performed in 131 of 132 (99.3%) NSCLC patients (70F/62M) with confirmed lymph node metastases (94/132 (71.2%) adenocarcinoma; 17/132 (12.8%) squamous cell; 2/132 (0.15%) large cell neuroendocrine; 1/132 (0.07%) large cell carcinoma; 18/132 (13.6%) NSCL-not otherwise specified (NOS)). Molecular analysis of all EGFR and KRAS target sequences was achieved in 126 of 132 (95.5%) and 130 of 132 (98.4%) of cases respectively. EGFR mutations were identified in 13 (10.5%) of fully evaluated cases (11 in adenocarcinoma and two in NSCLC-NOS) including two novel mutations. KRAS mutations were identified in 23 (17.5%) of fully analysed patient samples (18 adenocarcinoma and five NSCLC-NOS). We conclude that EBUS-TBNA of lymph nodes infiltrated by NSCLC can provide sufficient tumour material for EGFR and KRAS mutation analysis in most patients, and that COLD-PCR and sequencing is a robust screening assay for EGFR and KRAS mutation analysis in this clinical context.

Gender differences in medical students' attitudes towards male and female rape victims.

This study examines attitudes towards female and male rape victims (ARVS, Ward, 1988) among UK medical students (N = 240; 120 females and 120 males). The study's hypotheses, namely, that male respondents will view rape victims more negatively than female respondents and that male victims will be viewed more negatively than female victims, were supported. Implications of the findings in relation to the inclusion of sexual violence teaching in UK medical undergraduate curricula, and suggestions for further research are discussed.

The effect of a physical activity education programme on physical activity, fitness, quality of life and attitudes to exercise in obese females.

Obesity has reached epidemic proportions worldwide. Decline in physical activity has occurred simultaneously or before the increase in obesity. The aim of this pilot study was to investigate the effect of a physical activity group-based education programme delivered by a Physiotherapist on weight, physical activity, cardiovascular fitness, quality of life and attitudes to exercise in obese females. A sample of 18 obese Irish females (mean age 37.6 years, mean weight 117.9kg), took part in this study. The participants attended four physical activity education sessions in groups of 6-8, 1 month apart. Outcome measures were Cardiorespiratory fitness (CRF) measured by the Incremental Shuttle Walk test (ISWT) International Physical Activity Questionnaire-Short Form (IPAQ-Short) Impact of Weight on Quality of Life Questionnaire-Short Form (IWQOL-Lite), and a questionnaire adapted from the EU survey on Consumer Attitudes to Physical Activity. There were no significant decreases in participants' weight (p=0.444) and there were no significant improvements in IPAQ (p=0.496) and IWQOL-Lite scores (p=0.337). There were significant improvements in CRF (p<0.0002). Attitudes towards exercise improved as shown by decreased barriers to exercise, i.e. decreased shyness (17%) and increased energy (22%) and increased enjoyment (22%). A group education programme focusing on physical activity alone demonstrated a significant increase in CRF (ISWT) and had a positive influence on attitudes to exercise. Longer duration interventions may allow participants to make the necessary lifestyle changes to achieve weight loss.

Seasonal variation in assisted conception cycles and the influence of photoperiodism on outcome in in vitro fertilization cycles.

The effect of seasonality and daylight length on mammalian reproduction leading to spring births has been well established, and is known as photoperiodism. In assisted reproduction there is much greater uncertainty as to the effect of seasonality. This was a 4-year retrospective analysis of 2709 standardised cycles of IVF/ICSI. Data was analysed with regard to the 1642 cycles occurring during the months of extended daylight (Apr-Sept) and those 1067 cycles during winter months of restricted light length (Oct-Mar). The results showed that there was significant improvement in assisted conception outcomes in cycles performed in summer (lighter) months with more efficient ovarian stimulation 766iu v880iu/per oocyte retrieved (p=0.006). There was similarly a significantly improved implantation rate per embryo transferred 11.42% vs 9.35% (p=0.011) and greater clinical pregnancy rate 20% vs 15% (p=0.0033) during summer cycles. This study appears to demonstrate a significant benefit of increased daylight length on outcomes of IVF/ICSI cycles. Whilst the exact mechanism of this is unclear, it would seem probable that melatonin may have actions at multiple sites and on multiple levels of the reproductive tract, and may exert a more profound effect on outcomes of assisted conception cycles than has been previously considered.

The value of routine estradiol monitoring in assisted conception cycles.

BACKGROUND: Traditional monitoring of an in vitro fertilization (IVF) treatment cycle includes regular estradiol levels and ultrasound scans in an attempt to reduce the risk of ovarian hyperstimulation syndrome (OHSS). The need for estradiol monitoring remains controversial. METHODS: We reviewed 538 consecutive cycles of IVF that were carried out in our unit to ascertain whether routine estradiol monitoring was of help in preventing OHSS and could be used to predict treatment outcome. Two hundred and sixty-eight patients had their ovarian response monitored with ultrasound (USS) and estradiol levels on the day of hCG administration. The following 270 had USS monitoring but only had an estradiol level checked if they were deemed to be at high risk of OHSS (> 20 follicles on USS or symptomatic). RESULTS: Pregnancy rates per treatment cycle and per embryo transfer were similar in the two groups (all p > 0.05). There were two patients in each group requiring admission to hospital for OHSS. CONCLUSIONS: Estradiol levels did not correlate with IVF outcome. In summary therefore estradiol levels are a poor predictor of treatment success and done routinely do not reduce the incidence of OHSS. It is only necessary to measure the estradiol level in those patients at risk of OHSS on USS monitoring.