The impact of an adapted SPIKES protocol vs routine care in the delivery of bad news to IVF patients: an exploratory pilot multicenter randomized controlled trial.

PURPOSE: Determine if the SPIKES method was associated with less distress and more compassion than current modes of delivering negative pregnancy test results to patients undergoing in vitro fertilization. METHODS: Twenty-seven nurses from two centers were randomized to use the modified SPIKES script or continue their standard of care; 136 patients with a negative hCG following embryo transfer were included. SPIKES nurses received 1 h of training by a study psychologist; nurses in the control group were instructed to deliver the news as done previously. Patients who underwent embryo transfer and received a call by a participating nurse with a negative test result received an email invitation on the following day. RESULTS: Control patients reported significantly less distress than SPIKES patients; 33% of SPIKES patients reported that they had felt "extremely sad," compared to 15.2% of the control patients (p = 0.01). Perceived compassion did not differ between the groups (all p ≥ 0.22). CONCLUSION: Patients who received a negative pregnancy test result from the nurses who received a brief training and a script on how to deliver bad news via the modified SPIKES protocol reported significantly more distress than patients receiving negative results from nurses utilizing their standard of care. It is unclear whether a modified SPIKES method to deliver negative pregnancy test results will benefit patients undergoing in vitro fertilization. TRIAL REGISTRATION: Clinical trials.gov NCT04917445.

International clinical placement - Experiences of nursing students' cultural, personal and professional development; a qualitative study.

The purpose was to capture the experiences of cultural, personal and professional development during International Clinical Placement (ICP) among nursing students from three European countries. The paper presents findings based on the analysis of 23 reflections written by students immediately after returning from their ICP. The design builds on a qualitative study using a phenomenological approach and meaning condensation inspired by Kirsti Malterud. The analysis revealed four themes: Communication and barriers to be overcome, Culture as a serious business, Personal and professional achievements and Challenges and the importance of preceptorship. The ICP impacted on the participants' personal as well as professional way of understanding themselves as students and future nurses. A profound difference was seen between the achieved learning outcomes of participants completing an ICP in a high- or low-income country, respectively. Language barriers, the local culture and different nursing cultures were often challenging and pushed participants out of their comfort zone. All participants developed their cultural understanding in accordance with the Papadopoulos, Tilki and Taylor Model for Developing Cultural Competence. Findings indicate that educational institutions should establish well-planned exchange opportunities that adopt a two-way reciprocal (Erasmus) exchange programmes and be aware of the value of an appointed preceptor in the host country.

DNA methylation epi-signature is associated with two molecularly and phenotypically distinct clinical subtypes of Phelan-McDermid syndrome.

BACKGROUND: Phelan-McDermid syndrome is characterized by a range of neurodevelopmental phenotypes with incomplete penetrance and variable expressivity. It is caused by a variable size and breakpoint microdeletions in the distal long arm of chromosome 22, referred to as 22q13.3 deletion syndrome, including the SHANK3 gene. Genetic defects in a growing number of neurodevelopmental genes have been shown to cause genome-wide disruptions in epigenomic profiles referred to as epi-signatures in affected individuals. RESULTS: In this study we assessed genome-wide DNA methylation profiles in a cohort of 22 individuals with Phelan-McDermid syndrome, including 11 individuals with large (2 to 5.8 Mb) 22q13.3 deletions, 10 with small deletions (< 1 Mb) or intragenic variants in SHANK3 and one mosaic case. We describe a novel genome-wide DNA methylation epi-signature in a subset of individuals with Phelan-McDermid syndrome. CONCLUSION: We identified the critical region including the BRD1 gene as responsible for the Phelan-McDermid syndrome epi-signature. Metabolomic profiles of individuals with the DNA methylation epi-signature showed significantly different metabolomic profiles indicating evidence of two molecularly and phenotypically distinct clinical subtypes of Phelan-McDermid syndrome.

Metabolic and behavioural effects in offspring exposed to maternal sucrose consumption: a systematic review and meta-analysis of data from rodent models.

Consumption of sugar-sweetened beverages (SSBs) during pregnancy has been associated with childhood obesity. Research in which rodent dams have been given high-fat/high-sugar diets has consistently found metabolic alterations in their offspring. However, what remains unclear is the potential impact on the developing fetus of giving sugar in isolation at concentrations similar to SSBs to the mothers. Therefore, we conducted a systematic review and meta-analysis (Protocol No: 127115 on Prospero) to identify potential relationships between maternal sucrose consumption and metabolic outcomes in offspring of rodent (rat or mouse) models. We analysed studies that provided rodent mothers dams with access to sucrose solutions (8-20% w/v) prior to conception, during pregnancy and/or lactation and that reported offspring outcomes of body weight (BW), body composition and glycaemic control. Following a systematic search of four databases (PubMed, EMBASE, Web of Science and Scopus) performed on 15 January 2019, maternal and offspring data from 15 papers were identified for inclusion. Only rat studies were identified. Meta-analyses were performed on standardised mean differences for maternal and offspring BW and fasting glucose levels, with subgroup analyses of strain, sucrose concentration, exposure period and sex of offspring. A bias towards the inclusion of only data from male offspring was identified and this limited interpretation of potential sexually dimorphic outcomes. Maternal sucrose exposure was associated with an increased risk of obesity and poor glucose disposal in adult and aged offspring.

Metabolic and behavioural effects of prenatal exposure to non-nutritive sweeteners: A systematic review and meta-analysis of rodent models.

Little is known about possible effects of maternal non-nutritive sweetener (NNS) consumption on the metabolic health of a child. Animal models of maternal NNS consumption during pregnancy or weaning have yielded widely varying results, and there appears to be no clear consensus on the consequences for offspring body weight, glycaemic control or sweet preference choices. Moreover, heterogeneity in study design has hampered a clear focus for future research relevant to human health. In an effort to bring clarity, we have conducted a systematic review and meta-analysis (protocol no: CRD42018109509) in animal models (rat or mouse) of maternal NNS feeding (compared to water or basal diet) during pre-gestation, pregnancy or lactation. Four databases were searched from inception to 15th September 2018: PubMed, EMBASE, SCOPUS and Web of Science. We present maternal and offspring data from 24 included studies, which have been quantitatively analysed after study quality assessment, to identify relationships between maternal diet and offspring body weight (BW), feeding behaviour and glycaemic control. In 11 data sets, exposure to NNS reduced maternal BW during pregnancy, with no effect on litter outcomes. Meta-analyses on offspring BW during weaning (1123 offspring) and adulthood (646 offspring) identified small decreases in BW for both sexes. Subgroup analyses revealed reductions in BW of rat, but not mouse models. High dosage appears to be a potential factor for reduced palatability that could influence BW results; however, a lack of reported data limited our ability to confirm. Despite this, and the fact many papers were predisposed to bias, the balance of evidence suggests a maternal NNS diet during pregnancy or lactation did not increase the body weight in offspring.

The discrimination of quick Paediatric Early Warning Scores in the pre-hospital setting.

In our previous study, a Paediatric Early Warning Score could be calculated for only one-fifth of 102,993 children transported by ambulance to hospital, as components other than supplemental oxygen were not reliably measured: respiratory rate 90,358 (88%); Glasgow Coma Score 83,648 (81%); heart rate 83,330 (81%); time to capillary reperfusion 81,685 (79%); oxygen saturation 71,372 (69%); temperature 60,402 (59%); systolic blood pressure 37,088 (36%). We tested 12 abbreviated scores with 3-5 components. The discrimination of these 12 scores for the primary outcome (30-day mortality or admission to paediatric intensive care), as measured by the area under the receiving operator characteristic curve, ranged from 0.69 to 0.80. Scores could be calculated for at most 74,508 (72%) children when heart rate, conscious level and respiratory rate were measured, with or without supplemental oxygen: the discrimination of these two versions was 0.75 and 0.77, respectively. Optimal threshold scores of 3 and 2 for these two abbreviated versions discriminated an outcome rate of 2-3% in about one third of children from the other children who had < 1% rate of outcome.

Paediatric early warning scores are predictors of adverse outcome in the pre-hospital setting: A national cohort study.

INTRODUCTION: Physiological deterioration often precedes clinical deterioration as patients develop critical illness. Use of a specific Paediatric Early Warning Score (PEWS), based on basic physiological measurements, may help identify children prior to their clinical deterioration. NHS Scotland has adopted a single national PEWS - PEWS (Scotland). We aim to look at the utility of PEWS (Scotland) in unselected paediatric ambulance patients. METHODS: We performed a retrospective cohort of all ambulance patients aged under 16 years conveyed to hospital in Scotland between 2011 and 2015. Patients were matched to their 30 day mortality and ICU admission using data linkage. RESULTS: Full results were available for 21,202 children and young people (CYP). On multivariate logistic regression, PEWS (Scotland) was an independent predictor of the primary outcome (ICU admission within 48 h or death within 30 days) with an odds ratio of 1.403 (95%CI 1.349-1.460, p < 0.001). Area Under Receiving Operator Curve (AUROC) for aggregated PEWS was 0.797 (95% CI 0.759 to 0.836, p < 0.001). The optimal PEWS using Youlden's Index was 5. DISCUSSION: These data show PEWS (Scotland) to be a useful tool in a pre-hospital setting. A single set of physiological observations undertaken prior to arrival at hospital can identify a group of children at higher risk of an adverse in-hospital outcome. Paediatric care is becoming more specialised and focussed on a smaller number of centres. In this context, use of PEWS (Scotland) in the pre-hospital phase may allow changes to paediatric pre-hospital pathways to improve both admission to ICU and child mortality rates.

Intensity modulated radiotherapy in locally advanced thyroid cancer: Outcomes of a sequential phase I dose-escalation study.

BACKGROUND AND PURPOSE: To determine the safety and tolerability of dose-escalation using modestly accelerated IMRT in high-risk locally advanced thyroid cancer requiring post-operative radiotherapy, and to report preliminary data on efficacy. MATERIALS AND METHODS: A sequential Phase I dose-escalation design was used. Dose level one (DL1) received 58.8 Gy/28F to the post-operative bed and 50 Gy/28F to elective nodes. DL2 received 66.6 Gy/30F to the thyroid bed, 60 Gy/30F to post-operative nodal levels and 54 Gy/30F to elective nodal levels. Acute (NCICTCv.2.0) and late toxicities (RTOG and modified LENTSOM) were recorded. The primary endpoint was the number of patients with ≥Grade 3 (G3) toxicity at 12 months post-treatment. RESULTS: Fifteen patients were recruited to DL1 and twenty-nine to DL2. At 12 months ≥G3 toxicities were 8.3% in both DL1 and DL2. At 60 months, ≥G3 toxicity was reported in 3 (33%) patients in DL1 and 1 (7%) in DL2. One patient in DL2 died at 24 months from radiation-induced toxicity. Time to relapse and overall survival rates were higher in DL2, but this was not statistically significant. Dose-escalation using this accelerated regimen can be safely performed with a toxicity profile similar to reported series using conventional doses.

Associations between CD36 gene polymorphisms, fat tolerance and oral fat preference in a young-adult population.

BACKGROUND/OBJECTIVES: CD36 is known to be an orosensory receptor for dietary long-chain fatty acids, as well as being involved in the chemosensory mechanisms within the human gut. Recent data have demonstrated an association between CD36 single-nucleotide polymorphisms (SNPs) and lipid consumption behaviours in humans. This study aimed to test for associations between CD36 SNPs and response to a high-fat meal in a young healthy Australian cohort. Secondary associations were tested between CD36 gene variants and fasting lipid parameters, body composition, cardiovascular disease (CVD) risk factors and measures of oral fat preference. SUBJECTS/METHODS: Two SNPs (rs1527479 and rs1984112) were assessed for associations with response to a 75 g saturated fat oral fat tolerance test (OFTT), whole-body substrate oxidation, fasting plasma lipids, CVD risk factors and self-reported habitual diet questionnaires. Genotyping was performed using real-time polymerase chain reaction. RESULTS: Cross-sectional data were collected on 56 individuals (28 m, 28 f; 24.9±3.3 years), with 42 completing participation in a high-fat OFTT. No genotypic associations were evident in anthropometric data or self-reported fat preference measures. AA SNP carriers at rs1984112 exhibited significantly elevated fasting triglyceride when compared with non-carriers (P=0.024). This group also tended to have an elevated response to a high-fat meal (P=0.078). CONCLUSIONS: Although these data show the potential pleiotropic influence of CD36 SNP rs1984112 on lipoprotein accumulation in a young healthy cohort, further assessment in a larger cohort is warranted.

Total Mucosal Irradiation with Intensity-modulated Radiotherapy in Patients with Head and Neck Carcinoma of Unknown Primary: A Pooled Analysis of Two Prospective Studies.

AIMS: To determine the clinical outcomes of an intensity-modulated radiotherapy technique for total mucosal irradiation (TM-IMRT) in patients with head and neck carcinoma of unknown primary (HNCUP). MATERIALS AND METHODS: A single-centre prospective phase II trial design was used in two sequential studies to evaluate TM-IMRT for HNCUP. Patients were investigated for primary tumour site using examination under anaesthetic and biopsies, computed tomography ± magnetic resonance imaging (MRI) or 18-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT). Patients received IMRT to the potential primary tumour sites and elective cervical nodes. Concomitant chemotherapy was used in patients who received primary radiotherapy or those with nodal extracapsular extension. RESULTS: Thirty-six patients with HNCUP were recruited; 72% male. Twenty-five patients (69.4%) had p16-positive disease. Two year mucosal and local nodal control rates were 97.1% (95% confidence interval 91.4-100) and 89.8% (78.4-100), respectively. One mucosal primary was detected 7.3 months after TM-IMRT and three patients died from recurrent/metastatic squamous cell carcinoma of the head and neck. Twelve patients (33%) developed grade 3 (Late Effects in Normal Tissue-Subjective, Objective, Management and Analytical; LENT-SOMA) dysphagia with a 1 year enteric tube feeding rate of 2.7%. The high-grade subjective xerostomia rate (LENT-SOMA) at 24 months after IMRT was 15%. CONCLUSIONS: At a median follow-up of 36.1 months, the use of TM-IMRT was associated with good local control. Toxicity was comparable with previously reported TM-IMRT regimens encompassing similar mucosal volumes.

Implementation of the WHO Surgical Safety Checklist and surgical swab and instrument counts at a regional referral hospital in Uganda - a quality improvement project.

The World Health Organization (WHO) Surgical Safety Checklist is a cost-effective tool that has been shown to improve patient safety. We explored the applicability and effectiveness of quality improvement methodology to implement the WHO checklist and surgical counts at Mbarara Regional Referral Hospital in Uganda between October 2012 and September 2013. Compliance rates were evaluated prospectively and monthly structured feedback sessions were held. Checklist and surgical count compliance rates increased from a baseline median (IQR [range]) of 29.5% (0-63.5 [0-67.0]) to 85.0% (82.8-87.5 [79.0-93.0]) and from 25.5% (0-52.5 [0-60.0]) to 83.0% (80.8-85.5 [69.0-89.0]), respectively. The mean all-or-none completion rate of the checklist was 69.3% (SD 7.7, 95% CI [64.8-73.9]). Use of the checklist was associated with performance of surgical counts (p value < 0.001; r(2) = 0.91). Pareto analysis showed that understaffing, malfunctioning and lack of equipment were the main challenges. A carefully designed quality improvement project, including stepwise incremental change and standardisation of practice, can be an effective way of improving clinical practice in low-income settings.

The Impact of Colleague Peer Review on the Radiotherapy Treatment Planning Process in the Radical Treatment of Lung Cancer.

AIMS: Modern radiotherapy uses techniques to reliably identify tumour and reduce target volume margins. However, this can potentially lead to an increased risk of geographic miss. One source of error is the accuracy of target volume delineation (TVD). Colleague peer review (CPR) of all curative-intent lung cancer plans has been mandatory in our institution since May 2013. At least two clinical oncologists review plans, checking treatment paradigm, TVD, prescription dose tumour and critical organ tolerances. We report the impact of CPR in our institution. MATERIALS AND METHODS: Radiotherapy treatment plans of all patients receiving radical radiotherapy were presented at weekly CPR meetings after their target volumes were reviewed and signed off by the treating consultant. All cases and any resultant change to TVD (including organs at risk) or treatment intent were recorded in our prospective CPR database. The impact of CPR over a 13 month period from May 2013 to June 2014 is reported. RESULTS: One hundred and twenty-two patients (63% non-small cell lung carcinoma, 17% small cell lung carcinoma and 20% 'clinical diagnosis') were analysed. On average, 3.2 cases were discussed per meeting (range 1-8). CPR resulted in a change in treatment paradigm in 3% (one patient proceeded to induction chemotherapy, two patients had high-dose palliative radiotherapy). Twenty-one (17%) had a change in TVD and one (1%) patient had a change in dose prescription. In total, 6% of patients had plan adjustment after review of dose volume histogram. CONCLUSION: The introduction of CPR in our centre has resulted in a change in a component of the treatment plan for 27% of patients receiving curative-intent lung radiotherapy. We recommend CPR as a mandatory quality assurance step in the planning process of all radical lung plans.

A candidate gene approach for identifying differential iron responses in young overweight women to an energy-restricted haem iron-rich diet.

Although iron deficiency is common in women especially during dieting, weight management trials rarely examine the longitudinal impact of genetics on iron. This study examined the associations between the TMPRSS6 rs855791 polymorphism and iron indices at baseline and after a 12-month trial comparing two weight loss diets (higher-protein, higher-haem iron (HPHI) vs lower-protein, lower-haem iron (LPLI)). A total of 76 young overweight women (18-25y; BMI⩾27.5 kg/m(2)) were included at baseline, with 27 (HPHI: n=15; LPLI: n=12) completing the 12-month trial. At baseline, C allele homozygotes exhibited higher serum iron (P=0.047) and lower hepcidin (P=0.023) compared with T allele carriers. After 12 months, no genotypic differences were observed for ferritin and soluble transferrin receptor, although C homozygotes on HPHI showed higher serum iron and transferrin saturation (P<0.05). Results indicate that rs855791 can influence iron metabolism to some extent, but its impact on storage and functional iron status is small relative to dietary protein/iron manipulation.

Elevated levels of leukotriene C4 synthase mRNA distinguish a subpopulation of eosinophilic oesophagitis patients.

BACKGROUND: Cysteinyl leukotrienes contribute to Th2-type inflammatory immune responses. Their levels in oesophageal tissue, however, do not distinguish patients with eosinophilic oesophagitis (EoE) from controls. OBJECTIVE: We asked whether mRNA levels of leukotriene C4 synthase (LTC4 S), a key regulator of leukotriene production, could serve as a marker for EoE. METHODS: Digital mRNA expression profiling (nCounter(®) Technology) was performed on proximal and distal oesophageal biopsies of 30 paediatric EoE patients and 40 non-EoE controls. Expression data were confirmed with RT-qPCR. LTC4 S mRNA levels were quantified in whole blood samples. Leukotriene E4 was measured in urine. RESULTS: LTC4 S mRNA levels were elevated in proximal (2.6-fold, P < 0.001) and distal (2.9-fold, P < 0.001) oesophageal biopsies from EoE patients. Importantly, increased LTC4 S mRNA transcripts identified a subpopulation of EoE patients (28%). This patient subgroup had higher serum IgE levels (669 U/mL vs. 106 U/mL, P = 0.01), higher mRNA transcript numbers of thymic stromal lymphopoietin (TSLP) (1.6-fold, P = 0.009) and CD4 (1.4-fold, P = 0.04) but lower IL-23 mRNA levels (0.5-fold, P = 0.04). In contrast, elevated levels of IL-23 mRNA were found in oesophageal biopsies of patients with reflux oesophagitis. LTC4 S mRNA transcripts in whole blood and urinary excretion of leukotriene E4 were similar in EoE patient subgroups and non-EoE patients. CONCLUSION & CLINICAL RELEVANCE: Elevated oesophageal expression of LTC4 S mRNA is found in a subgroup of EoE patients, concomitant with higher serum IgE levels and an oesophageal transcriptome indicative of a more-pronounced allergic phenotype. Together with TSLP and IL-23 mRNA levels, oesophageal LTC4 S mRNA may facilitate diagnosis of an EoE subpopulation for personalized therapy.