Paediatric Residents and Fellows Ethics (PERFEct) survey: perceptions of European trainees regarding ethical dilemmas.

With an increasingly complex healthcare environment, ethics is becoming a more critical part of medical education. We aimed to explore European paediatric trainees' experiences of facing ethical dilemmas and their medical ethics education whilst assessing their perceptions of ethical dilemmas in current and future practice. The Young Sections of the European Academy of Paediatrics and European Society of Paediatric and Neonatal Intensive Care developed an explorative online survey covering demographics, ethical dilemmas faced and ethics training. The survey was made available in nine languages from November 2019 to January 2020 via newsletters and social media. Participants (n = 253) from 22 countries, predominantly female (82%) and residents (70%), with a median age of 29-years, completed the survey. The majority (58%) faced ethical dilemmas monthly or more frequently. Most ethics training was received by ethics lectures in medical school (81%) and on the job (60%). A disagreement between the healthcare team and patient/family was the most frequently faced moral dilemma (45%); the second was withholding/withdrawing life-prolonging measures (33%). The latter was considered the most challenging dilemma to resolve (50%). Respondents reported that ethical issues are not sufficiently addressed during their training and wished for more case-based teaching. Many have been personally affected by moral dilemmas, especially regarding withholding/withdrawing life-prolonging measures, and often felt inadequately supported.Conclusion: Paediatric trainees face many moral issues in daily practice and consider that training about managing current and future ethical dilemmas should be improved, such as by the provision of a core European paediatric ethics curriculum. What is Known: • Paediatric services are becoming more complex with an increase in ethical dilemmas asking for rigorous training in ethics. • Ethics training is often lacking or covered poorly in both pre- and postgraduate medical education curricula. • Existing ethics training for European paediatric trainees is haphazard and lacks standardisation. What is New: • The PaEdiatric Residents and Fellows Ethics (PERFEct) survey provides insight into the European paediatric trainees' views regarding ethical dilemmas in their current and future practice. • European paediatric trainees report a lack of ethics training during paediatric residency and fellowship. • This study provides content suggestions for standardised medical ethics training for paediatric trainees in Europe.

A Risk Score Model for Locoregional Recurrence Following Upfront Surgery for Pancreatic Adenocarcinoma: Implications for Adjuvant Therapy.

AIMS: The aims of the study were to identify predictors of locoregional failure (LRF) following surgery for pancreatic adenocarcinoma, develop a prediction risk score model of LRF and evaluate the impact of postoperative radiation therapy (PORT) on LRF. MATERIALS AND METHODS: A retrospective review was conducted on patients with stages I-III pancreatic adenocarcinoma who underwent surgery at our institution (2005-2016). Univariable and then multivariable analyses were used to evaluate clinicopathological factors associated with LRF for patients who did not receive PORT. The risk score of LRF was calculated based on the sum of coefficients of the predictors of LRF. The model was applied to the entire cohort to evaluate the impact of PORT on the high- and low-risk groups for LRF. RESULTS: In total, 467 patients were identified (median follow-up 22 months). Among patients who did not receive PORT (n = 440), predictors of LRF were pN+, involved or close ≤1 mm margin(s), moderately and poorly differentiated tumour grade and lymphovascular invasion. After adding patients who received PORT, the 2-year LRF in the high-risk group was 57% for patients who did not receive PORT (n = 242) and 32% among patients who received PORT (n = 22), with an absolute benefit to LRF of 25% (95% confidence interval 5-52%, P = 0.07). The 2-year overall survival for the high-versus the low-risk group was 36% versus 67% (P < 0.001). CONCLUSION: This risk group classification could be used to identify pancreatic adenocarcinoma patients with higher risk of LRF who may benefit from PORT. However, validation and prospective evaluation are warranted.

Real-Time PCR and LAMP Assays for the Detection of Spores of Alternaria solani and Sporangia of Phytophthora infestans to Inform Disease Risk Forecasting.

Real-time loop-mediated isothermal amplification (LAMP) assays for the detection of sporangia of the causal pathogen of late blight, Phytophthora infestans, and spores of the main causal pathogen of early blight, Alternaria solani, were developed to facilitate the in-field detection of airborne inoculum to improve disease forecasting. These assays were compared with an existing real-time PCR assay for P. infestans and a newly developed real-time PCR assay for A. solani. Primers were designed for real-time LAMP of P. infestans and A. solani. The specificity of the P. infestans real-time LAMP assay was similar to that of an existing real-time PCR assay: DNA of P. infestans was consistently amplified as was DNA of the taxonomically closely related species Phytophthora mirabilis, Phytophthora phaseoli, and Phytophthora ipomoea; no amplification of DNA from the potato pathogens Phytophthora erythroseptica or Phytophthora nicotianae occurred. Real-time LAMP and PCR assays were developed for A. solani, and the specificity was compared with an existing conventional PCR assay. Importantly, the A. solani real-time LAMP and PCR assays did not amplify the species Alternaria alternata. However, cross-reactivity with Alternaria dauci was observed with the real-time PCR assay and Alternaria brassicae with the real-time LAMP assay. The sensitivity of all assays for the detection of DNA extracted from sporangia/spores of the target pathogens was evaluated. The P. infestans real-time LAMP assay reliably detected 5 pg of DNA, equivalent to ∼1 sporangia per reaction. By comparison, 20 fg of DNA was detectable with the existing real-time PCR assay. In the case of A. solani, real-time LAMP detected 4.4 pg of DNA, equivalent to ∼1 spore per reaction, and real-time PCR detected 200 fg of DNA. In-field air samplers were deployed in two trial plots planted with potato: one infected with P. infestans, and the other infected with A. solani. Four additional samplers were located in commercial potato fields. Air samples were taken through the season, and detection of airborne inoculum of P. infestans and A. solani with both real-time PCR and LAMP was assessed.

Outcomes by treatment modality in elderly patients with localized gastric and esophageal cancer.

Background: We aimed to assess current treatment patterns and outcomes in elderly patients with localized gastric and esophageal (ge) cancers. Methods: This retrospective analysis considered patients 75 years of age or older with ge cancers treated during 2012-2014. Patient demographics and tumour characteristics were collected. Overall survival (os) and disease-free survival were assessed by univariable and multivariable Cox proportional hazards regression, adjusting for demographics. Logistic regression analyses were used to examine factors affecting treatment choices. Results: The 110 patients in the study cohort had a median age of 81 years (range: 75-99 years). Primary disease sites were esophageal (55%) and gastric (45%). Treatment received included radiation therapy alone (29%), surgery alone (26%), surgery plus perioperative therapy (14%), chemoradiation alone (10%), and supportive care alone (14%). In multivariable analyses, surgery (hazard ratio: 0.48; 95% confidence interval: 0.26 to 0.90; p = 0.02) was the only independent predictor for improved os. Patients with a good Eastern Cooperative Oncology Group performance status (p = 0.008), gastric disease site (p = 0.02), and adenocarcinoma histology (p = 0.01) were more likely to undergo surgery. Conclusions: At our institution, few patients 75 years of age and older received multimodality therapy for localized ge cancers. Outcomes were better for patients who underwent surgery than for those who did not. To ensure optimal treatment selection, comprehensive geriatric assessment should be considered for patients 75 years of age and older with localized ge cancers.

Patterns of failure in anaplastic and differentiated thyroid carcinoma treated with intensity-modulated radiotherapy.

BACKGROUND: The radiotherapy (rt) volumes in anaplastic (atc) and differentiated thyroid carcinoma (dtc) are controversial. METHODS: We retrospectively examined the patterns of failure after postoperative intensity-modulated rt for atc and dtc. Computed tomography images were rigidly registered with the original rt plans. Recurrences were considered in-field if more than 95% of the recurrence volume received 95% of the prescribed dose, out-of-field if less than 20% received 95% of the dose, and marginal otherwise. RESULTS: Of 30 dtc patients, 4 developed regional recurrence: 1 being in-field (level iii), and 3 being out-of-field (all level ii). Of 5 atc patients, all 5 recurred at 7 sites: 2 recurrences being local, and 5 being regional [2 marginal (intramuscular to the digastric and sternocleidomastoid), 3 out-of-field (retropharyngeal, soft tissues near the manubrium, and lateral to the sternocleidomastoid)]. CONCLUSIONS: In dtc, locoregional recurrence is unusual after rt. Out-of-field dtc recurrences infrequently occurred in level ii. Enlarged treatment volumes to level ii must be balanced against a potentially greater risk of toxicity.

A European Society of Paediatric and Neonatal Intensive Care (ESPNIC) survey of European critical care management of young people.

Adolescents have specific healthcare needs distinct from adults or younger children secondary to anatomical, physiological and socio-behavioural differences. Healthcare providers have been slow to address this, leading the UK Department of Health (2011) to publish 'You're Welcome' quality criteria for services for young people. (In the UK, the term young people is preferred to adolescent.) These generic criteria poorly fit the critical care environment, omitting key issues whilst insisting upon irrelevant standards. But as young people are infrequent patients for any individual unit, the research base to guide optimal management is poor and we could find no international or national guidance. Together with the hospital's young people's group, our intensive care team identified six areas important for critically ill young people, which are the 6Ps: privacy, permission, deep vein thrombosis (DVT) prophylaxis, personal life, puberty and practical issues. We then surveyed practice across Europe regarding these themes. Fifty-four hospitals from 16 countries participated, demonstrating disparate practice and widely differing policies to meet the requirements of critically ill young people. CONCLUSION: There is little consistency of practice in some areas such as pregnancy testing, DVT prophylaxis or partner visiting, whereas in others, such as involving young people in healthcare decisions where possible, practice is consistently good. Further research should focus on the young people's experience of critical care to refine healthcare policy. What is Known: • Adolescents have distinct health and psychosocial needs that are often poorly catered for in contemporary healthcare settings, including critical care. • As adolescents are infrequent patients for any intensive care unit, there is a poor research base and essentially no guidance, regarding optimal care. What is New: • We developed a mnemonic with adolescents and ICU staff to improve healthcare delivery to young people in critical care, the 6Ps: privacy, permission, DVT prophylaxis, personal life, puberty and practical issues. • Delivery of the adolescents' critical care varies greatly both between and within countries; the 6Ps offers a method of standardising and improving this across different countries.

Eastern Canadian Gastrointestinal Cancer Consensus Conference 2016.

The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2016 was held in Montreal, Quebec, 5-7 February. Experts in radiation oncology, medical oncology, surgical oncology, and infectious diseases involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses multiple topics: ■ Follow-up and survivorship of patients with resected colorectal cancer■ Indications for liver metastasectomy■ Treatment of oligometastases by stereotactic body radiation therapy■ Treatment of borderline resectable and unresectable pancreatic cancer■ Transarterial chemoembolization in hepatocellular carcinoma■ Infectious complications of antineoplastic agents.

The potential for neonatal organ donation in a children's hospital.

OBJECTIVE: Neonatal organ donation does not occur in the UK. Unlike in other European countries, Australasia and the USA death verification/certification standards effectively prohibit use of neurological criteria for diagnosing death in infants between 37 weeks' gestation and 2 months of age and therefore donation after neurological determination of death. Neonatal donation after circulatory definition of death is also possible but is not currently undertaken. There is currently no specific information about the potential neonatal organ donation in the UK; this study provides this in one tertiary children's hospital. DESIGN: Retrospective mortality database, clinical document database and patient notes review. SETTING: Neonatal and Paediatric Intensive Care in a tertiary children's hospital. PATIENTS: Infants dying between 37 weeks' gestation and 2 months of age between 1 January 2006 and 31 October 2012. Potential assessed using current UK guidelines for older children and neonatal criteria elsewhere. RESULTS: 84 infants died with 45 (54%) identified as potential donors. 34 (40%) were identified as potential donors after circulatory definition of death and 11 (13%) were identified as being theoretical potential donors after neurological determination of death. 10 (12%) were identified as unlikely donors due to relative contraindications and 39 (46%) were definitely not potential donors. CONCLUSIONS: With around 60 paediatric organ donors in the UK annually, there does appear significant potential for donation within the neonatal population. Reconsideration of current infant brain stem death guidelines is required to allow parents the opportunity of donation after neurological determination of death, together with mandatory training in organ donation for neonatal teams, which will also facilitate donation after circulatory definition of death.

Induction gemcitabine plus concurrent gemcitabine and radiotherapy for locally advanced unresectable or resected pancreatic cancer.

AIMS: To determine the efficacy of induction gemcitabine followed by biweekly gemcitabine concurrent with radiotherapy for locally advanced pancreatic cancer. MATERIALS AND METHODS: Between March 2001 and August 2009, 90 patients with unresectable (78) or resected (12) pancreatic cancer were treated with a standard treatment policy of induction gemcitabine (seven doses of weekly gemcitabine at 1000 mg/m(2)) followed by concurrent radiotherapy (52.5 Gy) and biweekly gemcitabine (40 mg/m(2)). RESULTS: After induction gemcitabine, 17.8% of patients did not proceed to chemoradiotherapy, due to either disease progression, performance status deterioration or gemcitabine toxicity. Of the patients who received chemoradiotherapy, 68.9% completed the course of 52.5 Gy, whereas 79.7% received more than 45 Gy. Chemoradiotherapy was stopped early due to treatment toxicity in 22.9% of patients. On intention to treat analysis, the median overall survival was 12.7 months in the locally advanced group and 18.2 months in the resected group. On multivariate analysis for the unresectable patients, a larger gross tumour volume was a significant poor prognostic factor for overall survival and local progression-free survival. CONCLUSION: This large series confirms, in a standard practice setting, similar efficacy and tolerability of treatment as previously reported in our phase I-II study. The benefit to patients with a gross tumour volume >48 cm(3) may be limited.

Degree of tumor shrinkage following neoadjuvant chemoradiotherapy: a potential predictor for complete pathological response in esophageal cancer?

Neoadjuvant chemoradiotherapy (CRT) before surgery results in a pathological complete response (pCR) rate in about 1/3 of the patients, which is correlated with survival. It was hypothesized that volumetric tumor response to CRT would correlate with outcomes. Patients who completed trimodality therapy, where planning, pre-, and post-CRT computed tomography scans were available, and pathology was reviewed by a central pathologist, were eligible for analysis. Absolute and relative tumor volume change pretreatment and post-treatment were correlated with pCR, locoregional recurrence (LRR), disease-free survival, and overall survival. Fifty-six patients were analyzed. pCR was observed in 30% of patients. Median follow up was 20.3 (range 4-89) months. The 2- and 4-year overall survival was 61.3% (95% confidence interval [CI]: 45-74) and 25.0% (95%CI: 11-41); proportion disease free was 32.1% (95% CI: 19-46) and 20.6% (9-36) at 2 and 4 years, respectively. The median relative volume reduction was 17% (95% CI: -24, -3%). Using 20% as the criteria, the proportion of patients with pCR of ≥20% versus <20% was 13/25 (52%) versus 4/31 (13%) for those who did not (odds ratio 7.3; 95% CI: 2-27). The LRR at 2 and 4 years were 29.5% (95% CI: 16-43) and 36.2% (95% CI: 23-50). The relative tumor reduction ≥20% was significantly correlated with LRR (hazard ratio 0.24; 95% CI: 0.07-0.8; p 0.02) at 2 and 4 years, respectively. Relative tumor volume reduction following CRT is correlated with pCR and LRR. Further investigations are warranted to examine the effect of volume change, alone or in conjunction with other factors as potential predictors for pathological response.

The impact of age and gender on papillary thyroid cancer survival.

CONTEXT: Thyroid cancer predominately affects women, carries a worse prognosis in older age, and may have higher mortality in men. Superimposed on these observations is the fact that most women have attained menopause by age 55 yr. OBJECTIVE: The objective of the study was to determine whether men contribute disproportionately to papillary thyroid cancer (PTC) mortality or whether menopause affects PTC prognosis. DESIGN: Gender-specific mortality was normalized using age-matched subjects from the U.S. population. Multivariate Cox proportional hazard regression models incorporating gender, age, and National Thyroid Cancer Treatment Cooperative Study Group stage were used to model disease-specific survival (DSS). PARTICIPANTS AND SETTING: Patients were followed in a prospective registry. MAIN OUTCOME MEASURE: The relationships between gender, age, and PTC outcomes were analyzed. RESULTS: The unadjusted hazard ratio (HR) for DSS for women was 0.40 [confidence interval (CI) 0.24-0.65]. This female advantage diminished when DSS was adjusted for age at diagnosis and stage with a HR encompassing unity (HR 0.72, CI 0.44-1.19). Additional multivariate models of DSS considering gender, disease stage, and various age groupings showed that the DSS for women diagnosed at under 55 yr was improved over men (HR 0.33, CI 0.13-0.81). However, the HR for DSS increased to become similar to men for women diagnosed at 55-69 yr (HR 1.01, CI 0.42-2.37) and at 70 yr or greater (HR 1.17, CI 0.48-2.85). CONCLUSIONS: Although the overall outcome of women with PTC is similar to men, subgroup analysis showed that this composite outcome is composed of two periods with different outcomes. The first period is a period with better outcomes for women than men when the diagnosis occurs at younger than 55 yr; the second is a period with similar outcomes for both women and men diagnosed at ages greater than 55 yr. These data raise the question of whether an older age cutoff would improve current staging systems. We hypothesize that older age modifies the effect of gender on outcomes due to menopause-associated hormonal alterations.

Aspects of deceased organ donation in paediatrics.

Organ transplantation offers children in acute or chronic severe organ failure similar opportunities to adults. However, while the number who might benefit is relatively low, significantly fewer cadaveric donors exist for any given child compared with an adult. Incompatible organ size and relatively low donation rates mean that despite living parental donation and innovations to reduce donated organ size, children die before organs become available. The severity of the UK situation is compounded by restrictions on paediatric living donation, uncertainties over the application of brain death criteria, and ethical concerns about the use of donation after circulatory death. The UK Department of Health's Organ Donation Task Force suggested the means by which the adult donor pool might be increased, recommending that outstanding ethical and legal issues be resolved, but made no specific recommendations about children.

Optic nerve sheath measurement and raised intracranial pressure in paediatric traumatic brain injury.

INTRODUCTION: The optimal management of children ventilated for more than 4 h with traumatic brain injury (TBI) necessitates invasive intracranial pressure (ICP) monitoring, though some patients never have raised ICP. If non-invasive screening can reliably rule out elevated ICP, invasive devices can be limited to those in whom neuro-intensive care measures are indicated. MATERIALS AND METHODS: We measured the optic nerve sheath diameter (ONSD) with a 10-MHz ultrasound probe in 11 children (age range 2-15 years, median 9.2 years) with severe TBI admitted to a regional neuro-surgical paediatric intensive care unit (PICU) requiring ICP monitoring and neuro-protection. Simultaneous invasive ICP was recorded and more than 15 mmHg was considered to be abnormal. ONSD >4.5 mm in children over 1 year of age was considered to be abnormal. RESULTS AND CONCLUSIONS: All children with clinically significantly raised ICP had abnormal ONSD, whereas those with normal ICP did not. Despite the small numbers, this study suggests that the ONSD may be useful in identifying children with TBI and normal ICP and, so, help avoid the insertion of unnecessary ICP monitors.

Thyroid cancer patients' involvement in adjuvant radioactive iodine treatment decision-making and decision regret: an exploratory study.

PURPOSE: We explored regret in thyroid cancer patients, relating to the decision to accept or reject adjuvant radioactive iodine treatment. METHODS: We studied patients with a recent diagnosis of early stage papillary thyroid carcinoma, in whom treatment decisions on adjuvant radioactive iodine had been finalized. Participants completed a Decision Regret Scale questionnaire. We asked the participants to identify who made the final decision about radioactive iodine treatment. We explored the relationship between decision regret and a) degree of patient involvement in decision-making and b) receipt of radioactive iodine treatment. RESULTS: We included 44 individuals, more than half of whom received adjuvant radioactive iodine treatment (26/44). Decision regret was generally low (mean 22.1, standard deviation [SD] 13.0). Participants reported that the final treatment decision was made by the following: patient and doctor (52.3%, 23/44), completely the patient (27.3%, 12/44), or completely the physician (20.5%, 9/44). Decision regret significantly differed according to who made the final decision: the patient (mean 19.0, SD 11.3), patient and doctor (mean 19.5, SD 7.4), and the doctor (mean 32.9, SD 20.37) (F = 4.569; degrees of freedom = 2, 41; p = 0.016). There was no significant difference in decision regret between patients who received radioactive iodine and those who did not (mean difference -2.5; 95% confidence interval -10.6, 5.6; p = 0.540). CONCLUSION: Thyroid cancer patients who reported being involved in the final treatment decision on adjuvant radioactive iodine had less regret than those who did not.

How can we meet the information needs of patients with early stage papillary thyroid cancer considering radioactive iodine remnant ablation?

In patients with early stage papillary thyroid carcinoma (PTC) who have had a thyroidectomy, the decision must be made to accept or reject radioactive iodine remnant ablation (RRA). Counselling patients about this decision can be challenging, given the medical evidence uncertainties and the complexity of related information. Although physicians are the primary source of medical information for patients considering RRA, some patients have a desire for supplemental information from sources such as the internet. Yet, thyroid cancer resources on the internet are of variable quality, and some may not be applicable to the individual case. We have developed a computerized educational tool [called a decision aid (DA)], directed to patients with early stage papillary thyroid cancer, and intended as an adjunct to physician counselling, to relay evidence-based medical information on disease prognosis and the choice to accept or reject RRA. DAs are tools used to inform patients about available treatment options and have been utilized in oncologic decision-making. We tested our web-based DA in fifty patients with early stage PTC and found that it improved medical knowledge. Furthermore, participants found the technical usability of the tool acceptable. We are currently conducting a randomized controlled trial comparing the use of the DA plus usual care to usual care alone to confirm the educational benefit of the website and examine its impact on the decision-making process. In the future, DAs may play an expanded role as an adjunct to physician counselling in the care of patients with thyroid cancer.

Adjuvant chemoradiation for gastric cancer with infusional 5-fluorouracil and cisplatin: a phase I study.

OBJECTIVE: This phase I study aimed to determine the maximal tolerated dose of cisplatin administered every 2 weeks with infusional 5-fluorouracil (5FU) and concurrent radiation therapy (RT) in patients after complete resection of gastric adenocarcinoma. METHODS: Patients with resected stage IB to IV (M0) gastric adenocarcinoma were treated with 12 weeks of infusional 5FU (200 mg/m(2) daily) and with RT (45 Gy in 25 fractions starting on day 16). Cisplatin was administered in escalating doses (0, 20, 30, and 40 mg/m(2)) in weeks 1, 3, 5, and 7. In the final cohort, patients received an additional dose of cisplatin (40 mg/m(2)) in week 9. RESULTS: Among the 34 patients [median age: 56 years (range: 31-77 years)] who were assessable for toxicity, 5 experienced dose-limiting toxicities: 1 sepsis (cohort 1), 1 fatigue (cohort 2), 3 upper gastrointestinal toxicity (1 in cohort 2, 2 in cohort 5). Cohort 5 exceeded the maximal tolerated dose. Median follow-up was 2.5 years (range: 0.3-5 years). The 3-year overall and relapse-free survival rates were 86% and 71% respectively; median survival was not reached. CONCLUSIONS: Cisplatin was well tolerated in combination with infusional 5FU and RT, showing promising activity in the adjuvant treatment of gastric cancer. Infusional 5FU 200 mg/m(2) daily for 12 weeks with cisplatin 40 mg/m(2) in weeks 1, 3, 5, and 7 and with concurrent RT 45 Gy in 25 fractions, starting at day 16, is being explored in a phase II study at our institution.