Sensitisation to the acrylate co-polymers glyceryl acrylate/acrylic acid co-polymer, sodium polyacrylate and acrylates/C10-30 alkyl acrylate cross-polymer (Carbopol®) is rare.

BACKGROUND: Acrylate polymers and cross-polymers (ACPs) are frequently used cosmetic ingredients. The British Society for Cutaneous Allergy (BSCA) and the UK Cosmetic, Toiletry and Perfumery Association (CTPA) collaborated to investigate the allergenic potential of three commonly-used ACPs. OBJECTIVES: The objective of this study is to determine the prevalence of allergic contact dermatitis (ACD) to three ACPs: glyceryl acrylate/acrylic acid co-polymer, sodium polyacrylate, and acrylates/C10-30 alkyl acrylate cross-polymer (Carbopol®). MATERIALS AND METHODS: The BSCA prospectively audited data collected from 20 centres in the UK and Ireland between 1st September 2021 and 1st September 2022. Patients with suspected ACD to (meth)acrylates, with facial dermatitis, or consecutive patients, were patch tested to glyceryl acrylate/acrylic acid co-polymer 10% aqueous (aq.) sodium polyacrylate 2% aq., and to acrylates/C10-30 alkyl acrylate cross-polymer 2% aq. (Carbopol®). The frequencies of positive, irritant, and doubtful reactions were recorded. RESULTS: In total, 1302 patients were patch tested. To glyceryl acrylate/acrylic acid co-polymer, there was one doubtful reaction in a patient allergic to multiple (meth)acrylates, and one irritant. To sodium polyacrylate, there were four irritant reactions, one doubtful, and one positive reaction; in all cases, relevance was unknown and there was no demonstrable (meth)acrylate allergy. There were no reactions to Carbopol®. CONCLUSIONS: Sensitisation to these concentrations of the three tested ACPs is rare. Elicitation of dermatitis in (meth)acrylate-sensitised patients by exposure to these three ACPs appears unlikely.

Activation of a cGAS-STING-mediated immune response predicts response to neoadjuvant chemotherapy in early breast cancer.

BACKGROUND: The DNA-damage immune-response (DDIR) signature is an immune-driven gene expression signature retrospectively validated as predicting response to anthracycline-based therapy. This feasibility study prospectively evaluates the use of this assay to predict neoadjuvant chemotherapy response in early breast cancer. METHODS: This feasibility study assessed the integration of a novel biomarker into clinical workflows. Tumour samples were collected from patients receiving standard of care neoadjuvant chemotherapy (FEC + /-taxane and anti-HER2 therapy as appropriate) at baseline, mid- and post-chemotherapy. Baseline DDIR signature scores were correlated with pathological treatment response. RNA sequencing was used to assess chemotherapy/response-related changes in biologically linked gene signatures. RESULTS: DDIR signature reports were available within 14 days for 97.8% of 46 patients (13 TNBC, 16 HER2 + ve, 27 ER + HER2-ve). Positive scores predicted response to treatment (odds ratio 4.67 for RCB 0-1 disease (95% CI 1.13-15.09, P = 0.032)). DDIR positivity correlated with immune infiltration and upregulated immune-checkpoint gene expression. CONCLUSIONS: This study validates the DDIR signature as predictive of response to neoadjuvant chemotherapy which can be integrated into clinical workflows, potentially identifying a subgroup with high sensitivity to anthracycline chemotherapy. Transcriptomic data suggest induction with anthracycline-containing regimens in immune restricted, "cold" tumours may be effective for immune priming. TRIAL REGISTRATION: Not applicable (non-interventional study). CRUK Internal Database Number 14232.

Development of a core outcome set for informed consent for therapy: An international key stakeholder consensus study.

BACKGROUND: 300 million operations and procedures are performed annually across the world, all of which require a patient's informed consent. No standardised measure of the consent process exists in current clinical practice. We aimed to define a core outcome set for informed consent for therapy. METHODS: The core outcome set was developed in accordance with a predefined research protocol and the Core OutcoMes in Effectiveness Trials (COMET) methodology comprising systematic review, qualitative semi structured interviews, a modified Delphi process and consensus webinars to ratify outcomes for inclusion in the final core outcome set. (Registration- https://www.comet-initiative.org/Studies/Details/1024 ). Participants from all key stakeholder groups took part in the process, including patients and the public, healthcare practitioners and consent researchers. RESULTS: 36 outcome domains were synthesised through systematic review and organised into a consent taxonomy. 41 semi-structured interviews were performed with all consent stakeholders groups. 164 participants from all stakeholder groups across 8 countries completed Delphi Round 1 and 125 completed Round 2. 11 outcomes met the 'consensus in' criteria. 6 met 'consensus in' all stakeholder groups and were included directly in the final core outcome set. 5 remaining outcomes meeting 'consensus in' were ratified over two consensus webinars. 9 core outcomes were included in the final core outcome set: Satisfaction with the quality and amount of information, Patient feeling that there was a choice, Patient feeling that the decision to consent was their own, Confidence in the decision made, Satisfaction with communication, Trust in the clinician, Patient satisfaction with the consent process, Patient rated adequacy of time and opportunity to ask questions. CONCLUSION: This international mixed-methods qualitative study is the first of its kind to define a core outcome set for informed consent for intervention. It defines what outcomes are of importance to key stakeholders in the consent process and is a forward step towards standardising future consent research.

Resilience in medical doctors: a systematic review.

INTRODUCTION: Resilience can be difficult to conceptualise and little is known about resilience in medical doctors. AIMS: This systematic review discusses the existing literature on influences on resilience levels of medical doctors. METHODS: The bibliographic databases PubMed, MEDLINE, EMBASE and PsycINFO were searched from 2008 to November 2018 using keyword search terms resilience* AND ("medical physician*" OR doctor* OR surgeon* OR medical trainee* or clinician*). RESULTS: Twenty-four studies were deemed eligible for inclusion. A narrative synthesis was performed. The following influences on resilience in doctors were identified: demographics, personality factors, organisational or environmental factors, social support, leisure activities, overcoming previous adversity and interventions to improve resilience. CONCLUSIONS: Resilience is not limited to a doctor's own personal resource. Published studies also highlight the influence of other modifiable factors.

Patch testing with alkyl glucosides: Concomitant reactions are common but not ubiquitous.

BACKGROUND: Alkyl glucosides contitute a family of mild surfactants that are increasingly being used in a wide range of cosmetics and household products. Contact allergy to alkyl glucosides may be more frequent than previously suspected, especially in atopic patients. OBJECTIVES: To investigate the frequency of contact allergy to alkyl glucosides, and to identify concomitant reactivity. METHOD: We retrospectively reviewed all cases of suspected allergic contact dermatitis (ACD) in which patients were patch tested with either a cosmetic series that includes five alkyl glucosides (decyl glucoside, lauryl glucoside, coco glucoside, cetearyl glucoside, and caprylyl/capryl glucoside) or a specific alkyl glucoside series from November 2013 to April 2017 in two UK centres. RESULTS: A total of 5775 patients were patch tested across the two centres. Twenty-nine (1.04%) of the 2796 patients tested with the cosmetic/alkyl glucoside series had a positive patch test reaction to at least one of the alkyl glucosides. Twenty-three (79.3%) patients were sensitized to multiple alkyl glucosides; 21 patients (72.4%) were female. The mean age was 43.5 years. Twelve patients (41.4%) had a background of atopic dermatitis. CONCLUSIONS: The prevalence of alkyl glucoside-induced ACD is relatively high, and there are frequent concomitant reactions between different alkyl glucosides. We recommend the inclusion of alkyl glucosides in all cosmetic series.

A study of the relationship between resilience, burnout and coping strategies in doctors.

PURPOSE OF THE STUDY: The aim of this study was to measure resilience, coping and professional quality of life in doctors. STUDY DESIGN: A cross-sectional study using an online questionnaire in a single National Health Service trust, including both primary and secondary care doctors. RESULTS: 283 doctors were included. Mean resilience was 68.9, higher than population norms. 100 (37%) doctors had high burnout, 194 (72%) doctors had high secondary traumatic stress and 64 (24%) had low compassion satisfaction. Burnout was positively associated with low resilience, low compassion satisfaction, high secondary traumatic stress and more frequent use of maladaptive coping mechanisms, including self-blame, behavioural disengagement and substance use. Non-clinical issues in the workplace were the main factor perceived to cause low resilience in doctors. CONCLUSIONS: Despite high levels of resilience, doctors had high levels of burnout and secondary traumatic stress. Doctors suffering from burnout were more likely to use maladaptive coping mechanisms. As doctors already have high resilience, improving personal resilience further may not offer much benefit to professional quality of life. A national study of professional Quality of Life, Coping And REsilience, which we are proposing to undertake, will for the first time assess the UK and Ireland medical workforce in this regard and guide future targeted interventions to improve professional quality of life.

Illness perception clusters at diagnosis predict psychological distress among women with breast cancer at 6 months post diagnosis.

OBJECTIVE: This study aimed to examine the extent to which illness perceptions and coping strategies among women diagnosed with breast cancer explain psychological distress at diagnosis and at 6 months post diagnosis relative to demographic and illness-related variables. METHODS: Women were recruited to the study shortly after diagnosis. A total of 90 women completed study materials (Illness Perception Questionnaire-Revised, the Cancer Coping Questionnaire and the Hospital Anxiety and Depression Scale) at time 1. The same questionnaires were sent approximately 6 months later to those who had consented at time 1, and completed questionnaires were returned by 72 women. RESULTS: Cluster analysis was used to identify groups of respondents who reported a similar profile of illness perception scores. Regression analysis demonstrated that one of these clusters was more likely to experience psychological distress than the other both at diagnosis and at 6 months post diagnosis. Illness perception cluster membership and positive focus type coping were the most important and consistent predictors of lower psychological distress at diagnosis and at 6 months post diagnosis. CONCLUSIONS: Illness perceptions remained relatively stable over the study period, and therefore we are unable to clarify whether changes in illness cognitions are associated with a corresponding change in psychological symptoms. Future research should evaluate the impact on psychological distress of interventions specifically designed to modify illness cognitions among women with breast cancer.

Zinc, cadmium, and mercury complexes of a pyridyloxy-substituted cyclotriphosphazene: syntheses, structures, and fluxional behavior.

The synthesis and characterization of the fluxional, d(10) cyclotriphosphazene complexes, [MLCl(2)] (M = Zn, Cd, and Hg; L = spiro-[(1,1'-biphenyl)-2,2'-dioxy]tetrakis(4-methyl-2-pyridyloxy)cyclotriphosphazene), are described. Single-crystal X-ray structures show that the zinc complex has crystallized into two crystal forms: one as a tetrahedral species, with a N(2)Cl(2) donor set in which a geminal pair of the pendant pyridyloxy nitrogen atoms binds to the zinc, and the other as a trigonal-bipyramidal (tbp) one, with an N(3)Cl(2) donor set. The third nitrogen atom comes from the phosphazene ring and the two pyridyl ligands are non-geminal. The asymmetric unit of the cadmium complex contains three structurally distinct molecules. One molecule has a tbp structure similar to that of the zinc complex. The second molecule has a six-coordinate, distorted octahedral geometry around the cadmium center with a N(4)Cl(2) donor set, with three of the nitrogen donor atoms coming from the pendant pyridyloxy arms. The third site contains a tbp complex and a distorted octahedral species with a relative occupancy of 3:1. The identification of these three different forms in the one crystal suggests that the energy difference between the tbp and distorted octahedral isomers is not large. Quantitative analysis of the (1)H NMR and variable-temperature (31)P NMR spectra of the zinc, cadmium, and mercury complexes in a CD(2)Cl(2) solution, coupled with the X-ray structural results, shows that an associative fluxional mechanism (ΔS(++) < -65 J mol(-1) K(-1)) is operating.

Resilience, burnout and coping mechanisms in UK doctors: a cross-sectional study.

AIMS: This cross-sectional study aimed to assess resilience, professional quality of life and coping mechanisms in UK doctors. It also aimed to assess the impact of demographic variables, such as sex, grade and specialty on these factors. METHODS: During October and November 2018, medical doctors in the UK were eligible to complete an online survey made up of validated psychological instruments. Royal Colleges and other medical organisations invited their membership to participate via newsletters, email invitations, websites and social media. RESULTS: 1651 doctors participated from a wide range of specialties and grades across the UK. The mean resilience score was 65.01 (SD 12.3), lower than population norms. Of those who responded, 31.5% had high burnout (BO), 26.2% had high secondary traumatic stress and 30.7% had low compassion satisfaction (CS). Doctors who responded from emergency medicine were more burned out than any other specialty group (F=2.62, p=0.001, df 14). Those who responded from general practice scored lowest for CS (F=6.43, p<0.001, df 14). 120 (8%) doctors met the criteria for all three of high BO, high STS and low CS. The most frequently reported coping mechanism was the maladaptive strategy of self-distraction. CONCLUSIONS: One-third of UK doctors who responded are burned out and suffering from STS. Those who responded from emergency medicine and general practice appear to be suffering the most. Over 100 doctors fell into the at-risk category of high BO, high STS and low CS. Future analysis of the free text responses from doctors may help to identify factors that are playing a role in the high levels of BO and STS being reported by medical staff.

Evaluating interventions for informed consent for surgery (ICONS): Protocol for the development of a core outcome set.

BACKGROUND: The concept of informed consent is fundamental to medical practice. Shortcomings in the process can lead to patient complaints, litigation, unmet expectations and poor outcomes. Consent research has focused on developing tools to improve patient recall and understanding. However, the definitions, methods of measurement and timing of measurement vary widely across the studies that have been done. Although a Cochrane review has reported that many of these interventions appear to work, the high level of heterogeneity in outcome reporting prevents the identification of those interventions that work best and why they do so. It is also not clear which outcomes are most important to each party involved in the consent process and why. METHODS/DESIGN: This project will develop a core outcome set for assessing the effects of interventions aimed at improving informed consent for surgery and other invasive procedures for adult patients with the capacity to consent for themselves. We will conduct a systematic review of the qualitative and quantitative literature to identify outcomes used to date in consent research and map these into domains. A series of semi-structured key stakeholder interviews will also be used to identify relevant outcomes. These processes will produce a list of potential outcomes for assessing the effects of interventions to improve consent, which will be refined through an international Delphi survey and consensus webinars involving key stakeholders to produce the core outcome set. DISCUSSION: The ICONS study aims to develop a core outcome set for use in trials and reviews of interventions designed to improve the informed consent process for surgery and other invasive procedures. Our aim is that this core outcome set will reduce the level of selection and reporting bias in consent research and help clinicians to compare tools to improve consent.

Survival after breast cancer treatment: the impact of provider volume.

BACKGROUND: Research has not paid sufficient attention to the need for adequate case-mix adjustment in studies of the relationship between provider volume and performance. This study attempted to address this limitation by capturing and including 5-year survival outcomes and a wide range of case-mix variables in multivariate analyses of the volume-outcome relationship relating to breast cancer treatments. METHODS: All patients diagnosed with invasive primary breast cancer during 1996 (n = 809) were included. Patient, disease and treatment data were extracted from medical records; survival data were corroborated using official death registrations. A Cox proportional hazards approach was used to model relationships between patient, disease and service variables and risk of death. RESULTS: There were 262 deaths among 807 patients followed up; overall 5-year survival was 70%. Advancing age, higher levels of co-morbidity, late-stage disease, more positive nodes, and high-grade tumour were independently associated with lower survival (P < 0.05). Patients who received hormonal therapy (HR 0.50, 95% CI 0.28-0.89) and radiotherapy (HR 0.73, 95% CI 0.53-1.03) had a survival advantage. Using a cut-off point of > or =30 cases per annum, survival was lower for patients treated in low volume settings (HR 1.47, 95% CI 1.09-1.96) after adjustment for case mix. CONCLUSIONS: There was some evidence to support treatment in high volume settings although patient and disease variables were the major determinants of survival for patients with breast cancer.

Teaching Medical Students, what do Consultants think?

BACKGROUND: The approach to and delivery of medical student education has undergone significant change within the last decade. There has been a shift away from didactic lectures to small group tutorials, facilitated by clinicians. Anecdotally there is an impression that enthusiasm for teaching is waning. The aim of this qualitative study is to assess the current attitudes of consultants, across all specialities, to teaching medical students in small group settings. METHODS: A Likert scale questionnaire, relating to teaching medical students in small group tutorials, was distributed via email to all consultants working in one region. Questions considered the categories: attitudes to teaching, financial considerations, time constraints and attitudes to students. RESULTS: 367 responses were received. 72% of responders were actively involved in teaching. 72% of respondents indicated that medical students should be taught by consultants and 80% felt that teaching medical students was enjoyable. 60% felt they were not financially remunerated for teaching and 50% indicated teaching was not included in job plans; despite this a significant proportion of these respondents remain involved in teaching (68%). Non-teachers were more likely to indicate that teaching was not paid for (p=0.003). 78% indicated consultants do not have adequate time to teach medical students. 82% felt that medical students appreciate consultant led teaching but only 55% felt students had an appropriate level of enthusiasm for learning. CONCLUSION: Consultants in this Deanery are actively involved in medical student teaching and enjoy it. Consultants perceive that they are not adequately financially rewarded but for the most part this is not a deterrent. Time constraints are an issue and there is a desire to have teaching included in job plans to counteract this. Most consultants are complimentary about student attitudes but there is a perception that medical students need to contribute more to their own learning.

Belly button piercings: a saving grace? A patent urachus presenting in a 17-year-old girl.

We report the case of a 17-year-old girl who presented to the accident and emergency department with dysuria and foul smelling, bloody discharge from her umbilicus. The definitive diagnosis was that of a patent urachus, which is a fistulous communication between the bladder and the umbilicus, usually diagnosed in early infancy. The incidence of a patent urachus is approximately 1 in 70,000 in the general population. It is highly likely that removal of a recent belly button piercing resulted in the acute presentation by completing the fistulous tract to the skin. This case is of clinical relevance as the diagnosis was missed 18 months prior with a milder presentation. The recommended treatment option is surgical excision due to the potential risk of malignant change, with urachal adenocarcinoma accounting for 0.3% of all bladder cancers.

Twenty-one bust: a case of chemical transformation of an ingested foreign body.

The majority of ingested foreign bodies pass of their own accord without causing any adverse impact on the patient, while others present a greater management dilemma. We present a case of a 36-year-old man admitted to the hospital with a 10-day history of colicky abdominal pain following voluntary ingestion of multiple pairs of vinyl gloves. The plain-film abdominal X-ray confirmed small bowel obstruction and gastric bezoar. After failed conservative management he opted for endoscopic retrieval. Following exposure to stomach acid the gloves had lost their structural integrity becoming hard, sharp and brittle. As a result endoscopic removal was abandoned due to the risk of traumatic injury to the oesophagus. A midline laparotomy was performed and the gloves were retrieved via enterotomy. While many foreign bodies are suitable for endoscopic extraction this case demonstrates that the retrieval of vinyl gloves is unlikely to be successful due to significant chemical change.

Referral patterns, clinical examination and the two-week-rule for breast cancer: a cohort study.

INTRODUCTION: Current NHS guidelines require patients with suspected breast cancer to be seen urgently at a specialist breast clinic. The aim of this study was to assess referral patterns and clinical findings of patients referred to a specialist breast clinic. MATERIALS AND METHODS: A prospective database was maintained for consecutive patients referred. Symptoms and clinical findings in primary and secondary care were recorded. Correlation with final diagnoses was made. Tertiary referral patients were excluded. RESULTS: 1098 patients attended a specialist breast clinic over six months. 588 (54%) were referred as urgent, 285 (26%) routinely and 225 (20%) were unspecified. 492 (45%) patients were referred with the incorrect referral priority. 42 patients were unexamined in primary care. Examination findings in primary and secondary care correlated in only 487 (46%) patients. Examination in primary care when compared with secondary care was highly sensitive for detecting breast lumps, but specificity was low. 86 patients (8%) were diagnosed with breast cancer, 72 (84%) were referred urgently, 6 (7%) routinely and 8 (9%) as unspecified priority. Regardless of the clinical expertise of the referrer, sensitivity and specificity of the two-week guidelines for cancer are low. CONCLUSIONS: Examination findings in primary and secondary care correlate in only 46% of referrals. Additionally, 55% of referrals were of the correct priority. The two-week rule guidelines have poor sensitivity and specificity for cancer. The safest and fairest policy would be to abandon the concept of urgent referral criteria and see all patients in a timely fashion. Alternatively, simplifying the referral criteria would improve sensitivity and specificity for cancer without leading to increased waiting times.

The barrier method as a new tool to assist in career selection: covert observational study.

OBJECTIVE: To determine if senior doctors' parking habits and skills are associated with clinical specialty and, if so, whether observation of junior doctors' parking could provide guidance in choice of specialty. DESIGN: Covert observational study. SETTING: Pass-card controlled consultants' car park (parking lot), December 2009. PARTICIPANTS: 103 consultants entering the car park on three consecutive mornings. MAIN OUTCOME MEASURES: The outcomes were specialty and sex of the consultants, manner of approaching the barrier (pass-card ready or not), and time taken to park, exit the vehicle, and walk to a designated point. RESULTS: Approaches to the barrier and parking were recorded for 103 consultants (79 men, 24 women): 28 anaesthetists (22 men, six women), 29 physicians (internists, 18 men, 11 women), 14 radiologists (nine men, five women), and 32 surgeons (30 men, two women). The manner of approaching the barrier (card ready) differed by specialty but not by sex. The total time taken to park (seconds) differed significantly between specialties: surgery (median 68, interquartile range 61-71 seconds), anaesthesia (82, 76-91), radiology (86, 70-103), and general medicine (112, 96-136). The time taken to park was overall longer among women, but this was explained by their specialty (men and women matched by specialty did not differ). CONCLUSIONS: The total time taken to park and manner of approaching the barrier to gain entry to the car park differed across specialties. Surgical consultants were fastest, followed by consultant anaesthetists and consultant radiologists, with physicians slowest. Sex was not an influencing factor. If reproducible in studies of a similar nature the "barrier method" could allow for a low cost means of guiding junior doctors in career selection.