Automated airway quantification associates with mortality in idiopathic pulmonary fibrosis.

OBJECTIVES: The study examined whether quantified airway metrics associate with mortality in idiopathic pulmonary fibrosis (IPF). METHODS: In an observational cohort study (n = 90) of IPF patients from Ege University Hospital, an airway analysis tool AirQuant calculated median airway intersegmental tapering and segmental tortuosity across the 2nd to 6th airway generations. Intersegmental tapering measures the difference in median diameter between adjacent airway segments. Tortuosity evaluates the ratio of measured segmental length against direct end-to-end segmental length. Univariable linear regression analyses examined relationships between AirQuant variables, clinical variables, and lung function tests. Univariable and multivariable Cox proportional hazards models estimated mortality risk with the latter adjusted for patient age, gender, smoking status, antifibrotic use, CT usual interstitial pneumonia (UIP) pattern, and either forced vital capacity (FVC) or diffusion capacity of carbon monoxide (DLco) if obtained within 3 months of the CT. RESULTS: No significant collinearity existed between AirQuant variables and clinical or functional variables. On univariable Cox analyses, male gender, smoking history, no antifibrotic use, reduced DLco, reduced intersegmental tapering, and increased segmental tortuosity associated with increased risk of death. On multivariable Cox analyses (adjusted using FVC), intersegmental tapering (hazard ratio (HR) = 0.75, 95% CI = 0.66-0.85, p < 0.001) and segmental tortuosity (HR = 1.74, 95% CI = 1.22-2.47, p = 0.002) independently associated with mortality. Results were maintained with adjustment using DLco. CONCLUSIONS: AirQuant generated measures of intersegmental tapering and segmental tortuosity independently associate with mortality in IPF patients. Abnormalities in proximal airway generations, which are not typically considered to be abnormal in IPF, have prognostic value. CLINICAL RELEVANCE STATEMENT: Quantitative measurements of intersegmental tapering and segmental tortuosity, in proximal (second to sixth) generation airway segments, independently associate with mortality in IPF. Automated airway analysis can estimate disease severity, which in IPF is not restricted to the distal airway tree. KEY POINTS: • AirQuant generates measures of intersegmental tapering and segmental tortuosity. • Automated airway quantification associates with mortality in IPF independent of established measures of disease severity. • Automated airway analysis could be used to refine patient selection for therapeutic trials in IPF.

A Phase II, Open-label study to assess safety and management change using 68Ga-THP PSMA PET/CT in patients with high risk primary prostate cancer or biochemical recurrence after radical treatment: The PRONOUNCED study.

Objectives: To assess the safety and clinical impact of a novel, kit-based formulation of 68Ga-THP PSMA positron emission tomography/computed tomography (PET/CT) when used to guide the management of patients with prostate cancer (PCa). Methods: Patients were prospectively recruited in to one of: Group A: high-risk untreated prostate cancer; Gleason score >4+3, or PSA >20 ng/mL or clinical stage >T2c. Group B: biochemical recurrence (BCR) and eligible for salvage treatment after radical prostatectomy with two consecutive rises in prostate specific antigen (PSA) with a three month interval in between reads and final PSA >0.1 ng/mL or a PSA level >0.5 ng/mL. Group C: BCR with radical curative radiotherapy or brachytherapy at least three months prior to enrolment, and an increase in PSA level >2.0 ng/mL above the nadir level after radiotherapy or brachytherapy. Patients underwent evaluation with PET/CT 60 minutes following intravenous administration of 160±30 MBq of 68Ga-THP PSMA. Safety was assessed by means including vital signs, cardiovascular profile, serum haematology, biochemistry, urinalysis, PSA, and Adverse Events (AEs). A change in management was reported when the predefined clinical management of the patient altered as a result of 68Ga-THP PSMA PET/CT findings. Results: Forty-nine patients were evaluated with PET/CT; 20 in Group A, 21 in Group B and 8 in Group C. No patients experienced serious AEs discontinued the study due to AEs, or died during the study. Two patients had Treatment Emergent AEs attributed to 68Ga-THP-PSMA (pruritus in one patient and intravenous catheter site rash in another). Management change secondary to PET/CT occurred in 42.9% of all patients; 30% in Group A, 42.9% in Group B and 75% in Group C. Conclusion: 68Ga-THP PSMA was safe to use with no serious AE and no AE resulting in withdrawal from the study. 68Ga-THP PSMA PET/CT changed the management of patients in 42.9% of the study population, comparable to studies using other PSMA tracers. These data form the basis of a planned Phase III study of 68Ga-THP PSMA in patients with prostate cancer.

The validity of the Annual Review of Competence Progression: a qualitative interview study of the perceptions of junior doctors and their trainers.

Objective To investigate trainee doctors' and trainers' perceptions of the validity of the Annual Review of Competence Progression (ARCP) using Messick's conceptualisation of construct validity. Design Qualitative semi-structured focus groups and interviews with trainees and trainers. Setting Postgraduate medical training in London, Kent Surrey and Sussex, Yorkshire and Humber, and Wales in November/December 2015. Part of a larger study about the fairness of postgraduate medical training. Participants Ninety-six trainees and 41 trainers, comprising UK and international medical graduates from Foundation, General Practice, Medicine, Obstetrics and Gynaecology, Psychiatry, Radiology, and Surgery, at all levels of training. Main outcome measures Trainee and trainer perceptions of the validity of the ARCP as an assessment tool. Results Participants recognised the need for assessment, but were generally dissatisfied with ARCPs, especially UK graduate trainees. Participants criticised the perceived tick-box nature of ARCPs as measuring clerical rather than clinical ability, and which they found detrimental to learning. Trainees described being able to populate their e-portfolios with just positive feedback; they also experienced difficulty getting assessments signed off by supervisors. ARCPs were perceived as poor at identifying struggling trainees and/or as discouraging excellence by focussing on minimal competency. Positive experiences of ARCPs arose when trainees could discuss their progress with interested supervisors. Conclusions Trainee and trainer criticisms of ARCPs can be conceptualised as evidence that ARCPs lack validity as an assessment tool. Ongoing reforms to workplace-based assessments could address negative perceptions of the 'tick-box' elements, encourage constructive input from seniors and allow trainees to demonstrate excellence as well as minimal competency, while keeping patients safe.

'You can't be a person and a doctor': the work-life balance of doctors in training-a qualitative study.

OBJECTIVES: Investigate the work-life balance of doctors in training in the UK from the perspectives of trainers and trainees. DESIGN: Qualitative semistructured focus groups and interviews with trainees and trainers. SETTING: Postgraduate medical training in London, Yorkshire and Humber, Kent, Surrey and Sussex, and Wales during the junior doctor contract dispute at the end of 2015. Part of a larger General Medical Council study about the fairness of postgraduate medical training. PARTICIPANTS: 96 trainees and 41 trainers. Trainees comprised UK graduates and International Medical Graduates, across all stages of training in 6 specialties (General Practice, Medicine, Obstetrics and Gynaecology, Psychiatry, Radiology, Surgery) and Foundation. RESULTS: Postgraduate training was characterised by work-life imbalance. Long hours at work were typically supplemented with revision and completion of the e-portfolio. Trainees regularly moved workplaces which could disrupt their personal lives and sometimes led to separation from friends and family. This made it challenging to cope with personal pressures, the stresses of which could then impinge on learning and training, while also leaving trainees with a lack of social support outside work to buffer against the considerable stresses of training. Low morale and harm to well-being resulted in some trainees feeling dehumanised. Work-life imbalance was particularly severe for those with children and especially women who faced a lack of less-than-full-time positions and discriminatory attitudes. Female trainees frequently talked about having to choose a specialty they felt was more conducive to a work-life balance such as General Practice. The proposed junior doctor contract was felt to exacerbate existing problems. CONCLUSIONS: A lack of work-life balance in postgraduate medical training negatively impacted on trainees' learning and well-being. Women with children were particularly affected, suggesting this group would benefit the greatest from changes to improve the work-life balance of trainees.

Perceived causes of differential attainment in UK postgraduate medical training: a national qualitative study.

OBJECTIVES: Explore trainee doctors' experiences of postgraduate training and perceptions of fairness in relation to ethnicity and country of primary medical qualification. DESIGN: Qualitative semistructured focus group and interview study. SETTING: Postgraduate training in England (London, Yorkshire and Humber, Kent Surrey and Sussex) and Wales. PARTICIPANTS: 137 participants (96 trainees, 41 trainers) were purposively sampled from a framework comprising: doctors from all stages of training in general practice, medicine, obstetrics and gynaecology, psychiatry, radiology, surgery or foundation, in 4 geographical areas, from white and black and minority ethnic (BME) backgrounds, who qualified in the UK and abroad. RESULTS: Most trainees described difficult experiences, but BME UK graduates (UKGs) and international medical graduates (IMGs) could face additional difficulties that affected their learning and performance. Relationships with senior doctors were crucial to learning but bias was perceived to make these relationships more problematic for BME UKGs and IMGs. IMGs also had to deal with cultural differences and lack of trust from seniors, often looking to IMG peers for support instead. Workplace-based assessment and recruitment were considered vulnerable to bias whereas examinations were typically considered more rigorous. In a system where success in recruitment and assessments determines where in the country you can get a job, and where work-life balance is often poor, UK BME and international graduates in our sample were more likely to face separation from family and support outside of work, and reported more stress, anxiety or burnout that hindered their learning and performance. A culture in which difficulties are a sign of weakness made seeking support and additional training stigmatising. CONCLUSIONS: BME UKGs and IMGs can face additional difficulties in training which may impede learning and performance. Non-stigmatising interventions should focus on trainee-trainer relationships at work and organisational changes to improve trainees' ability to seek social support outside work.

Radiation hazards in pregnancy and methods of prevention.

The incidence of malignancy in pregnancy is low and most commonly occurs in breast, gynaecological, skin and haematological sites. The management of pregnant cancer patients is complex requiring a multidisciplinary approach to ensure the welfare of both mother and baby. Foetal radiation exposure, both diagnostic and therapeutic, must be kept to a minimum. Following the description of the deterministic and stochastic effects of foetal radiation exposure doses, radiotherapy should be avoided in the first and early second trimester. This chapter describes the possible diagnostic techniques and treatment for the common malignancies in pregnancy; some case studies indicating supradiaphragmatic radiotherapy may be safe later in pregnancy. Pelvic radiotherapy for gynaecological malignancies is not appropriate.

Review of the ATAC study: tamoxifen versus anastrozole in early-stage breast cancer.

A 5-year regimen of tamoxifen hormone therapy has historically been the recommendation for hormone receptor-positive, postmenopausal women with early-stage breast cancer. With the advent of aromatase inhibitors, there has been extensive work carried out to investigate the role of these agents in the adjuvant setting. Studies have been designed to answer whether these agents should be used upfront (instead of tamoxifen) or in conjunction (either in a switch or extended program). The Arimidex, Tamoxifen Alone or in Combination (ATAC) trial is a landmark trial that demonstrated the superiority of upfront anastrozole over tamoxifen. This article reviews the trial and discusses both the optimum timing of initiation of aromatase inhibitors and the future approach of more individualized therapy, with the detection of predictive markers.

Aromatase inhibitors in early hormone receptor-positive breast cancer : what is the optimal initiation time for the maximum benefit?

Breast cancer is common, affecting one in nine women worldwide. As stipulated by the St Gallen consensus guidelines, hormone therapy is an integral part of treatment for hormone-responsive disease. Previously, this has been with tamoxifen; however, as a result of a number of recent studies, aromatase inhibitors are now competing for use as first-line agents. In addition, there is as yet no firm consensus as to when and how these drugs should be used within the adjuvant setting. This article reviews the use of aromatase inhibitors in early stage hormone-positive breast cancer. It describes the evidence from the studies involving the aromatase inhibitors in an upfront, switch and extended setting. It further discusses the mathematical models proposed to determine the optimum timing of initiation. In light of the ongoing research into predictive biomarkers, this review then concentrates on whether future focus should be on more individualized treatment strategies than the optimum timing of aromatase inhibitors.