The British Association of Dermatologists' Undergraduate Curriculum Update 2021.

The General Medical Council (GMC) plans to introduce a national Medical Licensing Assessment (MLA) in 2024 for all UK medical students as part of their primary medical qualification, with dermatology specified in its assessment blueprint. We present an Update to the British Association of Dermatologists' Undergraduate Curriculum, aligned both to the MLA Content Map and the GMC Outcomes for Graduates 2018.

Next steps in dermatology training: choosing to enter higher speciality training and the transition from trainee to consultant dermatologist.

BACKGROUND: Junior doctors are required to make career decisions at an early stage in their postgraduate training. Trainees also feel inadequately prepared for the transition to consultant roles. AIM: To explore the key factors influencing the choice of dermatology as a postgraduate medical career and to identify the training needs required for transition from trainee to consultant. METHODS: An online questionnaire was designed to identify (i) why trainees chose a postgraduate medical career in dermatology, and (ii) the training required for transition from trainee to consultant. RESULTS: In total, 46 responses were received from trainees in their first to final years (ST3-6), of whom 89% had undertaken an undergraduate dermatology placement, with a median duration of 2 weeks. Dermatology was considered as a career during medical school by 61% of trainees, and 41% confirmed their decision to pursue a career in dermatology during foundation training. The most influential factors involved in speciality selection were first, enjoyment of the work, second, postgraduate experience and equal third, the variety of the speciality and the regularity of working hours (P < 0.05). Mentoring was pivotal to career decision-making. Significant numbers of trainees expressed a need for training in medical leadership, such as running an outpatient clinic and supervising clinical multidisciplinary teams. Although larger numbers of trainees had training in management of dermatology services, such as service improvement (52%) and local governance/National Health Service structures (43%), significant numbers of trainees had no training in writing job plans (89%) or business plans (85%). Training was significantly deficient for personal management and self-awareness. CONCLUSION: Our study highlights important considerations in career decision-making for trainees. Training in medical leadership, management and self-awareness could be enhanced to ensure that trainees feel adequately equipped for consultant roles.

Distinctive clinical and histological characteristics of atrophic and hypertrophic facial photoageing.

BACKGROUND: Photoageing describes complex cutaneous changes which occur following chronic exposure to solar ultraviolet radiation (UVR). Amongst White Northern Europeans, facial photoageing appears as distinct clinical phenotypes: 'hypertrophic' photoageing (HP) and 'atrophic' photoageing (AP). Deep, coarse wrinkles predominate in individuals with HP, whereas those with AP have relatively smooth, unwrinkled skin with pronounced telangiectasia. AP individuals have an increased propensity for developing keratinocyte cancers. OBJECTIVES: To investigate whether histological differences underlie these distinct phenotypes of facial photoageing. METHODS: Facial skin biopsies were obtained from participants with AP (10 M, 10 F; mean age: 78.7 years) or HP (10 M, 10 F; mean age: 74.5 years) and were assessed histologically and by immunohistochemistry. RESULTS: Demographic characterization revealed 95% of AP subjects, as compared to 35% with HP, were Fitzpatrick skin type I/II; of these, 50% had a history of one or more keratinocyte cancers. There was no history of keratinocyte cancers in the HP cohort. Analysis of UVR-induced mitochondrial DNA damage confirmed that all volunteers had received similar lifetime cumulative doses of sun exposure. Histologically, male AP had a significantly thicker epidermis than did AP females or those of either sex with HP. HP facial skin exhibited severe solar elastosis, whereas in AP facial skin, solar elastosis was apparent only in females. Loss of papillary dermal fibrillin-rich microfibrils occurred in all HP and AP female subjects, but not in AP males. Furthermore, male AP had a significant reduction in collagen VII at the dermal-epidermal junction than did AP females or those of either sex with HP. CONCLUSIONS: This study provides further evidence that AP and HP represent distinct clinical and histological entities. Knowledge of these two phenotypes is clinically relevant due to the increased prevalence of keratinocyte cancers in those - particularly males - with the AP phenotype.

Paediatric nurses' adoption of aseptic non-touch technique.

BACKGROUND:: in 2015, NHS Wales introduced a national standardised approach to aseptic non-touch technique (ANTT). This approach aims to standardise practice and promote better clinical outcomes. AIM:: to provide insight into the challenges faced by clinical staff adopting ANTT during intravenous therapy. METHODS:: focused ethnography across two paediatric wards in NHS Wales. Data collection included participant observation, audit questionnaires and semi-structured interviews. Data were analysed according to Wolcott's (1994) process and emerging themes were reflected upon against the theoretical framework of Kirkpatrick's (1994) model of training evaluation. FINDINGS:: absence of feedback following training, individual preference, lack of opportunity to practise the ANTT technique, lack of clarity and standardisation and expectations of parents/medical staff are all challenges faced by registered nurses. IMPLICATIONS OF THE STUDY:: the findings may be used by NHS managers to support national initiatives within staff training and development programmes, and to improve infection prevention initiatives. Organisational culture is a modifier of healthcare worker behaviour and requires further attention locally and nationally. Quality assurance in the adoption of standardised best practice must take into account staff training and development needs, and workplace culture.

A photonumeric scale for the assessment of atrophic facial photodamage.

BACKGROUND: Photonumeric scales have consistently shown superiority over descriptive equivalents. They have the advantage of providing a consistent visual frame of reference by minimizing variability in perception and subjectivity. A photonumeric scale to assess hypertrophic facial photodamage already exists. However, there is currently no objective measure for atrophic facial photodamage. To address this, we have devised a nine-point photonumeric standardized scale. OBJECTIVES: To design, test and validate a photonumeric scale for the assessment of atrophic facial photodamage against a descriptive scale for the same indication. METHODS: A pool of 393 facial photographs (en face and 45° oblique) from 131 individuals with atrophic facial photodamage was created. Five photographic standards were selected and assigned grades zero through to eight, where zero is no photodamage and eight is severe atrophic photodamage, thus making a nine-point scale. Twenty photographs spanning the entire range of values were selected to test the scale. Testing was performed alongside a descriptive equivalent. A panel of 10 dermatologists, 10 nondermatology clinicians and 14 dermatology scientists marked the two scales; marking was repeated 1 week later. RESULTS: There was a significantly greater agreement between the graders using the photonumeric scale than the descriptive scale (kappa values 0·71 and 0·37 with standardized errors of 0·57 and 0·17, respectively) with no significant difference in repeatability between the two methods (P < 0·05). CONCLUSIONS: The study describes a new photonumeric scale for atrophic photodamage. This would be a useful adjunct in both the clinical and research settings.

Timely initiation of chemotherapy: a systematic literature review of six priority cancers - results and recommendations for clinical practice.

This review evaluated the association between time-to-chemotherapy (TTC) and survival in six priority cancers. A systematic review of the literature was undertaken for papers indexed in the MEDLINE and Cochrane Library databases from the earliest index until April 2014. The methodology used has been published in a separate paper (Guidelines for timely initiation of chemotherapy: a proposed framework for access to medical oncology and haematology cancer clinics and chemotherapy services). The optimal timing of chemotherapy in breast cancer is unclear as available studies are of low quality, report inconsistent results and are limited to the adjuvant setting. However, increased TTC may have a negative prognostic impact, and delays beyond 4 weeks should be avoided. Studies suggest that the optimal timing for initiation of adjuvant chemotherapy for surgically resected colorectal cancer is 4-8 weeks post-surgery. Timing of chemotherapy for metastatic colorectal cancer does not influence survival. There is a paucity of studies to guide the timing of chemotherapy for the treatment of lymphoma and myeloma; no definitive conclusions can be drawn, and clinician discretion should be applied. The optimal timing of chemotherapy in lung cancer is unclear; however, rapid tumour growth and poor disease prognosis suggest that delays should be avoided wherever possible. The optimal timing of chemotherapy in ovarian cancer is unclear as available studies are of low level, report inconsistent results and are limited to the post-surgery setting; however, increased TTC may have a negative prognostic impact; therefore, delays beyond 4 weeks should be avoided.

Biology of the eyelash hair follicle: an enigma in plain sight.

Because of their crucial impact on our perception of beauty, eyelashes constitute a prime target for the cosmetic industry. However, when compared with other hair shafts and the mini-organs that produce them [eyelash hair follicles (ELHFs)], knowledge on the biology underlying growth and pigmentation of eyelashes is still rudimentary. This is due in part to the extremely restricted availability of human ELHFs for experimental study, underappreciation of their important sensory and protective functions and insufficient interest in understanding why they are distinct from scalp hair follicles (HFs) (e.g. ELHFs produce shorter hair shafts, do not possess an arrector pili muscle, have a shorter hair cycle and undergo greying significantly later than scalp HFs). Here we synthesize the limited current knowledge on the biology of ELHFs, in humans and other species, their role in health and disease, the known similarities with and differences from other HF populations, and their intrinsic interethnic variations. We define major open questions in the biology of these intriguing mini-organs and conclude by proposing future research directions. These include dissecting the molecular and cellular mechanisms that underlie trichomegaly and the development of in vitro models in order to interrogate the distinct molecular controls of ELHF growth, cycling and pigmentation and to probe novel strategies for the therapeutic and cosmetic manipulation of ELHFs beyond prostaglandin receptor stimulation.

Is Immediate Radical Cystectomy Necessary for All Patients with Non-Muscle-Invasive Micropapillary Bladder Cancer?

INTRODUCTION: We aim to review the outcomes of micropapillary urothelial carcinoma (MPUC) of the bladder from a single institution. The hypothesis is that non-muscle-invasive (NMI) MPUC may have a heterogeneous prognosis, and detailed pathological analysis may identify patients that could be managed without immediate cystectomy. PATIENTS AND METHODS: This is a retrospective analysis of patients presenting with MPUC in a primary transurethral resection specimen (n = 40). The pattern of micropapillary (MP) differentiation [surface/non-invasive (sMP) or invasive (iMP)], extent of MP differentiation and lymphovascular invasion (LVI) were correlated with overall survival (OS), recurrence-free survival and upstaging at re-resection. RESULTS: Sixteen of 40 patients died after a median follow-up of 37 months. Tumour stage was strongly predictive of OS (p < 0.0001). LVI was associated with increased mortality (hazard ratio 12.4, 95% CI: 3.5-44.5, p = 0.0001), higher pathological stage (p = 0.001), lymph node involvement (p = 0.001) and iMP differentiation (p = 0.006). In NMI patients not undergoing cystectomy (n = 17), NMI-sMP compared with NMI-iMP differentiation was associated with an improved OS when compared with iMP (63 vs. 47 months, p = 0.05). CONCLUSIONS: MPUC is an aggressive variant of urothelial carcinoma (UC). Similar to conventional UC, LVI associated with MPUC is an adverse prognostic indicator. iMP is a morphological marker for LVI. Histopathological reports should distinguish between sMP and iMP differentiation.

Long-term safety and efficacy of bimatoprost solution 0·03% application to the eyelid margin for the treatment of idiopathic and chemotherapy-induced eyelash hypotrichosis: a randomized controlled trial.

BACKGROUND: Bimatoprost ophthalmic solution 0·03% is approved in several countries for the treatment of eyelash hypotrichosis. Previous trials were limited to 4 months of treatment and primarily idiopathic hypotrichosis. OBJECTIVES: To evaluate the long-term safety and efficacy of bimatoprost in patients with idiopathic or chemotherapy-induced hypotrichosis. METHODS: This multicentre, double-masked, randomized, parallel-group study included two 6-month treatment periods [treatment period 1 (TP1) and treatment period 2 (TP2)]. Patients with idiopathic hypotrichosis were randomized to three treatment groups: (i) bimatoprost (TP1 and TP2); (ii) bimatoprost (TP1) and vehicle (TP2); and (iii) vehicle (TP1) and bimatoprost (TP2). Patients with chemotherapy-induced hypotrichosis were randomized to two treatment groups: (i) bimatoprost or vehicle (TP1) and (ii) bimatoprost (TP2). Primary end point was a composite of at least a one-grade improvement in investigator-assessed Global Eyelash Assessment and at least a three-point improvement in patient-reported Eyelash Satisfaction Questionnaire Domain 2 at month 4. Secondary measures included digitally assessed eyelash characteristics. RESULTS: The primary efficacy end point was met in both populations (idiopathic responder rate was 40·2% for bimatoprost vs. 6·8% for vehicle; postchemotherapy responder rate was 37·5% for bimatoprost vs. 18·2% for vehicle). Efficacy by month 6 was maintained (idiopathic) or enhanced (postchemotherapy) at 12 months. Treatment effects were maintained for approximately 2 months but markedly diminished 4-6 months following treatment cessation in patients with idiopathic hypotrichosis. No drug-related serious adverse events were reported. CONCLUSIONS: Daily treatment with bimatoprost ophthalmic solution 0·03% for 1 year was effective and well tolerated in patients with idiopathic and chemotherapy-induced hypotrichosis.

Lifestyle and youthful looks.

BACKGROUND: Lifestyle has been proven to have a dramatic effect on the risk of age-related diseases. The association of lifestyle and facial ageing has been less well studied. OBJECTIVES: To identify lifestyle factors that associate with perceived facial age in white north European men and women. METHODS: Lifestyle, facial wrinkling and perceived facial age were studied in two cross-sectional studies consisting of 318 Dutch men and 329 women aged 45-75 years who were part of the Leiden Longevity Study, and 162 English women aged 45-75 years who were nonsmokers. RESULTS: In Dutch men, smoking, having skin that went red in the sun, being outside in the sun most of the summer, sunbed use, wearing false teeth and not flossing teeth were all significantly associated (P < 0·05) with a total 9·3-year higher perceived facial age in a multivariate model adjusting for chronological age. In Dutch women, smoking, sunbathing, sunbed use, few remaining teeth and a low body mass index (BMI) were associated with a total 10·9-year higher perceived facial age. In English women, cleaning teeth only once a day, wearing false teeth, irregular skin moisturization and having skin that went red in the sun were associated with a total 9·1-year higher perceived facial age. Smoking and sunbed use were associated more strongly with wrinkling in women than in men. BMI, sun exposure and skincare were associated predominantly with perceived facial age via wrinkling, whereas oral care was associated via other facial features. CONCLUSIONS: Although associative in nature, these results support the notion that lifestyle factors can have long-term beneficial effects on youthful looks.

Comet assay measures of DNA damage are predictive of bladder cancer cell treatment sensitivity in vitro and outcome in vivo.

Bladder cancer patients suffer significant treatment failure, including high rates of recurrence and poor outcomes for advanced disease. If mechanisms to improve tumour cell treatment sensitivity could be identified and/or if tumour response could be predicted, it should be possible to improve local-control and survival. Previously, we have shown that radiation-induced DNA damage, measured by alkaline Comet assay (ACA), correlates bladder cancer cell radiosensitivity in vitro. In this study we first show that modified-ACA measures of cisplatin and mitomycin-C-induced damage also correlate bladder cancer cell chemosensitivity in vitro, with essentially the same rank order for chemosensitivity as for radiosensitivity. Furthermore, ACA studies of radiation-induced damage in different cell-DNA substrates (nuclei, nucleoids and intact parent cells) suggest that it is a feature retained in the prepared nucleoids that is responsible for the relative damage sensitivity of bladder cancer cells, suggestive of differences in the organisation of DNA within resistant vs. sensitive cells. Second, we show that ACA analysis of biopsies from bladder tumours reveal that reduced DNA damage sensitivity associates with poorer treatment outcomes, notably that tumours with a reduced damage response show a significant association with local recurrence of non-invasive disease and that reduced damage response was a better predictor of recurrence than the presence of high-risk histology in this cohort. In conclusion, this study demonstrates that mechanisms governing treatment-induced DNA damage are both central to and predictive of bladder cancer cell treatment sensitivity and exemplifies a link between DNA damage resistance and both treatment response and tumour aggression.

Reduction of unwanted submental fat with ATX-101 (deoxycholic acid), an adipocytolytic injectable treatment: results from a phase III, randomized, placebo-controlled study.

BACKGROUND: Unwanted submental fat (SMF) is aesthetically unappealing, but methods of reduction are either invasive or lack evidence for their use. An injectable approach with ATX-101 (deoxycholic acid) is under investigation. OBJECTIVES: To evaluate the efficacy and safety of ATX-101 for the reduction of unwanted SMF. METHODS: In this double-blind, placebo-controlled, phase III study, 363 patients with moderate/severe SMF were randomized to receive ATX-101 (1 or 2 mg cm(-2) ) or placebo injections into their SMF at up to four treatment sessions ~28 days apart, with a 12-week follow-up. The co-primary efficacy endpoints were the proportions of treatment responders [patients with ≥ 1-point improvement in SMF on the 5-point Clinician-Reported Submental Fat Rating Scale (CR-SMFRS)] and patients satisfied with their face and chin appearance on the Subject Self-Rating Scale (SSRS). Secondary endpoints included skin laxity, calliper measurements and patient-reported outcomes. Adverse events were monitored. RESULTS: Significantly more ATX-101 recipients met the primary endpoint criteria vs. placebo: on the clinician scale, 59·2% and 65·3% of patients treated with ATX-101 1 and 2 mg cm(-2) , respectively, were treatment responders vs. 23·0% for placebo (CR-SMFRS; P < 0·001); on the patient scale, 53·3% and 66·1%, respectively, vs. 28·7%, were satisfied with their face/chin appearance (SSRS; P < 0·001). Calliper measurements showed a significant reduction in SMF (P < 0·001), skin laxity was not worsened and patients reported improvements in the severity and psychological impact of SMF with ATX-101 vs. placebo. Most adverse events were transient and associated with the treatment area. CONCLUSIONS: ATX-101 was effective and well tolerated for nonsurgical SMF reduction.

Brain Charts for the Rhesus Macaque Lifespan.

Recent efforts to chart human brain growth across the lifespan using large-scale MRI data have provided reference standards for human brain development. However, similar models for nonhuman primate (NHP) growth are lacking. The rhesus macaque, a widely used NHP in translational neuroscience due to its similarities in brain anatomy, phylogenetics, cognitive, and social behaviors to humans, serves as an ideal NHP model. This study aimed to create normative growth charts for brain structure across the macaque lifespan, enhancing our understanding of neurodevelopment and aging, and facilitating cross-species translational research. Leveraging data from the PRIMatE Data Exchange (PRIME-DE) and other sources, we aggregated 1,522 MRI scans from 1,024 rhesus macaques. We mapped non-linear developmental trajectories for global and regional brain structural changes in volume, cortical thickness, and surface area over the lifespan. Our findings provided normative charts with centile scores for macaque brain structures and revealed key developmental milestones from prenatal stages to aging, highlighting both species-specific and comparable brain maturation patterns between macaques and humans. The charts offer a valuable resource for future NHP studies, particularly those with small sample sizes. Furthermore, the interactive open resource (https://interspeciesmap.childmind.org) supports cross-species comparisons to advance translational neuroscience research.

Serum insulin-like growth factor 1 and facial ageing: high levels associate with reduced skin wrinkling in a cross-sectional study.

BACKGROUND: Insulin-like growth factor (IGF)-1 is a growth factor that can influence fibroblast functioning, with effects including the inhibition of collagenases and the induction of collagen expression. OBJECTIVES: To assess whether serum IGF-1, IGF-binding protein (IGFBP)3 and the ratio between IGF-1 and IGFBP3, as a measure of IGF-1 bioavailability, are associated with facial ageing and skin wrinkling. METHODS: From a random sample comprising 617 subjects from the Leiden Longevity Study, perceived age and skin wrinkling were assessed from facial photographs, and IGF-1 and IGFBP3 were measured in serum. The associations were assessed using linear regression models, adjusted for chronological age, sex, body mass index, smoking and sun exposure. RESULTS: Across tertiles of the ratio of IGF-1 to IGFBP3, and after adjusting for all potential confounding factors, the mean perceived age decreased from 60·6 years in the lowest tertile to 59·5 years in the highest (P = 0·045). Similarly, the mean skin wrinkling grade decreased from 4·8 in the lowest tertile to 4·5 in the highest (P = 0·011). Adding skin wrinkling as a covariate in the analysis between IGF-1 and perceived age diminished this association. CONCLUSIONS: This study demonstrates that a higher ratio of IGF-1 to IGFBP3 associates with a lower perceived age, via its association with reduced skin wrinkling. Whether high IGF-1 levels actually delay the accumulation of skin wrinkling now needs investigating.

Current perspectives in bladder cancer management.

More than 350,000 new cases of bladder cancer are diagnosed worldwide each year; the vast majority (> 90%) of these are transitional cell carcinomas (TCC). The most important risk factors for the development of bladder cancer are smoking and occupational exposure to toxic chemicals. Painless visible haematuria is the most common presenting symptom of bladder cancer; significant haematuria requires referral to a specialist urology service. Cystoscopy and urine cytology are currently the recommended tools for diagnosis of bladder cancer. Excluding muscle invasion is an important diagnostic step, as outcomes for patients with muscle invasive TCC are less favourable. For non-muscle invasive bladder cancer, transurethral resection followed by intravesical chemotherapy (typically Mitomycin C or epirubicin) or immunotherapy [bacillus Calmette-Guérin (BCG)] is the current standard of care. For patients failing BCG therapy, cystectomy is recommended; for patients unsuitable for surgery, the choice of treatment options is currently limited. However, novel interventions, such as chemohyperthermia and electromotive drug administration, enhance the effects of conventional chemotherapeutic agents and are being evaluated in Phase III trials. Radical cystectomy (with pelvic lymphadenectomy and urinary diversion) or radical radiotherapy are the current established treatments for muscle invasive TCC. Neoadjuvant chemotherapy is recommended before definitive treatment of muscle invasive TCC; cisplatin-containing combination chemotherapy is the recommended regimen. Palliative chemotherapy is the first-choice treatment in metastatic TCC.

A method for semi-automatic grading of human blastocyst microscope images.

BACKGROUND: The precise assessment of embryo viability is an extremely important factor for the optimization of IVF treatments. In order to assess embryo viability, several embryo scoring systems have been developed. However, they rely mostly on a subjective visual analysis of embryo morphological features and thus are subject to inter- and intra-observer variation. In this paper, we propose a method for image segmentation (the dividing of an image into its meaningful constituent regions) and classification of human blastocyst images with the aim of automating embryo grading. METHODS: The delineation of the boundaries (segmentation) of the zona pellucida, trophectoderm (TE) and inner cell mass (ICM) were performed using advanced image analysis techniques (level set, phase congruency and fitting of ellipse methods). The fractal dimension and mean thickness of TE and ICM image texture descriptors (texture spectrum and grey-level run lengths) were calculated to characterize the main morphological features of the blastocyst with the aim of automatic grading using Support Vector Machine classifiers. RESULTS: The fractal dimension calculated from the delineated TE boundary provided a good indication of cell number (presented a 0.81 Pearson correlation coefficient with the number of cells), a feature closely associated with blastocyst quality. The classifiers showed different accuracy levels for each grade. They presented accuracy ranges from 0.67 to 0.92 for the embryo development classification, 0.67-0.82 for the ICM classification and 0.53-0.92 for the TE classification. The value 0.92 was the highest accuracy achieved in the tests with 73 blastocysts. CONCLUSIONS: Semi-automatic grading of human blastocysts by a computer is feasible and may offer a more precise comparison of embryos, reducing subjectivity and allowing embryos with apparently identical morphological scores to be distinguished.