How the mapping of threshold concepts across a master's programme in health professions education could support the development of mastersness.

INTRODUCTION: Global trends towards the professionalization of Health Professions Education (HPE) have catalyzed the proliferation of degree-awarding programmes in HPE. We apply the theoretical lens of threshold concepts to explore the required levels of Master's in HPE (MHPE) learning and teaching, with a view to determining how students might be supported to engage meaningfully with learning. METHODS: Qualitative data were collected with a series of nominal group discussions. The methodology and data analysis followed a consensus building approach. RESULTS: Four threshold concepts were identified: Being in the HPE world, the nature of HPE knowledge, the nature of HPE practice and the nature of HPE scholarship. We also mapped the threshold concepts to the World Federation for Medical Education (WFME) master's level academic skills and the Scottish Quality Assurance Agency (QAA) facets of mastersness. CONCLUSION: It is envisaged that our findings will enhance alignment between the outcomes and assessment in an MHPE programme, form the basis of understanding feedback received from students, and inform teaching and supervisory practices. The findings also complement the WFME and QAA frameworks by clarifying the depth and complexity of academic skills expected at master's level and informing teaching and learning approaches to support the development of the identified threshold concepts.

Changes in the quality of life in patients undergoing orthognathic therapy - A systematic review.

The aim of this study was to investigate the impact of orthognathic therapy on patients' quality of life. Therefore, a systematic review was conducted including all prospective studies that compared pretherapeutic and posttherapeutic Oral Health Impact Profile (OHIP) or Overall Quality of Life (OQOL) questionnaire scores. Studies in patients with congenital deformities, clefts, or posttraumatic or cancer-associated deformities were excluded. Overall, 23 prospective studies were included; 8 used OHIP, 9 used OQOL and 6 used both questionnaires. A total of 1039 patients were identified (60.29% women, 39.71% men), with a mean age of 45.17 years. All analyzed studies showed in both OHIP and OQLQ an improvement of the quality of life in patients after orthognathic therapy. While improved scores could be observed in all investigated criteria, the studies demonstrated that social and aesthetic aspects showed the most prominent impact. Comparison of different Angle Classes showed, furthermore, that Class III patients had an even greater advantage over those with a Class II deformity. The review confirms that the quality of life in patients with orthognathic therapy improves significantly in all observed aspects. With regard to Angle Classes, Class III patients showed an even greater improvement than Class II patients.

The impact of antenatal and postnatal indoor air pollution or tobacco smoke exposure on lung function at 3 years in an African birth cohort.

BACKGROUND AND OBJECTIVE: Indoor air pollution (IAP) and tobacco smoke exposure (ETS) are global health concerns contributing to the burden of childhood respiratory disease. Studies assessing the effects of IAP and ETS in preschool children are limited. We assessed the impact of antenatal and postnatal IAP and ETS exposure on lung function in a South African birth cohort, the Drakenstein Child Health Study. METHODS: Antenatally enrolled mother-child pairs were followed from birth. Lung function measurements (oscillometry, multiple breath washout and tidal breathing) were performed at 6 weeks and 3 years. Quantitative antenatal and postnatal IAP (particulate matter [PM10 ], volatile organic compounds [VOC]) and ETS exposures were measured. Linear regression models explored the effects of antenatal and postnatal exposures on lung function at 3 years. RESULTS: Five hundred eighty-four children had successful lung function testing, mean (SD) age of 37.3 (0.7) months. Exposure to antenatal PM10 was associated with a decreased lung clearance index (p < 0.01) and postnatally an increase in the difference between resistance at end expiration (ReE) and inspiration (p = 0.05) and decrease in tidal volume (p = 0.06). Exposure to antenatal VOC was associated with an increase in functional residual capacity (p = 0.04) and a decrease in time of expiration over total breath time (tE /tTOT ) (p = 0.03) and postnatally an increase in respiratory rate (p = 0.05). High ETS exposure postnatally was associated with an increase in ReE (p = 0.03). CONCLUSION: Antenatal and postnatal IAP and ETS exposures were associated with impairment in lung function at 3 years. Strengthened efforts to reduce IAP and ETS exposure are needed.

Differential Response of Pelvic Bone Marrow Fluorodeoxyglucose Uptake in Patients Receiving Concurrent Chemoradiotherapy.

AIMS: Irradiation of pelvic bone marrow (PBM) at the level of the typical low dose bath of intensity-modulated radiotherapy delivery (10-20 Gy) is associated with an increased risk of haematological toxicity, particularly when combined with concurrent chemotherapy. Although sparing of the whole of the PBM at a 10-20 Gy dose level is unachievable, it is known that PBM is divided into haematopoietically active and inactive regions that are identifiable based on the threshold uptake of [18F]-fluorodeoxyglucose (FDG) seen on positron emission tomography-computed tomography (PET-CT). In published studies to date, the definition of active PBM widely used is that of a standardised uptake value (SUV) greater than the mean SUV of the whole PBM prior to the start of chemoradiation. These studies include those looking at developing an atlas-based approach to contouring active PBM. Using baseline and mid-treatment FDG PET scans acquired as part of a prospective clinical trial we sought to determine the suitability of the current definition of active bone marrow as representative of differential underlying cell physiology. MATERIALS AND METHODS: Active and inactive PBM were contoured on baseline PET-CT and using deformable registration mapped onto mid-treatment PET-CT. Volumes were cropped to exclude definitive bone, voxel SUV extracted and the change between scans calculated. Change was compared using Mann-Whitney U testing. RESULTS: Active and inactive PBM were shown to respond differentially to concurrent chemoradiotherapy. The median absolute response of active PBM for all patients was -0.25 g/ml, whereas the median inactive PBM response was -0.02 g/ml. Significantly, the inactive PBM median absolute response was shown to be near zero with a relatively unskewed distribution (0.12). CONCLUSIONS: These results would support the definition of active PBM as FDG uptake greater than the mean of the whole structure as being representative of underlying cell physiology. This work would support the development of atlas-based approaches published in the literature to contour active PBM based on the current definition as being suitable.

Urban Water Storage Capacity Inferred From Observed Evapotranspiration Recession.

Water storage plays an important role in mitigating heat and flooding in urban areas. Assessment of the water storage capacity of cities remains challenging due to the inherent heterogeneity of the urban surface. Traditionally, effective storage has been estimated from runoff. Here, we present a novel approach to estimate effective water storage capacity from recession rates of observed evaporation during precipitation-free periods. We test this approach for cities at neighborhood scale with eddy-covariance based latent heat flux observations from 14 contrasting sites with different local climate zones, vegetation cover and characteristics, and climates. Based on analysis of 583 drydowns, we find storage capacities to vary between 1.3 and 28.4 mm, corresponding to e-folding timescales of 1.8-20.1 days. This makes the urban storage capacity at least five times smaller than all the observed values for natural ecosystems, reflecting an evaporation regime characterized by extreme water limitation.

Concurrent chemo-endocrine treatment for early hormone-positive breast cancer: a no-go???

PURPOSE: Endocrine therapy is one of the cornerstones of early breast cancer treatment. While this medication could be initiated on the day of diagnosis, it is often postponed until after completion of surgery, radiotherapy, and chemotherapy. This practice is based on preclinical data suggesting an antagonistic effect between endocrine therapy and cytostatic agents, and on the interpretation of clinical trials comparing concurrent versus sequential use of tamoxifen and chemotherapy. These clinical trials, however, have never shown a statistically significant difference in overall survival or disease-free survival and focused on tamoxifen rather than aromatase inhibitors. Nevertheless, sequentially administered endocrine and chemotherapy have become standard of care worldwide. RESULTS: We performed a literature review and conclude that concurrent endocrine chemotherapy is at least as effective as sequential treatment. In fact, higher response rates have been observed in trials with aromatase inhibitors rather than tamoxifen in a neoadjuvant setting. CONCLUSION: We encourage breast cancer oncologists to re-consider concurrent endocrine chemotherapy as a possible treatment strategy enabling early start of potentially curative endocrine treatment.

Jewish cultural and religious factors and uptake of population-based BRCA testing across denominations: a cohort study.

OBJECTIVE: To evaluate the association of Jewish cultural and religious identity and denominational affiliation with interest in, intention to undertake and uptake of population-based BRCA (Breast Cancer Gene)-testing. DESIGN: Cohort-study set within recruitment to GCaPPS-trial (ISRCTN73338115). SETTING: London Ashkenazi-Jewish (AJ) population. POPULATION OR SAMPLE: AJ men and women, >18 years. METHODS: Participants were self-referred, and attended recruitment clinics (clusters) for pre-test counselling. Subsequently consenting individuals underwent BRCA testing. Participants self-identified to one Jewish denomination: Conservative/Liberal/Reform/Traditional/Orthodox/Unaffiliated. Validated scales measured Jewish Cultural-Identity (JI) and Jewish Religious-identity (JR). Four-item Likert-scales analysed initial 'interest' and 'intention to test' pre-counselling. Item-Response-Theory and graded-response models, modelled responses to JI and JR scales. Ordered/multinomial logistic regression modelling evaluated association of JI-scale, JR-scale and Jewish Denominational affiliation on interest, intention and uptake of BRCA testing. MAIN OUTCOME MEASURES: Interest, intention, uptake of BRCA testing. RESULTS: In all, 935 AJ women/men of mean age = 53.8 (S.D = 15.02) years, received pre-test education and counselling through 256 recruitment clinic clusters (median cluster size = 3). Denominational affiliations included Conservative/Masorti = 91 (10.2%); Liberal = 82 (9.2%), Reform = 135 (15.1%), Traditional = 212 (23.7%), Orthodox = 239 (26.7%); and Unaffiliated/Non-practising = 135 (15.1%). Overall BRCA testing uptake was 88%. Pre-counselling, 96% expressed interest and 60% intention to test. JI and JR scores were highest for Orthodox, followed by Conservative/Masorti, Traditional, Reform, Liberal and Unaffiliated Jewish denominations. Regression modelling showed no significant association between overall Jewish Cultural or Religious Identity with either interest, intention or uptake of BRCA testing. Interest, intention and uptake of BRCA testing was not significantly associated with denominational affiliation. CONCLUSIONS: Jewish religious/cultural identity and denominational affiliation do not appear to influence interest, intention or uptake of population-based BRCA testing. BRCA testing was robust across all Jewish denominations. TWEETABLE ABSTRACT: Jewish cultural/religious factors do not affect BRCA testing, with robust uptake seen across all denominational affiliations.

Combined versus single treatment regimens for keloid therapy using serial intralesional corticosteroid injections, surgical excision, silicone- and/or cryotherapy.

Efficacy comparison of several regimens in treating keloids as combined or standalone therapies could provide essential information for selecting appropriate therapy. This study retrospectively evaluated the treatment efficacy of corticosteroid injections, excision, silicone, cryotherapy, or combinations of these for treating keloids. Additionally, the use of corticosteroid injection schemes and combined cryotherapy regimens were analysed. Retrospective chart analysis was performed on 204 keloids treated patients at the plastic surgery department of the Máxima Medical Centre between 2009 and 2018. The patient's age, gender, treatment, anatomic location, scar aetiology, previous therapy, scar recurrence, additional therapy, and follow-up duration were retrieved. Treatment efficacy was assessed through treatment failure, defined by the recurrence or lack of response. Kaplan-Meier and Cox survival analyses were performed to compare treatment efficacy between the different regimens. Monotherapies exhibited a significantly higher chance of treatment failure (HR 2.4, 95% CI 1.4-4.2, p<0.05) when compared to combined therapies. Sporadic corticosteroid injections demonstrated more treatment failure overall (HR 3.5 95% CI 1,6-7,3; p=0.001), but did not differ significantly from injection schemes. Combined cryotherapy efficacy did not differ significantly from the other combined regimens (HR 1,6 95% CI 0,5-5,1; p=0.401). Combined therapies exhibited clear superiority over monotherapies. Sporadic corticosteroid injections demonstrated inferior results compared to all other therapies. Combined cryotherapy cases were insufficient, and more data are required for proper assessment. Future prospective assessments of corticosteroid injection schemes and combined regimens are warranted.

Serum 25-hydroxyvitamin D concentrations and mortality in dogs with blastomycosis.

Blastomycosis is a prominent fungal disease in the United States. Vitamin D status has been found to be altered in critical illness and various infectious diseases. The objectives of this study were to compare serum 25-hydroxyvitamin D (25[OH]D) concentrations in dogs with blastomycosis and healthy controls, to assess the change in serum 25(OH)D concentrations in dogs with blastomycosis after 30 days of treatment, and to determine if baseline serum 25(OH)D concentrations in dogs with blastomycosis were associated with in-hospital, 30-day, or end-of-study mortality. In this prospective cohort study, 19 dogs newly diagnosed with blastomycosis had serum 25(OH)D concentrations measured with a commercially available validated radioimmunoassay at the time of diagnosis and 30 days after start of treatment. These values were compared to 24 healthy control dogs. Serum 25(OH)D concentrations at the time of diagnosis were lower in dogs with blastomycosis (median, 203 nmol/L; range, 31-590 nmol/L) than in clinically healthy control dogs (259.5 nmol/L, 97-829 nmol/L; P = 0.01). Despite clinical improvement, there was no significant change in serum 25(OH)D concentrations from baseline to 30-day follow-up. Dogs with baseline serum 25(OH)D concentrations <180.5nmol/L had a greater odds of death during hospitalization (odds ratio [OR], 15.0; 95% confidence interval [CI], 1.4-191.3; P = 0.04) and at 30 days follow-up (OR, 30.0; 95% CI, 2.5-366.7; P = 0.006). These findings highlight the need for further studies evaluating the prognostic value of vitamin D status in dogs with blastomycosis at diagnosis and throughout treatment and remission.

The association between treatment and systemic inflammation in acromegaly.

OBJECTIVE: Acromegaly is characterized by an excess of growth hormone (GH) and insulin like growth-factor 1 (IGF1), and it is strongly associated with cardiovascular diseases (CVD). Both acute and long-lasting pro-inflammatory effects have been attributed to IGF1. Previous results suggest the presence of systemic inflammation in treated patients. Here we assessed the association between treatment of acromegaly, systemic inflammation and vascular function. DESIGN: Ex vivo cytokine production and circulating inflammatory markers were assessed in peripheral blood from treated and untreated acromegaly patients (N = 120), and compared them with healthy controls. A more comprehensive prospective inflammatory and vascular assessment was conducted in a subgroup of six treatment-naive patients with follow-up during treatment. RESULTS: Circulating concentrations of VCAM1, E-selectin and MMP2 were higher in patients with uncontrolled disease, whereas the concentrations of IL18 were lower. In stimulated whole blood, cytokine production was skewed towards a more pro-inflammatory profile in patients, especially those with untreated disease. Prospective vascular measurements in untreated patients showed improvement of endothelial function during treatment. CONCLUSIONS: Acromegaly patients are characterized by a pro-inflammatory phenotype, most pronounced in those with uncontrolled disease. Treatment only partially reverses this pro-inflammatory bias. These findings suggest that systemic inflammation could contribute to the increased risk of CVD in acromegaly patients.

Volumetric evaluation of CT images of adrenal glands in primary aldosteronism.

OBJECTIVES: To investigate whether adrenal volumetry provides better agreement with adrenal vein sampling (AVS) than conventional CT for subtyping PA. Furthermore, we evaluated whether the size of this contralateral adrenal was a prognostic factor for clinical outcome after unilateral adrenalectomy. METHODS: We retrospectively analyzed volumes of both adrenal glands of the 180 CT-scans (88/180 with unilateral and 92/180 with bilateral disease) of the patients with PA included in the SPARTACUS trial of which 85 also had undergone an AVS. In addition, we examined CT-scans of 20 healthy individuals to compare adrenal volumes with published normal values. RESULTS: Adrenal volume was higher for the left than the right adrenal (mean and SD: 6.49 ± 2.77 ml versus 5.25 ± 1.87 ml for the right adrenal; p < 0.001). Concordance between volumetry and AVS in subtyping was 58.8%, versus 51.8% between conventional CT results and AVS (p = NS). The volumes of the contralateral adrenals in the patients with unilateral disease (right 4.78 ± 1.37 ml; left 6.00 ± 2.73 ml) were higher than those of healthy controls reported in the literature (right 3.62 ± 1.23 ml p < 0.001; left 4.84 ± 1.67 ml p = 0.02). In a multivariable analysis the contralateral volume was not associated with biochemical or clinical success, nor with the defined daily doses of antihypertensive agents at 1 year follow-up. CONCLUSIONS: Volumetry of the adrenal glands is not superior to current assessment of adrenal size by CT for subtyping patients with PA. Furthermore, in patients with unilateral disease the size of the contralateral adrenal is enlarged but its size is not associated with outcome.

Surgical management for isolated macrodactyly in an adult PIK3CA mutant.

Isolated macrodactyly in adults caused by mosaic pattern PIK3CA mutation can result in significant functional impairment and psychological burden. Due to the rarity of this condition there are no clear treatment guidelines, and those few available are focused on paediatric cases. Reports on surgical management of isolated macrodactyly in adults are lacking. We present here the surgical management through partial amputation of enlarged rays of the right hand in an individual affected by low-grade mosaic PIK3CA mutation.

A Prospective Study of Diffusion-weighted Magnetic Resonance Imaging as an Early Prognostic Biomarker in Chemoradiotherapy in Squamous Cell Carcinomas of the Anus.

AIMS: The use of diffusion-weighted magnetic resonance imaging (DW-MRI) as a prognostic marker of treatment response would enable early individualisation of treatment. We aimed to quantify the changes in mean apparent diffusion coefficient (ΔADCmean) between a DW-MRI at diagnosis and on fraction 8-10 of chemoradiotherapy (CRT) as a biomarker for cellularity, and correlate these with anal squamous cell carcinoma recurrence. MATERIALS AND METHODS: This prospective study recruited patients with localised anal cancer between October 2014 and November 2017. DW-MRI was carried out at diagnosis and after fraction 8-10 of radical CRT. A region of interest was delineated for all primary tumours and any lymph nodes >2 cm on high-resolution T2-weighted images and propagated to the ADC map. Routine clinical follow-up was collected from Nation Health Service electronic systems. RESULTS: Twenty-three of 29 recruited patients underwent paired DW-MRI scans. Twenty-six regions of interest were delineated among the 23 evaluable patients. The median (range) tumour volume was 13.6 cm3 (2.8-84.9 cm3). Ten of 23 patients had lesions with ΔADCmean ≤ 20%. With a median follow-up of 41.2 months, four patients either failed to have a complete response to CRT or subsequently relapsed. Three of four patients with disease relapse had lesions demonstrating ΔADCmean <20%, the other patient with persistent disease had ΔADCmean of 20.3%. CONCLUSIONS: We demonstrated a potential correlation between patients with ΔADCmean <20% and disease relapse. Further investigation of the prognostic merit of DW-MRI change is needed in larger, prospective cohorts.

Diagnostic contribution of individual components of adrenal function tests to diagnose canine hyperadrenocorticism.

There is limited information regarding the value of constitutive components of the ACTH stimulation test (ACTHST) and low-dose dexamethasone suppression test (LDDST) including serum baseline cortisol (BC), difference between post-ACTH stimulation cortisol (PC) and BC (ΔACTHC), cortisol concentration 4h after dexamethasone administration (4HC), difference between 4HC and BC (Δ4C), and the difference between cortisol concentration 8h after dexamethasone administration and 4HC (Δ8C). Therefore, the objective of this study was to determine if these components can predict hyperadrenocorticism, pituitary-dependent hyperadrenocorticism (PDH), or functional adrenocortical tumor (FAT) in dogs. Cortisol concentrations were normalized, as fold change (FC), to the PC reference interval upper limit. A total of 1267 dogs were included, with hyperadrenocorticism diagnosed in 537 (PDH, n=356; FAT, n=28; undetermined, n=153) and excluded in 730. The area under the receiver operating curves for BC, ΔACTHC, 4HC, Δ4C, and Δ8C to predict hyperadrenocorticism were 0.76 (95% confidence interval (CI), 0.73-0.79), 0.91 (95% CI, 0.89-0.93), 0.83 (95% CI, 0.80-0.87), 0.55 (95% CI, 0.50-0.60), and 0.67 (95% CI, 0.62-0.72), respectively. A diagnostic limit of ≥0.78 FC for ΔACTHC had excellent sensitivity (1.00; 95% CI, 0.74-1.00), but poor specificity (0.67; 95% CI, 0.64-0.71), to predict FAT in dogs with a positive ACTHST. A diagnostic limit of ≥-0.26 FC for Δ4C had excellent sensitivity (1.00; 95% CI, 0.79-1.00), but poor specificity (0.21; 95% CI, 0.18-0.26), to predict FAT in dogs with a positive LDDST. In hyperadrenocorticoid dogs that have positive ACTHST or LDDST results, ΔACTHC or Δ4C, respectively, could be used to exclude FAT.

Anti-cyclic citrullinated peptide antibodies are associated with radiographic damage but not disease activity in early rheumatoid arthritis diagnosed in 2006-2011.

Objective: The discovery of anti-citrullinated protein antibodies (ACPAs) and the introduction of new therapeutic options have had profound impacts on early rheumatoid arthritis (RA) care. Since ACPA status, most widely assessed as reactivity to cyclic citrullinated peptides (CCPs), influences treatment decisions in early RA, we aimed to determine whether anti-CCP remains a predictor of disease activity and radiographic joint damage in more recent 'real-world' early RA. Method: Two observational early RA cohorts from Sweden enrolled patients in 1996-1999 (TIRA-1, n = 239) and 2006-2009 (TIRA-2, n = 444). Clinical and radiographic data and ongoing treatment were prospectively collected up to 3 years. Two other cohorts served as confirmation cohorts (TRAM-1, with enrolment 1996-2000, n = 249; and TRAM-2, 2006-2011, n = 528). Baseline anti-CCP status was related to disease activity, pharmacotherapy, and radiographic joint damage according to Larsen score. Results: In the TIRA-1 cohort, anti-CCP-positive patients had significantly higher 28-joint Disease Activity Score, swollen joint count, C-reactive protein level, and erythrocyte sedimentation rate during follow-up compared with anti-CCP-negative patients. In TIRA-2, no such differences were found, but baseline anti-CCP positivity was associated with higher 3 year Larsen score (5.4 vs 3.5, p = 0.039). In TRAM-2, anti-CCP also predicted radiographic damage (8.9 vs 6.7, p = 0.027), with no significant differences in disease activity. Conclusion: In the early RA cohorts recruiting patients in 2006-2011, baseline anti-CCP positivity was not associated with disease activity over time, but was associated with increased radiographic damage at follow-up. Hence, close radiographic monitoring is warranted in early anti-CCP-positive RA regardless of disease activity.

Influence of a programme for prevention of early childhood caries on early orthodontic treatment needs.

OBJECTIVES: The aim of this prospective birth cohort study was to evaluate the effect of the programme for prevention (PP) of early childhood caries and the resulting need for orthodontic treatment in 8-year-old German children. MATERIAL AND METHODS: Children who had been enrolled in a caries-risk-related recall system with continuous dental care starting at the time of birth (prevention group, PG) were compared with children of the same birth cohort whose parents decided not to participate in the programme (control group, CG). All children (n = 289) participating in the last PP evaluation at the age of 5 years were invited again and examined by blinded clinicians. Dental caries was scored using the WHO diagnostic criteria expanded to d1-level without radiography. Impressions were taken of children with premature tooth loss to analyse space conditions. RESULTS: Two hundred twenty-seven children (mean age 8.4 ± 0.6 years; 46.7% female) were examined. Children in the PG (n = 127) showed significantly lower caries prevalence and experience (3.1%, 0.4 ± 1.0 d3-4mft) than children in the CG (37.3%, 3.9 ± 3.5 d3-4mft). Orthodontic analysis found a higher prevalence of premature tooth extraction, followed by a greater extent of space loss in the CG (41.0%; 3.3 ± 4.4 mm) vs. PG (7.9%; 0.4 ± 1.9 mm) and an increase in early orthodontic treatment need (KIG P3, IOTN 5). CONCLUSIONS: The PP was an effective approach for preventing caries-related premature tooth loss in children and conserving relevant arch length. CLINICAL RELEVANCE: Children who received continuous dental care starting at the time of birth showed better oral health with less premature loss of deciduous teeth and lower need for orthodontic treatment at the age of 8 years. TRIAL REGISTRATION: German Clinical Trials Register DRKS00003438, https://drks-neu.uniklinik-freiburg.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00003438.