Practitioner characteristics, diagnostic accuracy metrics and discovering-individual with respect to 637 melanomas documented by 27 general practitioners on the Skin Cancer Audit Research Database.

BACKGROUND AND OBJECTIVE: Knowledge of accuracy for melanoma diagnosis and melanoma discovering-individual in primary care is limited. We describe general practitioner (GP) characteristics and analyse defined diagnostic accuracy metrics for GPs in the current study comparing this with a previous study for GPs common to both, and we analyse the individual first discovering each melanoma as a lesion of concern. METHODS: The characteristics and diagnostic accuracy of 27 Australasian GPs documenting 637 melanomas on the Skin Cancer Audit Research Database (SCARD) in 2013 were described and analysed. The number needed to treat (NNT) and percentage of melanomas that were in situ (percentage in situ) were analysed as surrogates for specificity and sensitivity, respectively. The discovering-individual was analysed according to patient age and sex and lesion Breslow thickness. RESULTS: The average NNT and percentage in situ were 5.73% and 65.07%, respectively. For 21 GPs in both a 2008-2010 study and the current study, the NNT was 10.78 and 5.56, respectively (p = 0.0037). A consistent trend of decreasing NNT and increasing percentage in situ through increasingly subspecialised GP categories did not reach statistical significance. NNT trended high at ages and sites for which melanoma was rare. While the patient or family member was more likely to discover thick melanomas and melanomas in patients under 40 years, GPs discovered 73.9% of the melanomas as lesions of concern. CONCLUSIONS: GPs were the discovering-individuals for the majority of melanomas in the current study and their accuracy metrics compared favourably with published figures for dermatologists and GPs.

Characteristics, treatment and outcomes of 589 melanoma patients documented by 27 general practitioners on the Skin Cancer Audit Research Database.

BACKGROUND AND OBJECTIVE: General practitioners manage more melanomas than dermatologists or surgeons in Australia. Previously undescribed, the management and outcomes of melanoma patients treated by multiple Australasian general practitioners are examined. METHODS: The characteristics, management and outcomes of 589 melanoma patients, managed by 27 Australasian general practitioners and documented on the Skin Cancer Audit Research Database (SCARD), were analysed. RESULTS: Most patients (58.9%) were males with mean age at diagnosis of 62.7 years (range 18-96), and most melanomas were in situ or thin-invasive. Patients aged under 40 years had fewer melanomas, but a higher proportion (the majority) were invasive, compared with older patients (P < 0.0001). Most (55.9%) melanomas were diagnosed following elliptical excision biopsy, the rate of unintended involved margins being eightfold higher for shave biopsies. Wide re-excision was performed by the treating general practitioner for most (74.9%) melanomas, with thick melanomas preferentially referred to surgeons. The average Breslow thickness of invasive melanomas re-excised by general practitioners was 0.67 mm compared with 1.99 mm for those referred to other specialists (P < 0.0001). Of 205 patients with invasive melanoma, 14 progressed to metastatic disease, 50% of these being associated with nodular melanoma. Nine patients progressed to melanoma-specific death. The 5-year survival rate for patients with invasive melanoma was 95.2% (95% CI: 91.2-98.5%). CONCLUSIONS: Diagnostic and therapeutic management of a series of melanoma patients by Australasian general practitioners were closely aligned with current guidelines and 5-year survival with respect to invasive melanoma was at least as favourable as national population-based metrics.

Characteristics of 637 melanomas documented by 27 general practitioners on the Skin Cancer Audit Research Database.

BACKGROUND AND OBJECTIVE: Most melanomas (including melanomas in situ), in Australasia, are treated by general practitioners (GPs). Previously undescribed, the characteristics of a series of melanomas treated by multiple GPs are examined. PATIENTS AND METHODS: Six hundred and thirty-seven melanomas treated by 27 Australasian GPs during 2013 and documented on the Skin Cancer Audit Research Database (SCARD) were analysed by anatomical site, subtype, Breslow thickness, diameter, associated naevi and linked adverse outcomes. RESULTS: Most melanomas (59.7%) were on males, mean age at diagnosis being 62.7 years (range 18-96). Most (65.0%) were in situ, with a high incidence of lentiginous melanoma (LM) (38.8%) and 32% were naevus associated. Most LM (86.4%) were in situ, compared to 55% of superficial spreading melanoma (SSM) (P < 0.0001). There was male predominance on the head, neck and trunk and female predominance on extremities. There was no significant association between Breslow thickness and diameter, with small melanomas as likely to be thick as large melanomas, and melanomas ≤3 mm diameter, on average, more likely to be invasive than larger melanomas. There was a positive correlation between age and both melanoma diameter and Breslow thickness. Seven cases progressed to melanoma-specific death: Five nodular melanoma (NM) and two SSM, one of which was thin (Breslow thickness 0.5 mm). CONCLUSIONS: A large series of melanomas treated by Australasian GPs were predominantly in situ, with a high proportion of LM subtype. With implications for GP training, NM linked to death was over-represented and there was a novel finding that older patients had larger diameter melanomas.

Pulmonary Arterial Hypertension.

This article provides an overview of pulmonary arterial hypertension (PAH), beginning with the initial pathologic recognition of pulmonary hypertension more than 100 years ago and progressing to the current diagnostic categorization of PAH. It reviews the epidemiology, pathophysiology, genetics, and modern treatment of PAH. The article discusses several important recent studies that have highlighted the importance of new management strategies, including serial risk assessment and combination pharmacotherapy.

A Stefan problem on an evolving surface.

We formulate a Stefan problem on an evolving hypersurface and study the well posedness of weak solutions given L(1) data. To do this, we first develop function spaces and results to handle equations on evolving surfaces in order to give a natural treatment of the problem. Then, we consider the existence of solutions for L(∞) data; this is done by regularization of the nonlinearity. The regularized problem is solved by a fixed point theorem and then uniform estimates are obtained in order to pass to the limit. By using a duality method, we show continuous dependence, which allows us to extend the results to L(1) data.

Parameter identification problems in the modelling of cell motility.

We present a novel parameter identification algorithm for the estimation of parameters in models of cell motility using imaging data of migrating cells. Two alternative formulations of the objective functional that measures the difference between the computed and observed data are proposed and the parameter identification problem is formulated as a minimisation problem of nonlinear least squares type. A Levenberg-Marquardt based optimisation method is applied to the solution of the minimisation problem and the details of the implementation are discussed. A number of numerical experiments are presented which illustrate the robustness of the algorithm to parameter identification in the presence of large deformations and noisy data and parameter identification in three dimensional models of cell motility. An application to experimental data is also presented in which we seek to identify parameters in a model for the monopolar growth of fission yeast cells using experimental imaging data. Our numerical tests allow us to compare the method with the two different formulations of the objective functional and we conclude that the results with both objective functionals seem to agree.

The association between pulmonary artery enlargement and mortality in an Emergency Department population undergoing computed tomography pulmonary angiography.

Findings of an enlarged pulmonary artery diameter (PAd) and increased pulmonary artery to ascending aorta ratio (PA:AA) on contrast-enhanced computed tomography pulmonary angiography (CTPA) are associated with increased mortality in particular groups of patients with cardiopulmonary disease. However, the frequency and prognostic significance of these incidental findings has not been studied in unselected patients evaluated in the Emergency Department (ED). This study aims to determine the prevalence and associated prognosis of enlarged pulmonary artery measurements in an ED cohort. We measured PA and AA diameters on 990 CTPA studies performed in the ED. An enlarged PA diameter was defined as >27 mm in females and >29 mm in males, while an increased PA:AA was defined as >0.9. Poisson regression was performed to calculate prevalence ratios for relevant comorbidities, and multivariable Cox regression was performed to calculate hazard ratios (HR) for mortality of patients with enlarged pulmonary artery measurements. An enlarged PAd was observed in 27.9% of 990 patients and was more commonly observed in older patients and in patients with obesity or heart failure. Conversely, PA:AA was increased in 34.2% of subjects, and was more common in younger patients and those with peripheral vascular disease or obesity. After controlling for age, sex, and comorbidities, both enlarged PAd (HR 1.29, 95% CI 1.00-1.68, p = 0.05) and PA:AA (HR 1.70, 95% CI 1.31-2.22 p < 0.01) were independently associated with mortality. In sum, enlarged PAd and increased PA:AA are common in patients undergoing CTPAs in the ED setting and both are independently associated with mortality.

Pre-Operative Antibiotic Agents for Facial Fractures: Is More than One Day Necessary?

Background: Despite a paucity of evidence, patients with facial fractures often receive long courses of pre-operative antibiotic agents. This study compared the effect of a short versus long pre-operative antibiotic course on the development of post-operative head/neck infections in this population. Patients and Methods: All adult patients admitted between January 2010 and May 2015 to a level 1 trauma center with isolated head/neck injuries who underwent surgery for facial fracture(s) were included. Patients with infections prior to surgery were excluded. Our primary analysis compared head/neck infections between patients given a short (≤24 hours) versus long (>24 hours) course of pre-operative antibiotic agents. Bivariate analysis and multivariate logistic regression (MLR) were performed to identify risk factors for head/neck infections. Results: This study included 188 patients; median age was 38.5 years, 83% were male, 81% had blunt injuries, 51.6% had fractures in multiple facial thirds, and 48.9% required intensive care unit (ICU) admission. One hundred twenty-five (66.5%) patients received a short course and 63 (33.5%) received a long course of pre-operative antibiotic agents. Head/neck infections were higher in the long course group (28.6% vs 15.2%; p = 0.034), but median days to infection were similar. Factors associated with head/neck infections included penetrating injury, mandible fracture, involvement of multiple facial thirds, ICU admission, operative time, and receiving a long pre-operative antibiotic course. Multivariable logistic regression found mandible fracture (odds ratio [OR], 2.9; p = 0.01) and ICU admission (OR, 3.3; p = 0.003) to be independent predictors of head/neck infections (area under the curve [AUC] = 0.706), but pre-operative antibiotic course was not. Patients with isolated mandible fractures (n = 42) had higher rates of head/neck infections in the long course group (29.4% vs 4.0%; p = 0.032), despite similar demographics. Conclusion: Long (>24 hours) course of continuous pre-operative antibiotic prophylaxis before surgery for facial fractures did not reduce the development of head/neck infections.

Quality of Life and Cost Implications of Pseudarthrosis After Anterior Cervical Discectomy and Fusion and its Subsequent Revision Surgery.

BACKGROUND: More than 120,000 anterior cervical discectomy and fusions (ACDFs) are performed annually. Pseudarthrosis is a potential delayed adverse event that affects up to 33% of patients. The degree to which this adverse event affects both patient quality-of-life (QOL) outcomes and health care costs is poorly understood. METHODS: Patients who underwent revision surgery for pseudarthrosis between 2007 and 2012 were identified and matched to controls not experiencing pseudarthrosis in a 1:2 fashion (case/control). Cases and controls were compared regarding total health care costs incurred in the year after the index ACDF and QOL outcomes on the following metrics: EuroQol Five-Dimensions Questionnaire, Patient Health Questionnaire-9, and Pain Disability Questionnaire. RESULTS: Of 738 patients who underwent ACDF, 11 underwent surgery for pseudarthrosis. No differences were noted between cases and controls regarding any of the matched variables. Patients in the pseudarthrosis cohort had poorer postoperative scores on the EuroQol Five-Dimensions Questionnaire mobility, usual activities, pain/discomfort, and quality-adjusted life-year dimensions. In addition, 64% of patients with pseudarthrosis had worsened quality-adjusted life-year scores compared with only 9% of controls (P < 0.01). Patients with pseudarthrosis also had poorer mental health (P < 0.01) and pain disability outcomes (P < 0.01) than did controls. Pseudarthrosis was associated with significant increases in direct costs, direct postoperative costs, and total costs (all P < 0.01). CONCLUSIONS: This is the first study to characterize the effect of surgical revision for pseudarthrosis on both QOL outcomes and care costs after ACDF. Patients requiring revision experienced significantly poorer QOL outcomes and higher care costs relative to controls.

Facing the facts on prophylactic antibiotics for facial fractures: 1 day or less.

BACKGROUND: To evaluate the role of initial prophylactic antibiotics on facial fractures, outcomes were compared between a short course (≤24 hours) of antibiotics to those who received an extended course (>24 hours). METHODS: Adults admitted (2010-2015) to a Level I trauma center intensive care unit with at least one facial bone fracture and major injuries isolated to the head and neck were included. Our primary analysis compared infectious complications of the head or neck (H/N infection) between patients given short or extended courses of antibiotic prophylaxis. Multivariate logistic regression and analysis of propensity score matched pairs were performed. RESULTS: A total of 403 patients were included, 85.6% had blunt injuries and 72.7% had their facial fracture managed nonoperatively. The H/N infection rate was 11.2%. Two hundred eighty patients received a short course of antibiotics and 123 patients received an extended course. Median Injury Severity Score was 14 in both groups (p = 0.78). Patients receiving an extended course of antibiotics had higher rates of H/N infection (20.3% vs. 7.1%, p < 0.001). Factors associated with development of H/N infection included younger age, penetrating injury, open fracture, upper face or mandible fracture, fractures in multiple facial thirds, vascular injury, hypertension, and extended antibiotic course. Multivariate logistic regression identified younger age (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.96-1.00; p = 0.02), multiple facial third fractures (OR, 4.9; 95% CI, 2.4-10.2; p < 0.001), and penetrating mechanism (OR, 3.1; 95% CI, 1.5-6.4; p = 0.003) as independent predictors of H/N infection, but not antibiotic duration. Propensity score-matched analysis found no differences in H/N infection between short and extended antibiotic courses (11.4% vs. 12.5%; p = 1.0). Subgroup analyses demonstrated no differences in H/N infection between short or extended antibiotic courses by injury pattern, mechanism, or treatment (operative or nonoperative). CONCLUSION: These results lead us to believe that we should limit antibiotics to 24 hours or less upon admission for facial fractures. LEVEL OF EVIDENCE: Therapeutic/care management, level IV.

Pulmonary Capillary Hemangiomatosis and Pulmonary Veno-occlusive Disease.

This article provides an overview of pulmonary veno-occlusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH), two disorders that challenge clinicians, radiologists, and pathologists because they often mimic pulmonary arterial hypertension (PAH). The article reviews the features that differentiate PVOD and PCH from PAH. The article also describes the overlap of PVOD and PCH, highlighted by recent reports of families diagnosed with PVOD or PCH caused by EIF2AK4 mutations. In addition, the article outlines current approaches to the diagnosis and treatment of PVOD and PCH.

A comparative study of cognitive behavior therapy versus general anesthesia for painful medical procedures in children.

A treatment outcome study was conducted to compare the efficacy of cognitive behavior therapy (CBT) versus general anesthesia in alleviating the distress of 18 pediatric cancer patients (ages: 3-12 years) undergoing bone marrow aspirations (BMAs). CBT and short-acting mask anesthesia were delivered within a repeated-measures counterbalance design. Results indicated that children exhibited more behavioral distress in the CBT condition for the 1st minute lying down on the treatment table. However, parents rated significantly more behavioral adjustment symptoms 24 h following the BMA when their children had received anesthesia. No differences were found in childrens' and parents' preference for CBT versus anesthesia.

Modelling cell motility and chemotaxis with evolving surface finite elements.

We present a mathematical and a computational framework for the modelling of cell motility. The cell membrane is represented by an evolving surface, with the movement of the cell determined by the interaction of various forces that act normal to the surface. We consider external forces such as those that may arise owing to inhomogeneities in the medium and a pressure that constrains the enclosed volume, as well as internal forces that arise from the reaction of the cells' surface to stretching and bending. We also consider a protrusive force associated with a reaction-diffusion system (RDS) posed on the cell membrane, with cell polarization modelled by this surface RDS. The computational method is based on an evolving surface finite-element method. The general method can account for the large deformations that arise in cell motility and allows the simulation of cell migration in three dimensions. We illustrate applications of the proposed modelling framework and numerical method by reporting on numerical simulations of a model for eukaryotic chemotaxis and a model for the persistent movement of keratocytes in two and three space dimensions. Movies of the simulated cells can be obtained from http://homepages.warwick.ac.uk/∼maskae/CV_Warwick/Chemotaxis.html.