Clinical consequences of antibody formation, serum concentrations, and HLA-Cw6 status in psoriasis patients on Ustekinumab

Background: Ustekinumab for the treatment of psoriasis is currently administered in a standard dosing regimen. However, some patients tend to benefit from alternative dosing regimens, a step toward personalized medicine. Methods: To investigate the role of ustekinumab serum concentrations, anti-ustekinumab antibodies [AUA] and HLA-Cw6 status as tools for optimizing ustekinumab treatment, a multicenter prospective cohort study was conducted at an academic hospital with affiliated nonacademic hospitals in Belgium (cohort 1) and 2 academic hospitals in the Netherlands (cohort 2 and 3). Patients with plaque-type psoriasis were eligible if treated with ustekinumab for >16 weeks. Serum samples and Psoriasis Area and Severity Index scores were obtained at baseline, week 16, 28, 40, 52, and/or >64 of ustekinumab treatment. Results: A total of 137 patients with 229 observations for serum concentrations and AUA and 61 observations for HLA-Cw6 status were included. Presence of AUA (prevalence of 8.7%) was significantly associated with a diminished clinical response (P = 0.032). The median ustekinumab trough concentration was 0.3 mcg/mL (<0.02-3.80). No differences in serum concentrations were observed between moderate to good responders and nonresponders (P = 0.948). Serum trough concentrations were not affected by methotrexate comedication. Prevalence of HLA-Cw6 positivity was 41% with no statistically significant difference in clinical response between HLA-Cw6-positive and HLA-Cw6-negative patients (P = 0.164). Conclusions: The presence of AUA was associated with treatment failure in this patient population; measurement of AUA may therefore be a candidate marker for personalized pharmacotherapy. The clinical utility of ustekinumab serum trough concentrations or HLA-Cw6 status determination remains less clear. Further exploration on the potential of measuring ustekinumab serum concentrations and other biomarkers in predicting therapy outcomes should be encouraged

Value of dermoscopy in a population-based screening sample by dermatologists

Background: The use of dermoscopy improves the diagnosis of skin cancer significantly in trained dermatologists. However, to evaluate its cost-effectiveness in daily practice, not only sensitivity but also the excision rate is important. Objective: We examined the diagnostic accuracy of cases from a true population-based sample scored by general dermatologists. Methods: One hundred twenty-six dermatologists were randomly assigned to 145 digital cases of lesions detected at a skin cancer screening. This resulted in 4,655 case evaluations using a web application. Accuracy of diagnosis and treatment was correlated with the histological diagnosis or expert opinion. Results: The larger portion (89.7%) of the participating dermatologists reported using their dermatoscope daily. The odds of making a correct diagnosis of melanoma using dermoscopy was 5.38 compared with naked-eye examination (NEE). Dermoscopy increased sensitivity for skin cancer diagnosis from 70.6% to 84.6%, but this was associated with a small but significant decrease in specificity of 3.5%. To detect 1 skin cancer, 5.23 lesions had to be biopsied/excised in this sample and this was not significantly improved by dermoscopic evaluation. Dermoscopy significantly increased the confidence about making a correct diagnosis, especially in seborrheic keratosis, Bowen disease, and melanoma. Conclusions: Dermoscopy significantly improved diagnostic accuracy, the sensitivity of skin cancer detection, and the confidence in diagnosis especially for seborrheic keratosis, Bowen disease, and melanoma. However, this finding was not reflected in a significant reduction in the number needed to excise in this sample

A qualitative interpretation of challenges associated with helping patients with multiple chronic diseases identify their goals

Background Patients with multiple chronic diseases are usually treated according to disease-specific guidelines, with outcome measurements focusing mostly on biomedical indicators (e.g. blood sugar levels or lung function). However, for multimorbidity, a goal-oriented approach focusing on the goals defined by the individual patient, may be more suitable. Despite the clear theoretical and conceptual advantages of including patient-defined goals in clinical decision-making for multimorbidity, it is not clear how patients define their goals and which aspects play a role in the process of defining them. Objective To explore goal-setting in patients with multimorbidity. Design Qualitative analysis of interviews with 19 patients diagnosed with chronic obstructive pulmonary disease and comorbidities. Results Patients do not naturally present their goals. Their goals are difficult to elicit, even when different interviewing techniques are used. Four underlying hypotheses which may explain this finding were identified from the interviews: (1) patients cannot identify with the concept of goal-setting; (2) goal-setting is reduced due to acceptation; (3) actual stressors predominate over personal goal-setting; and (4) patients may consider personal goals as selfish. Conclusions Our findings advocate for specific attention to provider skills and strategies that help patients identify their personal goals. The hypotheses on why patients may struggle with defining goals may be useful to prompt patients in this process and support the development of a clinical method for goal-oriented care

Comparison of ex vivo and in vivo dermoscopy in dermatopathologic evaluation of skin tumors

IMPORTANCE: Ex vivo dermoscopy (EVD) can be a valuable tool in routine diagnostic dermatopathologic evaluation. OBJECTIVES: To compare in vivo dermoscopy (IVD) and EVD and to provide guidance for routine dermatopathologic evaluations. DESIGN, SETTING, AND PARTICIPANTS: This observational study collected 101 consecutive IVD and EVD images of skin tumors from a private dermatology practice from March 1 to September 30, 2013. Four observers (3 dermatologists and 1 dermatopathologist) blinded to the histopathologic diagnoses independently scored and compared the colors, structures, and vessels of EVD images with those of the corresponding IVD images. Data were analyzed from January 1 to March 31, 2014. MAIN OUTCOMES AND MEASURES: Concordance between the EVD and IVD images and gain or loss of colors, structures, and vessels on EVD relative to IVD images. RESULTS: The final analysis included 404 observations of 101 images. The EVD image was generally similar to the corresponding IVD image but clearly darker, with new areas of blue in 130 of 404 observations (32.2%) and white in 100 of 404 observations (24.8%) and loss of red in 283 of 404 observations (70.0%). Most structures were well preserved. New structureless areas were found in 78 of 404 observations of EVD images (19.3%), and new crystalline structures were detected in 68 of 404 observations of EVD images (16.8%). On EVD images, squames and crusts were lost in 56 of 404 observations (13.9%) and 43 of 404 observations (10.6%), respectively. Blood vessels were lost in 142 of 404 observations of EVD images (35.1%). CONCLUSIONS AND RELEVANCE: The EVD image is an important new tool in dermatopathology and may give direction to targeted tissue processing and examination of skin tumors

Method For Making 2-Electron Response Reduced Density Matrices Approximately N-representable

In methods like geminal-based approaches or coupled cluster that are solved using the projected Schr\"odinger equation, direct computation of the 2-electron reduced density matrix (2-RDM) is impractical and one falls back to a 2-RDM based on response theory. However, the 2-RDMs from response theory are not $N$-representable. That is, the response 2-RDM does not correspond to an actual physical $N$-electron wave function. We present a new algorithm for making these non-$N$-representable 2-RDMs approximately $N$-representable, i.e. it has the right symmetry and normalization and it fulfills the $P$-, $Q$- and $G$-conditions. Next to an algorithm which can be applied to any 2-RDM, we have also developed a 2-RDM optimization procedure specifically for seniority-zero 2-RDMs. We aim to find the 2-RDM with the right properties that is the closest (in the sense of the Frobenius norm) to the non-N-representable 2-RDM by minimizing the square norm of the difference between the initial 2-RDM and the targeted 2-RDM under the constraint that the trace is normalized and the 2-RDM, $Q$- and $G$-matrices are positive semidefinite, i.e. their eigenvalues are non-negative. Our method is suitable for fixing non-N-respresentable 2-RDMs which are close to being N-representable. Through the N-representability optimization algorithm we add a small correction to the initial 2-RDM such that it fulfills the most important N-representability conditions.Comment: 13 pages, 8 figure

Home blood-pressure monitoring in a hypertensive pregnant population.

OBJECTIVE: The majority of patients with chronic or gestational hypertension do not develop pre-eclampsia. Home blood-pressure monitoring (HBPM) has the potential to offer a more accurate and acceptable means of monitoring hypertensive patients during pregnancy compared with traditional pathways of frequent outpatient monitoring. The aim of this study was to determine whether HBPM reduces visits to antenatal services and is safe in pregnancy. METHODS: This was a case-control study of 166 hypertensive pregnant women, which took place at St George's Hospital, University of London. Inclusion criteria were: chronic hypertension, gestational hypertension or high risk of developing pre-eclampsia, no significant proteinuria (≤ 1+ proteinuria on dipstick testing) and normal biochemical and hematological markers. Exclusion criteria were maternal age  155 mmHg or diastolic blood pressure > 100 mmHg, significant proteinuria (≥ 2+ proteinuria on dipstick testing or protein/creatinine ratio > 30 mg/mmol), evidence of small-for-gestational age (estimated fetal weight < 10th centile), signs of severe pre-eclampsia, significant mental health concerns or insufficient understanding of the English language. Pregnant women in the HBPM group were taught how to measure and record their blood pressure using a validated machine at home and attended every 1-2 weeks for assessment depending on clinical need. The control group was managed as per the local protocol prior to the implementation of HBPM. The two groups were compared with respect to number of visits to antenatal services and outcome. RESULTS: There were 108 women in the HBPM group and 58 in the control group. There was no difference in maternal age, parity, body mass index, ethnicity or smoking status between the groups, but there were more women with chronic hypertension in the HBPM group compared with the control group (49.1% vs 25.9%, P = 0.004). The HBPM group had significantly fewer outpatient attendances per patient (6.5 vs 8.0, P = 0.003) and this difference persisted when taking into account differences in duration of monitoring (0.8 vs 1.6 attendances per week, P < 0.001). There was no difference in the incidence of adverse maternal, fetal or neonatal outcome between the two groups. CONCLUSION: HBPM in hypertensive pregnancies has the potential to reduce the number of hospital visits required by patients without compromising maternal and pregnancy outcomes. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd

Impact of bias correction on climate change signals over central Europe and the Iberian Peninsula

Gefördert durch den Publikationsfonds der Universität Kasse