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Παρασκευή 15 Δεκεμβρίου 2017

Taking Multiple Exposure Into Account Can Improve Assessment of Chemical Risks

Abstract
During work, operators may be exposed to several chemicals simultaneously. Most exposure assessment approaches only determine exposure levels for each substance individually. However, such individual-substance approaches may not correctly estimate the toxicity of 'cocktails' of chemicals, as the toxicity of a cocktail may differ from the toxicity of substances on their own. This study presents an approach that can better take into account multiple exposure when assessing chemical risks. Almost 30000 work situations, monitored between 2005 and 2014 and recorded in two French databases, were analysed using MiXie software. The algorithms employed in MiXie can identify toxicological classes associated with several substances, based on the additivity of the selected effects of each substance. The results of our retrospective analysis show that MiXie was able to identify almost 20% more potentially hazardous situations than identified using a single-substance approach. It therefore appears essential to review the ways in which multiple exposure is taken into account during risk assessment.

Respiratory Symptoms in Hospital Cleaning Staff Exposed to a Product Containing Hydrogen Peroxide, Peracetic Acid, and Acetic Acid

Abstract
Cleaning and disinfecting products consisting of a mixture of hydrogen peroxide (HP), peracetic acid (PAA), and acetic acid (AA) are widely used as sporicidal agents in health care, childcare, agricultural, food service, and food production industries. HP and PAA are strong oxidants and their mixture is a recognized asthmagen. However, few exposure assessment studies to date have measured HP, PAA, and AA in a health care setting. In 2015, we performed a health and exposure assessment at a hospital where a new sporicidal product, consisting of HP, PAA, and AA was introduced 16 months prior. We collected 49 full-shift time-weighted average (TWA) air samples and analyzed samples for HP, AA, and PAA content. Study participants were observed while they performed cleaning duties, and duration and frequency of cleaning product use was recorded. Acute upper airway, eye, and lower airway symptoms were recorded in a post-shift survey (n = 50). A subset of 35 cleaning staff also completed an extended questionnaire that assessed symptoms reported by workers as regularly occurring or as having occurred in the previous 12 months. Air samples for HP (range: 5.5 to 511.4 ppb) and AA (range: 6.7 to 530.3 ppb) were all below established US occupational exposure limits (OEL). To date, no full-shift TWA OEL for PAA has been established in the United States, however an OEL of 0.2 ppm has been suggested by several research groups. Air samples for PAA ranged from 1.1 to 48.0 ppb and were well below the suggested OEL of 0.2 ppm. Hospital cleaning staff using a sporicidal product containing HP, PAA, and AA reported work-shift eye (44%), upper airway (58%), and lower airway (34%) symptoms. Acute nasal and eye irritation were significantly positively associated with increased exposure to the mixture of the two oxidants: HP and PAA, as well as the total mixture (TM)of HP, PAA, and AA. Shortness of breath when hurrying on level ground or walking up a slight hill was significantly associated with increased exposure to the oxidant mixture (P = 0.017), as well as the TM (P = 0.026). Our results suggest that exposure to a product containing HP, PAA, and AA contributed to eye and respiratory symptoms reported by hospital cleaning staff at low levels of measured exposure.

Job Tasks as Determinants of Thoracic Aerosol Exposure in the Cement Production Industry

Abstract
Background
The aims of this study were to identify important determinants and investigate the variance components of thoracic aerosol exposure for the workers in the production departments of European cement plants.
Methods
Personal thoracic aerosol measurements and questionnaire information (Notø et al., 2015) were the basis for this study. Determinants categorized in three levels were selected to describe the exposure relationships separately for the job types production, cleaning, maintenance, foreman, administration, laboratory, and other jobs by linear mixed models. The influence of plant and job determinants on variance components were explored separately and also combined in full models (plant&job) against models with no determinants (null). The best mixed models (best) describing the exposure for each job type were selected by the lowest Akaike information criterion (AIC; Akaike, 1974) after running all possible combination of the determinants.
Results
Tasks that significantly increased the thoracic aerosol exposure above the mean level for production workers were: packing and shipping, raw meal, cement and filter cleaning, and de-clogging of the cyclones. For maintenance workers, time spent with welding and dismantling before repair work increased the exposure while time with electrical maintenance and oiling decreased the exposure. Administration work decreased the exposure among foremen. A subjective tidiness factor scored by the research team explained up to a 3-fold (cleaners) variation in thoracic aerosol levels. Within-worker (WW) variance contained a major part of the total variance (35–58%) for all job types. Job determinants had little influence on the WW variance (0–4% reduction), some influence on the between-plant (BP) variance (from 5% to 39% reduction for production, maintenance, and other jobs respectively but an 79% increase for foremen) and a substantial influence on the between-worker within-plant variance (30–96% for production, foremen, and other workers). Plant determinants had little influence on the WW variance (0–2% reduction), some influence on the between-worker variance (0–1% reduction and 8% increase), and considerable influence on the BP variance (36–58% reduction) compared to the null models.
Conclusion
Some job tasks contribute to low levels of thoracic aerosol exposure and others to higher exposure among cement plant workers. Thus, job task may predict exposure in this industry. Dust control measures in the packing and shipping departments and in the areas of raw meal and cement handling could contribute substantially to reduce the exposure levels. Rotation between low and higher exposed tasks may contribute to equalize the exposure levels between high and low exposed workers as a temporary solution before more permanent dust reduction measures is implemented. A tidy plant may reduce the overall exposure for almost all workers no matter of job type.

ART, Stoffenmanager, and TRA: A Systematic Comparison of Exposure Estimates Using the TREXMO Translation System

Abstract
Several occupational exposure models are recommended under the EU's REACH legislation. Due to limited availability of high-quality exposure data, their validation is an ongoing process. It was shown, however, that different models may calculate significantly different estimates and thus lead to potentially dangerous conclusions about chemical risk. In this paper, the between-model translation rules defined in TREXMO were used to generate 319000 different in silico exposure situations in ART, Stoffenmanager, and ECETOC TRA v3. The three models' estimates were computed and the correlation and consistency between them were investigated. The best correlated pair was Stoffenmanager–ART (R, 0.52–0.90), whereas the ART–TRA and Stoffenmanager–TRA correlations were either lower (R, 0.36–0.69) or no correlation was found. Consistency varied significantly according to different exposure types (e.g. vapour versus dust) or settings (near-field versus far-field and indoors versus outdoors). The percentages of generated situations for which estimates differed by more than a factor of 100 ranged from 14 to 97%, 37 to 99%, and 1 to 68% for Stoffenmanager–ART, TRA–ART, and TRA–Stoffenmanager, respectively. Overall, the models were more consistent for vapours than for dusts and solids, near-fields than for far-fields, and indoor than for outdoor exposure. Multiple linear regression analyses evidenced the relationship between the models' parameters and the relative differences between the models' predictions. The relative difference can be used to estimate the consistency between the models. Furthermore, the study showed that the tiered approach is not generally applicable to all exposure situations. These findings emphasize the need for a multiple-model approach to assessing critical exposure scenarios under REACH. Moreover, in combination with occupational exposure measurements, they might also be used for future studies to improve prediction accuracy.

Efficacy and Safety of Ethanol Ablation for Branchial Cleft Cysts [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

Branchial cleft cyst is a common congenital lesion of the neck. This study evaluated the efficacy and safety of ethanol ablation as an alternative treatment to surgery for branchial cleft cyst.

MATERIALS AND METHODS:

Between September 2006 and October 2016, ethanol ablation was performed in 22 patients who refused an operation for a second branchial cleft cyst. After the exclusion of 2 patients who were lost to follow-up, the data of 20 patients were retrospectively evaluated. All index masses were confirmed as benign before treatment. Sonography-guided aspiration of the cystic fluid was followed by injection of absolute ethanol (99%) into the lesion. The injected volume of ethanol was 50%–80% of the volume of fluid aspirated. Therapeutic outcome, including the volume reduction ratio, therapeutic success rate (volume reduction ratio of >50% and/or no palpable mass), and complications, was evaluated.

RESULTS:

The mean index volume of the cysts was 26.4 ± 15.7 mL (range, 3.8–49.9 mL). After ablation, the mean volume of the cysts decreased to 1.2 ± 1.1 mL (range, 0.0–3.5 mL). The mean volume reduction ratio at last follow-up was 93.9% ± 7.9% (range, 75.5%–100.0%; P < .001). Therapeutic success was achieved in all nodules (20/20, 100%), and the symptomatic (P < .001) and cosmetic (P < .001) scores had improved significantly by the last follow-up. In 1 patient, intracystic hemorrhage developed during the aspiration; however, no major complications occurred in any patient.

CONCLUSIONS:

Ethanol ablation is an effective and safe treatment for patients with branchial cleft cysts who refuse, or are ineligible for, an operation.



Hemodynamic Characteristics of Ruptured and Unruptured Multiple Aneurysms at Mirror and Ipsilateral Locations [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

Different hemodynamic patterns have been associated with aneurysm rupture. The objective was to test whether hemodynamic characteristics of the ruptured aneurysm in patients with multiple aneurysms were different from those in unruptured aneurysms in the same patient.

MATERIALS AND METHODS:

Twenty-four mirror and 58 ipsilateral multiple aneurysms with 1 ruptured and the others unruptured were studied. Computational fluid dynamics models were created from 3D angiographies. Case-control studies of mirror and ipsilateral aneurysms were performed with paired Wilcoxon tests.

RESULTS:

In mirror pairs, the ruptured aneurysm had more oscillatory wall shear stress (P = .007) than the unruptured one and tended to be more elongated (higher aspect ratio), though this trend achieved only marginal significance (P = .03, 1-sided test). In ipsilateral aneurysms, ruptured aneurysms had larger maximum wall shear (P = .05), more concentrated (P < .001) and oscillatory wall shear stress (P < .001), stronger (P < .001) and more concentrated inflow jets (P < .001), larger maximum velocity (P < .001), and more complex flow patterns (P < .001) compared with unruptured aneurysms. Additionally, ruptured aneurysms were larger (P < .001) and more elongated (P < .001) and had wider necks (P < .001) and lower minimum wall shear stress (P < .001) than unruptured aneurysms.

CONCLUSIONS:

High wall shear stress oscillations and larger aspect ratios are associated with rupture in mirror aneurysms. Adverse flow conditions characterized by high and concentrated inflow jets; high, concentrated, and oscillatory wall shear stress; and strong, complex and unstable flow patterns are associated with rupture in ipsilateral multiple aneurysms. In multiple ipsilateral aneurysms, these unfavorable flow conditions are more likely to develop in larger, more elongated, more wide-necked, and more distal aneurysms.



Regarding "Perfusion MR Imaging Using a 3D Pulsed Continuous Arterial Spin-Labeling Method for Acute Cerebral Infarction Classified as Branch Atheromatous Disease Involving the Lenticulostriate Artery Territory" [LETTERS]



Zika Virus Iceberg: Very Large [LETTERS]



Reply: [LETTERS]



Preoperative Cerebral Oxygen Extraction Fraction Imaging Generated from 7T MR Quantitative Susceptibility Mapping Predicts Development of Cerebral Hyperperfusion following Carotid Endarterectomy [ADULT BRAIN]

BACKGROUND AND PURPOSE:

Preoperative hemodynamic impairment in the affected cerebral hemisphere is associated with the development of cerebral hyperperfusion following carotid endarterectomy. Cerebral oxygen extraction fraction images generated from 7T MR quantitative susceptibility mapping correlate with oxygen extraction fraction images on positron-emission tomography. The present study aimed to determine whether preoperative oxygen extraction fraction imaging generated from 7T MR quantitative susceptibility mapping could identify patients at risk for cerebral hyperperfusion following carotid endarterectomy.

MATERIALS AND METHODS:

Seventy-seven patients with unilateral internal carotid artery stenosis (≥70%) underwent preoperative 3D T2*-weighted imaging using a multiple dipole-inversion algorithm with a 7T MR imager. Quantitative susceptibility mapping images were then obtained, and oxygen extraction fraction maps were generated. Quantitative brain perfusion single-photon emission CT was also performed before and immediately after carotid endarterectomy. ROIs were automatically placed in the bilateral middle cerebral artery territories in all images using a 3D stereotactic ROI template, and affected-to-contralateral ratios in the ROIs were calculated on quantitative susceptibility mapping–oxygen extraction fraction images.

RESULTS:

Ten patients (13%) showed post-carotid endarterectomy hyperperfusion (cerebral blood flow increases of ≥100% compared with preoperative values in the ROIs on brain perfusion SPECT). Multivariate analysis showed that a high quantitative susceptibility mapping–oxygen extraction fraction ratio was significantly associated with the development of post-carotid endarterectomy hyperperfusion (95% confidence interval, 33.5–249.7; P = .002). Sensitivity, specificity, and positive- and negative-predictive values of the quantitative susceptibility mapping–oxygen extraction fraction ratio for the prediction of the development of post-carotid endarterectomy hyperperfusion were 90%, 84%, 45%, and 98%, respectively.

CONCLUSIONS:

Preoperative oxygen extraction fraction imaging generated from 7T MR quantitative susceptibility mapping identifies patients at risk for cerebral hyperperfusion following carotid endarterectomy.



Regarding "Determining the Orientation of Directional Deep Brain Stimulation Electrodes Using 3D Rotational Fluoroscopy" [LETTERS]



Basion-Cartilaginous Dens Interval: An Imaging Parameter for Craniovertebral Junction Assessment in Children [PEDIATRICS]

BACKGROUND AND PURPOSE:

Widening of the basion-dens interval is an important sign of cranioverterbral junction injury. The current literature on basion-dens interval in children is sparse and based on bony measurements with variable values. Our goal was to establish the normal values of a recently described new imaging parameter, the basion–cartilaginous dens interval in children.

MATERIALS AND METHODS:

Three hundred healthy pediatric patients (0–10 years of age) were selected retrospectively. These patients were divided into 3 different groups: A (0–3 years), B (3–6 years), and C (6–10 years). The basion–cartilaginous dens interval was calculated on the sagittal MPR image of cervical spine CT in a soft-tissue window. The mean, SD, and the upper limit of normal (mean +2 SDs) of the 3 groups were calculated, and statistical tests were used to check for significant differences of the basion–cartilaginous dens interval among these 3 groups.

RESULTS:

The upper limits of the basion–cartilaginous dens interval for the 3 groups were 5.34 mm in group A, 5.64 mm in group B, and 7.24 mm in group C. There were statistically significant differences in the basion–cartilaginous dens interval values among the 3 groups. There was no statistically significant difference in basion–cartilaginous dens interval values between groups A and B; however, values in group C were significantly different from those in both A and B. There was no statistically significant difference in the basion–cartilaginous dens interval values between males and females.

CONCLUSIONS:

The basion–cartilaginous dens interval is a novel imaging parameter to assess cranioverterbral junction integrity in children, which includes the nonossified cartilage in the measurement.



Reply: [LETTERS]



Treatment of Middle Cerebral Artery Aneurysms with Flow-Diverter Stents: A Systematic Review and Meta-Analysis [INTERVENTIONAL]

BACKGROUND:

The safety and efficacy of flow-diversion treatment of MCA aneurysms have not been well-established.

PURPOSE:

Our aim was to evaluate angiographic and clinical outcomes after flow diversions for MCA aneurysms.

DATA SOURCES:

A systematic search of PubMed, MEDLINE, and Embase was performed for studies published from 2008 to May 2017.

STUDY SELECTION:

According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we selected studies with >5 patients describing angiographic and clinical outcomes after flow-diversion treatment of MCA aneurysms.

DATA ANALYSIS:

Random-effects meta-analysis was used to pool the following outcomes: aneurysm occlusion rate, procedure-related complications, rupture rate of treated aneurysms, and occlusion of the jailed branches.

DATA SYNTHESIS:

Twelve studies evaluating 244 MCA aneurysms were included in this meta-analysis. Complete/near-complete occlusion was obtained in 78.7% (95% CI, 67.8%–89.7%) of aneurysms. The rupture rate of treated aneurysms during follow-up was 0.4% per aneurysm-year. The rate of treatment-related complications was 20.7% (95% CI, 14%–27.5%), and approximately 10% of complications were permanent. The mortality rate was close to 2%. Nearly 10% (95% CI, 4.7%–15.5%) of jailed arteries were occluded during follow-up, whereas 26% (95% CI, 14.4%–37.6%) had slow flow. Rates of symptoms related to occlusion and slow flow were close to 5%.

LIMITATIONS:

Small and retrospective series could affect the strength of the reported results.

CONCLUSIONS:

Given the not negligible rate of treatment-related complications, flow diversion for MCA aneurysms should be considered an alternative treatment when traditional treatment methods are not feasible. However, when performed in this select treatment group, high rates of aneurysm occlusion and protection against re-rupture can be achieved.



Safety and Efficacy of Aneurysm Treatment with the WEB [LETTERS]



Pial Artery Supply as an Anatomic Risk Factor for Ischemic Stroke in the Treatment of Intracranial Dural Arteriovenous Fistulas [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

Although intracranial dural arteriovenous fistulas are principally supplied by dural branches of the external carotid, internal carotid, and vertebral arteries, they can also be fed by pial arteries that supply the brain. We sought to determine the frequency of neurologic deficits following treatment of intracranial dural arteriovenous fistulas with and without pial artery supply.

MATERIALS AND METHODS:

One hundred twenty-two consecutive patients who underwent treatment for intracranial dural arteriovenous fistulas at our hospital from 2008 to 2015 were retrospectively reviewed. Patient data were examined for posttreatment neurologic deficits; patients with such deficits were evaluated for imaging evidence of cerebral infarction. Data were analyzed with multivariable logistic regression.

RESULTS:

Of 122 treated patients, 29 (23.8%) had dural arteriovenous fistulas with pial artery supply and 93 (76.2%) had dural arteriovenous fistulas without pial arterial supply. Of patients with pial artery supply, 4 (13.8%) had posttreatment neurologic deficits, compared with 2 patients (2.2%) without pial artery supply (P = .04). Imaging confirmed that 3 patients with pial artery supply (10.3%) had cerebral infarcts, compared with only 1 patient without pial artery supply (1.1%, P = .03). Increasing patient age was also positively associated with pial supply and treatment-related complications.

CONCLUSIONS:

Patients with dural arteriovenous fistulas supplied by the pial arteries were more likely to experience posttreatment complications, including ischemic strokes, than patients with no pial artery supply. The approach to dural arteriovenous fistula treatment should be made on a case-by-case basis so that the risk of complications can be minimized.



Reply: [LETTERS]



CT Texture Analysis: Defining and Integrating New Biomarkers for Advanced Oncologic Imaging in Precision Medicine: A Comment on "CT Texture Analysis Potentially Predicts Local Failure in Head and Neck Squamous Cell Carcinoma Treated with Chemoradiotherapy" [article-commentary]



[other]



Quantitative Synthetic MRI in Children: Normative Intracranial Tissue Segmentation Values during Development [PEDIATRICS]

BACKGROUND AND PURPOSE:

Synthetic MR imaging is a new technique to create absolute R1 relaxivity (1/T1), R2 relaxivity (1/T2), and proton-density maps using a single multiple-spin-echo saturation recovery sequence. These relaxivity maps allow rapid automated intracranial segmentation of tissue types. To assess its utility in children, we created a normative data base of intracranial volume and brain parenchymal, GM, WM, CSF, and myelin volumes in a pediatric population with normal brain MRI findings using synthetic MR imaging.

MATERIALS AND METHODS:

All multiple-spin-echo saturation recovery sequences containing brain MR imaging examinations performed during 34 months were retrospectively reviewed. Abnormal examination findings were excluded following a detailed radiographic and clinical chart review. The remaining normal examination findings were then quantitatively analyzed with synthetic MR imaging. Intracranial, brain parenchymal, GM, WM, CSF, and myelin volumes were plotted versus age. Qualitative assessment of segmentation accuracy was performed. Selected abnormal examination findings were compared with these normative curves.

RESULTS:

One hundred twenty-two MRI examinations with normal findings were included of individuals ranging from 0.1 to 21.5 years of age (median, 11.8 years). Resulting normative data plots compared favorably with previously published data obtained using more onerous techniques. Differentiation from pathologic states was possible using quantitative values in select cases.

CONCLUSIONS:

A pediatric data base of normal intracranial tissue volumes using a single sequence and rapid software analysis has been compiled and correlates with previously published data. This provides a framework for clinical interpretation of quantitative synthetic MR images during development. Improved age-based segmentation algorithms in young children are needed.



Bring Back the Joy in Neuroradiology [editorial]



Predictive Models in Differentiating Vertebral Lesions Using Multiparametric MRI [SPINE]

BACKGROUND AND PURPOSE:

Conventional MR imaging has high sensitivity but limited specificity in differentiating various vertebral lesions. We aimed to assess the ability of multiparametric MR imaging in differentiating spinal vertebral lesions and to develop statistical models for predicting the probability of malignant vertebral lesions.

MATERIALS AND METHODS:

One hundred twenty-six consecutive patients underwent multiparametric MRI (conventional MR imaging, diffusion-weighted MR imaging, and in-phase/opposed-phase imaging) for vertebral lesions. Vertebral lesions were divided into 3 subgroups: infectious, noninfectious benign, and malignant. The cutoffs for apparent diffusion coefficient (expressed as 10–3 mm2/s) and signal intensity ratio values were calculated, and 3 predictive models were established for differentiating these subgroups.

RESULTS:

Of the lesions of the 126 patients, 62 were infectious, 22 were noninfectious benign, and 42 were malignant. The mean ADC was 1.23 ± 0.16 for infectious, 1.41 ± 0.31 for noninfectious benign, and 1.01 ± 0.22 mm2/s for malignant lesions. The mean signal intensity ratio was 0.80 ± 0.13 for infectious, 0.75 ± 0.19 for noninfectious benign, and 0.98 ± 0.11 for the malignant group. The combination of ADC and signal intensity ratio showed strong discriminatory ability to differentiate lesion type. We found an area under the curve of 0.92 for the predictive model in differentiating infectious from malignant lesions and an area under the curve of 0.91 for the predictive model in differentiating noninfectious benign from malignant lesions. On the basis of the mean ADC and signal intensity ratio, we established automated statistical models that would be helpful in differentiating vertebral lesions.

CONCLUSIONS:

Our study shows that multiparametric MRI differentiates various vertebral lesions, and we established prediction models for the same.



Pacemakers in MRI for the Neuroradiologist [review-article]

SUMMARY:

Cardiac implantable electronic devices are frequently encountered in clinical practice in patients being screened for MR imaging examinations. Traditionally, the presence of these devices has been considered a contraindication to undergoing MR imaging. Growing evidence suggests that most of these patients can safely undergo an MR imaging examination if certain conditions are met. This document will review the relevant cardiac implantable electronic devices encountered in practice today, the background physics/technical factors related to scanning these devices, the multidisciplinary screening protocol used at our institution for scanning patients with implantable cardiac devices, and our experience in safely performing these examinations since 2010.



WEB Device: Ready for Ruptured Aneurysms? [article-commentary]



Financial development, income inequality, and CO 2 emissions in Asian countries using STIRPAT model

Abstract

The main purpose of this paper is to find the effects of financial development, income inequality, energy usage, and per capita GDP on carbon dioxide (CO2) emissions as well the environmental Kuznets curve (EKC) for the three developing Asian countries—Bangladesh, India, and Pakistan. Panel data during the period 1980–2014 and the Stochastic Impacts by Regression on Population, Affluence, and Technology model with fully modified ordinary least squares (FMOLS) are employed for empirical investigation. The results show that financial development has a significant negative relationship with CO2 emission in the three selected Asian countries with the exception of India. The results further reveal that income inequality in Pakistan and India reduce CO2 emission, while the result for Bangladesh is opposite. Likewise, energy usage has a significant positive effect on CO2 emission in Bangladesh, Pakistan, and India. Our empirical analysis based on long-run and short-run elasticity appraisal suggests the validation of the EKC in Pakistan and India. The study findings recommend an important policy insinuation. The study suggests introducing a motivational campaign for the inhabitant towards utilization of high-efficiency electrical appliances, constructing mutual cooperation for economic development rather involve in winning development race, and introducing effective pollution absorption measures along with big projects.



Passende Verordnungsmenge und Applikation von Topika

Zusammenfassung

Hintergrund

Die Abschätzung der notwendigen Verordnungsmenge sowie der Anwendungsmenge von Topika durch den Patienten bereitet in der Versorgung nicht selten Schwierigkeiten. Unzureichende oder unwirtschaftliche Versorgung kann die Folge sein. Um beide Fehlerbereiche zu minimieren, sind einfache Methoden und eine hinreichende Erfahrung in der Abschätzung passender Verordnungsmengen und der Vermittlung verständlicher Applikationsvorgaben wichtig.

Ziel der Arbeit

Es erfolgten die Aufzeigung des aktuellen Publikationsstandes und die Prüfung der Evidenz zur sachgerechten topischen Verordnungsmenge und deren Anwendung durch den Patienten.

Material und Methoden

Es wurde ein Literaturreview auf der Basis einer strukturierten Literaturrecherche in PubMed mit den einzeln und gepoolt eingesetzten Suchbegriffen „local therapy", „topical treatment", „prescription", „amount of ointment needed", „involved area", „BSA", „finger-tip-unit", „Rule of Hand", „calculated dosage" und „rule of nines" durchgeführt. Eingeschlossen wurden wissenschaftliche Originalarbeiten nach manuellem Screening des Titels und Abstracts hinsichtlich der Relevanz.

Ergebnisse

Die Suchstrategie identifizierte nach manueller Selektion 19 relevante Publikationen. Als Maß der genaueren Applikation wurde am häufigsten das Prinzip der Fingertip-Unit (Fingerspitzeneinheit; FTU) eingesetzt. Die sachgerechte Verordnungsmenge wird in Abhängigkeit des Bedarfs pro befallener Fläche berechnet.

Diskussion

Es besteht in Deutschland weiterhin Klärungsbedarf, inwieweit in der Versorgungsroutine optimierte Mengen verordnet und zur Anwendung empfohlen werden. Für die Patienteninstruktion ist die FTU in Verbindung mit der Handflächenregel („Rule of Hand") ein geeignetes Maß zur Selbstapplikation.



Cartilage Analogue of Fibromatosis in the Maxillary Alveolar Bone

Abstract

Cartilage analogue of fibromatosis is a relatively common tumor in the palms and soles of young children and adolescence. The characteristic histological finding of the tumor is the differentiation toward cartilage formation within a background of fibromatosis-like growth. Therefore, the tumor may cause potential diagnostic problems in the maxillofacial bones where it has not been described. The purpose of the present report is to describe the imaging characteristics, histological and immunohistochemical features of an extremely rare case of cartilage analogue of fibromatosis in the maxillary alveolar bone of a 25-year-old female.



Adjuvant everolimus in high-risk diffuse large B-cell lymphoma: final results from the PILLAR-2 randomized phase III trial

Abstract
Background
Patients with diffuse large B-cell lymphoma (DLBCL) with an International Prognostic Index (IPI) ≥3 are at higher risk for relapse after a complete response (CR) to first-line rituximab-based chemotherapy (R-chemo). Everolimus has single-agent activity in lymphoma. PILLAR-2 aimed to improve disease-free survival (DFS) with 1 year of adjuvant everolimus.
Patients and Methods
Patients with high-risk (IPI ≥3) DLBCL and a positron emission tomography/computed tomography-confirmed CR to first-line R-chemo were randomized to 1 year of everolimus 10 mg/day or placebo. The primary end point was DFS; secondary end points were overall survival (OS), lymphoma-specific survival (LSS), and safety.
Results
Between August 2009 and December 2013, 742 patients were randomized to everolimus (n = 372) or placebo (n = 370). Median follow-up was 50.4 months (range 24.0 to 76.9). Overall, 47% of patients were ≥65 years, 50% were male, and 42% had an IPI of 4 or 5. 48% and 67% completed everolimus and placebo, respectively. Primary reasons for everolimus discontinuation versus placebo were adverse events (AEs; 30% v 12%) and relapsed disease (6% v 13%). Everolimus did not significantly improve DFS compared with placebo (hazard ratio 0.92; 95% CI, 0.69 to 1.22; P = 0.276). Two-year DFS rate was 77.8% (95% CI, 72.7 to 82.1) with everolimus and 77.0% (95% CI, 72.1 to 81.1) with placebo. Common grade 3/4 AEs with everolimus were neutropenia, stomatitis, and decreased CD4 lymphocytes.
Conclusions
Adjuvant everolimus did not improve DFS in patients already in PET/CT-confirmed CR. Future approaches should incorporate targeted agents such as everolimus with R-CHOP rather than as adjuvant therapy after CR has been obtained.
ClinicalTrials.gov
NCT00790036

Funding sources of practice changing trials



Pertuzumab, trastuzumab, and standard anthracycline- and taxane-based chemotherapy for the neoadjuvant treatment of patients with HER2-positive localized breast cancer (BERENICE): a phase II, open-label, multicenter, multinational cardiac safety study

Abstract
Background
Anti-HER2 therapies are associated with a risk of increased cardiac toxicity, particularly when part of anthracycline-containing regimens. We report cardiac safety of pertuzumab, trastuzumab, and chemotherapy in the neoadjuvant treatment of HER2-positive early breast cancer.
Patients and methods
BERENICE (NCT02132949) is a nonrandomized, phase II, open-label, multicenter, multinational study in patients with normal cardiac function. In the neoadjuvant period, Cohort A patients received four cycles of dose-dense doxorubicin and cyclophosphamide, then 12 doses of standard paclitaxel plus four standard trastuzumab and pertuzumab cycles. Cohort B patients received four standard fluorouracil/epirubicin/cyclophosphamide cycles, then four docetaxel cycles with four standard trastuzumab and pertuzumab cycles. The primary endpoint was cardiac safety during neoadjuvant treatment, assessed by the incidence of New York Heart Association (NYHA) Class III/IV heart failure and of left ventricular ejection fraction (LVEF) declines (≥10 percentage points from baseline and to a value of < 50%). The main efficacy endpoint was pathological complete response (pCR, ypT0/is ypN0). Results are descriptive.
Results
Safety populations were 199 and 198 patients in Cohorts A and B, respectively. Three patients (1.5%; 95% confidence interval [CI]: 0.31–4.34) in Cohort A experienced four NYHA Class III/IV heart failure events. Thirteen patients (6.5%; 95% CI: 3.5–10.9) in Cohort A and four (2.0%; 95% CI: 0.6–5.1) in Cohort B experienced at least one LVEF decline. No new safety signals were identified. pCR rates were 61.8% and 60.7% in Cohorts A and B, respectively. The highest pCR rates were in the HER2-enriched PAM50 subtype (75.0% and 73.7%, respectively).
Conclusion
Treatment with pertuzumab, trastuzumab, and common anthracycline-containing regimens for the neoadjuvant treatment of early breast cancer resulted in cardiac and general safety profiles, and pCR rates, consistent with prior studies with pertuzumab.
Clinical Trial Information
NCT02132949

Role of up-front autologous stem cell transplantation in peripheral T-cell lymphoma for patients in response after induction: An analysis of patients from LYSA centers

Abstract
Background
Peripheral T-cell lymphoma (PTCL) remains a therapeutic challenge. Due to the rarity and the heterogeneity of PTCL, no consensus has been achieved regarding even the type of first-line treatment. The benefit of autologous stem cell transplant (ASCT) is, therefore, still intensely debated.
Patients and methods
In the absence of randomized trials addressing the role of ASCT, we performed a large multicentric retrospective study and used both a multivariate proportional hazard model and a propensity score matching approach to correct for sample selection bias between patients allocated or not to ASCT in intention-to-treat (ITT).
Results
Among 527 patients screened from 14 centers in France, Belgium, and Portugal, a final cohort of 269 patients ≤ 65 years old with PTCL-NOS (N=78, 29%), AITL (N=123, 46%) and ALK-ALCL (N=68, 25%) with partial (N=52, 19%) or complete responses (N=217, 81%) after induction was identified and information about treatment allocation was carefully collected before therapy initiation from medical records. One hundred and thirty-four patients were allocated to ASCT in ITT and 135 were not. Neither the Cox multivariate model (HR = 1.02; 95% CI 0.69-1.50 for PFS and HR = 1.08; 95% CI 0.68-1.69 for OS) nor the propensity score analysis after stringent matching for potential confounding factors (logrank P=0.90 and 0.66 for PFS and OS respectively) found a survival advantage in favor of ASCT as a consolidation procedure for patients in response after induction. Subgroup analyses did not reveal any further difference for patients according to response status, stage disease or risk category.
Conclusions
The present data do not support the use of ASCT for up-front consolidation for all patients with PTCL-NOS, AITL or ALK- ALCL with partial or complete response after induction.

Circulating cell-free DNA as predictor of treatment failure after neo-adjuvant chemo-radiotherapy before surgery in patients with locally advanced rectal cancer

Abstract
Background
Treatment of patients with locally advanced rectal cancer (LARC) is based on a combination of chemo-radiotherapy (CRT) and surgery. The rate of distant recurrences remains over 25%. Circulating cell-free DNA (cfDNA) in plasma is a mixture of normal and cancer-specific DNA segments, and is a promising biomarker in patients with colorectal cancer. The aim of our study was to investigate plasma cfDNA as a prognostic marker for outcome in patients with LARC treated with neoadjuvant CRT and surgery.
Patients and Methods
123 patients with LARC were included in two biomarker studies. Patients were treated with neoadjuvant CRT before TME surgery. Fifty-two (42%) of the patients received induction chemotherapy (ICT) with capecitabine + oxaliplatin. Total cfDNA was measured by direct fluorescent assay in EDTA plasma samples obtained at baseline, after ICT, and after CRT. Serial samples 5 years after surgery were collected in 51 patients (41%).
Results
Median follow-up was 55 months. Distant or local recurrence were seen in 30.9% of the patients. Patients with baseline cfDNA levels above the 75th quartile had a higher risk of local or distant recurrence and shorter time to recurrence compared to patients with plasma cfDNA below the 75th percentile (HR = 2.48, 95%CI:1.3–4.8, P = 0.007). The same applied to disease free survival (DFS) (HR = 2.43, 95%CI:1.27–4.7, P = 0.015). In multivariate analysis, a high cfDNA level was significantly associated with time to progression and DFS. During follow-up, the association remained significant regardless of time point for sample analysis.
Conclusion
We have demonstrated an association between a high baseline plasma level of cfDNA and increased risk of recurrence, shorter time to recurrence, and shorter DFS in patients with LARC. Consequently, cfDNA could potentially improve pre- and posttreatment risk assessment and facilitate individualized therapy for patients with LARC.

Respiratory syncytial virus during pregnancy



Burden of respiratory syncytial virus infection in South African HIV-infected and HIV-uninfected pregnant and post-partum women: A longitudinal cohort study

Abstract
Background
There are limited data on the burden of respiratory syncytial virus (RSV) illness among pregnant and post-partum women, to determine their potential benefit from maternal RSV vaccination aimed primarily at protecting their probands. We evaluated the incidence of RSV-illness from mid-pregnancy until 24-weeks post-partum in HIV-uninfected and HIV-infected women and their infants.
Methods
Mother-infant dyads were enrolled in phase-III maternal influenza vaccine efficacy trials. These included 1060 and 1056 HIV-uninfected pregnant women in 2011 and 2012, respectively, 194 HIV-infected pregnant women in 2011, and their infants. Upper respiratory tract samples obtained at illness visits were tested for RSV by PCR.
Results
The incidence (per 1000 person-months) of RSV-illness (n=43 overall) among HIV-uninfected women was lower in 2011 (1.2; 95%CI: 0.6, 2.2) than in 2012 (4.0; 95%CI: 2.8, 5.6; p=0.001). The incidence of RSV-illness (n=5) in HIV-infected women was 3.4 (95%CI: 1.4, 8.1) in 2011. Maternal RSV-infection was associated with respiratory symptoms including cough (72.1%), rhinorrhoea (39.5%), sore-throat (37.2%); and headache (42%), but fever was absent in all cases. RSV-infection during pregnancy was not associated with adverse pregnancy outcomes. Post-partum, RSV-infection in mothers (n=27) was associated with concurrent infection among 51.9% of their infants; and conversely 29.8% of mothers with an investigated respiratory illness within 7 days of their infants having a RSV illness also tested positive for RSV.
Conclusions
RSV-infection is associated with respiratory illness during pregnancy and post-partum in women. Vaccination of pregnant women against RSV could benefit the mother, albeit primarily against non-febrile illness, and her infant.

ACTG A5353: A pilot study of dolutegravir plus lamivudine for initial treatment of HIV-1-infected participants with HIV-1 RNA < 500,000 copies/mL

Abstract
Background
Limited data exist on initial HIV-1 treatment with dolutegravir plus lamivudine , particularly for pre-treatment HIV-1 RNA >100,000 copies/mL.
Materials and Methods
A5353 is a phase II, single-arm, pilot study of once-daily dolutegravir (50mg) plus lamivudine (300 mg) in treatment-naïve participants with HIV-1 RNA ≥1000 and < 500,000 copies/mL. Exclusion criteria included active hepatitis B, or major protease, reverse transcriptase, or integrase resistance. The primary efficacy measure was proportion with HIV-1 RNA < 50 copies/mL (FDA snapshot) at week 24. Virologic failure (VF) was confirmed HIV-1 RNA >400 copies/mL at week 16/20, or >200 copies/mL at/after week 24. Dolutegravir levels and drug resistance testing were performed at VF.
Results
One hundred and twenty participants (87% male, median age 30 years, 37 (31%) HIV-1 RNA > 100,000 copies/mL) initiated study treatment. Median entry HIV-1 RNA and CD4 count were 4.61 log10 copies/mL and 387 cells/mm 3. Virologic efficacy by FDA snapshot at week 24 was 108/120 (90%, CI [83%, 95%]) with comparable results in the >100,000 copies/mL and ≤100,000 copies/mL strata: 89% [75%, 97%] and 90% [82%, 96%], respectively. Three participants had VF, each with undetected plasma dolutegravir at ≥1 timepoints; the M184V reverse transcriptase and R263R/K integrase mutations developed in one participant. Two participants experienced Grade 3 possibly/probably treatment-related adverse events; none discontinued treatment due to adverse events.
Conclusion
Dolutegravir plus lamivudine demonstrated efficacy in individuals with pre-treatment HIV-1 RNA up to 500,000 copies/mL in this pilot trial, but a participant selected resistance mutations to lamivudine and dolutegravir

Surface properties of PM2.5 calcite fine particulate matter in the presence of same size bacterial cells and exocellular polymeric substances (EPS) of Bacillus mucitaginosus

Abstract

Microorganism cells and spores are the main components of PM2.5 (fine particulate matter) as well as fine mineral particles. In the microscopic system, the microorganisms will affect the minerals through attachment, charge neutralization, and dissolution related to the cell surface structure and metabolite. To explore the process and the results of microbial cells and their extracellular polymeric substances (EPS) acting on the surface properties of minerals of PM2.5 through the metabolism, a common native soil bacterium Bacillus mucitaginosus with abundant extracellular polymers was chosen as the tested strain. Meanwhile, as one of the PM2.5 common minerals, calcite fine particles were taken as the research object to explore the influence of microbial cells and extracellular polymers on its surface properties. High performance liquid chromatography (HPLC), inductively coupled plasma spectrometry (ICP), Zeta potential analysis, Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction spectroscopy (XRD), and scanning electron microscopy (SEM) were used to characterize the composition of EPS, the soluble ions, surface charge, surface groups, crystal form, and surface morphology of calcite residual solid after being treated by the bacterial cells and EPS. The results revealed the EPS of B. mucitaginosus mainly consisted of protein and polysaccharides. Both the whole cell and its EPS could promote the dissolution of calcite particles into calcium ions. Due to the adhesion of organic groups on the calcite surface, the surface potential shifted significantly in the negative direction and the solution pH was clearly increased. The morphology of calcite surface was significantly changed after dissolution and re-crystallization. Experimental results also showed that the existence of the bacteria cells and EPS significantly affected the surface properties of calcite and provide a theoretical basis for the mechanism of PM fine particulate matter on human health impact for further study.



Combination of in situ spectroscopy and chemometric techniques to discriminate different types of Roman bricks and the influence of microclimate environment

Abstract

Red and yellow bricks are the wall-building materials generally used in Roman masonries. The reasons for the different coloration are not always understood, causing loss of crucial information both for the conservation and for the archaeological knowledge of the cultural sites. In this work, a combination of in situ analyses, employing portable Raman spectroscopy and handheld energy dispersive X-ray fluorescence (HH-ED-XRF) spectroscopy along with chemometric analysis, was carried out on ancient Roman bricks of the "Casa di Diana" building (Ostia Antica, Italy-130 CE). Specifically, the compounds and the characteristic elements, which describe each type of brick (red and yellow), were studied avoiding destructive or invasive sampling. The molecular analysis allowed us to identify the major and minor compounds that characterise the bricks (anatase, hematite, quartz, calcite and silicates). However, the elemental analysis gave more useful information. Thus, the complex HH-ED-XRF data matrix generated was treated by a specific principal component analysis (PCA) to identify behavioural differences of the coloured bricks. The results revealed that Ca and Fe are the discriminatory elements for the two types of bricks. The PCA outcomes suggest that the contribution of certain elements is different in the bricks (mainly Ca, P, Sr, As and S, for yellow bricks), which could indicate different raw materials. Even among bricks with the same red colour (Al, Si, Ti, K, Fe, Cr, Mn, Ni, Zn, Cu, Rb and Zr, seemed to be the elements linked to raw materials), as a function of the surface impacts (orientation and microclimate affect the salts' formation), a distinction was made. Furthermore, the PCA pointed out that the yellow bricks are those more affected by decaying processes (related with Ca, P and S), complying with the Raman spectroscopy results in which the efflorescences (gypsum) affect especially the surface of these types of bricks.



Seasonal and spatial variations of microcystins in Poyang Lake, the largest freshwater lake in China

Abstract

Poyang Lake is the largest freshwater lake in China and an important drinking water source. Since the year 2000, toxic cyanobacteria have been observed frequently in Poyang Lake. In the present study, spatial and seasonal variations of microcystins (MCs; MC-RR, MC-YR, and MC-LR) in water column were examined monthly from January to December (except the months of March, May, and November) in 2013, by using ultra-high-performance liquid chromatography-electrospray ionization tandem triple quadrupole/mass spectrometry (UPLC-MS/MS). MC-RR was the most dominant variant, followed by MC-LR, while MC-YR was detected in low concentration. Total MC concentrations (intracellular + extracellular MCs) ranged from 1.26 to 9916.05 ng/L, with an average of 469.99 ng/L, and only 3.14% (6 out of 192 samples) of the water samples contained MC concentrations that exceeded the drinking water guideline level of 1 μg/L for MC-LR proposed by the World Health Organization (WHO). MC concentrations in water column showed obvious seasonal variations in Poyang Lake. Intracellular and extracellular MCs were both at a low level from January to April but increased quickly from June to August and decreased dramatically thereafter. Intracellular MCs exhibited similar spatial distribution pattern with extracellular MCs. Both intracellular and extracellular MC concentrations in eastern bays and around Songmen Mountain of Poyang Lake were higher than other regions. Intracellular MC concentrations were positively correlated with Chl a (r = 046, P < 0.01), pH (r = 0.25, P < 0.01), cyanobacterial biomass (r = 0.40, P < 0.01), and temperature (r = 0.36, P < 0.01) but negatively correlated with TN (r = − 0.28, P < 0.01), suggesting that TN, cyanobacteria biomass, pH, and temperature might be regulating factors for MC production in Poyang Lake.



The association of windmills with conservation of pollinating insects and wild plants in homogeneous farmland of western Poland

Abstract

Loss of suitable seminatural habitats and homogenization of crop types have led to the population decline of pollinating insects in farmland. As these insects support crop production, many practical efforts aim to sustain pollinator diversity which is especially challenging in intensively managed and homogeneous farmland. However, there are ongoing changes of the farmland toward its multifunctionality that includes, for example, wind farm development. Windmills are often built within crops; thus, we examined if the noncropped area around windmills can be valuable habitats for wild plants and pollinating insects: bees, butterflies, and flies. Species richness, abundances, and species diversity index of plants and pollinators around windmills were similar to those found in grassland patches (a typical habitat for these insects) and higher than in the adjacent crops. Pollinator diversity index and species richness at windmills increased with the distance to the nearest grassland patch and windmill. The population sizes of pollinating insects were also positively associated with plant diversity. Particular groups of pollinators showed specific habitat associations: bees occurred mostly at windmills, butterflies were highly associated with grasslands, while flies occurred in a similar number at windmill and on grasslands. Since windmills are frequently built within extensive homogeneous fields, thus, they introduce pollination services into the interior of cropped areas, contrary to field margins, road verges, or seminatural grasslands. Thus, although the development of wind farms has various negative environmental consequences, they can be alleviated by the increase of the local population size and diversity of wild plants and pollinating insects at windmills.



Testing Pneumonia Vaccines in the Elderly: Determining a Case Definition for Pneumococcal Pneumonia in the Absence of a Gold Standard

Abstract
Clinical assessments of vaccines to prevent pneumococcal (Pnc) community-acquired pneumonia (CAP) require sensitive and specific case definitions, but there is no gold standard diagnostic test. To develop a new case definition suitable for vaccine efficacy studies, we applied latent class analysis (LCA) to the results from seven diagnostic tests for Pnc etiology on clinical specimens from 323 elderly radiologically-confirmed pneumonia cases enrolled in The Finnish Community-Acquired Pneumonia Epidemiology study during 2005–2007. Compared to the conventional use of LCA, which is mainly to determine sensitivities and specificities of different tests, we instead used LCA as an appropriate instrument to predict the probability of Pnc etiology for each CAP case based on their test profiles, and utilized the predictions to minimize the sample size that would be needed for a vaccine efficacy trial. When compared to the conventional laboratory criteria of encapsulated Pnc in blood culture or in high-quality sputum culture or urine antigen positivity, our optimized case definition for PncCAP resulted in a trial sample size which was almost 20,000 subjects smaller. We believe that our novel application of LCA detailed here to determine a case definition for PncCAP could also be similarly applied to other diseases without a gold standard.

Therapeutic patient education in children with moderate to severe atopic dermatitis: A multicenter randomized controlled trial in China

Abstract

Background

Therapeutic patient education is a continuous, systematic, patient-centered learning process to help patients and their families acquire and maintain the skills they need to manage their lives with a chronic disease. It has been proven effective in increasing treatment adherence and improving quality of life for patients with atopic dermatitis (AD) in Western countries. We introduce the first multicenter, randomized controlled clinical trial of therapeutic patient education in Chinese children with AD.

Objectives

To evaluate the effects of therapeutic patient education on the severity of AD, quality of life, and understanding and successful use of emollients in Chinese children with eczema.

Methods

We recruited 580 children, ages 2-14 years, with moderate to severe AD from six hospitals in China. Participants were randomized (1:1) to an intervention (n = 293) or control (n = 249) group. In addition to the severity of AD, data on quality of life and a questionnaire on family and patient knowledge of emollients were evaluated at the 6-month follow-up.

Results

On study completion, we found that the intervention group showed a significantly greater reduction in mean SCORing Atopic Dermatitis (P < .001) and Infant's Dermatology Life Quality Index (P = .030) scores than the control group. In addition, knowledge about the use of emollients improved significantly in the intervention group. There was no significant difference between groups in Children's Dermatology Life Quality Index scores.

Conclusions

The first randomized controlled trial of a therapeutic patient education program in China had positive long-term effects on decreasing eczema severity and improvement of quality of life in children 2-4 years of age with AD, as well as in promoting greater understanding of the use of emollients.



Kenneth Warren and the Great Neglected Diseases of Mankind Programme: The Transformation of Geographical Medicine in the US and BeyondBy Conrad Keating

ISBN 978-3-319-50145-1, Springer International Publishing, Cham, Switzerland (Telephone: 800-777-4643, E-mail: onlineservice@springer.com, Website: http://ift.tt/2lK1H8r), 2016, 150 pp., $29.99 Hardcover

A Decade of War: Prospective Trajectories of Posttraumatic Stress Disorder Symptoms Among Deployed US Military Personnel and the Influence of Combat Exposure

Abstract
Posttraumatic stress disorder (PTSD) is a common psychiatric disorder among service members and veterans. The clinical course of PTSD varies between individuals, and patterns of symptom development have yet to be clearly delineated. Previous studies have been limited by convenience sampling, short follow-up periods, and the inability to account for combat-related trauma. To determine the trajectories of PTSD symptoms among deployed military personnel with and without combat exposure, we used data from a population-based representative sample of 8,178 US service members who participated in the Millennium Cohort Study from 2001 to 2011. Using latent growth mixture modeling, trajectories of PTSD symptoms were determined in the total sample, as well as in individuals with and without combat exposure, respectively. Overall, 4 trajectories of PTSD were characterized: resilient, pre-existing, new-onset, and moderate stable. Across all trajectories, combat-deployed service members diverged from non–combat-deployed service members, even after a single deployment. The former also generally had higher PTSD symptoms. Based on the models, nearly 90% of those without combat exposure remained resilient over the 10-year period, compared with 80% of those with combat exposure. Findings demonstrate that although the clinical course of PTSD symptoms shows heterogeneous patterns of development, combat exposure is uniformly associated with poor mental health.

Best Practices for Gauging Evidence of Causality in Air Pollution Epidemiology

Abstract
The contentious political climate surrounding air pollution regulations has brought some researchers and policy-makers to argue that evidence of causality is necessary before implementing more stringent regulations. Recently, investigators in an increasing number of air pollution studies have purported to have used "causal analysis," generating the impression that studies not explicitly labeled as such are merely "associational" and therefore less rigorous. Using 3 prominent air pollution studies as examples, we review good practices for how to critically evaluate the extent to which an air pollution study provides evidence of causality. We argue that evidence of causality should be gauged by a critical evaluation of design decisions such as 1) what actions or exposure levels are being compared, 2) whether an adequate comparison group was constructed, and 3) how closely these design decisions approximate an idealized randomized study. We argue that air pollution studies that are more scientifically rigorous in terms of the decisions made to approximate a randomized experiment are more likely to provide evidence of causality and should be prioritized among the body of evidence for regulatory review accordingly. Our considerations, although presented in the context of air pollution epidemiology, can be broadly applied to other fields of epidemiology.

Estimating the Comparative Effectiveness of Feeding Interventions in the Pediatric Intensive Care Unit: A Demonstration of Longitudinal Targeted Maximum Likelihood Estimation

Abstract
Longitudinal data sources offer new opportunities for the evaluation of sequential interventions. To adjust for time-dependent confounding in these settings, longitudinal targeted maximum likelihood based estimation (TMLE), a doubly robust method that can be coupled with machine learning, has been proposed. This paper provides a tutorial in applying longitudinal TMLE, in contrast to inverse probability of treatment weighting and g-computation based on iterative conditional expectations. We apply these methods to estimate the causal effect of nutritional interventions on clinical outcomes among critically ill children in a United Kingdom study (Control of Hyperglycemia in Paediatric Intensive Care, 2008–2011). We estimate the probability of a child's being discharged alive from the pediatric intensive care unit by a given day, under a range of static and dynamic feeding regimes. We find that before adjustment, patients who follow the static regime "never feed" are discharged by the end of the fifth day with a probability of 0.88 (95% confidence interval: 0.87, 0.90), while for the patients who follow the regime "feed from day 3," the probability of discharge is 0.64 (95% confidence interval: 0.62, 0.66). After adjustment for time-dependent confounding, most of this difference disappears, and the statistical methods produce similar results. TMLE offers a flexible estimation approach; hence, we provide practical guidance on implementation to encourage its wider use.

Racial and Ethnic Disparities in the Incidence of Esophageal Cancer in the United States, 1992–2013

Abstract
Racial and ethnic disparities in the incidence of esophageal cancer have not been thoroughly characterized with quantitative health-disparity measures. Using data from 1992–2013 from 13 US cancer registries in the Surveillance, Epidemiology, and End Results database, we assessed such disparities according to histological type, based on a variety of disparity metrics. The age-standardized incidence rate of squamous cell carcinoma (SCC) was highest among black persons, while adenocarcinoma mainly affected white men. The rate of SCC decreased over time in all racial/ethnic groups, and this was most pronounced in black persons (by 5.7% per year among men and 5.0% among women). The adenocarcinoma rate rose among non-Hispanic whites and among black men. Racial/ethnic disparities in the incidence of total esophageal cancer decreased over time, which was due mainly to reduced disparities in SCC. The 2 absolute disparity measures—range difference and between-group variance—for adenocarcinoma rose by 3.2% and 6.8% per year, respectively, in men and by 1.8% and 5.3% per year, respectively, in women. This study demonstrates decreased racial/ethnic disparities in the incidence of esophageal SCC over time in the United States, while disparities increased in adenocarcinoma incidence as measured on the absolute scale.

Epidemiologic Risk Factors for In Situ and Invasive Breast Cancers Among Postmenopausal Women in the National Institutes of Health-AARP Diet and Health Study

Abstract
Comparing risk factor associations between invasive breast cancers and possible precursors may further our understanding of factors related to initiation versus progression. Accordingly, among 190,325 postmenopausal participants in the National Institutes of Health-AARP Diet and Health Study (1995–2011), we compared the association between risk factors and incident ductal carcinoma in situ (DCIS; n = 1,453) with that of risk factors and invasive ductal carcinomas (n = 7,525); in addition, we compared the association between risk factors and lobular carcinoma in situ (LCIS; n = 186) with that of risk factors and invasive lobular carcinomas (n = 1,191). Hazard ratios and 95% confidence intervals were estimated from multivariable Cox proportional hazards regression models. We used case-only multivariable logistic regression to test for heterogeneity in associations. Younger age at menopause was associated with a higher risk of DCIS but lower risks of LCIS and invasive ductal carcinomas (P for heterogeneity < 0.01). Prior breast biopsy was more strongly associated with the risk of LCIS than the risk of DCIS (P for heterogeneity = 0.04). Increased risks associated with use of menopausal hormone therapy were stronger for LCIS than DCIS (P for heterogeneity = 0.03) and invasive lobular carcinomas (P for heterogeneity < 0.01). Associations were similar for race, age at menarche, age at first birth, family history, alcohol consumption, and smoking status, which suggests that most risk factor associations are similar for in situ and invasive cancers and may influence early stages of tumorigenesis. The differential associations observed for various factors may provide important clues for understanding the etiology of certain breast cancers.

TMPRSS2:ERG Gene Fusions in Prostate Cancer of West African Men and a Meta-Analysis of Racial Differences

Abstract
The prevalence of fusions of the transmembrane protease, serine 2, gene (TMPRSS2) with the erythroblast transformation-specific–related gene (ERG), or TMPRSS2:ERG, in prostate cancer varies by race. However, such somatic aberration and its association with prognostic factors have neither been studied in a West African population nor been systematically reviewed in the context of racial differences. We used immunohistochemistry to assess oncoprotein encoded by the ERG gene as the established surrogate of ERG fusion genes among 262 prostate cancer biopsies from the Ghana Prostate Study (2004–2006). Poisson regression with robust variance estimation provided prevalence ratios and 95% confidence intervals of ERG expression in relation to patient characteristics. We found that 47 of 262 (18%) prostate cancers were ERG-positive, and being negative for ERG staining was associated with higher Gleason score. We further conducted a systematic review and meta-analysis of TMPRSS2:ERG fusions in relation to race, Gleason score, and tumor stage, combining results from Ghana with 40 additional studies. Meta-analysis showed the prevalence of TMPRSS2:ERG fusions in prostate cancer to be highest in men of European descent (49%), followed by men of Asian (27%) and then African (25%) descent. The lower prevalence of TMPRSS2:ERG fusions in men of African descent implies that alternative genomic mechanisms might explain the disproportionately high prostate cancer burden in such populations.

Application of an Individual-Based Transmission Hazard Model for Estimation of Influenza Vaccine Effectiveness in a Household Cohort

Abstract
Household cohort studies are an important design for the study of respiratory virus transmission. Inferences from these studies can be improved through the use of mechanistic models to account for household structure and risk as an alternative to traditional regression models. We adapted a previously described individual-based transmission hazard (TH) model and assessed its utility for analyzing data from a household cohort maintained in part for study of influenza vaccine effectiveness (VE). Households with ≥4 individuals, including ≥2 children <18 years of age, were enrolled and followed during the 2010–2011 influenza season. VE was estimated in both TH and Cox proportional hazards (PH) models. For each individual, TH models estimated hazards of infection from the community and each infected household contact. Influenza A(H3N2) infection was laboratory-confirmed in 58 (4%) subjects. VE estimates from both models were similarly low overall (Cox PH: 20%, 95% confidence interval: −57, 59; TH: 27%, 95% credible interval: −23, 58) and highest for children <9 years of age (Cox PH: 40%, 95% confidence interval: −49, 76; TH: 52%, 95% credible interval: 7, 75). VE estimates were robust to model choice, although the ability of the TH model to accurately describe transmission of influenza presents continued opportunity for analyses.

Measurement Error Due to Patient Flow in Estimates of Intensive Care Unit Length of Stay

Abstract
Clinical endpoints measured in terms of duration, such as intensive care unit (ICU) length of stay (LOS), are widely used in randomized clinical trials (RCTs) and observational research. In analyses of patient-level data from a recent RCT, in which ICU LOS was the primary endpoint, and in administrative data, we showed that additional ICU time is often accrued by patients after they are deemed ready for discharge. This "immutable" time (which cannot plausibly be altered by interventions under study) varies by day, week, and year, adding on average one-third of a day to total LOS. We then used statistical simulations, informed by the administrative data and RCT, to assess the impact of immutable time on the measurement and statistical comparison of patients' ICU LOS. These simulations demonstrated that immutable time combines with clinically necessary ICU time (neither of which is likely to be normally distributed) to produce overall LOS distributions that might either mask true treatment effects or suggest false treatment effects relative to analyses of time to discharge readiness. The extent and direction of bias were complex functions of the statistical method used, mortality rates and distributions, and the magnitude of immutable time relative to intervention-associated reductions in LOS.

Neonatal Outcomes Associated With Placental Abruption

Abstract
Placental abruption (early separation of the placenta) is associated with preterm birth and perinatal mortality, but associations with other neonatal morbidities remain understudied. We examined the association between abruption and newborn outcomes. We analyzed 223,341 singleton deliveries from the Consortium on Safe Labor study, a retrospective, multisite, observational study (2002–2008) of electronic medical records in the United States. Adjusted relative risks, incidence rate ratios, and 99% confidence intervals were estimated. Direct effects attributable to abruption were examined by conditioning on intermediates (preterm birth and small for gestational age) with sensitivity analyses. Incidence of abruption was 1.6% (n = 3,619). Abruption was associated with an elevated risk of newborn resuscitation (relative risk (RR) = 1.5, 99% confidence interval (CI): 1.5, 1.6), apnea (RR = 5.8, 99% CI: 5.1, 6.5), asphyxia (RR = 8.5, 99% CI: 5.7, 11.3), respiratory distress syndrome (RR = 6.5, 99% CI: 5.9, 7.1), neonatal intensive care unit admission (RR = 3.4, 99% CI: 3.2, 3.6), longer intensive care length of stay (incidence rate ratio = 2.0, 99% CI: 1.9, 2.2), stillbirth (RR = 6.3, 99% CI: 4.7, 7.9), and neonatal mortality (RR = 7.6, 99% CI: 5.2, 10.1). In sensitivity analyses, there was a direct effect of abruption associated with increased neonatal risks. These findings expand our knowledge of the association between abruption and perinatal and neonatal outcomes.

Impact of Targeted Tuberculosis Vaccination Among a Mining Population in South Africa: A Model-Based Study

Abstract
Optimizing the use of new tools, such as vaccines, may play a crucial role in reaching global targets for tuberculosis (TB) control. Some of the most promising candidate vaccines target adults, although high-coverage mass vaccinations may be logistically more challenging among this population than among children. Vaccine-delivery strategies that target high-risk groups or settings might yield proportionally greater impact than do those that target the general population. We developed an individual-based TB transmission model representing a hypothetical population consisting of people who worked in South African gold mines or lived in associated labor-sending communities. We simulated the implementation of a postinfection adult vaccine with 60% efficacy and a mean effect duration of 10 years. We then compared the impact of a mine-targeted vaccination strategy, in which miners were vaccinated while in the mines, with that of a community-targeted strategy, in which random individuals within the labor-sending communities were vaccinated. Mine-targeted vaccination averted an estimated 0.37 TB cases per vaccine dose compared with 0.25 for community-targeted vaccination, for a relative efficacy of 1.46 (95% range, 1.13–1.91). The added benefit of mine-targeted vaccination primarily reflected the disproportionate demographic burden of TB among the population of adult males as a whole. As novel vaccines for TB are developed, venue-based vaccine delivery that targets high-risk demographic groups may improve both vaccine feasibility and the impact on transmission.

The "Boomerang Lift": A 3-Step Compartment Based Approach to the Youthful Cheek.

The "Boomerang Lift": A 3-Step Compartment Based Approach to the Youthful Cheek.

Plast Reconstr Surg. 2017 Dec 13;:

Authors: Schreiber JE, Terner J, Stern CS, Beut J, Jelks EB, Jelks GW, Tepper OM

Abstract
BACKGROUND: Autologous fat grafting (AFG) is an important tool for plastic surgeons treating the aging face. Malar augmentation with fat is often targeted to restore the youthful facial contour and provides support to the lower eyelid. The existence of distinct facial fat compartments suggests a step-wise approach may be appropriate in this regard [1]. Here we describe a three-step approach to malar augmentation using targeted deep malar fat compartmental augmentation, termed the "Boomerang Lift".
METHODS: Clinical patients undergoing AFG for malar augmentation were injected in three distinct deep malar fat compartments: 1. the lateral sub-orbicularis oculi fat (LSOOF), medial sub-orbicularis oculi fat (MSOOF), and lastly to the deep medial cheek (DMC) (n=9). Intra-operative 3D images were taken at baseline and following compartmental injections(Canfield® VECTRA H1). Images were overlaid between the augmented and baseline captures, and the 3D surface changes were analyzed, which represented the resulting "augmentation zone" (AZ).
RESULTS: 3D analysis of patients (n=9) demonstrated a unique pattern for AZ consistent across patients. The AZ resembled a boomerang, with the short tail supporting the medial lower lid, and the long tail extending laterally along the zygomatic arch. The upper border was restricted by the level of the naso-jugal interface, and the lower border was defined medially by the nasolabial fold and laterally by the level of the zygomatico-cutaneous ligament. Injections to the lateral and medial SOOF defined the boundaries of the boomerang shape, while the injection to the deep medial cheek provided maximum projection.
CONCLUSIONS: This is the first description of deep malar augmentation zones described in clinical patients. 3D surface imaging was an ideal method for analyzing the surface change in response to targeted facial fat grafting. Our technique resulted in a reproducible surface shape, which we term the "Boomerang Lift".

PMID: 29240637 [PubMed - as supplied by publisher]



How to Deal with Future Existence: sarvāstivāda , Yogic Perception, and Causality

Abstract

This paper mainly addresses the following issues: how Buddhists deal with future existence, the difference between yogic perception and the cognition of ordinary people with regard to future entities, and how Buddhists resolve the contradiction between the theory of momentariness and that of action and its fruit. According to the Sarvāstivādins, a future entity exists in reality as long as there is cognition that has this entity as its object. According to the Sautrāntikas, however, that theory does not hold true. A future entity is just what will occur hereafter, and it is never the case that such an entity exists at present. Śāntarakṣita and Kamalaśīla do not directly negate an opponent's argument that the distinction between past and future entities is made by yogic perception, but implicitly accept it. They state that because a future entity is situated in a causal stream (saṃtāna), yogis can cognize it through purified worldly cognition (śuddhalaukikajñāna). As for an effect that will occur in the future, Buddhists do not seem to follow the model that one and the same agent of action will necessarily receive the fruit of past action, which is often seen in other schools such as the Naiyāyikas and Mīmāṃsakas. Rather, Buddhists adopt the theory of the uninterrupted succession of cause and effect.



Zygomatic Hypoplasia in Patients with Non-syndromic Cleft Lip and Palate: A Case–Control Study

Abstract

Background

Patients operated for cleft deformities may have zygomatic hypoplasia secondary to impaired growth of the maxilla. This has, however, not been evaluated in the past.

Subjects and Methods

This study was a prospective, case–control study. This included 32 patients, aged between 19 and 25 years, who were divided into cleft and non-cleft groups. The cleft group was further divided into unilateral clefts, bilateral clefts and isolated palatal clefts. In both groups, the zygoma was assessed and compared on both sides clinically using indirect photogrammetry and radiographically using 3D CT. The results were analyzed statistically using the unpaired t test.

Results

There was a significant difference in the zygomatic projection on cleft and non-cleft sides in the unilateral cleft group. There was no significant difference in the zygomatic projection of both sides in the other subgroups and the control group.

Conclusion

The present study shows that there is a global effect of palato-alveolar cleft repair on the midfacial skeleton. Further studies are required to correlate the impact of age, gender and the technique of palato-alveolar cleft repair with the quantum of malar hypoplasia.



Excimer light devices: are they really monochromatic?



Notalgia paresthetica: a review for dermatologists

Abstract

Notalgia paresthetica (NP) is an underdiagnosed condition that presents with unilateral pruritus medial to the scapula on the midback with or without an associated hyperpigmented or hypopigmented macule. There is a paucity of recent reviews on this chronic cutaneous neuropathy in peer-reviewed journals. Current theories propose the condition is likely multifactorial, including spinal entrapment and muscular compressive neuropathy. An extensive literature review was performed by searching the MEDLINE database to review all published works on notalgia paresthetica. This review will provide a useful update for clinicians on the pathogenesis, clinical features, biopsy features, risk factors, and management options for this condition including pharmacological and nonpharmacological methods detailing published treatment options to date for this difficult to treat condition.



Decrease of superficial serine and lactate in the stratum corneum due to repetitive frictional trauma

Abstract

Background

Repetitive frictional trauma can be induced in daily and occupational activities, such as daily ablutions with washcloths. The influence of frictional trauma on the skin barrier function, especially in the perspective of the components of stratum corneum (SC), has not yet been studied in detail. Raman spectroscopy is a noninvasive optical technique based on inelastic light scattering that is capable of measuring several components in the skin. In this study, we used Raman spectroscopy to investigate the change in natural moisturizing factor (NMF) components in the SC following repetitive physical friction.

Methods

Six healthy volunteers, who were included in the study after obtaining an informed consent, performed repetitive washing with soap using nylon towels on the forearm twice a day for 2 weeks and used Raman spectroscopy to investigate the change in NMF components in the SC.

Results

Compared with the control, which was washed with soap at the same frequency on the opposite forearm, a significant increase in the transepidermal water loss (TEWL) and a decrease in NMF, serine, and total lactate, responsible for maintenance the SC hydration and structuring and maintaining the epidermal barrier function, in the SC were found.

Conclusions

Increased TEWL and decreased NMF are considered as an etiology of atopic dermatitis (AD); therefore, our findings provide evidence that daily activities with repetitive frictional trauma may be related to the predisposition of AD.



Association between atopic dermatitis and squamous cell carcinoma: a case–control study

Abstract

Background

Conflicting data have been published on whether an association exists between atopic dermatitis (AD) and nonmelanoma skin cancer. This study aimed to determine whether individuals with AD had an increased risk of squamous cell carcinoma (SCC) development.

Methods

We conducted a retrospective, case–control study of patients residing in Olmsted County, Minnesota. Cases were selected from patients seen at Mayo Clinic (Rochester, Minnesota) who had an initial SCC diagnosis (either invasive SCC or SCC in situ) from January 1, 1996, through December 23, 2010. Age- and sex-matched controls were selected from patients seen at Mayo Clinic with no history of SCC before the case event date.

Results

Three hundred ninety-nine individuals with a documented history of SCC were identified and matched with 780 controls who did not have a history of SCC. After adjusting for race, smoking history, ionizing radiation exposure, corticosteroid and cyclosporine use, and non-SCC skin cancers, the odds ratio for SCC development between patients with history of AD versus patients without history of AD was 1.75 (95% CI, 1.05–2.93).

Conclusions

Our findings support an increased risk of SCC development in the setting of AD.



Dermatologic manifestations among human immunodeficiency virus patients in Morocco and association with immune status

Abstract

Objective

The objective was to determine if the type and number of skin diseases can be clinical indicators of underlying immune status in HIV1 disease by estimating and correlating with the CD4 count and CDC stage.

Materials and methods

This was a retrospective cross-sectional descriptive study. All consecutive patients infected with HIV1 followed at the Dermatology Department of Rabat Military Hospital between January 2008 and January 2017 were studied for dermatological manifestations, CD4 count and CDC clinical stage.

Results

A total of 170 patients with 304 dermatological manifestations were included. The most common dermatoses were fold dermatophytic infections (67%), genital warts (43%), herpes zoster (21%), xerosis (21%), and oral candidiasis (12%). The number of dermatologic manifestations was significantly greater in patients with CD4 count less than 200/mm3 or in stage C of the CDC classification. Five types of skin diseases (dermatophyte infections of the folds, genital warts, shingles, oral candidiasis, and seborrheic dermatitis) were significantly associated (P < 0.05) with CD4 count <200/mm3. Seborrheic dermatitis was the only one skin disease significantly associated with AIDS stage. In multivariate analysis, genital warts (OR = 0.3, 95% CI 0.10–0.92) are independently associated with CD4 count less than 200 CD4/mm3.

Conclusions

Skin manifestations not only act as markers but also reflect the underlying immune status. Seborrheic dermatitis and genital warts appear to be a marker of immune status, and seborrheic dermatitis appears to be associated with CDC stage C, especially in their chronic and severe forms.



Correlation of vitamin D and vitamin D receptor expression in patients with alopecia areata: a clinical paradigm

Abstract

Background

Vitamin D (Vit.D) deficiency has been reported in alopecia areata (AA). Downregulation of Vitamin D receptor (VDR) on hair follicles is associated with reduced hair growth.

Objective

To correlate serum Vit.D levels with severity, pattern, and duration of AA, and density of VDR expression over hair follicles in AA patients.

Methods

Prospective study including 30 AA patients and 30 healthy controls. Clinical details and serum Vit.D measurement and scalp biopsy for histopathology and VDR expression was performed in patients and controls at baseline and after 6 months of treatment of AA.

Results

Mean age of patients and controls was 28.9 ± 9.96 and 31.17 ± 9.43 years, respectively. Mean SALT score in patients was 35.8 ± 27.5 with a median disease duration of 48 weeks. Mean serum Vit.D levels was 7.65 ± 4.50 ng/ml and 15.8 ± 11.47 ng/ml in patients and controls, respectively. Twenty-nine (96.7%) patients were Vit.D deficient (<20 ng/ml), compared to 22 (73.3%) controls (P = 0.001). Serum Vit.D levels inversely correlated with severity of the disease (r = -256), P = 0.17, and duration of disease but did not correlate with pattern of AA and VDR expression in tissue samples. VDR expression was reduced in all patients and was normal in controls. Inverse correlation of VDR was noted with presence of inflammation on histology (P = 0.02). VDR upregulation post treatment was seen only in 13% of patients and demonstrated no correlation with response to treatment.

Conclusion

Vit.D deficiency in AA correlates inversely with disease severity and duration. VDR expression is reduced in AA and inversely correlate with inflammation histologically but does not correlates with serum Vit.D levels, severity, pattern, or duration of illness.



Generalized eruptive histiocytosis diagnosed in light of dermoscopic findings



Organochlorine pesticides in placenta in Kyrgyzstan and the effect on pregnancy, childbirth, and newborn health

Abstract

Organochlorine pesticides (OCPs) were determined by gas chromatography in 241 placentas from cotton-growing regions, 121 placentas from an urban area (city of Osh), and 146 placentas from unpolluted mountain regions of Kyrgyzstan. Manifestations of disease were recorded in the mothers during pregnancy and parturition and in their newborns during the first 6 days of life. OCPs were detected in 240 out of 508 placentas (47.2%), with increased incidence in the two polluted regions (65%), particularly in placentas from women living near former pesticide storehouses and agro air-strips (99%), but only in 2.7% of placentas from the unpolluted region. α-, β-, and γ-hexachlorocyclohexane (HCH); DDT; DDE; aldrin; and heptachlor were detected. The sum of concentrations of all OCPs (total OCPs) was calculated for each of the 240 placentas with detectable OCPs (median 9.5 μg/kg placenta, mean 88.3 μg/kg, range 0.1–3070 μg/kg). The incidence of health problems in four subgroups of this data set, with increasing levels of total OCPs, was compared with the incidence of health problems in the group of 268 placentas, where OCPs were undetectable. Relative risk of health problems in both, mothers and newborns, increased significantly, in a concentration-dependent manner, with increasing levels of total OCPs (p < 0.0001). Health complications with increased incidence in OCP-exposed newborns included, i.a., low birth weight, congenital malformations, infections, and stillbirths, in OCP-exposed mothers preterm delivery, (pre-)eclampsia/gestosis, and frequency of hospitalizations after delivery (infections). Women living near former pesticide storehouses and agro airstrips should be considered as being at risk. Reduction of exposure is urgently needed.



Contrasted effects of an anti-cyanobacterial ultrasound device on the non-target freshwater invertebrate species Gammarus roeseli

Abstract

The aim of this work was to investigate the effects of an anti-cyanobacterial ultrasound device (supplied by an electrical power of 15 W and emitting at 23 and 46 kHz) on the widespread freshwater amphipod species Gammarus roeseli. First, laboratory scale experiments in 8-L glass tanks showed that an ultrasound exposure of 2 h and 40 min was sufficient to produce 50% mortality, along with a 6.5 °C water temperature increase. Avoiding excessive heating by using a water-cooling and recirculation system permitted an exposure time of 29 h for the same mortality rate. A potential relationship between temperature's rise and amphipod mortality was hence highlighted. Moreover, the use of plastic mesh bag (0.5 mm mesh size) as a physical barrier has not shown any lethal effects of ultrasound exposure. Furthermore, the induction of GPx or GST activity as oxidative stress biomarkers was not observed. This could be explained by reduced ultrasound intensity inside the mesh bags. Thus, according to these results, the tested ultrasound system is not expected to be acutely harmful in the field.



A prospective study of topical carteolol therapy in Chinese infants with superficial infantile hemangioma

Abstract

Background/Objective

To report our observations from a trial of the short-term effectiveness and safety of topical carteolol hydrochloride drops to treat infantile hemangiomas (IHs).

Methods

From October 2012 to September 2015, the study recruited 349 children with superficial IHs. Participants were randomized to two groups: treatment (n = 224 who received 2% carteolol hydrochloride drops administered to the lesion surface twice daily) and observation (n = 125 who did not receive treatment). Therapy duration was 6 months.

Results

The mean age at the beginning of treatment was 3.2 months. Treatment responses were categorized as class 1 (total regression), class 2 (partial regression or controlled growth), or class 3 (no response). Of infants receiving carteolol treatment, 10.7% (24 patients) were categorized as class 1, 72.3% (162 patients) as class 2, and 17.0% (38 patients) as class 3. Of infants in the observation group, 5.6% (7 patients) were categorized as class 1, 25.6% (32 patients) as class 2, and 68.8% (86 patients) as class 3. No adverse effects were noted during treatment.

Conclusion

Carteolol is an effective, safe topical treatment for superficial IHs. Carteolol may be used to treat proliferative superficial IHs, particularly in infants younger than 6 months.



Holmes heart and tetralogy of Fallot in association with PHACE

Abstract

PHACE is an association between large infantile hemangiomas and brain, arterial, cardiac, and/or ocular abnormalities. Aortic or subclavian aberrations are the most common cardiovascular anomalies in PHACE, whereas complex congenital heart disease is rare. We report a case of Holmes heart and three cases of tetralogy of Fallot in PHACE association.



Pulmonary nodules and nodular scleritis in a teenager with superficial granulomatous pyoderma gangrenosum

Abstract

Superficial granulomatous pyoderma gangrenosum, a rare variant of pyoderma gangrenosum, has been considered to be the most benign form of the disease. We present the case of a 15-year-old boy with pulmonary involvement and nodular scleritis associated with this unusual type of pyoderma gangrenosum and discuss its differential diagnosis.



Local anesthesia in pediatric dermatologic surgery: Evaluation of a patient-centered approach

Abstract

Background/Objectives

A few studies have documented the effect of local anesthesia for minor dermatologic surgical procedures on children and their parents. Our objective was to evaluate the psychological effect and global satisfaction of a patient-centered approach to dermatologic surgery under local anesthesia.

Methods

Two self-administered questionnaires were used to evaluate the distress and global satisfaction of 388 children who underwent dermatologic surgery under local anesthesia, accompanied by oral and written therapeutic education measures (structured information and a cartoon brochure illustrating the procedure) addressed to children and parents. Distraction techniques were also used during the procedures.

Results

Although 54.5% of patients manifested some degree of fear, all other parameters analyzed (pain, surgery-related distress, surgical team–patient and –family relationship, global satisfaction) indicated that the procedures resulted in limited distress and that the large majority of children and parents tolerated them well.

Conclusion

Specific measures for therapeutic pediatric patient education may be helpful in limiting discomfort, anxiety, and pain perception linked to procedures performed under local anesthesia. Further controlled studies are required to more precisely assess the benefits of specific therapeutic education measures.



Issue Information



Corrigendum



Clinical diagnosis of crusted scabies: Reverse focal pattern of plantar keratoderma



Traction haemostasis



A 2000 patient retrospective assessment of a new strategy for burn wound management in view of infection prevention and treatment

Infections in burn patients are still the principal cause of complications in burn injuries. The aim of this study is to assess a new strategy for burn wound management in view of infection prevention and treatment in the experience of the Burn Treatment Center in Siemianowice Śląskie. The applied methodology involved the analysis of patient records describing the hospital's epidemiological situation between 2014 and 2016. The analysis also included the use and cost of antibiotics, silver-containing dressings, and other antiseptics relative to the number of sepsis cases, including those caused by Pseudomonas aeruginosa, as well as the mortality ratio. The total costs of prevention and treatment of infections were reduced, while the use of silver-containing dressings and antiseptics increased. The number of patients with sepsis decreased, including cases caused by P. aeruginosa, and the mortality ratio was reduced. Introducing a strategy for burn wound-oriented infection prevention and treatment in burn patients provides a number of benefits. It is also cost-effective. Using locally applied active dressings and antiseptics can be a welcome choice for often-unnecessary antibiotic therapy of a suspected or existing burn wound infection.



Turning frequency in adult bedridden patients to prevent hospital-acquired pressure ulcer: A scoping review

The aim of this study was to identify current research on turning frequencies of adult bed-bound patients and inform future turning practices for hospitals based on evidence-based practice. We undertook a scoping review framework that provided a transparent and systematic methodology using 8 electronic databases (CINAHL, PubMed, Cochrane Library, ScienceDirect, PsycINFO, Scopus, ProQuest, and Web of Science) to identify articles published from 2000 to 2016. Articles were included if they focused on the prevention of hospital-acquired pressure ulcers related to the frequency of turning or repositioning of bed-bound patients. Literature search and data extraction were performed independently by 3 authors. The study followed the PRISMA guidelines. In total, 911 articles were identified, of which 10 were eligible. Of the eligible articles, 8 studies could not reach a conclusion on the effective frequency of turning and duration for repositioning patients to prevent the development of pressure ulcers. Only 2 studies found significant differences among the intervention and control groups. Results regarding turning and repositioning schedules are inconclusive; however, the topic needs further exploration to improve the outdated guidelines surrounding pressure ulcer prevention. This may, in turn, make the work of nurses more efficient and make treatment cost-effective for both the patients and the hospitals.



Health-related quality of life and patient burden in patients with split-thickness skin graft donor site wounds

Split-thickness skin grafting is a common procedure to treat different kinds of wounds. This systematic, multicentre, observational, cross-sectional study of adult patients with split-thickness skin graft (STSG) donor site wounds was conducted to evaluate quality of life (QoL) impairments caused by donor site wounds following split-thickness skin grafting. Therefore, 112 patients from 12 wound centres in Germany were examined based on patient and physician questionnaires as well as a physical examination of the donor site wound. Most indications for skin grafting were postsurgical treatment (n = 51; 42.5%) and chronic wounds (n = 47; 39.2%). European QoL visual analoque scale (EQ VAS) averaged 64.7 ± 23.3, European QoL 5 dimensions (EQ-5D) averaged 77.4 ± 30.0.

Wound-QoL (range: 0-4) was rated 0.8 ± 0.8 post-surgery and 0.4 ± 0.6 at the time of survey (on average 21 weeks between the time points). Compared to averaged Wound-QoL scores of chronic wounds donor site-related QoL impairments in split-thickness skin-graft patients were less pronounced. There were significant differences in patient burden immediately after surgery compared to the time of the survey, with medium effect sizes. This supports the hypothesis that faster healing of the donor site wound leads to more favourable patient-reported outcomes.



Diabetic foot ulcer management in clinical practice in the UK: costs and outcomes

ABSTRACT

The aim of this study was to estimate the patterns of care and annual levels of health care resource use attributable to managing diabetic foot ulcers (DFUs) in clinical practice by the UK's National Health Service (NHS), and the associated costs of patient management.

This was a retrospective cohort analysis of the records of 130 patients with a newly diagnosed DFU in The Health Improvement Network (THIN) database. Patients' characteristics, wound-related health outcomes and health care resource use were quantified, and the total NHS cost of patient management was estimated at 2015–2016 prices.

Patients were predominantly managed in the community by nurses, with minimal clinical involvement of specialist physicians. 5% of patients saw a podiatrist, and 5% received a pressure-offloading device. Additionally, 17% of patients had at least one amputation within the first 12 months from initial presentation of their DFU. 14% of DFUs were documented as being clinically infected at initial presentation, although an additional 31% of patients were prescribed an antimicrobial dressing at the time of presentation. Of all the DFUs, 35% healed within 12 months, and the mean time to healing was 4·4 months. Over the study period, 48% of all patients received at least one prescription for a compression system, but significantly more patients healed if they never received compression (67% versus 16%; P < 0·001). The mean NHS cost of wound care over 12 months was an estimated £7800 per DFU (of which 13% was attributable to amputations), ranging from £2140 to £8800 per healed and unhealed DFU, respectively, and £16 900 per amputated wound.

Consolidated medical records from a primary care held database provided 'real-world evidence' highlighting the consequences of inefficient and inadequate management of DFUs in clinical practice in the UK. Clinical and economic benefits to both patients and the NHS could accrue from strategies that focus on (i) wound prevention, (ii) improving wound-healing rates and (iii) reducing infection and amputation rates.



Venous leg ulcer management in clinical practice in the UK: costs and outcomes

ABSTRACT

The aim of this study was to estimate the patterns of care and annual levels of health care resource use attributable to managing venous leg ulcers (VLUs) in clinical practice by the UK's National Health Service (NHS) and the associated costs of patient management. This was a retrospective cohort analysis of the records of 505 patients in The Health Improvement Network (THIN) Database. Patients' characteristics, wound-related health outcomes and health care resource use were quantified, and the total NHS cost of patient management was estimated at 2015/2016 prices. Overall, 53% of all VLUs healed within 12 months, and the mean time to healing was 3·0 months. 13% of patients were never prescribed any recognised compression system, and 78% of their wounds healed. Of the 87% who were prescribed a recognised compression system, 52% of wounds healed. Patients were predominantly managed in the community by nurses with minimal clinical involvement of specialist clinicians. Up to 30% of all the VLUs may have been clinically infected at the time of presentation, and only 22% of patients had an ankle brachial pressure index documented in their records. The mean NHS cost of wound care over 12 months was an estimated £7600 per VLU. However, the cost of managing an unhealed VLU was 4·5 times more than that of managing a healed VLU (£3000 per healed VLU and £13 500 per unhealed VLU). This study provides important insights into a number of aspects of VLU management in clinical practice that have been difficult to ascertain from other studies and provides the best estimate available of NHS resource use and costs with which to inform policy and budgetary decisions.



Associations between total mercury and methyl mercury exposure and cardiovascular risk factors in US adolescents

Abstract

Low levels of chronic heavy metal exposure are associated with a range of adverse health effects. However, whether total blood mercury (Hg) and methyl mercury (MeHg) exposure affect risk factors for cardiovascular disease (CVD) in adolescents remains unclear. The associations between CVD risk factors and total blood Hg and MeHg in adolescents were evaluated using data from the National Health and Nutrition Examination Survey (NHANES), 2011–2012. Data for 1129 adolescents (age 12–19 years) who participated in the US NHANES 2011–2012 were analyzed. A multivariate linear regression was performed to investigate the associations between CVD risk factors and blood Hg and MeHg concentrations. We identified a strong positive association between blood Hg and MeHg and total cholesterol in adolescents in adjusted model. No associations with other CVD risk factors were found in the overall population. In the gender-stratified generalized linear models, girls with the highest MeHg levels demonstrated a 4.22% (95% CI 0.80%, 7.76%) greater increase in serum total cholesterol (P for trend = 0.029) when compared with girls with the lowest MeHg levels. Our findings suggest that blood MeHg may be positively associated with total cholesterol in adolescent girls. More research is needed to verify this association and to elucidate its underlying mechanisms.



Mixed histiocytosis: A case report and published work review

Abstract

Histiocytoses are a group of heterogeneous diseases that encompass Langerhans cell histiocytosis and non-Langerhans cell histiocytosis. Cutaneous plane xanthoma is a non-Langerhans cell histiocytic disorder characterized by the presence of yellow-orange plaques on the face, neck, upper trunk and extremities. It can appear in association with several systemic diseases (including dyslipidemias, paraproteinemias, cardiovascular diseases and lymphoproliferative disorders), but is rarely connected with Langerhans cell histiocytoses. Eosinophilic granuloma is one of the clinical entities of Langerhans cell histiocytoses, characterized by skeletal lesions and occurring prominently in children. Mixed histiocytosis, the concomitant occurrence of Langerhans cell histiocytosis and non-Langerhans cell histiocytosis in a single patient, is exceptional. We herein report a case of eosinophilic granuloma in an adult Chinese man who also developed plane xanthoma on his scalp and face, and we also include a published work review of the comorbid cases of eosinophilic granuloma and non-Langerhans cell histiocytosis. To the best of our knowledge, this is the first report on the mixed histiocytosis of cutaneous plane xanthoma and eosinophilic granuloma in China.



STRATAFIX for Abdominal Wall Repair following Abdominal Flap Harvest

imageNo abstract available