Omalizumab is effective and safe in chronic inducible urticaria (CIndU): Real-world data from a large multi-national UCARE study.

BACKGROUND: Long-term data on the effectiveness and safety of omalizumab for chronic inducible urticaria (CIndU) in large populations are lacking. OBJECTIVE: To evaluate the effectiveness, safety, estimated omalizumab treatment duration and its predictors, as well as differences between CIndU subtypes, in a large long-term CIndU cohort. METHODS: A multinational multicenter study was conducted at 14 specialized urticaria centres (UCAREs), including all CIndU patients ever treated with omalizumab from 2009 until July 2022. Kaplan-Meier survival and regression analyses were performed. RESULTS: Across 234 CIndU patients (55% female; mean age 37 years), 76% (n = 178) had standalone CIndU and 24% (n = 56) had predominant CIndU plus minor CSU, with an observation period up to 13 years. Most CIndU patients (73%, n = 145/200 with available data on response) had complete/good response to omalizumab treatment, without significant differences between CIndU subtypes. Sixty-two (26%) patients discontinued omalizumab; due to well-controlled disease (47%, n = 29), ineffectiveness (34%, n = 21), side effects (3%, n = 2), combination of ineffectiveness and side effects (3%, n = 2) and other reasons (13%, n = 8). The median estimated omalizumab treatment duration exceeded 5 years (54% drug survival at 5 years) and was mostly determined by well-controlled disease. Higher age predicted a lower chance to discontinue omalizumab due to well-controlled disease (HR 0.969, 95%CI 0.945-0.995). CIndU subtype and presence of minor CSU were not related to response and time until omalizumab discontinuation for any reason. CONCLUSION: Omalizumab is highly effective and safe in CIndU patients, with long estimated treatment duration mainly reflecting long disease duration. Our data show omalizumab's high potential as treatment in any subtype of CIndU and support its clinical use for these patients.

Postoperative pressure injuries in adults having surgery under general anaesthesia: systematic review of perioperative risk factors.

BACKGROUND: Pressure injuries (PIs) after surgery affect thousands of people worldwide. Their management is expensive, a cost that can be reduced with proper preventive measures. Patients having surgery under general anaesthesia are at risk of developing PI, yet no specific tool has been developed to assess the risk in these patients. This review aimed to summarize the published data on perioperative risk factors associated with the development of PI in adults having surgery under general anaesthesia. METHODS: All studies reporting on risk factors associated with the development of PI were included. Data were extracted from all articles and meta-analysis was performed when three or more studies reported on a specific variable. RESULTS: The analysis identified five factors significantly associated with the development of PIs: cardiovascular disease, respiratory disease, diabetes mellitus, low haemoglobin level and longer duration of surgery. Factors not associated included serum albumin concentration, use of vasopressors during surgery, use of corticosteroids, sex and age. CONCLUSION: Cardiovascular disease, respiratory disease, diabetes mellitus, anaemia and duration of surgery should be taken into consideration when trying to identify surgical patients at high risk of developing PIs. These factors could be used to predict PIs after surgery.

ANTECEDENTES: Las úlceras por presión (pressure injuries, PI) son un problema de salud importante que afecta a millones de personas en todo el mundo. El tratamiento de las PI conlleva un coste elevado, que podría reducirse con medidas preventivas adecuadas. Aunque los pacientes a los que se realiza una cirugía bajo anestesia general tienen un mayor riesgo de desarrollar PI, no se han creado herramientas específicas para evaluar su riesgo. El objetivo de este trabajo es resumir los datos disponibles acerca de los factores de riesgo perioperatorios asociados al desarrollo de PI en pacientes adultos en los que se realiza un procedimiento quirúrgico bajo anestesia general. Un mejor conocimiento de los factores de riesgo de las PI podría permitir la estratificación de los pacientes antes de la cirugía y establecer mecanismos de prevención específicos. Número de registro Prospero CRD42019111877. MÉTODOS: Se incluyeron todos los estudios que analizaron los factores de riesgo asociados a las PI. Se obtuvieron los datos de todos los artículos y se realizó un metaanálisis cuando tres o más estudios presentaban información de una determinada variable. RESULTADOS: El análisis identificó cinco factores estadísticamente significativos asociados con el desarrollo de PI: enfermedad cardiovascular, enfermedad respiratoria, diabetes mellitus, mayor duración de la cirugía y hemoglobina baja. No se asociaron factores como la s-albúmina, la utilización de vasopresores durante la cirugía, el uso de corticoides, el sexo o la edad. CONCLUSIÓN: Se recomienda tener en cuenta la existencia de enfermedades cardiovasculares o respiratorias, diabetes mellitus, niveles bajos de hemoglobina y la duración de la cirugía a la hora de identificar a los pacientes quirúrgicos con riesgo elevado de desarrollar PI.

Temporal variation of Staphylococcus aureus clonal complexes in atopic dermatitis: a follow-up study.

BACKGROUND: A strong link between disease severity and Staphylococcus aureus colonization of the skin has been reported in patients with atopic dermatitis (AD). OBJECTIVES: To examine temporal variations in S. aureus colonization and S. aureus CC type in patients with AD, and to investigate links to disease severity, skin barrier properties and filaggrin gene (FLG) mutations. METHODS: This was a follow-up study of a cohort of 101 adult patients with AD recruited from an outpatient clinic. Bacterial swabs were taken at baseline and follow-up from lesional skin, nonlesional skin and the nose. Swabs positive for S. aureus were characterized by spa and the respective clonal complex (CC) type was assigned. Patients were characterized with respect to disease severity [Scoring Atopic Dermatitis (SCORAD)], skin barrier properties [transepidermal water loss (TEWL), pH] and FLG mutations. RESULTS: In total, 63 patients participated in a follow-up visit. Twenty-seven patients (43%) were colonized at both visits, 27 were colonized at only one visit and nine (14%) were not colonized at either visit. Of patients colonized at both visits, 52% remained colonized with the same CC type at follow-up. Change in CC type was related to an increase in SCORAD of 10·7 points; patients who carried the same CC type had a reduction in SCORAD of 4·4 points. Significantly higher skin pH was found in patients colonized at both visits, while change in CC type was not related to TEWL, pH or FLG mutations. CONCLUSIONS: The data indicate that temporal variation in S. aureus CC type is linked to flares of the disease.

Cost-effectiveness of incisional negative pressure wound therapy compared with standard care after caesarean section in obese women: a trial-based economic evaluation.

OBJECTIVE: To evaluate the cost-effectiveness of incisional negative pressure wound therapy (iNPWT) in preventing surgical site infection in obese women after caesarean section. DESIGN: A cost-effectiveness analysis conducted alongside a clinical trial. SETTING: Five obstetric departments in Denmark. POPULATION: Women with a pregestational body mass index (BMI) ≥30 kg/m2 . METHOD: We used data from a randomised controlled trial of 876 obese women who underwent elective or emergency caesarean section and were subsequently treated with iNPWT (n = 432) or a standard dressing (n = 444). Costs were estimated using data from four Danish National Databases and analysed from a healthcare perspective with a time horizon of 3 months after birth. MAIN OUTCOME MEASURES: Cost-effectiveness based on incremental cost per surgical site infection avoided and per quality-adjusted life-year (QALY) gained. RESULTS: The total healthcare costs per woman were €5793.60 for iNPWT and €5840.89 for standard dressings. Incisional NPWT was the dominant strategy because it was both less expensive and more effective; however, no statistically significant difference was found for costs or QALYs. At a willingness-to-pay threshold of €30,000, the probability of the intervention being cost-effective was 92.8%. A subgroup analysis stratifying by BMI shows that the cost saving of the intervention was mainly driven by the benefit to women with a pre-pregnancy BMI ≥35 kg/m2 . CONCLUSION: Incisional NPWT appears to be cost saving compared with standard dressings but this finding is not statistically significant. The cost savings were primarily found in women with a pre-pregnancy BMI ≥35 kg/m2 . TWEETABLE ABSTRACT: Prophylactic incisional NPWT reduces the risk of SSI after caesarean section and is probably dominant compared with standard dressings #healtheconomics.

Prophylactic incisional negative pressure wound therapy reduces the risk of surgical site infection after caesarean section in obese women: a pragmatic randomised clinical trial.

OBJECTIVE: To evaluate the reduction of surgical site infections by prophylactic incisional negative pressure wound therapy compared with standard postoperative dressings in obese women giving birth by caesarean section. DESIGN: Multicentre randomised controlled trial. SETTING: Five hospitals in Denmark. POPULATION: Obese women (prepregnancy body mass index (BMI) ≥30 kg/m2 ) undergoing elective or emergency caesarean section. METHOD: The participants were randomly assigned to incisional negative pressure wound therapy or a standard dressing after caesarean section and analysed by intention-to-treat. Blinding was not possible due to the nature of the intervention. MAIN OUTCOME MEASURES: The primary outcome was surgical site infection requiring antibiotic treatment within the first 30 days after surgery. Secondary outcomes included wound exudate, dehiscence and health-related quality of life. RESULTS: Incisional negative pressure wound therapy was applied to 432 women and 444 women had a standard dressing. Demographics were similar between groups. Surgical site infection occurred in 20 (4.6%) women treated with incisional negative pressure wound therapy and in 41 (9.2%) women treated with a standard dressing (relative risk 0.50, 95% CI 0.30-0.84; number needed to treat 22; P = 0.007). The effect remained statistically significant when adjusted for BMI and other potential risk factors. Incisional negative pressure wound therapy significantly reduced wound exudate whereas no difference was found for dehiscence and quality of life between the two groups. CONCLUSION: Prophylactic use of incisional negative pressure wound therapy reduced the risk of surgical site infection in obese women giving birth by caesarean section. TWEETABLE ABSTRACT: RCT: prophylactic incisional NPWT versus standard dressings postcaesarean in 876 women significantly reduces the risk of SSI.

Meta-analysis of negative-pressure wound therapy for closed surgical incisions.

BACKGROUND: Postoperative wound complications are common following surgical procedures. Negative-pressure wound therapy (NPWT) is well recognized for the management of open wounds and has been applied recently to closed surgical incisions. The evidence base to support this intervention is limited. The aim of this study was to assess whether NPWT reduces postoperative wound complications when applied to closed surgical incisions. METHODS: This was a systematic review and meta-analysis of randomized clinical trials of NPWT compared with standard postoperative dressings on closed surgical incisions. RESULTS: Ten studies met the inclusion criteria, reporting on 1311 incisions in 1089 patients. NPWT was associated with a significant reduction in wound infection (relative risk (RR) 0·54, 95 per cent c.i. 0·33 to 0·89) and seroma formation (RR 0·48, 0·27 to 0·84) compared with standard care. The reduction in wound dehiscence was not significant. The numbers needed to treat were three (seroma), 17 (dehiscence) and 25 (infection). Methodological heterogeneity across studies led to downgrading of the quality of evidence to moderate for infection and seroma, and low for dehiscence. CONCLUSION: Compared with standard postoperative dressings, NPWT significantly reduced the rate of wound infection and seroma when applied to closed surgical wounds. Heterogeneity between the included studies means that no general recommendations can be made yet.

Effect of detergents on the physicochemical properties of skin stratum corneum: a two-photon excitation fluorescence microscopy study.

OBJECTIVE: Understanding the structural and dynamical features of skin is critical for advancing innovation in personal care and drug discovery. Synthetic detergent mixtures used in commercially available body wash products are thought to be less aggressive towards the skin barrier when compared to conventional detergents. The aim of this work is to comparatively characterize the effect of a mild synthetic cleanser mixture (SCM) and sodium dodecyl sulphate (SDS) on the hydration state of the intercellular lipid matrix and on proton activity of excised skin stratum corneum (SC). METHOD: Experiments were performed using two-photon excitation fluorescence microscopy. Fluorescent images of fluorescence reporters sensitive to proton activity and hydration of SC were obtained in excised skin and examined in the presence and absence of SCM and SDS detergents. RESULTS: Hydration of the intercellular lipid matrix to a depth of 10 µm into the SC was increased upon treatment with SCM, whereas SDS shows this effect only at the very surface of SC. The proton activity of SC remained unaffected by treatment with either detergent. CONCLUSION: While our study indicates that the SC is very resistant to external stimuli, it also shows that, in contrast to the response to SDS, SCM to some extent modulates the in-depth hydration properties of the intercellular lipid matrix within excised skin SC.

Chronological age affects the permeation of fentanyl through human skin in vitro.

AIM: To study the influence of chronological age on fentanyl permeation through human skin in vitro using static diffusion cells. Elderly individuals are known to be more sensitive to opioids and obtain higher plasma concentrations following dermal application of fentanyl compared to younger individuals. The influence of age - as an isolated pharmacokinetic term - on the absorption of fentanyl has not been previously studied. METHOD: Human skin from 30 female donors was mounted in static diffusion cells, and samples were collected during 48 h. Donors were divided into three age groups: <30 years of age (n = 6), ≥30 and <60 years of age (n = 18) and ≥60 years of age (n = 6). RESULTS: The youngest group had a significantly higher mean absorption (3,100 ng/cm(2)) than the two other groups (2,000 and 1,475 ng/cm(2), respectively) and a significant larger AUC (young age group: 9,393 ng; middle and old age groups: 5,922 and 4,050 ng, respectively). Furthermore, the lag time and absorption rate were different between the three groups, with a significantly higher rate in the young participants versus the oldest participants. CONCLUSION: We demonstrate that fentanyl permeates the skin of young individuals in greater amounts and at a higher absorption rate than in middle-aged and old individuals in vitro.

Mesenchymal stem cells in oral reconstructive surgery: a systematic review of the literature.

This study evaluated clinical outcomes following intraoperative use of adult mesenchymal stem cells (MSCs) in various oral reconstructive procedures. PubMed was searched without language restrictions from 2000 to 2011 using the search words stem cell, oral surgery, tissue engineering, sinus lift, bone regeneration and combinations of these. Inclusion criteria were intraoperative use of MSCs in the study design. Reference lists of the articles found were searched for other related studies. Eighteen clinical trials using MSCs for sinus augmentation were found: five case reports on the repair of large bony defects and six studies on ridge augmentation and healing of alveolar sockets after third molar extraction. The findings suggest that MSCs are capable of producing in vivo bone, re-establishing lost tissue and facilitating placement of dental implants. Use of MSCs would reduce patient morbidity because of a less stressful harvesting technique than that of autogenous bone. The majority of clinical trials indicate that MSCs can produce bone in vivo. However, a satisfactory outcome was not seen in all studies, and due to the diversity of study designs, a 'golden approach' cannot be determined. Before use of MSCs can be considered as a first-choice treatment, more predictable outcomes and better long-term prognoses need to be established. Conventional bone grafting remains the gold standard.

Comparison of open-flow microperfusion and microdialysis methodologies when sampling topically applied fentanyl and benzoic acid in human dermis ex vivo.

PURPOSE: The purpose of this study is to compare two sampling methods--dermal Open-Flow Microperfusion (dOFM) and dermal Microdialysis (dMD) in an international joint experiment in a single-laboratory setting. We used human ex-vivo skin and sampled topically administered Fentanyl and Benzoic Acid. The second purpose was to provide guidance to researchers in choosing the most efficient method for a given penetrant and give suggestions concerning critical choices for successful dermal sampling. METHODS: The dOFM and dMD techniques are compared in equal set-ups using three probe-types (one dOFM probe and two dMD probe-types) in donor skin (n = 9)--27 probes of each type sampling each penetrant in solutions applied in penetrationchambers glued to the skin surface over a time range of 20 h. RESULTS: Pharmacokinetic results demonstrated concordance between dOFM and dMD sampling technique under the given experimental conditions. The methods each had advantages and limitations in technical, practical and hands-on comparisons. CONCLUSION: When planning a study of cutaneous penetration the advantages and limitations of each probe-type have to be considered in relation to the scientific question posed, the physico-chemical characteristics of the substance of interest, the choice of experimental setting e.g. ex vivo/in vivo and the analytical skills available.

Probe depth matters in dermal microdialysis sampling of benzoic acid after topical application: an ex vivo study in human skin.

Microdialysis (MD) in the skin - dermal microdialysis (DMD) - is a unique technique for sampling of topically as well as systemically administered drugs at the site of action, e.g. sampling of dermatological drug concentrations in the dermis. Debate has concerned the existence of a correlation between the depth of the sampling device - the probe - in the dermis and the amount of drug sampled following topical drug administration. This study evaluates the relation between probe depth and drug sampling using dermal DMD sampling ex vivo in human skin. We used superficial (<1 mm), intermediate (1-2 mm) and deep (>2 mm) positioning of the linear MD probe in the dermis of human abdominal skin, followed by topical application of 4 mg/ml of benzoic acid (BA) in skin chambers overlying the probes. Dialysate was sampled every hour for 12 h and analysed for BA content by high-performance liquid chromatography. Probe depth was measured by 20-MHz ultrasound scanning. The area under the time-versus-concentration curve (AUC) describes the drug exposure in the tissue during the experiment and is a relevant parameter to compare for the 3 dermal probe depths investigated. The AUC(0-12) were: superficial probes: 3,335 ± 1,094 µg·h/ml (mean ± SD); intermediate probes: 2,178 ± 1,068 µg·h/ml, and deep probes: 1,159 ± 306 µg·h/ml. AUC(0-12) sampled by the superficial probes was significantly higher than that of samples from the intermediate and deeply positioned probes (p value <0.05). There was a significant inverse correlation between probe depth and AUC(0-12) sampled by the same probe (p value <0.001, r(2) value = 0.5). The mean extrapolated lag-times (±SD) for the superficial probes were 0.8 ± 0.1 h, for the intermediate probes 1.7 ± 0.5 h, and for the deep probes 2.7 ± 0.5 h, which were all significantly different from each other (p value <0.05). In conclusion, this paper demonstrates that there is an inverse relationship between the depth of the probe in the dermis and the amount of drug sampled following topical penetration ex vivo. The result is of relevance to the in vivo situation, and it can be predicted that the differences in sampling at different probe depths will have a more significant impact in the beginning of a study or in studies of short duration. Based on this study it can be recommended that studies of topical drug penetration using DMD sampling should include measurements of probe depth and that efforts should be made to minimize probe depth variability.

Storage conditions of skin affect tissue structure and subsequent in vitro percutaneous penetration.

Storage of skin at low temperatures may affect its structure. There is no report in the literature on the correlation between spatially resolved skin structure and percutaneous penetration after different storage conditions. The present study applies imaging techniques (multiphoton excitation fluorescence microscopy) and in vitro percutaneous penetration of caffeine under four different storage conditions using skin samples from the same donors: fresh skin, skin kept at -20°C for 3 weeks (with or without the use of polyethylene glycol) and at -80°C. Our results show a correlation between increasing permeation of caffeine and tissue structural damage caused by the storage conditions, most so after skin storage at -80°C. The presented approach, which combines imaging techniques with studies on percutaneous penetration, enables the link between tissue damage at selected depths and penetration into the upper layers of the epidermis to be investigated.

Joint practice guidelines for radionuclide lymphoscintigraphy for sentinel node localization in oral/oropharyngeal squamous cell carcinoma.

Involvement of the cervical lymph nodes is the most important prognostic factor for patients with oral/oropharyngeal squamous cell carcinoma (OSCC), and the decision of whether to electively treat patients with clinically negative necks remains a controversial topic. Sentinel node biopsy (SNB) provides a minimally invasive method for determining the disease status of the cervical node basin, without the need for a formal neck dissection. This technique potentially improves the accuracy of histologic nodal staging and avoids overtreating three-quarters of this patient population, minimizing associated morbidity. The technique has been validated for patients with OSCC, and larger-scale studies are in progress to determine its exact role in the management of this patient population. This document is designed to outline the current best practice guidelines for the provision of SNB in patients with early-stage OSCC, and to provide a framework for the currently evolving recommendations for its use. Preparation of this guideline was carried out by a multidisciplinary surgical/nuclear medicine/pathology expert panel under the joint auspices of the European Association of Nuclear Medicine (EANM) Oncology Committee and the Sentinel European Node Trial (SENT) Committee.

The prognostic significance of histological features in oral squamous cell carcinoma.

BACKGROUND: Different factors predict nodal metastasis, recurrence and survival in oral cancer. The aim was to assess the prognostic value of histological features related to the primary tumour. METHODS: A total of 144 patients surgically treated at Odense University Hospital for oral cancer between 1999 and 2004 were included in the study. Postoperative radiation therapy was given in case of close and involved margins or high TNM stages (UICC 1997). Median follow-up time was 38 months. All surgical resections were reviewed and 22 histological characteristics were assessed. RESULTS: The predominant sites were floor of mouth (FOM, 39%) and lateral tongue (35%). Fifty-nine per cent had UICC97 stage I-II disease. Five-year cause-specific survival was observed in 65%. Nodal involvement at diagnosis was observed in 36% which was significantly related to grade, neural and vascular invasion; surgical margins and increasing tumour depth. A cut-off value of 2 mm (4 mm for FOM) separated patients without and with nodal metastasis at the time of diagnosis. However, on multivariate analysis, neck disease was only associated with tumour depth and grade. Cox analysis of local recurrence in the oral cavity over time showed that tumour diameter and surgical margins were significant predictors while cause-specific survival was related to diameter, depth of invasion, surgical margins and extracapsular spread (ECS). CONCLUSIONS: Tumour depth and grade were strong prognostic factors for nodal metastasis, independently of other histological features. Tumour diameter and margins independently predict local recurrences in the oral cavity as well as cause-specific survival. Nodal involvement and ECS were associated with adverse prognosis.

The nanoscopic molecular pathway through human skin.

BACKGROUND: Knowledge regarding the barrier properties of human skin is important for understanding skin pathology, developing of transdermal drug delivery systems and computational skin absorption models; however, the molecular pathways through human skin remains to be fully investigated on a nanoscopic level. In particular the nanoscopic pathway of molecules passing the intercellular lipid bilayers separating the corneocytes in the stratum corneum (SC) is not fully elucidated. METHODS: Using stimulated emission depletion microscopy (STED) and Förster resonance energy transfer (FRET) the molecular pathways through the SC, the main barrier of the skin, are determined for lipophilic and water-soluble molecules at a nanoscopic resolution. RESULTS: Using STED and confocal microscopy, water-soluble dyes, were observed to be present in both the corneocytes and in the intercellular lipid matrix, whereas the lipophilic dyes were predominately in the intercellular lipid bilayers. FRET was observed in the SC between the lipophilic and water-soluble dyes, the existence of a minimum possible distance between acceptor and donor molecules of 4.0 ±â€¯0.1 nm was found. CONCLUSIONS: The results indicate that lipophilic molecules penetrate the stratum corneum via the intercellular lipids bilayers separating the corneocytes in the SC, while the more water-soluble molecules penetrate the stratum corneum via the transcellular route through the corneocytes and intercellular lipid bilayers via the polar head groups of lipid molecules in the bilayers. GENERAL SIGNIFICANCE: Knowledge of the nanoscopic molecular pathways through human skin will help understand the skin barrier function and will be of use for computational skin absorption models and transdermal drug delivery strategies.

Adipose-derived regenerative cells and fat grafting for treating breast cancer-related lymphedema: Lymphoscintigraphic evaluation with 1 year of follow-up.

BACKGROUND: Breast cancer-related lymphedema (BCRL) is a feared late complication. Treatment options are lacking at present. Recent studies have suggested that mesenchymal stromal cells can alleviate lymphedema. Herein, we report the results from the first human pilot study with adipose-derived regenerative cells (ADRCs) for treating BCRL with 1 year of follow-up. MATERIAL AND METHODS: We included 10 patients with BCRL. ADRCs were injected directly into the axillary region together with a scar-releasing fat grafting procedure. Primary endpoint was change in arm volume. Secondary endpoints were change in patient-reported outcomes, changes in lymph flow, and safety. RESULTS: During follow-up, no significant change in volume was noted. Patient-reported outcomes improved significantly with time. Five patients reduced their use of conservative management. Quantitative lymphoscintigraphy did not improve on the lymphedema-affected arms. ADRCs were well tolerated, and only minor transient adverse events related to liposuction were noted. CONCLUSIONS: In this pilot study, a single injection of ADRCs improved lymphedema based on patient-reported outcome measures, and there were no serious adverse events during the follow-up period. Lymphoscintigraphic evaluation showed no improvement after ADRC treatment. There was no change in excess arm volume. Results of this trial need to be confirmed in randomized clinical trials.

Moving towards personalised therapy in head and neck squamous cell carcinoma through analysis of next generation sequencing data.

Personalised medicine tumour boards, which leverage genomic data to improve clinical management, are becoming standard for the treatment of many cancers. This paper is designed as a primer to assist clinicians treating head and neck squamous cell carcinoma (HNSCC) patients with an understanding of the discovery and functional impact of recurrent genetic lesions that are likely to influence the management of this disease in the near future. This manuscript integrates genetic data from publicly available array comparative genome hybridization (aCGH) and next-generation sequencing genetics databases to identify the most common molecular alterations in HNSCC. The importance of these genetic discoveries is reviewed and how they may be incorporated into clinical care decisions is discussed. Considerations for the role of genetic stratification in the clinical management of head and neck cancer are maturing rapidly and can be improved by integrating data sets. This article is meant to summarise the discoveries made using multiple genomic platforms so that the head and neck cancer care provider can apply these discoveries to improve clinical care.

Creating a National Coalition to Address Tractor Overturn Fatalities.

Tractor overturns continue to be the leading cause of death on U.S. farms. While rollover protective structures (ROPS) are effective in preventing these fatalities, they are underutilized due to a number of barriers. Past programs in the U.S. and abroad have targeted this area of agricultural safety; however, a national program is not yet in place for U.S. farmers. This study seeks to build a national partnership to address tractor overturn fatalities by increasing the number of tractors with ROPS. A diverse, multisector steering committee has been organized and is working together using Whole System in a Room methods. This method brings together partners from nine stakeholder groups to identify and commit to a collaborative solution to the issue.

Concept identification for a power take-off shielding campaign.

ABSTRACT Machinery entanglements, specifically power take-off (PTO) entanglements, are a leading cause of injuries and fatalities on farms. In order to address this life-threatening issue, a social marketing campaign is being developed to reduce barriers and emphasize motivators to shielding. This article discusses the process of designing, testing, and selecting concepts to be used in the campaign. Small-group discussions (triads) were held to test 13 message concepts. Participants were asked to provide feedback and select the two messages that they believed to be most powerful. Upon completion, three message concepts were selected to be finalized.