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Atopic dermatitis (AD) is associated with substantial financial cost, including increased out-of-pocket (OOP) expenses. Associations and impact of OOP costs are poorly understood.The aim of the study was to characterize the impact and associations of OOP health care expenses for AD.A 25-question online survey was administered to National Eczema Association members (N = 113,502). Inclusion criteria (US residents aged ≥18 years; self-reported AD or primary caregiver of individual with AD) were met by 77.3% (1118 of 1447).Respondents with monthly OOP expenses greater than $200 were more likely to have increased AD severity, flares, health care provider visits, prescription polypharmacy, use of step-up therapy, frequent skin infections, and poorer disease control ( P0.005 for all). Respondents with OOP yearly expenditures greater than $1000 had similar associations and additionally increased rates of comorbid asthma, allergic rhinitis, and anxiety/depression ( P0.005 for all). A total of 64.6% (n = 624) reported harmful household financial impact of OOP expenses. Predictors of harmful impact included severe AD (adjusted odds ratio [95% confidence interval], 2.62 [1.11-6.19], P = 0.04), comorbid asthma (1.42 [1.07-1.87], P = 0.03), 5 health care provider visits or more in a year (2.80 [1.62-4.82], P = 0.0007), greater than $200 OOP monthly expenditures (2.16 [1.45-3.22], 0.0006), and $1000 annual OOP expenditures or more (4.56 [3.31-6.27], P0.0001).Out-of-pocket expenses for AD significantly impact household finances. Clinical interventions are needed to minimize OOP expenses while optimizing care outcomes.Capsule Summary:• Atopic dermatitis (AD) is associated with significant financial cost, including increased out-of-pocket (OOP) expenses, although the impact and associations of OOP health care expenses for AD management are not well understood.• The OOP health care expenses related to AD are associated with increased disease severity and health care utilization and significantly impact the household finances of patients and caregivers.• Health care providers should be mindful of the OOP financial burden related to AD management and engage in shared decision making to create a treatment plan that is practical and effective and minimizes household financial impact.

Black race is associated with increased atopic dermatitis (AD) severity and healthcare resource utilization. However, the burden of out-of-pocket (OOP) expenses among black individuals with AD is not well understood. We sought to characterize the categories and impact of OOP healthcare expenses associated with AD management among black individuals. A 25-question voluntary online survey was administered to National Eczema Association members (N = 113,502). Inclusion criteria (US residents age ≥ 18 years; self-report of AD or primary caregivers of individuals with AD) was met by 77.3% (1118/1447) of respondents. Black individuals with AD were younger, had lower household income, Medicaid, urban residence, poor AD control and frequent skin infections (P ≤ 0.02). Blacks vs. non-blacks reported more OOP costs for prescription medications covered (74.2% vs. 63.6%, P = 0.04) and not covered (65.1% vs. 46.5%, P = 0.0004) by insurance, emergency room visits (22.1% vs. 11.8%, P = 0.005), and outpatient laboratory testing (33.3% vs. 21.8%, P = 0.01). Black race was associated with increased household financial impact from OOP expenses (P = 0.0009), and predictors of financial impact included minimally controlled AD (adjusted OR [95% CI] 13.88 [1.63–117.96], P = 0.02), systemic therapy (4.34 [1.63–11.54], 0.003), > $200 monthly OOP expenses (14.28 [3.42–59.60], P = 0.0003), and Medicaid (4.02 [1.15–14.07], P = 0.03). Blacks with Medicaid had higher odds of harmful financial impact (3.32 [1.77–6.24], P = 0.0002) than those of black race (1.81 [1.04–3.15], P = 0.04) or with Medicaid (1.39 [1.02–1.88], P = 0.04) alone. Black race is associated with increased OOP costs for AD and significant household financial impact. Targeted interventions are needed to address financial disparities in AD.

Background Atopic dermatitis (AD) is associated with considerable financial cost. However, the full burden of out-of-pocket (OOP) expenses is not well understood. Objective We sought to characterize the OOP health care expenses associated with AD management. Methods A 25-question voluntary online survey was administered to National Eczema Association members worldwide (n = 113,502). Inclusion criteria (US residents age ≥18 years who either self-reported had AD or were primary caregivers of individuals with AD) were met by 77.3% (1118/1447) of respondents. Results Respondents reported OOP expenses in 3 categories: (1) health care providers and prescriptions, including health care provider visit deductibles (68.7% [686]), prescription co-pays (64.3% [635]), and prescriptions not covered by insurance (48.6% [468]); (2) nonprescription health care products, including moisturizers (94.3% [934]), hygiene products (85.0% [824], allergy medications (75.1% [715]), itch relievers (68.25% [647]), dietary supplements (52.2% [491]), and sleep aids (37.0% [336]); and (3) complementary approaches, including cleaning products (74.7% [732]), clothing/bedding (44.8% [430]), alternative medications (19.0% [180]), and adjunctive therapies (15.9% [150]). The median annual AD OOP expense was US $600 (range, US $0-$200,000), with 41.9% (364) reporting expenditures US $1000 or greater. Conclusions Out-of-pocket expenses place a significant financial burden on individuals with AD. Additional studies are needed to better understand associations and impact of OOP costs.

Carcinoid crisis is a life-threatening manifestation of carcinoid syndrome characterized by profound autonomic instability in the setting of catecholamine release from stress, tumor manipulation, or anesthesia. Here, we present an unusual case of carcinoid crisis leading to acute systolic heart failure requiring mechanical circulatory support. (Level of Difficulty: Intermediate.), Graphical abstract

This study quantified plan quality differences across the 4 cancer centers in Alberta, Canada for plans that followed the PROstate Fractionated Irradiation Trial protocol.Prostate plans of 235 patients were retrospectively reviewed. Interinstitutional plan quality comparisons were made based on distributions of protocol-specified parameters using 1-way analysis of variance with Games-Howell post hoc analysis. Dosimetrically representative cases were selected from each center using k-medoid clustering, enabling side-by-side comparison of dose-volume histograms and dose distributions. Fourteen anatomic features were investigated to explore interinstitutional patient population differences. Anatomically representative cases were selected from each center to explore differences in planning practices. Tumor control probability (TCP), as well as rectal wall and bladder wall normal tissue complication probabilities (NTCPs), were calculated to quantify the clinical effect of the differences in plan quality.Comparing the mean value of each center to the other 3, statistically significant differences were observed for bladder wall D30% and D50%, left and right femoral heads D5%, planning target volume D99% and D1cc, and clinical target volume D99%. Dosimetrically representative cases demonstrated consistent results. Although anatomic differences were observed between the center-specific populations, an analysis using anatomically similar cases demonstrated consistent trends in the dosimetric differences, suggesting the dosimetric variation is not exclusively due to anatomic differences. Minimal differences (1%) among the 4 centers were noted for TCP and NTCPs, suggesting the reported differences in plan quality may not have any clinical significance.Despite common guidelines, statistically significant differences in plan quality metrics occurred among the 4 investigated centers. The differences are due at least in part to variation in local planning practices. TCP and NTCP calculations suggest that the clinical significance of the differences is minimal. These results can serve as a reference for the degree of variation among centers that can be accepted when a common protocol is adopted.

IntroductionBehavioural interventions in early life appear to show some effect in reducing childhood overweight and obesity. However, uncertainty remains regarding their overall effectiveness, and whether effectiveness differs among key subgroups. These evidence gaps have prompted an increase in very early childhood obesity prevention trials worldwide. Combining the individual participant data (IPD) from these trials will enhance statistical power to determine overall effectiveness and enable examination of intervention-covariate interactions. We present a protocol for a systematic review with IPD meta-analysis to evaluate the effectiveness of obesity prevention interventions commencing antenatally or in the first year after birth, and to explore whether there are differential effects among key subgroups.Methods and analysisSystematic searches of Medline, Embase, CENTRAL, CINAHL, PsycInfo, and trial registries for all ongoing and completed randomised controlled trials evaluating behavioural interventions for the prevention of early childhood obesity have been completed up to March 2020 and will be updated annually to include additional trials. Eligible trialists will be asked to share their IPD; if unavailable, aggregate data will be used where possible. An IPD meta-analysis and a nested prospective meta-analysis (PMA) will be performed using methodologies recommended by the Cochrane Collaboration. The primary outcome will be body mass index (BMI) z-score at age 24 +/- 6 months using World Health Organisation Growth Standards, and effect differences will be explored among pre-specified individual and trial-level subgroups. Secondary outcomes include other child weight-related measures, infant feeding, dietary intake, physical activity, sedentary behaviours, sleep, parenting measures and adverse events.Ethics and disseminationApproved by The University of Sydney Human Research Ethics Committee (2020/273) and Flinders University Social and Behavioural Research Ethics Committee (project no. HREC CIA2133-1). Results will be relevant to clinicians, child health services, researchers, policy-makers and families, and will be disseminated via publications, presentations, and media releases.RegistrationProspectively registered on PROSPERO: CRD42020177408STRENGTHS AND LIMITATIONS OF THIS STUDYThis will be the largest individual participant data (IPD) meta-analysis evaluating behavioural interventions for the prevention of early childhood obesity to date, and will provide the most reliable and precise estimates of early intervention effects to inform future decision-making.IPD meta-analysis methodology will enable unprecedented exploration of important individual and trial-level characteristics that may be associated with childhood obesity or that may be effect modifiers.The proposed innovative methodologies are feasible and have been successfully piloted by members of our group.It may not be possible to obtain IPD from all eligible trials; in this instance, aggregate data will be used where available, and sensitivity analyses will be conducted to assess inclusion bias.Outcome measures may be collected and reported differently across included trials, potentially increasing imprecision; however, we will harmonise available data where possible, and encourage those planning or conducting ongoing trials to collect common core outcomes following prospective meta-analysis methodology.

IntroductionLittle is known about how early (e.g., commencing antenatally or in the first 12 months after birth) obesity prevention interventions seek to change behaviour and which components are or are not effective. This study aims to 1) characterise early obesity prevention interventions in terms of target behaviours, delivery features, and behaviour change techniques (BCTs), 2) explore similarities and differences in BCTs used to target behaviours, and 3) explore effectiveness of intervention components in preventing childhood obesity.Methods and analysisAnnual comprehensive systematic searches will be performed in Epub Ahead of Print/MEDLINE, Embase, Cochrane (CENTRAL), CINAHL, PsycINFO, as well as clinical trial registries. Eligible randomised controlled trials of behavioural interventions to prevent childhood obesity commencing antenatally or in the first year after birth will be invited to join the TOPCHILD Collaboration. Standard ontologies will be used to code target behaviours, delivery features and BCTs in both published and unpublished intervention materials provided by trialists. Narrative syntheses will be performed to summarise intervention components and compare applied BCTs by types of target behaviours. Exploratory analyses will be undertaken to assess effectiveness of intervention components.Ethics and disseminationThe study has been approved by The University of Sydney Human Research Ethics Committee (project no. 2020/273) and Flinders University Social and Behavioural Research Ethics Committee (project no. HREC CIA2133-1). The study’s findings will be disseminated through peer-reviewed publications, conference presentations, and targeted communication with key stakeholders.DiscussionOur study will provide an in depth understanding of behavioural components and delivery features used in obesity prevention interventions starting antenatally or in the first 12 months after birth. Understanding common intervention approaches in a systematic way will provide much needed insight to advance the design of early obesity prevention interventions and provide the opportunity to undertake future quantitative predictive modelling.RegistrationPROSPERO registration no. CRD42020177408STRENGTHS AND LIMITATIONS OF THIS STUDYThis study provides an understanding of behaviours targeted, behaviour change techniques and delivery features used in early childhood obesity prevention trials identified in a systematic review as being eligible for inclusion in the Transforming Obesity Prevention in CHILDren (TOPCHILD) Collaboration.Extends previous methods by coding behaviour change techniques in published and unpublished intervention materials and performing cross validation with trialists through the TOPCHILD Collaboration.Using standardised coding taxonomies will allow for comparisons across studies, and we will pilot test new ontologies from the Human Behaviour Change Project.Explores the complex area of targeting parent and caregivers’ behaviours to impact child outcomes across four key obesity prevention behavioural domains (relating to infant feeding practices, food provision and parent feeding practices, movement practices, sleep health practices).This study will provide preliminary results regarding the examination of intervention components’ effectiveness based on exploratory analysis. Yet, the internationally unique database this project creates will further our understanding of effective intervention components in future research.To date we already have 38 out of 65 eligible trials agreeing to share data, since not all trials may provide unpublished material we may perform sensitivity analyses comparing trials that have shared data to trials that have not shared materials.

PurposeTo identify which patient-reported outcomes (PROs) may be most improved through adaptive radiation therapy (ART) with the goal of reducing toxicity incidence among head and neck cancer patients.MethodsOne hundred fifty-five head and neck cancer patients receiving radical VMAT (chemo)radiotherapy (66-70 Gy in 30-35 fractions) completed the MD Anderson Symptom Inventory, MD Anderson Dysphagia Inventory (MDADI), and Xerostomia Questionnaire while attending routine follow-up clinics between June-October 2019. Hierarchical clustering characterized symptom endorsement. Conventional statistical approaches indicated associations between dose and commonly reported symptoms. These associations, and the potential benefit of interfractional dose corrections, were further explored via logistic regression.ResultsRadiotherapy-related symptoms were commonly reported (dry mouth, difficulty swallowing/chewing). Clustering identified three patient subgroups reporting: none/mild symptoms for most items (60.6% of patients); moderate/severe symptoms affecting some aspects of general well-being (32.9%); and moderate/severe symptom reporting for most items (6.5%). Clusters of PRO items broadly consisted of acute toxicities, general well-being, and head and neck-specific symptoms (xerostomia, dysphagia). Dose-PRO relationships were strongest between delivered pharyngeal constrictor Dmean and patient-reported dysphagia, with MDADI composite scores (mean ± SD) of 25.7 ± 18.9 for patients with Dmean vs. 32.4 ± 17.1 with Dmean ≥50 Gy. Based on logistic regression models, during-treatment dose corrections back to planned values may confer ≥5% decrease in the absolute risk of self-reported physical dysphagia symptoms ≥1 year post-treatment in 1.2% of patients, with a ≥5% decrease in relative risk in 23.3% of patients.ConclusionsPatient-reported dysphagia symptoms are strongly associated with delivered dose to the pharyngeal constrictor. Dysphagia-focused ART may provide the greatest toxicity benefit to head and neck cancer patients, and represent a potential new direction for ART, given that the existing ART literature has focused almost exclusively on xerostomia reduction.

PurposeTo determine which head and neck adaptive radiotherapy (ART) correction objectives are feasible and to derive efficient ART patient selection guidelines.MethodsWe considered various head and neck ART objectives including independent consideration of dose-sparing of the brainstem/spinal cord, parotid glands, and pharyngeal constrictor, as well as prediction of patient weight loss. Two-hundred head and neck cancer patients were used for model development and an additional 50 for model validation. Patient chart data, pre-treatment images, treatment plans, on-unit patient measurements, and combinations thereof were assessed as potential predictors of each objective. A stepwise approach identified combinations of predictors maximizing the Youden index of random forest (RF) models. A heuristic translated RF results into simple patient selection guidelines which were further refined to balance predictive capability and practical resource costs. Generalizability of the RF models and simplified guidelines to new data was tested using the validation set.ResultsTop performing RF models used various categories of predictors, however, final simplified patient selection guidelines only required pre-treatment information for ART predictions, indicating the potential for significant ART process streamlining. The simplified guidelines for each objective predicted which patients would experience increases in dose to: brainstem/spinal cord with sensitivity = 1.0, specificity = 0.66; parotid glands with sensitivity = 0.82, specificity = 0.70; and pharyngeal constrictor with sensitivity = 0.84, specificity = 0.68. Weight loss could be predicted with sensitivity = 0.60 and specificity = 0.55. Furthermore, depending on the ART objective, 28%-58% of patients required replan assessment, less than for previous studies, indicating a step towards more effective patient selection.ConclusionsThe above ART objectives appear to be practically achievable, with patients selected for ART according to simple clinical patient selection guidelines. Explicit ART guidelines are rare in the literature, and our guidelines may aid in balancing the potential clinical gains of ART with high associated resource costs, formalizing ART trials, and ensuring the reproducibility of clinical successes.

Atopic dermatitis (AD) causes sleep disturbance but the epidemiology is not known.To estimate the US prevalence of sleep disturbance and its impact on psychological and neurocognitive function.We conducted a cross-sectional survey of 180 parent-child dyads with AD using stratified sampling based on disease severity (Patient Oriented Eczema Measure: mild [n = 30), moderate (n = 75) or severe (n = 75]), age, and race (White or Black or African American or other). Symptoms of sleep and psychologic health were assessed using the Patient-Reported Outcome Measurement Information System. To estimate the prevalence of sleep disturbance, we calculated weights using poststratification adjustment making marginal frequencies of AD severity, race, and age similar to marginal frequencies in the 2007 National Survey of Children's Health. Unweighted regression models examined associations with sleep disturbance.In children age 5 to 17 years with AD, we estimated that sleep disturbance occurred in 66.9% (95% confidence interval, 53.3% to 80.5%; 3,116,305 children). The odds of severe sleep disturbance (worse than 95% of US children) were highest in moderate to severe versus mild AD (2.03 [1.00-4.10]; P = .0495; compared with 8.68 [1.82-41.49]; P = .0068). Predictors of parent proxy-reported sleep disturbance were itch intensity (adjusted β [95% confidence interval] 1.33 [0.62-2.04]) and low income ($50,000: 6.64 [2.05-11.23]; and $50,000 to less than 100,000: 4.75 [0.35-9.14]). Controlling for disease severity, itch intensity, and significant sociodemographics-parent-proxy, reported sleep disturbance was associated with increased severity of sleep-related impairment, depression, fatigue, and anxiety, in addition to worse inattention and impulsivity. In fully adjusted models, children who self-reported sleep disturbance (T-score ≥60) had increased odds of sleep-related impairment (1.20 [1.11-1.29]), depression (1.13 [1.03, 1.24]), fatigue (1.28 [1.06-1.54]), and anxiety (1.16 [1.02-1.31]).Sleep disturbance is a common symptom of AD. It affects about 3 million US children and is associated with neuropsychiatric impairment, including depression, anxiety, and inattention. Clinicians should screen for these symptoms in school-aged children, particularly those with moderate to severe AD.

Introduction: It is an established practice to use non-EPI DWI MRI scans to detect the presence of cholesteatoma post operatively. In the present era of Covid-19 where routine surgery to remove cholesteatoma has been suspended resulting in potentially unprecedented demands on the service, a review of serial MRI scans performed over a 7 year period was undertaken to determine the rate of growth of cholesteatoma. Materials and methods: A retrospective longitudinal study identified 24 middle ear cholesteatomas in 17 patients with serial non-EPI DWI MRI scans (having excluded those having surgical intervention between scans) for a median period of 33 months (range of 6-91 months). Cholesteatomas were measured by the first author and by the consultant radiologist. Results: Of 24 cholesteatomas, 1 resolved completely, 5 reduced, 6 stayed the same size, 4 grew slowly and 8 grew significantly. Conclusion: Non-EPI DWI MRI scans to determine cholesteatoma growth in asymptomatic ears is useful in triaging patients in the Covid-19 era. Key words: Cholesteatoma MRI scans covid-19

Purpose Two dose calculation algorithms are available in Varian Eclipse software: Anisotropic Analytical Algorithm (AAA) and Acuros External Beam (AXB). Many Varian Eclipse‐based centers have access to AXB; however, a thorough understanding of how it will affect plan characteristics and, subsequently, clinical practice is necessary prior to implementation. We characterized the difference in breast plan quality between AXB and AAA for dissemination to clinicians during implementation. Methods Locoregional irradiation plans were created with AAA for 30 breast cancer patients with a prescription dose of 50 Gy to the breast and 45 Gy to the regional node, in 25 fractions. The internal mammary chain (IMCCTV) nodes were covered by 80% of the breast dose. AXB, both dose‐to‐water and dose‐to‐medium reporting, was used to recalculate plans while maintaining constant monitor units. Target coverage and organ‐at‐risk doses were compared between the two algorithms using dose–volume parameters. An analysis to assess location‐specific changes was performed by dividing the breast into nine subvolumes in the superior–inferior and left–right directions. Results There were minimal differences found between the AXB and AAA calculated plans. The median difference between AXB and AAA for breastCTV V 95%, was

Basal cell carcinoma (BCC) is the most common form of human cancer, with a continually increasing annual incidence in the United States. When diagnosed early, the majority of BCCs are readily treated with office-based therapy, which is highly curative. In these evidence-based guidelines of care, we provide recommendations for the management of patients with BCC, as well as an in-depth review of the best available literature in support of these recommendations. We discuss biopsy techniques for a clinically suspicious lesion and offer recommendations for the histopathologic interpretation of BCC. In the absence of a formal staging system, the best available stratification based on risk for recurrence is reviewed. With regard to treatment, we provide recommendations on treatment modalities along a broad therapeutic spectrum, ranging from topical agents and superficially destructive modalities to surgical techniques and systemic therapy. Finally, we review the available literature and provide recommendations on prevention and the most appropriate follow-up for patients in whom BCC has been diagnosed.

Knee osteoarthritis (OA) is the most common cause of musculoskeletal pain and disability in the knee. Though traditionally thought a mechanical wear-and-tear disease, in recent years, knee OA as a low-grade, chronic inflammatory disease has been increasingly recognized. In this study, we examined the Treg responses in non-obese knee OA patients at different stages. Significantly elevated frequencies of CD4(+)CD25(+)Foxp3(+) Tregs were found in OA patients, while on the other hand, lower IL-10 secretion from Tregs in OA patients was observed. Importantly, this decrease in IL-10 was associated with reduced Tim-3 expression on Tregs. Although both Tim-3(-) and Tim3(+) Tregs could secrete IL-10, the majority of IL-10 was observed in Tim-3(+) Tregs. Reduction of Tim-3(+) Tregs in OA patients resulted in less IL-10-producing Tregs. Interestingly, the OA patients in more advanced stages showed further reductions in IL-10 and Tim-3 expression. In conclusion, our results revealed an immunoregulatory disorder in OA independent of obesity, and demonstrated a potential mechanism in establishing the proinflammatory status of OA patients.

To describe fluocinolone acetonide implant dissociations in the Multicenter Uveitis Steroid Treatment (MUST) Trial.Randomized clinical trial with extended follow-up.Review of data collected on the first implant in the eye(s) of participants. Dissociation was defined as the drug pellet no longer being affixed to the strut and categorized as spontaneous or surgically related.A total of 250 eyes (146 patients) had at least 1 implant placed. Median follow-up time after implant placement was 6 years (range 0.5-9.2 years). Thirty-four dissociations were reported in 30 participants. There were 22 spontaneous events in 22 participants; 6-year cumulative risk of a spontaneous dissociation was 4.8% (95% confidence interval [CI]: 2.4%-9.1%). The earliest event occurred 4.8 years after placement. Nine of 22 eyes with data had a decline in visual acuity ≥5 letters temporally related to the dissociation. Thirty-nine implant removal surgeries were performed, 33 with replacement. Twelve dissociations were noted during implant removal surgeries in 10 participants (26%, 95% CI 15%-48%); 5 of these eyes had a decline in visual acuity ≥5 letters after surgery. The time from implant placement to removal surgery was longer for the surgeries at which dissociated implants were identified than for those without one (5.7 vs 3.7 years, P.001). Overall, visual acuity declined 15 or more letters from pre-implant values in 22% of affected eyes; declines were frequently associated with complications of uveitis or its treatment.There is an increasing risk of dissociation of Retisert implants during follow-up; the risk is greater with removal/exchange surgeries, but the risk of both spontaneous and surgically related events increases with longevity of the implants. In 22% of affected eyes visual acuity declined by 15 letters. In the context of eyes with moderate to severe uveitis for years, this rate is not unexpected.

On October 7, 2016, Hurricane Matthew traveled along the coasts of Florida, Georgia, and South Carolina causing flooding and power outages. The Georgia Department of Public Health (DPH) developed the Web-based Responder Safety, Tracking, and Resilience (R-STaR) system to monitor the health and safety of public health responders and to inform disaster response planning for Hurricane Matthew. Using R-STaR, responders (n = 126) were e-mailed a daily survey while deployed to document injuries or harmful exposures and a post-deployment survey on their post-deployment health and satisfaction with using R-STaR. DPH epidemiologists contacted responders reporting injuries or exposures to determine the need for medical care. Frequencies were tabulated for quantitative survey responses, and qualitative data were summarized into key themes. Five percent (6/126) of responders reported injuries, and 81% (43/53) found R-STaR easy to use. Suggestions for R-STaR improvement included improving accessibility using mobile platforms and conducting pre-event training of responders on R-STaR. Lessons learned from R-STaR development and evaluation can inform the development and improvement of responder health surveillance systems at other local and state health departments and disaster and emergency response agencies. (Disaster Med Public Health Preparedness. 2019;13:74–81).

Objective: To describe how the Georgia Department of Public Health (DPH) uses ICD-9 and ICD-10-based discharge diagnoses (DDx) codes assigned to Emergency Department (ED) patients to support the early detection and investigation of outbreaks, clusters, and individual cases of reportable diseases. Introduction: The Georgia DPH has used its State Electronic Notifiable Disease Surveillance System (SendSS) Syndromic Surveillance (SS) module to collect, analyze and display analyses of ED patient visits, including DDx data from hospitals throughout Georgia for early detection and investigation of cases of reportable diseases before laboratory test results are available. Evidence on the value of syndromic surveillance approaches for outbreak or event detection is limited (1, 2). Use of the DDx field within datasets, specifically as it might be used for investigation of outbreaks, clusters, and / or individual cases of reportable diseases, has not been widely discussed. Methods: The DDx field of the ED data set sent to DPH by 120 facilities was queried for diseases that are immediately-reportable, as well as those reportable within 7 days of diagnosis. The query was performed twice a day using a combination of SAS 9.4 and the internal query capabilities of SendSS. District Epidemiologists (DE) were notified by email, with an Excel file attached that includes the details of the patient’s visit. DEs contacted Infection Control Practitioners (ICPs) of the facilities where the patients had received a discharge diagnosis of a reportable disease. True or false positives were determined after the outcome of the follow-up with the ICP had been known and after the patient had been entered as a case of reportable disease in SendSS by the DE. Hence, if the patient was a confirmed or probable case of a reportable disease, it was recorded as a True Positive, and True Negative otherwise. This led to the calculation of Predictive Value Positive (PVP) by reportable disease. Results: Table 1 shows the number of notifications sent to DEs that were later demonstrated to be True Positives and False Positives. It also shows the PVP by diseases being reported, for the period spanning from 05/01/2016 to 08/31/2017. Use of these notifications has allowed early investigation and identification of 158 cases of notifiable diseases by DEs. This includes 25 epi-linked cases (varicella=12, pertussis=4, cryptosporidiosis=3, shigellosis=2, malaria=2, and viral meningitis=2), as well as two clusters of varicella, one cluster of pertussis, and one outbreak of varicella in an elementary school that had not been reported to the local health department. A notable limitation of this study is that no systematic and exhaustive tracking is done of all notifications, as DEs have latitude to decide whether to follow up on a specific notification, depending on other local data that could be related to the event. Therefore, the PPVs may be biased due to over- / under-estimation of unknown size and direction. One exception to this is varicella notifications, whose outcomes have been exhaustively tracked by the DPH surveillance coordinator of this disease. Conclusions: The use of ED discharge diagnoses to examine potential cases of reportable diseases can help improve detection and early response by local health departments to outbreaks, clusters, and individual cases of reportable diseases. Exhaustive tracking of all the notifications by specific diseases may improve the estimation of the PPVs of the notifications sent to DEs.

Purpose We recently developed a novel, open-source in vivo dosimetry that uses the electronic portal imaging device to detect dose delivery discrepancies. We applied our method on patients with rectal cancer treated on a belly board device. Methods In vivo dosimetry was performed on 10 patients with rectal cancer treated prone on the belly board with a 4-field box arrangement. Portal images were acquired approximately once per week from each treatment beam. Our dosimetry method used these images along with the planning CT to reconstruct patient planar dose at isocenter depth. Results Our algorithm proved sensitive to dose discrepancies and detected discordances in 7 patients. The majority of these were due to soft tissue differences between planning and treatment, present despite matching to bony anatomy. As a result of this work, quality assurance procedures have been implemented for our immobilization devices. Conclusion In vivo dosimetry is a powerful quality assurance tool that can detect delivery discrepancies, including changes in patient setup and position. The added information on actual dose delivery may be used to evaluate equipment and process quality and to guide for adaptive radiotherapy.

Atopic dermatitis is a common, chronic inflammatory dermatosis that can affect all age groups. This evidence-based guideline addresses important clinical questions that arise in its management. In this final section, treatments for flare prevention and adjunctive and complementary therapies and approaches are reviewed. Suggestions on use are given based on available evidence.

Objective Describe how the Georgia Department of Public Health (DPH) uses syndromic surveillance to initiate review by District Epidemiologists (DEs) to events that may warrant a public health response ( 1 ). Introduction DPH uses its State Electronic Notifiable Disease Surveillance System (SendSS) Syndromic Surveillance (SS) Module to collect, analyze and display results of emergency department patient chief complaint data from hospitals throughout Georgia. Methods DPH prepares a daily SS report, based upon the analysis of daily visits to 112 Emergency Department (EDs). The visits are classified in 33 syndromes. Queries of chief complaint and discharge diagnosis are done using the internal query capability of SendSS-SS and programming in SAS/BASE. Charting of the absolute counts or percentage of ED visits by syndromes is done using the internal charting capability of SendSS-SS. A daily SS report includes the following sections: Statewide Emergency Department Visits by Priority Syndromes ( Bioterrorism, BloodyRespiratory, FeverRespiratory, FeverChest, FeverFluAdmit, FeverFluDeaths, VeryIll , and PoxRashFever, Botulism, Poison, BloodyDiarrhea, BloodyVomit, FeverGI, ILI, FeverFlu, RashFever, Diarrhea, Vomit ). Statewide Flag Analysis : Is intended to detect statewide flags, by using the Charts capability in SendSS SS. Possible cases with presumptive diagnosis of potentially notifiable diseases : Is intended to provide early-warning to the DEs of possible cases that are reportable to public health immediately or within 7 days using queries in the Chief Complaint and Preliminary Diagnosis fields of SendSS-SS. Possible clusters of illness : Since any cluster of illness must be reported immediately to DPH, this analysis is aimed at querying and identifying possible clusters of patients with similar symptoms ( 2 ). Possible travel-related illness : Is intended to identify patients with symptoms and recent travel history. Other events of interest : Exposures to ill patients in institutional settings (e.g. chief complaint indicates that other children in the daycare have similar symptoms). Trend Analysis : Weekly analysis of seasonality and trends of 14 syndromes. Finally, specific events are notified to and reviewed by the 18 DEs, who follow up by contacting the Infection Preventionists of the hospitals to identify the patients using medical records or other hospital-specific identification numbers and follow up on the laboratory test results. Results Since 05/15/2016, 12 travel-related illnesses, 29 vaccine- preventable diseases, 14 clusters, and 3 chemical exposures have been notified to DEs. For instance, a cluster of chickenpox in children was identified after the DE contacted the Infection Preventionist of a hospital, who provided the DE with the laboratory results and the physician notes about the symptoms of the patients. These actions have resulted in earlier awareness of single cases or cluster of illness, prompt reporting of notifiable diseases, and successful interaction between DEs and health care providers. In addition, SS continues to track the onset, peak, and decline of seasonal illnesses. Conclusions The implementation of SS in the State of Georgia is helping with the timely detection and early responses to disease events and could prove useful in reducing the disease burden caused by a bioterrorist attack.

Objective To describe how flexible surveillance systems can be rapidly adapted and deployed, and increase the efficiency and accuracy of surveillance, during responses to outbreaks and all hazard emergent events. Introduction Georgia Department of Public Health (DPH) epidemiologists have responded to multiple emergent outbreaks with diverse surveillance needs. During the 2009 H1N1 influenza response, it was necessary to electronically integrate multiple reporting sources and view population-level data, while during the 2014–2015 West African Ebola epidemic, it was necessary to easily collect and view individual level data from travelers to facilitate early detection of potential imported Ebola disease. DPH in-house information technology (IT) staff work closely with epidemiologists to understand and accommodate surveillance needs. Through this collaboration, IT created a robust electronic surveillance and outbreak management system (OMS) to accommodate routine reporting of notifiable diseases and outbreak investigations, and surveillance during emergent events. Methods OMS was created within the State Electronic Notifiable Disease Surveillance System (SendSS); a secure, HIPAA-compliant, Oracle and web-based platform which collects data on all notifiable diseases in Georgia. This flexible platform has multi-functionality including dynamic web-based surveys that link to case records or outbreaks, online case reporting, electronic laboratory reporting, contact tracing, visual dashboards summarizing outbreak data, electronic alerts, and individual accounts for users with varying privileges to limit access to specific modules. These features can be customized for any emergent event. Results SendSS and OMS are widely used by state and district epidemiologists. Individual case and outbreak management activities include but are not limited to: notifiable disease and condition cases; all disease clusters; animal bites surveillance including bite investigation and laboratory results; and syndromic surveillance data automatically collected from 90 emergency facilities. OMS has been rapidly modified to facilitate efficient epidemiologic responses to emergent events such as: integrating multiple reporting sources during the H1N1 outbreak; shelter surveillance during hurricanes Katrina and Rita in 2005; active monitoring of >2,500 travelers in Georgia during the Ebola response; tracking cases investigations during the Zika response, and future monitoring of poultry workers if highly- pathogenic avian influenza occurs in Georgia. Conclusions The flexible and customizable features of SendSS and OMS accommodate the changing needs of epidemiologists to monitor a variety of diseases. Rapid implementation has enabled DPH epidemiologists to respond efficiently to emergent events using limited human resources, achieving immediate situational awareness by incorporating multiple data sources into user friendly dashboards and notifications, and easily sharing information among state and federal stakeholders to facilitate rapid risk assessment and response as needed. The success of these systems illustrates the return on DPH’s preparedness investment in retaining technical staff to work with epidemiologists to meet urgent surveillance needs.

Purpose The aim of this study is to report the long-term outcomes and toxicities from a large cohort of patients with localized prostate cancer treated with low-dose-rate intraoperatively planned brachytherapy. Methods and Materials Prostate-specific antigen levels, urinary symptoms, and erectile function were recorded at baseline, and each followup visit was then entered into a prospective database. Urinary toxicity requiring procedural intervention was retrospectively verified using an integrated electronic medical system. A separate cross-sectional survey was performed to measure postimplant sexual function. Results A total of 822 patients with low and favorable intermediate-risk prostate cancer were treated at our institution between 2003 and 2013. The Kaplan–Meier estimates for biochemical recurrence for our cohort were 95% and 87% at 5 and 10 years, respectively. Cystoscopy, transurethral resection of prostate, or dilatation was required for 7.1% of 720 patients with more than 2 years of followup. At a median followup of 3.7 years, 64.4% of patients retained adequate erectile function for intercourse, with 54% of patients who were no longer sexually active postimplant reporting social factors as the primary reason. Conclusions Our institutional experience with intraoperative low-dose-rate prostate brachytherapy yielded excellent long-term results with a low incidence of urinary and sexual toxicity.

Atopic dermatitis is a chronic, pruritic inflammatory dermatosis that affects up to 25% of children and 2% to 3% of adults. This guideline addresses important clinical questions that arise in atopic dermatitis management and care, providing recommendations based on the available evidence. In this third of 4 sections, treatment of atopic dermatitis with phototherapy and systemic immunomodulators, antimicrobials, and antihistamines is reviewed, including indications for use and the risk-benefit profile of each treatment option.

Purpose External beam partial breast irradiation intensity modulated radiotherapy (PBI IMRT) plans experience degradation in coverage and dose homogeneity when delivered during respiration. We examine which characteristics of the breast and seroma result in unacceptable plan degradation due to respiration. Methods Thirty-six patient datasets were planned with inverse-optimised PBI IMRT. Population respiratory data were used to create a probability density function. This probability density function (PDF) was convolved with the static plan fluences to calculate the delivered dose with respiration. To quantify the difference between static and respiratory plan quality, we analysed the mean dose shift of the target dose volume histogram (DVH), the dose shift at 95% of the volume and the dose shift at the hotspot to 2 cm 3 of the volume. We explore which patient characteristics indicate a clinically significant degradation in delivered plan quality due to respiration. Results Dose homogeneity constraints, rather than dosimetric coverage, were the limiting factors for all patient plans. We propose the dose evaluation volume-to-planning target volume (DEV-to-PTV) ratio as a delineating metric for identifying patient plans that will be more degraded by respiratory motion. The DEV-to-PTV ratio may be a more robust metric than ipsilateral breast volume because the seroma volume is contoured more consistently between physicians and clinics. Conclusions For patients with a DEV-to-PTV ratio less than 55% we recommend either not using PBI IMRT or employing motion management. Small DEV-to-PTV ratios occur when the seroma is close to inhomogeneities (i.e. air/lung), which exacerbates the dosimetric effect of respiratory motion. For small breast sizes it is unlikely that the DEV-to-PTV ratio will meet these criteria.

Atopic dermatitis is a common and chronic, pruritic inflammatory skin condition that can affect all age groups. This evidence-based guideline addresses important clinical questions that arise in its management. In this second of 4 sections, treatment of atopic dermatitis with nonpharmacologic interventions and pharmacologic topical therapies are reviewed. Where possible, suggestions on dosing and monitoring are given based on available evidence.

Atopic dermatitis (AD) is a chronic, pruritic, inflammatory dermatosis that affects up to 25% of children and 2% to 3% of adults. This guideline addresses important clinical questions that arise in the management and care of AD, providing updated and expanded recommendations based on the available evidence. In this first of 4 sections, methods for the diagnosis and monitoring of disease, outcomes measures for assessment, and common clinical associations that affect patients with AD are discussed. Known risk factors for the development of disease are also reviewed.

Background: Although head and neck (H&N) cancer survival is steadily increasing, the close proximity of tumor volumes to organs at risk (OARs) makes radiotherapy planning and delivery challenging for these patients. Changes in patient anatomy (i.e. weight-loss, tumor shrinkage) over 7 weeks of daily radiotherapy may result in increased dosages of radiation to OARs relative to the original treatment plan, consequently hindering post-treatment quality of life. Artificial intelligence-based approaches can improve prediction and monitoring of these effects through identification of systematic changes. Objective: To collect and perform an analysis of on-unit CT measurements as surrogate measures of dose changes. Correlations among CT measures may indicate random vs. systematic changes in dose deposition (i.e. dosimetry) and further improve artificial intelligence-based approaches that determine which patients benefit most from treatment re-planning. Methods: 250 H&N cancer patients treated with curative chemo-radiotherapy were retrospectively analyzed. Five CT measures including face and neck diameter, chin and shoulder position, and head shift were calculated motivated by current literature. Dosimetric changes were calculated for OARs (pharyngeal constrictor, brainstem, parotid and submandibular glands) and tumour volumes. Conventional correlation analysis and hierarchical clustering were performed to assess group-wise correlations. K-medoid clustering and principal components analysis were conducted to infer groupings of the patients as random or systematic. Results: There is a positive correlation between increased dosages to central-axis anatomical structures (spinal cord, pharyngeal constrictor, submandibular glands) and systematic weight-loss effects (change in BMI and weight loss through the face and neck). In line with current literature, clustering indicated that 30.4% of the cohort exhibited systematic anatomical changes, potentially correctable by re-planning. MANOVA confirmed that the systematic anatomical changes corresponded to the spinal cord and brain stem (p

The goal of the work described here was to determine whether deep inspiration breath-hold (DIBH) produces a clinically meaningful reduction in pulmonary dose compared with free breathing (FB) during locoregional radiation for right-sided breast cancer.Four-field, modified-wide tangent plans with full nodal coverage were developed for 30 consecutive patients on paired DIBH and FB CT scans. Nodes were contoured according to European Society for Radiotherapy and Oncology guidelines. Plan metrics were compared using Wilcoxon signed-rank testing.In 21 patients (70%), there was a ≥5% reduction in ipsilateral lung V20Gy with DIBH compared with FB. The mean decrease in ipsilateral lung V20Gy was 7.8% (0%-20%, P.001). The mean lung dose decreased on average by 3.4 Gy with DIBH (-0.2 to 9.1, P.001). The mean reduction in liver volume receiving 50% of the prescribed dose was 42.3 cmDIBH reduced ipsilateral lung V20Gy by ≥5% in the majority of patients. For some patients, the volume of liver receiving a potentially toxic dose decreased with DIBH. DIBH should be available as a treatment strategy to reduce ipsilateral lung V20Gy prior to compromising internal mammary chain nodal coverage for patients with right-sided breast cancer during locoregional radiation therapy if the V20Gy on FB exceeds 30%.

Purpose It has been suggested that the Real-time Position Management (RPM) marker block should be placed directly on the breast or sternum to verify deep inspiration breath hold (DIBH) level for breast radiotherapy. We explore three potential issues with this practice: (a) surface dose effect of placing the marker block in the primary beam; (b) effect of marker block tilt on the accuracy of the RPM system; and (c) correlation between marker block positions on the patient surface and internal chest wall position. Methods (a) The surface dose under the two-, four-, and six-dot marker blocks was measured at incident angles of 0° and 30°; (b) the motion amplitude detected when using the two- and six-dot marker blocks was recorded for block tilts from 0° to 60° about the RPM camera line of sight; (c) the correlation between median displacement of the chest wall and median displacement of the surface contour between breath holds was investigated for superior, middle, and inferior block positions using contours extracted from portal images of eight left-sided breast cancer patients. Results (a) The marker blocks increased the surface dose for a 6 MV direct field by 48.2–52.2% of Dmax; (b) at lateral tilts greater than 10°, the two-dot marker block overestimated the motion amplitude; however, the six-dot marker block amplitude remained accurate up to 60°; (c) the whole, superior, and middle surface positions were strongly correlated with chest wall displacement (R2 = 0.83; R2 = 0.90; R2 = 0.83), whereas the inferior position was moderately correlated (R2 = 0.36). Conclusions The RPM marker block can be placed on the breast for DIBH treatments; however, caution should be used regarding surface dose effects. The two-dot marker block should not be used for block tilts beyond 20°. Marker block placement at a middle or superior position on the breast results in the strongest correlation with chest wall position.

The incidence of primary cutaneous melanoma has been increasing dramatically for several decades. Melanoma accounts for the majority of skin cancer–related deaths, but treatment is nearly always curative with early detection of disease. In this update of the guidelines of care, we will discuss the treatment of patients with primary cutaneous melanoma. We will discuss biopsy techniques of a lesion clinically suspicious for melanoma and offer recommendations for the histopathologic interpretation of cutaneous melanoma. We will offer recommendations for the use of laboratory and imaging tests in the initial workup of patients with newly diagnosed melanoma and for follow-up of asymptomatic patients. With regard to treatment of primary cutaneous melanoma, we will provide recommendations for surgical margins and briefly discuss nonsurgical treatments. Finally, we will discuss the value and limitations of sentinel lymph node biopsy and offer recommendations for its use in patients with primary cutaneous melanoma.

The National Lung Screening Trial (NLST) is a randomized multicenter study comparing low-dose helical computed tomography (CT) with chest radiography in the screening of older current and former heavy smokers for early detection of lung cancer, which is the leading cause of cancer-related death in the United States. Five-year survival rates approach 70% with surgical resection of stage IA disease; however, more than 75% of individuals have incurable locally advanced or metastatic disease, the latter having a 5-year survival of less than 5%. It is plausible that treatment should be more effective and the likelihood of death decreased if asymptomatic lung cancer is detected through screening early enough in its preclinical phase. For these reasons, there is intense interest and intuitive appeal in lung cancer screening with low-dose CT. The use of survival as the determinant of screening effectiveness is, however, confounded by the well-described biases of lead time, length, and overdiagnosis. Despite previous attempts, no test has been shown to reduce lung cancer mortality, an endpoint that circumvents screening biases and provides a definitive measure of benefit when assessed in a randomized controlled trial that enables comparison of mortality rates between screened individuals and a control group that does not undergo the screening intervention of interest. The NLST is such a trial. The rationale for and design of the NLST are presented.

The goals of this retrospective case review were to analyze the long-term results of surgery for petrous temporal bone cholesteatomas and to propose a new classification system for these lesions. Patients with a surgically confirmed petrous temporal bone cholesteatoma were treated at Addenbrooke's Hospital, a tertiary referral center. Postoperative facial function, hearing, residual/recurrent cholesteatoma, and other complications were assessed in relation to preoperative signs, intraoperative findings, and surgical approach. Between 1983 and 2004, 43 patients were treated. There were no perioperative deaths. There was no long-term recurrence in 95.4% of the patients, possibly because of meticulous surgical technique, bipolar diathermy, and use of the laser to denature the cholesteatoma matrix that was adherent to the dura. At presentation, 95% of the patients had no socially useful hearing in the affected ear. Facial nerve function, however, was usually preserved. Both direct anastomosis and nerve grafting can improve facial nerve function from House-Brackmann grade VI to grade III if the palsy is not longstanding. Four patients had cerebrospinal fluid leakage; other complications were rare. The proposed classification facilitates surgical planning and predicts the postoperative outcome with regards to hearing.

Perisylvian syndrome is a rare neurological disorder characterised by the partial paralysis of muscles, epilepsy and mild to severe mental retardation. It is associated with hearing loss and delay in language and speech development. This presents additional challenges in the assessment of whether a child is suitable for cochlea implantation. The method to determine whether the hearing loss is of cochlear or central origin and the progress of a child with Perisylvian syndrome who received a cochlear implant is discussed. Copyright © 2007 John Wiley & Sons, Ltd.

Background Plantar pressure measurements are a useful screening tool to assess foot function and identify patients at risk of developing ulceration. The validity and reliability of PressureStat™ for measuring plantar pressures in patients with rheumatoid arthritis has not been addressed. Methods Bench testing placed the PressureStat™ under loads throughout the range reported for PressureStat™ (0–15.0kg/cm 2 ). The outputs were digitised to measure pixel density in comparison with the PressureStat™ calibration card. In clinical testing, simultaneous barefoot plantar pressure measurements were recorded from 10 rheumatoid arthritis patients using the PressureStat™ and EMED-ST systems. Reliability was examined by four independent examiners using kappa statistics. The absolute peak pressure values in each mask region were determined from the EMED-ST platform by masking in the same manner using a real size plantar pressure printout. Findings In all test conditions, the pixel density recorded from the PressureStat™ outputs exceeded the range recorded on the calibration card, with the largest difference in the lower ranges. In clinical testing, correcting the PressureStat™ scores for ‘background noise' (not suggested by manufacturer) inverted and improved these comparisons. Inter-observer kappa values between the first and second readings ranged from 0.26 to 0.59, with some evidence of a learning effect. Intra-observer kappa values were 0.57, 0.51, 0.33 and 0.43 for observers 1–4 respectively. Interpretation Pressure data obtained with the PressureStat™ system in bench testing and patients with RA is inaccurate, particularly in the lower ranges. The grading of PressureStat™ readings taken from rheumatoid arthritis patients found fair to moderate intra and inter-observer agreement suggesting that interpretation is also imprecise.

There are an increasing number and variety of dermatologic surgical procedures performed safely in the office setting. This evidence-based guideline addresses important clinical questions that arise regarding the use and safety of local anesthesia for dermatologic office-based procedures. In addition to recommendations for dermatologists, this guideline also takes into account patient preferences while optimizing their safety and quality of care. The clinical recommendations presented here are based on the best evidence available as well as expert opinion.

Purpose: Deep inspiration breath hold (DIBH) can reduce cardiac dose during left-sided breast cancer radiotherapy. This study uses cine imaging with edge detection to evaluate a visually-monitored DIBH technique (VM-DIBH)

BACKGROUND In vivo dosimetry can record the delivered dose during radiotherapy, which may be used to trigger adaptive radiotherapy or other user intervention. We demonstrate the use of our in-house in vivo electronic portal imaging dosimetry in quantifying interfraction dose variability in rectal cancer. METHODS We recorded MV images from nine treatment beams for six patients prone on the belly board, during 4-7 fractions, for a total of 50 measurements. Images were processed with our dosimetry system to produce dose maps. The dose map from the reference fraction was compared to all subsequent ones to determine interfraction delivery variation, yielding 41 dose difference maps. RESULTS We identified a number of dose discrepancies. In several patients, persistent gas bubbles may result in cumulative dose deviations large enough to warrant adaptive radiotherapy. In three patients, discrepancies in dose resulted from variability of patient positioning on the belly board. These issues were not readily identified by standard imaging procedures. CONCLUSION We are developing an open-source in vivo portal dosimetry method to automatically track delivered dose at every fraction. Results can be used to flag unexpected discrepancies, guide adaptive radiotherapy, or warrant image guidance. Further data is needed to test applicability with other treatment sites and setups.

Gender differences in outcomes from major trauma have been described previously, and exogenous female hormone administration appears to be neuroprotective following traumatic brain injury (TBI). This analysis explored outcomes in pre- and post-menopausal females versus age-matched males. A total of 13,437 patients (n = 3,178 females, n = 10,259 males) with moderate-to-severe TBI (head AISor = 3) were identified from our county trauma registry. Overall mortality was similar between males and females (22% for both). Logistic regression was used to compare gender outcome differences, with a separate analysis performed for premenopausal (50 years) versus postmenopausal (or = 50 years) patients, and after stratification by decade of life. No statistically significant difference in outcomes was observed for pre-menopausal females versus males (odds ratio [OR] 1.06; 95% confidence interval [CI] 0.83, 1.35; p = 0.633), but outcomes were significantly better in postmenopausal females versus males (OR 0.63, 95% CI 0.48-0.81, p0.001) after adjusting for age, mechanism of injury, Glasgow Coma Scale (GCS), hypotension (SBPor = 90 mm Hg), head Abbreviated Injury Score (AIS), and Injury Severity Score (ISS). Stratification by decade of life revealed the gender survival differential inflection point to occur between ages 40-49 (OR 1.06, 95% CI 0.66-1.71, p = 0.798) and ages 50-59 (OR 0.38, 95% CI 0.20-0.74, p = 0.005). In addition, Revised Trauma Score and Injury Severity Score (TRISS) was used to calculate probability of survival (PS); all patients were then stratified by decade of life, and males and females were compared with regard to mean survival differential (outcome - PS). The identical pattern of improved outcomes in post-menopausal but not pre-menopausal females versus age-matched males was observed. These data suggest that endogenous female sex hormone production is not neuroprotective.

Rationale and Objectives No single method is generally accepted for evaluating the accuracy of breast biopsy techniques before their clinical implementation. The purpose of this study was to test a new process for evaluating biopsy techniques by using it in the evaluation of a prototype three-dimensional ultrasound (US)–guided biopsy device. Materials and Methods The biopsy accuracy of a new three-dimensional US–guided breast biopsy device was compared to that of the accepted clinical practice of biopsy by expert radiologists with two-dimensional freehand US guidance. Biopsies were performed in chicken tissue phantoms containing 3.2-mm lesions made of poly(vinyl alcohol) cryogel. The criterion for a successful biopsy was the presence of lesion in the sample. The equivalence limit difference tested was 10% by using a power of 90% and a two-sided test significance level, α, of 10%. Results The biopsy success rate of the three-dimensional US–guided system (96%) was equivalent to that of expert radiologists using two-dimensional freehand US guidance (94.5%) in tissue phantoms containing poly(vinyl alcohol) cryogel lesions. Conclusion This evaluation procedure is a valuable precursor to clinical trials in the assessment of biopsy techniques. The three-dimensional US–guided breast biopsy system provides a suitable alternative to two-dimensional freehand US guidance for biopsy of breast cancer.

Background Despite significant advances in breast imaging, the ability to detect breast cancer (BC) remains a challenge. To address the unmet needs of the current BC detection paradigm, 2 prospective clinical trials were conducted to develop a blood-based combinatorial proteomic biomarker assay (Videssa Breast) to accurately detect BC and reduce false positives (FPs) from suspicious imaging findings. Patients and Methods Provista-001 and Provista-002 (cohort one) enrolled Breast Imaging Reporting and Data System 3 or 4 women aged under 50 years. Serum was evaluated for 11 serum protein biomarkers and 33 tumor-associated autoantibodies. Individual biomarker expression, demographics, and clinical characteristics data from Provista-001 were combined to develop a logistic regression model to detect BC. The performance was tested using Provista-002 cohort one (validation set). Results The training model had a sensitivity and specificity of 92.3% and 85.3% (BC prevalence, 7.7%), respectively. In the validation set (BC prevalence, 2.9%), the sensitivity and specificity were 66.7% and 81.5%, respectively. The negative predictive value was high in both sets (99.3% and 98.8%, respectively). Videssa Breast performance in the combined training and validation set was 99.1% negative predictive value, 87.5% sensitivity, 83.8% specificity, and 25.2% positive predictive value (BC prevalence, 5.87%). Overall, imaging resulted in 341 participants receiving follow-up procedures to detect 30 cancers (90.6% FP rate). Videssa Breast would have recommended 111 participants for follow-up, a 67% reduction in FPs ( P Conclusions Videssa Breast can effectively detect BC when used in conjunction with imaging and can substantially reduce unnecessary medical procedures, as well as provide assurance to women that they likely do not have BC.

Lesbian couples seek to become parents in a heteronormative world and in the context of complex biological, social, and legal challenges that may constrain same-sex parenting. Because of these constraints and challenges, lesbian couples experiencing a reproductive loss may encounter issues that heterosexual couples typically will not. Prior to pregnancy, lesbians may experience loss and grief because they cannot conceive a child together without the assistance of a third party. Same-sex families are marginalized; simply deciding to become parents leaves them open to criticism and negative judgment. If pregnancy is not achieved or does not end in a live birth, lesbian couples face decisions about how, whether, and who to conceive a subsequent pregnancy. Although laws vary by state, the social (nonbiological) mother may not have legal status as the child's parent; therefore, the decision of which partner to become pregnant is especially significant. In the event of a reproductive loss, the grief of the social mother might not be acknowledged. Lesbian couples will benefit from the care of a nurse who understands and is accepting of the complex contexts within which they face the challenges of reproductive loss.

Theiler's murine encephalomyelitis virus (TMEV) infection of the central nervous system (CNS) induces a chronic, progressive demyelinating disease in susceptible mouse strains characterized by inflammatory mononuclear infiltrates and spastic hind limb paralysis. Our lab has previously demonstrated a critical role for TMEV- and myelin-specific CD4(+) T cells in initiating and perpetuating this pathology. It has however, also been shown that the MHC class I loci are associated with susceptibility/resistance to TMEV infection and persistence. For this reason, we investigated the contribution of CD8(+) T cells to the TMEV-induced demyelinating pathology in the highly susceptible SJL/J mouse strain. Here we show that beta2M-deficient SJL mice have similar disease incidence rates to wild-type controls, however beta2M-deficient mice demonstrated earlier onset of clinical disease, elevated in vitro responses to TMEV and myelin proteolipid (PLP) epitopes, and significantly higher levels of CNS demyelination and macrophage infiltration at 50 days post-infection. beta2M-deficient mice also displayed a significant elevation in persisting viral titers, as well as an increase in macrophage-derived pro-inflammatory cytokine mRNA expression in the spinal cord at this same time point. Taken together, these results indicate that CD8(+) T cells are not required for clinical or histologic disease initiation or progression in TMEV-infected SJL mice. Rather, these data stress the critical role of CD4(+) T cells in this capacity and further emphasize the potential for CD8(+) T cells to contribute to protection from TMEV-induced demyelination.

Purpose The aim of this study was to determine whether color Doppler or power Doppler sonography can aid in the diagnosis of hepatic cavernous hemangiomas. Methods We imaged 25 hepatic cavernous hemangiomas in 17 patients with gray-scale, color Doppler, and power Doppler sonography. Five malignant lesions were also imaged in the same manner for reference. Hemangiomas had been previously diagnosed by biopsy in 8 patients (15 lesions) and by CT, MRI, and/or tagged red blood cell scanning in 9 patients (10 lesions). Results Of the 25 hemangiomas, color or power Doppler imaging showed no internal blood flow in 23. Of these 23 lesions, 11 showed a peripheral flow pattern believed to represent flow in displaced blood vessels. This pattern was better visualized with power Doppler imaging in 3 lesions and equally well visualized with color and power Doppler imaging in 8 lesions. Two hemangiomas that had unusual central fibrosis with large vessels in 1 patient showed diffusely increased blood flow on power Doppler study. All 5 malignant lesions showed flow in peripheral vessels, and 1 showed internal vascularity as well. Conclusions Neither color nor power Doppler imaging improved the capability of sonography for making a specific diagnosis of benign hepatic cavernous hemangioma. © 2000 John Wiley & Sons, Inc. J Clin Ultrasound 28:159–165, 2000.