Impact of reactive changes on multigene testing: histopathologic analysis of low-grade breast cancers with high-risk 21-gene recurrence scores.

PURPOSE: The 21-gene recurrence score (RS) assay predicts the recurrence risk and magnitude of chemotherapy benefit in patients with invasive breast cancer (BC). This study examined low-grade tumors yielding a high-risk RS and their outcomes.Kindly check the edit made in the article titleOk  METHODS: We compared patients with grade 1 BC and a high-risk RS to those with low-risk RS. Histologic sections were reviewed and features reported to elevate the RS were noted, mainly biopsy cavity and reactive stromal changes (BXC). RESULTS: A total of 54 patients had high-risk RS (median RS of 28, range 26-36). On review, BXC were seen in all cases. Thirty BCs in this group also had low to negative PR. Treatment regimens included: chemoendocrine therapy (63%), endocrine therapy alone (31%) and no adjuvant therapy (6%). There were no additional breast cancer events over a median follow-up of 54.0 months (range 6.2 to 145.3). A total of 108 patients had low-risk RS (median RS of 7, range 0-9). BXC were seen in 47% of cases and none were PR negative. One patient had a recurrence at 64.8 months while the rest had no additional events over a median of 68.1 months (2.4 to 100). CONCLUSION: We provide further evidence that reactive stromal changes and/or low-PR scores enhance the elevation of the RS. A high-RS result in low grade, PR-positive BC may not reflect actual risk and any suspected discrepancies should be discussed with the management teams. Multigene testing results should be interpreted after correlation with pathologic findings to optimize patient care.

Recommendation to update the British Society for Cutaneous Allergy corticosteroid series.

BACKGROUND: Patch testing is an important investigation when dermatitis is unresponsive to, or worsened by, topical corticosteroid treatment. There is a balance to be struck between testing too many allergens, which is expensive, time consuming and risks causing sensitization, and testing too few, which risks missing the diagnosis. The current British Society for Cutaneous Allergy (BSCA) corticosteroid series comprises eight allergens and was last updated in February 2007. AIM: To review and update the BSCA corticosteroid series. METHODS: We retrospectively analysed data from 16 patch test centres in the UK and Ireland for all patients who were patch tested to a corticosteroid series between August 2017 and July 2019. We recorded the allergens tested, the number and percentage tested to a corticosteroid series and the number of positive results for each allergen. We identified the allergens that test positive in ≥ 0.1% of selectively tested patients. RESULTS: Overall, 3531 patients were tested to a corticosteroid series in the 16 centres. The number of allergens tested ranged from 7 to 18 (mean 10). The proportion of patch test patients who were tested to a corticosteroid series ranged from 1% to 99%. Six allergens in the 2017 BSCA series tested positive in ≥ 0.1% of patients. Nine allergens not in the BSCA corticosteroid series tested positive in ≥ 0.1% of patients. CONCLUSION: This audit demonstrates the importance of regular review of recommended series and the significant variations in practice. The new BSCA corticosteroid series that we recommend contains 13 haptens, with the addition of the patient's own steroid creams as appropriate.

Use of a supervised machine learning model to predict Oncotype DX risk category in node-positive patients older than 50 years of age.

PURPOSE: The use of the Oncotype DX recurrence score (RS) to predict chemotherapy benefit in patients with hormone receptor-positive/HER2 negative (HR+/HER2-) breast cancer has recently expanded to include postmenopausal patients with N1 disease. RS availability is limited in resource-poor settings, however, prompting the development of statistical models that predict RS using clinicopathologic features. We sought to assess the performance of our supervised machine learning model in a cohort of patients > 50 years of age with N1 disease. METHODS: We identified patients > 50 years of age with pT1-2N1 HR+/HER2- breast cancer and applied the statistical model previously developed in a node-negative cohort, which uses age, pathologic tumor size, histology, progesterone receptor expression, lymphovascular invasion, and tumor grade to predict RS. We measured the model's ability to predict RS risk category (low: RS ≤ 25; high: RS > 25). RESULTS: Our cohort included 401 patients, 60.6% of whom had macrometastases, with a median of 1 positive node. The majority of patients had a low-risk observed RS (85.8%). For predicting RS category, the model had specificity of 97.3%, sensitivity of 31.8%, a negative predictive value of 87.9%, and a positive predictive value of 70.0%. CONCLUSION: Our model, developed in a cohort of node-negative patients, was highly specific for identifying cN1 patients > 50 years of age with a low RS who could safely avoid chemotherapy. The use of this model for identifying patients in whom genomic testing is unnecessary would help decrease the cost burden in resource-poor settings as reliance on RS for adjuvant treatment recommendations increases.

Supervised machine learning model to predict oncotype DX risk category in patients over age 50.

PURPOSE: Routine use of the oncotype DX recurrence score (RS) in patients with early-stage, estrogen receptor-positive, HER2-negative (ER+/HER2-) breast cancer is limited internationally by cost and availability. We created a supervised machine learning model using clinicopathologic variables to predict RS risk category in patients aged over 50 years. METHODS: From January 2012 to December 2018, we identified patients aged over 50 years with T1-2, ER+/HER2-, node-negative tumors. Clinicopathologic data and RS results were randomly split into training and validation cohorts. A random forest model with 500 trees was developed on the training cohort, using age, pathologic tumor size, histology, progesterone receptor (PR) expression, lymphovascular invasion (LVI), and grade as predictors. We predicted risk category (low: RS ≤ 25, high: RS > 25) using the validation cohort. RESULTS: Of the 3880 tumors identified, 1293 tumors comprised the validation cohort in patients of median (IQR) age 62 years (56-68) with median (IQR) tumor size 1.2 cm (0.8-1.7). Most tumors were invasive ductal (80.3%) of low-intermediate grade (80.5%) without LVI (80.9%). PR expression was ≤ 20% in 27.3% of tumors. Specificity for identifying RS ≤ 25 was 96.3% (95% CI 95.0-97.4) and the negative predictive value was 92.9% (95% CI 91.2-94.4). Sensitivity and positive predictive value for predicting RS > 25 was lower (48.3 and 65.1%, respectively). CONCLUSION: Our model was highly specific for identifying eligible patients aged over 50 years for whom chemotherapy can be omitted. Following external validation, it may be used to triage patients for RS testing, if predicted to be high risk, in resource-limited settings.

A Mobile- and Web-Based Health Intervention Program for Diabetes and Prediabetes Self-Management (BetaMe/Melon): Process Evaluation Following a Randomized Controlled Trial.

BACKGROUND: Technology-assisted self-management programs are increasingly recommended to patients with long-term conditions such as diabetes. However, there are a number of personal and external factors that affect patients' abilities to engage with and effectively utilize such programs. A randomized controlled trial of a multi-modal online program for diabetes self-management (BetaMe/Melon) was conducted in a primary care setting, and a process evaluation was completed at the end of the study period. OBJECTIVE: This process evaluation aimed to examine the utilization patterns of BetaMe/Melon, identify which components participants found most (and least) useful, and identify areas of future improvement. METHODS: Process evaluation data were collected for intervention arm participants from 3 sources: (1) the mobile/web platform (to identify key usage patterns over the 16-week core program), (2) an online questionnaire completed during the final study assessment, and (3) interviews conducted with a subset of participants following the study period. Participants were classified as "actively engaged" if any usage data was recorded for the participant (in any week), and patterns were reported by age, gender, ethnicity, and diabetes/prediabetes status. The online questionnaire asked participants about the usefulness of the program and whether they would recommend BetaMe/Melon to others according to a 5-point Likert Scale. Of 23 invited participants, 18 participated in a digitally recorded, semistructured telephone interview. Interview data were thematically analyzed. RESULTS: Out of the 215 participants, 198 (92%) received an initial health coaching session, and 160 (74%) were actively engaged with the program at some point during the 16-week core program. Engagement varied by demographic, with women, younger participants, and ethnic majority populations having higher rates of engagement. Usage steadily declined from 50% at Week 0 to 23% at Week 15. Participants ranked component usefulness as education resources (63.7%), health coaches (59.2%), goal tracking (48.8%), and online peer support (42.1%). Although 53% agreed that the program was easy to use, 64% would recommend the program to others. Interview participants found BetaMe/Melon useful overall, with most identifying beneficial outcomes such as increased knowledge, behavioral changes, and weight loss. Barriers to engagement were program functionality, internet connectivity, incomplete delivery of all program components, and participant motivation. Participants suggested a range of improvements to the BetaMe/Melon program. CONCLUSIONS: The program was generally well received by participants; active engagement was initially high, although it declined steadily. Maintaining participant engagement over time, individualizing programs, and addressing technical barriers are important to maximize potential health benefits from online diabetes self-management programs. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry ACTRN12617000549325; https://tinyurl.com/y622b27q.

Interventions Post Catheter Removal (iPCaRe) in the Acute Care Setting: An Evidence- and Consensus-Based Algorithm.

Despite advances in the prevention of catheter-acquired urinary tract infections achieved by programs that include removal of the indwelling urinary catheter at the earliest possible time, evidence guiding bladder and incontinence management strategies following discontinuation of a catheter is sparse. To address this gap and guide best practice, the WOCN Society appointed a Task Force to develop an evidence- and consensus-based algorithm guiding clinical decision-making for effective bladder and incontinence management strategies after indwelling urinary catheter removal. This article describes the design and development of the algorithm, consensus-based statements used to guide best practice in this area, and its content validation.

Impact of a comprehensive digital health programme on HbA1c and weight after 12 months for people with diabetes and prediabetes: a randomised controlled trial.

AIMS/HYPOTHESIS: The aim of this RCT was to evaluate the effectiveness of a digital health programme (BetaMe/Melon) vs usual care in improving the control of type 2 diabetes and prediabetes in a primary care population. METHODS: We conducted a randomised parallel-group two-arm single-blinded superiority trial in the primary care setting in two regions of New Zealand. Eligible participants were identified through Primary Health Organisations and participating practices. Eligibility criteria were as follows: age 18-75 years, HbA1c 41-70 mmol/mol (5.9-8.6%), not taking insulin, and daily access to the internet. BetaMe/Melon is a 12 month mobile-device and web-based programme with four components: health coaching; evidence-based resources; peer support; and goal tracking. Participants were randomised into the intervention or control arm (1:1 allocation) based upon baseline HbA1c (prediabetes or diabetes range), stratified by practice and ethnicity. Research nurses and the study biostatistician were blind to study arm. Primary outcomes of the study were changes in HbA1c and weight at 12 months, using an intention-to-treat analysis. RESULTS: Four hundred and twenty-nine individuals were recruited between 20 June 2017 and 11 May 2018 (n = 215 intervention arm, n = 214 control arm), most of whom were included in analyses of co-primary outcomes (n = 210/215, 97.7% and n = 213/214, 99.5%). HbA1c levels at 12 months did not differ between study arms: mean difference was -0.9 mmol/mol (95% CI -2.9, 1.1) (-0.1% [95% CI -0.3, 0.1]) for the diabetes group and was 0.0 mmol/mol (95% CI -0.9, 0.9) (0.0% [95% CI -0.1, 0.1]) for the prediabetes group. Weight reduced slightly at 12 months for participants in both study arms, with no difference between arms (mean difference -0.4 kg [95% CI -1.3, 0.5]). CONCLUSIONS/INTERPRETATION: This study did not demonstrate clinical effectiveness for this particular programme. Given their high costs, technology-assisted self-management programmes need to be individually assessed for their effectiveness in improving clinical outcomes for people with diabetes. TRIAL REGISTRATION: www.anzctr.org.au ACTRN12617000549325 (universal trial number U1111-1189-9094) FUNDING: This study was funded by the Health Research Council of New Zealand, the Ministry of Health New Zealand and the Healthier Lives National Science Challenge. Graphical abstract.

First trial outcome but not training difficulty predicts performance in goldfish visual discrimination.

The easy-to-hard effect in perceptual learning shows that training with easier examples can facilitate initially difficult or impossible distinctions between very similar stimuli. This effect has been reported in humans and other species. We tested whether easy-to-hard training could facilitate visual discrimination in common goldfish (Carassius auratus). Fish (n = 6) performed a two-alternative forced choice discrimination task, which consisted of simultaneously presenting two striped patterns at a constant distance away on the outside of the tank. Fish were required to approach and bite a porthole corresponding to one of the stimuli for a food reward. Half of the fish were randomly assigned to a training schedule where stimuli became more similar as training progressed. The rest were trained only on the most difficult to distinguish version of the stimuli. All fish received a similar total amount of training regardless of the assigned schedule. We also examined whether performance on the first training trial for a given day was related to overall performance. Contrary to our hypothesis, fish in the easy-to-hard group did not perform significantly better than those in the constant-hard group. However, performance was found to be significantly higher on days when the first trial was correct compared to days on which it was incorrect, regardless of the type of training schedule. The current results contribute to understanding individual differences in perceptual learning in fish, and are consistent with research in humans, and other species, reporting better learning after initial reward.

Current Evidence Related to Intermittent Catheterization: A Scoping Review.

PURPOSE: The purpose was to summarize evidence related to adherence to intermittent catheterization (IC), complication rates, satisfaction with IC, and its effect on health-related quality of life. PROBLEM: Intermittent catheterization is frequently used to manage lower urinary tract dysfunctions including urinary retention and urinary incontinence, but research suggests that care for patients using IC may not always be based on evidence. METHODS: Scoping review. SEARCH STRATEGY: We searched the PubMed, EMBASE, CINAHL databases, and the Cochrane Database for Systematic Reviews to identify studies published between January 2009 and March 2019. Seventy studies met inclusion criteria and were evaluated for adherence, complication rates, satisfaction, and health-related quality in adults and children using IC for bladder management. FINDINGS: Recent research was variable in both quantity and quality. The evidence suggests that (1) most patients can successfully master IC and that functional status is likely the most important predictor of success; (2) adherence to IC probably decreases over time; (3) urinary tract infections (UTIs) are the most common complication of IC and that prophylactic antibiotic therapy may reduce the risk of recurrent UTIs; (4) urinary incontinence is also a common complication; and (5) other complications such as urethral strictures, bladder stones, hematuria, and urethral false passage do occur but are less prevalent than UTIs and incontinence between catheterizations. Our review also revealed multiple gaps in the evidence to support care for patients using IC. CONCLUSIONS: Research priorities include a need for prospective studies of the epidemiology and risk factors for IC-related complications, along with intervention studies to determine how to improve outcomes for patients using IC to manage bladder function.

Role of the Wound, Ostomy and Continence Nurse in Continence Care: 2018 Update.

The Wound, Ostomy and Continence Nurses Society believes the tri-specialty certified nurse (Certified Wound Ostomy Continence Nurse [CWOCN]) or advanced practice tri-specialty certified nurse (Certified Wound Ostomy Continence Nurse-Advanced Practice [CWOCN-AP]) possesses unique knowledge, expertise for assessment, and first-line management of incontinence as well as for prevention of incontinence. The CWOCN or CWOCN-AP provides care and consultation in the treatment of potential and actual skin complications through absorption, and containment, in persons with urinary, fecal, or dual incontinence. This executive summary describes the role of the CWOCN or CWOCN-AP in the delivery of continence care across care settings. The original statement is available at https://cdn.ymaws.com/www.wocn.org/resource/collection/6D79B935-1AA0-4791-886F-E361D29F152D/Role_of_Continence_Nurse__2018_.pdf.

A Multipronged Initiative to Improve Productivity and Patient Access in a Federally Qualified Health Center Network.

In 2012, Access Community Health Network, a Federally Qualified Health Center (FQHC) network with 36 health centers serving the greater Chicago area, embarked on a 3-year initiative to improve patient access. "Dramatic Performance Improvement" (DPI) included the adoption of modified open access scheduling and practice changes designed to improve capacity and the ability to balance supply and demand. This article describes DPI implementation, strategies, and associated outcomes, including a 20% decrease in no-show rate, a 33% drop in time to the third next available appointment (TNAA), a 37% decrease in cycle time, and a 13% increase in patient satisfaction.

Aberrant pro-atrial natriuretic peptide/corin/natriuretic peptide receptor signaling is present in maternal vascular endothelium in preeclampsia.

OBJECTIVE: Corin is a serine protease that converts pro-atrial natriuretic peptide (pro-ANP) to atrial natriuretic peptide (ANP), a cardiac hormone that regulates salt-water balance and blood pressure. ANP is degraded by natriuretic peptide receptor (NPR). This study was to determine if aberrant pro-ANP/corin/NPR signaling is present in maternal vascular system in preeclampsia. STUDY DESIGN: Maternal venous blood was obtained from 197 pregnant women (84 normotensive, 16 complicated with chronic hypertension (CHT), 11 mild and 86 severe preeclampsia). Plasma corin and pro-ANP concentrations were measured by enzyme-linked immunosorbent assay. Maternal subcutaneous fat tissue was obtained from 12 pregnant women with cesarean section delivery (6 normotensive and 6 preeclampsia). Vascular ANP and its receptors NPR-A, NPR-B, and NPR-C expression were examined by immunostaining of paraffin embedded subcutaneous fat tissue sections. RESULTS: Corin concentrations were significantly higher in mild (2.78 ±â€¯0.67 ng/ml, p < .05) and severe (2.53 ±â€¯0.18 ng/ml, p < .01) preeclampsia than in normotensive (1.58 ±â€¯0.08 ng/ml) and CHT (1.55 ±â€¯0.20 ng/ml) groups. Pro-ANP concentrations were significantly higher in CHT (1.59 ±â€¯0.53 ng/ml, p < .05) and severe preeclampsia (1.42 ±â€¯0.24 ng/ml, p < .01) than in normotensive (0.48 ±â€¯0.06 ng/ml) and mild preeclampsia (0.52 ±â€¯0.09 ng/ml) groups. ANP and NPR-B expression was undetectable in maternal vessels from normotensive and preeclamptic pregnancies, but reduced NPR-A expression and increased NPR-C expression was found in maternal vessel endothelium in preeclampsia. CONCLUSIONS: ANP is a vasodilator and NPR-C is a clearance receptor for ANP. The finding of upregulation of NPR-C expression suggests that circulating ANP clearance or degradation is increased in preeclampsia. These results also suggest that pro-ANP/corin/NPR signaling is dominant in the vascular system in preeclampsia.

Contributions of Look Duration and Gaze Shift Patterns to Infants' Novelty Preferences.

Data from 72 infants, tested using a serial paired-comparison paradigm, were analyzed to better understand infant novelty preferences. Infants between the ages of 15 and 26 weeks were tested in three studies with familiar stimuli displayed adjacent to novel stimuli on each trial. Differences in look duration, look number, and gaze shifts directed at novel versus familiar stimuli were assessed to measure their contributions to group and individual novelty preferences. Infants produced longer looks for novel stimuli in all three studies, and stimulus differences in look duration accounted for more than 50% of the variability in individual novelty preferences. Infants that produced more looks to novel rather than familiar stimuli did not produce overall novelty preferences unless they also looked longer at novel stimuli. Gaze shift patterns did not predict individual novelty preferences, and novel stimuli did not determine where infants looked. The infants' visual exploration was constrained by memories for the direction of the previous look as well as by the attention-holding features of novel stimuli.

Development of a multi stakeholder partnership to improve access to and delivery of neurosurgical services in Ontario.

Neurosurgical emergencies require expedient access to definitive care at neurosurgical centers. Neurosurgical resources in province of Ontario are highly centralized, and subsequently, most patients with neurosurgical emergencies will present to non-neurosurgical centers. From 2000-2010, metrics demonstrated the organization of neurosurgical resources might not be optimal. In response to this a program entitled Provincial Neurosurgery Ontario (PNO)- was formed to address these issues in cooperation with neurosurgeons, hospitals and the provincial government. PNO worked with multiple stakeholders to implement interventions to not only prevent out of country transfer, but to also improve the flow of neurosurgical patients in the province and potentially improve outcome. The main interventions undertaken by PNO were: 1) implementation and development of a province-wide tele-radiology system; 2) development of neurosurgery as a provincially-funded program; 3) significant outreach to non-neurosurgical centers; and 4) specialized funding packages for highly specialized level care. This report provides background on the challenges faced by neurosurgery in the province of Ontario and the process developed to address these challenges. Finally, we describe the impact provincial strategies have had on improving access to emergency neurosurgical care in the Ontario.

Acrylate and methacrylate contact allergy and allergic contact disease: a 13-year review.

BACKGROUND: (Meth)acrylates are important causes of contact allergy and allergic contact disease, such as dermatitis and stomatitis, with new and emerging sources resulting in changing clinical presentations. OBJECTIVES: To identify the (meth)acrylates that most commonly cause allergic contact disease, highlight their usefulness for screening, and examine their relationship with occupational and clinical data. METHODS: A retrospective review of results from patch tests performed between July 2002 and September 2015, in one tertiary Cutaneous Allergy Unit, was performed RESULTS: A series of 28 (meth)acrylates was applied to 475 patients. Results were positive in 52 cases, with occupational sources being identified in 24. Industrial exposures and acrylic nails were responsible for 13 and 10 cases, respectively, with wound dressings being implicated in 7. We found that four individual (meth)acrylates (2-hydroxyethyl acrylate, 2-hydroxypropyl methacrylate, bisphenol A glycerolate dimethacrylate, and ethyl acrylate), if used as a screening tool, could have identified 47 (90.4%) of our positive cases. CONCLUSIONS: Our 13-year experience indicates a changing landscape of (meth)acrylate contact allergy and allergic contact disease, with an observed shift in exposures away from manufacturing and towards acrylic nail sources. Wound dressings are highlighted as emerging sources of sensitization. Larger studies are required to establish the sensitivity and specificity of the four (meth)acrylates proposed for potential screening.