Infiltrating ductal carcinoma breast with central necrosis closely mimicking ductal carcinoma in situ (comedo type): a case series

Here we present a series of infiltrative ductal carcinoma breast cases (infiltrative ductal carcinoma with central necrosis) so closely mimicking \u27DCIS with central comedo necrosis\u27 that on initial morphological analysis these foci of tumors were labeled as DCIS (high grade, comedo). However on further histological work up and by using immunohistochemistry (IHC) for myoepithelial markers it was later confirmed that these were foci of infiltrative ductal carcinoma breast with central necrosis. This case series gives the realization that a breast carcinoma may be partly or entirely DCIS like yet invasive. In such a dilemma IHC especially for assessment of myoepithelial lining is very useful to differentiate DCIS comedo from invasive carcinoma with central necrosis

Utility of WT-1, p63, MOC31, mesothelin, and cytokeratin (K903 and CK5/6) immunostains in differentiating adenocarcinoma, squamous cell carcinoma, and malignant mesothelioma in effusions

To distinguish carcinoma, either adenocarcinoma (ADC) or squamous cell carcinoma (SCC), and malignant mesothelioma (MM) in effusion can be a diagnostic challenge based on morphology alone. This study evaluates the utility of WT-1, p63, MOC31, mesothelin, and cytokeratin (K903 and CK5/6) immunostains in effusions when ADC and SCC of the lung are in the differential diagnosis with MM. A cohort of 43 effusions consisting of lung ADC ( N = 10), SCC ( N = 15), and MM ( N = 18, mostly (16) pleural based), was subjected to immunostains using the above mentioned antibodies. WT-1 was positive in 100% MM, 0% ADC, and 0% SCC cases while p63 was positive in 0% MM, 30% ADC, and 80% SCC cases. Stain for MOC31 was positive in 100% ADC, 67% SCC, and 35% MM cases. Similarly, mesothelin antibody stained 100% ADC, 60% SCC, and 47% MM cases. Antibodies for K903 and CK5/6 stained 100% SCC cases but fewer ADC cases (40 and 10%, respectively). In conclusion, in this cohort of mostly pleural malignant effusion, MM can be identified with positive staining for WT-1 and negative staining for p63. Conversely, negative staining with WT-1 and positive staining for p63 exclude MM. Used as part of an immunostain panel, cytokeratin markers (CK5/6 and K903) are useful in differentiating SCC from ADC when MM is already excluded, and MOC31 might have limited value in differentiating ADC from MM. A negative stain with MOC31 can exclude lung ADC. Mesothelin, on the other hand, is not useful in the differential diagnosis of ADC, SCC, and MM. Diagn. Cytopathol. 2008;36:20–25. © 2007 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/57547/1/20747_ftp.pd

Evaluating specialist intensive support teams for adults with intellectual disabilities who display behaviours that challenge: The IST-ID mixed methods study

Background Intensive Support Teams (ISTs) are recommended for individuals with intellectual disabilities who display behaviours that challenge. However, there is currently little evidence about the clinical and cost effectiveness of IST models operating in England. Aims To investigate the clinical and cost effectiveness of IST models. Methods We carried out a cohort study to evaluate the clinical and cost-effectiveness of two previously identified IST models (independent and enhanced) in England. Adult participants (n=226) from 21 ISTs (10 independent and 11 enhanced) were enrolled. The primary outcome was change in challenging behaviour between baseline and 9 months measured by the Aberrant Behaviour Checklist-Community 2. Results We found no statistically significant differences between models for the primary outcome (adjusted β: 4.27; 95% CI: -6.34 to 14.87; p=0.430) or any secondary outcomes. Quality Adjusted Life Years (0.0158; 95% CI: -0.0088 to 0.0508) and costs (£3409.95; 95% CI: -£9957.92 to £4039.89) of the two models were comparable. Conclusions The study provides evidence that both models were associated with clinical improvement for similar costs at follow-up. We recommend that the choice of service model should rest with local services. Further research should investigate the critical components of IST care to inform the development of fidelity criteria, and policy makers should consider whether roll out of such teams should be mandated. Study registration number ClinicalTrials.gov NCT03586375 ; IRAS 239820; National Institute for Health Research (NIHR) Central Portfolio Management System (CPMS) 38554

Clinical and cost evaluation of two models of specialist intensive support teams for adults with intellectual disabilities who display behaviours that challenge: the IST-ID mixed-methods study

Background: Intensive support teams (ISTs) are recommended for individuals with intellectual disabilities who display behaviours that challenge. However, there is currently little evidence about the clinical and cost-effectiveness of IST models operating in England.// Aims: To investigate the clinical and cost-effectiveness of IST models.// Method: We carried out a cohort study to evaluate the clinical and cost-effectiveness of two previously identified IST models (independent and enhanced) in England. Adult participants (n = 226) from 21 ISTs (ten independent and 11 enhanced) were enrolled. The primary outcome was change in challenging behaviour between baseline and 9 months as measured by the Aberrant Behaviour Checklist-Community version 2.// Results: We found no statistically significant differences between models for the primary outcome (adjusted β = 4.27; 95% CI −6.34 to 14.87; P = 0.430) or any secondary outcomes. Quality-adjusted life-years (0.0158; 95% CI: −0.0088 to 0.0508) and costs (£3409.95; 95% CI −£9957.92 to £4039.89) of the two models were comparable. Conclusions The study provides evidence that both models were associated with clinical improvement for similar costs at follow-up. We recommend that the choice of service model should rest with local services. Further research should investigate the critical components of IST care to inform the development of fidelity criteria, and policy makers should consider whether roll out of such teams should be mandated

Cholangiocarcinoma: Epidemiology and risk factors

Cholangiocarcinoma (CCA) is a heterogeneous disease arising from a complex interaction between host-specific genetic background and multiple risk factors. Globally, CCA incidence rates exhibit geographical variation, with much higher incidence in parts of the Eastern world compared to the West. These differences are likely to reflect differences in geographical risk factors as well as genetic determinants. Of note, over the past few decades, the incidence rates of CCA appear to change and subtypes of CCA appear to show distinct epidemiological trends. These trends need to be interpreted with caution given the issues of diagnosis, recording and coding of subtypes of CCA. Epidemiological evidences suggest that in general population some risk factors are less frequent but associated with a higher CCA risk, while others are more common but associated with a lower risk. Moreover, while some risk factors are shared by intrahepatic and both extrahepatic forms, others seem more specific for one of the two forms. Currently some pathological conditions have been clearly associated with CCA development, and other conditions are emerging; however, while their impact in increasing CCA risk as single etiological factors has been provided in many studies, less is known when two or more risk factors co-occur in the same patient. Moreover, despite the advancements in the knowledge of CCA aetiology, in Western countries about 50% of cases are still diagnosed without any identifiable risk factor. It is therefore conceivable that other still undefined etiologic factors are responsible for the recent increase of CCA (especially iCCA) incidence worldwide

Beta-blockers or Placebo for Primary Prophylaxis (BOPPP) of oesophageal varices:study protocol for a randomised controlled trial

BACKGROUND: Liver disease is within the top five causes of premature death in adults. Deaths caused by complications of cirrhosis continue to rise, whilst deaths related to other non-liver disease areas are declining. Portal hypertension is the primary sequelae of cirrhosis and is associated with the development of variceal haemorrhage, ascites, hepatic encephalopathy and infection, collectively termed hepatic decompensation, which leads to hospitalisation and mortality. It remains uncertain whether administering a non-selective beta-blocker (NSBB), specifically carvedilol, at an earlier stage, i.e. when oesophageal varices are small, can prevent VH and reduce all-cause decompensation (ACD).METHODS/DESIGN: The BOPPP trial is a pragmatic, multicentre, placebo-controlled, triple-blinded, randomised controlled trial (RCT) in England, Scotland, Wales and Northern Ireland. Patients aged 18 years or older with cirrhosis and small oesophageal varices that have never bled will be recruited, subject to exclusion criteria. The trial aims to enrol 740 patients across 55 hospitals in the UK. Patients are allocated randomly on a 1:1 ratio to receive either carvedilol 6.25 mg (a NSBB) or a matched placebo, once or twice daily, for 36 months, to attain adequate power to determine the effectiveness of carvedilol in preventing or reducing ACD. The primary outcome is the time to first decompensating event. It is a composite primary outcome made up of variceal haemorrhage (VH, new or worsening ascites, new or worsening hepatic encephalopathy (HE), spontaneous bacterial peritonitis (SBP), hepatorenal syndrome, an increase in Child-Pugh grade by 1 grade or MELD score by 5 points, and liver-related mortality. Secondary outcomes include progression to medium or large oesophageal varices, development of gastric, duodenal, or ectopic varices, participant quality of life, healthcare costs and transplant-free survival.DISCUSSION: The BOPPP trial aims to investigate the clinical and cost-effectiveness of carvedilol in patients with cirrhosis and small oesophageal varices to determine whether this non-selective beta-blocker can prevent or reduce hepatic decompensation. There is clinical equipoise on whether intervening in cirrhosis, at an earlier stage of portal hypertension, with NSBB therapy is beneficial. Should the trial yield a positive result, we anticipate that the administration and use of carvedilol will become widespread with pathways developed to standardise the administration of the medication in primary care.ETHICS AND DISSEMINATION: The trial has been approved by the National Health Service (NHS) Research Ethics Committee (REC) (reference number: 19/YH/0015). The results of the trial will be submitted for publication in a peer-reviewed scientific journal. Participants will be informed of the results via the BOPPP website ( www.boppp-trial.org ) and partners in the British Liver Trust (BLT) organisation.TRIAL REGISTRATION: EUDRACT reference number: 2018-002509-78. ISRCTN reference number: ISRCTN10324656. Registered on April 24 2019.</p

Cost evaluation of point-of-care testing for community-acquired influenza in adults presenting to the emergency department

Background Rapid molecular point-of-care tests (POCTs) for influenza have potential to produce cost savings in emergency departments (EDs) and acute care settings. To date, published projected savings have been based on estimated costs. Objectives This study aimed to describe the cost implications of a rapid influenza POCT using accurate real-world patient level costing data. 204 adult patients receiving point-of-care (POC) influenza testing in the ED as part of a routine clinical service were identified retrospectively, alongside a control cohort of 104 patients from the same influenza season. Costs for all were calculated at the individual patient level. Cost comparison was performed using an instrumental variable (IV) regression to overcome potential bias within the observational dataset. Results Patients who had a POCT on average cost 67 % less than those who did not (average cost reduction: £2066: 95 % CI: £624 and £2665). Moderate to high NEWS score at arrival, presence of ≥1 comorbidity, and age ≥70 years increased overall costs across both groups (p < 0.05). Conclusions Savings from POC testing can be attributed to more targeted treatments, fewer admissions and reduced lengths of stay. The IV regression results are supported by a second method (ordinary least square against baseline characteristics). They are also in line with existing work that use estimated costs but indicate greater savings than predicted previously. In conclusion, POC influenza testing in the emergency department produces significant cost savings, this is demonstrated here through an analysis using individual real-world patient level costing data

Adolescents accept digital mental health support in schools: A co-design and feasibility study of a school-based app for UK adolescents

Schools in the UK are required to provide frontline mental health promotion and prevention to adolescents, but with few resources. School-hosted mHealth is one option which could meet needs. This study co-designed and feasibility tested a self-help, school hosted, digital intervention for adolescents showing early symptoms of deteriorating mental health. Via extensive co-design, we produced a youth-targeted web-app (MindMate2) and a low-intensity parent component (Partner2U). Feasibility was tested in four UK high schools with n = 31 young people (15-17y). We specified rules for progression to an effectiveness trial, tested candidate primary outcome measures and conducted an exploratory cost-effectiveness analysis. Co-design produced MindMate2U to be a six-week, self-help, smartphone-delivered program targeting risk and protective factors for adolescent mental health. Young people's MindMate2U account was set up by school after which they progressed independently through six topics of their choosing. User ratings (n = 19) and post- intervention interviews (n = 6) showed resource acceptability. We met our recruitment, retention and pre-post measure completion targets and identified the Strengths and Difficulties Questionnaire as the most sensitive outcome measure. This study established the feasibility of a co-designed, mental health app as a low-burden, school-hosted resource for symptomatic young people and opens up new possibilities for the integration of mHealth in schools. Support via schools to parents of symptomatic young people may need to be universal rather than targeted. Following some refinements of MindMate2U, a phase 2 randomised controlled trial is warranted to test its effectiveness