Potential Role of Convolutional Neural Network Based Algorithm in Patient Selection for DCIS Observation Trials Using a Mammogram Dataset.

RATIONALE AND OBJECTIVES: We investigated the feasibility of utilizing convolutional neural network (CNN) for predicting patients with pure Ductal Carcinoma In Situ (DCIS) versus DCIS with invasion using mammographic images. MATERIALS AND METHODS: An IRB-approved retrospective study was performed. 246 unique images from 123 patients were used for our CNN algorithm. In total, 164 images in 82 patients diagnosed with DCIS by stereotactic-guided biopsy of calcifications without any upgrade at the time of surgical excision (pure DCIS group). A total of 82 images in 41 patients with mammographic calcifications yielding occult invasive carcinoma as the final upgraded diagnosis on surgery (occult invasive group). Two standard mammographic magnification views (CC and ML/LM) of the calcifications were used for analysis. Calcifications were segmented using an open source software platform 3D Slicer and resized to fit a 128 × 128 pixel bounding box. A 15 hidden layer topology was used to implement the neural network. The network architecture contained five residual layers and dropout of 0.25 after each convolution. Five-fold cross validation was performed using training set (80%) and validation set (20%). Code was implemented in open source software Keras with TensorFlow on a Linux workstation with NVIDIA GTX 1070 Pascal GPU. RESULTS: Our CNN algorithm for predicting patients with pure DCIS achieved an overall diagnostic accuracy of 74.6% (95% CI, ±5) with area under the ROC curve of 0.71 (95% CI, ±0.04), specificity of 91.6% (95% CI, ±5%) and sensitivity of 49.4% (95% CI, ±6%). CONCLUSION: It's feasible to apply CNN to distinguish pure DCIS from DCIS with invasion with high specificity using mammographic images.

Training probation officers in case formulation for personality disordered offenders.

BACKGROUND: The UK Strategy on Managing High Risk of Serious Harm Offenders with Severe Personality Disorder proposes an important role for offender managers in completing case formulations about such offenders. There is little evidence on whether this can be achieved. AIM: Our primary aims were to devise, implement and evaluate training in case formulation for offender managers. A secondary aim was to assess whether the training led to changes in offender manager attitudes towards working with offenders with personality disorder. METHOD: A 5-day training programme was delivered to 20 offender managers, whose ability to carry out case formulation was assessed before and after the training using a 10-point quality checklist. Attitudes towards personality disorder were also assessed before and after. Qualitative feedback on the training was used to provide further insight into the findings. RESULTS: Offender managers showed a significant improvement in their ability to carry out case formulation following training, with 7 of the 10 quality domains on the quality checklist rated as at least 'satisfactory' post training. Qualitative feedback highlighted reasons for some of the shortfalls in two of the three areas that did not show improvement. Improvements were shown in attitudes towards working with offenders with personality disorder in two of three domains. CONCLUSION: Our findings provide further evidence for the effectiveness of training offender managers in case formulation. This is encouraging in terms of extending implementation of the Offender Personality Disorder Pathway, but a full trial is indicated, partly not only because sample sizes have been small so far, but also because the participants have been enthusiastic volunteers rather than randomly selected offender managers, and there are indications from other work that we know too little about optimal extent of training and about whether its effects are sustained. Copyright © 2016 John Wiley & Sons, Ltd.

Brain metastases from prostate cancer: an 11-year analysis in the MRI era with emphasis on imaging characteristics, incidence, and prognosis.

BACKGROUND AND PURPOSE: Brain metastases from prostate cancer are uncommon and their imaging appearance has not been well defined. The main objectives of this study were to evaluate the incidence, MRI characteristics, and prognosis of parenchymal brain metastases originating in prostate cancer. METHODS: We retrospectively identified 21 patients with prostate cancer and evidence of brain metastases from 2000 to 2010. We reviewed the initial brain MRI scans and characterized the lesions according to location and appearance on MRI, while also determining patient demography, staging, and survival. RESULTS: The incidence of brain metastasis from prostate cancer was .16%. At the time of brain metastasis detection, 95% of the patients had concurrent osseous metastases, 86% lymph node metastases, and 76% liver and/or lung metastases. Brain metastases were multifocal in 71% of patients, hemorrhagic in 33%, diffusion restricted in 19%, and partially cystic/necrotic in 19%. The median overall survival after brain metastasis detection was 2.8 months. CONCLUSIONS: Brain metastasis from prostate cancer remains a rare phenomenon that most frequently occurs in the setting of widely disseminated bone and soft tissue disease. Patients with nonadenocarcinoma pathology are more likely to develop brain metastases. The MRI appearance is highly variable and prognosis is poor.

Mitogen-activated protein kinase-activated protein kinase 2 (MAPKAP-K2) as an antiinflammatory target: discovery and in vivo activity of selective pyrazolo[1,5-a]pyrimidine inhibitors using a focused library and structure-based optimization approach.

A novel class of mitogen-activated protein kinase-activated protein kinase 2 (MAPKAP-K2) inhibitors was discovered through screening a kinase-focused library. A homology model of MAPKAP-K2 was generated and used to guide the initial SAR studies and to rationalize the observed selectivity over CDK2. An X-ray crystal structure of a compound from the active series bound to crystalline MAPKAP-K2 confirmed the predicted binding mode. This has enabled the discovery of a series of pyrazolo[1,5-a]pyrimidine derivatives showing good in vitro cellular potency as anti-TNF-α agents and in vivo efficacy in a mouse model of endotoxin shock.

Antimicrobial stewardship: a collaborative partnership between infection preventionists and health care epidemiologists.

It is clear that the widespread and injudicious use of antimicrobials has greatly increased the presence of MDROs that threaten the health of all. There is worldwide acknowledgement that this threat is growing, and that prudent use of antimicrobials combined with infection prevention can prevent harm and improve patient safety. Antimicrobial stewardship programs must harness the talents of all members of the health care team to effectively identify the organism, determine its susceptibility, institute any precautions required, and prescribe the narrowest-acting antibiotic that will destroy it. IPs/HEs play a pivotal role in this approach, by assisting with early organism and infected patient identification, by promoting compliance with standard and transmission-based precautions and other infection prevention strategies such as care bundle practices, hand hygiene, and by educating staff, patients, and visitors.

Assessing the effect of the Surviving Sepsis Campaign treatment guidelines on clinical outcomes in a community hospital.

BACKGROUND: Bundles yield a reduction in mortality in patients with sepsis, but the majority of the data is from large academic centers. The ability of a community hospital to implement a sepsis bundle successfully, however, has not been investigated. OBJECTIVE: To examine the effect of a collaborative 2-part sepsis bundle on clinical outcomes and mortality at a community hospital. METHODS: The study included all patients with severe sepsis/septic shock over the age of 18 years admitted to the intensive care unit (ICU) from 2006 to 2007 who were not treated with a bundle (n = 53) and those who were treated with a bundle (n = 59). Data collected included demographics; initiation of vasopressors; days on vasopressors; blood glucose; use of drotrecogin alfa (activated), steroids, and ventilator; ICU/hospital lengths of stay; ventilator days; time to culture; time to first dose of antibiotics; time to transfer from emergency department to ICU; fluid resuscitation in the first 24 hours; percentage of patients started on dialysis; and mortality. RESULTS: Demographics; blood glucose; use of drotrecogin alfa (activated), steroids and ventilator; ICU/hospital lengths of stay; and ventilator days were statistically similar between groups. Median time to cultures, first dose of antibiotics, and transfer to ICU were all reduced with the bundle. Percentage of non-bundle patients on vasopressors was 87% versus 66.7% of bundle patients (p = 0.011) and number of median days on vasopressors was reduced. Fewer bundle patients were initiated on dialysis (0%) versus non-bundle patients (14.8%) (p = 0.02). Median fluid administered in the first 24 hours was 2200 mL (10-13,996 mL) for non-bundle patients and 7143 mL (1000-19,104 mL) for bundle patients (p < 0.001). Mortality was 61.1% in the non-bundle group versus 20% with the bundle (p < 0.001). CONCLUSIONS: Implementation of a 2-part sepsis bundle based on the Surviving Sepsis Campaign Guidelines can yield a positive impact on clinical outcome and mortality in a nonacademic, community hospital setting.

An empirical evaluation of reasons for non-completion of treatment in a dangerous and severe personality disorder unit.

BACKGROUND: Individuals deemed to be of high risk to others, and diagnosed with severe personality disorders have become the focus for developing clinical services in England. Such services often require highly secure accommodation and labour-intensive therapeutic interventions. There is, however, uncertainty about the capacity to engage such patients effectively in therapies. AIM: Here, we examine service evaluation monitoring data to identify the level of completion of therapeutic programmes in a high secure severe personality disordered population, and analyse reasons for failure to complete. METHOD: Guidelines for classifying reasons for non-completion were developed, based on the multifactorial offender readiness model (MORM). Electronic case notes were searched for references to non-completion, and recorded reasons for non-completion were classified. RESULTS: Non-completion was at a relatively modest level. The main reasons for non-completion were: (1) affective: general distress of the patient or specific emotional reactions to previous offending, e.g. shame; (2) volitional: pursuing goals other than treatment; and (3) cognitive: negative self-efficacy beliefs and negative evaluations (low trust) of staff and the programme. External factors included exclusion from treatment and transfer to another unit. CONCLUSION: This study identifies specific readiness areas that might need to be addressed in efforts to improve engagement and retention in treatment. A wider range of methodologies is required for future studies.

Sliding scale versus tight glycemic control in the noncritically ill at a community hospital.

BACKGROUND: Development of hyperglycemia during hospitalization is an area of concern in patients with and without diabetes mellitus. Tight glycemic control has been debated for critically ill and noncritically ill patients with hyperglycemia. Although many studies have been performed in the critically ill, adequate data are not available in the noncritically ill population. OBJECTIVE: To compare traditional sliding scale (SS) with a tight glycemic control (TC) algorithm. The primary endpoint was the percentage of total blood glucose measurements in the target range of 80-150 mg/dL. The secondary endpoint evaluated was safety, defined as percentage of all blood glucose measurements that were 0-60 mg/dL. METHODS: A 1-year, retrospective analysis from June 1, 2007, to May 31, 2008, was performed evaluating all inpatients with hyperglycemia within the first 48 hours of admission to the Medical Center of Plano, Plano, TX. A cohort of patients managed with SS (n =121) was compared with those treated with TC (n = 210). Patients on SS insulin received a traditional SS regimen with regular insulin or insulin aspart based on physician preference. RESULTS: Demographics and comorbidities were similar between the 2 groups; however, the TC cohort was younger (64.8 + or - 14.1 vs 70.8 + or - 13.7 y; p < 0.001). There were more persons with type 2 diabetes mellitus in the TC cohort (81.9%) versus the SS cohort (60.3%; p < 0.001). In the TC cohort, 42.9% of blood glucose measurements were in the target range of 80-150 mg/dL compared with 30.6% of the measurements in the SS cohort (p < 0.001). Regarding safety, 2% of blood glucose measurements of the TC cohort were in the range of 0-60 mg/dL versus 0.3% of the SS cohort (p < 0.001). No clinical sequelae of hypoglycemia were observed. Patients achieved more blood glucose measurements in the target range when treated with TC versus SS insulin, without regard to prior history of diabetes. CONCLUSIONS: Patients treated with TC experienced more blood glucose measurements in the target range as compared with patients treated with SS with relatively low hypoglycemia rates.

Outcomes of extended infusion piperacillin/tazobactam for documented Gram-negative infections.

This comparison of intermittent versus extended-infusion piperacillin-tazobactam among patients with Gram-negative infections revealed similar mortality and length of stay. Outcomes remained similar when stratified by MIC value.

A retrospective analysis of joint salvage procedures for grades III and IV hallux rigidus.

UNLABELLED: The purpose of this study was to evaluate the outcome of the use of a decompression osteotomy for the treatment of end-stage hallux rigidus. We conducted a retrospective analysis of 28 feet (23 patients) with grades III and IV hallux rigidus that underwent a first metatarsal head decompression osteotomy with preservation of the articular surfaces of the first metatarsophalangeal joint. We also devised a 9-item questionnaire to explore the patients' perceptions of preoperative and postoperative pain, limitations of activity, influence on shoe wear, and the total range of motion of the first metatarsophalangeal joint. Furthermore, we used a modified version of the AOFAS forefoot scoring system to compare the patients' foot-related health status in relative to the operative repair of hallux rigidus. Comparisons of the pre- and postoperative results revealed statistically significant improvements in pain (P< .001), functional limitation (P< .001), shoe restrictions (P= .0072), total range of motion (P= .0449), and the AOFAS forefoot score (P< .001). Overall patient satisfaction with the results of the surgery was more than 85%, and the patients' chief complaint was alleviated in more than 75% of the participants. The results of this investigation demonstrated that a decompression first metatarsal osteotomy is an acceptable alternative to joint destructive procedures for the treatment of end-stage hallux rigidus. LEVEL OF CLINICAL EVIDENCE: 4.

Clinical outcomes and cost minimization with an alternative dosing regimen for meropenem in a community hospital.

STUDY OBJECTIVE: To compare outcomes and cost for the traditional United States Food and Drug Administration-approved dosing regimen for meropenem versus an alternative dosing regimen providing similar pharmacodynamic exposure with a lower total daily dose. DESIGN: Retrospective cohort study with a cost-minimization analysis. SETTING: A 417-bed, privately owned community hospital. PATIENTS: One hundred patients who received meropenem 1 g every 8 or 12 hours (traditional dosing regimen) between January 1 and September 30, 2004 (historical controls), and 192 patients who received meropenem 500 mg every 6 or 8 hours (alternative dosing regimen) between October 1, 2004, and September 30, 2005. MEASUREMENTS AND MAIN RESULTS: Demographic and clinical data were collected for all patients. Cost-minimization analysis was performed by using the drug acquisition cost for meropenem. Demographics, sources of infection, distributions of organisms, and Charlson Comorbidity Index scores were similar between patients in the traditionally and alternatively dosed groups. Concomitant therapy, duration of therapy, success rates, lengths of stay, and in-hospital mortality rates were also similar between groups. Median time to the resolution of symptoms was 3 days for traditional dosing and 1.5 days for alternative dosing (p<0.0001). A logistic regression model including the dosing strategy showed that only polymicrobial infections and sepsis were associated with increased failure rates. The median cost for antibiotics was $439.05/patient for traditional dosing and $234.08/patient for alternative dosing (p<0.0001). CONCLUSION: An alternative dosing regimen for meropenem with a lower total daily dose yielded patient outcomes, including success rates and duration of therapy, equivalent to those of the traditional dosing regimen. Alternative dosing decreased total drug exposure, costs for antibiotics, and time to the resolution of infections.

The role of second autografts in the management of myeloma at first relapse.

We report an analysis of the value of a second high-dose melphalan autograft, performed at relapse, on a series of newly diagnosed myeloma patients entered into the high-dose program at our center. We conclude that relapse-free survival after the first autograft is a major prognostic factor in determining outcome.

Long-term outcomes of previously untreated myeloma patients: responses to induction chemotherapy and high-dose melphalan incorporated within a risk stratification model can help to direct the use of novel treatments.

Induction chemotherapy followed by high-dose melphalan (HDM) is the standard treatment for fitter patients with myeloma. The place of bortezomib and the thalidomide analogues within this treatment paradigm is yet to be established. We sought to identify patients who may benefit from the introduction of novel agents during their initial management. An intention-to-treat analysis was performed on 383 patients with newly diagnosed myeloma eligible for HDM to determine whether the extent of response to induction therapy and HDM correlated with long-term survival. Early response [complete response (CR) and partial response (PR)] to induction therapy was predictive of overall survival (OS) [median OS, 7.47 years for responders (CR and PR) versus 4.89 years for non-responders; P = 0.035]. The attainment of CR at 3 months post-HDM correlated with a prolonged progression-free survival (PFS) (median PFS, 7.4 years in CR group versus 5.3 years in non-CR group; P = 0.023). This data suggests that, at every stage of treatment, the aim should be to achieve CR. Patients with suboptimal responses could be offered alternative therapy. We propose a multiparametric risk-adapted model that includes response to induction chemotherapy and HDM, for identifying patients who may benefit from novel approaches to treatment.