Adrenal lesions found incidentally: how to improve clinical and cost-effectiveness

Introduction Adrenal incidentalomas are lesions that are incidentally identified while scanning for other conditions. While most are benign and hormonally non-functional, around 20% are malignant and/or hormonally active, requiring prompt intervention. Malignant lesions can be aggressive and life-threatening, while hormonally active tumours cause various endocrine disorders, with significant morbidity and mortality. Despite this, management of patients with adrenal incidentalomas is variable, with no robust evidence base. This project aimed to establish more effective and timely management of these patients. Methods We developed a web-based, electronic Adrenal Incidentaloma Management System (eAIMS), which incorporated the evidence-based and National Health Service–aligned 2016 European guidelines. The system captures key clinical, biochemical and radiological information necessary for adrenal incidentaloma patient management and generates a pre-populated outcome letter, saving clinical and administrative time while ensuring timely management plans with enhanced safety. Furthermore, we developed a prioritisation strategy, with members of the multidisciplinary team, which prioritised high-risk individuals for detailed discussion and management. Patient focus groups informed process-mapping and multidisciplinary team process re-design and patient information leaflet development. The project was partnered by University Hospital of South Manchester to maximise generalisability. Results Implementation of eAIMS, along with improvements in the prioritisation strategy, resulted in a 49% reduction in staff hands-on time, as well as a 78% reduction in the time from adrenal incidentaloma identification to multidisciplinary team decision. A health economic analysis identified a 28% reduction in costs. Conclusions The system’s in-built data validation and the automatic generation of the multidisciplinary team outcome letter improved patient safety through a reduction in transcription errors. We are currently developing the next stage of the programme to proactively identify all new adrenal incidentaloma cases

Evaluating Prescriber Adherence to Guideline-Based Treatment Pathways of a Newly Initiated Antimicrobial Stewardship Program at a Rehabilitation Hospital

Background: Inappropriate use of antimicrobials in the healthcare setting is associated with consequences including antimicrobial resistance, Clostridium difficile infection (CDI), adverse drug reactions, and increased healthcare costs. To combat this, hospitals are creating antimicrobial stewardship programs (ASPs) which seek to optimize antimicrobial utilization. To date, no studies have been done to assess adherence to an ASP in a rehabilitation hospital setting. The objective of this study is to evaluate prescriber compliance to treatment pathways for common infections before and after ASP implementation. Methods: This was a retrospective cohort study of patients admitted to the Rehabilitation Hospital of Indiana (RHI) who received an antibiotic between October 1, 2015-December 31, 2015 (pre-ASP group) and January 1, 2016-September 30, 2016 (post-ASP group) for one of the following indications: pneumonia, urinary tract infection, CDI, bone and joint infection, skin or skin structure infection, febrile neutropenia, or central/peripherally inserted central catheter line bloodstream infection. Data extracted from the hospital’s electronic medical record system included patient demographic and clinical information, laboratory data, culture and susceptibility results, and antibiotic information. The primary outcome of this study was prescriber compliance to treatment pathways defined as correct drug based on the documented indication before and after the implementation of the antimicrobial stewardship program on January 1, 2016. Descriptive statistics were performed to analyze baseline characteristics and culture data, as well as antimicrobial class, indication, and overall compliance to the guideline-based treatment pathways. Results: Data was extracted from the hospital’s electronic medical record system for 381 patients (n=381) who received an antibiotic at RHI. There were 121 and 260 patients included in the pre- and post-ASP study groups, respectively. Urinary tract infections were the most common infection for which antibiotics were prescribed (n=293; 76.9%). The three most common antibiotics prescribed were ciprofloxacin (n=101; 26.5%), sulfamethoxazole/trimethoprim (n=81; 21.3%), and nitrofurantoin (n=49; 12.9%). Compliance was found to be 81% in the pre-ASP group and 78.5% in the post-ASP group (p=0.571). Overall compliance was found to be the highest (100% in both pre- and postASP groups) for osteomyelitis infections and CDI. Urinary tract infections had the next highest rate of compliance in both the pre- and post-ASP groups (86.5% and 81.7% respectively). Conclusions: No difference in rates of prescriber compliance to guideline-based treatment pathways was found in the pre- and post-ASP groups. Urinary tract infections were found to be the most common indication requiring antimicrobial usage at RHI and had the third highest rate of compliance out of the infections included in this study. Our study highlights a need for further investigation regarding the impact of the ASP on appropriate antimicrobial dose, duration of therapy, administration, and de-escalation based on culture data. Additionally, our study identified a need for formal prescriber education focusing on how to utilize the treatment pathways, especially for those infections with the lowest compliance rates

The gaps between healthcare service and building design : a state of the art review

Healthcare buildings are designed to achieve diverse objectives, ranging from providing appropriate environments where care can be delivered to communities to increasing operational efficiency and improving patient flows and the patient experience. Improvements in operational efficiency should result from state-of-the-art buildings, more appropriate layouts, departmental adjacencies, efficient clinical and business processes and enhanced information systems. However, complexities around requirements and stakeholders management may prevent the achievement of such objectives. The aim of this article is to identify and understand how healthcare services (re)design and building design can be integrated to facilitate increased performance both in terms of service delivery and future changes. Findings indicate that current approaches and innovation are restricted due to functional barriers in the design process, and that there is a need to support the development of operations driven design through time (e.g. flexible and durable) that satisfies diverse needs

Hysterectomy, endometrial ablation, and levonorgestrel releasing intrauterine system (Mirena) for treatment of heavy menstrual bleeding : cost effectiveness analysis

Peer reviewedPublisher PD

A Robust Gene Expression Prognostic Signature for Overall Survival in High-Grade Serous Ovarian Cancer.

The objective of this research was to develop a robust gene expression-based prognostic signature and scoring system for predicting overall survival (OS) of patients with high-grade serous ovarian cancer (HGSOC). Transcriptomic data of HGSOC patients were obtained from six independent studies in the NCBI GEO database. Genes significantly deregulated and associated with OS in HGSOCs were selected using GEO2R and Kaplan-Meier analysis with log-rank testing, respectively. Enrichment analysis for biological processes and pathways was performed using Gene Ontology analysis. A resampling/cross-validation method with Cox regression analysis was used to identify a novel gene expression-based signature associated with OS, and a prognostic scoring system was developed and further validated in nine independent HGSOC datasets. We first identified 488 significantly deregulated genes in HGSOC patients, of which 232 were found to be significantly associated with their OS. These genes were significantly enriched for cell cycle division, epithelial cell differentiation, p53 signaling pathway, vasculature development, and other processes. A novel 11-gene prognostic signature was identified and a prognostic scoring system was developed, which robustly predicted OS in HGSOC patients in 100 sampling test sets. The scoring system was further validated successfully in nine additional HGSOC public datasets. In conclusion, our integrative bioinformatics study combining transcriptomic and clinical data established an 11-gene prognostic signature for robust and reproducible prediction of OS in HGSOC patients. This signature could be of clinical value for guiding therapeutic selection and individualized treatment

Genomic Profiling of Childhood Tumor Patient-Derived Xenograft Models to Enable Rational Clinical Trial Design.

Accelerating cures for children with cancer remains an immediate challenge as a result of extensive oncogenic heterogeneity between and within histologies, distinct molecular mechanisms evolving between diagnosis and relapsed disease, and limited therapeutic options. To systematically prioritize and rationally test novel agents in preclinical murine models, researchers within the Pediatric Preclinical Testing Consortium are continuously developing patient-derived xenografts (PDXs)-many of which are refractory to current standard-of-care treatments-from high-risk childhood cancers. Here, we genomically characterize 261 PDX models from 37 unique pediatric cancers; demonstrate faithful recapitulation of histologies and subtypes; and refine our understanding of relapsed disease. In addition, we use expression signatures to classify tumors for TP53 and NF1 pathway inactivation. We anticipate that these data will serve as a resource for pediatric oncology drug development and will guide rational clinical trial design for children with cancer

Molecularly defined diffuse leptomeningeal glioneuronal tumor (DLGNT) comprises two subgroups with distinct clinical and genetic features

Diffuse leptomeningeal glioneuronal tumors (DLGNT) represent rare CNS neoplasms which have been included in the 2016 update of the WHO classification. The wide spectrum of histopathological and radiological features can make this enigmatic tumor entity difficult to diagnose. In recent years, large-scale genomic and epigenomic analyses have afforded insight into key genetic alterations occurring in multiple types of brain tumors and provide unbiased, complementary tools to improve diagnostic accuracy. Through genome-wide DNA methylation screening of > 25,000 tumors, we discovered a molecularly distinct class comprising 30 tumors, mostly diagnosed histologically as DLGNTs. Copy-number profiles derived from the methylation arrays revealed unifying characteristics, including loss of chromosomal arm 1p in all cases. Furthermore, this molecular DLGNT class can be subdivided into two subgroups [DLGNT methylation class (MC)-1 and DLGNT methylation class (MC)-2], with all DLGNT-MC-2 additionally displaying a gain of chromosomal arm 1q. Co-deletion of 1p/19q, commonly seen in IDH-mutant oligodendroglioma, was frequently observed in DLGNT, especially in DLGNT-MC-1 cases. Both subgroups also had recurrent genetic alterations leading to an aberrant MAPK/ERK pathway, with KIAA1549:BRAF fusion being the most frequent event. Other alterations included fusions of NTRK1/2/3 and TRIM33:RAF1, adding up to an MAPK/ERK pathway activation identified in 80% of cases. In the DLGNT-MC-1 group, age at diagnosis was significantly lower (median 5 vs 14 years, p < 0.01) and clinical course less aggressive (5-year OS 100, vs 43% in DLGNT-MC-2). Our study proposes an additional molecular layer to the current histopathological classification of DLGNT, of particular use for cases without typical morphological or radiological characteristics, such as diffuse growth and radiologic leptomeningeal dissemination. Recurrent 1p deletion and MAPK/ERK pathway activation represent diagnostic biomarkers and therapeutic targets, respectively—laying the foundation for future clinical trials with, e.g., MEK inhibitors that may improve the clinical outcome of patients with DLGNT

Simultaneous evolutionary expansion and constraint of genomic heterogeneity in multifocal lung cancer.

Recent genomic analyses have revealed substantial tumor heterogeneity across various cancers. However, it remains unclear whether and how genomic heterogeneity is constrained during tumor evolution. Here, we sequence a unique cohort of multiple synchronous lung cancers (MSLCs) to determine the relative diversity and uniformity of genetic drivers upon identical germline and environmental background. We find that each multicentric primary tumor harbors distinct oncogenic alterations, including novel mutations that are experimentally demonstrated to be functional and therapeutically targetable. However, functional studies show a strikingly constrained tumorigenic pathway underlying heterogeneous genetic variants. These results suggest that although the mutation-specific routes that cells take during oncogenesis are stochastic, genetic trajectories may be constrained by selection for functional convergence on key signaling pathways. Our findings highlight the robust evolutionary pressures that simultaneously shape the expansion and constraint of genomic diversity, a principle that holds important implications for understanding tumor evolution and optimizing therapeutic strategies.Across cancer types tumor heterogeneity has been observed, but how this relates to tumor evolution is unclear. Here, the authors sequence multiple synchronous lung cancers, highlighting the evolutionary pressures that simultaneously shape the expansion and constraint of genomic heterogeneity