Perspectives on Clinical Adoption Barriers to Blood-Based Multi-Cancer Early Detection Tests across Stakeholders.

Current United States Preventive Services Task Force (USPSTF) recommendations include routine screening for breast, cervical, colorectal, and lung cancer; however, two out of every three cancer cases occur in other indications, leading to diagnoses in advanced stages of the disease and a higher likelihood of mortality. Blood-based multi-cancer early detection (MCED) tests can impact cancer screening and early detection by monitoring for multiple different cancer types at once, including indications where screening is not performed routinely today. We conducted a survey amongst healthcare providers (HCPs), payers, and patients within the U.S. health system to understand the current utilization of cancer screening tests and the anticipated barriers to widespread adoption of blood-based MCED tests. The results indicated that the community favors the adoption of blood-based MCED tests and that there is broad agreement on the value proposition. Despite this recognition, the survey highlighted that there is limited use today due to the perceived lack of clinical accuracy and utility data, high out-of-pocket patient costs, and lack of payer coverage. To overcome the hurdles for future widespread adoption of blood-based MCED tests, increased investment in data generation, education, and implementation of logistical support for HCPs will be critical.

Effectiveness of an Intervention to Improve Decision Making for Older Patients With Advanced Chronic Kidney Disease : A Randomized Controlled Trial.

BACKGROUND: Older patients with advanced chronic kidney disease (CKD) face difficult decisions about managing kidney failure, frequently experiencing decisional conflict, regret, and treatment misaligned with preferences. OBJECTIVE: To assess whether a decision aid about kidney replacement therapy improved decisional quality compared with usual care. DESIGN: Multicenter, randomized, controlled trial. (ClinicalTrials.gov: NCT03522740). SETTING: 8 outpatient nephrology clinics associated with 4 U.S. centers. PARTICIPANTS: English-fluent patients, 70 years and older with nondialysis CKD stages 4 to 5 recruited from 2018 to 2020. INTERVENTION: DART (Decision-Aid for Renal Therapy) is an interactive, web-based decision aid for older adults with CKD. Both groups received written education about treatments. MEASUREMENTS: Change in the decisional conflict scale (DCS) score from baseline to 3, 6, 12, and 18 months. Secondary outcomes included change in prognostic and treatment knowledge and change in uncertainty. RESULTS: Among 400 participants, 363 were randomly assigned: 180 to usual care, 183 to DART. Decisional quality improved with DART with mean DCS declining compared with control (mean difference, -8.5 [95% CI, -12.0 to -5.0]; P < 0.001), with similar findings at 6 months, attenuating thereafter. At 3 months, knowledge improved with DART versus usual care (mean difference, 7.2 [CI, 3.7 to 10.7]; P < 0.001); similar findings at 6 months were modestly attenuated at 18 months (mean difference, 5.9 [CI, 1.4 to 10.3]; P = 0.010). Treatment preferences changed from 58% "unsure" at baseline to 28%, 20%, 23%, and 14% at 3, 6, 12, and 18 months, respectively, with DART, versus 51% to 38%, 35%, 32%, and 18% with usual care. LIMITATION: Latinx patients were underrepresented. CONCLUSION: DART improved decision quality and clarified treatment preferences among older adults with advanced CKD for 6 months after the DART intervention. PRIMARY FUNDING SOURCE: Patient-Centered Outcomes Research Institute (PCORI).

Stakeholders Perceptions of Barriers to Precision Medicine Adoption in the United States.

Despite evidence that precision medicine (PM) results in improved patient care, the broad adoption and implementation has been challenging across the United States (US). To better understand the perceived barriers associated with PM adoption, a quantitative survey was conducted across five stakeholders including medical oncologists, surgeons, lab directors, payers, and patients. The results of the survey reveal that stakeholders are often not aligned on the perceived challenges with PM awareness, education and reimbursement, with there being stark contrast in viewpoints particularly between clinicians, payers, and patients. The output of this study aims to help raise the awareness that misalignment on the challenges to PM adoption is contributing to broader lack of implementation that ultimately impacts patients. With better understanding of stakeholder viewpoints, we can help alleviate the challenges by focusing on multi-disciplinary education and awareness to ultimately improve patient outcomes.

SU086, an inhibitor of HSP90, impairs glycolysis and represents a treatment strategy for advanced prostate cancer.

Among men, prostate cancer is the second leading cause of cancer-associated mortality, with advanced disease remaining a major clinical challenge. We describe a small molecule, SU086, as a therapeutic strategy for advanced prostate cancer. We demonstrate that SU086 inhibits the growth of prostate cancer cells in vitro, cell-line and patient-derived xenografts in vivo, and ex vivo prostate cancer patient specimens. Furthermore, SU086 in combination with standard of care second-generation anti-androgen therapies displays increased impairment of prostate cancer cell and tumor growth in vitro and in vivo. Cellular thermal shift assay reveals that SU086 binds to heat shock protein 90 (HSP90) and leads to a decrease in HSP90 levels. Proteomic profiling demonstrates that SU086 binds to and decreases HSP90. Metabolomic profiling reveals that SU086 leads to perturbation of glycolysis. Our study identifies SU086 as a treatment for advanced prostate cancer as a single agent or when combined with second-generation anti-androgens.

Metabolic syndrome in childhood cancer survivors: delta BMI a risk factor in lower-middle-income countries.

PURPOSE: Metabolic syndrome (MetSyn) is an important late effect of childhood cancer. The combination of rising obesity and high prevalence of under-nutrition at diagnosis makes this a unique population to study in LMIC (lower middle-income countries). METHODS: Children ≤ 18 years of age at cancer diagnosis, in a single center in a LMIC, who were disease free and had completed treatment at least 2 years prior to study were included. MetSyn was defined using International Federation for Diabetes criteria for Asian Indians. Logistic regression analyses were carried out to evaluate the influence of various risk factors, including delta BMI (increase in body mass index from diagnosis to evaluation), on MetSyn. RESULTS: A high prevalence of MetSyn (12.2%), central obesity (33%), and dyslipidemia (61.8%) were found in a cohort of 500 Asian Indian childhood cancer survivors (CCS) at a median follow-up age of 17 years. Multivariable analysis revealed older age at diagnosis ≥ 10 years, OR 2.9 (1.6-5); longer survival duration ≥ 10 years, OR 2.2 (1.3-3.8); high BMI at diagnosis, OR 3.2 (1.5-6.9); and large delta BMI ≥ 50, OR 3.15(1.7-5.9) to be independent predictors of MetSyn. Patients who were underweight or normal at diagnosis with large delta BMI ≥ 50 had very high odds (OR, 12.5, 1.7-92) of developing MetSyn compared to those with lower delta BMI. CONCLUSIONS AND IMPLICATIONS FOR CANCER SURVIVORS: A high prevalence of MetSyn was observed in CCS with early age at onset. Timely screening and early intervention are proven to be beneficial and delta BMI could be a useful screening tool for LMIC.

Incidence and Prognostic Impact of TCF3-PBX1 Fusion in Childhood Acute Lymphoblastic Leukemia: A Single Centre Experience.

Molecular abnormalities in leukemic cells are important determinants of risk stratification in Pediatric acute lymphoblastic leukemia (ALL). TCF3-PBX1 fusion is one of the common aberrations in ALL with doubtful prognostic significance. Therefore, aim of our study is to revisit the clinical characteristics and outcome of this abnormality in children with ALL treated at our institute.Demographic, Clinical and treatment related characteristics of 539 newly diagnosed ALL patients from January 2009 and December 2018, < 18 years of age treated on BFM-95 protocol, was abstracted from the medical records. Clinical characteristics and outcome of children with and without TCF3-PBX1 fusion was compared.Incidence of TCF3-PBX1 fusion was observed in 24/539(4.4%) patients with a median age of 4 years (range 1-17). None of the patients in TCF3-PBX1 group had CNS or testicular disease at presentation. Day -8 prednisolone response and morphological remission at the end of induction was similar in both study groups. 5-year overall and event free survival for those with and without fusion was 75%, 70.1% and 79.5%, 69.5% respectively.The incidence of TCF3-PBX1 fusion in the present study was 4.4% and it does not have an independent prognostic significance.

Classification model for accuracy and intrusion detection using machine learning approach.

In today's cyber world, the demand for the internet is increasing day by day, increasing the concern of network security. The aim of an Intrusion Detection System (IDS) is to provide approaches against many fast-growing network attacks (e.g., DDoS attack, Ransomware attack, Botnet attack, etc.), as it blocks the harmful activities occurring in the network system. In this work, three different classification machine learning algorithms-Naïve Bayes (NB), Support Vector Machine (SVM), and K-nearest neighbor (KNN)-were used to detect the accuracy and reducing the processing time of an algorithm on the UNSW-NB15 dataset and to find the best-suited algorithm which can efficiently learn the pattern of the suspicious network activities. The data gathered from the feature set comparison was then applied as input to IDS as data feeds to train the system for future intrusion behavior prediction and analysis using the best-fit algorithm chosen from the above three algorithms based on the performance metrics found. Also, the classification reports (Precision, Recall, and F1-score) and confusion matrix were generated and compared to finalize the support-validation status found throughout the testing phase of the model used in this approach.

A Quantitative Framework for Measuring Personalized Medicine Integration into US Healthcare Delivery Organizations.

Personalized medicine (PM) approaches have revolutionized healthcare delivery by offering new insights that enable healthcare providers to select the optimal treatment approach for their patients. However, despite the consensus that these approaches have significant value, implementation across the US is highly variable. In order to address barriers to widespread PM adoption, a comprehensive and methodical approach to assessing the current level of PM integration within a given organization and the broader healthcare system is needed. A quantitative framework encompassing a multifactorial approach to assessing PM adoption has been developed and used to generate a rating of PM integration in 153 organizations across the US. The results suggest significant heterogeneity in adoption levels but also some consistent themes in what defines a high-performing organization, including the sophistication of data collected, data sharing practices, and the level of internal funding committed to supporting PM initiatives. A longitudinal approach to data collection will be valuable to track continued progress and adapt to new challenges and barriers to PM adoption as they arise.

Patient Education for Kidney Failure Treatment: A Mixed-Methods Study.

RATIONALE & OBJECTIVE: Education programs are needed for people with advanced chronic kidney disease to understand kidney failure treatment options and participate in shared decision-making (SDM). Little is known about the content and accessibility of current education programs or whether they support SDM. STUDY DESIGN: Stakeholder-engaged, mixed-methods design incorporating qualitative observations and interviews, and a quantitative content analysis of slide presentations. SETTING & PARTICIPANTS: Four sites located in Boston, Chicago, Portland (Maine), and San Diego. ANALYTICAL APPROACH: Thematic analysis based on the Ottawa Framework (observations and interviews) and descriptive statistical analysis (slide presentations). RESULTS: Data were collected from observations of 9 education sessions, 5 semistructured interviews with educators, and 133 educational slide presentations. Sites offered group classes or one-on-one sessions. Development, quality, and accuracy of educational materials varied widely. Educators emphasized dialysis (often in-center hemodialysis), with little mention of conservative management. Educators reported patients were often referred too late to education sessions and that some patients become overwhelmed if they learn of the implications of kidney failure in a group setting. Commonly, sessions were general and did not provide opportunities for tailored information most supportive of SDM. Few nephrologists were involved in education sessions or aware of the educational content. Content gaps included prognosis, decision support, mental health and cognition, advance care planning, cost, and diet. Slide presentations used did not consistently reflect best practices related to health literacy. LIMITATIONS: Findings may not be broadly generalizable. CONCLUSIONS: Education sessions focused on kidney failure treatment options do not consistently follow best practices related to health literacy or for supporting SDM. To facilitate SDM, the establishment of expectations for kidney failure treatment options should be clearly defined and integrated into the clinical workflow. Addressing content gaps, health literacy, and communication with nephrologists is necessary to improve patient education in the setting of advanced chronic kidney disease.

Comparative Evaluation of Clinical, Cytological and Microbiological Profile in Abdominal vs. Cervical Lymph Nodal Tuberculosis with Special Emphasis on Utility of Auramine-O Staining.

CONTEXT: Extrapulmonary tuberculosis (EPTB) especially abdominal lymph nodal tuberculosis (LNTB) poses a unique diagnostic challenge. The clinical, cytological, and microbiological profiles, especially with respect to the use and role of Auramine -O (AO) stain, are not as well characterized in abdominal LNTB as cervical LNTB and were evaluated in the present comparative study. SUBJECTS AND METHODS: This study was conducted in the Department of Pathology of a tertiary care hospital in Shillong, Meghalaya in 540 clinical suspected cases of tuberculosis who underwent FNAC. The smears were submitted for Leishman's stain for cytological analysis, along with ZN and Auramine O stain for demonstration of the organism, analyzed, and scored and the results were compared with culture wherever available. The results from abdominal and cervical lymph nodal tuberculosis were compared using Microsoft Excel and SPSS software. RESULTS: Out of 540 cases, most were tuberculosis (266) followed by reactive lymphadenitis (162), malignancy, and acute necrotizing lesion. On comparing, abdominal lymph nodes (n = 163) were more likely to reveal cheesy/purulent material macroscopically, necrotizing lymphadenitis along with ZN stain and Auramine positivity (P < 0.05) while cervical lymph nodes (n = 66) revealed a higher proportion of granulomatous lymphadenitis and culture positivity (P < 0.05). The sensitivity, NPV, and diagnostic accuracy of AO stain (85.9%, 48.0%, and 62.3%) were higher as compared to ZN stain (47.4%, 39.3%, and 51.9%) with culture as the gold standard. The combined sensitivity of Ziehl Neelsen stain and Auramine stain was 92.05%. CONCLUSION: Cytological and microbiologic features of abdominal LNTB differ from cervical LNTB. Moreover, AO stain increases the smear positivity, is almost twice as sensitive as ZN stain and should be used as an adjunct in cytological material wherever available.

Nevus Lipomatosus Cutaneous Superficialis Associated with Trichofolliculoma: An Uncommon Duet of Rare Pathologies.

Nevus lipomatosus cutaneous superficialis (NLCS) and trichofolliculoma (TF) are both rare cutaneous hamartomatous lesions. However, the coexistence of NLCS and TF as a single lesion has been reported only in two other cases, that too in middle-aged individuals. We report the first case of NLCS associated with TF in pediatric age group and also, to the best of our knowledge, the first case reported from India.

Spectrum of Congenital Anomalies among Surgical Patients at a Tertiary Care Centre over 4 Years.

Introduction. Congenital anomalies are important causes of childhood death, chronic illness, and disability in many countries. Congenital malformations are rapidly emerging as one of the major worldwide problems. Aim. To study the percentage of various congenital anomalies among the patients admitted in Department of Pediatric Surgery at a tertiary care centre over a period of four years from 2011 to 2015 in our centre. Results. Neural tube defects were found to be the most common anomalies in 24.3% of the children admitted. Other common anomalies were anorectal malformation (20.7%), tracheoesophageal fistula (20%), and intestinal obstruction (14.84%). Majority (60.5%) of the patients were males. Conclusion. Congenital malformations are rapidly emerging as one of the major worldwide problems as they can result in long-term disability, which may have significant impacts on individuals, families, health-care systems, and societies. Regular antenatal visits and prenatal diagnosis are recommended for prevention, early intervention, and even planned termination, when needed.

Congenital Lumbar Hernia: A 15-Year Experience at a Single Tertiary Centre.

Aim. Congenital lumbar hernia is an uncommon anomaly with only few cases reported in the English literature. This study was done to study the incidence, age at presentation, sex, associated anomalies, surgical management, and postoperative morbidity and mortality of congenital lumbar hernia in pediatric patients. Methods. Retrospective analysis of all patients of CLH over a period of 15 years (January 2000 to December 2015) was analyzed. Results. A total of 14 patients were encountered in this series. All presented within first 2 years of age. 12 were males and 2 were females. All of them presented with swelling in lumbar region. 13 were unilateral and 1 was bilateral. Left sided hernia was observed in 2 cases only. Lumbocostovertebral syndrome was found in all the patients in addition to other rare anomalies. All cases were managed with open surgical repair. Wound infection was seen in 2 cases. There was no mortality in our series. Conclusion. CLH is very rare among hernias. Surgery should be carried out within 1 year of age. For a defect of <5 cm, primary repair is done. For a defect of >5 cm, meshplasty should be considered. Prognosis is excellent.