Search

Background The Scientific Registry for Transplant Recipients (SRTR) publishes outcomes of all transplant centres in the USA two times a year. The outcomes are publicly available and used by insurance payers and patients to assess the performance of a programme. Poor performance can result in temporary suspension or termination of a transplant programme. The estimated 1-year survival hazard ratio (EHR) is an important metric publicly reported by the SRTR.Problem The EHR at our institution was 1.13, indicating a graft loss rate that was 13% higher than the national average.Methods/INTERVENTION We defined an improvement in this metric as achieving an EHR of

This article seeks to highlight an aspect of the illegal pharmaceutical trade in the Caribbean. With the advent of COVID-19 there has been a shortage of a number of drugs in the formal sector. This is largely due to restrictions on foreign exchange, importation delays and sensationalized reporting of unrecommended drugs having a curative effect on COVID-19 patients. This article examines the issue of “the informal suitcase trading” of these drugs. It posits a need for a collaborative and multi-sectoral approach to mitigate the negative effects of the practice on health, trade and national security.

Heidi Chwan Ko,1,* RJ Seager,2,* Sarabjot Pabla,2 Maria-Fernanda Senosain,2 Erik Van Roey,2 Shuang Gao,2 Kyle C Strickland,1,3 Rebecca Ann Previs,1,4 Michelle F Green,1 Maureen Cooper,1 Mary K Nesline,1 Stephanie B Hastings,1 Kobina Agyaful Amoah,1 Shengle Zhang,2 Jeffrey M Conroy,2 Taylor J Jensen,1 Marcia Eisenberg,5 Brian Caveney,5 Eric A Severson,1 Shakti Ramkissoon,1,6 Shipra Gandhi7 1Labcorp Oncology, Durham, NC, USA; 2Labcorp Oncology, Buffalo, NY, USA; 3Department of Pathology, Duke University Medical Center, Duke Cancer Institute, Durham, NC, USA; 4Department of Obstetrics & Gynecology, Division of Gynecologic Oncology, Duke University Medical Center, Duke Cancer Institute, Durham, NC, USA; 5Labcorp, Burlington, NC, USA; 6Department of Pathology, Wake Forest Comprehensive Cancer Center, Wake Forest School of Medicine, Winston-Salem, NC, USA; 7Department of Hematology and Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA*These authors contributed equally to this workCorrespondence: Heidi Chwan Ko, Email Heidi.ko@labcorp.comBackground: The understanding of molecular characteristics of HER2-low breast cancer is evolving since the establishment of trastuzumab deruxtecan. Here, we explore the differences in expression patterns of immune-related genes in the tumor immune microenvironment (TME) and survival between HER2-low and HER2-zero breast cancers.Methods: Comprehensive genomic and immune profiling, including RNA-seq gene expression assessment of 395 immune genes, was performed on FFPE samples from 129 patients with advanced HER2-negative (immunohistochemistry (IHC) 0, 1+ or 2+ with negative ERBB2 amplification by in-situ hybridization) breast cancer. Both estrogen receptor (ER) and HER2 statuses were obtained from available pathology reports. mRNA expressions of immune biomarkers, except for PD-L1 IHC and TMB, were derived from RNA-seq. Statistical comparisons were performed using the Kruskal–Wallis or Wilcoxon Rank-Sum test or the two-sample test for equality of proportions with continuity correction (p≤ 0.05 for significance). Survival differences were calculated using Kaplan-Meier analysis (p≤ 0.05 for significance).Results: There were no significant differences in mRNA expressions of immune-related genes between HER2-low and HER2-zero breast cancers. However, HER2-low breast cancers were associated with a higher proportion of ER-positivity. When ER was analyzed along with HER2, we observed a significantly higher tumor immunogenic signature (TIGS) expression in HER2-zero/ER-negative tumors than in HER2-low/ER-positive tumors (p=0.0088). Similarly, lower expression of PD-L1 and T cell immunoglobulin and ITIM domain (TIGIT) mRNA was observed in HER2-low/ER-positive tumors when compared to HER2-zero/ER-negative tumors (p=0.014 and 0.012, respectively). Patients with HER2-low tumors had a longer median OS than those with HER2-zero tumors (94 months vs 42 months, p=0.0044).Conclusion: Patients with HER2-low breast cancer have longer survivals yet display no differences in immune-related gene expression when compared to those with HER2-zero cancers. The differences in survival can be attributed to the higher rate of ER-positivity seen in HER2-low breast cancers, compared to HER2-zero tumors.Keywords: HER2-low breast cancer, estrogen receptor, tumor immune microenvironment, immune checkpoint biomarkers, gene expression profiling, immune profiling

IntroductionMatching patients to an effective targeted therapy or immunotherapy is a challenge for advanced and metastatic non-small cell lung cancer (NSCLC), especially when relying on assays that test one marker at a time. Unlike traditional single marker tests, comprehensive genomic profiling (CGP) can simultaneously assess NSCLC tumors for hundreds of genomic biomarkers and markers for immunotherapy response, leading to quicker and more precise matches to therapeutics.MethodsIn this study, we performed CGP on 7,606 patients with advanced or metastatic NSCLC using the Illumina TruSight Oncology 500 (TSO 500) CGP assay to show its coverage and utility in detecting known and novel features of NSCLC.ResultsTesting revealed distinct genomic profiles of lung adenocarcinoma and squamous cell carcinomas and detected variants with a current targeted therapy or clinical trial in >72% of patient tumors. Known associations between genomic alterations and immunotherapy markers were observed including significantly lower TMB levels in tumors with therapy-associated alterations and significantly higher PD-L1 levels in tumors with ALK, MET, BRAF, or ROS1 driver mutations. Co-occurrence analysis followed by network analysis with gene module detection revealed known and novel co-occurrences between genomic alterations. Further, certain modules of genes with co-occurring genomic alterations had dose-dependent relationships with histology and increasing or decreasing levels of PD-L1 and TMB, suggesting a complex relationship between PD-L1, TMB, and genomic alterations in these gene modules.DiscussionThis study is the largest clinical study to date utilizing the TSO 500. It provides an opportunity to further characterize the landscape of NSCLC using this newer technology and show its clinical utility in detecting known and novel facets of NSCLC to inform treatment decision-making.

Clinical management of non-small cell lung cancer (NSCLC) requires accurate identification of tumor-specific genetic alterations to inform treatment options. Historically, providers have relied on single-gene testing (SGT) for actionable variants due to a perception of cost-effectiveness and/or efficient turnaround time compared to next-generation sequencing (NGS). However, not all actionable variants may be evaluated through SGT modalities, and an SGT approach can exhaust valuable tissue needed for more comprehensive analyses. In contrast, comprehensive genomic profiling (CGP) tests employ NGS to sequence megabases of DNA and RNA to evaluate all relevant molecular alterations, providing a broader genetic profile to identify actionable alterations that SGT may not accurately or efficiently assess. Here, we briefly describe four cases from a large reference laboratory in which actionable alterations were identified by CGP but not SGT. The discussion highlights the utility and advantages of using CGP to provide complete and timely treatment options and clinical trial opportunities for patients with NSCLC.

Heparin-induced thrombocytopenia (HIT) is a rare but severe prothrombotic disorder that develops in patients exposed to heparin products. Diagnosis is associated with significant morbidity and mortality. The mainstay of treatment for HIT involves discontinuing all heparin products and administering non-heparin anticoagulants. Since the publication of the American Society of Hematology (ASH) guidelines in 2018, factor Xa inhibitors have become an attractive alternative. We systematically reviewed the literature to determine the efficacy and safety of factor Xa inhibitors in managing HIT. We included any case series, retrospective, or prospective study that evaluated the efficacy of factor Xa inhibitors. We searched PubMed, Ovid, Embase, Cochrane Central Register of Controlled Trials, and Google Scholar from inception to September 2023. Three reviewers independently reviewed titles, abstracts, and full-text articles to determine eligibility using prespecified inclusion and exclusion criteria. Disagreements were resolved by discussion and consensus. Nine hundred sixty-four articles were screened against title and abstract, and 75 studies were selected for full-text review. Fifteen studies eventually met the inclusion criteria. Two hundred eighty-five patients across 15 studies were treated with factor Xa inhibitor. Across all study arms combined, HIT thrombosis-associated mortality was 0 % (n = 0), recurrent thrombosis was 4.56 % (n = 13), and major bleeding was 2.80 % (n = 8). Factor Xa inhibitors showed positive outcomes in HIT in terms of both safety and efficacy. Major limitation of this review is that the studies included are primarily retrospective and, thus, are subject to inherent limitations of observational study design. More randomized controlled trials (RCT) or prospective studies examining non-inferiority or superiority of transitioning to direct oral anticoagulant (DOAC) vs primary treatment with DOAC are needed.

With the advent of e-learning, advocates use the term interactivity instead of interaction among students, and between the teacher and the students. Many universities use Moodle for online teaching and learning. This paper explores the perceptions and experiences of students in three Higher Education Institutions (HEIs) in Mauritius. A mixed-methods approach was used, with an online survey questionnaire administered to 600 students and focus group discussions were conducted with 15 students from these institutions. It was found that 68.4% of respondents used WhatsApp compared to only 23.6% of them who used the e-learning platform, Moodle. There were no associations between the use or frequency of using WhatsApp or Facebook and the types of HEI to which the students belonged. Students preferred WhatsApp due to its facility for knowledge sharing and construction, its interactivity, its usability, respect for privacy and instant communication. From the findings, it is recommended that HEIs bring a shift in their approaches to teaching and learning from cognitivism to socio-constructivism, connectivism and heutagogy.

Executing global clinical trials for cancer is a long, expensive, and complex undertaking. While selecting countries global studies, sponsors must consider several aspects including patient pool, quality of trained investigators, competing trials, availability of infrastructure, and financial investment versus returns. With a large, often treatment-naïve, and diverse patient pool, relatively low cost, good quality health care facilities in urban areas, and a robust and well-trained workforce, India offers several advantages for conducting oncology clinical trials. However, there remains challenges, including a shifting regulatory environment in recent decades. With the implementation of the New Drugs and Clinical Trial Rules in 2019, India's regulatory atmosphere seems to have stabilized. In this article, we present a review of the evolving clinical trial landscape in India, highlight the current regulatory scenario, and discuss the advantages and challenges of selecting India as a potential location for conducting global oncology clinical trials.

IntroductionYounger patients with non-small cell lung cancer (NSCLC) (

There is an emerging view that remittances improve health outcomes in developing countries, though less is known about the conditions under which they may be effective. This study investigates whether and how the impact of remittances on child mortality depends on the level of mortality itself. Using a sample of 134 developing countries over the period 1990 to 2018, we estimate unconditional quantile treatment effects with an endogenous treatment variable, on aggregate child mortality and the three leading cause-specific child mortality rates: mortality from neonatal disorders, lower respiratory infections, and diarrheal diseases. We find that the impact of remittances differs systematically across the mortality distribution and across mortality indicators. Remittances appear less effective at reducing child mortality at the lowest and highest mortality rates than at the average.

BackgroundWorkplace atmospheric exposure monitoring is the standard method to assess and control hazardous dust exposure; however, feasibility and cost constraints often limit its application. In recent decades, evidence-based tools supporting exposure modelling and control banding have been developed to aid in predicting and/or controlling occupational exposure to various contaminants. However, there is limited information on the availability and applicability of evidence-based tools for predicting and/or controlling occupational dust exposure, as well as on the methods for evaluating these tools across different exposure scenarios. Therefore, this planned scoping review aims to identify existing evidence-based tools for dust exposure predicting and/or controlling and to present evaluation approaches.MethodsWe will employ the scoping review methods developed by the Joanna Briggs Institute (JBI). The search will be conducted on PubMed, Scopus, and Web of Science databases, in addition to grey literature from the National Institute for Occupational Safety and Health (NIOSH) and advanced Google searches. Studies will be included if they report evidence-based tools for predicting and/or controlling dust exposure using quantitative or semi-quantitative designs and provide a detailed explanation of the methods used for tool development. There will be no restrictions on publication date or geographical location; however, only studies published in English will be considered. Studies focusing exclusively on dust exposure in environmental settings will be excluded. Each member of the review team will screen titles, abstracts, and full texts independently and in collaboration, based on the inclusion criteria. The extracted data will encompass details such as author, title, country, accessible platforms, method/tool names, intended users, types of dust, and occupational settings. Descriptions of the identified tools will include numerical data and narrative summaries to ensure a comprehensive overview.Trial registrationOSF (https://doi.org/10.17605/OSF.IO/S6EZJ).

Abstract Introduction New treatment strategies for advanced non‐small‐cell lung carcinoma (NSCLC) include synthetic lethality targets focused on protein arginine methyl transferases such as PRMT5 that exploit the impact of genomic loss of methylthioadenosine phosphorylase (MTAP). Methods Twenty nine thousand three hundred seventy nine advanced NSCLC cases underwent hybrid‐capture based comprehensive genomic profiling between June 1, 2018 and May 31, 2020. PD‐L1 expression was determined by immunohistochemistry (Dako 22C3 PharmDx assay). Results 13.4% (3928/29,379) NSCLC cases exhibited MTAP loss distributed in adenocarcinoma (59%), squamous cell carcinoma (22%), NSCLC not otherwise specified (16%), and 1% each for large‐cell neuroendocrine, sarcomatoid, and adenosquamous carcinoma. Statistically significant differences in mitogenic driver alterations included more KRAS G12C mutations in MTAP‐intact versus MTAP‐lost (12% vs. 10%, p = 0.0003) and fewer EGFR short variant mutations in MTAP‐intact versus MTAP‐lost NSCLC (10% vs. 13%, p

Abstract BackgroundOverexposure to occupational noise can lead to hearing loss. Occupational noise mapping is conventionally performed with a calibrated sound level meter (SLM). With the rise of mobile apps, there is a growing number of SLM apps available on mobile phones. However, few studies have evaluated such apps for accuracy and usefulness to guide those with occupational noise detection needs in selecting a quality app. ObjectiveThe purpose of this study was to evaluate the accuracy and usefulness of SLM mobile apps to guide workplace health and safety professionals in determining these apps’ suitability for assessing occupational noise exposure. MethodsThe following three iOS apps were assessed: the NIOSH (National Institute for Occupational Safety and Health) Sound Level Meter, Decibel X, and SoundMeter X apps. The selected apps were evaluated for their accuracy in measuring sound levels in low-, moderate-, and high-noise settings within both simulated environments and real-world environments by comparing them to a conventional SLM. The usefulness of the apps was then assessed by occupational health specialists using the Mobile App Rating Scale (MARS). ResultsThe NIOSH Sound Level Meter app accurately measured noise across a range of sound levels in both simulated settings and real-world settings. However, considerable variation was observed between readings. In comparison, the Decibel X and SoundMeter X apps showed more consistent readings but consistently underestimated noise levels, suggesting that they may pose a risk for workers. Nevertheless, none of the differences in sound measurements between the three apps and the conventional SLM were statistically significant (NIOSH Sound Level Meter: PPP ConclusionsUnder the conditions of this study, the NIOSH Sound Level Meter app had equivalent accuracy to the calibrated SLM and a degree of usefulness according to the MARS. This suggests that the NIOSH Sound Level Meter app may be suitable for mapping noise levels as part of a monitoring strategy in workplaces. However, it is important to understand its limitations. Mobile apps should complement but not replace conventional SLMs when trying to assess occupational noise exposure risk. Our outcomes also suggest that the MARS tool may have limited applicability to measurement-based apps and may be more suited to information-based apps that collect, record, and store information.