The objective of this assessment was to determine the benefit of using a next-generation sequencing gene panel for the clinical management of patients with non-small cell lung cancer. The aim was to assess the diagnostic performance, identify the molecular alterations of interest, and define the role of this technology in the therapeutic care of these patients.

The method used for this assessment were based on: (i) a critical analysis of systematic reviews and meta-analyses and clinical practice guidelines identified by a systematic search based on PICO criteria (Population, Intervention, Comparator, Outcome); (ii) the identification of the level of evidence of the clinical actionability of molecular targets, as set out by the European Society for Medical Oncology scale, and targeted therapies included on the list of reimbursable drugs, or drugs that have compassionate use authorizations; and (iii) stakeholder consultations, as well as public health institutions.

Assessment of the evidence and data demonstrated that next-generation sequencing gene panel testing (EGFR, ALK, ROS1, BRAF, RET, and KRAS): (i) is highly concordant with the comparators (Kappa coefficient of 0.884); (ii) can detect additional targetable molecular alterations (marginal increase in the detection capacity of 2%); (iii) makes better use of the tumor tissue; and (iv) has clinical utility, demonstrated by the benefits provided by targeted therapies.

The next-generation sequencing gene panel (EGFR, ALK, ROS1, BRAF, RET, KRAS) was recommended for patients with locally advanced or metastatic non-small cell lung cancer, following diagnosis or in cases of progression, excluding any emergency situations. The composition of the gene panel may be subject to change, in accordance with favorable assessments of new gene alterations.

The objective of this assessment was to determine the benefit of using a next-generation sequencing (NGS) gene panel for the clinical management of gastrointestinal stromal tumor (GIST) among patients in routine clinical practice. The aim was to assess the clinical utility of this procedure, the somatic molecular alterations of specific interest, and to define its role in the therapeutic care of patients with GIST.

The method used for this fast-track assessment were based on: (i) a critical analysis of systematic reviews, meta-analyses, and clinical practice guidelines identified by a systematic literature search; (ii) identification of the level of evidence of molecular alteration clinical actionability as set out by the European Society for Medical Oncology Scale, of targeted therapies included on the list of reimbursable drugs assessed by the French National Authority for Health, or drugs that have compassionate use authorizations issued by the French National Agency for Medicines and Health Products Safety; and (iii) stakeholder consultations and observations by public health institutions.

Assessment of the evidence and data demonstrated that NGS gene panel testing has: (i) superior diagnostic performance for detecting KIT and PDGFRA molecular alterations, compared with Sanger sequencing; (ii) superior diagnostic performance for detecting NTRK1/2/3 fusion, compared with immunohistochemistry; and (iii) evidence of clinical utility of the targeted gene panel considering the benefits provided by targeted therapies.

The composition of the NGS gene panel may be subject to change, in accordance with favorable assessments of new gene alterations. New assessments will be conducted in a dynamic manner in response to developments in scientific knowledge.

The French National Authority for Health deemed that funding the NGS gene panel for GIST was justified for: (i) KIT and PDGFRA genes in cases of locally advanced or metastatic GIST at an intermediate or high risk of recurrence, and in cases of suspected GIST when histology is inconclusive for diagnosis; and (ii) the NTRK1/2/3 gene in cases of refractory or relapsed locally advanced or metastatic pediatric wild-type GIST.

Instrumental activities of daily living (iADLs) are critical in aging and neurodegenerative research, both diagnostically (e.g., distinguishing dementia from mild cognitive impairment) and as endpoints for trials maintaining or improving functioning. However, measurement has not consistently kept pace with a changed world wherein the ability to navigate technology is pertinent to maintaining independent functioning. The current study used harmonization approaches to link traditional and technological iADLs measures using two samples.

262 individuals (53.4% women, 91.7% non-Hispanic White, Mage = 76.2, Meducation = 15.6) completed both measures: (1), the Functional Activities Questionnaire (FAQ), and (2), the new Expanded FAQ. Item response theory (IRT) analyses extracted item parameters to characterize measure psychometrics and accurately determine individual functional ability. Harmonization was done using both nonequivalent groups anchor test (NEAT) and equipercentile linking methods with supplementary traditional iADL parameter estimates from the National Alzheimer Coordinating Center (n = 48,605).

Correlations verified the measures were sufficiently related (rs = .79), and confirmatory factor analyses and reliability determined all items assessed a single construct. Items from both measures complemented each other to provide more information about milder and more severe functional change. NEAT models converged to provide IRT linking equations and equipercentile conversation tables.

This study provides critical information for harmonizing evolving technological iADLs with traditional iADLs that are assessed in longstanding cohorts. It further provides support for use of an expanded FAQ.

In the neonatal intensive care unit (NICU), outbreaks caused by methicillin-susceptible Staphylococcus aureus (MSSA) are less commonly described than outbreaks caused by methicillin-resistant Staphylococcus aureus (MRSA) despite the increased burden of MSSA infections.

To investigate a NICU MSSA outbreak utilizing whole-genome sequencing (WGS) and multi-locus sequencing typing (MLST) to identify transmission events.

An investigation was initiated in a level IV NICU after four patients developed MSSA skin and soft tissue infections (SSTI) within three weeks. MLST and WGS were performed on MSSA isolates obtained from clinical and surveillance specimens.

During the outbreak, 16 infants developed MSSA infections including SSTIs (n = 15) and bacteremia (n = 1). Thirteen SSTIs presented on neonates’ faces, all of whom were on non-invasive respiratory support. During 7 rounds of surveillance, an additional 31 patients were found to be colonized with MSSA. MLST identified a predominant cluster (ST-121). WGS found that all ST-121 isolates were closely related (≤10 genetic variants between isolates) suggesting likely transmission events, harbored the mupA gene, exhibited mupirocin MIC values ≥1,024 µg/mL, and were associated with infection. Multiple infection control measures were implemented including the “bare below the elbows” practice. No further mupirocin-resistant isolates were recovered or ST-121 SSTIs identified after Week 26.

WGS analysis furthered the MLST analysis and identified a single MLST as the outbreak-related strain. Successful control of this outbreak was achieved with a multitude of infection prevention and control methods.

Lesbian, gay, bisexual, transgender, queer and related community (LGBTQ+) individuals have significantly increased risk for mental health problems. However, research on inequalities in LGBTQ+ mental healthcare is limited because LGBTQ+ status is usually only contained in unstructured, free-text sections of electronic health records.

This study investigated whether natural language processing (NLP), specifically the large language model, Bi-directional Encoder Representations from Transformers (BERT), can identify LGBTQ+ status from this unstructured text in mental health records.

Using electronic health records from a large mental healthcare provider in south London, UK, relevant search terms were identified and a random sample of 10 000 strings extracted. Each string contained 100 characters either side of a search term. A BERT model was trained to classify LGBTQ+ status.

Among 10 000 annotations, 14% (1449) confirmed LGBTQ+ status while 86% (8551) did not. These other categories included LGBTQ+ negative status, irrelevant annotations and unclear cases. The final BERT model, tested on 2000 annotations, achieved a precision of 0.95 (95% CI 0.93–0.98), a recall of 0.93 (95% CI 0.91–0.96) and an F1 score of 0.94 (95% CI 0.92–0.97).

LGBTQ+ status can be determined using this NLP application with a high success rate. The NLP application produced through this work has opened up mental health records to a variety of research questions involving LGBTQ+ status, and should be explored further. Additional work should aim to extend what has been done here by developing an application that can distinguish between different LGBTQ+ groups to examine inequalities between these groups.

The urgency and scale of the COVID-19 pandemic demanded a coordinated response from public health agencies and the biomedical research community. The National COVID Cohort Collaborative (N3C) was established as a centralized enclave in 2020 to support the study of COVID-19 across the U.S. The Institutional Development Award for Clinical and Translational Research (IDeA-CTR) centers enhanced N3C’s national response by bringing representation from rural and medically underserved communities. This improved the representation of our diverse populations in the N3C Enclave and its use for research by IDeA-state investigators.

We developed an organizational structure across the IDeA-CTRs to improve research productivity in resource-challenged areas of the U.S. This socio-technical ecosystem, informed by community input, included a governance committee and two workstreams. The operations workstream focused on data management and regulatory compliance, while the navigation, education, analysis, and training (NEAT) workstream supported educational and analytical activities for the N3C Enclave.

Our collaborative approach led to participation by 12 IDeA-CTRs, representing over 400 investigators from 23 sites. The shared governance, investigator engagement, and resource pooling enhanced research productivity and engagement with researchers across IDeA states. Participation in this IDeA-CTR N3C consortium enhanced informatics research capacity and collaboration across the IDeA-CTRs for participating networks.

This collaborative model provides a roadmap and framework for future efforts among IDeA-CTRs and other academic partnerships. The socio-technical ecosystem fostered collectivism and team science, enabling the consortium to achieve far more than isolated efforts could, offering valuable insights for interdisciplinary research across geographically dispersed communities.

Bipolar depression remains difficult to treat, and people often experience ongoing residual symptoms, decreased functioning and impaired quality of life. Adjunctive therapies targeting novel pathways can provide wider treatment options and improve clinical outcomes. Garcinia mangostana Linn. (mangosteen) pericarp has serotonogenic, antioxidant anti-inflammatory and neurogenic properties of relevance to the mechanisms of bipolar depression.

The current 28-week randomised, multisite, double-blind, placebo-controlled trial investigated mangosteen pericarp extract as an adjunct to treatment-as-usual for treatment of bipolar depression.

This trial was prospectively registered on the Australia New Zealand Clinical Trials Registry (no. ACTRN12616000028404). Participants aged 18 years and older with a diagnosis of bipolar I or II and with at least moderate depressive symptoms were eligible for the study. A total of 1016 participants were initially approached or volunteered for the study, of whom 712 did not progress to screening, with an additional 152 screened out. Seventy participants were randomly allocated to mangosteen and 82 to a placebo control. Fifty participants in the mangosteen and 64 participants in the placebo condition completed the treatment period and were analysed.

Results indicated limited support for the primary hypothesis of superior depression symptom reduction following 24 weeks of treatment. Although overall changes in depressive symptoms did not substantially differ between conditions over the course of the trial, we observed significantly greater improvements for the mangosteen condition at 24 weeks, compared with baseline, for mood symptoms, clinical impressions of bipolar severity and social functioning compared with controls. These differences were attenuated at week 28 post-discontinuation assessment.

Adjunctive mangosteen pericarp treatment appeared to have limited efficacy in mood and functional symptoms associated with bipolar disorder, but not with manic symptoms or quality of life, suggesting a novel therapeutic approach that should be verified by replication.

In the UK, around 1 in 4 adults over 65 years suffers from depression. Depression case finding followed by alerting patients and their general practioners (GPs) (screening + GP) is a promising strategy to facilitate depression management, but its cost-effectiveness remains unclear.

To investigate the cost-effectiveness of screening + GP compared with standard of care (SoC) in northern England.

Conducted alongside the CASCADE study, 1020 adults aged 65+ years were recruited. Participants with baseline Geriatric Depression Scale (GDS) ≥5 were allocated to the intervention arm and those >5 to SoC. Resource use and EQ-5D-5L data were collected at baseline and 6 months. Incremental cost-effectiveness ratio was calculated. Non-parametric bootstrapping was performed to capture sampling uncertainty. The results are presented using cost-effectiveness acceptability curves. Sensitivity analyses were conducted to assess the robustness of primary findings. Subgroup analyses were undertaken to examine the cost-effectiveness among participants with more comparable baseline characteristics across treatment groups.

Screening + GP incurred £37 more costs and 0.006 fewer quality-adjusted life years than SoC; the probability of the former being cost-effective was <5% at a £30 000 cost-effectiveness threshold. Sensitivity analyses confirmed the base-case findings. Subgroup analyses indicated that screening + GP was cost-effective when patients with baseline GDS 2–7, 3–6 and 4–5, respectively, were analysed.

Screening + GP was dominated by SoC in northern England. However, subgroup analyses suggested it could be cost-effective if patients with more balanced baseline characteristics were analysed. Economic evaluations alongside randomised controlled trials are warranted to validate these findings.