Recommendations for the optimal introduction of novel antibiotics to treat uncomplicated gonorrhoea in the face of increasing antimicrobial resistance: a case study with zoliflodacin.

New, first-in-class oral antibiotics like zoliflodacin, developed in a public-private partnership, require an optimal introduction strategy while ensuring antibiotic stewardship. Zoliflodacin, given as a single dose for uncomplicated urogenital gonorrhoea, recently demonstrated non-inferiority to ceftriaxone plus azithromycin and safety in a phase 3 randomised controlled trial. Following regulatory approval, zoliflodacin could improve sexually transmitted infection (STI) management and help address the threat of untreatable gonorrhoea, as levels of resistance to current first-line treatments increase.

Approach to the paediatric patient with suspected pheochromocytoma or paraganglioma versus neuroblastoma.

Catecholamine producing tumours of childhood include neuroblastic tumours, phaeochromocytoma and paraganglioma (PPGL). PPGL and neuroblastic tumours can arise in similar anatomical locations and clinical presentations can overlap resulting in diagnostic challenges. Distinguishing between these tumour types is critical as management and long-term surveillance strategies differ depending on the diagnosis.

Bloodstain classification methods: A critical review and a look to the future.

Classifying bloodstains is an essential part of Bloodstain Pattern Analysis. Various experts have developed methods. Each method considers the same basic bloodstain pattern types.

Modelling the Effectiveness of Tepotinib in Comparison to Standard-of-Care Treatments in Patients with Advanced Non-small Cell Lung Cancer (NSCLC) Harbouring METex14 Skipping in the UK.

Background: Patients with non-small cell lung cancer harbouring mesenchymal-epithelial transition exon 14 (METex14) skipping typically demonstrate poorer prognosis than overall non-small cell lung cancer. Until recently, no targeted treatments were available for patients with non-small cell lung cancer harbouring METex14 skipping in the UK, with limited treatments available.

Objective: This study estimates the long-term survival and quality-adjusted life-year benefit of MET inhibitor tepotinib versus current standard of care from a UK perspective.

Challenging our understanding of B-cell lymphomagenesis and risk: Paediatric high-grade B-cell lymphoma, not otherwise specified with a DDX3X::MLLT10 fusion and an IGH deletion.

We report a unique case of high-grade B-cell lymphoma, not otherwise specified in a 5-year-old child. Whole-genome sequencing revealed a DDX3X::MLLT10 fusion, usually seen in T-cell acute lymphoblastic leukaemia (ALL). This suggests the novel idea that MLLT10 fusions are capable of driving B-cell malignancies.

De Novo Cost-Effectiveness Model Framework for Nonalcoholic Steatohepatitis-Modeling Approach and Validation.

Background: Nonalcoholic steatohepatitis (NASH) is a chronic liver disease associated with hepatic morbidity and mortality and extra-hepatic comorbidities. Published NASH cost-effectiveness models (CEMs) are heterogeneous and consistently omit comorbid conditions that frequently co-exist alongside NASH. We aimed to develop a de novo CEM framework that incorporates extra-hepatic disease states and outcomes alongside hepatic components to enable future estimation of the cost-effectiveness of NASH interventions.

Optimization of orthogonal separations for the analysis of oligonucleotides using 2D-LC.

Oligonucleotides are commonly analysed using one dimensional chromatography (1D-LC) to resolve and characterise manufacturing impurities, structural isomers and (in respect to emerging oligonucleotide therapeutics) drug substance and drug product. Due to low selectivity and co-elution of closely related oligonucleotides using 1D-LC, analyte resolution is challenged. This leads to the requirement for improved analytical methods.

A UK cost-effectiveness analysis of trifluridine/tipiracil for heavily pretreated metastatic gastroesophageal cancers.

The current work was designed to estimate the cost-effectiveness of trifluridine/tipiracil (T/T) versus best supportive care (BSC) for patients with advanced stage or metastatic gastroesophageal cancer (mGC) from a UK perspective. A partitioned survival analysis was undertaken using data from the phase III TAGS trial. A jointly fitted lognormal model was selected for overall survival and individual generalized gamma models were chosen for progression-free survival and time-to-treatment-discontinuation.

Health Utility Analysis of Tepotinib in Patients With Non-Small Cell Lung Cancer Harboring MET Exon 14 Skipping.

Objectives: The VISION trial showed durable activity of tepotinib in MET exon 14 (METex14) skipping non-small cell lung cancer. We analyzed health state utilities using patient-reported outcomes from VISION.

Methods: 5-level version of EQ-5D (EQ-5D-5L) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 responses were collected at baseline, every 6 to 12 weeks during treatment, and at the end of treatment and safety follow-up.

High-throughput nanopore sequencing of tandem repeat genes and reveals clade-specific patterns and recapitulates global whole genome phylogeny.

Sequencing of most genomes excludes repeat regions in and the gene, encoding the acidic repeat protein (). As a first step to understanding the evolution and function of these genes and the proteins they encode, we developed a protocol to nanopore sequence and genes from 212 clinical samples collected from ten countries on six continents. Both and repeat structures recapitulate the whole genome phylogeny, with subclade-specific patterns emerging.

Coinfection With Chlamydial and Gonorrheal Infection Among US Adults With Early Syphilis.

Among 865 adults with early syphilis considered for a multicenter treatment trial, 234 (27%) were excluded before enrollment because of bacterial sexually transmitted infection coinfection. Coinfection with Neisseria gonorrhoeae (29%), Chlamydia trachomatis (22%), or both (23%) was common. Study findings highlight the need for comprehensive bacterial sexually transmitted infection screening in patients with syphilis.

Treponema pallidum genome sequencing from six continents reveals variability in vaccine candidate genes and dominance of Nichols clade strains in Madagascar.

In spite of its immutable susceptibility to penicillin, Treponema pallidum (T. pallidum) subsp. pallidum continues to cause millions of cases of syphilis each year worldwide, resulting in significant morbidity and mortality and underscoring the urgency of developing an effective vaccine to curtail the spread of the infection.

Selection of Analytical Technology and Development of Analytical Procedures Using the Analytical Target Profile.

A structured approach to method development can help to ensure an analytical procedure is robust across the lifecycle of its use. The analytical target profile (ATP), which describes the required quality of the reportable value to be produced by the analytical procedure, enables the analytical scientist to select the best analytical technology on which to develop their procedure(s). Once the technology has been identified, screening of potentially fit for purpose analytical procedures should take place.

Multicenter Comparison of Nucleic Acid Amplification Tests for the Diagnosis of Rectal and Oropharyngeal Chlamydia trachomatis and Neisseria gonorrhoeae Infections.

Research using nucleic acid amplification tests (NAATs) have repeatedly found rectal and oropharyngeal infections with Chlamydia trachomatis and Neisseria gonorrhoeae to be common and potentially more difficult to treat than genital infections. Unfortunately, public health and patient care efforts have been hampered by the lack of FDA-cleared NAATs with claims for anorectal or oropharyngeal samples. At the time of the initiation of this study, no commercially available assays had these claims.

Report From the National Academies of Sciences, Engineering and Medicine-STI: Adopting a Sexual Health Paradigm-A Synopsis for Sexually Transmitted Infection Practitioners, Clinicians, and Researchers.

Despite decades of medical, diagnostic, and public health advances related to diagnosis and management of sexually transmitted infections (STIs), rates of reportable STIs continue to grow. A 2021 National Academies of Sciences, Engineering, and Medicine report on the current state of STI management and prevention in the United States, entitled Sexually Transmitted Infections: Adopting a Sexual Health Paradigm, offers recommendations on future public health programs, policy, and research. This new report builds upon the 1997 Institute of Medicine report, The Hidden Epidemic: Confronting Sexually Transmitted Diseases, and provides 11 recommendations organized under 4 action areas: (1) adopt a sexual health paradigm, (2) broaden ownership and accountability for responding to STIs, (3) bolster existing systems and programs for responding to STIs, and (4) embrace innovation and policy change to improve sexual health.

The National Academies Report on Sexually Transmitted Infections: Implications for Clinical Training, Licensing, and Practice Guidelines.

Sexually transmitted infections (STIs) represent a sizable, longstanding, and growing challenge and a national public health priority. A recent National Academies report outlines new directions for STI prevention and control, including the adoption of a new sexual health paradigm and broader ownership and accountability for addressing sexual health and STIs among diverse clinical and nonclinical actors. These recommendations have important implications for infectious disease providers with STI and human immunodeficiency virus (HIV) expertise.

Chlamydial Pgp3 Seropositivity and Population-Attributable Fraction Among Women With Tubal Factor Infertility.

Background: Chlamydial infection is associated with tubal factor infertility (TFI); however, assessment of prior chlamydial infection and TFI is imperfect. We previously evaluated a combination of serological assays for association with TFI. We now describe the chlamydial contribution to TFI using a newer Chlamydia trachomatis Pgp3-enhanced serological (Pgp3) assay.