Tobias Kurth

Editorial: Towards control of the HIV epidemic: trends in epidemiology and emerging drug resistance in the integrase inhibitor era

Diego Ripamonti, Maria Santoro, Joseph Fokam, Francesca Ceccherini Silberstein, Josep M. Llibre

Practical guidance for collecting reproducible time-to-event endpoints in retrospective observational oncology studies

Emily C. Zabor, Nathan A. Pennell, Sujata Patil

Time-to-event endpoints such as progression-free survival, overall survival, and recurrence-free survival are among the most commonly reported outcomes in cancer research, yet the practical decisions required to collect and structure these data appropriately in retrospective observational studies remain poorly described in the literature. While substantial regulatory and methodological guidance exists for prospective clinical trials, investigators working with data collated retrospectively must navigate consequential decisions about index date selection, event definition, censoring, and follow-up time without equivalent support. Decisions at the data extraction stage can bias results and undermine reproducibility regardless of the rigor of the statistical analysis that follows. In this paper, we provide a practical, decision-focused guide to collating and updating time-to-event endpoints in retrospective oncology studies. Specific topics include how to define the index date, event date, and follow-up end date for different endpoints; what counts as an event and how competing events should be handled; how to manage missing and interval-censored data; how to update outcomes over time; and how to identify potential data quality issues through exploratory analysis and sensitivity testing. We illustrate key concepts using a publicly available lung cancer dataset and a worked example that follows endpoint creation from source records to analysis-ready variables, and we provide a practical checklist that researchers can apply directly to their own work. Our goal is to help epidemiologists, clinicians, and statisticians build time-to-event analyses on a foundation of rigorously collected data, resulting in more reliable and reproducible inference.

Cancer prevention and interception studies registered in ClinicalTrials.gov: a landscape analysis of trial characteristics and reporting gaps

Martha Fors, Paloma González, Ariel Torres, Lizbeth Silva-Guayasamín, Christian Silva-Sarabia

Cancer interception has emerged as a prevention-oriented approach that seeks to intervene during early stages of carcinogenesis, before the development of clinically manifest invasive disease. However, the extent to which prevention and interception research is represented and classified in clinical trial registries remains unclear. We conducted a cross-sectional, registry-based analysis of cancer prevention and interception-related studies registered in ClinicalTrials.gov through September 2025. Records identified using terms related to cancer prevention, interception, chemoprevention, risk reduction, premalignant lesions, precursor lesions, and minimal residual disease were screened for eligibility. Study characteristics, including study type, recruitment status, participant eligibility, enrollment, intervention model, allocation, masking, cancer localization, study phase, and funding category, were summarized descriptively. Associations between categorical variables were assessed using exact tests when appropriate. Among 209 eligible studies, 157 (75.1%) were interventional and 52 (24.9%) were observational. Most studies included adults and older adults, and 52.6% were classified as completed. Among interventional studies, randomized allocation and parallel-group designs predominated, while most studies were unmasked. Gynecological and gastrointestinal malignancies were the most frequently represented cancer localizations. Funding was classified as ‘Other’ in most records, reflecting a heterogeneous registry category that could not be further disaggregated. Study type was associated with funding category (p = 0.028), whereas the association between study type and cancer localization was not statistically significant (p = 0.09, with a Cramér's V of 0.32). Among interventional studies, 54 (34.4%) focused on early detection and diagnosis, aligning with the registry's ’Screening’ and ‘Diagnostic’ fields. Cancer interception and post-treatment disease control accounted for 52 studies (33.1%) but lacked distinct registry designations, while 51 (32.5%) addressed primary prevention and chemoprevention, corresponding to the ‘Prevention’ category. Cancer prevention and interception research registered in ClinicalTrials.gov is heterogeneous and encompasses distinct clinical objectives. Our findings highlight the need for explicit operational definitions and more granular, standardized reporting fields to improve the visibility, interpretability, and comparability of preventive oncology.

Low prevalence of Plasmodium falciparum pfhrp 2 and pfhrp 3 gene deletions in archived samples collected before and after nationwide malaria-RDT rollout in Kenya

Martha N. Kivecu, Victor Mobegi, Cavin Mgawe, Brenda M. Kania, Gladys C. Chemwor, Raphael O. Okoth, Edwin W. Mwakio, George Obiero, Jennifer M. Mutisya, Jackline A. Juma, Agnes C. Cheruiyot, Benjamin H. Opot, Amanda L. Roth, Bernhards R. Ogutu, Dennis W. Juma, Lynette Isabella Ochola-Oyier, Ben Andagalu, Hoseah M. Akala

Rapid and accurate malaria diagnosis is essential for effective treatment and malaria control. In Kenya, most malaria testing relies on P. falciparum histidine-rich protein 2 (PfHRP2)-based rapid diagnostic tests (RDTs). However, deletions in the pfhrp 2/ pfhrp 3 genes can lead to false-negative RDT results, which can sustain transmission and worsen clinical outcomes. This study assessed the prevalence and pattern of pfhrp 2, pfhrp 3 and their respective flanking genes in archived samples collected before and after the nationwide rollout of PfHRP2-based RDTs in Kenya in 2012. A total of 350 archived whole-blood samples were analysed, comprising 95 pre-RDT samples (collected before the nationwide rollout of RDTs in Kenya) from 2003 to 2005 and 255 post-RDT samples (collected after the nationwide rollout of RDTs in Kenya) from 2013 to 2017 from multiple malaria-endemic regions of Kenya. Samples were first screened by quantitative Real-Time PCR to identify those with adequate parasite density for genotyping. Nested PCR assays were then used to genotype pfhrp 2, pfhrp 3 and their flanking genes. Where available, PfHRP2-based RDT results were compared with molecular genotyping outcomes to investigate potential causes of false-negative RDT results. The overall prevalence of single pfhrp 2 or pfhrp 3 deletions was low, at 0.3% (1/317) and 1.3% (4/317), respectively. All pre-RDT samples carried intact pfhrp 2 and pfhrp 3 genes. Among post-RDT samples, deletions were rare 0.4% (1/224) for pfhrp 2 gene only and 1.8% (4/224) for pfhrp 3 gene only. No sample exhibited a triple deletion of pfhrp 2 and both of its flanking genes or triple deletion of pfhrp 3 and both of its flanking genes. The sensitivity of the PfHRP2-based RDT was 89.2% (174/195). Notably, 95.2% of false-negative RDT results occurred in samples with intact pfhrp 2 and pfhrp 3, suggesting that low parasitemia or other factors, rather than gene deletions, were the primary cause of diagnostic failure. Overall, pfhrp 2 and pfhrp 3 deletions remained rare in the samples collected up to five years after the nationwide rollout of PfHRP2-RDTs in Kenya. However, continuous molecular surveillance is essential to identify emerging deletion hotspots and to ensure the sustained reliability of PfHRP2-based diagnostics as testing practices and parasites continue to evolve.

β-lactam infusion strategies in critical illness: is continuous superior to extended infusion? A systematic review and network meta-analysis

Fei Peng, Ziyi Tang, Zihan Hu, Xing Zhou, Liqin Kang, Wei Chang, Qin Sun, Jianfeng Xie, Haibo Qiu, Yi Yang

Prolonged β-lactam infusion is common in critical care, but whether continuous infusion (CI) improves outcomes more than extended infusion (EI) is unclear. We conducted a systematic review and random-effects Bayesian network meta-analysis of randomized controlled trials in critically ill adults comparing intravenous β-lactam administration by continuous infusion (24-hour infusion), extended infusion (≥3 h per dose), and intermittent infusion (≤1 h per dose). We searched PubMed, EMBASE, Web of Science, and the Cochrane Library from January 1, 2000, to July 25, 2025. Two reviewers independently screened records, extracted data, and assessed risk of bias. Relative risks (RRs) and mean differences (MDs) were synthesized using random-effects models. Network meta-analysis used Markov chain Monte Carlo methods in R, with complementary pairwise analyses in Stata. Certainty of evidence was assessed using GRADE for network meta-analysis. Twenty-five randomized trials (N = 9,915) were included; no direct CI vs. EI trials were identified. Versus II, CI reduced mortality (RR 0.85, 95% CI 0.66–0.98; moderate certainty); EI had uncertain mortality effects (RR 0.80, 95% CI 0.60–1.10; low certainty). Clinical cure improved versus II for CI (RR 1.10, 95% CI 1.03–1.20) and EI (RR 1.28, 95% CI 1.07–1.55). ICU length of stay was uncertain (CI vs. II: MD −0.47 days, 95% CI −2.10–1.28; EI vs. II: MD −1.32 days, 95% CI −4.65–2.52). Indirect CI vs. EI comparisons showed no significant differences in mortality (RR 1.06, 95% CI 0.73–1.44), clinical cure (RR 0.86, 95% CI 0.70–1.05), or ICU length of stay (MD 0.86 days, 95% CI −3.32–4.54). Bayesian posterior probability analysis suggested a 93.2% probability that EI is superior to CI for clinical cure. CI did not demonstrate greater clinical benefit than EI. CI can reduce patient mortality, and both CI and EI appear to improve clinical cure rates compared with II. CI conferred no additional benefit over EI, suggesting that EI may be sufficient as a prolonged-infusion strategy in clinical practice. However, this finding is based on indirect evidence. The apparent advantage of EI should therefore be regarded as hypothesis-generating and requires confirmation in adequately powered head-to-head randomized controlled trials. https://www.crd.york.ac.uk/PROSPERO/view/CRD42023452814, PROSPERO CRD42023452814.