Breath analysis has emerged as an experimental method of non-invasive screening of gastric cancer and identification of individuals suitable for confirmatory, diagnostic upper gastrointestinal endoscopy. We aimed to evaluate the accuracy and applicability of breath analysis for gastric cancer detection in adults.We searched MEDLINE, EMBASE, BIOSIS, CENTRAL, and Compendex up to 27 September 2020 for original studies analysing exhaled breath to detect gastric cancer in patients. Summary sensitivity and specificity analyses were obtained using a hierarchical bivariate method. Non-quantitative results were descriptively summarized. Risk of bias was assessed using the QUADAS-2 tool. This study protocol was pre-registered in PROSPERO (CRD42020139422).Twenty-four studies were included. Within these, breath analysis technologies most commonly used were mass spectrometry (MS)-based methods; other methods included volatile organic compound sensors and silicon nanowire field effect transistors. Fourteen studies (total n = 3028) involving all technologies reported quantitative results, with sensitivities ranging from 67%–100% and specificities from 71%–98%. The summary sensitivity across six studies utilizing MS-based breath analysis methods was 82.4% (95% CI: 78%–86%); summary specificity was 91.3% (95% CI: 83%–96%). Based on these values, we estimated that screening with MS-based breath tests could lower the number needed to screen (NNS) by more than eight-fold in the 15 countries with the highest prevalence of gastric cancer.Breath analysis is a promising method for gastric cancer detection with good diagnostic performance and potential to decrease the NNS for endoscopy-based gastric cancer detection. However, due to the heterogeneity of breath analysis technologies, rigorous studies with standardized, reproducible methods are needed to evaluate the clinical applicability of these technologies.

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175 Background: In its early stages, gastric cancer symptoms are frequently lacking, resulting in an often late and incurable diagnosis. A non-invasive, cheap, and reliable screening method for gastric cancer could improve outcomes and increase the number of surgically resectable gastric cancers. Breath analysis has emerged as an experimental method of non-invasive screening of gastric cancer and identification of individuals suitable for confirmatory, diagnostic upper gastrointestinal endoscopy. We aimed to evaluate the accuracy and applicability of breath analysis for gastric cancer detection in adults. Methods: This systematic review searched MEDLINE, EMBASE, BIOSIS, CENTRAL, and Compendex until 11 July 2019 for original studies analyzing exhaled breath to detect gastric cancer in patients. Two authors then independently screened the abstracts, titles, and full texts. Summary sensitivity and specificity analyses were obtained using a hierarchical bivariate method. Positive predictive value and number needed to screen (NNS) of breath analysis methods for gastric cancer detection were calculated for each country using gastric cancer prevalence by country obtained from the Global Cancer Observatory. Non-quantitative results were descriptively summarized. Risk of bias was assessed using the QUADAS-2 tool. This study protocol was pre-registered in PROSPERO (CRD42020139422). Results: Twenty studies were included. Together, the studies included 2,976 subjects. The pooled mean age of the subjects in the gastric cancer groups was 60.5 ± 11 years while the pooled mean age for control groups was 55.4 ± 12 years. Within these twenty studies, breath analysis technologies most commonly used were mass spectrometry (MS)-based methods; other methods included volatile organic compound sensors, thermal desorption tubes, and silicon nanowire field effect transistors. Across all included studies, we found and summarized the characteristics of 131 chemical compounds found in the exhaled breath of study subjects. Eleven studies (total n = 1905) involving all technologies reported quantitative results, with sensitivities ranging from 67-100% and specificities from 71-98%. The summary sensitivity across six studies utilizing MS-based breath analysis methods was 85.3% (95% CI: 82-96%); summary specificity was 81.7%. (95% CI: 78-85%). Based on the MS-based values, we estimated that screening with MS-based breath tests could lower the NNS by more than four-fold in the 15 countries with the highest prevalence of gastric cancer. Conclusions: Breath analysis is a promising method for gastric cancer detection with good diagnostic performance and potential to decrease the NNS for endoscopy-based gastric cancer detection. However, due to the heterogeneity of breath analysis technologies, rigorous studies with standardized, reproducible methods are needed to evaluate the clinical applicability of these technologies.

Innovative and sustainable sampling strategies for bioanalytical quantification of drugs and metabolites have gained considerable interest. Scavenging can be stratified as a sustainable sampling strategy using residual material because it aligns with the green principles of waste reduction and sampling optimization. Scavenged sampling includes all biological fluids' (eg, blood, liquor, and urine) leftover from standard clinical care. This review elaborates on the past and current landscape of sustainable sampling within therapeutic drug monitoring, with a focus on scavenged sampling.Methods: In February 2021, 4 databases were searched to assess the literature on the clinical use of innovative and sustainable sampling techniques without applying publication date restrictions. Studies reporting the clinical use of scavenged blood sampling and bridging studies of scavenged sampling and normal blood sampling were eligible for inclusion.Results: Overall, 19 eligible studies concerning scavenged sampling were identified from 1441 records. Scavenged sampling is mainly applied in the pediatric population, although other patient groups may benefit from this strategy. The infrastructure required for scavenged sampling encounters several challenges, including logistic hurdles, storage and handling conditions, and documentation errors.A workflow is proposed with identified opportunities that guide the implementation of scavenged sampling.Conclusions: This review presents current evidence on the clinical use of scavenged sampling strategies. Scavenged sampling can be a suitable approach for drug quantification to improve dosage regimens, perform pharmacokinetic studies, and explore the value of therapeutic drug monitoring without additional sample collection.

Background: Emerging evidence supports the importance of optimized antibiotic exposure in pediatric intensive care unit (PICU) patients. Traditional antibiotic dosing is not designed for PICU patients, as the extreme pharmacokinetic (PK) behavior of drugs threatens the achievement of optimal antibiotic treatment outcomes. Scavenged sampling is a sampling strategy which may have positive implications for routine TDM and PK research, as well as monitoring other biomarkers. EXPAT Kids study was designed to analyze whether current empiric dosing regimens of frequently used beta-lactam antibiotics achieve defined therapeutic target concentrations in PICU patients.Methods: A mono-centre, exploratory pharmacokinetic and pharmacodynamic study was designed to assess target attainment of beta-lactam antibiotics. One hundred forty patients will be included within 24 months after start of inclusion. At various time points serum concentration of the study antibiotic (cefotaxime, ceftazidime, ceftriaxone, cefuroxime, flucloxacillin, and meropenem) are determined. In parallel with these sampling moments, residual material is collected to validate the use of blood of scavenged heparinized astrup syringes for the quantification of antibiotic exposure. The primary outcome is the time that the free (unbound) concentration of the study antibiotic remains above one to four the minimal inhibitory concentration during a dosing interval (100%ƒT > MIC and 100%ƒT>4xMIC). Other included outcomes are disease severity, safety, length of stay, and inflammatory biomarkers.Discussion: Potentially, scavenged sampling may enrich the EXPAT Kids dataset, and reduce additional blood sampling and workload for clinical personnel. The findings from the EXPAT Kids study will lead to new insights in the PK parameters of beta-lactams and consecutive effects on target attainment and clinical outcomes. Is there a need for more precision in dosing? Netherlands Trial Register Number: Trial NL9326.