The lipidomics reporting checklist a framework for transparency of lipidomic experiments and repurposing resource data.

The rapid increase in lipidomic studies has led to a collaborative effort within the community to establish standards and criteria for producing, documenting, and disseminating data. Creating a dynamic easy-to-use checklist that condenses key information about lipidomic experiments into common terminology will enhance the field's consistency, comparability, and repeatability. Here, we describe the structure and rationale of the established Lipidomics Minimal Reporting Checklist to increase transparency in lipidomics research.

Stroke of Consistency: Streamlining Multicenter Protocols for Enhanced Reproducibility of Infarct Volumes in Preclinical Stroke Research.

BACKGROUND: The discrepancy between experimental research and clinical trial outcomes is a persistent challenge in preclinical studies, particularly in stroke research. A possible factor contributing to this issue is the lack of standardization across experimental stroke models, leading to poor reproducibility in multicenter studies. This study addresses this gap by aiming to enhance reproducibility and the efficacy of multicenter studies through the harmonization of protocols and training of involved personnel. METHODS: We established a set of standard operating procedures for various stroke models and the Neuroscore. These standard operating procedures were implemented across multiple research centers, followed by specialized, in-person training for all participants. We measured the variability in infarct volume both before and after the implementation of these standardized protocols and training sessions. RESULTS: The standardization process led to a significant reduction in variability of infarct volume across different stroke models (40%-50% reduction), demonstrating the effectiveness of our harmonized protocols and training. Additionally, the implementation of the Neuroscore system across centers showed low variability and consistent results up to 28 days poststroke, underscoring its utility in chronic phase evaluations. CONCLUSIONS: The harmonization of protocols and surgeon training significantly reduced variability in experimental outcomes across different centers. This improvement can increase the comparability of data between research groups and enhance the statistical power of multicenter studies. Our findings also establish the Neuroscore as a reliable tool for long-term assessment in stroke research, paving the way for more consistent and impactful multicenter preclinical studies.

Canadian Multicentric Pan-TRK (CANTRK) Immunohistochemistry Harmonization Study.

Tumor-agnostic testing for NTRK1-3 gene rearrangements is required to identify patients who may benefit from TRK inhibitor therapies. The overarching objective of this study was to establish a high-quality pan-TRK immunohistochemistry (IHC) screening assay among 18 large regional pathology laboratories across Canada using pan-TRK monoclonal antibody clone EPR17341 in a ring study design. TRK-fusion positive and negative tumor samples were collected from participating sites, with fusion status confirmed by panel next-generation sequencing assays. Each laboratory received: (1) unstained sections from 30 cases of TRK-fusion-positive or -negative tumors, (2) 2 types of reference standards: TRK calibrator slides and IHC critical assay performance controls (iCAPCs), (3) EPR17341 antibody, and (4) suggestions for developing IHC protocols. Participants were asked to optimize the IHC protocol for their instruments and detection systems by using iCAPCs, to stain the 30 study cases, and to report the percentage scores for membranous, cytoplasmic, and nuclear staining. TRK calibrators were used to assess the analytical sensitivity of IHC protocols developed by using the 2 reference standards. Fifteen of 18 laboratories achieved diagnostic sensitivity of 100% against next-generation sequencing. The diagnostic specificity ranged from 40% to 90%. The results did not differ significantly between positive scores based on the presence of any type of staining vs the presence of overall staining in ≥1% of cells. The median limit of detection measured by TRK calibrators was 76,000 molecules/cell (range 38,000 to >200,000 molecules/cell). Three different patterns of staining were observed in 19 TRK-positive cases, cytoplasmic-only in 7 samples, nuclear and cytoplasmic in 9 samples, and cytoplasmic and membranous in 3 samples. The Canadian multicentric pan-TRK study illustrates a successful strategy to accelerate the multicenter harmonization and implementation of pan-TRK immunohistochemical screening that achieves high diagnostic sensitivity by using laboratory-developed tests where laboratories used centrally developed reference materials. The measurement of analytical sensitivity by using TRK calibrators provided additional insights into IHC protocol performance.

MR imaging signs of shoulder adhesive capsulitis: analysis of potential differentials and improved diagnostic criteria.

OBJECTIVE: To evaluate the prevalence of shoulder adhesive capsulitis (AC) signs on MR studies of patients with various common shoulder conditions. METHODS: MR images of 316 patients were retrospectively evaluated. Patients were divided into three groups: controls (66 patients), clinical AC (63 patients), and study group (187 patients). The final diagnosis of AC was reached clinically. The study group was composed of patients with focal and massive rotator cuff tears, active hydroxyapatite deposition disease, fractures around the shoulder, and post-surgery. The following AC signs were evaluated: inferior glenohumeral ligament (IGHL) thickening; coracohumeral ligament (CHL) thickening; and hyperintensity of the inferior glenohumeral ligament, which was graded in four classes. RESULTS: The IGHL signal intensity was statistically higher in patients with fractures than in controls (P = 0.008). There was no statistically significant difference in IGHL signal between the AC group and patients with massive rotator cuff tears and active hydroxyapatite deposition disease (P > 0.1). IGHL thickness in patients with fractures, massive rotator ruptures, and active hydroxyapatite deposition disease was significantly higher compared to controls (P < 0.02) and significantly lower compared to the AC group (P < 0.0001). Based on these findings, a grading system for fibro-inflammatory capsular changes is proposed. CONCLUSION: MR AC signs are frequent in patients with shoulder conditions other than AC; however, in these patients, capsular changes are less prominent than in patients with clinical AC.

A Deep-Learning-Based CPR Action Standardization Method.

In emergency situations, ensuring standardized cardiopulmonary resuscitation (CPR) actions is crucial. However, current automated external defibrillators (AEDs) lack methods to determine whether CPR actions are performed correctly, leading to inconsistent CPR quality. To address this issue, we introduce a novel method called deep-learning-based CPR action standardization (DLCAS). This method involves three parts. First, it detects correct posture using OpenPose to recognize skeletal points. Second, it identifies a marker wristband with our CPR-Detection algorithm and measures compression depth, count, and frequency using a depth algorithm. Finally, we optimize the algorithm for edge devices to enhance real-time processing speed. Extensive experiments on our custom dataset have shown that the CPR-Detection algorithm achieves a mAP0.5 of 97.04%, while reducing parameters to 0.20 M and FLOPs to 132.15 K. In a complete CPR operation procedure, the depth measurement solution achieves an accuracy of 90% with a margin of error less than 1 cm, while the count and frequency measurements achieve 98% accuracy with a margin of error less than two counts. Our method meets the real-time requirements in medical scenarios, and the processing speed on edge devices has increased from 8 fps to 25 fps.

Clinically Adjudicated Reference Standards for Evaluation of Infectious Diseases Diagnostics.

Lack of a gold standard can present a challenge for evaluation of diagnostic test accuracy of some infectious diseases tests, particularly when the test's accuracy potentially exceeds that of its predecessors. This approach may measure agreement with an imperfect reference, rather than correctness, because the right answer is unknown. Solutions consist of multitest comparators, including those that involve a test under evaluation if multiple new tests are being evaluated together, using latent class modeling, and clinically adjudicated reference standards. Clinically adjudicated reference standards may be considered as comparator methods when no predefined test or composite of tests is sufficiently accurate; they emulate clinical practice in that multiple data pieces are clinically assessed together.

Evaluation of a Quantitative Dual-Target EBV DNA Test on a Fully Automated Molecular Testing System.

The measurement of Epstein-Barr virus (EBV) deoxyribonucleic acid (DNA) is key to diagnosing and managing EBV-associated complications in transplant recipients. The performance of the new Conformité Européenne (CE) and Food and Drug Administration (FDA)-cleared quantitative Roche cobas EBV real-time PCR assay was determined by using EDTA-plasma dilution panels and clinical samples that were spiked with either the World Health Organization's EBV international standard or high-titer EBV lambda stock. Correlation with the Abbott Realtime EBV assay was assessed in clinical specimens and conducted at two independent laboratories. An in silico analysis revealed that the dual-target test (EBNA1 and BMRF2) was 100% inclusive for the known diversity of EBV. The overall limit of detection (LoD) was 16.6 IU/mL for genotype 1 (GT1). GT2 LoD was verified at 18.8 IU/mL. The linear ranges were from 1.40 × 101 to 2.30 × 108 IU/mL and from 2.97 × 101 to 9.90 × 107 IU/mL for GT1 and GT2, respectively. Accuracy was confirmed across the linear range (mean difference not exceeding ±0.18 log10). Precision was not influenced by the factors analyzed (standard deviation of 0.02 to 0.17 log10), including the presence of potentially interfering endogenous or exogenous substances. Plasma samples were stable under several conditions (variable time points, storage, and freeze/thaw cycles). In clinical EBV DNA-positive samples, correlation between the cobas EBV test and the comparator was high (n = 126 valid results; R2 = 0.96) with a 0.1 mean log10 titer difference. The cobas EBV test is an accurate, sensitive, specific, and reproducible assay for the detection of EBV DNAemia in plasma. In general, high levels of automation and calibration to the international standard will lead to improvements in the harmonization of quantitative EBV DNA test results across laboratories.

Has the STARD statement improved the quality of reporting of diagnostic accuracy studies published in European Radiology?

OBJECTIVES: To investigate whether encouraging authors to follow the Standards for Reporting Diagnostic Accuracy (STARD) guidelines improves the quality of reporting of diagnostic accuracy studies. METHODS: In mid-2017, European Radiology started encouraging its authors to follow the STARD guidelines. Our MEDLINE search identified 114 diagnostic accuracy studies published in European Radiology in 2015 and 2019. The quality of reporting was evaluated by two independent reviewers using the revised STARD statement. Item 11 was excluded because a meaningful decision about adherence was not possible. Student's t test for independent samples was used to analyze differences in the mean number of reported STARD items between studies published in 2015 and in 2019. In addition, we calculated differences related to the study design, data collection, and citation rate. RESULTS: The mean total number of reported STARD items for all 114 diagnostic accuracy studies analyzed was 15.9 ± 2.6 (54.8%) of 29 items (range 9.5-22.5). The quality of reporting of diagnostic accuracy studies was significantly better in 2019 (mean ± standard deviation (SD), 16.3 ± 2.7) than in 2015 (mean ± SD, 15.1 ± 2.3; p < 0.02). No significant differences in the reported STARD items were identified in relation to study design (p = 0.13), data collection (p = 0.87), and citation rate (p = 0.09). CONCLUSION: The quality of reporting of diagnostic accuracy studies according to the STARD statement was moderate with a slight improvement since European Radiology started to recommend its authors to follow the STARD guidelines. KEY POINTS: • The quality of reporting of diagnostic accuracy studies was moderate with a mean total number of reported STARD items of 15.9 ± 2.6. • The adherence to STARD was significantly better in 2019 than in 2015 (16.3 ± 2.7 vs. 15.1 ± 2.3; p = 0.016). • No significant differences in the reported STARD items were identified in relation to study design (p = 0.13), data collection (p = 0.87), and citation rate (p = 0.09).

Reference Standards to Support Quality of Synthetic Peptide Therapeutics.

PURPOSE: Peptides are an important class of therapeutics. Their quality is evaluated using a series of analytical tests, many of which depend on well-characterized reference standards to determine identity, purity, and strength. OBJECTIVE: Discuss approaches to producing peptide reference standards, including vialing, lyophilization, analytical testing and stability studies. METHODS: Case studies are used to illustrate analytical approaches to characterize reference standards, including methods for value assignment, content uniformity, and identity testing. Methods described include NMR, mass spectrometry, and chromatography techniques for identity testing and HPLC and GC methods for assessing peptide content and impurities. RESULTS: This report describes the analytical strategy used to establish peptide reference standard and illustrates how results from multiple labs are integrated to assign a value to the final lyophilized vial. A two-step process for value assignment is described, which uses a mass balance approach to assign a quantitative value to a bulk peptide material. The bulk material is then used as a standard to assign a final value to the vialed material. Testing to confirm peptide identity and to ensure consistency of the vialed material is also described. Considerations for addressing variability, identifying outliers, and implementing stability studies are also presented. CONCLUSION: The methods and case studies described provide a benchmark for best practices in establishing the preparation, analytical testing, handling, and storage of peptide reference standards for the pharmaceutical industry. Some peptide features, such as chiral or isobaric amino acids, may require additional techniques to ensure a full characterization of the peptide reference standard.

Establishing severity levels for patient-reported measures of functional communication, participation, and perceived cognitive function for adults with acquired cognitive and language disorders.

PURPOSE: To empirically assign severity levels (e.g., mild, moderate) to four relatively new patient-reported outcome measures (PROMs) for adults with acquired cognitive/language disorders. They include the Communicative Participation Item Bank, the Aphasia Communication Outcome Measure, and Neuro-QoL's item banks of Cognitive Function (v2.0) and Ability to Participate in Social Roles and Activities (v1.0). METHOD: We conducted 17 focus groups that comprised 22 adults with an acquired cognitive/language disorder from stroke, Parkinson's disease, or traumatic brain injury; 30 care partners of an adult with an acquired cognitive/language disorder; and 42 speech-language pathologists who had experience assessing/treating individuals with those and other cognitive/language disorders. In a small, moderated focus-group format, participants completed "PROM-bookmarking" procedures: They discussed hypothetical vignettes based on PROM item responses about people with cognitive/language disorders and had to reach consensus regarding whether their symptoms/function should be categorized as within normal limits or mild, moderate, or severe challenges. RESULTS: There was generally good agreement among the stakeholder groups about how to classify vignettes, particularly when they reflected very high or low functioning. People with aphasia described a larger range of functional communication challenges as "mild" compared to other stakeholder types. Based on a consensus across groups, we present severity levels for specific score ranges for each PROM. CONCLUSION: Standardized, stakeholder-informed severity levels that aid interpretation of PROM scores can help clinicians and researchers derive better clinical meaning from those scores, for example, by identifying important clinical windows of opportunity and assessing when symptoms have returned to a "normal" range.

Reference standard analysis of multiple new and old plasma clearance models and renal clearance with special attention to measurement of reduced glomerular filtration rate.

Nine models were evaluated as candidate glomerular filtration rate (GFR) reference standards in three datasets using [51Cr(EDTA)]- or [169Yb(DTPA)]2- anions in 98 studies. Noncompartmental methods formed an upper limit for estimating mass excreted and voluntary urine collection formed a lower limit. For current models and methods, reduced GFR in adults resulted in inflated clearance estimates. Two different logarithmic models with exponential tails were created and may have underestimated reduced clearance. The logarithmic formulae can be used with only two plasma samples, and fit 13 multiple time-samples from 5 min to 24 h with an 8% standard deviation of residuals compared to 20% error for monoexponentials. For shorter times (4 or 5 h) the fit errors decreased but the ratio of errors remained at circa 2.5 times lesser for the logarithmic versus monoexponential models. Adaptively regularised gamma variate, Tk-GV, models that are well documented, but not in common use, were largely contained within the reference extreme values, were unbiased for different levels of clearance and were the only models to be uncorrelated to volume of distribution from mean residence time divided by weight. Using Tk-GV as a candidate reference standard, potentially better methods for routine clinical usage were discussed. Prospective clinical testing, and metabolic scaling of decreased renal function is advised for potential changes to patient triage.

Validated method for polystyrene nanoplastic separation in aqueous matrices by asymmetric-flow field flow fraction coupled to MALS and UV-Vis detectors.

Plastics with nanosize (nanoplastics, NPLs) must be characterized, since they can be toxic or act as carriers of organic and inorganic pollutants, but there is a lack of reference materials and validated methods in the nanosize range. Therefore, this study has focused on the development and validation of a separation and size characterization methodology of polystyrene latex nanospheres, by using an asymmetric-flow field flow fraction system coupled to multi-angle light scattering and ultraviolet-visible detectors (AF4-MALS-UV). Hence, this work presents a fully validated methodology in the particle size range 30 to 490 nm, with bias between 95 and 109%, precision between 1 and 18%, LOD and LOQ below 0.2 and 0.3 µg respectively, except for 30-nm standard, for both detectors, and showing stable results for 100 analyses.

Influence of age and diet consistency on the oral muscle pressure of orthodontically treated and untreated subjects with normal occlusion and comparison of their 3D facial shape.

OBJECTIVES: (1) To investigate the effect of age and diet consistency on maximum lips, tongue and cheek pressure of orthodontically treated and untreated subjects with normal, Class I dental occlusion, (2) to find out whether there is a muscle imbalance between anterior tongue and lip pressure in the same subjects at different ages and (3) to compare the 3D facial shape of treated and untreated individuals. MATERIAL AND METHODS: Subjects with normal occlusion were prospectively grouped into orthodontically treated/untreated and in children/adolescents/adults. Iowa Oral Performance Instrument was used to record the maximum muscle pressure. Two-way ANOVA and Tukey post hoc test analysed age-specific differences in muscle pressure. Two-way ANCOVA analysed the effect of diet consistency on muscle pressure. Lips and tongue imbalance was analysed using z-scores and 3D faces using a generalized Procrustes analysis. RESULTS: One hundred thirty-five orthodontically untreated and 114 treated participants were included. Muscle pressure was found to increase with age in both groups, except for the tongue in treated subjects. No differences in the balance between lips and tongue muscle pressure were found, but a higher cheek pressure in untreated adults (p<0.05) was observed. 3D facial shapes showed subtle differences. Untreated subjects with soft diet consistency showed lower lip pressure (p<0.05). CONCLUSION: Oral muscle pressure of orthodontically treated patients without relapse does not differ from that of untreated patients with Class-I occlusion. CLINICAL RELEVANCE: This study provides normative lip, tongue and cheek muscle pressure in subjects with normal occlusion, which can be used for diagnosis, treatment planning and stability.

On the Use of Deuterated Organic Solvents without TMS to Report 1H/13C NMR Spectral Data of Organic Compounds: Current State of the Method, Its Pitfalls and Benefits, and Related Issues.

The quite popular, simple but imperfect method of referencing NMR spectra to residual 1H and 13C signals of TMS-free deuterated organic solvents (referred to as Method A) is critically discussed for six commonly used NMR solvents with respect to their δH and δC values that exist in the literature. Taking into account the most reliable data, it was possible to recommend 'best' δX values for such secondary internal standards. The position of these reference points on the δ scale strongly depends on the concentration and type of analyte under study and the solvent medium used. For some solvents, chemically induced shifts (CISs) of residual 1H lines were considered, also taking into account the formation of 1:1 molecular complexes (for CDCl3). Typical potential errors that can occur as a result of improper application of Method A are considered in detail. An overview of all found δX values adopted by users of this method revealed a discrepancy of up to 1.9 ppm in δC reported for CDCl3, most likely caused by the CIS mentioned above. The drawbacks of Method A are discussed in relation to the classical use of an internal standard (Method B), two 'instrumental' schemes in which Method A is often implicitly applied, that is, the default Method C using 2H lock frequencies and Method D based on Ξ values, recommended by the IUPAC but only occasionally used for 1H/13C spectra, and external referencing (Method E). Analysis of current needs and opportunities for NMR spectrometers led to the conclusion that, for the most accurate application of Method A, it is necessary to (a) use dilute solutions in a single NMR solvent and (b) to report δX data applied for the reference 1H/13C signals to the nearest 0.001/0.01 ppm to ensure the precise characterization of new synthesized or isolated organic systems, especially those with complex or unexpected structures. However, the use of TMS in Method B is strongly recommended in all such cases.

How Can Out-of-Hospital Cardiac Arrest (OHCA) Data Collection in Slovenia Be Improved?

Background and Objectives: The prevalence of out-of-hospital cardiac arrest (OHCA) has been established as a significant contributor to mortality rates in developed nations. Due to the challenges associated with conducting controlled randomized trials, there exists a necessity for the collection of high-quality data to enhance the comprehension of the impact of interventions. Several nations have initiated efforts to gather information pertaining to out-of-hospital cardiac arrest (OHCA). The Republic of Slovenia has been collecting data from interventions; however, the variables and data attributes have not yet been standardized to comply with international standards. This lack of conformity poses a challenge in making comparisons or drawing inferences. The aim of this study is to identify how to better gather OHCA data in Slovenia. Materials and methods: The Utstein resuscitation registry protocol (UP) was compared to the Slovenian data points that must be gathered in accordance with the Rules on Emergency Medical Service (REMS) during interventions. In addition, we have proposed alternative measures of digitization to enhance pre-hospital data. Results: Missing data points and attribute mismatches were detected in Slovenia. Eight data points necessitated by the UP are gathered in several databases (hospitals, the National Institute of Public Health, dispatch services, intervention reports from first responders, and defibrillator files), but not in the mandated protocols based on REMS. Two data points have variables that do not match those of the UP. A total of 16 data points according to UP are currently not being collected in Slovenia. The advantages and potential drawbacks of digitizing emergency medical services have been discussed. Conclusions: The study has identified gaps in the methods employed for collecting data on OHCA in Slovenia. The assessment conducted serves as a basis for enhancing the process of data collection, integrating quality control measures across the nation, and establishing a nationwide registry for out-of-hospital cardiac arrest (OHCA) in Slovenia.

Ensuring the quality of medicines in India: An update on the development, modernization, and harmonization of drug standards in the Indian Pharmacopoeia.

India has a sparkling pharmaceutical sector that holds a distinguished place by producing and supplying high-quality and affordable medicines across the globe. Ensuring the quality and safety of the marketed medicinal products is one of the most important components of the drug regulatory framework and assessment of the quality of medicines is usually achieved by referring to the public standards of the official Pharmacopoeia. In India, the Indian Pharmacopoeia (IP) is published at regular intervals to fulfill the requirements of the Drugs and Cosmetics Act, 1940 to ensure the quality of medicines being manufactured and/or marketed in India. The present article aims to provide an overview of the history of the IP, its standards-setting process, and the current status of monographs in the 9th edition of the IP 2022. Special focus is placed on the newly added and upgraded general chapters and monographs within the IP 2022. There are a total of 223 general chapters and 3152 drug monographs available under various categories in the IP 2022. This study also highlights a total of 92 new drug monograph additions and 412 monograph revisions in the IP 2022. It is anticipated that the standards laid down in the IP 2022 will play an imperative role in delivering quality medicines to patients within and outside India.

A Reference Standard for Analytical Testing of Erythropoietin.

PURPOSE: Erythropoietin (EPO) is a 165 amino acid protein that promotes the proliferation of erythrocytic progenitors. A decrease in endogenous EPO production causes anemia that can be treated with recombinant Human EPO (rHuEPO). OBJECTIVE: To ensure the safety and efficacy of the rHuEPO, manufacturers must use analytical methods to demonstrate similarity across batches and between different products. To do this they need reference standards to validate their equipment and methods. METHOD: We used peptide mapping, size-exclusion chromatography, glycoprofiling, and isoelectric focusing to analyze a rHuEPO reference standard. RESULTS: Characterization demonstrates that our rHuEPO reference standard meets the criteria for quality. CONCLUSION: The rHuEPO reference standard is fit for purpose as a tool for validating system suitability and methods.

HbA1c percentiles and the association between BMI, age, gender, puberty, and HbA1c levels in healthy German children and adolescents.

OBJECTIVE: The measurement of glycated hemoglobin (HbA1c) represents one way to detect type 1 and 2 diabetes in children at an early stage. However, to date, variations in HbA1c levels are not fully understood, even in healthy children. With this in mind, the present study aimed to establish HbA1c reference values in healthy children and to investigate the influence of various independent variables. STUDY DESIGN AND METHODS: Two thousand four hundred fifty-five healthy children and adolescents aged between 0.5 and 18 years participated in the population-based cohort study LIFE Child, Germany. Age- and gender-dependent percentiles were estimated, enabling HbA1c values to be converted into standard deviation scores (SDS). Logistic regression models were applied to assess associations between HbA1c-SDS (as outcome) and age, gender, BMI, birth weight, physical activity, pubertal status, and socioeconomic status (SES; as explanatory variables). RESULTS: The mean HbA1c value was 31.79 mmol/mol or 5.06% (SD = 3.3 mmol/mol, SD = 0.3%). Positive associations with HbA1c values were identified for age (b = 0.09, p < 0.001), gender (b = 0.25, p = 0.007), and BMI-SDS (b = 0.06, p < 0.001). In addition, obesity was related to higher HbA1c values (b = 0.29, p < 0.001). Compared to prepuberty, the pubertal and postpubertal stages were associated with higher HbA1c levels. Furthermore, higher SES was associated with higher HbA1c-SDS (b = 0.01, p = 0.04). CONCLUSION: The present study established HbA1c reference values based on a large sample of healthy German children and adolescents. Age, gender, SES, pubertal stage, and BMI were found to be associated with higher HbA1c levels.

Individualised care or anaesthetist preference: an uncomfortable question.

There is widespread variation in how anaesthesia is provided to individual patients even for the same types of surgery. This variation exists within departments, between hospitals, and between countries. Patient and surgical factors are often cited as a justification for variation. Local and national norms, guidance, and standards, and the positive or negative roles of key opinion leaders likely all play a part. Although clinicians may disagree where the line falls between warranted and unwarranted variations, at least some of this variation is down to anaesthetist preference, not individualised patient care.

Avoidable mortality due to long-term exposure to PM2.5 in Colombia 2014-2019.

OBJECTIVE: To compare estimates of spatiotemporal variations of surface PM2.5 concentrations in Colombia from 2014 to 2019 derived from two global air quality models, as well as to quantify the avoidable deaths attributable to the long-term exposure to concentrations above the current and projected Colombian standard for PM2.5 annual mean at municipality level. METHODS: We retrieved PM2.5 concentrations at the surface level from the ACAG and CAMSRA global air quality models for all 1,122 municipalities, and compare 28 of them with available concentrations from monitor stations. Annual mortality data 2014-2019 by municipality of residence and pooled effect measures for total, natural and specific causes of mortality were used to calculate the number of annual avoidable deaths and years of potential life lost (YPLL) related to the excess of PM2.5 concentration over the current mean annual national standard of 25 µg/m3 and projected standard of 15 µg/m3. RESULTS: Compared to surface data from 28 municipalities with monitoring stations in 2019, ACAG and CAMSRA models under or overestimated annual mean PM2.5 concentrations. Estimations from ACAG model had a mean bias 1,7 µg/m3 compared to a mean bias of 4,7 µg/m3 from CAMSRA model. Using ACAG model, estimations of total nationally attributable deaths to PM2.5 exposure over 25 and 15 µg/m3 were 142 and 34,341, respectively. Cardiopulmonary diseases accounted for most of the attributable deaths due to PM2.5 excess of exposure (38%). Estimates of YPLL due to all-cause mortality for exceeding the national standard of 25 µg/m3 were 2,381 years. CONCLUSION: Comparison of two global air quality models for estimating surface PM2.5 concentrations during 2014-2019 at municipality scale in Colombia showed important differences. Avoidable deaths estimations represent the total number of deaths that could be avoided if the current and projected national standard for PM2.5 annual mean have been met, and show the health-benefit of the implementation of more restrictive air quality standards.