Theratyping cystic fibrosis patients to guide elexacaftor/tezacaftor/ivacaftor out-of-label prescription.

BACKGROUND: Around 20% of people with cystic fibrosis (pwCF) do not have access to the triple combination elexacaftor/tezacaftor/ivacaftor (ETI) in Europe because they do not carry the F508del allele on the CF transmembrane conductance regulator (CFTR) gene. Considering that pwCF carrying rare variants may benefit from ETI, including variants already validated by the US Food and Drug Administration (FDA), a compassionate use programme was launched in France. PwCF were invited to undergo a nasal brushing to investigate whether the pharmacological rescue of CFTR activity by ETI in human nasal epithelial cell (HNEC) cultures was predictive of the clinical response. METHODS: CFTR activity correction was studied by short-circuit current in HNEC cultures at basal state (dimethyl sulfoxide (DMSO)) and after ETI incubation and expressed as percentage of normal (wild-type (WT)) CFTR activity after sequential addition of forskolin and Inh-172 (ΔI ETI/DMSO%WT). RESULTS: 11 pwCF carried variants eligible for ETI according to the FDA label and 28 carried variants not listed by the FDA. ETI significantly increased CFTR activity of FDA-approved CFTR variants (I601F, G85E, S492F, M1101K, R347P, R74W;V201M;D1270N and H1085R). We point out ETI correction of non-FDA-approved variants, including N1303K, R334W, R1066C, Q552P and terminal splicing variants (4374+1G>A and 4096-3C>G). ΔI ETI/DMSO%WT was significantly correlated to change in percentage predicted forced expiratory volume in 1 s and sweat chloride concentration (p<0.0001 for both). G85E, R74W;V201M;D1270N, Q552P and M1101K were rescued more efficiently by other CFTR modulator combinations than ETI. CONCLUSIONS: Primary nasal epithelial cells hold promise for expanding the prescription of CFTR modulators in pwCF carrying rare mutants. Additional variants should be discussed for ETI indication.

Evaluation of long-term sequelae by cardiopulmonary exercise testing 12 months after hospitalization for severe COVID-19.

BACKGROUND: Cardiopulmonary exercise testing (CPET) is an important clinical tool that provides a global assessment of the respiratory, circulatory and metabolic responses to exercise which are not adequately reflected through the measurement of individual organ system function at rest. In the context of critical COVID-19, CPET is an ideal approach for assessing long term sequelae. METHODS: In this prospective single-center study, we performed CPET 12 months after symptom onset in 60 patients that had required intensive care unit treatment for a severe COVID-19 infection. Lung function at rest and chest computed tomography (CT) scan were also performed. RESULTS: Twelve months after severe COVID-19 pneumonia, dyspnea was the most frequently reported symptom although only a minority of patients had impaired respiratory function at rest. Mild ground-glass opacities, reticulations and bronchiectasis were the most common CT scan abnormalities. The majority of the patients (80%) had a peak O2 uptake (V'O2) considered within normal limits (median peak predicted O2 uptake (V'O2) of 98% [87.2-106.3]). Length of ICU stay remained an independent predictor of V'O2. More than half of the patients with a normal peak predicted V'O2 showed ventilatory inefficiency during exercise with an abnormal increase of physiological dead space ventilation (VD/Vt) (median VD/VT of 0.27 [0.21-0.32] at anaerobic threshold (AT) and 0.29 [0.25-0.34] at peak) and a widened median peak alveolar-arterial gradient for O2 (35.2 mmHg [31.2-44.8]. Peak PetCO2 was significantly lower in subjects with an abnormal increase of VD/Vt (p = 0.001). Impairments were more pronounced in patients with dyspnea. Peak VD/Vt values were positively correlated with peak D-Dimer plasma concentrations from blood samples collected during ICU stay (r2 = 0.12; p = 0.02) and to predicted diffusion capacity of the lung for carbon monoxide (DLCO) (r2 = - 0.15; p = 0.01). CONCLUSIONS: Twelve months after severe COVID-19 pneumonia, most of the patients had a peak V'O2 considered within normal limits but showed ventilatory inefficiency during exercise with increased dead space ventilation that was more pronounced in patients with persistent dyspnea. TRIAL REGISTRATION: NCT04519320 (19/08/2020).

Retrieving forensic information about the donor through bacterial profiling.

When fingermarks are left on a surface, bacteria originating from the donor's skin are also deposited. The skin microbiome is believed to be extremely diverse between individuals, allowing for potential matching between the bacterial communities and touched objects, known as "bacterial profiling". This study stepped further and investigated how the bacterial profile could be used as an indicator of donor characteristics of potential forensic intelligence interest. Forty-five participants were asked to touch DNA-free playing cards with their dominant and non-dominant hands. Cards were swabbed and bacterial communities determined through 16S rRNA sequencing. Diversity and abundance of bacteria were compared to donor characteristics of gender, age, ethnicity, handedness, home location, sample location, occupation, diet type, use of moisturisers, use of hand sanitisers and use of public transport. Correlations between the bacterial profile with gender, ethnicity, diet type and hand sanitiser use were found. Specifically, the absence of Lactococcus indicated a primarily Chinese diet, while the absence of Alloiococcus indicated female gender, Asian ethnicity and hand sanitiser use. Testing of the prediction models demonstrated highest accuracy for gender estimation, while the prediction of other characteristics showed lower success. This study showed a correlation between the presence of certain bacterial species on donor's hands and personal characteristics of potential forensic relevance, thus demonstrating a novel application of microbiome genotyping in forensic science.

Secondary transfer of organic gunshot residues: Empirical data to assist the evaluation of three scenarios.

The present study aimed at providing data to assess the secondary transfer of organic gunshot residues (OGSR). Three scenarios were evaluated in controlled conditions, namely displacing a firearm from point A to point B, a simple handshake and an arrest involving handcuffing on the ground. Specimens were collected from the firearm, the hands of the shooter and the non-shooter undergoing the secondary transfer in order to compare the amounts detected. Secondary transfer was observed for the three scenarios, but to a different extent. It was found that displacing a firearm resulted in secondary transfer in <50% of the experiments. The firearm also had an influence, as contrary to the pistol, no secondary OGSR were detected using the revolver. Shaking the hand of the shooter also transferred OGSR to the non-shooter's hand. In that case, the amount of OGSR was generally higher on the shooter than on the non-shooter. Finally, the largest secondary transfer was observed after the arrest with handcuffing with positive results in all cases using the pistol. In that scenario, the amounts on the shooter and the non-shooter were in the same range. This study highlights that the secondary transfer must be taken into account in the interpretation of OGSR. Indeed, an individual's hands might be contaminated by handling a firearm or having physical contact with a shooter.

The use of handwriting examinations beyond the traditional court purpose.

Traditionally, forensic science has predominantly focused its resources and objectives on addressing court related questions. However, this view restricts the contribution of forensic science to one function and results in lost opportunities as investigative and intelligence roles are often overlooked. A change of perspective and expansion of the contributions of forensic science is required to take advantage of the benefits of abductive and inductive thought processes throughout the investigative and intelligence functions. One forensic discipline that has the potential to broaden its traditional focus is handwriting examination. Typically used in investigations that are focused on both criminal and civil cases, the examination procedure and outcome are time consuming and subjective, requiring a detailed study of the features of the handwriting in question. Traditionally, the major handwriting features exploited are characteristics that are often considered individual (or at least highly polymorphic) and habitual. However, handwriting can be considered as an information vector in an intelligence framework. One such example is the recognition of key elements related to the author's native language. This paper discusses the traditional method generally used around the world and proposes a theoretical approach to expand the application of handwriting examination towards gaining additional information for intelligence purposes. This concept will be designed and tested in a future research project.

The development and comparison of collection techniques for inorganic and organic gunshot residues.

The detection and interpretation of gunshot residues (GSR) plays an important role in the investigation of firearm-related events. Commonly, the analysis focuses on inorganic particles incorporating elements derived from the primer. However, recent changes in ammunition formulations and possibility that particles from non-firearm sources can be indistinguishable from certain primer particles challenge the standard operational protocol and call for adjustments, namely the combination of inorganic and organic GSR analysis. Two protocols for the combined collection and subsequent analysis of inorganic and organic GSR were developed and optimised for 15 compounds potentially present in organic GSR (OGSR). These protocols were conceptualised to enable OGSR analysis by ultrahigh-performance liquid chromatography (UHPLC) coupled with UV detection and triple quadrupole tandem mass spectrometry (confirmation) and IGSR analysis by scanning electron microscopy coupled with energy dispersive X-ray spectroscopy (SEM-EDX). Using liquid extraction, the extraction recoveries from spiked swabs and stubs were ~80 % (50-98 % for swabs, 64-98 % for stubs). When the mixed OGSR standard was applied to the hands and recovered in the way that is usual for IGSR collection, GSR stubs performed significantly better than swabs (~30 %) for the collection of OGSR. The optimised protocols were tested and compared for combined OGSR and inorganic GSR analysis using samples taken at a shooting range. The most suitable protocol for combined collection and analysis of IGSR and OGSR involved collection using GSR stubs followed by SEM-EDX analysis and liquid extraction using acetone followed by analysis with UHPLC.

Coupling paper-based microfluidics and lab on a chip technologies for confirmatory analysis of trinitro aromatic explosives.

A new microfluidic paper-based analytical device (µPAD) in conjunction with confirmation by a lab on chip analysis was developed for detection of three trinitro aromatic explosives. Potassium hydroxide was deposited on the µPADs (0.5 µL, 1.5 M), creating a color change reaction when explosives are present, with detection limits of approximately 7.5 ± 1.0 ng for TNB, 12.5 ± 2.0 ng for TNT and 15.0 ± 2.0 ng for tetryl. For confirmatory analysis, positive µPADs were sampled using a 5 mm hole-punch, followed by extraction of explosives from the punched chad in 30 s using 20 µL borate/SDS buffer. The extractions had efficiencies of 96.5 ± 1.7%. The extracted explosives were then analyzed with the Agilent 2100 Bioanalyzer lab on a chip device with minimum detectable amounts of 3.8 ± 0.1 ng for TNB, 7.0 ± 0.9 ng for TNT, and 4.7 ± 0.2 ng for tetryl. A simulated in-field scenario demonstrated the feasibility of coupling the µPAD technique with the lab on a chip device to detect and identify 1 µg of explosives distributed on a surface of 100 cm(2).

The use of organic and inorganic impurities found in MDMA police seizures in a drug intelligence perspective.

Traditional forensic drug profiling involves numerous analytical techniques, and the whole process is typically costly and may be time consuming. The aim of this study was to investigate the possibility of prioritising techniques utilised at the Australian Federal Police (AFP) for the chemical profiling of 3,4-methylenedioxymethylamphetamine (MDMA). The outcome would provide the AFP with the ability to obtain more timely and valuable results that could be used in an intelligence perspective. Correlation coefficients were used to obtain a similarity degree between a population of linked samples (within seizures) and a population of unlinked samples (between different seizures) and discrimination between the two populations was ultimately achieved. The results showed that gas chromatography-mass spectrometry (GC-MS) was well suited as a single technique to detect links between seizures and could be used in priority for operational intelligence purposes. Furthermore, the method was applied to seizures known or suspected (through their case information) to be linked to each other to assess the chemical similarity between samples. It was found that half of the seizures previously linked by the case number were also linked by the chemical profile. This procedure was also able to highlight links between cases that were previously unsuspected and retrospectively confirmed by circumstantial information. The findings are finally discussed in the broader forensic intelligence context, with a focus on how they could be successfully incorporated into investigations and in an intelligence-led policing perspective in order to understand trafficking markets.

Geographical variation of shoeprint comparison class correspondences.

The underlying principles involved in the interpretation of shoeprint comparisons have become a topical subject due to criticisms in the 2009 National Academy of Science (NAS) report on forensic sciences[1]. Difficulties in the application and understanding of these principles were also highlighted in a recent court ruling [2-5] and subsequent discussion of the ruling. We report here a survey that may inform some aspects of this interpretation and discuss the implications of findings from this survey in the light of that court ruling and more importantly the NAS report. 1,511 shoeprints were taken from student volunteers in Auckland, Wellington and Dunedin, New Zealand. 500 shoeprints were sampled from student volunteers at Australian universities. 100 from each of the University of Technology in Sydney, University of Queensland in Brisbane, University of Newcastle, Charles Sturt University in Bathurst and University of Canberra, Australia. These cities are distributed along the east coast of Australia. The shoeprints, taken from each country, were compared against each other for the presence of any pattern correspondences However shoeprints have not been compared between countries. In all locations the pattern of some common and many rare outsole patterns was repeated, with Converse Chuck Taylor All Stars and Vans Canvas Era common in all locations.

Fibre persistence on submerged substrates: The effect of flow rate over extended submersion periods.

Through both casework and research, fibres have been found to have the particularly useful ability to persist and remain exploitable after submersion. However, direct analysis of the persistence ability remains in early stages, and in particular, submersion times above a day have not been thoroughly studied. This study aims to both extend understanding of the impact of flow rate and submersion periods of up to 28 days. A blended polyester/cotton green fabric was abraded to increase transfer and then dragged over a black cotton substrate. Six replicates of these substrates were then submerged in artificial flow cells at various flow rates for 28 days. These were illuminated under UV light and photographed prior to submersion, at set times during submersion and after submersion. Another set of six replicates were imaged, submerged into a river and then recovered and re-imaged after 28 days. The population of fibres was then counted using these photographs, and a mix of one-way and two-way ANOVA tests were applied, in combination with Tukey's HSD, to detect significant differences across time and flow rate categories. Loss predominantly occurred on within the first 24 hours, in agreement with previous work. However, distinct from previous work there was a slow, approximately logarithmic loss over the balance of the submersion period. While significant differences were found between flow categories, there was no clear relationship between flow rate and persistence. The behaviour of the river samples was well-predicted by laboratory samples. 100 % fibre loss was never observed, with the maximum instead being 95.45 %. These results extend the understanding of fibre persistence on submerged substrates beyond the short submersion times in previous literature, and provide some deeper understanding of the impact of flow rate.

A snapshot of injecting drug consumption from the analysis of used syringes within the Medically Supervised Injecting Centre in Sydney, Australia.

INTRODUCTION: The administration of illicit drugs by injection is associated with considerable harm, including an increased risk of overdose. The chemical analysis of used syringes can enhance knowledge on injecting drug consumption beyond traditional data sources (self-report surveys). This additional information may be useful during significant global events like the COVID-19 pandemic. This study aimed to examine a snapshot of the drugs injected at the Medically Supervised Injecting Centre (MSIC) in Sydney, Australia, in 2019-2020. METHODS: Used syringes were collected from MSIC across three periods throughout 2019 and 2020 (February 2019, March-April 2020 and June-September 2020). Drug residues were extracted from used syringes using methanol before detection by gas chromatography-mass spectrometry and ultra-performance liquid chromatography-tandem mass spectrometry. The chemical analysis results were compared to self-report data obtained from MSIC clients. RESULTS: Heroin (46-53%), methamphetamine (24-34%) and pharmaceutical opioids (15-27%) were the most common drug residues detected. The chemically detected drugs had declining coherence with the drugs self-reported by MSIC clients across the time periods examined. DISCUSSION AND CONCLUSIONS: There was no significant change in the drugs injected (heroin, methamphetamine and pharmaceutical opioids) across the three periods collected throughout varying COVID-19 lockdown restrictions. Changes in the frequency of other drugs injected and discrepancies between chemical analysis and self-report were potentially related to regulatory changes, degradation or misinformed sales. Routine chemical analysis of used syringes has provided an alternative information source to promote awareness of current drug trends and aid harm reduction.

Production of artificial fingermarks. Part II - The use of a modified inkjet printer for the deposition of synthetic secretions.

This study is the second part of a larger body of research dedicated to the production of synthetic secretions and the use of an inkjet printer to deposit realistic artificial fingermarks. An artificial emulsion combining eccrine and sebaceous compounds, which was described and tested in the first part of this research, was used as it showed a promising compatibility with common detection techniques. An inkjet printer was modified to print the emulsion on two different substrates: paper (porous) and acetate (non-porous). After optimisation of the printing parameters, multiple fingermarks were printed and processed with a range of standalone detection techniques: 1,2-indanedione-zinc, ninhydrin, Oil Red O, and physical developer on paper, and cyanoacrylate fuming, rhodamine 6G, gold/zinc vacuum metal deposition, and silver black powder on acetate. The detection techniques were also applied in sequence, which is considered one of the biggest advantages of the emulsion over simpler amino acid mixtures that are usable with amino acid reagents only. Natural fingermarks deposited by a single donor were processed with the same techniques for comparison. The effect of water immersion was also investigated, where fingermarks printed on paper were immersed in water for 15 min, before being processed with 1,2-indanedione-zinc and Oil Red O. The results showed that realistic-looking fingermarks could be printed on paper and that printing on acetate was also possible albeit of lower quality due to the nature of the substrate. The artificial fingermarks were successfully enhanced by all the detection techniques tested, at the notable exception of physical developer. The results obtained were very similar to what is generally observed with real fingermarks, and it was observed that the impact of water immersion on the artificial fingermarks was comparable as well. These findings open new perspectives for the development of multi-target quality control test strips or for the standardisation of proficiency testing and interlaboratory collaborative exercises where ground truth is crucial to guarantee comparable results and objective assessment.

The transfer of fibres between garments in a choreographed assault scenario.

Our fundamental understanding of fibre transfer remains based on early seminal transfer studies that were largely mechanical simulations. However, transfer events in the real world are uncontrolled in nature. This study takes a novel approach to address this discrepancy, with skilled jiu-jitsu practitioners performing a choreographed 'standard' assault scenario to investigate the transfer of fibres between a cotton T-shirt and cotton/polyester hoody. Garments were collected immediately after the scenario and examined for the number, length and zonal distribution of transferred fibres. It was observed that cotton transferred the most fibres, on average twice as many from blended hoodies than T-shirts; whilst polyester transferred the least. Shorter fibres transferred and were recovered more readily than longer fibres; however, it was more likely to recover polyester fibres> 5 mm. The number and length of fibres transferred from the attacker's garment mainly depended on the construction of the donor textile (including sheddability) and properties of the fibres. Conversely, properties of the recipient textile were more significant factors when considering transfer from the victim's garment. Location of recovered fibres was found to be dependent on the wearer's role, but generally, upper zones and sleeves of both garments were most populated. Overall, these results will contribute to grow our current knowledge base regarding fibre transfer between donor and recipient textiles in a common assault situation. This will ultimately aid experts support evaluation with regards to competing hypotheses such as in a Bayesian framework.

Towards more relevance in forensic science research and development.

Many different issues have been identified in forensic science for more than 10 years. While quality management has often been suggested as a path forward, research is generally considered as an essential part of the solution. Through an overview of current forensic science research, this paper aims at evaluating if and how research answer the challenges forensic science is currently facing. While forensic related publications have massively increased over the years, approximately half of the publications were published in non-forensic sources, indicating that forensic science research tends to be led by other disciplines. Over the years, forensic science research has remained largely oriented towards methodological and technological development rather than relevance to the forensic science discipline and practice. Practical implementation of the techniques is rarely discussed from a forensic perspective, and thus research rarely move from the "proof-of-concept" stage to its utilisation in case investigation. The digital transformation also generated a massive increase of data, making it challenging to find the relevant pieces of information in the mass of "forensic" publications available on-line. Thus, we propose to refocus forensic science research on forensic fundamental and practical questions to strengthen the discipline and its impact on crime investigation and security issues. Our propositions represent an incentive to further discuss forensic science research and knowledge transmission through the definition of a common culture within the community, focusing on common fundamental knowledge such as a better understanding of the concept of trace and its case-based information content.

The impact of substrate dampness on the transfer of glass fragments to upper garments when breaking windows.

Glass fragments are often recovered from garments worn by the authors of certain types of crimes and are useful as they present strong connections to the scene at both the source and activity level. It is known that the transfer of glass fragments is impacted when recipient garments are dampened, such as by rain, however, the details of the effect are not clear. This research aimed to determine the impact of substrate dampness on glass retention. Across the three test garments, a cotton t-shirt was found to increase in retentiveness with increasing dampness, while a wool/polyester blend jumper and a cotton hoodie were both found to increase only to a point, before decreasing again when the garment was saturated. This is attributed to the construction of the fabrics, as it does not appear to be related to the identity of the textile itself. It was also found that the size distribution of fragments changed with dampness. All the garments retained a smaller proportion of fragments less than 0.5 mm in size when saturated or dampened than when dry, along with an increase in the proportion of fragments in the 1-1.5 mm and greater than 1.5 mm size categories. These results indicate that is important to consider the impact of substrate dampening when relevant, and that this consideration must be done holistically as different substrates respond to dampening in different ways. It also indicates that consideration of the size distribution in fragment populations may reveal additional information in complex scenarios.

Quality Management in forensic science: A closer inspection.

An international survey was conducted on the benefits and limitations of accreditation to ISO17025 in forensic science, and how quality management could be improved to reflect the complexities of the end-to-end process. The survey was in response to growing concern within the forensic science community that the standard ISO17025 (and ISO17020), which is the backbone of forensic science accreditation, does not have sufficient depth and reach to properly address the quality of both the inputs (crime scene traces) and outputs (e.g., opinions in a report) of forensic science. The survey was developed around three themes: (1) fitness for purpose, (2) competences and (3) education & training. It targeted directors and senior managers, including quality managers, of forensic science laboratories/facilities. The survey was developed by the research team and disseminated with the cooperation of the International Forensic Strategic Alliance (IFSA) and six regional Networks: the American Society of Crime Laboratory Directors (ASCLD), the European Network of Forensic Science institutes (ENFSI), the Australian and New Zealand Forensic Executive Committee (ANZFEC) (formerly SMANZFL), Acadamia Iberoamericana de Criminalistica Estudios Forenses (AICEF), Asian Forensic Sciences Network (AFSN) and Southern Africa Regional Forensic Science Network (SARFS). What emerged for each of the three themes of the survey are areas of concern where the forensic science community should reconsider its approach to quality management if it is to have continuing value and relevance into the future. The results are evaluated and discussed. Briefly, the results include evidence of a lack of fitness for purpose of ISO17025 as a standard for the forensic science continuum, a lack of agreement on what forensic science is and poor levels of recognition of crime scene investigation, many competences, particularly cognitive competences, are not identified, monitored or assessed and the incentive to gain accreditation and maintain continuous improvement is intrinsic rather than customer driven.

A comparison of the natural and groomed fingermark lipid composition of different donors using GC/MS.

The lipid composition of natural fingermarks was studied and compared with the composition of groomed residue. Approximately 100 specimens were collected from 6 donors over three sessions (in October, December and July) and analysed using gas chromatography / mass spectrometry (GC/MS). The measured lipid content was generally lower and more variable in natural fingermarks than in groomed fingermarks. Some significant variability was noticed. Relative standard deviations were the highest between donors (generally above 100%) but were also relatively high within donor within a session (from 21% to 80%) and between sessions (from 34% to 126%). The fingermarks from one of the donors generally contained higher relative amounts of lipids in both groomed and natural residue compared to the others. All other fingermarks led to very variable amounts and did not allow classifying the other donors as constantly "good" or "poor" donors. Squalene was the major compound in all marks, particularly in groomed specimens. A correlation between squalene, cholesterol, myristic acid, palmitoleic acid, stearyl palmitoleate and pentadecanoic acid was highlighted. Oleic and stearic were also correlated together but generally more in natural than groomed marks. The obtained results may be particularly useful to better understand the detection mechanisms for techniques targeting lipids and to develop artificial fingermark secretions to further support the development of detection techniques.

Analysis of Stimulants in Sweat and Urine Using Disposable Pipette Extraction and Gas Chromatography Coupled to Mass Spectrometry in the Context of Doping Control.

Urine is initially collected from athletes to screen for the presence of illicit drugs. Sweat is an alternative sample matrix that provides advantages over urine including reduced opportunity for sample adulteration, longer detection-time window and non-invasive collection. Sweat is suitable for analysis of the parent drug and metabolites. In this study, a method was developed and validated to determine the presence of 13 amphetamine- and cocaine-related substances and their metabolites in sweat and urine using disposable pipette extraction (DPX) by gas chromatography coupled to mass spectrometry. The DPX extraction was performed using 0.1 M HCl and dichloromethane:isopropanol:ammonium hydroxide (78:20:2, v/v/v) followed by derivatization with N-methyl-N-(trimethylsilyl) trifluoroacetamide at 90°C for 20 min. DPX extraction efficiencies ranged between 65.0% and 96.0% in urine and 68.0% and 101.0% in sweat. Method accuracy was from 90.0% to 104.0% in urine and from 89.0% to 105.0% in sweat. Intra-assay precision in urine and in sweat were <15.6% and <17.8%, respectively, and inter-assay precision ranged from 4.70% to 15.3% in urine and from 4.05% to 15.4% in sweat. Calibration curves presented a correlation coefficient -0.99 for all analytes in both matrices. The validated method was applied to urine and sweat samples collected from 40 professional athletes who knowingly took one or more of the target illicit drugs. Thirteen of 40 athletes were positive for at least one drug. All the drugs detected in the urine were also detected in sweat samples indicating that sweat is a viable matrix for screening or confirmatory drug testing.

[The role of the cardiopulmonary exercise test and pulmonary rehabilitation in long COVID-19]. / Apports de l'exploration fonctionnelle à l'exercice et de la réhabilitation respiratoire dans le COVID long.

INTRODUCTION: Long COVID refers to persistent symptoms, lasting more than 4 weeks after acute SARS-CoV-2 infection, even though the infection itself has been successfully controlled and remedied. Patient complaints are diverse, and the underlying physiopathological mechanisms are not well understood. Dyspnea and muscle fatigue are among the most commonly reported symptoms. STATE OF THE ART: Cardiopulmonary exercise test (CPET) has been recognized as a useful tool in investigation of unexplained dyspnea. In patients with chronic lung disease, pulmonary rehabilitation is a program designed to counteract dyspnea, to increase exercise capacity and to improve quality of life. PERSPECTIVES: Publications on CPET and pulmonary rehabilitation are needed in order to deepen comprehension and enhance management of long-COVID-19. CONCLUSIONS: CPET reports have shown that symptoms persisting in the aftermath of acute SARS-CoV-2 infection may be related to deconditioning, a common occurrence after ICU stay, to cardiac dysautonomia subsequent to critical infections and, finally, to dysfunctional breathing subsequent to mild infections. These findings justify pulmonary rehabilitation, which has proven to be effective regardless of the severity of the initial infection, not only immediately after hospital discharge, but also at later points in time.

Monitoring for fentanyl within Australian supervised injecting facilities: Findings from feasibility testing of novel methods and collaborative workshops.

BACKGROUND: Australia is yet to see widespread fentanyl-contaminated heroin, despite the established presence of fentanyl in other countries. International mortality trends alongside a local cluster of fentanyl-related deaths prompted interest in developing methods to monitor for fentanyl and other potentially harmful novel psychoactive substances (NPS) in Australia. METHODS: We tested novel methods to monitor for fentanyl and other NPS. From 2017-2021, clients from supervised injecting facilities (SIFs) in Melbourne and Sydney, Australia, contributed urine screens (UDS) with BTNX Rapid Response™ fentanyl test strips (FTS) paired with surveys, and injecting equipment associated with opioid overdoses for laboratory analysis. A single site piloted drug checking using FTS with laboratory confirmation. Two workshops were conducted with SIF staff, content experts and people with lived experience to determine how results can inform practices within SIFs. RESULTS: Of the 911 UDS with FTS conducted, less than 1% (n=8) yielded positive results that were not explained by self-reported pharmaceutical fentanyl use, with two laboratory confirmed fentanyl positive results. Injecting equipment from 59 overdoses was tested and neither fentanyl nor other NPS were identified. Drug checking with FTS (n=34) indicated the presence of fentanyl on three tests. Two specimens were subsequently sent for laboratory testing and classified as false positives as the presence of fentanyl was not confirmed. Workshop participants (n=21) felt routine monitoring with FTS currently had limited value. A process for using pre-defined signals to trigger surveillance was developed. CONCLUSION: The high false positive rates with FTS, relative to the small number of positive results and potential for them to undermine confidence in FTS emphasised the need for confirmatory testing. The role of routine surveillance was unclear within the current low-fentanyl context, however, a process was developed to upscale testing should signals of increased fentanyl prevalence in the Australian heroin market emerge.