| 1. |
- Börve, Alexander, et al.
(författare)
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Smartphone Teledermoscopy Referrals: A Novel Process for Improved Triage of Skin Cancer Patients.
- 2015
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Ingår i: Acta dermato-venereologica. - : Medical Journals Sweden AB. - 1651-2057 .- 0001-5555. ; 95:2, s. 186-190
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Tidskriftsartikel (refereegranskat)abstract
- In this open, controlled, multicentre and prospective observational study, smartphone teledermoscopy referrals were sent from 20 primary healthcare centres to 2 dermatology departments for triage of skin lesions of concern using a smartphone application and a compatible digital dermoscope. The outcome for 816 patients referred via smartphone teledermoscopy was compared with 746 patients referred via the traditional paper-based system. When surgical treatment was required, the waiting time was significantly shorter using teledermoscopy for patients with melanoma, melanoma in situ, squamous cell carcinoma, squamous cell carcinoma in situ and basal cell carcinoma. Triage decisions were also more reliable with teledermoscopy and over 40% of the teledermoscopy patients could potentially have avoided face-to-face visits. Only 4 teledermoscopy referrals (0.4%) had to be excluded due to poor image quality. Smartphone teledermoscopy referrals allow for faster and more efficient management of patients with skin cancer as compared to traditional paper referrals.
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| 2. |
- Dahlén Gyllencreutz, Johan, et al.
(författare)
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Diagnostic agreement and interobserver concordance with teledermoscopy referrals
- 2017
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Ingår i: Journal of the European Academy of Dermatology and Venereology. - : Wiley. - 0926-9959 .- 1468-3083. ; 31:5, s. 898-903
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundMalignant melanoma and non-melanoma skin cancers are among the fastest increasing malignancies in many countries. With the help of new tools, such as teledermoscopy referrals between primary health care and dermatology clinics, the management of these patients could be made more efficient. ObjectiveTo evaluate the diagnostic agreement and interobserver concordance achieved when assessing referrals sent through a mobile teledermoscopic referral system as compared to referrals sent via the current paper-based system without images. MethodsThe referral information from 80 teledermoscopy referrals and 77 paper referrals were evaluated by six Swedish dermatologists. They were asked to answer questions about the probable diagnosis, the priority, and a management decision. ResultsTeledermoscopy generally resulted in higher diagnostic agreement, better triaging and more malignant tumours being booked directly to surgery. The largest difference between the referral methods was seen for invasive melanomas. Referrals for benign lesions were significantly more often correctly resent to primary health care with teledermoscopy. However, referrals for cases of melanoma in situ were also incorrectly resent five times. The interobserver concordance was moderate with both methods. ConclusionBy adding clinical and dermoscopic images to referrals, the triage process for both benign and dangerous skin tumours can be improved. With teledermoscopy, patients with melanoma especially can receive treatment more swiftly.
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| 3. |
- Dahlén, Johan, 1969-
(författare)
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Capillary electrophoresis and multivariate calibration in the analysis of natural waters
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this work was to explore the applicability of capillary zone electrophoresis (CZE) and multivariate partial least squares (PLS) regression in the analysis of organic compounds and inorganic ions in natural waters. A new CZE application was developed to analyze low molecular weight (LMW) organic acids. A UV-absorbing co-ion (trimellitic acid) was used to allow indirect detection, and a cationic electrolyte additive (Ca2+) was employed to optimize separation selectivity. The method was applied to determine LMW organic acids in surface waters and precipitation samples. The use of CZE to characterize humic substances was evaluated. Small, but significant, differences in electrophoretic mobility were observed between the analyzed humic samples. A new CZE method using on-capillary complexation with 2,4,6-tri(2'-pyridyl)-1,3,5-triazine (TPTZ) was developed to analyze FE(II) in natural waters. The procedure is easy to use and requires a minimum of sample pretreatment. Multivariate calibration by means of PLS regression, using spectroscopic data in the UV/VIS range, was applied to calculate models to estimate the molecular weight of isolated aquatic fulvic acids. A combination of PLS and UV/VIS spectroscopy was also employed to establish models to predict levels of nitrate and non-purgeable organic carbon (NPOC), as well as other common parameters of groundwater quality. In conclusion, the examined methods are highly useful for analyzing natural waters-CZE due to its extreme flexibility, and PLS due to its ability to extract information from complex data matrices.
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| 4. |
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| 5. |
- Gustafsson, Linnea, et al.
(författare)
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Characteristics, survival and neurological outcome in out-of-hospital cardiac arrest in young adults in Sweden : A nationwide study.
- 2023
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Ingår i: Resuscitation Plus. - 2666-5204. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- AIM: The aim of this study was to present a comprehensive overview of out-of-hospital cardiac arrests (OHCA) in young adults.METHODS: The data set analyzed included all cases of OHCA from 1990 to 2020 in the age-range 16-49 years in the Swedish Registry of Cardiopulmonary Resuscitation (SRCR). OHCA between 2010 and 2020 were analyzed in more detail. Clinical characteristics, survival, neurological outcomes, and long-time trends in survival were studied. Logistic regression was used to study 30-days survival, neurological outcomes and Utstein determinants of survival.RESULTS: Trends were assessed in 11,180 cases. The annual increase in 30-days survival during 1990-2020 was 5.9% with no decline in neurological function among survivors. Odds ratio (OR) for heart disease as the cause was 0.55 (95% CI 0.44 to 0.67) in 2017-2020 compared to 1990-1993. Corresponding ORs for overdoses and suicide attempts were 1.61 (95% CI 1.23-2.13) and 2.06 (95% CI 1.48-2.94), respectively. Exercise related OHCA was noted in roughly 5%. OR for bystander CPR in 2017-2020 vs 1990-1993 was 3.11 (95% CI 2.57 to 3.78); in 2020 88 % received bystander CPR. EMS response time increased from 6 to 10 minutes.CONCLUSION: Survival has increased 6% annually, resulting in a three-fold increase over 30 years, with stable neurological outcome. EMS response time increased with 66% but the majority now receive bystander CPR. Cardiac arrest due to overdoses and suicide attempts are increasing.
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| 6. |
- Höjer Holmgren, Karin
(författare)
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Route attribution of chemical warfare agents : Retrospective classification of unknown threat samples
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Although chemical warfare agents (CWAs) are prohibited under international law, there have been numerous crimes that violates the 1997 Chemical Weapons Convention (CWC) during the last decade, especially in the civil war in Syria where sarin, mustard gas and chlorine have all been used. CWAs have also been used in political assassinations and attempts thereof. In such situations, it is important to identify the deployed CWA and to find information on how it was produced, as this information is potentially of considerable value for any ensuing judicial process. The development and use of advanced analytical methods and multivariate data analysis methods are required to produce this kind of robust forensic evidence and intelligence. This thesis describes conducted research that aims at retrospectively tracing the synthesis methods applied in the production of CWAs. In three studies, methods for the determination of the employed synthetic route have been assessed. The relative distribution of the impurities gave a unique profile – in effect a “chemical fingerprint” - that was used for retrospective determination of the production method of a specific CWA. The study in paper I was done on the nerve agent Russian VX, S-[2-(diethylamino)ethyl] O-isobutyl metylphosphonothioate, while paper II and III focused on sulfur mustard, bis(2-chloroethyl)sulfide. This thesis discusses the study set up, the choice of analytical methods, methods for data processing and the manner in which classification methods have been employed. The studies shows that the classification models could clearly separate the six production routes used in paper I and the five routes used in paper II. In paper III, a novel non-targeted approach in combination with high-resolution mass spectrometry allowed detection of additional low-concentration compounds in the sulfur mustard samples. This method produced data with sufficient information for classifying samples according to the production method of the precursor thiodiglycol (TDG). The performance of the classification models was successfully validated with test set samples. All test set samples were correctly assigned in paper I and paper II. The classification of TDG in paper III was more demanding, but still as much as 56-89% of the test set samples were correctly assigned. In addition to the established classification models, compounds with importance for route differentiation were identified, which gave enhanced information on the chemicals formed during the employed synthesis conditions. Their stability has also been investigated, and the results showed that the majority of the chemical attribution signatures (CASs) were stable at room temperature. The fourth study in this thesis (paper IV) is an international inter-laboratory comparison jointly conducted by eight defence research laboratories based in Europe, North America, Asia and Australia respectively. All participating laboratories analysed the same samples prepared at the Swedish Defence Research Agency (FOI). The impurity profiles in nerve agent precursor metylphosphonyl dichloride samples were compared by a gas chromatography mass spectrometry (GC/MS) method using a retention index to facilitate data comparison. Retention indices of 16 CASs were calculated and compared, and this showed that the between-laboratory variation was low. This work is a first step towards a harmonised laboratory method for the profiling of CWA samples. The methods developed in this thesis will enhance accurate source attribution of CWAs and could potentially be used when alleged use of a CWA is being investigated.
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| 7. |
- Paoli, John, 1975, et al.
(författare)
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Response to the letter by Leitch et al.
- 2015
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Ingår i: Acta dermato-venereologica. - 1651-2057. ; 95:7, s. 870-1
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 8. |
- Rautio, Tobias, et al.
(författare)
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An improved procedure for the synthesis of fourteen 4-OH and 3-MeO-4OH metabolites of fentanyl analogues from two intermediates on multi-gram scale
- 2022
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Ingår i: Synthetic Communications. - : Taylor & Francis Inc. - 0039-7911 .- 1532-2432. ; 52:3, s. 392-401
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Tidskriftsartikel (refereegranskat)abstract
- Fentanyl analogues have appeared on the recreational drug market during the last ten years and caused many fatal overdoses around the world due to their high potencies. Their metabolites are of great interest for toxicology, metabolism and identification studies. According to the literature, fentanyl analogues with similar structures have similar metabolism profile. Therefore, a synthetic route that enables synthesis of the corresponding metabolites for several fentanyl analogues would be valuable. Fentanyl analogue metabolites are often polar and tailing on silica gel. Hence, the purification of these substances could be challengeable. In this work, a general synthetic route was developed and described for the multi-gram scale synthesis of 14 potential metabolites of seven fentanyl analogues. The synthetic route is concise and optimized, does not require any use of silica gel purification and is therefore convenient for large-scale synthesis. The overall yields of the metabolites were in the range of 25-57%.
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| 9. |
- Rautio, Tobias, et al.
(författare)
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In vitro metabolite identification of acetylbenzylfentanyl, benzoylbenzylfentanyl, 3-fluoro-methoxyacetylfentanyl, and 3-phenylpropanoylfentanyl using LC-QTOF-HRMS together with synthesized references
- 2023
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Ingår i: Drug Testing and Analysis. - : WILEY. - 1942-7603 .- 1942-7611. ; 15:7, s. 711-729
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Tidskriftsartikel (refereegranskat)abstract
- Acetylbenzylfentanyl, benzoylbenzylfentanyl, 3-fluoro-methoxyacetylfentanyl, and 3-phenylpropanoylfentanyl are fentanyl analogs that have been reported to the European Monitoring Centre for Drugs and Drug Addiction in recent years. The aim of this study was to identify metabolic pathways and potential biomarker metabolites of these fentanyl analogs. The compounds were incubated (5 mu M) with cryopreserved hepatocytes for up to 5 h in vitro. Metabolites were analyzed with liquid chromatography-quadrupole time of flight-high-resolution mass spectrometry (LC-QTOF-HRMS). The experiments showed that acetylbenzylfentanyl, benzoylbenzylfentanyl, and 3-phenylpropanoylfentanyl were mainly metabolized through N-dealkylation (forming nor-metabolites) and 3-fluoro-methoxyacetylfentanyl mainly through demethylation. Other observed metabolites were formed by mono-/dihydroxylation, dihydrodiol formation, demethylation, dehydrogenation, amide hydrolysis, and/or glucuronidation. The experiments showed that a large number of metabolites of 3-phenylpropanoylfentanyl were formed. The exact position of hydroxy groups in formed monohydroxy metabolites could not be established solely based upon recorded MSMS spectra of hepatocyte samples. Therefore, potential monohydroxy metabolites of 3-phenylpropanoylfentanyl, with the hydroxy group in different positions, were synthesized and analyzed together with the hepatocyte samples. This approach could reveal that the beta position of the phenylpropanoyl moiety was highly favored; beta-OH-phenylpropanoylfentanyl was the most abundant metabolite after the nor-metabolite. Both metabolites have the potential to serve as biomarkers for 3-phenylpropanoylfentanyl. The nor-metabolites of acetylbenzylfentanyl, benzoylbenzylfentanyl, and 3-fluoro-methoxyacetylfentanyl do also seem to be suitable biomarker metabolites, as do the demethylated metabolite of 3-fluoro-methoxyacetylfentanyl. Identified metabolic pathways and formed metabolites were in agreement with findings in previous studies of similar fentanyl analogs.
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| 10. |
- Tärnqvist, J., et al.
(författare)
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On-scene and final assessments and their interrelationship among patients who use the EMS on multiple occasions
- 2017
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Ingår i: Prehospital and Disaster Medicine. - : Cambridge University Press. - 1049-023X .- 1945-1938. ; 32:5, s. 528-535
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The use of Emergency Medical Services (EMS) is increasing. A number of patients call repeatedly for EMS. Early studies of frequent callers show that they form a heterogenous group. Problem: There is a lack of research on frequent EMS callers. There is furthermore a lack of knowledge about characteristics and the prehospital assessment of the patients who call for EMS on several occasions. Finally, there is a general lack of knowledge with regard to the association between the prehospital assessment by health care providers and the final diagnosis. Method: Patients in Skaraborg in Western Sweden, who used the EMS at least four times in 2014, were included, excluding transport between hospitals. Information on the prehospital assessment on-scene and the final diagnosis was collected from the EMS and hospital case records. Results: In all, 339 individual patients who used the EMS on 1,855 occasions were included, accounting for five percent of all missions. Fifty percent were women. The age range was 10-98 years, but more than 50.0% were in the age range of 70-89 years. The most common emergency signs and symptoms (ESS) codes on the scene were dyspnea, chest pain, and abdominal pain. The most common final diagnosis was chronic obstructive pulmonary disease (eight percent). Thirteen percent of all cases had a final diagnosis defined as a potentially life-threatening condition. Among these, 22.0% of prehospital assessments were retrospectively judged as potentially inappropriate. Forty-nine percent had a defined final diagnosis not fulfilling the criteria for a potentially life-threatening condition. Among these cases, 30.0% of prehospital assessments were retrospectively judged as potentially inappropriate. Conclusion:: Among patients who used EMS on multiple occasions, the most common symptoms on-scene were dyspnea, chest pain, and abdominal pain. The most common final diagnosis was chronic obstructive pulmonary disease. In 13.0%, the final diagnosis of a potentially life-threatening condition was indicated. In a minority of these cases, the assessment on-scene was judged as potentially inappropriate.
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| 11. |
- Wallgren, Jakob, 1987-
(författare)
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An insight into the metabolism of New Psychoactive Substances : Structural elucidation of urinary metabolites of synthetic cannabinoids and fentanyl analogues using synthesized reference standards
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- New Psychoactive Substances (NPS) is an umbrella term covering hundreds of substances across different drug groups. Many of these substances were originally developed for therapeutic use but have later appeared on the recreational drug market. The use of NPS has been associated with many outbreaks leading to hospitalizations and has been implicated in numerous fatalities worldwide. To be able to analytically detect drugs in a forensic setting is vital in the fight against the abuse of NPS. One of the most notable challenges in detection of NPS is the identification of major urinary metabolites for use as biomarkers. Furthermore, given the lack of reference standards in most metabolism studies, the major urinary metabolites can often only be tentatively determined.This thesis describes the synthesis and analysis of potential metabolites used to identify the exact structures of major metabolites of the synthetic cannabinoid AKB-48, fentanyl and five fentanyl analogues in authentic human urine samples and/or hepatocyte incubations. Synthetic targets were chosen based on previous metabolism studies by our research group. Subsequently, synthetic routes were developed to produce numerous potential metabolites across the studied NPS. The synthesized reference standards were analyzed by LC-QTOF-MS alongside hepatocyte drug incubations and authentic human urine samples. Comparison of the resulting analytical data was used to determine the exact structures of many metabolites. This includes urinary metabolites of AKB-48 with a single hydroxyl group situated on a secondary carbon of the adamantane moiety, or position 3 or 5 of the pentyl side chain. For the studied fentanyls, the β-OH and the 4’-OH metabolites were abundant metabolites identified in hepatocyte incubations while the 4’-OH, 4’-OH-3’-OMe and 3’,4’-diOH were the favored metabolic motifs among the metabolites identified in urine.Additionally, a concise synthetic route to produce synthetic cannabinoid metabolites with the 4-OH-5F pentyl side chain motif was developed and demonstrated for four synthetic cannabinoids. These findings and the developed synthetic routes can be used to provide forensic toxicology laboratories with urinary biomarkers for drug detection. Moreover, the synthesized reference standards of major metabolites can be studied to better understand the toxicity of their parent drugs.
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| 12. |
- Wallgren, Jakob, 1987-, et al.
(författare)
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Structure elucidation of urinary metabolites of fentanyl and five fentanyl analogues using LC-QTOF-MS, hepatocyte incubations and synthesized reference standards
- 2020
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Ingår i: Journal of Analytical Toxicology. - : Oxford University Press. - 0146-4760 .- 1945-2403. ; 44:9
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Tidskriftsartikel (refereegranskat)abstract
- Fentanyl analogues constitute a particularly dangerous group of new psychoactive compounds responsible for many deaths around the world. Little is known about their metabolism and studies utilizing LC-QTOF-MS analysis of hepatocyte incubations and/or authentic urine samples does not allow for determination of the exact metabolite structures, especially when it comes to hydroxylated metabolites. In this study seven motifs (2-, 3-, 4- and β-OH as well as 3,4-diOH, 4-OH-3-OMe and 3-OH-4-OMe) of fentanyl and five fentanyl analogues, acetylfentanyl, acrylfentanyl, cyclopropylfentanyl, isobutyrylfentanyl and 4F-isobutyrylfentanyl were synthesized. The reference standards were analyzed by LC-QTOF-MS, which enabled identification of the major metabolites formed in hepatocyte incubations of the studied fentanyls. By comparison with our previous data sets, major urinary metabolites could tentatively be identified. For all analogues, β-OH, 4-OH and 4-OH-3-OMe were identified after hepatocyte incubation. β-OH was the major hydroxylated metabolite for all studied fentanyls, except for acetylfentanyl where 4-OH was more abundant. However, the ratio 4-OH/β-OH was higher in urine samples than in hepatocyte incubations for all studied fentanyls. Also, 3-OH-4-OMe was not detected in any hepatocyte samples, indicating a clear preference for the 4-OH-3-OMe, which was also found to be more abundant in urine compared to hepatocytes. The patterns appear to be consistent across all studied fentanyls and could serve as a starting point in the development of methods and synthesis of reference standards of novel fentanyl analogues where nothing is known about the metabolism.
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