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Background In Japan, newborn and high‐risk screening for Fabry disease (FD), an inherited X‐linked disorder caused by GLA mutations, using dried blood spots was initiated in 2006. In newborn screening, 599,711 newborns were screened by December 2018, and 57 newborns from 54 families with 26 FD‐associated variants were detected. In high‐risk screening, 18,235 individuals who had symptoms and/or a family history of FD were screened by March 2019, and 236 individuals from 143 families with 101 FD‐associated variants were detected. Totally 3, 116 variants were detected; 41 of these were not registered in Fabry‐database.org or ClinVar and 33 were definitely novel. Herein, we report the clinical outcomes and discuss the pathogenicity of the 41 variants. Methods We traced nine newborns and 46 individuals with the 33 novel variants, and nine newborns and 10 individuals with eight other variants not registered in the FD database, and analyzed the information on symptoms, treatments, and outcomes. Results Thirty‐eight of the 46 individuals with the 33 novel variants showed symptoms and received enzyme‐replacement therapy and/or chaperone treatment. Conclusion Delayed diagnosis should be avoided in patients with FD. Our results will help clinicians diagnose FD and determine the appropriate treatment for patients with these variants. Nine newborns and 46 individuals with 33 novel variants, and nine newborns and 10 individuals with eight other variants not registered in the FD database were traced and the information on symptoms, treatments, and outcomes was analyzed. Thirty‐eight of 46 individuals with 33 novel variants had symptoms and received enzyme replacement therapy and/or chaperone treatment.

Background Virus neutralising antibodies in serum are considered key correlates of protection for vaccines and monoclonal antibodies against respiratory syncytial virus (RSV). RSM01 is a novel, highly-potent, half-life-extended and fully-human monoclonal antibody candidate targeting the RSV prefusion F protein. Currently in Phase 1 development, RSM01 is primarily being developed to potentially provide an effective and affordable RSV prevention strategy in low- and middle-income countries. To evaluate the ability of dried blood collection to generate data sets and conclusions comparable to serum collection, we compared pharmacokinetics (PK) of RSM01, immunogenicity, and virus neutralisation for dried capillary blood samples with serum samples. Methods RSM01 PK, anti-drug antibodies (ADA), and RSV-neutralising antibodies from the Phase 1 trial were analyzed and compared between matched serum and dried blood samples. Deming regression analysis was performed using baseline-corrected values to evaluate correlation between measurements in liquid serum versus dried blood. Results The analysis showed good correlation (R 2  > 0.95) between individual RSM01 concentrations measured in both serum and capillary blood. Analysis of RSM01 PK parameters in capillary blood yielded equivalent conclusions as from serum. A strong correlation (R 2  > 0.95) was observed between RSV neutralising activity measured in both serum and capillary blood. In addition, RSV neutralising activity was correlated with RSM01 concentrations in both serum and capillary blood data sets. For ADA, individual sample results had 96% agreement (290/302) and overall participant ADA status had 93% agreement (52/56). Conclusions Both RSM01 concentrations and RSV neutralising activity showed a strong correlation between the serum and blood measurements. ADA measurements also had an agreement of > 90% for individual samples and overall participant status. Our results demonstrate that dried blood is a suitable specimen type for collection and evaluation in the RSM01 clinical development program and shows promise as a useful approach to reduce patient burden in clinical trials, particularly for infants in low- and middle-income countries. Trial Registration Clinicaltrials.gov NCT05118386 November 12, 2021.

Background and Objective Phenotyping cocktails use a combination of cytochrome P450 (CYP)-specific probe drugs to simultaneously assess the activity of different CYP isoforms. To improve the clinical applicability of CYP phenotyping, the main objectives of this study were to develop a new cocktail based on probe drugs that are widely used in clinical practice and to test whether alternative sampling methods such as collection of dried blood spots (DBS) or saliva could be used to simplify the sampling process. Methods In a randomized crossover study, a new combination of commercially available probe drugs (the Basel cocktail) was tested for simultaneous phenotyping of CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP3A4. Sixteen subjects received low doses of caffeine, efavirenz, losartan, omeprazole, metoprolol and midazolam in different combinations. All subjects were genotyped, and full pharmacokinetic profiles of the probe drugs and their main metabolites were determined in plasma, dried blood spots and saliva samples. Results The Basel cocktail was well tolerated, and bioequivalence tests showed no evidence of mutual interactions between the probe drugs. In plasma, single timepoint metabolic ratios at 2 h (for CYP2C19 and CYP3A4) or at 8 h (for the other isoforms) after dosing showed high correlations with corresponding area under the concentration–time curve (AUC) ratios (AUC 0–24h parent /AUC 0–24h metabolite ) and are proposed as simple phenotyping metrics. Metabolic ratios in dried blood spots (for CYP1A2 and CYP2C19) or in saliva samples (for CYP1A2) were comparable to plasma ratios and offer the option of minimally invasive or non-invasive phenotyping of these isoforms. Conclusions This new combination of phenotyping probe drugs can be used without mutual interactions. The proposed sampling timepoints have the potential to facilitate clinical application of phenotyping but require further validation in conditions of altered CYP activity. The use of DBS or saliva samples seems feasible for phenotyping of the selected CYP isoforms.

Dried blood spot (DBS) collection offers various advantages over conventional methods of blood collection, especially when collecting and transporting samples for a serosurvey. Yet use of DBS requires additional processing steps in the laboratory that can add to variability in results. Blood collection using dried blood spots (DBS) provides an easier alternative to venipuncture for sample collection, transport, and storage but requires additional processing that can cause variability in results. Whole-blood samples spotted on four DBS devices and respective paired serum samples were tested for antimeasles and antirubella IgG antibody concentrations by enzyme immunoassay. Elution protocols for DBS devices were optimized for comparability relative to serum samples using 12 adult volunteers. Stability of DBS collected on HemaSpot HF was assessed under various temperature conditions (+4, 22 to 25, and 45°C) at six time points (0, 7, 15, 30, 60, and 90 days) in a controlled laboratory setting using six adult volunteers. Devices were shipped and stored for 30 days at four settings with variable temperature and humidity conditions to assess the impact on antibody concentrations. Three DBS devices demonstrated comparable antibody concentrations with paired sera following optimization. Antibodies recovered from DBS were stable for at least 90 days at 4°C and for 30 days at ambient temperature (22 to 25°C) using the HemaSpot HF device. A drastic decline in antibody concentrations was observed at 45°C, resulting in quantitative and qualitative discrepancies by day 7. HemaSpot HF devices shipped to field sites and stored at ambient temperature and humidity resulted in quantitative, but not qualitative, variability. Measurement of antimeasles and antirubella IgG antibodies with DBS devices is an accurate alternative to testing serum, provided elution protocols are optimized. Stability of HemaSpot HF devices at ambient temperature enables broader use in surveys when serum processing and cold storage are not feasible. IMPORTANCE Dried blood spot (DBS) collection offers various advantages over conventional methods of blood collection, especially when collecting and transporting samples for a serosurvey. Yet use of DBS requires additional processing steps in the laboratory that can add to variability in results. We optimized a protocol to elute IgG antibodies against measles and rubella viruses in four DBS devices, demonstrating high concordance with paired venous sera for most devices. Extensive stability studies with various temperature and storage conditions in the laboratory and in the field were conducted using HemaSpot HF DBS devices prior to its use in one of the largest community-based measles and rubella serological surveys in the world.

Dexmedetomidine is an imidazole derivative, with high affinity for α2 adrenergic receptors, used for sedation, analgesia and adjuvant anaesthesia. In this study, an analytical method for the quantification of dexmedetomidine in dried blood spots was developed, validated and applied. The drug was extracted from dried blood spot by liquid extraction; the separation was carried out by ultra high-resolution liquid chromatography in reverse phase coupled to tandem mass spectrometry method. An X Select cyano 5 μm HSS column (2.1 X 150 mm, Waters) and a mobile phase composed of 0.1% formic acid: acetonitrile [50:50 v/v], were used. The test was linear over the concentration range of 50 to 2000 pg/mL. The coefficients of variation for the intra and interday trials were less than 15%. The drug was stable under the conditions tested. The method was successfully applied for the quantification of 6 patients, aged 0 to 2 years, with classification ASA I, who underwent ambulatory surgeries, receiving a dose of 1 μg/Kg dexmedetomidine IV. The drug concentrations in the different sampling times were in the range of 76 to 868 pg/mL.

Dried blood spot (DBS) samples can be used for the detection of severe acute respiratory syndrome coronavirus 2 spike antibodies. DBS sampling is comparable to matched serum samples with a relative 98.1% sensitivity and 100% specificity. Thus, DBS sampling offers an alternative for population-wide serologic testing in the coronavirus pandemic.

This article discusses dried blood spot (DBS) sampling in therapeutic drug monitoring (TDM). The most important advantages of DBS sampling in TDM are the minimally invasive procedure of a finger prick (home sampling), the small volume (children), and the stability of the analyte. Many assays in DBS have been reported in the literature over the previous 5 years. These assays and their analytical techniques are reviewed here. Factors that may influence the accuracy and reproducibility of DBS methods are also discussed. Important issues are the correlation with plasma/serum concentrations and the influence of hematocrit on spot size and recovery. The different substrate materials are considered. DBS sampling can be a valid alternative to conventional venous sampling. However, patient correlation studies are indispensable to prove this. Promising developments are dried plasma spots using membrane and hematocrit correction using the potassium concentration.

Accurate surveillance of coronavirus disease 2019 (COVID-19) incidence requires large-scale testing of the population. Current testing methods require in-person collection of biospecimens by a healthcare worker, limiting access of individuals who do not have access to testing facilities while placing both patients and healthcare workers at risk of exposure to infection. We report the development and validation of a at-home finger-prick dried blood spot collection kit and an analysis method. We demonstrated 100% sensitivity and specificity using at-home collected specimens across the US. Such methods may facilitate the conduct of unbiased serosurveys within hard to reach populations and help reduce the sample collection burden of serological testing on both health care systems and individuals alike.

Several external and internal factors can affect the performance and variability of Hemoglobin concentration [Hb] measurements using HemoCue, and documentation on the contribution of different sources of [Hb] variation is limited. We used an experimental repeated measurements design with nine randomly selected participants, three HemoCue devices, and three trained field workers. HemoCue measurements for all samples were repeated three times. The [Hb] measurement system considers four sources of error: 1) HemoCue devices, 2) field workers, 3) between individuals, and 4) within individuals. A concordance analysis was used to assess accuracy and precision, and a linear mixed model was used to estimate mean differences (bias) from blood specimens, anticoagulants, and to estimate the contribution of the 4 sources of error to [Hb] measurements. Positive mean [Hb] differences were found: 1.34 g/dL for capillary drops, 0.81 g/dL for pooled capillary blood samples, 0.756 g/dL for venous blood stored with EDTA, and 0.911 g/dL for venous blood stored with heparin. The mean [Hb] difference for venous blood with EDTA was used as a correction factor for all results measured using a HemoCue. After adjustment, capillary drops showed a mean difference of 0.585 g/dL, and pooled capillary samples were not significantly different. The individual variability was 95.8% of total variance, HemoCue devices contributed 2.1% of measurement error, field staff contributed 0.4%, and the residual was 1.7%. The HemoCue [Hb] measurement system is reliable in controlled environments, with a small measurement error of 4.2%.

The added value of dried blood spot (DBS) samples complementing the information obtained from commonly routine doping control matrices is continuously increasing in sports drug testing. In this project, a robotic-assisted non-destructive hematocrit measurement from dried blood spots by near-infrared spectroscopy followed by a fully automated sample preparation including strong cation exchange solid-phase extraction and evaporation enabled the detection of 46 lower molecular mass (< 2 kDa) peptide and non-peptide drugs and drug candidates by means of LC-HRMS. The target analytes included, amongst others, agonists of the gonadotropin-releasing hormone receptor, the ghrelin receptor, the human growth hormone receptor, and the antidiuretic hormone receptor. Furthermore, several glycine derivatives of growth hormone–releasing peptides (GHRPs), arguably designed to undermine current anti-doping testing approaches, were implemented to the presented detection method. The initial testing assay was validated according to the World Anti-Doping Agency guidelines with estimated LODs between 0.5 and 20 ng/mL. As a proof of concept, authentic post-administration specimens containing GHRP-2 and GHRP-6 were successfully analyzed. Furthermore, DBS obtained from a sampling device operating with microneedles for blood collection from the upper arm were analyzed and the matrix was cross-validated for selected parameters. The introduction of the hematocrit measurement method can be of great value for doping analysis as it allows for quantitative DBS applications by managing the well-recognized “hematocrit effect.”