Feasibility of newborn screening for pyridoxine-dependent epilepsy.

Background: Pyridoxine-dependent epilepsy (PDE-ALDH7A1) is a developmental epileptic encephalopathy historically characterized by seizures that are resistant to antiseizure medications. Treatment with pyridoxine and lysine reduction therapies are associated with seizure control and improved developmental outcomes. In rare circumstances, patients have died prior to diagnosis and treatment with pyridoxine, and many patients are diagnosed after six months of age when lysine reduction therapies have limited efficacy.

Thoracic manifestations of rheumatic disease: a radiologist's view.

With varying prevalence and manifestations depending on the underlying disease, thoracic involvement is one of the major factors determining morbidity and mortality in patients with rheumatic diseases (RDs). The most frequent pulmonary complication is interstitial lung disease (ILD), but other thoracic manifestations can also be present. Often, the only way to depict these extra-articular manifestations of disease is through imaging.

Testing for normality: a user's (cautionary) guide.

The normality assumption postulates that empirical data derives from a normal (Gaussian) population. It is a pillar of inferential statistics that enables the theorization of probability functions and the computation of p-values thereof. The breach of this assumption may not impose a formal mathematical constraint on the computation of inferential outputs (e.

Assessing Direct Oral Anticoagulants in the Clinical Laboratory.

Direct oral anticoagulants (DOACs) have significant advantages over vitamin K antagonists including lack of need for routine laboratory monitoring. However, assessment of DOAC effect and concentration may be important to guide clinical management including need for DOAC reversal, particularly in acute or emergent situations. In this manuscript, the authors describe tests to screen for DOAC presence and tests that have demonstrated equivalence to gold standard testing for quantifying DOAC exposure.

International Council for Standardization in Haematology (ICSH) recommendations for the performance and interpretation of activated partial thromboplastin time and prothrombin time mixing tests.

This guidance document has been prepared on behalf of the International Council for Standardization in Haematology (ICSH). The aim of the document is to provide guidance and recommendations for the performance and interpretation of activated partial thromboplastin time (APTT) and prothrombin time (PT) plasma mixing tests in clinical laboratories in all regions of the world. The following areas are included in this document: preanalytical, analytical, postanalytical, and quality assurance considerations as they relate to the proper performance and interpretation of plasma mixing tests.

Algorithm for Rapid Exclusion of Clinically Relevant Plasma Levels of Direct Oral Anticoagulants in Patients Using the DOAC Dipstick: An Expert Consensus Paper.

Background:  With the widespread use of direct oral anticoagulants (DOACs), there is an urgent need for a rapid assay to exclude clinically relevant plasma levels. Accurate and rapid determination of DOAC levels would guide medical decision-making to (1) determine the potential contribution of the DOAC to spontaneous or trauma-induced hemorrhage; (2) identify appropriate candidates for reversal, or (3) optimize the timing of urgent surgery or intervention.

Methods And Results:  The DOAC Dipstick test uses a disposable strip to identify factor Xa- or thrombin inhibitors in a urine sample.

PFA-100 System: A New Method for Assessment of Platelet Dysfunction.

This is a celebratory reprint of a historical paper published in STH in 1998. The original Abstract follows.The PFA-100 system is a platelet function analyzer designed to measure platelet-related primary hemostasis.

International Council for Standardization in Haematology Field Study Evaluating Optimal Interpretation Methods for Activated Partial Thromboplastin Time and Prothrombin Time Mixing Studies.

Context.—: The prothrombin time (PT) and activated partial thromboplastin time (APTT) are screening tests used to detect congenital or acquired bleeding disorders. An unexpected PT and/or APTT prolongation is often evaluated using a mixing test with normal plasma.

International Council for Standardization in Haematology Guidance for New Lot Verification of Coagulation Reagents, Calibrators, and Controls.

The clinical laboratory uses commercial products with limited shelf life or certain expiry dates requiring frequent lot changes. Prior to implementation for clinical use, laboratories should determine the performance of the new reagent lot to ensure that there is no significant shift in reagent performance or reporting of patient data. This guideline has been written on behalf of the International Council for Standardization in Haematology (ICSH) to provide the framework and provisional guidance for clinical laboratories for evaluating and verifying the performance of new lot reagents used for coagulation testing.

Effects of tableting process parameters and powder lubrication levels on tablet surface temperature and moisture content.

Punch sticking is a recurrent problem during the pharmaceutical tableting process. Powder moisture content plays a key role in the buildup of sticking; it evaporates due to increased tablet temperature, accumulates at the punch-tablet interface, and causes sticking through capillary force. This study investigated the effects of compaction pressure (CP), compaction speed (CS), and lubrication level (magnesium stearate (MgSt) ratio) on tablet surface temperature (TST) and tablet surface moisture content (TSMC).

Wafer-scale detachable monocrystalline germanium nanomembranes for the growth of III-V materials and substrate reuse.

Germanium (Ge) is increasingly used as a substrate for high-performance optoelectronics, photovoltaics, and electronic devices. These devices are usually grown on thick and rigid Ge substrates manufactured by classical wafering techniques. Nanomembranes (NMs) provide an alternative to this approach while offering wafer-scale lateral dimensions, weight reduction, waste limitation, and cost effectiveness.

Moisture Behavior of Pharmaceutical Powder during the Tableting Process.

The moisture content of pharmaceutical powder is a key parameter contributing to tablet sticking during the tableting process. This study investigates powder moisture behavior during the compaction phase of the tableting process. Finite element analysis software COMSOL Multiphysics 5.

Post-analytical Issues in Hemostasis and Thrombosis Testing: An Update.

There are typically three phases identified as contributing to the total testing process. The preanalytical phase starts with the clinician and the patient, when laboratory testing is being considered. This phase also includes decisions about which tests to order (or not), patient identification, blood collection, blood transport, sample processing, and storage to name a few.

Preparing Surrogate Abnormal Quality Control Samples for Platelet Function Studies and Viscoelastic Testing.

In the United States, published options for clinical laboratories to perform quality control (QC) procedures less stringent than the regulatory requirements (Clinical and Laboratory Improvement Act, CLIA) based on risk assessment, although the laboratory must perform to manufacturer's minimum requirements. The US requirements for internal quality control requires at least two levels of control material every 24 h of patient testing. For some coagulation testing, the recommended quality control may be a normal sample or commercial controls that do not address all reporting components of the test.

Ecarin-Based Methods for Measuring Thrombin Inhibitors.

Ecarin is a venom from the saw-scaled viper, Echis carinatus, which catalyzes prothrombin into meizothrombin. This venom is used in several hemostasis laboratory assays, including ecarin clotting time (ECT) and ecarin chromogenic assays (ECA). The use of these ecarin-based assays was first implemented as a tool for monitoring the infusion of a direct thrombin inhibitor, hirudin.

An Acute Need Inspiration: Autoneutralization of Lupus Anticoagulants in Affected Prothrombin Times (PT) and Activated Partial Thromboplastin Times (APTT).

Lupus anticoagulants are antibodies directed to phospholipids (PL) and in particular represent an in vitro phenomenon where these antibodies bind to PL in coagulation reagents creating an artificial prolongation of the activated partial thromboplastin time (APTT) and sometimes also prothrombin time (PT) clotting times. Prolongation of LA-induced clotting times is typically not associated with bleeding risk. However, the degree of prolongation may cause some trepidation for clinicians that will be performing delicate surgeries or those with high bleeding risks, so a mechanism to alleviate their anxiety may be prudent.

Protocols for D-Dimer Measurements for Aid to Diagnosis or Exclusion of Venous Thromboembolism.

Measuring D-dimer is commonly used as a surrogate to indicate a clot-forming process, with subsequent lysis. This test has two primary intended uses: (1) as aid to diagnosis of various conditions and (2) venous thromboembolism (VTE) exclusion. If the manufacturer cites a VTE exclusion claim, the D-dimer test must only be used in evaluating patients with a non-high or unlikely pretest probability for pulmonary embolism and deep vein thrombosis.

Ultracentrifugation for Coagulation Testing.

Lipemia is known to potentially affect coagulation testing. It may be detected with newer coagulation analyzers that are validated to assess hemolysis, icterus, and lipemia (HIL) in a plasma sample. In samples with lipemia where accuracy of the test result is compromised, strategies for mitigating the lipemia interferences would be required.

Preanalytical Variables in Hemostasis Testing.

Hemostasis testing performed in clinical laboratories are critical for assessing hemorrhagic and thrombotic disorders. The assays performed can be used to provide the information required for diagnosis, risk assessment, efficacy of therapy, and therapeutic monitoring. As such, hemostasis tests should be performed to the highest level of quality, including the standardization, implementation, and monitoring of all phases of the testing, which include the preanalytical, analytical, and post-analytical phases.

Hemostasis and Thrombosis: An Overview Focusing on Associated Laboratory Testing to Diagnose and Help Manage Related Disorders.

Hemostasis is a complex but balanced process that permit normal blood flow, without adverse events. Disruption of the balance may lead to bleeding or thrombotic events, and clinical interventions may be required. Hemostasis laboratories typically offer an array of tests, including routine coagulation and specialized hemostasis assays used to guide clinicians for diagnosing and managing patients.

The Future of Laboratory-Developed Tests in Hemostasis Laboratories.

Laboratory-developed tests (LDTs) are widely used in clinical hemostasis laboratories. The extent to which LDTs are regulated varies greatly around the world, and proposed changes to regulations have raised concerns about the future of LDTs in clinical laboratories. It is increasingly difficult to justify the use of an LDT where a commercially available method with regulatory approval is available.

Insights into tablet sticking: a quantitative case study with an ibuprofen and methocarbamol-based formulation.

Objectives And Methods: Tablet sticking is a continuous accumulation of pharmaceutical powder onto tooling surfaces during compression. Its occurrence greatly impacts tablet productivity, quality attributes, and tooling age. In a previous study, the authors proposed a multivariate data analysis approach to gain insights into tablet sticking directly on the industrial stage.