Objective evaluation of analyzer performance based on a retrospective meta-analysis of instrument validation studies: point-of-care hematology analyzers.

BACKGROUND: Information on quality requirements and objective evaluation of performance of veterinary point-of-care analyzers (POCAs) is scarce. OBJECTIVES: The study was aimed at assessing observed total errors (TEobs s) for veterinary hematology POCAs via meta-analysis and comparing TEobs to allowable total error (TEa ) specifications based on experts' opinions. METHODS: The TEobs for POCAs (impedance and laser-based) was calculated based on data from instrument validation studies published between 2006 and 2013 as follows: TEobs = 2 × CV [%] + bias [%]. The CV was taken from published studies; the bias was estimated from the regression equation at 2 different concentration levels of measurands. To fulfill quality requirements, TEobs should be < TEa . Measurands were considered as globally acceptable if > 60% of analyzers showed TEobs < TEa . RESULTS: Six studies evaluating 11 analyzers and 5 studies evaluating 5 analyzers were included for canine and feline hematology variables, respectively. For the CBC, TEobs was < 15% for canine and < 13% for feline measurands, except for HGB and platelet counts. Measurands of the CBC, excluding differential WBC and platelet counts, and HGB concentration were considered globally acceptable. For most of the cell types in the WBC differential count, TEobs was > TEa (data from 3 analyzers). CONCLUSION: This meta-analysis is considered a pilot study. Experts' requirements (TEobs < TEa ) were fulfilled for most measurands except HGB (due to instrument-related bias for the ADVIA 2120) and platelet counts. Available data on the WBC differential count suggest an analytic bias, so nonstatistical quality control is recommended.

[Alimentary thyrotoxcicosis in two dogs]. / Alimentäre Thyreotoxikose bei zwei Hunden.

Two dogs with increased thyroxin concentrations compatible with hyperthyroidism were referred for further examinations. One dog displayed clinical signs of hyperthyroidism. Based on history, clinical examination, laboratory evaluation and scintigraphy an alimentary thyrotoxicosis was identified. It was caused by feeding a BARF diet containing thyroidal tissue in one dog and by conventional dog food in the other patient. After changing the diet the clinical signs resolved in the affected dog. A control examination revealed thyroxin concentrations within the reference range in both dogs.

[Neutropenia in dogs: etiology and prognostic factors]. / Neutropenie beim Hund: Ätiologie und prognostische Faktoren.

OBJECTIVE: The aim of this retrospective study was to evaluate frequency, prognostic factors, and differences for various etiologies of neutropenia in dogs. MATERIAL AND METHODS: A total of 391 dogs with neutrophil counts < 2.78 x 109/l (January 2008 to December 2012) were included and, depending on the etiology of neutropenia, assigned to seven diagnostic groups: nonbacterial infectious disease, increased demand due to marked inflammation, drug-associated, bone-marrow diseases, immune-mediated, physiologic, miscellaneous. Absolute neutrophil counts, evidence of neutrophil toxicity or left shift, case history, rectal temperature, hospitalization, and survival were compared among groups. RESULTS: Increased demand due to marked inflammation (90/391, 23%) and nonbacterial infectious disease (70/391, 18%) were the most common causes for neutropenia, followed by drug-associated neutropenia (43/391, 11%) and bone-marrow disease (32/391, 8%). Immune-mediated and physiologic neutropenia (both 16/391, 4%) were uncommon. Almost one third (124/391, 32%) of dogs were assigned to the miscellaneous group. Absolute neutrophil counts were significantly higher (p < 0.01) in dogs of the physiologic and miscellaneous groups than in the other groups. Dogs with immune-mediated neutropenia or nonbacterial infectious disease displayed significantly lower absolute neutrophil counts than dogs with neutropenia due to an increased demand (p < 0.001) and were most commonly referred with a history of fever (11/16, 69%) or gastrointestinal signs (52/70, 74%), respectively. Neutrophil toxicity and left shift were most commonly associated with an increased demand due to marked inflammation (60/90 and 25/90, 67% and 28%, respectively) and the mortality rate was highest in this group (32/90, 36%). CONCLUSION: Neutrophil toxicity and left shift are associated with an increased demand due to marked inflammation and may indicate a poor prognosis. The lower the absolute neutrophil count, the greater the probability of an immune-mediated neutropenia. CLINICAL RELEVANCE: Neutropenia should be assessed in context with case history, clinical examination, and neutrophil morphology.

Quality requirements for veterinary hematology analyzers in small animals-a survey about veterinary experts' requirements and objective evaluation of analyzer performance based on a meta-analysis of method validation studies: bench top hematology analyzer.

BACKGROUND: Scarce information exists about quality requirements and objective evaluation of performance of large veterinary bench top hematology analyzers. OBJECTIVE: The study was aimed at comparing the observed total error (TEobs ) derived from meta-analysis of published method validation data to the total allowable error (TEa ) for veterinary hematology variables in small animals based on experts' opinions. Ideally, TEobs should be < TEa . METHODS: An online survey was sent to veterinary experts in clinical pathology and small animal internal medicine for providing the maximal allowable deviation from a given result for each variable. Percent of TEa = (allowable median deviation/clinical threshold) * 100%. Second, TEobs for 3 laser-based bench top hematology analyzers (ADVIA 2120; Sysmex XT2000iV, and CellDyn 3500) was calculated based on method validation studies published between 2005 and 2013 (n = 4). The percent TEobs = 2 * CV (%) + bias (%). The CV was derived from published studies except for the ADVIA 2120 (internal data), and bias was estimated from the regression equation. RESULTS: A total of 41 veterinary experts (19 diplomates, 8 residents, 10 postgraduate students, 4 anonymous specialists) responded. The proposed range of TEa was wide, but generally ≤ 20%. The TEobs was < TEa for all variables and analyzers except for canine and feline HGB (high bias, low CV) and platelet counts (high bias, high CV). CONCLUSIONS: Overall, veterinary bench top analyzers fulfilled experts' requirements except for HGB due to method-related bias, and platelet counts due to known preanalytic/analytic issues.

Efficient Access to Multifunctional Trifluoromethyl Alcohols through Base-Free Catalytic Asymmetric C-C Bond Formation with Terminal Ynamides.

The asymmetric addition of terminal ynamides to trifluoromethyl ketones with a readily available chiral zinc catalyst gives CF3 -substituted tertiary propargylic alcohols in up to 99 % yield and 96 % ee. The exclusion of organozinc additives and base as well as the general synthetic utility of the products are key features of this reaction. The value of the ß-hydroxy-ß-trifluoromethyl ynamides is exemplified by selective transformations to chiral Z- and E-enamides, an amide, and N,O-ketene acetals. The highly regioselective hydration, stereoselective reduction, and hydroacyloxylation reactions proceed with high yields and without erosion of the ee value of the parent ß-hydroxy ynamides.

S3S63 Terminal Ynamides: Synthesis, Coupling Reactions and Additions to Common Electrophiles.

Ynamides consist of a polarized triple bond that is directly attached to a nitrogen atom carrying a sulfonyl, an alkoxycarbonyl, an acyl or another electron withdrawing group. The triple bond polarization renders ynamides broadly useful building blocks with synthetic opportunities that go far beyond traditional alkyne chemistry. The versatile reactivity of ynamides in cycloadditions, cycloisomerizations, regioselective additions with various nucleophiles or electrophiles, ring-closing metathesis, and many other reactions has been investigated in detail during the past decades. A common feature of these methods is that the triple bond is consumed and either cleaved or transformed to a new functionality. The wealth of reports on these ynamide reactions is in stark contrast to the dearth of carbon-carbon bond formations that leave the triple bond of terminal ynamides intact. The recent introduction of effective synthetic methods for the preparation of terminal ynamides has set the stage to fully explore the synthetic potential of this intriguing class of compounds. This digest letter summarizes the most effective routes to terminal ynamides and the current state of selective nucleophilic addition, substitution and coupling reactions, including the first examples of asymmetric synthesis.

Copper(I)-catalyzed nucleophilic addition of ynamides to acyl chlorides and activated N-heterocycles.

The addition of ynamides to acyl chlorides and N-heterocycles activated in situ with ethyl chloroformate has been accomplished at room temperature using copper iodide as catalyst. This economical and practical carbon-carbon bond formation provides convenient access to a variety of 3-aminoynones from aliphatic and aromatic acyl chlorides in up to 99% yield. The addition to pyridines and quinolines occurs under almost identical conditions and proceeds with good to high regioselectivity, producing the corresponding 1,2-dihydro-N-heterocycles in up to 95% yield.

Catalytic enantioselective nucleophilic addition of ynamides to aldehydes.

The first catalytic asymmetric addition of ynamides to aliphatic and aromatic aldehydes is described. This reaction provides unprecedented access to a diverse family of N-substituted propargylic alcohols that are obtained in high yield and ee in the presence of 10 mol% of zinc triflate and N-methylephedrine. The use of apolar solvent mixtures is essential to avoid product racemization and to optimize ee's without compromising conversion.