Analytical aspects of the antinuclear antibody test by HEp-2 indirect immunofluorescence: EFLM report on an international survey.

OBJECTIVES: Detection of antinuclear antibodies (ANA) by indirect immunofluorescence assay using HEp-2 cells (HEp-2 IFA) is used to screen for various autoimmune diseases. HEp-2 IFA suffers from variability, which hampers harmonization. METHODS: A questionnaire was developed to collect information on HEp-2 IFA methodology, computer-assisted diagnosis (CAD) systems, training, inter-observer variability, quality assessment, reagent lot change control, and method verification. The questionnaire was distributed to laboratories by Sciensano (Belgium), national EASI groups (Italy, Croatia, Portugal, Estonia, Greece) and ICAP (worldwide). Answers were obtained by 414 laboratories. The results were analysed in the framework of the recent EFLM/EASI/ICAP ANA recommendations (companion paper). RESULTS: Laboratories used either HEp-2, HEp-2000, or HEp-20-10 cells and most laboratories (80%) applied the same screening dilution for children and adults. The conjugate used varied between laboratories [IgG-specific (in 57% of laboratories) vs. polyvalent]. Sixty-nine percent of CAD users reviewed the automatic nuclear pattern and 53% of CAD users did not fully exploit the fluorescence intensity for quality assurance. Internal quality control was performed by 96% of the laboratories, in 52% of the laboratories only with strongly positive samples. Interobserver variation was controlled by 79% of the laboratories. Limited lot-to-lot evaluation was performed by 68% of the laboratories. Method verification was done by 80% of the respondents. CONCLUSIONS: Even though many laboratories embrace high-quality HEp-2 IFA, substantial differences in how HEp-2 IFA is performed and controlled remain. Acting according to the EFLM/EASI/ICAP ANA recommendations can improve the global performance and quality of HEp-2 IFA and nurture harmonization.

Retrospective cohort assessment of survival and complications of zygomatic implants in atrophic maxillae.

OBJECTIVES: To report on zygomatic implant (ZI) survival rate and associated complications through a longitudinal retrospective cohort assessment. MATERIAL AND METHODS: A total of 940 ZIs (rough: 781, machined: 159; immediate loading: 454, delayed loading: 486) and 451 standard implants (rough: 195, machined: 256; immediate loading: 58, delayed loading: 393) were placed in 302 adult patients with atrophic maxilla from December 1998 till September 2020. Following data collection reported complications were grouped based on their origin as infectious/ non-infectious biological and mechanical. Statistical analysis was performed to identify risk factors and preceding complications leading to implant loss (P < 0.05). RESULTS: The survival rate of ZI was found to be 89.9% and the average time between implant placement and an eventual loss was 4.8 years. The mean ZI follow-up period was 7.9 ± 4.9 years. Amongst the infectious biological complications, sinusitis was the most reported (n = 138) occurring at a mean follow-up time-point of 4.5 years, whereas infraorbital nerve hypoesthesia occurred more frequently in the non-infectious biological category (n = 8, meantime: 0.3 years). The prosthetic screw fracture was the most reported complication of mechanical origin (n = 29, meantime: 4 years). Furthermore, sinusitis, standard implant loss, zygomatic/peri-zygomatic region infection, and oroantral communication were significantly associated with ZI loss. CONCLUSIONS: ZI placement offered a high survival rate for the rehabilitation of severely atrophied maxilla with most losses occurring within the first 5 years at follow-up. The most frequently observed complication was sinusitis which tends to develop several years following implant placement.

Local radiographic risk factors for MRONJ in osteoporotic patients undergoing tooth extraction.

OBJECTIVE: To identify local radiographic risk factors for Medication-Related Osteonecrosis of the Jaws (MRONJ) in osteoporotic patients treated with antiresorptive drugs (ARD) and undergoing tooth extraction. MATERIAL AND METHODS: Patients were included in this retrospective, longitudinal, case-control study, if having at least one administration of ARD, underwent tooth extraction(s), and had pre- and post-operative panoramic radiographs. Additionally, a matched control group was selected. Three calibrated, blinded, and independent observers assessed each tooth extraction site. Statistical analysis compared control against study group, and within the latter, sites MRONJ+ and MRONJ-. RESULTS: In total, 120 patients (99 females/21 males) with 354 tooth extractions were included, from which nine patients (7.5%) and eleven tooth extraction sites (3.1%) developed MRONJ. When comparing control with study group, the latter showed significantly more thickened lamina dura, persistence of the alveolar socket, heterogeneous bone patterns, and sequestrum formation. In the study group, MRONJ developed significantly more in males (19%, p = 0.049), smokers (25%, p = 0.008), in the mandible (82%, p = 0.027), when identifying a radiolucent or sclerotic trabecular pattern (p = 0.004) or when extracting teeth with furcation involvement (p < 0.001), root remnants (p = 0.017), or unrestored caries lesions (p = 0.005). CONCLUSIONS: Tooth extraction sites showing radiographic signs of chronic dental infection are prone to MRONJ.

Glucose and redox metabolism in meiotically blocked in vitro grown mouse antral follicles.

PURPOSE: Glucose and redox metabolism characterization in mouse antral follicles with meiotically blocked oocytes, after in vitro follicle culture (IFC) from the early secondary stage. METHODS: Following IFC (10 days), oocytes, corresponding cumulus (CC), and granulosa cells (GC) were collected from antral follicles: (i) on day 9-immature, germinal vesicle (GV) stage; (ii) on day 10, after hCG/EGF stimulation-mature, metaphase II (MII) stage and meiotically blocked (MB) immature GV stage. The metabolic profiles of all samples (GV, MII, and MB) were compared by measuring changes in metabolites involved in glycolysis, tricarboxylic acid (TCA) cycle, pentose phosphate pathway (PPP), and redox activity via enzymatic spectrophotometric assays in each cell type. RESULTS: Within MB follicles, GCs drive higher levels of glycolysis and lactic acid fermentation (LAF) while oocytes exert more PPP activity. MB-oocytes had significantly larger diameters compared to day 9 GVs. MB follicles revealed limited metabolic changes in the somatic compartment compared to their GV counterparts (before stimulation). MB-CCs showed increased aconitase and glucose-6-phosphate dehydrogenase activities with lower malate levels comparted to GV-CCs. MB and MII in vitro grown follicles displayed comparable metabolic profiles, suggesting culture induces metabolic exhaustion regardless of the maturation stage. CONCLUSIONS: Current results suggest that in addition to impaired nuclear maturation, metabolic disruption is present in MB follicles. MB follicles either compensate with high levels of TCA cycle and PPP activities in CCs, or are unable to drive proper levels of aerobic metabolism, which might be due to the current culture conditions.

Characterization of carbohydrate metabolism in in vivo- and in vitro-grown and matured mouse antral follicles†.

Establishing an ideal human follicle culture system for oncofertility patients relies mainly on animal models since donor tissue is scarce and often of suboptimal quality. The in vitro system developed in our laboratory supports the growth of prepubertal mouse secondary follicles up to mature oocytes. Given the importance of glucose in preparing the oocyte for proper maturation, a baseline characterization of follicle metabolism both in the culture system and in vivo was carried out. Markers of glucose-related pathways (glycolysis, tricarboxylic acid [TCA] cycle, pentose phosphate pathway [PPP], polyol pathway, and hexosamine biosynthetic pathway), as well as the antioxidant capacity, were measured in the different follicle cell types by both enzymatic activities (spectrophotometric detection) and gene expression (qPCR). This study confirmed that in vivo the somatic cells, mainly granulosa, exhibit intense glycolytic activity, while oocytes perform PPP. Throughout the final maturation step, oocytes in vivo and in vitro showed steady levels for all the key enzymes and metabolites. On the other hand, ovulation triggers a boost of pyruvate and lactate uptake in cumulus cells in vivo, consumes reduced nicotinamide adenine dinucleotide phosphate, and increases TCA cycle and small molecules antioxidant capacity activities, while in vitro, the metabolic upregulation in all the studied pathways is limited. This altered metabolic pattern might be a consequence of cell exhaustion because of culture conditions, impeding cumulus cells to fulfill their role in providing proper support for acquiring oocyte competence.

Analytical performance of eight enzymatic assays for ethanol in serum evaluated by data from the Belgian external quality assessment scheme.

OBJECTIVES: Fast and reliable ethanol assays analysis are used in a clinical context for patients suspected of ethanol intoxication. Mostly, automated systems using an enzymatic reaction based on ethanol dehydrogenase are used. The manuscript focusses on the evaluation of the performance of these assays. METHODS: Data included 30 serum samples used in the Belgian EQA scheme from 2019 to 2021 and concentrations ranged from 0.13 to 3.70 g/L. A regression line between target concentrations and reported values was calculated to evaluate outliers, bias, variability and measurement uncertainty. RESULTS: A total of 1,611 results were taken into account. Bias was the highest for Alinity c over the whole concentration range and the lowest for Vitros for low concentrations and Cobas 8000 using the c702 module for high concentrations. The Architect and Cobas c501/c502 systems showed the lowest variability over the whole concentration range. Highest variability was observed for Cobas 8000 using the 702 module, Thermo Scientific and Alinity c. Cobas 8000 using the c702 module showed the highest measurement uncertainty for lower concentrations. For higher concentrations, Alinity c, Thermo Scientific and Vitros were the methods with the highest measurement uncertainty. CONCLUSIONS: The bias of the enzymatic techniques is nearly negligible for all methods except Alinity c. Variability differs strongly between measurement procedures. This study shows that the Alinity c has a worse measurement uncertainty than other systems for concentrations above 0.5 g/L. Overall, we found the differences in measurement uncertainty to be mainly influenced by the differences in variability.

External quality assessment providers' services appear to more impact the immunohaematology performance of laboratories than national regulatory and economic conditions.

OBJECTIVES: Medical laboratories may, at their own discretion, exceed but not undercut regulatory quality requirements. Available economic resources, however, may drive or hinder eagerness to exceed minimum requirements. Depending on the respective scopes of regulatory and economic framework conditions, differing levels of quality efforts to safeguard laboratory performance can be anticipated. However, this has not yet been investigated. METHODS: Immunohaematology external quality assessment (EQA) results collected by 26 EQA providers from their participant laboratories in 73 countries from 2004 to 2019 were evaluated. Error rates were aggregated in groups according to the respective national regulatory and economic framework conditions, to whether or not expert advice was provided in case of incorrect results, and the frequency of EQA samples. RESULTS: These representative data indicate no association between national regulatory (mandatory participation in EQA, monitoring of performance of individual laboratories by authorities, financial consequences of incorrect results) and economic (level of national income, share of national health expenditure) conditions to the quality performance of medical laboratories in immunohaematology. However, EQA providers' support for laboratories in the event of incorrect results appear to be associated with lower error rates, but a high EQA sample frequency with higher error rates. CONCLUSIONS: Further research into the impact of introducing or changing services of EQA providers is needed to confirm the results found in this first of its kind study.

Mechanical properties and cellular content of leukocyte- and platelet-rich fibrin membranes of patients on antithrombotic drugs.

INTRODUCTION: The aim of this study was to examine the potential influence of antithrombotics on leukocyte- and platelet-rich fibrin (L-PRF) membranes. METHODS: Tensile tests and cell counts were performed with L-PRF membranes originating from patients on anticoagulants and antiplatelets versus patients not taking antithrombotics. RESULTS: For the tensile tests, 13 control patients, 12 on anticoagulants, and 10 on antiplatelets donated blood. Compared to controls, membranes from anticoagulated donors were weaker (strength 0.57 ± 0.24 MPa vs. 0.80 ± 0.27 MPa, p = .03) and could not be stretched as far (1.8 ± 0.3 vs. 2.1 ± 0.3 times the initial length, p = .01). For the cell counting, 23 control patients, 16 on anticoagulants, and 16 on antiplatelets donated blood. The percentage of platelets was ±50% in the three groups. The percentage of leukocytes was lower in the anticoagulant group compared with controls (69 ± 10% vs. 78 ± 8%, p = .04). However, because of the unknown error of method, it is questionable whether the statistical significance is meaningful. There was no difference between membranes from the control group and the group on antiplatelets. CONCLUSION: Our results indicate that L-PRF membranes originating from patients on anticoagulants are weaker, stretch less far, and contain less leukocytes than L-PRF membranes of patients not taking these drugs.

Peri-zygomatic infection associated with zygomatic implants: A retrospective longitudinal cohort study.

OBJECTIVES: The main objective of this retrospective, longitudinal, cohort study was to describe the occurrence of peri-zygomatic infection (PZI) as a complication associated with zygomatic implant (ZI) placement in a period of 22 years. MATERIALS AND METHODS: A retrospective search was carried out in the department of oral and maxillofacial surgery of Saint John's hospital in Genk, Belgium. Patients that had a severely atrophic fully or partially edentulous maxilla, and at least one ZI placed, were included. RESULTS: A total of 302 eligible patients, underwent ZI surgery between 1998 and 2020. From a total of 940 ZI, 45 were associated with the development of PZI. PZI was located in the upper portion of the cheek in relation to the external corner of the eye, one or two centimeters under the lower lid. The total number of affected patients was 25 (8.3%), who had a mean age of 58.1 years. In this subset, PZI occurred in 15 cases on the right side, in eight cases on the left side, and in two cases bilaterally. Ultimately, 16 ZI were lost in the PZI site. The mean time since the implant placement to the diagnosis of PZI was 1.9 years (SD ±2.4) and to the ZI removal of 3.8 years (SD ±3.7). After implant removal, the PZI symptomatology dissipated in all patients. CONCLUSION: Peri-zygomatic infection should be informed to the patients as a possible complication after ZI placement. Once identified, it should be acknowledged as a risk factor for ZI failure.

Pre-surgical radiographic and clinical features as predictors for temporomandibular joint discectomy prognosis.

OBJECTIVES: This study aimed to identify potential clinical and radiological predictors associated with the outcome of discectomies. METHODS: In this retrospective observational study, the material comprised preoperative CBCT images and medical records of 62 patients with disc derangement disorders, who had undergone discectomy because of disc displacement with reduction (DDwR), disc displacement without reduction (DDwoR), systemic arthritis (SA), or joint hypermobility. Clinical and radiographic variables were analysed in relation to success rate determined by subjective, objective and combined outcomes. RESULTS: The success odds ratio was 11 times higher in patients with painful DDwR versus that of SA (p = 0.03), and even 25.9 times higher when considering solely objective outcome (p = 0.03). In the absence of subchondral pseudocyst, there were 5.2 times higher odds to have a successful subjective outcome (p = 0.04). Extensive bone apposition on the temporal joint component indicated a 9.3 times higher likelihood of a failed objective outcome (p = 0.04). CONCLUSIONS: There is a significant higher risk for combined outcome failure for the diagnosis SA involving the TMJ compared with DDwR. Predictors of importance based on CBCT findings related to the objective outcome failure were extensive bone apposition on the temporal joint component and condylar subchondral pseudocysts for the subjective outcome failure.

Postoperative complications following orthognathic surgery in patients with rheumatic diseases: A 2-year follow-up study.

OBJECTIVE: The purpose of this study was to describe the complications following orthognathic surgery in patients with rheumatic diseases and to evaluate rheumatic disease as a possible risk factor. METHODS: A retrospective cohort study was conducted during a 6-year period. The sample consisted of rheumatic and healthy patients who underwent orthognathic surgery. The outcome variables included infection, relapse, respiratory complications, hemorrhage, neurosensory disturbances, temporomandibular joint complications, and removal of osteosynthesis material. Bivariate analysis and logistic regression were applied to identify rheumatic disease as an independent risk factor for complications after orthognathic surgery. RESULTS: Twenty patients were identified as having rheumatic diseases (male: 2; female: 18; mean age: 37.8 ± 13.6 years), and 278 patients were systemically healthy (male: 105; female: 173; mean age: 25.8 ± 11.8 years). The most frequent complications in rheumatic and healthy patients were delayed recovery from neurosensory disturbance (55% and 33%), removal of osteosynthesis material (45% and 26%), and infection (35% and 7%). Following adjustment for possible confounders, rheumatic disease showed a significant association with infection (OR = 4.191, p = 0.016). CONCLUSION: Patients with rheumatic diseases are at a higher risk of postoperative infection following orthognathic surgery compared to healthy patients.

Improved clinical outcomes after non-invasive oocyte selection and Day 3 eSET in ICSI patients.

BACKGROUND: Non-invasive oocyte quality scoring, based on cumulus gene expression analysis, in combination with morphology scoring, can increase the clinical pregnancy (CPR) and live birth rates (LBR) in Day 3 eSET (elective single embryo transfer) ICSI patients. This was first investigated in a pilot study and is now confirmed in a large patient cohort of 633 patients. It was investigated whether CPR, LBR and time-to-pregnancy could be improved by analyzing the gene expression profile of three predictive genes in the cumulus cells, compared to patients with morphology-based embryo selection only. METHODS: A large interventional, non-randomized, assessor-blinded cohort study with 633 ICSI patients was conducted in a tertiary fertility center. Non-PCOS patients, 22-39 years old, with good ovarian reserve, were stimulated with HP-hMG using a GnRH antagonist protocol and planned for fresh Day 3 eSET. The cumulus cells from individually denuded oocytes were ranked by a lab-developed cumulus cell test: qRT-PCR for three predictive genes (CAMK1D, EFNB2 and SASH1) and two control genes (UBC, B2M). The embryo selected for transfer was highest ranked from the pool of morphologically transferable Day 3 embryos. Patients in the control (n = 520) and experimental arm (n = 113) were compared for clinical pregnancy and live birth, using a weighted generalized linear model, and time-to-pregnancy using Kaplan-Meier curves. RESULTS: The CPR was 61% in the experimental arm (n = 113) vs 29% in the control arm (n = 520, p < 0.0001). The LBR in the experimental arm (50%) was significantly higher than in the control arm (27%,p < 0.0001). Time-to-pregnancy was significantly shortened by 3 transfer cycles independent of the number of embryos available on Day 3 (Kaplan-Meier, p < 0.0001). Cumulus cell tested patients < 35 years (n = 65) or ≥ 35 years (n = 48) had a CPR of 62 and 60% respectively (ns). For cumulus cell tested patients with 2, 3-4, or > 4 transferable embryos, the CPR was 66, 52, and 67% (ns) respectively, and thus independent of the number of transferable embryos on Day 3. CONCLUSIONS: This study provides further evidence of the clinical usefulness of the non-invasive cumulus cell test over time in a larger patient cohort. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03659786 / NCT02962466 (Registered 6Sep2018/11Nov2016, retrospectively registered.

Osteomyelitis, osteoradionecrosis, or medication-related osteonecrosis of the jaws? Can CBCT enhance radiographic diagnosis?

OBJECTIVE: To attempt defining differential radiographic diagnostic characteristics for osteonecrotic lesions using 2D as opposed to 3D images. MATERIALS AND METHODS: This was a cross-sectional study. Subjects presenting mandibular osteonecrotic lesions (osteomyelitis, osteoradionecrosis, and medication-related osteonecrosis of the jaws) were selected and compared to a group of age- and gender-matched controls, all having both cone-beam computed tomographic images (CBCT) and panoramic radiographs (PANO). Both imaging modalities (predictor variables) were evaluated by two radiologists that scored lesion presence, eight additional radiological features, and a composite severity index (outcome variables). For each pathologic condition, characteristic features were assessed in PANO and CBCT by the Wilcoxon signed-rank test. Regression tree analysis revealed the predictive value of PANO and CBCT (α = 5%). RESULTS: Overall, the predictive value of PANO reached 74%, while for CBCT it became 90%. Regarding the composite severity index, CBCT enabled to detect more subtle lesions. Also, CBCT imaging allowed showing more distinct radiographic diagnostic features as compared to PANO imaging, more specifically when distinguishing osteomyelitis from both other lesions. CONCLUSIONS: Cone-beam computed tomography enabled showing more differences in radiological features between distinct osteonecrosis disease entities. CBCT imaging might be a better contributor for the detection of early lesions and to monitor further pathological developments in the mandible.

A critical view at the ISO 13528 and IUPAC's harmonized protocol approach for proficiency testing for homogeneity assessment for quantitative variables.

To ensure a correct interpretation of Proficiency Testing (PT) or External Quality Assessment (EQA) results, sample batches need to be homogeneous. The importance of homogeneity testing has been underlined by ISO 13528 and the IUPAC harmonized protocol for proficiency testing. They require that the batch heterogeneity should be smaller than 0.3σpt, with σpt the standard deviation for proficiency assessment according to ISO/IEC 17043:2010 and provide procedures for assessing the batch heterogeneity. In this study, a critical appraisal of these procedures is given. Firstly, an assessment is made of the influence of the criterion of 0.3σpt on laboratory evaluation. Secondly, the assessment procedure of the batch heterogeneity is evaluated, with an emphasis on the calculation and the evaluation of the measured batch standard deviation. It was found that the 0.3σpt criterion may be loosened without a detrimental effect on laboratory evaluation. In addition, it was shown that a flaw in the calculation procedure forces the batch standard deviation to be 0 with a probability of 21.4% for batch standard deviations of 0.3σpt and repeatability of 0.5σpt. The hypothesis test for accepting a batch exhibits a high probability of accepting the batch, even for batch standard deviations that are a multiple of 0.3σpt. To conclude, this study shows that the criteria for homogeneity check of PT items by ISO 13528 and the IUPAC protocol do not assure batch homogeneity. They may be a combination of a criterion that is too strict and a permissive assessment. Alternative assessment procedures should be followed.

Molecular Study of Toxoplasma gondii Isolates Originating from Humans and Organic Pigs in Belgium.

Toxoplasma gondii is a worldwide prevalent, zoonotic parasite of major importance for public health, which can infect any warm-blooded animal species, including humans. Humans can get infected by consumption of meat from a chronically infected animal, by ingestion of sporulated oocysts (resulting from the sexual replication in felids), via contaminated water, soil, or vegetables, and by vertical transmission via the placenta. Infection through meat consumption is estimated to be one of the main sources of human toxoplasmosis cases in developed countries, and more specifically pork is considered to be responsible for 41% of foodborne human toxoplasmosis cases in the United States. To better assess the role of pork as a source of T. gondii infection in humans in Belgium, parasites were isolated from pigs to compare with human clinical isolates in a molecular epidemiological study. A positive result was obtained by magnetic capture-quantitative polymerase chain reaction for T. gondii in 14 out of the 92 hearts sampled during 2016 and 2017 from pigs raised in organic farms. From 9 of these 14 samples, parasites were isolated by mouse bioassay, demonstrating the presence of viable T. gondii in animals intended for human consumption. When genotyped and compared with 15 human isolates obtained during 2015 and 2016, a highly related structured population was demonstrated. Overall, these findings demonstrate the presence of infectious T. gondii in pigs intended for human consumption. Therefore, a potential transmission of T. gondii strains from pigs to humans could occur. However, both species could also be infected via a common source of infection such as oocysts. Furthermore, Belgium does not have an official surveillance program for T. gondii in human cases or food-producing animals; as a consequence, the detection of the infection source of a patient is very rare. Overall, this study reinforces the identification of pork as a potential risk for the consumers.

To Win the Battle, First Know Your Enemy: Error Rates in Immunohematology External Quality Assessment Results.

BACKGROUND: As some errors in pretransfusion testing remain unrecognized, error rates and the resulting need for corrective measures are probably underestimated. External quality assessment (EQA) schemes could provide valuable input for identifying error-prone laboratory tests because they are designed to monitor test performance and errors. So far, however, there are only limited published data on error rates in such schemes. METHODS: The types and incidence of incorrect results in an EQA scheme for red cell immunohematology with 187 participating laboratories were examined. The results of 58 distributions between 1999 and 2017 were evaluated, considering also the employed determination methods. RESULTS: Out of a total of 58,726 results, 563 (0.96%) were incorrect. Error rates were 5.45% for antibody identification, 1.39% for Rh phenotyping, 0.83% for serologic cross-match, 0.60% for direct antiglobulin test, 0.20% for Kell phenotyping, 0.16% for antibody screening, and 0.14% for ABO phenotyping. During the observation period, 53 participants reported error-free results, while 37 reported one incorrect result and 97 repeatedly reported incorrect results for one or more analytes. Error rates obtained by manual methods significantly surpassed those obtained by automated methods (1.04 vs. 0.42%). The introduction of double testing with two different systems reduced error rates in Rh phenotyping from 1.55 to 0.50%. CONCLUSION: Risk assessment should consider that error rates in pretransfusion test results vary. These data delineate the error risk potential of individual laboratory tests and thus should aid in tailoring appropriate improvement measures.

Alternative Sample-Homogeneity Test for Quantitative and Qualitative Proficiency Testing Schemes.

Proficiency Testing (PT) External Quality Assessment (EQA) schemes are designed to ascertain the ability of individual laboratories to perform satisfactorily with respect to their peer laboratories or to limits imposed by external sources. Observed deviation of a laboratory result for a PT sample must be entirely attributed to the laboratory and not to the PT provider. To minimize the probability that deviations could be attributed to the PT provider, sample homogeneity should be assured. It is generally required that for quantitative parameters, the standard deviation among PT units should be calculated on the basis of duplicate measurements of at least 10 samples chosen at random, and the standard deviation among PT units should not exceed 0.3 times the standard deviation used to evaluate laboratories. Because this approach has important drawbacks, an alternative procedure is proposed by applying the theory of acceptance sampling to the assessment of sample heterogeneity for both quantitative and qualitative data and deriving acceptance limits on the basis of minimizing the probability of falsely evaluating laboratories. For obtaining acceptance limits for quantitative parameters, a distinction is made between laboratory evaluation using fixed limits on the one hand and laboratory evaluation using limits that are based on the variability of the reported results on the other hand. Sequential tests are proposed to evaluate sample heterogeneity by means of a comparison with the χ2 distribution. For qualitative parameters, acceptance-sampling plans are proposed that are based on minimizing the joint probability of rejecting batches that have a satisfactory amount of defective samples and accepting batches unnecessarily. The approach for quantitative parameters is applied on samples for a PT scheme of ethanol quantification and for qualitative parameters on the presence of monoblasts in a blood smear. It was found that five samples could already be enough to prove that the batch was homogeneous for quantitative parameters, although more than 20 samples were needed to prove homogeneity for qualitative parameters. This study describes a direct relation among the objective of an PT round, the criteria for evaluating the results, and the sample heterogeneity. When samples are effectively homogeneous, less measurements are needed than current practices require. A drawback of the proposed approach is that the number of samples to be tested is not known beforehand, and good knowledge of the analytical variability is crucial. The formulas to be applied are relatively simple. Despite the drawbacks, the proposed approach is generally applicable for both quantitative and qualitative data.

Radiographic prediction of mandibular third molar eruption and mandibular canal involvement based on angulation.

OBJECTIVES: The aim of our study was to identify and predict patients at risk of impeded mandibular third molar eruption and potential relation between the third molar roots and the mandibular canal, based on molar angulations in an early development stage. SETTING AND SAMPLE POPULATION: A total of 1011 adolescent orthodontic patients were included in this longitudinal study. MATERIALS AND METHODS: We analysed pre-eruptive rotational changes and root development of mandibular third molars on 2022 panoramic radiographs (two time-points). Five variables were evaluated: third molar eruption level, development stage, risk of relation between the third molar and the mandibular canal, the molar angulations and orthodontic treatment. The relation between early third molar angulation and mean annual angulation change was assessed using a linear mixed model. Logistic regression was applied to investigate a potential correlation of the radiographic variables with the eruption potential and risk of developing a relation between the third molar and the mandibular canal. RESULTS: Mandibular third molar follicles with an initial angulation exceeding 27.0° relative to the second molar tend to progressively increase their angulation during further development. A significant correlation was found between the hemimandibular molar angulations and the probability of eruption (P < 0.0001). The second to first molar angulation was predictive for potential development of a relation with the mandibular canal (P = 0.005). CONCLUSION: From the present data, it appears that severely angulated mandibular third molars (>27.0°) have a minimal chance of future eruption and a maximal risk of developing a relation with the mandibular canal.

Randomized controlled trial comparing immediate loading with conventional loading using cone-anchored implant-supported screw-retained removable prostheses: A 2-year follow-up clinical trial.

STATEMENT OF PROBLEM: Implant-based prosthetic solutions can be time consuming. If implants can be loaded immediately, treatment time can be reduced. PURPOSE: The purpose of this prospective randomized controlled trial was to monitor the survival rate of Ankylos implants, comparing conventional with immediate loading by using abutments with the SynCone concept for screw-retained removable prostheses in the edentulous maxilla. MATERIAL AND METHODS: A total of 90 implants were placed in 15 study participants. The participants were randomly assigned to the immediate or conventional loading treatment group. Radiographic and clinical parameters were recorded at the time of permanent prosthesis installment and at 1- and 2-year follow-up examinations, and participants' satisfaction was measured by using questionnaires before and after prosthesis installation. A linear mixed model was used to measure differences. RESULTS: One implant in the conventional group was lost during abutment placement; hence, 89 implants could be followed for 2 years. Approximately 90% of these implants showed no bone loss or even bone gain at 1 and 2 years follow-up. Mean values for the immediate group were, respectively, 0.09 ±0.35 mm and 0.13 ±0.38 mm and 0.01 ±0.41 mm and -0.06 ±0.32 mm for the conventional method. No significant differences (P=.053) were found in bone level alterations between the groups. For all participants, the mean number of surfaces (4 per implant) with bleeding on probing (BoP) and plaque were 0.76 ±0.81 and 0.16 ±0.42 at 1 year follow-up and 0.44 ±0.66 and 0.02 ±0.15, respectively, at the second-year follow-up. The mean pocket probing depths were 2.05 ±0.54 mm at 1 year and 2.18 ±0.64 mm at 2 years. For both groups, a significant rise in satisfaction and quality of life was observed (P≤.001) at 1 and 2 years compared with pretreatment. CONCLUSIONS: Ankylos implants placed in the edentulous maxilla, immediately or conventionally loaded by a detachable prosthesis, showed favorable bone-level preservation after 2 years of follow-up. No significant differences could be found between the immediate and conventional groups. A significant increase in quality of life was observed for both loading modes.

Evidence for the positive impact of ISO 9001 and ISO 15189 quality systems on laboratory performance - evaluation of immunohaematology external quality assessment results during 19 years in Austria.

Background ISO 9001 and ISO 15189 have been established as continuative models for quality systems beyond national laws, mandatory standards and guidelines of expert associations regarding analytical and organisational performance of medical laboratories and transfusion services. Although widely used, their impact on laboratory performance has not been investigated. Methods We retrospectively analysed the results of 167 laboratories in 59 distributions of the Austrian red cell immunohaematology external quality assessment (EQA) scheme in the years 1999-2017. The performance for each parameter and trends of individual participants were compared with respect to certification or accreditation status of participants' quality systems and to laboratory type. Results Considering more than 52,000 EQA results, the absence or presence of a laboratory quality management system showed different error rates. Laboratories with ISO 9001 or ISO 15189 certification/accreditation had 0.7% incorrect results, while this rate was doubled without such quality systems (1.4%, p=0.0002). Statistically significant error reductions were seen upon ISO 9001/ISO 15189 implementation (1.3% before vs. 0.7% after; p=0.0468). Transfusion services had fewer errors (0.9%) compared to hospital and independent laboratories (both 1.2%). Conclusions Implementation and maintenance of quality systems according to ISO 9001 or ISO 15189 as well as laboratory specialisation result in better analytical performance as can be seen in immunohaematology EQA results. The conclusion is that these results apply to other laboratory tests and perhaps to other areas of health care.