Administration Criteria Research Articles

Protocols for perioperative management of direct oral anticoagulants in hospitals: opportunities for improvement

Objectives To investigate and describe the protocolized perioperative management in patient using Direct oral anticoagulants (DOACs) in Dutch hospitals. Methods Between August and December 2020, a nationwide survey in 70 hospitals in the Netherlands was conducted. We asked hospital pharmacists to submit their protocols for perioperative management of DOAC (apixaban, dabigatran, edoxaban and rivaroxaban) users. The protocols were assessed for a number of parameters divided into categories: interruption and restart timetables DOACs for elective procedures, criteria for the start of an urgent procedure without antidotes, criteria for the use of antidotes and advised antidotes for urgent procedures. Results A total of 49 hospitals (70%) sent a protocol for perioperative management of DOACs. Two pairs of protocols were identical because hospitals cooperated closely, leaving 47 individual protocols for analysis. Thirty-five of these protocols contained a policy for both elective and urgent procedure; five protocols contained only a policy for elective and seven only for urgent procedures. In protocols for elective procedure, we found great variation in interruption and restart timetables intended for patients with renal impairment (Estimated Glomerular Filtration Ratio < 80 ml/min). In case of urgent procedures, there is variation in choice of antidote, criteria for administration of an antidote and antidote dosing. Conclusion This study provides an overview of the current state of the perioperative protocols in the Netherlands in patients treated with direct oral anticoagulants. Protocols are often not complete and show important and unwanted variation. We have found that national guidelines do not provide unambiguous advice on all points (urgent procedures) and are therefore often elaborated at a local level. The results of this research can help in improving and harmonizing the perioperative protocols on a national level.

Human Capital as a Source of Energy for Rural Areas’ Socio-Economic Development—Empirical Evidence for Rural Areas in Poland

This article deals with the issue of human capital as a factor responsible for the emergence of development inequalities in rural areas. Its main goal is to analyze and evaluate the existing differences in the distribution of human capital resources in rural areas in Poland in relation to their socio-economic situation. The essence of human capital is expressed through the analogy of energy and capital in relation to the concept of homo energeticus. The essence of human capital is also expressed in terms of two components of its structure, i.e., health and the labor market. The level of human capital was expressed using two synthetic measures, i.e., the human capital ratio in the field of health (HCH) and the labor market (HCLM). The obtained research results indicate the existing differences in the spatial distribution of human capital, resulting in a polarization effect in the center-periphery system, and showing relations with the socio-economic structure of rural areas, their agricultural function, and the ongoing population processes. The assumption about the existing relations between the individual components of the structure of human capital, i.e., health and the labor market, with the socio-economic situation of individual communes should be considered correct. The obtained results of the empirical analysis constitute an important contribution to the description of the mechanism explaining the causes of the existing disproportions in the level of rural development; they allow for a more optimal planning of the instruments supporting their development at the local level. The empirical analysis was carried out in spatial terms with regard to rural areas in Poland defined in accordance with the administrative criterion of the Central Statistical Office at the lowest local (rural) level of data aggregation. The analysis covers rural and urban-rural communes in Poland, i.e., 2172 spatial units. The source of data for the synthetic measures (HCH and HCLM) was Local Data Bank Statistics Poland (LDB SP), and that for the indicator of the level of socio-economic development for rural areas (S-EDI) was the European Fund for Polish Rural Development (EFRWP).

PARANOID SCHIZOPHRENIA SECONDARY TO PHYSICAL AND EMOTIONAL ABUSE BY SPOUSE: A CASE REPORT

Schizophrenia, which is distinguished by psychotic symptoms and frequently leads to social and vocational decline, persists to be a challenge in terms of its aetiology and treatment. Physical and emotional abuse from the partner can lead to paranoid schizophrenia. Paranoid schizophrenia patient shows disturbed thought process due to several causative agents such as chemical and structural dysfunction and environmental influences. Further patient have poor insight, experience disorder of thought and have negative symptoms. A 32 year old female patient was brought to psychiatric department by her mother with the presenting complaints of acute symptoms which include delusion of percussion, delusion of reference, delusion of infidelity, auditory hallucination, suspicious behavior and restlessness. Prior to the current situation patient have taken I week of treatment and visit the psychiatrist for follow up. Clinical features and mental status examination met the criteria for paranoid schizophrenia and administration of antipsychotics to the patient. The client was under the observation for 1 week. The drug therapy was helpful to the client. The course of the disorder in the client was ‘episodic with stable deficit’. The symptoms of the client were reduced and she was stable.

Visual Outcomes of Photorefractive Keratectomy Enhancement After Primary LASIK.

To evaluate the safety, efficacy, and predictability of photorefractive keratectomy (PRK) at least 4 years after primary laser in situ keratomileusis (LASIK) and compare it to the United States Food and Drug Administration (FDA) criteria. This retrospective, single-site study compared patients who underwent PRK enhancement from 2014 to 2019 after primary LASIK to those who only underwent primary LASIK without re-treatment from the same time period. Patient demographics and clinical information were compared between the two groups. Visual outcomes and postoperative complications were evaluated in the enhancement group. A total of 374 eyes with PRK enhancement were compared to 472 without re-treatment. Age, sex, surgical eye, and preoperative sphere, and spherical equivalent (SE) were significantly different between the enhancement and control groups (P < .05). At 12 months post-enhancement, 67% had uncorrected distance visual acuity (UDVA) of 20/20 or better, 98% had UDVA of 20/40 or better, and 0.4% of eyes lost at least two lines of corrected distance visual acuity (CDVA). A total of 83% and 98% of eyes were within ±0.50 and ±1.00 diopters of the target, respectively. Post-enhancement complications (n = 66) included dryness (6.1%), epithelial ingrowth (2.7%), and haze (2.7%). Older age at the time of the primary LASIK, female sex, right surgical eye, and more myopic sphere and SE were risk factors for enhancement. Although PRK enhancements are considered off-label procedures, they produce favorable outcomes at 3 and 12 months postoperatively while meeting FDA benchmarks for safety, efficacy, and predictability. [J Refract Surg. 2022;38(11):733-740.].

COMMENCEMENT OF NEGOTIATIONS AND PRESENCE OF THE EU AS THE BASIS OF STABLE GROWTH AND DEVELOPMENT OF BOSNIA AND HERZEGOVINA

It is important for Bosnia and Herzegovina, but also for the European Union, that the negotiation process begins as soon as possible. Real changes in the legal, administrative and political sense commence only with fulfilment of benchmarks for opening and closing of chapters. The negotiation process is also important for learning and progressing in the understanding of European policies which help to strengthen state institutions, democracy and openness to grow and result with stronger economic growth due to an increased level of trust and safety. It is important for the European Union that the country at the very heart of Europe, which belongs to Europe not only geographically, but also historically and in terms of tradition and culture, becomes a part of it as soon as possible and also in terms of the standards it applies. In this paper we give an overview of recommendations that the European Commission has provided to Bosnia and Herzegovina since 2002, and it is precisely from the recommendations which are being repeated each year that the most important challenges which Bosnia and Herzegovina needs to solve are still visible. Rule of law, respecting human rights and rights of minorities, as well as the constitutionality of the three nations, in addition to a fast and efficient judicial system and the public sector as a whole are the key elements for fulfilling political, legal and administrative criteria. At the moment B&amp;H is significantly lagging behind even the least developed Member States and convergence towards the EU average is necessary because on the current level B&amp;H could not equally participate in the EU Single Market, and accession would create more obstacles than advantages. The EU is expected to take a more active approach in solving the challenges of economic convergence of B&amp;H, therefore in this paper an overview is provided of the priorities of the new EU Enlargement Strategy in which support to socioeconomic development is pointed out as one of the initiatives. Keywords: EU programs; BiH; Croats; sustainable development; economy.

TIME TO EXPAND THE USE OF CASIRIVIMAB/IMDEVIMAB MONOCLONAL ANTIBODY THERAPY? A CASE OF COMPASSIONATE USE IN SEVERE COVID-19 PNEUMONIA

TIME TO EXPAND THE USE OF CASIRIVIMAB/IMDEVIMAB MONOCLONAL ANTIBODY THERAPY? A CASE OF COMPASSIONATE USE IN SEVERE COVID-19 PNEUMONIA

Spray drying siRNA-lipid nanoparticles for dry powder pulmonary delivery.

While all the siRNA drugs on the market target the liver, the lungs offer a variety of currently undruggable targets which could potentially be treated with RNA therapeutics. Hence, local, pulmonary delivery of RNA nanoparticles could finally enable delivery beyond the liver. The administration of RNA drugs via dry powder inhalers offers many advantages related to physical, chemical and microbial stability of RNA and nanosuspensions. The present study was therefore designed to test the feasibility of engineering spray dried lipid nanoparticle (LNP) powders. Spray drying was performed using 5% lactose solution (m/V), and the targets were set to obtain nanoparticle sizes after redispersion of spray-dried powders around 150 nm, a residual moisture level below 5%, and RNA loss below 15% at maintained RNA bioactivity. The LNPs consisted of an ionizable cationic lipid which is a sulfur-containing analog of DLin-MC3-DMA, a helper lipid, cholesterol, and PEG-DMG encapsulating siRNA. Prior to the spray drying, the latter process was simulated with a novel dual emission fluorescence spectroscopy method to preselect the highest possible drying temperature and excipient solution maintaining LNP integrity and stability. Through characterization of physicochemical and aerodynamic properties of the spray dried powders, administration criteria for delivery to the lower respiratory tract were fulfilled. Spray dried LNPs penetrated the lung mucus layer and maintained bioactivity for >90% protein downregulation with a confirmed safety profile in a lung adenocarcinoma cell line. Additionally, the spray dried LNPs successfully achieved up to 50% gene silencing of the house keeping gene GAPDH in ex vivo human precision-cut lung slices at without increasing cytokine levels. This study verifies the successful spray drying procedure of LNP-siRNA systems maintaining their integrity and mediating strong gene silencing efficiency on mRNA and protein levels both in vitro and ex vivo. The successful spray drying procedure of LNP-siRNA formulations in 5% lactose solution creates a novel siRNA-based therapy option to target respiratory diseases such as lung cancer, asthma, COPD, cystic fibrosis and viral infections.

C3d(g), iron nanoparticles, hemin and cytochrome c may induce oxidative cytotoxicity in tumors and reduce tumor-associated myeloid cells-mediated immunosuppression

A variety of tumors are sensitive to cell death by ferroptosis, a type of regulated necrosis characterized by iron accumulation, failure of cellular antioxidant defence systems, unrestrained accumulation of lipid peroxides and membrane rupture. Efficient removal of apoptotic and necrotic cells via tumor-associated phagocytes results in local immune suppression. Phagocytosis inhibition reduces tumor growth and metastasis. Here I hypothesize that accumulating iron nanoparticles, hemin, cytochrome c and preformed lipid peroxides in tumors combined with phagocytosis inhibition may induce the generation of oxidizing species to high levels within tumor tissue, thus causing increased oxidative damage and tumor cell death. I propose that C3d(g), the final degradation product of the third component of complement (C3) can be utilized to limit phagocytosis and stimulate anti-tumor responses. Furthermore, the plasticity and the multiple subtypes of tumor-associated myeloid cells mainly represented by tumor-associated macrophages and myeloid-derived suppressor cells hinder inhibition by targeted approaches or monotherapies. Here I provide insights into a novel, integrative therapeutic model that aims at both killing tumor cells and counteracting tumor-associated myeloid cells via the induction of excessive oxidative conditions in tumors. In conclusion, accumulating iron and lipid peroxides in both tumor- and myeloid cells and extracellularly in the tumor microenvironment combined with limiting phagocytosis due to C3d(g) may synergistically increase the oxidized burden and induce tumor cytotoxicity. Future directions include detailed suggestions on criteria for intermittent administration of the proposed therapeutics so that newly recruited myeloid cells could differentiate/be activated to functional anti-tumor phenotypes in a more antigenic tumor microenvironment. Furthermore, combination with other therapeutic forms might be promising. Optimizing the delivery of ION-containing liposomes at tumor sites is also important, thus enhancing their efficiency and safety profiles.

Clinical auditing for surfactant therapy in preterms with respiratory distress syndrome

Background Respiratory distress syndrome (RDS) of prematurity is a major cause of morbidity and mortality in preterm infants, caused by deficiency of pulmonary surfactant and structural immaturity of the lungs. Preterms with RDS should be given a natural surfactant as early as possible. Early surfactant therapy (within 2 h of birth) should be considered for preterms with gestation periods less than or equal to 31 weeks if the need for intubation in the delivery room arises. Lack and unavailability of surfactant in middle-income and low-income countries can occur, and preterms with RDS are treated with ventilation only. Aim The aim of this study was to study the effectiveness of surfactant application in preterms less than 36 weeks with RDS. Short-term effectiveness was monitored by improvement of chest radiograph, oxygen saturation (SpO2), and blood gases with decreasing ventilatory settings after 6 h. Long-term effectiveness was monitored by fate, duration of oxygen therapy, and duration of hospital stay. Moreover, the adverse effects of surfactant were detected. Patients and methods This cross-sectional study was carried out over a period of 18 months in the neonatal ICUs of the Department of Pediatrics, Cairo University hospitals, and included 180 preterms less than 36 weeks of gestational age. We compared 90 preterms less than 36 weeks with RDS who received more than or equal to one dose of surfactant therapy, with 90 controls who had RDS and were eligible for the criteria of administration of surfactant but could not receive surfactant because of its unavailability in the unit at their time of admission. The two groups were compared regarding the period of ventilation, the improvement in ventilator settings and the capillary blood gases after surfactant application, hospital stay, and complications of prematurity. Results Surfactant application significantly improved the preterms, as seen in improvement of radiograph, capillary blood gases, and SpO2. Six hours after administration of surfactant in the case group, 59 (65.6%) cases showed an improvement in capillary blood gases, and after 6 h of ventilation in the control group, only 21 (23.3%) showed improvement in capillary blood gases, with a P value of 0.001. A total of 60 (66.7%) cases had an improved SpO2 after 4 h, but this was seen in only 17 (18.9%) controls, with a P value less than 0.001. Findings of RDS in chest radiograph showed improvement in 60 (66.7%) preterms in the cases group, whereas in the control group, 37 (41.1%) preterms were only improved. However, the mortality rates and the incidence of bronchopulmonary dysplasia were slightly higher in the group that received surfactant, with P values of 0.488 and 0.530, respectively. Conclusion Surfactant application showed significant improvement in preterms with RDS, as seen in improvement of radiograph, capillary blood gases, and SpO2. The mortality rate and the incidence of bronchopulmonary dysplasia were significantly higher in the surfactant group. Risk factors that significantly increased the mortality rates and the hospital stay in cases that received surfactant were very low body weight, gestational age less than 32 weeks, Downe’s score more than 7, severe pulmonary hypertension, and late-onset sepsis. Sustainable efforts to provide all preterms with RDS in low-middle income countries with surfactant therapy should be encouraged.

Laser-Assisted In Situ Keratomileusis (LASIK) Enhancement for Residual Refractive Error after Primary LASIK.

Background: To evaluate the safety, efficacy, and predictability of laser-assisted in situ keratomileusis (LASIK) enhancement after primary LASIK and compare to Food and Drug Administration (FDA) criteria. Methods: Patients who underwent LASIK enhancement after primary LASIK between 2002 and 2019 were compared to those who underwent LASIK without retreatment. Patient demographics, preoperative characteristics, visual outcomes, and postoperative complications were compared between groups. Epithelial ingrowth (EI) development was stratified based on duration between primary and secondary procedures. Results: We compared 901 eyes with LASIK enhancement to 1127 eyes without retreatment. Age, sex, surgical eye, sphere, cylinder, and spherical equivalent (SE) were significantly different between groups (p < 0.05). At 12 months post-enhancement, 86% of the eyes had an uncorrected distance visual acuity of 20/20 or better and 93% of eyes were within ±0.50 D of the target. Development of EI (6.1%) demonstrated an odds ratio of 16.3 in the long-term compared to the short-term (95% CI: 5.9 to 45.18; p < 0.0001). Conclusions: Older age at primary LASIK, female sex, right eye, and larger sphere, cylinder and SE were risk factors for enhancement. Risk of EI significantly increased when duration between primary and enhancement procedures exceeded five years. LASIK enhancements produce favorable outcomes and meet FDA benchmarks for safety, efficacy, and predictability.

Quantification of phosphatidylethanol combining dried blood spots sampling with Orbitrap-based LC-HRMS platform: Method validation and proficiency testing

Phosphatidylethanols (PEth) are phospholipids specifically synthetised by an enzymatic reaction in presence of ethanol. PEth is a mid-term direct biomarker for alcohol consumption or abstinence, leading to a growing interest for forensic toxicology purposes. Blood deposition onto a filter paper card as dried blood spots (DBS) allows PEth stabilisation which is otherwise easily degraded at room temperature. The goal of this study was to develop and validate a procedure for the quantification of PEth 16:0/18:1, the most abundant analogue, in DBS samples benefiting from the selectivity brought by Orbitrap-based high-resolution mass spectrometry (HRMS). Calibration samples and quality controls (QCs) are volumetrically spotted (10 μL) onto filter paper card (Whatman 903 protein saver) either using HemaXis DB10™ device, or using laboratory micropipette. The whole DBS is manually punched out and the PEth is then directly extracted using an in vial approach with 100 μL of PEth 16:0/18:1-D5 in methanol. Analyses are then performed by LC-HRMS in PRM mode using a QExactive Orbitrap platform. Validation was carried out on with respect to the Food and Drug Administration (FDA) criteria, using three different QC concentrations (39, 87 and 350 ng/mL) over three non-consecutive days. To assess the robustness of our method, an interlaboratory proficiency testing was carried out using 3 different commercial standards at 4 levels (50, 100, 200, and 300 ng/mL) of quality controls (QCs) provided by ACQ Science (Germany). The method was fully validated according to guidelines set forth by the FDA. Calibration curve was built using a weighting factor of 1/x. Trueness was measured between 100.1 and 103.6% for the tested concentrations. Repeatability and intermediate precision were found to be lower than 5%. Linearity was evaluated between the lower limit of quantification of 20 ng/mL and the upper limit of quantification of 2000 ng/mL with an R2 greater than 0.998. Recovery (RE) and matrix effect (ME) evaluated at 2 concentrations ranged from 76 to 99% and 8 to 10%, respectively. During the proficiency test, precision was evaluated below 8.0%, while the accuracy ranged from 93.8% to 105.9% and from 101 to 104.5% when compared with the expected concentration and the mean measured value of all the labs participating respectively. The validation results demonstrate that the use of Orbitrap-based PRM quantification present an interesting alternative over triple quadrupole platforms considered as the gold standard for LC-MS/MS quantitative approaches. Indeed, multiple reaction monitoring (MRM) and PRM provide comparable performance in terms of sensitivity, linearity, dynamic range, precision and repeatability. Moreover, the use of PRM provides access to the full fragmentation spectra without any preanalytical considerations. The proficiency testing results confirm the suitability of PRM mode showing great quantification performances. In addition, those results and especially the repeatability exhibit the precision of the volume control provided by the use of HemaXis™ device. This tool enables the standardisation of the DBS collection at the fingertip in a non-hospital environment either by minimally-trained medical staff or by the patient himself. A rapid, sensitive, and robust method was developed and fully validated for the detection and quantification of PEth 16:0/18:1 in DBS samples. The results of the validation process and the proficiency testing confirm that the use of DBS associated with HRMS PRM-based analyses does not hinder the analytical performances, while providing full information over the MS-MS spectra. The development of analytical tools enabling the use of DBS microsampling that can be performed in almost every environment opens new opportunities toward clinical and forensic toxicological applications.

Khảo sát nồng độ kháng thể kháng miền liên kết thụ thể của SARS-CoV-2 sau tiêm 2 mũi vắc xin phòng COVID-19 trên đối tượng nhân viên y tế của trường Đại học Y Hà Nội

Vaccination against COVID-19 is considered as the most effective way to prevent the spread and mitigate the consequences of the COVID-19 pandemic. However, in order to ensure the effectiveness of vaccination, monitoring and evaluation of the effect of vaccines to produce antibodies are always important. In this study, we evaluated the antibody concentration against the receptor-binding domain (RBD) of SARS-CoV-2 after 2 doses of COVID-19 vaccine on medical staffs at the Hanoi Medical University. There were 66 out of 68 (97.06%) study participants whose anti-RBD antibody concentration of SARS-CoV-2 reached the threshold that could make convalescent plasma products with high antibody titers according to the criteria of Food and Drug Administration (FDA) standards. The average anti-RBD antibody concentration of SARS-CoV-2 of the group receiving 2 doses of AZD1222 (AstraZeneca) vaccine and the group receiving at least 1 dose of BTN162b2 (Pfizer) vaccine were 1202.33 and 4312.92 U/mL, respectively. In a total of 56 study subjects who received 2 doses of AZD1222 vaccine, we found a decrease in the anti-RBD antibody concentration of SARS-CoV-2 in the group that received the 2nd dose over 90 days compared to the group under 90 days (p=0.044). At the same time, we did not find an association between adverse effects and anti-RBD antibody concentration of SARS-CoV-2 after the AZD1222 vaccination. These results once again emphasize the effectiveness of the vaccination campaign in Vietnam, as well as contribute to the importance of deploying booster vaccinations to ensure the maintenance of the protective effectiveness of the vaccine.

비교행정의 새로운 국가분류기준

In the era of globalization in which the validity of the New Public Management (NPM) is suspected, comparative administrative research is necessary in order to strengthen the competitiveness of the government. This study presented the new national classification criteria for comparative administration as a social integration and political-administrative relationship, and classified 56 developing countries into four types through the fuzzy set ideal analysis method. As a result of the analysis, 10 countries with “integrated/administrative state” (Type A), 17 countries with “integrated/legislative state” (Type B), 16 countries with “non-integrated/administrative state” (Type C), and 10 countries with “non-integrated/legislative state” (Type D) were derived. This study contributes to future comparative administrative research by presenting new national classification criteria.

Relaxation of the criteria for entry to the UK Clozapine Central Non-Rechallenge Database: a modelling study

Clozapine is uniquely effective in treatment-resistant psychosis. In the UK, patients must discontinue clozapine indefinitely if they are placed on the Central Non-Rechallenge Database (CNRD) after their haematological parameters fall below particular thresholds. Under exceptional circumstances, patients can be rechallenged on clozapine under an off-licence agreement. In the USA in 2015, restrictive practice was discontinued to allow greater flexibility for clozapine maintenance. The absolute neutrophil count leading to treatment interruption was lowered from less than 1·5 × 109/L to less than 1·0 × 109/L and platelet and white cell count monitoring were ceased. We aimed to investigate the implications of a similar policy change on clozapine use in the UK. This was a modelling study of all patients registered on the UK CNRD. First, we determined the proportion of patients placed on the database in the UK who would have had to discontinue clozapine treatment under the US Food and Drug Administration (FDA) criteria. Second, we compared the haematological characteristics of patients who did or did not meet FDA criteria for discontinuing clozapine, including the time to registration from clozapine initiation and the proportion of cases of severe neutropenia at registration. Third, we investigated the success rates of clozapine re-challenge for patients that had been placed on the CNRD. Successful rechallenge was defined as no recurrence of CNRD registration. Between May 2, 2002 and March 1, 2021, 3731 patients were placed on the CNRD, with a mean age of 47 years (SD 15), including 1420 (38%) women and 2311 (62%) men, of whom 3089 (83%) were White, 360 (10%) were Black, 190 (5%) were Asian, and 92 (2%) were classified as other. 566 (15%) of 3731 patients met the equivalent criteria for clozapine discontinuation under the FDA guidelines. The median time to CNRD registration from clozapine initiation was 1·6 years (IQR 0·2-4·9). Data for 519 rechallenged patients were examined; 419 (81%) were successful. Clozapine rechallenge success rates were broadly similar between individuals who did not meet the US CNRD registration criteria (36 [78%] of 46) and those who did meet the criteria (383 [81%] of 473). Implementing the revised FDA monitoring criteria in the UK would substantially reduce clozapine discontinuation for haematological reasons, which would greatly improve the mental health outcomes of these patients without having a major effect on their physical health. None.

External validation of WGS-based antimicrobial susceptibility prediction tools, KOVER-AMR and ResFinder 4.1, for Escherichia coli clinical isolates

ObjectiveTo externally validate whole genome sequence-antimicrobial susceptibility testing phenotype prediction tools KOVER-AMR and ResFinder 4.1 for Escherichia coli clinical isolates from Dutch routine care. MethodsA random sample of 234 E. coli and 283 third generation cephalosporin-resistant E. coli isolates from urine and blood were collected (2014–2017). Culture-antimicrobial susceptibility testing was performed using VITEK 2 and BD Phoenix. Sequences were used as input for KOVER-AMR-SCM, KOVER-AMR-CART, and ResFinder 4.1. The concordance, major error rate (MER), and very major error rate (VMER) were calculated, with subsequent comparison to U.S. Food and Drug Administration (FDA) criteria (MER ≤3% and VMER with a 95% confidence interval ≤1.5–≤7.5%). ResultsResFinder 4.1 performed better than KOVER-AMR-models; however, neither tool achieved overall (V)MERs below FDA criteria. KOVER-AMR-SCM, KOVER-AMR-CART, and ResFinder 4.1, MER (cumulative all antimicrobials) were: 5.1% (4.4–5.9), 4.3% (3.6–5.0), and 5.1% (4.5–5.8), respectively. MERs ≤3% were achieved for 6 (SCM) and 5 (CART) of the 11 tested antimicrobials for KOVER-AMR-models and for 9/13 antimicrobials tested with ResFinder 4.1. KOVER-AMR-SCM, KOVER-AMR-CART, and ResFinder 4.1 cumulative VMERs were: 26% (24–28), 29% (27–31), and 11% (9.2–12). VMERs with a 95% CI ≤ 1.5–≤7.5 were only achieved for 4/13 tested antimicrobials with ResFinder 4.1. DiscussionIn this study, whole genome sequence-antimicrobial susceptibility testing phenotype prediction tools KOVER-AMR and ResFinder 4.1 did not meet the FDA criteria needed for clinical diagnostic use in 517 E. coli clinical isolates from Dutch routine care. The tested tools should be further improved before they can be used for clinical decision making.

1386-P: Confirmation of the Criteria for Insulin Administration at the Start of Steroid Therapy

Blood glucose elevates at initial high-dose steroid (HDS) administration and is prolonged by persistent amplification of glucagon-induced glycogenesis. Insulin (INS) administration at initial dose of HDS will avoid this. However, INS administration criteria regarding BS elevation are not defined. HDS were given based on COVID-treatment guidelines. HDS administration circumstances in clinical settings may clarify these criteria. The necessity of INS therapy at initial HDS administration is studied. COVID-inpatients receiving HDS, regarding a COVID-period in Japan comprising 5 waves, were sub-grouped into those requiring INS therapy and those not, and analyzed with respect to age, BMI, fasting blood glucose (FBS) , A1c, C-peptide (CPR) index, CPR/glucagon (GCG) . INS was administered, target BS level 200 mg/dL or less at 14:00, depending on BS level after HDS administration. From 396 patients, 257 received HDS as follows, 1of the 154 patients in Wave 1-3 (69.5 ± 16.7 years, BMI 23.9 ± 4.8%, A1c 6.3 ± 1.1%) , 79 of the 83 patients in Wave 4 (64.5 ± 14.6 years, BMI 24.9 ± 4.78, A1c 6.6 ± 1.1%) , and 73 of the 117 patients in Wave 5 (54.4 ± 15.2 years, BMI 25.2 ± 5.1, A1c 6.2 ± 0.8%) . Of the 257 patients above, 145 were treated with INS. In all Waves, only FBS and A1c differed significantly between INS-treated and non-INS-treated patients. ROC analysis in Wave 1-3, Wave 4 and Wave 5 showed cut-off values of A1c (sensitivity/specificity) and FBS (sensitivity/specificity) measuring 6.1% (0.85/0.62) and 121.5 mg/dL (1.00/ 0.62) , 6.5% (0.44/0.83) and133.5 mg/dL (0.40/0.93) , and 6.4% (0.49/1.0) and 112.5 mg/dL (0.81/0.85) , respectively. In patients with FBS levels of 112.5 mg/dL or higher or A1c levels of 6.3% or higher, the use of INS from the initial HDS administration reduced prolongation of hyperglycemia. Variables BMI, CPR, and GCG secretion cannot determine the need for INS therapy. It is important to use FBS and A1c levels, according to conventional practice, to ascertain if INS administration is necessary. Disclosure S.Kaneko: None. K.Motohashi: None. T.Minami: None. Y.Ueba: None. T.Osugi: None. S.Tokumoto: None. Funding Reiwa 2nd year cookie test clinical research grant

Administrative records-based criterion measures

ABSTRACT This paper covers considerations in using criterion measures based on administrative data. We begin with a conceptual framework for understanding and evaluating administrative criterion measures as “objective” rather than (ratings-based) assessments of job performance. We then describe the associated advantages (e.g., availability) and disadvantages (e.g., contamination) of using administrative data for criterion-related validation purposes. Best practices in the use of administrative data for validation purposes, including procedures for (a) handling missing data, (b) performing data checks, and (c) reporting detailed decision rules so future researchers can replicate the analyses are also described. Finally, we discuss “modern data management” approaches for improving administrative data for supporting organizational decision-making.

Quantitative Analysis of Fat-Soluble Vitamins in Feed Additives Using an In-House Developed and Validated HPLC Method

Quantification of vitamins in complex matrices such as feed additives is a time-consuming analytical procedure. In this study, a simple and precise in-house High Performance Liquid Chromatography (HPLC) method was developed and validated for the simultaneous detection and quantification of four fat-soluble vitamins such as vitamin A, D3 , E, and K3 in feed additives. The HPLC method was developed and validated using reversed-phase column chromatography. The chromatographic separation of the vitamins was carried out at 25° C temperature on a reverse-phase C18 column using a binary gradient pump mode. Mobile phase constituents were solvent (a): deionized water and (b) methanol. Detection was performed with HPLC ultraviolet/visible detection set at 325, 265, 230, and 254 nm wavelength for vitamin A, D3 , E, and K3 respectively. The flow rate was 1.0mL/min and the total run time was 20min. The method was validated according to the guidelines of the International Conference on Harmonization (ICH) and Food and Drug Administration (FDA), USA, and acceptance criteria for system suitability, specificity, linearity, accuracy, and precision were met in all the cases. The Relative Standard Deviation (RSD) for system suitability and precision was &lt;2% for all the studied vitamins. The linearity of the calibration curves was excellent (R2 &gt;0.999) at concentrations of 2.5, 5.0, 7.5, 10.0, 15.0, and 20.0 µg/mL for all vitamins, and the range of linearity of this method was 0.0-50.0 μg/mL with R2 value greater than 0.999. The limits of detection values were 0.0022, 0.0012, 0.0022, and 0.0020 µg/ mL for vitamin A, D3 , E, and K3 , respectively, and the limits of quantification values were 0.0066, 0.0038, 0.0066, and 0.0061 µg/mL for vitamin- A, D3 , E, and K3 respectively. The recovery percentages ranged from 85% to 103%, and the robustness of the method is also high with excellent reproducibility. The overall parameters of the proposed method met the validation criteria and this method could be a precise and highly desirable analytical procedure for accurate quantification of four fat-soluble vitamins such as A, D3 , E, and K3 in feed additives using a single chromatographic run.

Diuretic Renal Scintigraphy Protocol Considerations.

Diuretic renal scintigraphy plays a critical diagnostic role by providing a physiologic means for differentiating between obstructive and nonobstructive hydronephrosis as well as assessing the function of the affected kidney. The exam accuracy is highly dependent upon and benefits from close attention to the protocol. This article reviews kidney anatomy and physiology, patient preparation, available radiopharmaceuticals, diuretic administration, acquisition, processing, quantification, and interpretation criteria.

Trust in the State Border Guard Service of Ukraine: theoretical and legal context

The article emphasizes that the determining factor in the process of reforming law enforcement agencies, including the State Border Guard Service of Ukraine, is the level of public confidence in them. The provisions of certain by-laws, which regulate the issues of public trust in the specified law enforcement agency of special purpose, are characterized.&#x0D; The paper analyzes the level of public confidence in the border agency during 2015–2021. It is emphasized that it directly affects, on the one hand, the building of institutional capacity, and on the other – the level of trust in law enforcement agencies in general as components of the security and defense sector. During the period under review, there has been a positive trend in increasing public confidence in the State Border Guard Service of Ukraine. At the same time, studies of independent sociological structures showed the highest level of trust in the border agency in the public security and rule of law sector in 2021, which indicates its effective operational and service and other activities in general.&#x0D; To more objectively determine the state of public confidence in the State Border Guard Service of Ukraine, as well as to clarify the peculiarities of its manifestation, it is proposed to classify the studied category according to some of the most important criteria in the context of specific tasks performed by the Border composition of the subjects of trust, taking into account the region of residence, administrative criteria, as well as the density of the population, etc. According to the subject composition between interpersonal trust (micro level) and institutional trust (macro level), trust in the State Border Guard Service of Ukraine belongs to institutional trust, which occupies a prominent place in building the institutional architecture of society.&#x0D; The factors influencing the level of public confidence in the State Border Guard Service of Ukraine are summarized and characterized, which must be taken into account when summarizing the operational and service activities of the agency for a certain reporting period and setting tasks for the next period.