Prescription of Aminoglycosides in 23 French Neonatal Intensive Care Units

Background: Aminoglycosides are the most prescribed antibiotics in neonatal intensive care units (NICU). Reducing exposure to antibiotics in the NICU is highly desirable, particularly through benchmarking methods. Methods: Description of aminoglycosides prescriptions in 23 French NICU using the same computerized system over a 4-year period (2017–2020). A benchmarking program of antibiotics prescription was associated. Results: The population included 53,818 patients. Exposition rates to gentamicin and amikacin were 31.7% (n = 17,049) and 9.1% (n = 4894), respectively. Among neonates exposed to gentamicin, 90.4% of gentamicin and 77.6% of amikacin treatments were started within the 1st week of life. Among neonates exposed to amikacin, 77.6% started amikacin within the 1st week. The average daily dose of gentamicin at first prescription increased over the study period from 3.9 in 2017 to 4.4 mg/kg/d in 2020 (p < 0.0001). Conversely, the corresponding amikacin daily doses decreased from 13.0 in 2017 to 12.3 mg/kg/d in 2020 (p = 0.001). The time interval between the first 2 doses of gentamicin was mainly distributed in 3 values during the first week of life: 49.4% at 24 h, 26.4% at 36 h, and 22.9% at 48 h. At first amikacin prescription, the time interval was distributed in 4 categories: 48% at 24 h, 4.1% at 30 h, 8.5% at 36 h, and 37.1% at 48 h. As compared to literature guidelines, the rates of overdose and underdose in gentamicin (1.5% and 2.7%) and amikacin (0.3% and 1.0%). They significantly decreased for gentamicin over the study period. In multivariate analysis, the factors significantly associated with GENT overdose were the year of admission, prematurity, length of stay, and duration of the treatment. Conclusion: This prescription strategy ensured a low rate of overdose and underdose, and some benefits of the benchmarking program is suggested.

Occurrence and Health Risk Assessment of Aflatoxins through Intake of Eastern Herbal Medicines Collected from Four Districts of Southern Punjab—Pakistan

Eastern herbal medicines (HMs) are plant-derived naturally occurring substances with minimum or no industrial processing that have long been used in traditional medicine. Aflatoxins are frequent contaminants of plants. Therefore, these mycotoxins are likely to contaminate HMs and pose a health risk to individuals using them on a regular basis as preventive or curative treatments of various diseases. The present study aimed to determine aflatoxin levels in the most popular Pakistani HM formulations and to assess the health risk associated with the intake of aflatoxins. A total of 400 samples of HM formulations collected from four districts of Punjab were analyzed for the quantification of aflatoxins, out of which 52.5% were found to be contaminated. The average daily dose (ADD) of AFB1 and AFs through the intake of HM formulations ranged between 0.00483 and 0.118 ng/kg bw/day and between 0.00579 and 1.714 ng/kg bw/day, respectively. The margin of exposure (MOE) and population cancer risk ranged from 99.49 to 29378.8 and from 0.00011 to 0.0325 liver cancer cases/105 individuals/year (0.0075–2.455 liver cancer cases/105 individuals/75 years), respectively. Despite the low exposure to aflatoxins from HM formulations in the four studied Punjab (Pakistan) districts, the frequent contamination of the analyzed samples suggests that official measures should be considered to manage the associated risk.

Identifying Prescription Patterns and Iron Supplementation With Chinese Herbal Medicine for Uterine Myoma in Taiwan: A Social Network Analysis of the Chang Gung Research Database

Background: Uterine myoma is a common gynecological disease in women of reproductive age. Owing to surgery and treatment-related complications, many patients opt for alternative therapy, such as traditional Chinese medicine (TCM). However, there is no standard treatment protocol for TCM. This study aimed to investigate the prescription patterns of TCM for uterine myoma and compare differences between the Chang Gung Research Database (CGRD) and the National Health Insurance Research Database (NHIRD). Methods: Data of 217040 patients newly diagnosed with uterine myoma between 2005 and 2014 were retrieved from the CGRD using the International Classification of Diseases, Ninth Revision, Clinical Modification code for myoma and related symptoms. We analyzed patient demographics, frequencies and average daily doses of prescribed Chinese herbal formulas and single herbs, and iron supplementation doses. Associations between Chinese herbal formulas and single herbs commonly used for uterine myoma were analyzed by association rule mining (ARM) and social network analysis (SNA).Results: In total 45,436 patients used TCM. Most participants (49.1%) were aged 30–44 years. Jia-Wei-Xiao-Yao-San (28.2%; average daily dose 4.85 g) and Xiang-Fu (22.0%; average daily dose 1.10 g) were the most frequently prescribed herbal formula and single herb, respectively. Additionally, the Si-Wu-Tang decoction was often used for uterine fibroids. Common prescription patterns and herbal pairs were identified. Western medicine (WM) outpatient visits (12 ± 19.6) and iron supplement prescriptions (prescription code PLB001M, 62.5 ± 115.3 pills; PLB012M, 24.6 ± 78 pills) were more prevalent in the combined therapy group than in the WM-only group (outpatient visits: 5.9 ± 6.7 times; iron supplements: PLB001M, 48.3 ± 98.4 pills; PLB012M, 20.9 ± 67.5) in the CGRD. Conclusions: We characterized the prescription patterns for uterine myoma in the CGRD. Chinese herbal medicine prescriptions may aim to improve anemia related to hypermenorrhea caused by uterine myoma. Ours is the first study of TCM myoma treatment within the CGRD, and we compared our findings to the TCM NHIRD myoma study results. ARM and SNA of TCM prescription patterns provide an evidence base to inform medical education and medical decision-making.

AB0474 THE USE OF NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS) IN WOMEN WITH ANKYLOSING SPONDYLITIS (AS) DURING PREGNANCY

Background:NSAIDs remain the first-line drugs in treatment of AS. During pregnancy, COX-2 non-selective NSAIDs are allowed for intake up to 32 weeks, but the question of the dose-dependent effect of NSAIDs on fetal organogenesis in the 1st trimester and on fetal kidney function and the increased risk of bleeding in childbirth when taken in the second half of pregnancy continues to be discussed. At the same time, data on the effectiveness of NSAIDs, including their low and medium doses, during pregnancy are extremely small.Objectives:to describe the frequency of using NSAIDs during pregnancy, to determine relationship between the dose of NSAIDs, adherence to therapy with the activity of AS.Methods:50 pregnancies were followed in 49 pregnant women with confirmed AS (modified New York criteria, 1984). The average age of the pts was 31.6 ± 4.9 years, the duration of the disease was 134.4 ± 85.8 months. The visits were conducted at 10-11, 20-21, and 31-32 weeks of pregnancy. The BASDAI in the month of conception and in the trimesters (trim.) of pregnancy was: 1,4[0,6; 3,3]; 2,3[1,2; 4,4]; 2,8[1,4; 4,2] and 2,2[1,6; 4,0], respectively. The level of nocturnal back pain according to the NRS in the first, second and third trim. was: 3.2±2.0; 5.4±2.5 and 5.2±2.6, respectively. The drug of choice was ibuprofen at a maximum daily dose of 1200 mg, its withdrawal - no later than 32 weeks of pregnancy.Adherence to NSAID therapy was defined as the ratio of the actual dose taken to the prescribed dose; an indicator of less than 80% was regarded as non-adherence to therapy. The total dose of NSAIDs was determined by the NSAID intake index (M. Dougados, 2001). The” actual daily dose” of ibuprofen was the sum of the doses of ibuprofen taken, divided by the number of actual days of taking the drug. The “average daily dose” was defined as the sum of the ibuprofen doses taken, divided by the number of days in the trimester.Results:At the time of conception and in the first, second and third trim. of pregnancy, NSAIDs were taken 23 (46%), 20 (40%), 30 (60%) and 21 (43.8%) women, respectively. The NSAID intake index, the actual and average daily dose of ibuprofen are shown in the Table 1.month of conceptiontrim. 1trim. 2trim. 3the actual daily dose, mg-700[425; 800]800[400; 1000]750[400; 1200]the average daily dose, mg-158[87,9; 307,7]355,1[138,5; 685,7]580[320; 1200]NSAIDs intake index28,6 [16,7; 50]5,8 [2,9; 11,8]15,5 [4,7; 30,9]24,4 [9,5; 50]The index of NSAID intake in the first trim. was lower than before pregnancy and in the second half of gestation (p<0.05 compared to the month of conception, II and III trim.). The average daily dose of ibuprofen was also lower in the first trim. than in the second and third trim. (p<0.05), while the actual daily dose in the second trim. was higher than in the first and third trim. (p<0.05 in all cases).There was no correlation between BASDAI AS activity, the level of nocturnal pain and the ibuprofen intake index, likewise the fact of NSAID withdrawal throughout pregnancy. In addition, there were no differences in BASDAI levels and back pain in women with a subjective need for NSAIDs, who did and did’t take ibuprofen.50% of women were committed to NSAID therapy in the first trim., 43.5% in the second trim., and 67.4% in the third trim. In pts with non-adherence to NSAID therapy, the BASDAI level was higher than in those who followed the recommendations of the rheumatologist throughout pregnancy: in the first trim. – 3.8[3.4; 4.7] and 1.7[0.8; 2.2]; in the second trim. - 3[2.3; 4.6] and 1.4[0.8; 2.7]; in the third trim. - 3.1[2.1; 4.0] and 1.7[1.1; 4.0], p<0.05 in all cases. However, women with adherence > 80% were initially less active and NSAIDs were prescribed “on demand”, which increased their compliance.Conclusion:intake of ibuprofen in low doses does not affect the activity of AS. Due to the ongoing discussion about the effect of NSAIDs on neonatal outcomes, further international studies are required for development an optimal treatment regimen during pregnancy with a possible extension of the indications for the appointment of TNF inhibitors (BASDAI<4).Disclosure of Interests:None declared.

9 Impact of Methadone Initiation in Intubated Burn Patients: A Retrospective Review

Introduction Methadone can be used to wean opiates and reduce length of mechanical ventilation (MV) in critical care and burn patients. The objective of this study was to assess the impact of methadone use on ventilator-free days and clinical outcomes in burned patients requiring MV. Methods This was a retrospective study of adult patients admitted to a burn center for initial management of burn injuries who required MV for at least 48 hours between September 2013 and November 2019. Patients were excluded from the study if they had prior methadone use, total body surface area (TBSA) of less than 5%, or expired within the first 28 days of admission. The primary endpoint was the difference in ventilator-free days among those who received methadone compared to those who did not. Secondary endpoints include length of stay, mortality, sedative agent and average daily dose, analgesic agent and average daily dose, and incidence of delirium. Baseline demographics were compared using descriptive statistics. Nominal data was compared using Chi-square test. Continuous data was analyzed using student’s t-test or Mann-Whitney U test, as appropriate. Multivariate regression was used to identify variables for possible association with MV duration. Results A total of 83 patients were included in the study; 52 received methadone and 31 were controls. Patients were generally well-matched between groups, however patients receiving methadone were younger (45.3 vs 56.2 years, p = 0.002) and had a larger TBSA (30.4 vs 19.1%, p = 0.001). Patients who received methadone had fewer ventilator free days of the first 28 (9.5 vs 15.0 days, p = 0.009) and a longer ICU stay (57.2 vs 35.8 days, p = 0.025). There was no difference between groups in terms of mortality, reintubations, and incidence of delirium. Patients who received methadone had longer duration of analgesia (20.7 vs 12.0 days, p = 0.011) and sedation (19.0 vs 12.4 days, p = 0.026) while on MV. Conclusions This study found that methadone use contributed to fewer ventilator-free days and longer ICU stays, which was unexpected but worth discussing. There are several limitations to this study. This study occurred during a time period in which the pain management and sedation strategies of this burn unit were evolving, and strategies may not have been consistent between providers. The study included a small sample size and baseline demographics demonstrated significant differences in age and TBSA between the two groups. Additionally, pain scores were not collected as part of this study, which would have provided better insight into the effectiveness of pain management. The use of methadone as an adjunct for pain control remains undetermined.

Human health risk assessment of potentially toxic elements (PTEs) and polycyclic aromatic hydrocarbons (PAHs) in urban topsoils of Tyumen city, Russia

&lt;p&gt;Cities are the key centers of technogenesis, which leads to environmental pollution. The state of the soil cover reflects the long-term anthropogenic impact as a result of urbanization processes. In the urban environment, the priority pollutants are potentially toxic elements (PTEs) and polycyclic aromatic hydrocarbons (PAHs), since they are not only an environmental hazard, but also a risk factor for the public health. Tyumen city, with a population of 807,300 people, is a large transport and trade center in Western Siberia, Russia, with a developed service sector, construction and manufacturing industries. The aim of the study is to evaluate possible carcinogenic and noncarcinogenic risks related to PTEs and PAHs in urban topsoils of Tyumen, as representative of urban environment in Western Siberia.&lt;/p&gt;&lt;p&gt;Topsoil samples (0-10 cm) were collected according to the regular grid at 241 sampling points. The total content of V, Cr, Co, Ni, Cu, Zn, As, Sr, and Pb was determined using X-Ray fluorescence spectrometry. Content of twelve priority PAHs was measured using high-performance liquid chromatograph Agilent 1260 Infinity. Human health risk assessment was based on the US EPA model (1989). The noncarcinogenic risk for different age groups of the population, expressed as a hazard quotient (HQ), was evaluated by comparing the average daily dose of pollutant (ADD) with a reference dose (RfD). Carcinogenic risk (CR) reflects the probability of developing cancer in an individual throughout their life, taking into account the lifetime average daily dose of a pollutant (LADD) and carcinogen slope factor (SF). Values of RfD and SF were based on toxicological data (U. S. EPA 1997, 2004, 2020; ATSDR 2020; OEHHA 2020). The combined effects were assessed using the total hazard index (THI) and the total carcinogenic risk (TCR).&lt;/p&gt;&lt;p&gt;Noncarcinogenic risks were more likely caused by intake of V, Co, As, Pb, Ni and Cu. For both children and adults, the risk associated with the oral intake of pollutants was the greatest. For children, significant risks arose from exposure to V, Co, As and Pb (HQ&gt; 1). The THI values for children varied from 0.78 to 7.25, on average 2.72, for adults - from 0.08 to 0.79, on average 0.27. Most of the territory was characterized by a medium non-carcinogenic risk for children and a low risk for adults.&lt;/p&gt;&lt;p&gt;Significant CR was associated with long-term exposure to Co, As, Pb and benzo[a]pyrene. The TCR values under the combined effect of PTEs and PAHs ranged from 1.2 &amp;#215; 10&lt;sup&gt;-5&lt;/sup&gt; to 2.2 &amp;#215; 10&lt;sup&gt;-4&lt;/sup&gt;, on average 6.9 &amp;#215; 10&lt;sup&gt;-5&lt;/sup&gt;. In general, the level of carcinogenic risk in the city was assessed as low. Medium carcinogenic risk was established in the soils of impact zones of enterprises for the production and disposal of batteries, CHPP-1 and some large transport hubs. An extensive zone of increased carcinogenic risk was established in the residential area of the central part of the city.&lt;/p&gt;&lt;p&gt;The research was funded by RFBR and Tyumen Region, project no. 20-45-720003, and by Ministry of Science and Higher Education of the Russian Federation, no. 0852-2020-0029.&lt;/p&gt;

Influence of renal insufficiency on anticoagulant effects and safety of warfarin in Chinese patients: analysis from a randomized controlled trial

This study aimed to analyze the influence of renal insufficiency on the anticoagulant effects and safety of warfarin in Chinese patients. Data on the creatinine levels of participants enrolled in a randomized controlled study were screened and divided into the non-renal insufficiency group, mild renal insufficiency group, and moderate renal insufficiency group, according to the creatinine clearance rate. The primary outcome measures were stable dose and average daily dose of warfarin. Secondary outcome measures were percentage of time in the therapeutic international normalized ratio (INR) (%TTR), and the first time to reach the therapeutic INR. Adverse events included bleeding events, thromboembolic events, and mortality. All participants with renal function test results and a baseline INR of less than 1.5 were included in the primary and secondary outcome analysis. The SPSS Statistics 21.0 software was used for statistical analysis. The randomized controlled trial was registered in Clinicaltrials.gov (NCT02211326). A total of 571 patients were included in this analysis. Multiple regression analysis showed that the renal function was correlated with stable dose, average daily dose, and the first time to reach therapeutic INR after adjusting for confounding factors. However, no correlation was noted between kidney function and %TTR. No significant differences were observed across the various safety parameters among the three groups. Renal function is an important consideration in patients using warfarin.

Corticosteroid dosing and opioid use are high in patients with SLE and remain elevated after belimumab initiation: a retrospective claims database analysis

ObjectivesTo investigate corticosteroid and opioid use among patients with SLE and to examine the impact of belimumab initiation on the use of other SLE therapies.MethodsWe identified adult patients with SLE (International Classification of Diseases, 9th Revision/10th Revision 710.0 and M32) between 1 January 2012 and 31 May 2018 (earliest SLE diagnosis=index date) within MarketScan administrative claims data. Patients were followed from index date for a minimum of 12 months and until the earlier of disenrolment in their health plan or study end (31 May 2018). Corticosteroid utilisation, corticosteroid dose (in prednisone equivalents) and opioid utilisation (overall, by strength (weak, strong) and by duration (chronic use defined as >90 days of cumulative drug supply)) were measured during follow-up. Oral corticosteroid and opioid use were compared in the 6 months before and after initiation of belimumab.ResultsThere were 49 413 patients with SLE eligible for analysis (mean (SD) age: 50.1 (14.0) years, 90.2% female). Of these, 68.5% received corticosteroids, and the average number of prescriptions was 4.59 (4.11) over the first 12 months of follow-up. Among patients with oral corticosteroids, average daily dose was 19.4 (14.2) mg and 59.6% had an average daily dose of ≥15 mg. Half (52.6%) had at least one opioid prescription and of these, 34.6% had chronic use over the first 12 months of follow-up. Among patients initiating belimumab during follow-up (n=1710), oral corticosteroid use decreased by 9.1% (p=0.001), and average daily dose decreased from 14.5 (18.4) mg to 11.9 (18.0) mg (p<0.001) in the 6 months after initiation compared with the 6 months prior. Initiation of belimumab had no impact on prevalence of opioid use.ConclusionsA high proportion of patients with SLE are treated with corticosteroids to control SLE and opioid therapy to manage chronic pain. While there was no change in opioid use, oral corticosteroid use and dose intensity decreased following initiation of belimumab.

Radiological and chemical risk assessment from uranium concentrations in groundwater samples collected from Al-Kufa area, Iraq

In nature, uranium is composed of three isotopes, 238U, 235U, and 234U. Emitting alpha particles leads to radionuclides decay. The aim of this work is to set up a database for uranium concentrations in groundwater samples collected from Kufa city, Al-Najaf governorate, Iraq. Twenty four samples have been examined for detecting the presence of uranium levels using a CR-39 detector. The measured uranium concentrations were used to determine uranium isotopes with their ingested radiological toxicity risk (annual effective dose of uranium isotopes and excess cancer risk) and chemical toxicity risk (lifetime average daily dose and hazard quotient) from consumption of the water samples in the present study. The results show that the average value of uranium concentrations, uranium isotopes 238U, 235U, and 234U (1.20 ± 0.04) μg/L, (1.48 ± 0.06) Bq/L, (0.069 ± 0.002) Bq/L and (1.49 ± 0.06) Bq/L respectively. Also, it is concluded that the total average annual effective dose and excess cancer risk in all regions under study were (0.10 ± 0.004) mSv/y and (0.31 ± 0.013) × 10−3 respectively. Moreover, the average value lifetime average daily dose, and hazard quotient was 0.0389 ± 0.0016 μg/kg.day and 0.0649 ± 0.0026 respectively. All results of radiological and chemical risk assessment from uranium concentrations in groundwater samples collected from the Al-Kufa area when used as drinking water were within the global limitations of the organization International Commission on Radiological Protection (1.9 μg/L; 1 mSv/y and 0.18 mSv/y) and World Health Organization recommended (0.6 μg/kg/day). Finally, it can be concluded that uranium concentrations do not affect human health according to radiation contents.