Administrative Reasons Research Articles

Antiviral combination treatment strategies for SARS-CoV-2 infection in immunocompromised patients.

The purpose of this review is to report the available evidence regarding the use of combination regimens of antivirals and/or antibody-based therapy in the treatment of SARS-CoV-2 in immunocompromised patients. Literature search identified 24 articles, excluding single case reports, which included mainly patients with hematological malignancies and/or B-cell depletion. Data were divided based on the timing and reason for administration of combination treatment, that is, early treatment to prevent progression to severe COVID-19 and treatment of prolonged or relapsed infection. We described the treated populations, treatment duration and composition of combination treatment. We briefly addressed new treatment options and we proposed an algorithm for the management of COVID-19 infection in patients affected by hematological malignancies. Combination treatment seems an effective (73-100%) and well tolerated (<5% reported bradycardia, hepatotoxicity, neutropenia) strategy for treating prolonged/relapsed SARS-CoV-2 infections in the immunocompromised host, although its optimal composition and duration cannot be defined based on the currently available evidence. The role of combination treatment as an early treatment strategy for immunocompromised patients at a high risk of progression to severe disease/persistent shedding requires further evidence from comparison with monotherapy, even though high efficacy was reported for combinations of antivirals plus mAbs in case of previous viral variants.

Dogs receiving cyclooxygenase-2-sparing nonsteroidal anti-inflammatory drugs and/or nonphysiologic steroids are at risk of severe gastrointestinal ulceration.

To report the incidence and characteristics of gastrointestinal ulceration lesions in dogs receiving an NSAID and/or corticosteroid. 33 dogs. Medical records of dogs with gastrointestinal ulceration receiving NSAIDs and/or corticosteroids within 30 days of diagnosis between January 2012 and July 2022 at multiple referral institutions were reviewed. Diagnosis was confirmed via endoscopy, surgery, or necropsy. Clinical data were collected from the medical record, including the dose and reason for administration of NSAIDs or steroids. Dogs received a single NSAID (n = 22, most commonly carprofen [9], meloxicam [4], and deracoxib [3]), 2 NSAIDs (5), a single steroid (5: prednisolone [2], prednisone [2], or dexamethasone SP [1]), or an NSAID and steroid (1). Eleven dogs receiving a single cyclooxygenase (COX)-2-sparing NSAID at an appropriate dose had ulcerations. All dogs receiving 2 NSAIDs concurrently experienced full-thickness perforation (5 of 5). The most common ulcer locations were duodenum (n = 18) and pylorus (11). Abdominal ultrasound correctly identified the site of ulceration in 5 of 24 dogs. Dogs receiving COX-2 sparing NSAIDs at recommended doses are at risk of severe GI ulceration. Carprofen was the most common NSAID resulting in ulceration; however, it is one of the most prescribed NSAIDs. Adding another NSAID and steroid could increase this risk. Careful monitoring is crucial for dogs on NSAIDs, regardless of duration.

Amiodarone or Implantable Cardioverter-Defibrillator in Chagas Cardiomyopathy

Over 10 000 people with Chagas disease experience sudden cardiac death (SCD) annually, mostly caused by ventricular fibrillation. Amiodarone hydrochloride and the implantable cardioverter-defibrillator (ICD) have been empirically used to prevent SCD in patients with chronic Chagas cardiomyopathy. To test the hypothesis that ICD is more effective than amiodarone therapy for primary prevention of all-cause mortality in patients with chronic Chagas cardiomyopathy and moderate to high mortality risk, assessed by the Rassi score. CHAGASICS is an open-label, randomized clinical trial. The study enrolled patients from 13 centers in Brazil from May 30, 2014, to August 13, 2021, with the last follow-up November 8, 2021. Patients with serological findings positive for Chagas disease, a Rassi risk score of at least 10 points (intermediate to high risk), and at least 1 episode of nonsustained ventricular tachycardia were eligible to participate. Data were analyzed from May 3, 2022, to June 16, 2023. Patients were randomized 1:1 to receive ICD or amiodarone (with a loading dose of 600 mg after randomization). The primary outcome was all-cause mortality, and secondary outcomes included SCD, hospitalization for heart failure, and necessity of a pacemaker during the entire follow-up. The study was stopped prematurely for administrative reasons, with 323 patients randomized (166 in the amiodarone group and 157 in the ICD group), rather than the intended 1100 patients. Analysis was by intention to treat at a median follow-up of 3.6 (IQR, 1.8-4.4) years. Mean (SD) age was 57.4 (9.8) years, 185 patients (57.3%) were male, and the mean (SD) left ventricular ejection fraction was 37.0% (11.6%). There were 60 deaths (38.2%) in the ICD arm and 64 (38.6%) in the amiodarone group (hazard ratio [HR], 0.86 [95% CI, 0.60-1.22]; P = .40). The rates of SCD (6 [3.8%] vs 23 [13.9%]; HR, 0.25 [95% CI, 0.10-0.61]; P = .001), bradycardia requiring pacing (3 [1.9%] vs 27 [16.3%]; HR, 0.10 [95% CI, 0.03-0.34]; P < .001), and heart failure hospitalization (14 [8.9%] vs 28 [16.9%]; HR, 0.46 [95% CI, 0.24-0.87]; P = .01) were lower in the ICD group compared with the amiodarone arm. In patients with chronic Chagas cardiomyopathy at moderate to high risk of mortality, ICD did not reduce the risk of all-cause mortality. However, ICD significantly reduced the risk of SCD, pacing need, and heart failure hospitalization compared with amiodarone therapy. Further studies are warranted to confirm the evidence generated by this trial. ClinicalTrials.gov Identifier: NCT01722942.

Patterns of Corticosteroid Prescriptions among Patients at Community Pharmacies in Lahore, Pakistan

Background: Corticosteroids are a class of steroid hormones produced by the adrenal gland and are used to treat many diseases, including autoimmune diseases and inflammatory diseases. Besides their role in many diseases, long-term use, misuse, and overuse cause side effects including hypertension, diabetes mellitus, and osteoporosis. Objective: The aim of current study is to evaluate the prescription pattern of corticosteroids in different community pharmacies, among patients, in Lahore. Methods: The cross-sectional stratified convenient study performed using a validated questionnaire to analyse the prescription pattern of corticosteroids in patients at different community pharmacies in Lahore. Total 92 patients are participating in this study. Results: A total of 92 patients take part in the study. In this research 67.4% females are participated. The average age of patients is above 30 years. Asthma is the most common reason for corticosteroids administration (19.6%) followed by rheumatoid arthritis (12.0%) whereas in inflammatory bowel disease they are least prescribed (1.1%). Prednisolone is the most prescribed drug (33.7%) and Oral route is the frequently given route. Conclusion: Our data shows that the prescription pattern of corticosteroid must be improved. Health care providers should pay attention to counseling of patients and guide them about dose tapering to avoid adverse effects.

Olokizumab effect on chronic pain in rheumatoid arthritis: Results of the PROLOGUE observational study.

Evaluate the efficacy and safety ® (olokizumab) in patients with rheumatoid arthritis (RA) in real-world clinical practice, with a targeted assessment of patient report outcomes (PRO) and central sensitization. An open-label observational non-interventional study was conducted, enrolling 183 patients with moderate and severe RA activity. All patients received OKZ 64 mg SC as injections every 4 weeks (Q4W) with methotrexate. The patients' follow-up period was 24 weeks or less. RA activity (DAS28-CRP), pain severity (NRS), patient global assessment (PGA, NRS), functional impairment (NRS), fatigue (FACIT-F), central sensitization (central sensitization inventory, CSI), and symptoms of neuropathic pain (PainDETECT) were evaluated. The study cohort was comprised of 144 patients. And 39 patients were lost to follow-up, refused OKZ treatment, or were not dosed with OKZ for administrative reasons. In 6 months, DAS28-CRP decreased to 3.3 ± 0.9 (p < .001) and statistically significant reductions in pain intensity, PGA, functional impairment, and fatigue were achieved. Pain intensity decreased as early as 2 days after the first OKZ administration (p < .05). The number of patients with CSI >40 in 24 weeks decreased from 71.0% to 21.0% (p < .001), with PainDETECT >18 - from 21.5% to 13.2%. NSAIDs use decreased from 70.8% to 33.8% (р < .001), steroids - from 54.2% to 32.6%. AEs were reported in 14.2% patients, serious events were observed in three patients. OKZ is effective in reducing RA activity and controlling chronic pain related to dysfunction of the nociceptive system.

Safety and Effectiveness of Four-Factor Prothrombin Complex Concentrate in Special Populations with INR Below 2: A Post-Marketing Surveillance Study.

We previously conducted a prospective, observational post-marketing surveillance study to assess the safety and effectiveness of four-factor prothrombin complex concentrate (4F-PCC) for rapid vitaminK antagonist (VKA) reversal in Japanese patients. This subgroup analysis compared the safety, especially thromboembolic events (TEEs), and effectiveness of 4F-PCC by stratifying patients into two subgroups according to baseline international normalized ratio (INR) levels with < 2.0 and ≥ 2.0. Of 1271 eligible patients, 215 (17.9%) had INR < 2.0 and 987 (82.1%) had INR ≥ 2.0. Overall baseline characteristics were similar between groups; age (74.0years vs 74.0years), body mass index (22.1kg/m2 vs 21.9kg/m2), ratio of inpatients (90.2% vs 88.7%), manifested atrial fibrillation (46.0% vs 48.8%). Median INRs at baseline were 1.72 (minimum 0.92, maximum 1.99) in the INR < 2.0 group and 2.95 (2.00, 27.11) in the INR ≥ 2.0 group. The most common reason for 4F-PCC administration was intracranial hemorrhage (67.0% vs 59.5%), and lesser gastrointestinal bleeding (0.9% vs 7.5%). After 4F-PCC administration (average doses 24.5IU/kg [INR < 2.0 group] and 29.2IU/kg [INR ≥ 2.0 group]), INRs were significantly reduced to 1.21 (- 28%) and 1.31 (- 68%), respectively, and resulted in hemostasis in a similarly rapid manner. The incidences of adverse drug reactions were 3.7% in each group. TEEs occurred in 4 (1.9%) patients in the INR < 2.0 group and 11 (1.1%) patients in the INR ≥ 2.0 group and were predominantly composed of stroke, while similar rates (67.0% vs 62.9%) of bleeding events post-anticoagulant resumption were observed between groups. This study supports the favorable tolerability and efficacy of 4F-PCC regardless of baseline INR (< 2.0 or ≥ 2.0), with a prompt reduction of INR and substantial hemostatic effectiveness in the real-world setting for patients requiring urgent VKA reversal, although no indicated 4F-PCC dose for VKA reversal exists for INR < 2.0 to date.

Political determinants of government transparency: Evidence from open government data initiatives

AbstractThe increasing availability of extensive governmental data, technological advancements, and a rising standard for government openness are encouraging global governments to implement open data initiatives. While some governments are actively adapting to these trends, others remain behind, despite the pressure. This research explores the political and administrative reasons behind these differences. By analyzing how local governments in South Korea handled requests for open data from citizens between 2007 and 2016, the study highlights the importance of political competition and administrative strength in fostering government transparency and effectively addressing citizen data requests. The study assesses open government data based on its scope, time, and quality, finding that higher levels of electoral competition and better administrative capabilities contribute to increased transparency and responsiveness. However, the study's use of a regression discontinuity design reveals that the political party controlling local governments had minimal influence on these factors.Related ArticlesHeo, Inhye. 2013. “The Political Economy of Policy Gridlock in South Korea: The Case of the Lee Myung‐bak Government's Green Growth Policy.” Politics &amp; Policy 41(4): 509–35. https://doi.org/10.1111/polp.12029.Heo, Inhye. 2022. “Energy Democratization Policy without Democratization of Policy Governance in South Korea: A Participatory Democracy Perspective.” Politics &amp; Policy 50(4): 834–50. https://doi.org/10.1111/polp.12480.Nam, Aerang, and Christopher M. Weible. 2023. “Examining Experts' Discourse in South Korea's Nuclear Power Policy Making: An Advocacy Coalition Framework Approach to Policy Knowledge.” Politics &amp; Policy 51(2): 201–21. https://doi.org/10.1111/polp.12522.

Dolutegravir plus boosted darunavir versus recommended standard-of-care antiretroviral regimens in people with HIV-1 for whom recommended first-line non-nucleoside reverse transcriptase inhibitor therapy has failed (D2EFT): an open-label, randomised, phase 3b/4 trial

Randomised comparative data on efficacy and safety of second-line antiretroviral therapy (ART) after failure of non-nucleoside reverse transcriptase inhibitors (NNRTIs) across diverse geographical settings are scarce. The aim of this study was to evaluate optimal second-line ART for people with HIV. D2EFT is a completed international, randomised, open-label, phase 3b/4 trial evaluating three second-line ART strategies in adults (aged ≥18 years) with HIV-1 for whom first-line NNRTI therapy has failed. The study was done at 28 sites across 14 countries in Asia, Africa, and Latin America. It was originally designed to compare recommended standard of care (ritonavir-boosted darunavir [800 mg darunavir plus 100 mg ritonavir once daily] plus two nucleoside reverse transcriptase inhibitors [NRTIs; dosed once or twice daily]) with a novel nucleoside sparing regimen of dolutegravir (50 mg once daily) with ritonavir-boosted darunavir. The study was adapted during the first year to add a third arm of dolutegravir (50 mg once daily) with fixed tenofovir disoproxil fumarate (300 mg once daily) plus either lamivudine (300 mg once daily) or emtricitabine (200 mg once daily). Participants were randomly assigned with a computer-generated, blocked randomisation scheme (block size of two) stratified by site, previous tenofovir disoproxil fumarate use, and HIV viral load. The trial was designed to evaluate non-inferiority of either interventional arm against standard of care for the primary outcome of virological suppression, as determined by HIV RNA load of less than 50 copies per mL at 48 weeks. The prespecified non-inferiority margin was 12%. Comparisons were made with a modified intention-to-treat population, including all participants randomly assigned but excluding administrative withdrawals. This study is registered with ClinicalTrials.gov, NCT03017872. 1190 individuals were screened; 828 participants were enrolled between Nov 1, 2017, and Dec 31, 2021. Two participants were unable to receive their assigned regimen for administrative reasons; and 826 participants were included in analyses. Median age was 39 years (IQR 33-46), and 450 (54%) participants were female. Baseline median CD4 count was 206 cells per μL (23-354) and median HIV RNA was 15 400 copies per mL (3600-65 986). The proportion of participants with HIV RNA of less than 50 copies per mL at 48 weeks was 194 (75%) of 257 in the ritonavir-boosted darunavir plus two NRTIs group, 222 (84%) of 264 in the ritonavir-boosted darunavir plus dolutegravir group, and 227 (78%) of 291 in the dolutegravir with tenofovir disoproxil fumarate plus either lamivudine or emtricitabine group. Compared with ritonavir-boosted darunavir plus two NRTIs, the difference in virological suppression was 8·6% (95% CI 1·7 to 15·5; p=0·016) for dolutegravir plus ritonavir-boosted darunavir and 6·7% (-1·2 to 14·4; p=0·093) for dolutegravir with tenofovir disoproxil fumarate plus either lamivudine or emtricitabine. Six deaths occurred, none of which were related to treatment. 19 pregnancies (11 livebirths) occurred with no congenital defects. In individuals experiencing failure of an NNRTI-based first-line ART, a switch to either dolutegravir plus ritonavir-boosted darunavir or dolutegravir with tenofovir disoproxil fumarate plus either lamivudine or emtricitabine, without universal access to genotyping, was non-inferior in achieving viral suppression compared with ritonavir-boosted darunavir plus two NRTIs. These global data support the most recent WHO treatment guidelines. UNITAID; National Institute of Allergy and Infectious Diseases, USA; National Health and Medical Research Council, Australia; ViiV Healthcare; and Janssen.

Abstract PO2-27-03: Clinical Results of Subjects Remaining in the Phase 3 ARTEST Study Enobosarm Therapy in AR+ER+HER2- Metastatic Breast Cancer with 3 or Greater Prior Lines of Therapy

Abstract Background: Targeting the androgen receptor (AR) with an oral selective AR agonist, enobosarm, is a novel approach to overcome ER and CDK4/6 inhibitor resistance to suppress AR+ER+HER2- metastatic breast cancer (mBC). Preclinical studies in CDK4/6 inhibitor and estrogen blocking agent resistant PDX mBC models demonstrated that enobosarm alone suppressed tumor growth. In a small subgroup analysis of patients with ER+HER2- mBC who progressed on estrogen blocking agent and a CDK 4/6 inhibitor from the Phase 2 802 study, enobosarm treatment resulted in a best overall response rate of 30% (2 CRs and 1 PR) and a 6-month clinical benefit rate (CBR) of 50%. Methods: The clinical activity of enobosarm 9mg alone was evaluated compared to standard of care (SOC) in the Phase 3 ARTEST, open-label, randomized, multicenter study in AR+ER+HER2-mBC who have progressed on 2 or greater lines of prior therapies, including estrogen blocking agents and CDK4/6 inhibitors. The study was discontinued for administrative reasons not related to efficacy or safety. Results: At the time study was discontinued, 34 patients with confirmed AR positivity were randomized to either enobosarm (n=16) or SOC control (n=18). SOC control treatment group received an average of 2.6 (range 1-5) and enobosarm 9mg monotherapy an average of 2.9 (range 1-5) prior lines of treatment. On average, enobosarm or the SOC control was given in the 4th line treatment for AR+ER+HER2- metastatic breast cancer. In the evaluable population, two partial responses were observed in the enobosarm treatment arm versus no responses in the SOC control arm. In patients with ≤3 lines of prior endocrine therapy, the best objective response rate (ORR) was 18.8% for enobosarm and 0% for control. In patients with ≤3 lines of prior endocrine therapy with ≤1 prior treatment with CDK 4/6 inhibitor, best ORR was 33% in the enobosarm group versus no responses in the SOC control (Table 1). CBR on day 180 was 33.3% (4/12) in the enobosarm group vs 0% (0/11) in the control group. Enobosarm treatment was well tolerated without masculinizing adverse events and no increases in hematocrit changes. Conclusions: Activity of enobosarm in this heavily pretreated patient population is encouraging and supports further clinical investigation. The Phase 3 ENABLAR-2 study is underway to further evaluate enobosarm alone or in combination with abemaciclib for the second-line treatment of AR+ER+HER2- metastatic breast cancer in patients who have received a prior estrogen blocking agent and a CDK 4/6 inhibitor. Clinical trial information: NCT04869943. Research Sponsor: Veru Inc. Table 1. Responses in patients with enobosarm versus SOC treatment. Citation Format: Kristine Rinn, Elisa Krill Jackson, Gary Barnette, Domingo Rodriguez, Itay Shalev, Mitchell Steiner, Joyce O'Shaughnessy, Hope Rugo, Adam Brufsky. Clinical Results of Subjects Remaining in the Phase 3 ARTEST Study Enobosarm Therapy in AR+ER+HER2- Metastatic Breast Cancer with 3 or Greater Prior Lines of Therapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-27-03.

Online-Assisted Survey on Antibiotic Use by Pet Owners in Dogs and Cats.

The aim of the study was two-fold: first, to collect data on the use of antibiotics in Germany for dogs and cats and, second, their owners' experiences and opinions. Using an anonymous online survey, dog and cat owners were asked about the last antibiotic administration in their pet. The inclusion criterion was any antibiotic administration within the last year. A total of 708 questionnaires from 463 dogs and 245 cats could be evaluated. Diarrhea was reported as the most common reason for antibiotic administration in dogs (18.4%). Wound infection/abscess/bite injury was the second most common reason in dogs (16.0%). In cats wound infection/abscess/bite injury was the most common reason (23.3%), followed by dental treatment (21.2%) and upper respiratory tract infections (16.7%). The most common antibiotics used systemically in both species were amoxicillin/clavulanic acid (32.5%), amoxicillin (14.8%), metronidazole (6.9%), and doxycycline (6.8%). While efficacy (99.9%) and tolerability (94.8%) were rated as most important for the choice of antibiotics, costs (51.6%) were cited as predominantly unimportant. First-line antibiotics were used significantly more often than critically important antibiotics. The majority of animal owners show awareness for avoidance of antibiotic resistance and the use of critically important antibiotics.

Traumatic brain injury and occupational risk of low-level blast exposure on adverse career outcomes: an examination of administrative and medical separations from Service (2005-2015).

Although traumatic brain injury (TBI) has been linked with adverse long-term health, less research has examined whether TBI is linked with non-clinical outcomes including involuntary job loss. Symptoms associated with TBI may influence one's ability to maintain gainful employment including employment in the U.S. military. That influence may impact military service members with exposure to repetitive low-level blast (LLB). Understanding the association between TBI and involuntary job loss outcomes among military populations is particularly important as it may be associated with differences in eligibility for post-service benefits. The purpose of the present research was to determine whether (1) TBI and related conditions are associated with involuntary job loss (i.e., medical and administrative separations from service) among military personnel, and (2) occupational risk of LLB is associated with involuntary job loss in both the presence and absence of clinical diagnoses of TBI and related conditions. This research leveraged population-level data from the Career History Archival Medical and Personnel System for enlisted personnel who served on active duty between 2005-2015. Risk of LLB exposure was categorized using military occupational specialty as a proxy. Medical diagnoses were identified using ICD-9 codes. Separations for medical and administrative reasons were identified. Risk for administrative separation differed across medical diagnoses of interest, but those who worked in high-risk occupations were more likely to be administratively separated than those working in low-risk occupations. Risk for medical separation was associated with occupational risk of LLB and each of the diagnoses of interest, though significant interactions suggested that the effects of certain diagnoses of interest (e.g., concussion, cognitive problems, postconcussive syndrome, migraines) on medical separations was greater among those working in high-risk occupations. Taken together, the present research suggests that TBI and associated medical conditions, as well as occupational risk of LLB, are associated with long-term involuntary job loss for medical reasons. This study is the first to demonstrate involuntary military job loss outcomes associated with TBI, mental health conditions, and conditions associated with blast exposure using both inpatient and outpatient population-level data and may have important implications for civilian employment and post-service benefits.

Reasons for Undergraduates’ Attitudes toward Online Learning

While online learning was implemented voluntarily in some countries, the pandemic forced many countries to embrace online learning as the only strategy for continuing the education of university students. Even though Sri Lanka was returning to some normalcy, the current economic catastrophe in Sri Lanka still forces online learning. Although the previous studies focused on many aspects of online learning, students’ attitudes toward online learning and the reasons behind those attitudes received rare attention. In this background, our paper explores the reasons for university students’ attitudes toward online learning based on nearly two and a half years of experience. Under the qualitative methodology, 20 semi-structured interviews were held with private and state university students. Our data analyses revealed that while no students have extremely positive or negative attitudes, many believe in online learning during crises. Also, in general, our participants’ attitudes toward online learning were mixed since they felt positive and negative about it depending on psychological factors, teaching methods, online learning environment, administration, colleagues, and crisis-driven reasons. While online learning was implemented voluntarily in some countries, the pandemic forced many countries to embrace online learning as the only strategy for continuing the education of university students. Even though Sri Lanka was returning to some normalcy, the current economic catastrophe in Sri Lanka still forces online learning. Although the previous studies focused on many aspects of online learning, students’ attitudes toward online learning and the reasons behind those attitudes received rare attention. In this background, our paper explores the reasons for university students’ attitudes toward online learning based on nearly two and a half years of experience. Under the qualitative methodology, 20 semi-structured interviews were held with private and state university students. Our data analyses revealed that while no students have extremely positive or negative attitudes, many believe in online learning during crises. Also, in general, our participants’ attitudes toward online learning were mixed since they felt positive and negative about it depending on psychological factors, teaching methods, online learning environment, administration, colleagues, and crisis-driven reasons.

Typology and classification of water quality in an intermittent river in a semi-arid Mediterranean climate.

The typology and classification of rivers are highly relevant concepts in the field of limnology and freshwater ecology. Water body typology systematically categorizes water bodies based on their natural attributes, while water body classification groups them based on specific criteria or purposes for management, regulatory, or administrative reasons. Both concepts play important roles in understanding and managing water resources effectively. This scientific article focuses on the ZAT River in Morocco as a model for studying low-flow and intermittent rivers. The objective is to develop an accurate model for the typology and classification of small, low-flow rivers into homogeneous classes based on natural and anthropogenic factors. The study also investigates the impact of human activities on altering the uniformity and reference nature of the water body. The typology of water bodies is carried out according to the European methodology specified in The European Commission's Water Framework Directive (WFD) in 2000. The classification of water bodies is conducted by assessing their chemical and biological quality using the weighted index (WI), the Iberian Biological Monitoring Working Group (IBMWP) index, and multivariate statistical methods such as principal component analysis (PCA) for confirming water quality assessment. The results indicate the possibility of dividing the basin into four water bodies. Water bodies show homogeneity in terms of chemical quality when human influence is minimal or during periods of high river flow. However, increased human influence and decreased river flows lead to heterogeneity in chemical quality, indicating an unstable state. This study is the first of its kind in arid and semi-arid intermittent rivers, where such an approach could be suggested to determine their typology and classification.

Real-World Safety and Effectiveness of a 4-Factor Prothrombin Complex Concentrate in Japanese Patients Experiencing Major Bleeding: A Post-marketing Surveillance Study.

Limited data are available regarding the safety and effectiveness of 4-factor prothrombin complex concentrate (4F-PCC) in patients experiencing major hemorrhage or requiring expeditious surgical intervention, both globally and within Japan. We executed a prospective, observational post-marketing surveillance study of patients receiving 4F-PCC for the first time between September 19, 2017 and August 15, 2018 in Japan. Patients were subjected to a comprehensive follow-up for a duration of 4weeks. Of 1381 eligible patients, 1271 (92%) received a vitaminK antagonist. Among these, 58% were aged ≥ 75years, 49% manifested atrial fibrillation, 17% presented with valvular heart disease, and 6% exhibited venous thromboembolism. The median (range) international normalized ratio was 2.67 (0.96-27.11) at baseline and 1.21 (0.45-6.61) at first measurement post-administration of 4F-PCC. The most common reason for 4F-PCC administration was intracranial hemorrhage (59.6%), followed by gastrointestinal bleeding (6.6%). Hemostatic effectiveness was achieved in 85.8% of patients. The incidences of adverse drug reactions (ADRs) and serious ADRs were 3.9% and 2.8%, respectively. Thromboembolic events (TEEs) occurred in 20 (1.5%) patients, with a mean onset of 10days. The majority of TEEs were classified as nervous system disorders (55%). At the time of TEE, only 13% of patients resumed anticoagulant therapy. The incidence of TEEs following treatment with 4F-PCC did not surpass those observed in phase3 trials. No novel safety signals were identified. The safety and effectiveness of 4F-PCC in Japanese real-world practice were in harmony with the observations of prior studies.

Pembrolizumab with favezelimab or vibostolimab for patients with bacillus Calmette-Guérin (BCG)–unresponsive high-risk (HR) non–muscle-invasive bladder cancer (NMIBC): Phase 2 KEYNOTE-057 cohort C.

TPS719 Background: In cohort A of the phase 2 KEYNOTE-057 study (NCT02625961), the PD-1 inhibitor pembrolizumab demonstrated antitumor activity (3-month complete response rate, 41%) in patients with BCG-unresponsive HR NMIBC with carcinoma in situ (CIS) ± papillary tumors who are ineligible for or declined radical cystectomy (RC). However, treatment combinations that improve outcomes and durability of response with pembrolizumab monotherapy are needed. Coinhibitory receptors LAG-3 and TIGIT contribute to immune tolerance in the tumor microenvironment, and co-blockade of PD-1 with LAG-3 or TIGIT has demonstrated antitumor activity in clinical studies. In cohort C of KEYNOTE-057, efficacy and safety of coformulations of pembrolizumab and the LAG-3 inhibitor favezelimab or the TIGIT inhibitor vibostolimab are being evaluated in patients with BCG-unresponsive HR NMIBC with CIS ± papillary tumors. Methods: Key eligibility criteria include adults with histologically confirmed HR NMIBC (CIS ± high-grade Ta or T1 at baseline) that is BCG-unresponsive (persistent or recurrent CIS ± Ta/T1 ≤12 month of completing adequate BCG therapy) who are ineligible for or declined RC and have an ECOG PS of 0-2. Enrollment is planned for 60 patients. Patients will be randomly assigned 1:1 to receive the coformulation of pembrolizumab 200 mg and vibostolimab 200 mg or the coformulation of pembrolizumab 200 mg and favezelimab 800 mg intravenously every 3 weeks for ≤35 cycles or until central pathology–confirmed ≥T1 at any time point, persistent or recurrent CIS or high-grade Ta at 24-week efficacy review or thereafter, unacceptable toxicity, patient or physician decision to withdraw, or administrative reasons to discontinue. Tumor assessment will be performed every 12 weeks for 2 years and every 24 weeks thereafter for up to 5 years. Primary end point is 12-month complete response rate of HR NMIBC by cystoscopy, cytology, biopsy, and radiologic imaging by central pathology and radiology review. Secondary end points include duration of response of HR NMIBC; overall complete response rate and complete response rates at 3 and 6 months; progression-free survival (PFS) to worsening of grade, stage, or death; PFS to muscle-invasive or metastatic disease or death; and overall survival. Efficacy will be evaluated in patients who receive ≥1 dose of treatment and have a baseline evaluation consisting of pre-enrollment cystoscopy, TURBT/biopsy, urine cytology, and baseline CTU imaging. Safety and tolerability will be evaluated in patients who receive ≥1 dose of treatment. Enrollment is ongoing in Asia, Australia, Europe, North America, and South America. Clinical trial information: NCT02625961 .

The Role of Performance Evaluation in Reducing Oil Losses: Field Research in the Two Companies of the Middle Refineries and Oil Products Distribution Company

The idea of the research came in conducting a field research for the companies of the oil sector, including the Oil Products Distribution Company and the Middle Refineries Company, given the importance of this organization primarily in refining crude oil and distributing oil derivatives through supply outlets. And the delivery of these products to the citizen and meet the economic needs of the country in general, where the research can focus on two types of oil losses: the first: either within the permissible natural proportions and in accordance with international standards. The second: It is outside those permissible percentages, and is considered a real loss, either for technical or administrative reasons, or due to the poor performance of the companies concerned, which requires a real pause to preserve natural resources, and it is a right. future generations. We are interested in finding weaknesses in activities by evaluating performance in the oil industry.

Linguistic Landscape of a Modern Post-Soviet Capital — Case of Chișinău, Republic of Moldova

The study of linguistic landscape considers the hierarchy of languages motivated by political, administrative, and economic reasons, as reflected in the graphic design and order of inscriptions. In this research, we will present the linguistic landscape of Chișinău by analyzing top-down and bottom-up signs and commercial billboards. The choice fell on this city because it is multiethnic, home for Moldovans/Romanians and other nationalities. The relevance of the topic is explained by the fact that Moldova aspires to join the European Union, and in 2018 Chișinău became one of the country’s pilot municipalities for the application of the European Charter for Regional or Minority Languages, which the country has adopted, but has not yet ratified. The new signs must indicate direction to public and cultural institutions, monuments and memorials, parks and major streets, university buildings, the railway station, and the airport with trilingual inscriptions in Moldovan, a local minority language (Russian, Ukrainian, Bulgarian, German or Yiddish) and English. The investigation of the linguistic landscape will help identify the dominant language(s) in the Moldovan capital, understand the relations between linguistic communities and the linguistic situation in Chișinău.

Learning, Teaching, and Demonstration of Unique Chemistry for the Indonesian Generation at Sanggar Bimbingan Mulia, Kuala Lumpur Malaysia

As a form of concern for the issues faced by the descendants of Indonesian nationals in Malaysia, especially for the Human Resources, we provide the unique theoretical and practical chemistry mentorship for future capability. Sanggar Bimbingan Sungai Mulia 5 is an organization that offers educational services for Indonesian descendants whose citizenship status is still unclear due to administrative reasons. Based on the Chemistry Department UM and Sanggar Bimbingan Mulia cooperation, It is important to enhance the nation's intellectual capacity, especially in ensuring the success of the mandatory 9-year education program. This community service aims to combat illiteracy, in still character education, and prepare students for higher education. The expected outcomes of this program is a unique chemistry Massive Open Online Course (MOOC), a service article published, a service report, and a poster. Our program successfully developed the interest of children to love a simple chemistry experiment and improved for reading and learning through various MOOC, books, and educational materials.

Pleomorphic dermal sarcoma of the scalp - A single-centre experience

BackgroundPleomorphic dermal sarcoma (PDS) of the scalp is a rare tumour which is usually slow growing, but occasionally displays rapid growth and has a low rate of local recurrence. Surgical resection is the mainstay of treatment, with or without radiotherapy. The aim of this study is to describe the surgical approach and the additional benefit of radiotherapy to the treatment of these patients. MethodsRetrospective, single-centre analysis of patients with PDS of the scalp that underwent surgical resection between 2007 and 2021 (n = 24). Treatment variables including depth of resection (superficial or deep to the galea aponeurotica) and adjuvant radiotherapy were investigated. ResultsTwenty-four patients were included in this study. Median age was 80 (range, 52–95), with a median ASA score of 3 (2–3). Sixteen (66.6 %) patients underwent surgical resection including the galea, while the rest (n = 8) did not or was not known. Radiotherapy was given in 7 (29 %) patients in which only 3 (12.5 %) were in the galeal resection group. Reasons for radiotherapy administration were concomitant SCC found at the same area of resection and close margins. In a median follow-up of was 26.2 months (range, 13.6–102.5) there was only one recurrence event. ConclusionsPDS of the scalp can be safely managed with a surgical resection if clear surgical margins are achieved without radiotherapy with good oncological outcomes.

State of the Art of Probiotic Use in Neonatal Intensive Care Units in French-Speaking European Countries.

The effectiveness of probiotics in reducing the incidence of necrotizing enterocolitis has been supported by a very large number of studies. However, the utilization of probiotics in preterm infants remains a topic of debate. This study aims to assess the rate of probiotic use in European neonatal intensive care units (NICUs), compare administration protocols, and identify barriers and concerns associated with probiotic use. An online questionnaire was distributed via email to European NICUs between October 2020 and June 2021. Different questions related to the frequency of probiotic use were proposed. Data on probiotic administration protocols and reasons for non-utilization were collected. The majority of responses were from France and Switzerland, with response rates of 85% and 89%, respectively. A total of 21% of French NICUs and 100% of Swiss NICUs reported routine probiotic use. There was significant heterogeneity in probiotic administration protocols, including variations in probiotic strains, administration, and treatment duration. The main obstacles to routine probiotic use were the absence of recommendations, lack of consensus on strain selection, insufficient scientific evidence, and concerns regarding potential adverse effects. The rate of routine probiotic administration remains low in European NICUs, with heterogeneity among protocols. Further trials are necessary to elucidate optimal treatment modalities and ensure safety of administration.