Small Trials Research Articles

Non-Steroidal Anti-Inflammatory Drugs Administered Intra-Articularly in Temporomandibular Joint Disorders: A Systematic Review and Meta-Analysis.

Objectives: This systematic review was designed to summarize randomized controlled trials of intra-articular administration of non-steroidal anti-inflammatory drugs (NSAIDs) for temporomandibular disorders. Methods: Randomized controlled trials regarding intra-articular injections of non-steroidal anti-inflammatory drugs for temporomandibular disorders were included in the review. The final search was conducted on 16 June 2024 in the Bielefeld Academic Search Engine, PubMed, and Scopus databases. Results: Of the 173 identified studies, 6 were eligible for review. In trials comparing arthrocentesis alone to arthrocentesis with NSAIDs, slight differences in joint pain were noted. For tenoxicam, differences were under 1 point on a 0-10 scale after 4 weeks, with inconsistent results. Piroxicam showed no significant difference, and pain levels were minimal in both groups. For maximum mouth opening (MMO), tenoxicam showed no significant difference. Piroxicam increased MMO by nearly 5 mm, based on one small trial with bias concerns. Conclusions: Currently, there is no strong scientific evidence supporting the injection of NSAIDs into the temporomandibular joint to relieve pain or increase jaw movement. Preliminary reports on piroxicam with arthrocentesis and tenoxicam or diclofenac without rinsing justify further research.

Lidocaine patch for treatment of acute localized pain in the emergency department: a systematic review and meta-analysis.

Lidocaine patches are commonly prescribed for acute localized pain. Most of the existing evidence is, however, derived from postoperative or chronic pain. The objective of this study is to assess the efficacy and safety of lidocaine patch compared to placebo patch or nonsteroidal anti-inflammatory drugs (NSAIDs) for acute localized pain. Systematic review and meta-analysis of trials randomizing patients with acute localized pain to lidocaine patch versus placebo patch or NSAIDs. Change in pain score (any validated scale) from baseline to a specific time endpoint (primary efficacy); adverse events (primary harm), and time to exit the study due to reaching a pain relief target (secondary). We used Cochrane revised tool to assess the risk of bias and GRADE to rate the quality of evidence. The meta-analysis was performed using a random-effects model and Cochrane Q test for heterogeneity. Data were summarized as risk ratios and weighted mean differences with 95% confidence interval (CI). We conducted a comprehensive search of MEDLINE, EMBASE, and other major databases, identifying 10 randomized controlled trials with a total of 523 patients. These trials collectively found that lidocaine patches were more effective in controlling both musculoskeletal and neuropathic pain compared to placebo patches. Due to heterogeneity among the studies, we did not pool the efficacy data. The risk of adverse events was similar between the groups (risk ratio: 0.90; 95% CI: 0.48-1.67; moderate-quality evidence). In the two trials comparing lidocaine patches with NSAIDs, there was no statistically significant difference in pain relief between the treatments. Low to moderate-quality evidence from small trials supports the efficacy and safety of lidocaine patch for the treatment of acute localized pain.

The Modern Clinician as an "Argonaut" Guiding Through the "Symplegades" of Evidence for PFO Closure in Patients With Migraine.

Patent foramen ovale (PFO) has been associated with migraine, especially migraine with aura, and 30-50% of individuals with migraine with aura have a PFO, suggesting it could be more than just an "innocent bystander''. Observational data showed a reduction of the frequency and severity of migraine attacks, particularly those with aura, following transcatheter PFO closure for established indications. Three small randomized controlled trials have demonstrated significant benefits of PFO closure in most of their secondary endpoints, such as reductions in the mean number of monthly migraine attacks and migraine days. Since a significant proportion of patients experience important side effects from traditional migraine medications and newer highly effective migraine prevention strategies may need to be instituted. PFO closure could in this regard to be a valuable add-on in the armamentarium of migraine treatment, improving the quality of life by alleviating the need for medications. The effect of percutaneous PFO closure on migraine treatment is needed to be clarified. As the underlying pathophysiology remains poorly understood and largely hypothetical, future investigations, focusing on the causal relationship between PFO and migraine, will help to define the subgroup of patients most likely to benefit from PFO closure. More accurate patient recruitment may lead to greater postprocedural benefits and more significant symptom improvement. Additionally, randomized controlled trials need to be reported adequately with more realistic endpoints, sufficient duration of follow-up, and statistical power to detect differences between closure and placebo groups to ensure precise and reliable findings.

The multifaceted role of beta-blockers in overcoming cancer progression and drug resistance: Extending beyond cardiovascular disorders.

Beta-blockers are commonly used medications that antagonize β-adrenoceptors, reducing sympathetic nervous system activity. Emerging evidence suggests that beta-blockers may also have anticancer effects and help overcome drug resistance in cancer treatment. This review summarizes the contribution of different isoforms of beta-adrenoceptors in cancer progression, the current preclinical and clinical data on associations between beta-blockers use and cancer outcomes, as well as their ability to enhance responses to chemotherapy and other standard therapies. We discuss proposed mechanisms, including effects on angiogenesis, metastasis, cancer stem cells, and apoptotic pathways. Overall, results from epidemiological studies and small clinical trials largely indicate the beneficial effects of beta-blockers on cancer progression and drug resistance. However, larger randomized controlled trials are needed to firmly establish their clinical efficacy and optimal utilization as adjuvant agents in cancer therapy.

New pacing strategies for heart failure

In patients with areduced left ventricular (LV) systolic function (ejection fraction < 35%) and aleft bundle branch block with a QRS duration > 130 ms, cardiac resynchronization therapy (CRT) can contribute to an improvement in the quality of life and areduction in mortality. The resynchronization is mostly achieved by pacing via an epicardial LV lead in the coronary sinus; however, this approach is often limited by the patient's venous anatomy and an increase in the stimulation threshold over time. In addition, up to 30% of patients do not respond to the intervention. New treatment approaches involve direct stimulation of the conduction system by pacing of the bundle of His or left bundle branch. This enables a more physiological propagation of the stimulus. Pacing of the left bundle branch is achieved by advancing the lead into the right ventricle and screwing it deep into the interventricular septum. Due to the relatively large target area of the left bundle branch the success rate is very high (currently > 90%). Observational studies have shown agreater reduction in the QRS duration, amore pronounced improvement in systolic function and alower hospitalization rate for heart failure associated with conduction system pacing compared to CRT using acoronary sinus lead. These findings have been confirmed in small randomized trials. Therefore, the use of left bundle branch pacing should be considered not only as abail out in the case of failed resynchronization using coronary sinus lead placement but increasingly also as an initial pacing strategy. The results of the first large randomized trials are expected to be released in late 2024.

632 Hepatitis C Positive Organ Donation and Direct Acting Antivirals in Pancreas Transplantation: A Systematic Review

Abstract Background Pancreas transplantation (PT) provides diabetic cure for patients with complicated diabetes mellitus. However, there is a paucity of suitable donor organs to fulfil requirements resulting in deaths on the waiting list. Organs from otherwise suitable hepatitis C virus positive (HCV+) donors alongside direct-acting antiviral agents (DAAs) have been used in kidney and liver transplants in small trials. We aimed to review this strategy in PT. Method A literature search was conducted on OVID MedLINE, PubMed and EMBASE to evaluate evidence on the use of HCV+ organ donors for PT in HCV- recipients alongside DAA therapy. Results Database analysis produced 5 articles (4 single centre retrospective, 1 case report). This included a total of 65 patients, 15 of which received PT. Two studies examined multiple organ transplants whilst 3 evaluated PT alone. Three studies employed prophylactic perioperative therapy, while 2 examined treatment post-transplantation. 100% of patients achieved a sustained virological response (SVR) at 12 weeks across all 5 studies. There were no episodes of acute rejection or complications directly associated with DAA therapy or HCV infection. HCV transmission occurred in only 1 of 15 patients, which was successfully treated. Pancreatic graft function and outcome after 7-12 months was good. Conclusions The use of DAA therapy is safe and effective for HCV+ donors to HCV- transplant in early reported studies. This approach could facilitate the successful utilisation of HCV+ organs for transplantation thereby minimising impact on supply and demand disparities. Pancreas transplantation specific studies are required to further analyse outcomes.

Safety and Efficacy of N-Acetylcysteine as an Adjuvant Therapy in Critically Ill COVID-19 Patients

Abstract Background COVID-19 may cause pneumonia, acute respiratory distress syndrome, cardiovascular alterations, and multiple organ failure, which have been ascribed to a cytokinestorm, a systemic inflammatory response, and an attack by the immune system. Moreover, an oxidative stress imbalance has been demonstrated to occur in COVID- 19 patients. N- Acetyl-L-cysteine (NAC) is a precursor of reduced glutathione (GSH). Aim of the Work we retrospectively will investigate safety and efficacy of NAC dose given in paracetamol toxicity as an adjuvant therapy in critically ill COVID-19 patients with acute respiratory distress and determine whether NAC in high doses can avoid respiratory failure in patients with COVID-19. Patients and Methods This was a retrospective observational study in which all cases were collected from ICU of Ain shams university hospitals during COVID-19 outbreak. All data were extracted from clinical records. All patients initially admitted to ICU with SPO2 less than 94 % were included between December 2020 to February 2022. Exclusion Criteria included Need for immediate mechanical ventilation on admission, known allergy or hypersensitivity to NAC, end stage renal and liver diseases, heart failure and pregnancy. All patients with severe COVID-19 (confirmed or suspected received standard care, according to the institutional protocol. Results Patients were randomized into two equal groups (number (n)=40 each) as the N1(NAC) group who was given intravenously, initially 150 mg/kg in 200 mL of 0.9% NaCL for 60 minutes (first bag), followed by 50 mg/kg in 500 mL of 0.9% NaCL for 4 hours (second bag), and then 100 mg/kg in 1000 mL of 0.9%NaCL for 16 hours (third bag) and N2(Non NAC) group who received intravenously N-acetylcysteine (NAC) 600mg /12hr and The primary endpoint was the need for mechanical ventilation. Secondary endpoints were time of mechanical ventilation, admission to the intensive care unit (ICU), time in ICU, and mortality. There were no statistically significant differences between the two groups (p &amp;gt; 0.05) The effect of NAC on mechanical ventilations, mortality, ICU stays, and hospital stays is a matter of controverse in ARDS patients. We found that intravenous high dose of NAC did not improve oxygenation, mortality rate and did not reduce the requirement for mechanical ventilation when administered for COVID 19 patients with ARDS. Also, the duration of ICU and hospital stays were relatively prolonged in the NAC-treated patients. These might be due to prolonged survival time with NAC-treated patients, but not to be detected with the small single centered trial.. Conclusion Use of high doses of NAC administration can not affect the need of mechanical ventilation, rate of mortality, the need, duration of ICU admission and hospital stays for patients with severe COVID-19.

Pandemic and Pregnancy: Impact of COVID-19 Medication on Pregnant Women Outcomes

Abstract: The devastating outcomes of the Coronavirus disease 2019 (COVID-19) outbreak have traumatized the world, as they are highly infectious and mainly attack the respiratory tract. Although pregnant women are not at a higher risk of infection, it may result in more severe consequences than in the general population. Treatment of pregnant women with COVID-19 is challenging for doctors, as they need to consider the safety of both the mother and fetus. In addition, there is a lack of knowledge regarding the safety, effectiveness, and possible adverse outcomes of drugs used in COVID-19 pregnant women because they are generally excluded from clinical trials. We briefly reviewed the pathophysiology of drugs currently used in the treatment of COVID-19 in pregnant women and excluded drugs contraindicated during pregnancy. The safety of these drugs is derived from small case studies or clinical trials on other diseases. This article may be useful to physicians, researchers, and people interested in treating COVID-19.

Rehabilitation of Executive Function in Pediatric Traumatic Brain Injury (REPeaT): Outcomes of a pilot randomized controlled trial.

To evaluate the effectiveness of Cogmed Working Memory Training (Cogmed) in improving working memory (WM) and decision making (DM) in childhood traumatic brain injury (TBI), and any associated increases in functional outcomes such as academic achievement in mathematics, behavior, social skills, and quality of life. A randomized controlled trial of the Cogmed (RM version) intervention for children with TBI. A total of 69 children post-TBI were screened for WM impairments, of which 31 eligible participants (Mage: 10.6 years; male n = 21) were recruited and randomized to either the treatment group (Cogmed, n = 16) or the active-control group (Lexia Reading Core5, n = 15). Both groups completed computerized training for 5 weeks with clinician support via an online video platform. Immediately posttraining and at 6 months follow-up, primary (WM and DM) and secondary functional outcomes were assessed. Immediately postintervention, significant improvement was found in one primary outcome (WM verbal component) for the Cogmed group, but this was not maintained at the 6 months follow-up. No immediate improvements or maintenance gains (small effect sizes) in other primary outcomes of visuospatial WM or DM were reported in the Cogmed group. No other significant group differences were detected for other functional outcomes. Despite the limited benefits observed in this small randomized controlled trial, it will be beneficial to investigate Cogmed's efficacy in a case-series methodology, to further determine its effectiveness in a pediatric TBI population. Furthermore, a cautious approach in clinical implementation of Cogmed is advised. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Development of Interactive Learning Media Based on Problem-Based Learning: Improving Geography Learning Outcomes

The aim of this research is to produce interactive learning media based on a problem-based learning model that is feasible, practical, and effective in improving student learning outcomes in geography subjects. The ADDIE development model was the type of research used. The results of the research show: the material validation test obtained a score of 98% in the very feasible category, the media validation test obtained a score of 94% in the very feasible category, the design validation test obtained a score of 100% in the very feasible category, the individual and small group trials obtained a score of 86% in the very feasible category. , and the field trial obtained a score of 91% in the very worthy category, with an overall average result from the respondent category of 93%. The use of PBL-based interactive learning media in the experimental class obtained an average learning outcome of 84.17, while in the control class, which used video media and printed books, it obtained an average learning outcome of 79.50. The research data was declared normal and homogeneous. The results of the independent samples t test show tcount = 2.38 and ttable = 2.00 with a significance level of α = 0.05, so tcount &gt; ttable. It can be interpreted that H0 is rejected and H1 is accepted, which means that the PBL-based interactive learning media product developed is effective. Furthermore, based on the results of the N-Gain calculation, a score of 60.78% was obtained, so this PBL-based interactive learning medium is classified as "quite effective" in the "medium" category

Development of a Web-Based Interactive Multimedia Problem-Based Learning Approach on Algorithms and Programming Material

This research and development aims to produce interactive multimedia based on problem-based learning (PBL) using the Web to improve student learning outcomes in algorithms and programming material that is feasible, practical, and effective. This type of development research uses the ADDIE model. This research was carried out at SMK Negeri 6 Mukomuko, the material on algorithms and programming in the informatics class X Phase E. The results of the research show: (1) Expert validation test on product material in the very feasible category, namely 88.14%. (2) The Instructional Design Expert validation test is in the very feasible category, namely 95.56%. (3) The Media Expert validation test is in the very feasible category, namely 91.46%. (4) Individual trials in the very good category, namely 87.55%. (5) The small group trial was in the very feasible category, namely 89.65%. And (6) field trials in the very feasible category, namely 89.15%. The practicality test was very practical, namely 96.67%, while the practicality test results for students were 95.59% in the very practical category. The results of the experiment using PBL-based interactive multimedia in the experimental class gave an average learning outcome of 84, while students who were taught without using PBL-based interactive multimedia got an average score of 60.9. Hypothesis testing uses an independent t-test with significant results. (2-tailed) of 0.00, where the result is &lt;0.05, it is concluded that there is a significant difference between classes taught using PBL-based interactive multimedia and classes taught without using PBL-based interactive multimedia

Development of a Biology Learning Media-Flipped Classroom Model Using Edpuzzle

This research and development aims to produce biology learning media using the flipped classroom model with Edpuzzle that is feasible, practical, and effective in improving student learning outcomes on excretory system material. This type of research is development research using the ADDIE development model with stages: (1) analysis stage, (2) design stage, (3) development stage, (4) implementation stage, and (5) evaluation stage. The research results show: (1) Material expert validation test that the material in the media developed is very worthy with an average score of 88.72%. (2) The Instructional Design Expert validation test is very worthy, with an average score of 96.87%. (3) The Media Expert validation test is very worthy, with an average score of 94.20%. (4) Individual trials are very worthy, with an average score of 87.73%. (5) The small group trial was very feasible, with an average score of 90.90%. And (6) field trials are very worthy of an average score of 90.20%. The practicality test by very practical teachers had an average score of 90.20%, while the practicality test results for students had an average score of 94.90%, which was in the very practical category. Using the flipped classroom model, biology learning media with Edpuzzle in the experimental class got an average learning outcome of 89.68, while students who were taught without this media got an average score of 69.14. Testing the hypothesis using the independent t-test, there is a significant difference between classes taught using the flipped classroom model of biology learning media with Edpuzzle and classes taught without using this media.

재판업무 지원 AI 도입에 관한 헌법적 고찰

In the contemporary intelligence information society, artificial intelligence (AI) is being utilized in various sectors due to the advancement of science and technology. Amidst this trend, the legal technology (LegalTech) industry, which integrates technology with legal advisory and litigation services, has been experiencing a leap in growth. Furthermore, the application of artificial intelligence in the judicial duties of judges is garnering significant interest and expectation for speeding up legal proceedings and enhancing the efficiency of judicial administration. Artificial intelligence used in the judiciary can be broadly classified into two types. First, there is AI that entirely replaces human judgment, exemplified by the initiative in Estonia in 2019 to implement AI for conducting small claims trials. Second, there is AI designed to assist human judges, such as algorithms that help draft verdicts based on similar case precedents or provide appropriate sentencing recommendations for defendants in criminal trials. In this regard, some state courts in the United States have incorporated the COMPAS algorithm into sentencing procedures within criminal justice processes. This surge in AI development seems to have an international impact on judicial procedures, influencing the judicial policies of the courts in South Korea significantly. Specifically, National Court Administration has announced plans to alleviate the workload of judges and address the issue of trial delays through the introduction of what is referred to as the ‘Next-Generation Electronic Litigation System.’ However, while AI technology may assist in accelerating trial processes, there are considerable concerns regarding the protection of litigants' right to a fair trial and democratic legitimacy. Above all, the potential for data and algorithm errors in judicial-use AI could compromise the fairness of trials or lead to miscalculation due to biased legal decisions. This study examines the constitutional issues concerning the advent of AI judges in the era of artificial intelligence are explored, particularly the infringement of the litigants' right to a fair trial, the problems of restoring the original state following miscalculation, and the responsibilities of judges. Furthermore, the study examines legislative trends abroad concerning the use of AI in judicial tasks, and seeks legislative improvement strategies for the principles and premises that must be adhered to by AI utilized in the judiciary during the era of artificial intelligence.

Pharmacological Treatment of Degenerative Cervical Myelopathy: A Critical Review of Current Evidence.

Degenerative cervical myelopathy (DCM) is the leading cause of spinal cord dysfunction in adults, representing substantial morbidity and significant financial and resource burdens. Typically, patients with progressive DCM will eventually receive surgical treatment. Nonetheless, despite advancements in pharmacotherapeutics, evidence for pharmacological therapy remains limited. Health professionals from various fields would find interest in pharmacological agents that could benefit patients with mild DCM or enhance surgical outcomes. This review aims to consolidate all clinical and experimental evidence on the pharmacological treatment of DCM. We conducted a comprehensive narrative review that presents all pharmacological agents that have been investigated for DCM treatment in both humans and animal models. Riluzole exhibits effectiveness solely in rat models, but not in treating mild DCM in humans. Cerebrolysin emerges as a potential neuroprotective agent for myelopathy in animals but had contradictory results in clinical trials. Limaprost alfadex demonstrates motor function improvement in animal models and exhibits promising outcomes in a small clinical trial. Glucocorticoids not only fail to provide clinical benefits but may also lead to adverse events. Cilostazol, anti-Fas ligand antibody, and Jingshu Keli display promise in animal studies, while erythropoietin, granulocyte colony-stimulating factor and limaprost alfadex exhibit potential in both animal and human research. Existing evidence mainly rests on weak clinical data and animal experimentation. Current pharmacological efforts target ion channels, stem cell differentiation, inflammatory, vascular, and apoptotic pathways. The inherent nature and pathogenesis of DCM offer substantial prospects for developing neurodegenerative or neuroprotective therapies capable of altering disease progression, potentially delaying surgical intervention, and optimizing outcomes for those undergoing surgical decompression.

Development of Linktree-Based Interactive Learning Media to Improve History Learning Outcomes

The aim of this research is to produce Linktree learning media products aimed at testing aspects of the feasibility, practicality, and effectiveness of Linktree-based interactive learning media to improve history learning outcomes in class XI MAN 2 Medan Model. The research and development method used is the ADDIE model. The research results show: (1) The material expert validation test is very feasible with 93.75%. (2) The validation test for media experts is very feasible at 95%. (3) validation test of learning design experts in the very feasible category with 100%. (4) Individual trials in very feasible criteria with 83.92%. (5) The small group trial criteria were very feasible, with 89.83%. (6) Field trials met very feasible criteria with 94.06%, with an overall average result of 93.02%. Then the results of the experiment using Linktree-based interactive learning media using the problem-based learning model approach in the experimental class had an average learning outcome of 89.9, while using Linktree-based interactive learning media with the cooperative learning jigsaw model approach in the control class had an average value of 83.8. Based on the independent T-test, the effectiveness test showed a Sig value. (2-tailed) 0.000 is &lt;0.05, which means it is significant. It was concluded that the Linktree-based interactive learning media with the problem-based learning model approach was effectively used to improve history learning outcomes. Based on the N-Gain calculation, a result of 60.96 was obtained in the quite effective category.

Development of A Drama Text Writing Module Based On Character Education for Students Junior High School

This research aims to produce a drama text writing module based on character education for students at SMP Negeri 1 Batang Angkola. The research method used is the Research and Development research method which refers to the Borg and Gall model. The process of developing teaching materials for writing drama texts based on character education is carried out in three stages, namely the preliminary study stage, initial product development and product testing. The results of material expert validation on content suitability obtained an average of 88% in the very good category, the presentation feasibility aspect obtained an average of 84.33% in the very good category and the language assessment obtained an average of 82.5% in the very good category. for graphic assessment by design experts, an average of 80.08% was obtained in the good category. Individual trials obtained an average percentage of 79.77 in the "good" category. Small group trials obtained an average percentage of 85.96 in the "very good" category. Limited field trials obtained an average percentage of 91.87 in the "very good" category. Based on these data, teaching materials that are suitable for teachers and students to use in learning are obtained. Teaching materials for writing drama texts based on character education were declared effective in generating student activity and learning outcomes. This is proven by tests on student learning outcomes in writing drama texts. At the pretest the average was 69 and at the posttest the average was 80. The difference between the pretest and the posttest was 11%, which indicated that learning using teaching materials for writing drama texts based on character education was better than before.

Pengembangan E-Modul Berbasis Stem pada Materi Genetika

This study aims to develop stem-based e-modules on genetic material in an effort to improve the quality of biology learning. The research method used is Research and Development (R&amp;D) with a 4D development model. The results showed that the stem-based e-module in genetics had gone through the validation process by material experts and media experts, with the percentage of validity and materials of 95%, the ability and contextualization of 87.5%, and a score of 100% for appearance and programming and 97.2% for presentation from media experts. This e-module is considered very practical based on the assessment of teachers and students in small and large-scale trials, with a percentage of practicality of 94.23% for the teacher, 76.538% for small scale students, and 78.32% for large scale students. The implementation of e-modules in biological learning is also proven to be quite effective, with a percentage of effectiveness of 58.46% and the N-Gain value of 0.58, which is included in the medium category. The conclusion is that the development of stem-based e-modules in genetic material is an effective innovation in improving the quality of biology learning, providing interactive learning experiences, encouraging students to be more active in the learning process, and increasing students' understanding of genetic material. Keywords: E-Modules, Genetics, Stem, 4D

Upakara Bali-based Electronic Student Worksheets on Geometry Topic for Second Grade of Elementary School

The lack of contextualization and innovation in developing learning materials for 2nd-grade elementary school geometry has become a major issue leading to students' difficulty in understanding concepts. This research aims to develop an Electronic Student Worksheets Based on Ethnomathematics Upakara Bali in Geometry for 2nd-Grade Elementary School. Trial subjects in this study include two material experts, two media experts, one 2nd-grade teacher, 6 individual trial students, and 10 small group trial students. This research utilizes the ADDIE model (analyze, design, development, implementation, evaluation). Data collection methods used were questionnaires, interviews, and observations. Data analysis techniques involved quantitative and qualitative descriptive analyses. The results of this developmental research are the Electronic Student Worksheets product, covering: (a) the design and development of an ethnomathematics-based Electronic Student Worksheets on Upakara Bali for 2nd-grade Elementary School Geometry, including analysis, design, and development stages; (b) validity test results gain criteria of excellent qualification; (c) effectiveness test belongs to teacher response, individual trial score, small group trial score belongs to excellent qualification. Hence, it can be concluded that this Electronic Student Worksheets is suitable for use in the learning process. The implication of this research is the existence of a valid and suitable Electronic Student Worksheets to enhance 2nd-grade Elementary School geometry learning within the local cultural context.

The Immunotherapy of Acute Myeloid Leukemia: A Clinical Point of View.

The potential of the immune system to eradicate leukemic cells has been consistently demonstrated by the Graft vs. Leukemia effect occurring after allo-HSCT and in the context of donor leukocyte infusions. Various immunotherapeutic approaches, ranging from the use of antibodies, antibody-drug conjugates, bispecific T-cell engagers, chimeric antigen receptor (CAR) T-cells, and therapeutic infusions of NK cells, are thus currently being tested with promising, yet conflicting, results. This review will concentrate on various types of immunotherapies in preclinical and clinical development, from the point of view of a clinical hematologist. The most promising therapies for clinical translation are the use of bispecific T-cell engagers and CAR-T cells aimed at lineage-restricted antigens, where overall responses (ORR) ranging from 20 to 40% can be achieved in a small series of heavily pretreated patients affected by refractory or relapsing leukemia. Toxicity consists mainly in the occurrence of cytokine-release syndrome, which is mostly manageable with step-up dosing, the early use of cytokine-blocking agents and corticosteroids, and myelosuppression. Various cytokine-enhanced natural killer products are also being tested, mainly as allogeneic off-the-shelf therapies, with a good tolerability profile and promising results (ORR: 20-37.5% in small trials). The in vivo activation of T lymphocytes and NK cells via the inhibition of their immune checkpoints also yielded interesting, yet limited, results (ORR: 33-59%) but with an increased risk of severe Graft vs. Host disease in transplanted patients. Therefore, there are still several hurdles to overcome before the widespread clinical use of these novel compounds.

Treatment of palmoplantar psoriasis with oral roflumilast: a case series.

Palmoplantar psoriasis (PP) is a special area of psoriasis, which can justify systemic treatment. Roflumilast is a targeted inhibitor of phosphodiesterase (IPDE)-4 that has been recently approved by FDA as a cream for the treatment of plaque psoriasis. Also, oral roflumilast has demonstrated efficacy in the treatment of plaque psoriasis in a small randomized clinical trial and single case reports. To the best of our knowledge, we present the first case series of PP treated with oral roflumilast.