Reviews on recent clinical trials最新文献

Background: Over the past decade, there has been a significant shift from paper-based to digital medical record management, driven largely by advances in digital technology. This transition has led to widespread adoption of Electronic Medical Records (EMRs), with the expectation that paper documentation will soon be fully replaced. In response, the European Medicines Agency's "Guideline on Computerised Systems in Clinical Trials" outlines essential criteria for validated EMR systems to ensure data integrity and security, and sets standards for electronic source documents in clinical trials.

Methods: From December 2023 to March 2024, the Italian Group of Data Managers and Clinical Research Coordinators (GIDMcrc) conducted an online survey across clinical research sites in Italy, France and Belgium to assess the characteristics of medical records and source documents.

Results: The survey was completed by 37 centres: 70.3% from Italy, 16.2% from France and 13.5% from Belgium. Most sites use a mixed paper/electronic Source Document (SD) system (72.3%), with fewer centres having fully electronic SD systems (13.5%) or fully paper-based systems (16.2%). EMR systems are used in 70.3% of sites, but only 23.8% comply with EMA guidelines for computerised systems. A country-specific analysis was also conducted to further explore the situations in Italy and France/Belgium.

Conclusion: Despite the widespread use of Electronic Medical Records (EMRs) in Italy, France and Belgium, Italy lags behind the other two countries in terms of digitization. Despite the presence of an EMR, many centres still use a mixed system of paper and electronic source documents. There is also a lack of awareness regarding EMA and GCP standards, particularly concerning training and system testing. The higher response rate from Italian centres highlights the need for a larger sample in France and Belgium, and a follow-up survey would be beneficial for assessing progress and refining corrective actions.

Angioedema is a health issue that affects parts of the body like the upper pulmonary and gastric pathways and is identified by abrupt, nonpitting enlargement of the skin, mucous membranes, or both. The swelling usually lasts a few hours to 72 hours and may appear as non-puritic, subcutaneous, or submucosal organ edema. It is characterized by localized swelling brought on by the release of histamine. Itching is rare, and usual areas of appearance include the hands, feet, face, and genitalia, with periorbital swelling being the most often. The main objective of this review article is to study in brief the classifications, etiology, pathophysiology, and clinical trial data by describing the recent advancement in the treatment of angioedema. Various research articles obtained from different journals indexed under Scopus and SCI were used to prepare the review article and for illustrative work software such as Biorender and Microsoft Word was used. Histaminemediated angioedema, linked to allergic reactions, coexists with urticaria. Bradykinin-mediated angioedema, exemplified by hereditary angioedema and acquired forms, lacks urticaria. Idiopathic angioedema, with uncertain etiology. Imitated angioedema results from non-IgE-mediated reactions, often induced by medications. It is a complicated medical condition with a variety of causes and mechanisms. Over time, outcomes for patients have been greatly improved by a growing understanding of its etiology, pathophysiology, and available treatments. The field of medical treatment for this difficult problem is always changing, and this is partly due to clinical trials.

Introduction: In the present study, we evaluated the impact of empagliflozin on serum levels of oxidative stress parameters in individuals with type 2 diabetes (T2DM) who also suffer from heart failure with Reduced Ejection Fraction (HFrEF).

Methods: In this prospective, single-center clinical trial, 80 patients with T2DM and HFrEF, stabilized on guideline-directed heart failure therapy and classified as New York Heart Association functional (NYHA) functional classes II or III, were randomized to receive either empagliflozin (10 mg/daily) or a matching placebo for a duration of 12 weeks. Serum levels of malondialdehyde (MDA), along with the activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx), were measured at baseline and after the 12-week treatment period.

Results: The baseline demographic and clinical characteristics of the randomized patients were comparable across the study groups. As anticipated, empagliflozin demonstrated a significant reduction in fasting blood glucose (FBG) and glycated hemoglobin (HbA1c) compared to the placebo after 12 weeks of treatment. Additionally, in comparison to the placebo, empagliflozin significantly increased the antioxidant capacity by elevating serum activity of SOD and GPx, while reducing oxidative damage, as evidenced by diminished MDA levels. Empagliflozin-treated patients also experienced greater improvement in their NYHA functional classes by week 12, though no significant changes in Left Ventricular Ejection Fraction (LVEF) were observed.

Conclusion: The findings of this study shed light on the potential mechanisms through which SGLT2 inhibitors exert their beneficial effects on clinical outcomes in diabetic patients with HFrEF. This provides compelling evidence supporting the cardio-protective of SGLT2 inhibitors in this patient population.

Clinical trial registration number: The trial was registered at the Iranian Registry of Clinical Trials (https://irct.behdasht.gov.ir/trial/72825, identifier code: IRCT20120215009014N484). Registration date: 2022-09-30.

Background: Millions of people worldwide suffer from dry eye disease. Dry eye, a multifunctional condition of the ocular surface, typically occurs in conjunction with an unbalanced tear film. With increasing age, the dry eye problem becomes worse. Aqueous-deficit dry eye and evaporative dry eye are the two traditional classifications for dry eye. Various examination tools are used to diagnose dry eye. Clinical trials are conducted in four phases to check the safety and efficacy of drugs. The quick clearance from the precorneal space is ensured by the eye's advanced defense mechanism. It restricts the integrated medicine's entry into the eyes, resulting in a usually low bioavailability for topical eyedrops. In this study, we focus on recently developed formulations for curing dry eye.

Objective: This review's goal was to outline the etiology, clinical discovery and development, patents, and recent advancements for dry eye disease.

Results: The current study has described the widespread incidence of dry eye, which was found to be more common as people aged and recently developed formulations are treating dry eyes. According to research, novel formulations are enhancing ocular drug delivery.

Conclusion: In this review, etiology, clinical data, dry eye formulation patents, and recent advancements are all included.

Introduction: Wernicke Encephalopathy (W.E.) is an acute neurological disorder induced by thiamine deficiency. Alcohol abuse is considered to be the leading cause of the disease; however, numerous other conditions, such as malnutrition or cancer, have been identified as potential risk factors.

Case presentation: Clinical manifestations include a typical triad of mental status alteration, nystagmus, and ataxia and are attributed to damage in brain regions of high thiamine demand. The diagnosis is mainly clinical and further supported by the immediate response of neurological signs to parenteral thiamine administration. Among paraclinical examinations, brain MRI is considered substantial for diagnosis and is supported by the determination of thiamine blood levels.

Conclusion: Non-alcoholic W.E. is trickier to diagnose due to its atypical clinical course and risk factors. We herein describe a case of non-alcoholic W.E. in a woman with colon cancer who gradually developed the classic symptoms of thiamine deficiency.

Management of infections in heart transplant recipients is complex and crucial. In this population, there is a need for a better understanding of immunosuppressive trough levels (C0), infectious complications, and urinary tract infections (UTIs). The purpose of this review was to understand the association between immunosuppressive trough levels and UTIs after heart transplantation. A review of scientific literature (n= 100) was conducted based on the topic of interest by searching PUBMED.Gov (https://pubmed.ncbi.nlm.nih.gov/), Web of Science, and Scopus. The analysis of bacterial pulmonary infection required the occurrence of new or deteriorating pulmonary infiltrates and the development of organisms in cultures of sputum specimens. The diagnosis of UTIs was based on the result of related signs, pyuria, and a positive urine culture. The incidence of UTIs was reported as 0.07 episodes/1000 regarding heart transplantation days. An eightfold increase in the rate of rejection was noted in heart transplant recipients with higher variability in tacrolimus C0. There are associations between C0 of immunosuppressive drugs and clinical presentation of infection complications. Recipients with a low metabolism of immunosuppressive drugs are more susceptible to infectious complications. Attention to the biology of herpes viruses, Escherichia coli, Enterococcus spp., Pseudomonas aeruginosa, and Staphylococcus saprophyticus after heart transplantation are important, in which some of them are the most common pathogens responsible for UTIs. Pneumocystis and cytomegalovirus affect all transplant recipients. Pneumonia due to bacterial, viral, protozoa, and fungal infections, in addition to UTIs, are more specific reported types of infections in heart transplant recipients. Bacterial infections produced by extensively drug-resistant Enterobacteriaceae, vancomycin-resistant enterococci, and non-fermenting gramnegative bacteria were reported to increase after transplantation.

Aim: The aim of this study was to assess the role of seminal Malondialdehyde Acid (MDA) in the diagnosis of male infertility.

Background: Both male and female infertility is increasing all over the world.

Objective: The purpose of this study was to assess the impact of seminal MDA levels on various semen parameters of healthy fertile men and men with infertility, and to know the efficacy of seminal MDA in the diagnosis of male infertility.

Methods: This case-control study was carried out at the Department of Obstetrics and Gynaecology of a tertiary care center in rural Southern India over a period of two years. The study included 90 infertile men (≥21-50 years) having some pathology in semen reports as cases and 90 fertile men (having biological children) with normal semen reports as controls. Biochemical tests for MDA were performed using Human MDA Assay kits on 180 cryopreserved semen samples following the standard protocol. Results of seminal MDA levels were assessed among cases and controls and correlated with different semen parameters.

Results: The mean±SD age for cases was 30.10 ± 4.75 years, and for controls, it was 29.79 ± 5.08 years. Of all the cases, 44 (48.9%) had asthenozoospermia, 22 (24.4%) had oligoasthenozoospermia, 14(15.6%) had oligozoospermia, and 10 (11.1%) had azoospermia. A statistically substantial variance was observed in mean values of MDA (1.03 ± 0.31 mmol/mL vs. 0.60 ± 0.14 mmol/mL; p =0.001) between fertile men and men with abnormal semen reports. A negative association was observed between semen MDA levels with sperm motility, concentration, and normal morphology in 180 participants. The sensitivity of MDA for male infertility prediction was 86.67% at 76.67% specificity, 78.79% positive predictive value, and 78.79% negative predictive value.

Conclusion: MDA has been found to be a promising biomarker for predicting male infertility. However, large sample sizes and prospective cohort studies are required to further confirm its predictive accuracy across various populations.

Background: The HSP90 marker is believed to play a constructive role in facilitating neoplastic transformation mainly via interaction with multiple pro-survival proteins. Welldesigned studies are needed to elucidate the role of HSP90 as a diagnostic marker and therapeutic target in testicular tumors.

Objective: The current study aimed to investigate the expression of HSP90 in various types of testicular cancer and highlight its expression in embryonal testicular cancer.

Material and methods: Immunohistochemical staining for HSP90 in 84 male patients, with nonmetastatic testicular cancer, who underwent orchiectomy from 2000 to 2023, was retrospectively performed at the Laboratory Department of General Hospital of Nikaia in Greece.

Results: A total of 84 males, with a mean age of 36.2 years, who have undergone high-cord radical orchiectomy, were included in this study. Out of the included males, 28.57% had embryonal carcinoma, 23.81% had seminoma, 19.05% had yolk sac tumor, 11.9% had mature teratoma, 9.52% had immature teratoma, and 7.14% had choriocarcinoma. HSP90b was positive in all embryonal carcinoma, seminoma, and choriocarcinoma cases, while it was positive in 75% of the yolk sac tumor, 75% of mature teratoma, and 75% of immature teratoma specimens. HSP90 was found negative in all choriocarcinoma, mature teratoma, and immature teratoma specimens, while it was positive in 25% of yolk sac tumor, 8.33% of embryonal carcinoma, and 10% of seminoma cases. Concerning the expression of HSP90b, a statistically significant relationship was found between excised tumor specimens and normal parenchyma specimens, especially in sac cases (p <0.001). Regarding HSP90a expression, a statistically significant relationship (OR=21.5, p =0.021) was found between excised tumor specimens and normal parenchyma specimens, especially in embryonal carcinoma cases (p <0.001).

Conclusion: HSP90b is highly expressed in the majority of the types of testicular tumors, both in tumor and normal parenchyma specimens, while HSP90a staining is negative in resected specimens. Further well-designed studies are needed to elucidate the role of HSP90 as a diagnostic marker and therapeutic target in testicular tumors.

The use of antibodies to neutralize cytotoxic soluble amyloid-β aggregates rather than remove plaque has raised cautious hope since the monoclonal antibody BAN2401 seems to halt the course of prodromal Alzheimer's Disease (AD). By immobilizing cytotoxic amyloid-β, rather than the causative factor, plaques can help prevent Alzheimer's disease. A preventive immunity against Alzheimer's disease is shown by natural antibodies against cytotoxic amyloid-β. Vaccines should include adjuvants that promote anti-inflammatory Th2 immunity and immunogens that guard against different cytotoxic amyloid-β conformers to prevent or delay the onsetof Alzheimer's disease. The lack of long-term protection with monoclonal antibodies that neutralize single conformers, such as aducanumab, may be due to amyloid-β pleomorphism. In this scenario, novel cytotoxic conformers might evade neutralization by monoclonal antibodies that were previously successful. A vaccine's ability to elicit a polarized Th2 immunity would depend on both priming and the simultaneous delivery of immunogen to dendritic cells. In addition to neutralizing antibodies against neurotoxic amyloid-β oligomers, an immune response may also release anti-inflammatory cytokines, which can help prevent inflammation that exacerbates Alzheimer's disease. Vaccines would be significantly more successful in preventing Alzheimer's disease than treating it because of age-related immunological decrease. Since both amyloid-β and tau contribute to pathological hyperphosphorylation and work in tandem to cause Alzheimer's disease, preventive vaccinations against both should be taken into consideration. Given their affordability and simplicity, vaccines may be the only way to stop the looming Alzheimer's pandemic in many nations.

The present study focuses on the possible use of the emerging technology of blockchain in ensuring data management security in clinical trials. With the determination of the chief researchers and clinical investigations becoming more and more complex and international, achieving data quality and integrity, transparency, and legal compliance becomes imperative. By offering a distributed and immutable time-stamped ledger, issues of data revisions, selective data release, and the usually time-consuming issue of compliance auditing are well addressed. With this technology, it is possible to conduct surveillance of multi-center studies without compromising the confidentiality of patients while allowing the researchers to have unbiased information. When it comes to internal accountability, the use of the blockchain will create a situation whereby no alteration of the documents will take place. Thus, regulatory oversight is improved with the engagement of these parties. In addition, it makes sure that the need for bias in the reporting of outcomes is avoided in all trials and all results reported whether positive or negative. In order to address clinical trial data management and clinical trial outcomes' validity and reliability, this review provides reputation management through digital ledger technology in the real world.