Reviews on Recent Clinical Trials - Online First

The intersection of drug discovery and cybersecurity is becoming critical as the pharmaceutical sector adopts digital technologies to drive research and development. Drug discovery entails extensive collaboration and large volumes of data, making it highly susceptible to cyberattacks. Emerging technologies, such as big data analytics, artificial intelligence (AI), and cloud computing, hold significant innovation potential but also pose risks to the industry that can undermine intellectual property (IP), clinical trial results, and collaborative research. This review discusses the importance of cybersecurity in the drug discovery process. The focus is on determining major threats, defining best practices for protecting sensitive information, and ensuring compliance with regulatory requirements. The objective is to highlight the strategic significance of cybersecurity practices in protecting research integrity and fostering innovation.

The review-based approach is employed to analyze present-day trends in drug discovery cybersecurity. Emerging technologies, security issues, regulatory needs, and the security controls most frequently utilized in the industry, such as encryption, multi-factor authentication, and secure data sharing, are discussed in the chapter.

The pharmaceutical sector has advanced significantly in securing sensitive research information through robust cybersecurity measures. However, the vulnerabilities remain for cloud security as well as for protecting AI models. Adhering to the regulatory guidelines of GDPR (General Data Protection Regulation) and HIPAA (Health Insurance Portability and Accountability Act) remains a concern as international norms evolve.

As digital technologies transform drug discovery, cybersecurity has become crucial in protecting sensitive data and intellectual property rights. Strengthening compliance with evolving regulations is key to ensuring safety and innovative pharmaceutical research.

Cybersecurity is critical in preserving the integrity of drug discovery. With the increasing adoption of digital technologies, pharmaceutical firms must implement robust cybersecurity measures to protect sensitive information, ensure compliance, and foster innovation in a secure environment.

Probiotics and prebiotics have shown promise in Ulcerative Colitis (UC) through effects on gut homeostasis and barrier integrity. We investigated the efficacy of a symbiotic preparation containing inulin, fructo-oligosaccharides (FOS), Lactobacillus rhamnosus GG, bromelin, boswellia, vitamin D3, quercetin, and L-tryptophan in patients with active mild-to-moderate UC.

This was a multicenter, retrospective, observational study conducted between January and June 2023. Disease activity was assessed using the Partial Mayo Score (PMS). Patients were evaluated at baseline, 8 weeks, and 16 weeks. The primary endpoint was clinical response, defined as a PMS reduction of ≥2 points. Secondary endpoints included changes in C-Reactive Protein (CRP), Fecal Calprotectin (FC), and safety outcomes.

Seventeen patients (8 males, 9 females) were enrolled. The median age at diagnosis was 48 years (IQR: 20–80), and the median disease duration was 10 years (IQR: 2-23). Clinical response was observed in 9/17 (52%) patients at week 8 and in 11/17 (64%) at week 16 (p = 0.697). The CRP values did not change significantly at follow-up. FC decreased significantly from baseline [252 µg/g (IQR: 76–359)] to week 8 [98 µg/g (IQR: 20–448), p < 0.02], but not at week 16. No adverse events were reported.

The symbiotic mixture demonstrated potential as an add-on therapy in UC, with favorable short-term effects on FC. However, the lack of sustained biomarker changes highlights the need for further studies.

This preliminary study suggests that supplementation with the evaluated symbiotic preparation is safe and may improve clinical outcomes in mild-to-moderate UC. Larger randomized controlled trials are required to validate these findings and assess long-term efficacy.

Breast cancer is a very common disease affecting females on a global scale. It is responsible for approximately 10% of breast cancer-related fatalities. In 2022, approximately 2,308,897 new cases were reported globally. Recent studies focused on breast tumors have successfully recognized somatic mutations. This study aimed to identify previously unidentified somatic mutations in breast cancer patients belonging to Pakistan.

The breast tumor sample was obtained from Jinnah Hospital, Lahore. The DNA was extracted, and whole-exome sequencing was conducted on six samples.

Gene mutations found include 58.69% synonymous SNV, 28.37% nonsynonymous SNV, 3.89% Frameshift deletion, 6.68% Nonframeshift deletion, 2.09% stopgain, and 0.28% stop loss. Among 39 genes analyzed, the prevalence of gene mutations varied, with HYDIN (100%), ENTHD1 (33.33%), ADRA1B (66.67%), GATA3 (50%), CDH1 (16.67%), RB1 (50%), MAP3K1 (100%), EGFR (50%), TRPM6 (33.33%), KHDRBS1 (33.33%), RBM25 (66.67%), SF3B3 (50%), TEK (16.67%), PGK2 (33.33%), CBFB (33.33%), ARID1A (66.67%), KMT2C (100%), HECTD1 (100%), LAMA3 (66.67%), FLG2 (83.33%), UGT2B4 (16.67%), STK33 (66.67%), ACP4 (50%), DNAH8 (100%), TNN (66.67%), IGSF3 (100%), TRIM67 (83.33%), DNMBP (100%), CORO7 (16.67%), CDC27 (33.33%), ZNF544 (50%), MST1 (16.67%), DENND2A (33.33%), NCKAP5 (50%), PCDHB10 (50%), FBXW7 (50%), EIF4G3 (66.67%), IL12RB2 (50%), and PDE4B (50%).

Breast cancer is a fatal disease. The high frequency of synonymous mutations was observed. The HYDIN, MAP3K1, KMT2C, HECTD1, DNAH8, IGSF3, DNMBP genes were 100% mutated then other genes.

This study unveils new somatic alterations in different genes among early-onset Pakistani breast cancer patients, offering valuable insights for drug design targeting breast carcinoma.

Reduction in the quantity and quality of ova during the reproductive period of women is a physiological phenomenon. However, in some women, the deterioration of the ovaries occurs suddenly, and they experience infertility due to premature ovarian failure. This study aimed to explore the correlation between Primary ovarian insufficiency (POI) and the pregnancy rate of women in relation to the Tajik lifestyle modification diet.

In this clinical randomized controlled trial study conducted in 2023, 72 infertile couples were randomly assigned to two groups, control and intervention. The intervention group received Tajik counseling sessions. In cases of normal distribution, the ANCOVA test was used to evaluate the difference between the two groups, and within-group comparisons were made using a paired t-test, while between-group comparisons were made using an independent t-test. A significance level of less than 0.05 was considered.

In comparison to the control group, women with POI exhibited notably lower levels of follicle-stimulating hormone, luteinizing hormone, and prolactin, along with higher anti-mullein levels. Within the intervention group, there were 17 successful pregnancies, two miscarriages, and 14 instances of improved menstrual status, resulting in a pregnancy rate of 52.7%.

After receiving lifestyle modification advice using the Tajik method, women with POI experienced improvements in their FSH, LH, AMH, and PRL hormone levels, leading to an increase in their pregnancy rate.

According to the results of the present study, the use of the Tajik method is recommended to help treat POI.

Gestational diabetes mellitus (GDM) is a prevalent metabolic disorder that can occur during pregnancy, leading to various complications for both the mother and the fetus. Additionally, women with gestational diabetes are at a higher risk of experiencing mental health disorders. This study was conducted to investigate the impact of group counselling based on mindfulness on perceived stress in pregnant women with gestational diabetes, given the influence of cognitive-behavioral interventions such as mindfulness on stress and anxiety.

In this research, 80 pregnant women diagnosed with gestational diabetes were randomly divided into two groups: an intervention and a control. Before the intervention, participants completed a questionnaire that included demographic and obstetric information as well as the Cohen Perceived Stress Questionnaire. The intervention group participated in 8 sessions of mindfulness counselling, with each session lasting between 45 and 60 minutes. Mindfulness sessions focused on emotion regulation. The control group did not receive any intervention. Participants completed the questionnaires one month after the initial intervention in the control group and right after the counselling ended in the intervention group.

The mean score of perceived stress among pregnant women decreased significantly after the intervention (p ˂0.001). There was no difference in socio-demographic characteristics between the groups (p ˃0.05). After the intervention, the perceived stress levels of pregnant women significantly decreased compared to before (from 29.72 (5.33) to 26.10 (5.07)), and after the ANCOVA test, the difference was statistically significant (p ˂0.001).

Mindfulness-based counseling plays an important role in reducing the stress of pregnant women with gestational diabetes through increased awareness, and it can help them control disease conditions, reduce stress, and apply effective coping strategies for stress. Mindfulness-based counseling reduces the perceived stress of pregnant women and thus reduces adverse physical and psychological consequences during pregnancy.

Healthcare data management, especially in the context of clinical trials, has been completely transformed by cloud computing. It makes it easier to store data, collaborate in real time, and perform advanced analytics across international research networks by providing scalable, secure, and affordable solutions. This paper explores how cloud computing is revolutionizing clinical trials, tackling issues including data integration, accessibility, and regulatory compliance.

Key factors assessed include cloud platform-enabled analytical tools, collaborative features, and data storage capacity. To ensure the safe management of sensitive healthcare data, adherence to laws like GDPR and HIPAA was emphasized.

Real-time updates and integration of multicenter trial data were made possible by cloud systems, which also showed notable gains in collaborative workflows and data sharing. High scalability storage options reduced infrastructure expenses while upholding security requirements. Rapid interpretation of complicated datasets was made possible by sophisticated analytical tools driven by machine learning and artificial intelligence, which expedited decision-making. Improved patient recruitment tactics and flexible trial designs are noteworthy examples.

Cloud computing has become essential for international clinical trials because it provides unmatched efficiency in data analysis, communication, and storage. It is a pillar of contemporary healthcare research due to its capacity to guarantee data security and regulatory compliance as well as its creative analytical capabilities. Subsequent research ought to concentrate on further refining cloud solutions to tackle new issues and utilizing their complete capabilities in clinical trial administration.

Pressure injuries (PIs) pose a significant threat to the safety of hospitalized, mobility-compromised patients globally. Olive oil has shown promising results in preventing PIs due to its high concentrations of monounsaturated fatty acids and phenol antioxidants, known for their anti-inflammatory and cell-protective properties. This study aimed to evaluate the effectiveness of topical olive oil combined with routine preventive interventions in reducing PI incidence.

A single-blinded, cluster-randomized study was conducted among 80 hospitalized patients at risk of developing PIs. Participants were randomized into two clusters: the intervention group (IVG, n=40) received standard PI preventive care (skin assessment, repositioning, support surfaces) plus topical olive oil application for 7 consecutive days; the control group (CG, n=40) received only standard care. PI prevalence and Braden Scale scores were assessed at baseline and post-intervention (days 3-8). Data were analyzed using descriptive statistics and paired sample t-tests.

At baseline, both groups had a PI prevalence of 52.5% (n=21). After the intervention, prevalence reduced to 5% (n=2) in IVG and 22.5% (n=9) in CG. The Braden Scale score in the IVG declined from 12.45±0.50 to 11.75±1.13. Statistically significant improvements were observed in Braden scores between day 1 and day 3 (IVG: x̄= -0.28±0.55, t= -3.14, p <0.05; CG: x̄= -0.58±4.69, t= -4.66, p <0.05) and between day 1 and day 8 (IVG: x̄= -0.70±1.07, t= -4.15, p <0.05; CG: x̄= 1.38±1.58, t= -5.50, p <0.05).

The findings underscore the clinical benefit of incorporating topical olive oil into standard PI preventive care. The significant reduction in PI prevalence and improved Braden Scale scores suggest olive oil’s potential role as a protective agent due to its anti-inflammatory and antioxidant properties. These results align with existing literature on natural oil-based interventions for skin integrity. However, limitations include the small sample size and short duration, warranting further large-scale studies.

Topical olive oil, when used alongside standard care practices, significantly reduced the incidence of pressure injuries in hospitalized, at risk patients. This approach could serve as a cost-effective, natural adjunct to PI prevention protocols, particularly in resource-limited healthcare settings.

Colonoscopy is a critical tool for the management of Ulcerative Colitis (UC). In this study, we aim to explore the accuracy of Virtual Chromoendoscopy (VCE) using Narrow Banding Imaging (NBI), and magnification using Near Focus (NF) for a better definition of endoscopic inflammation grade in UC patients compared to standard white light (WL) endoscopy alone.

This is a non-randomized prospective study including all the patients who underwent a colonoscopy (for any reason) between April and September 2023 (with protocol number n. 60/2019.20). During the endoscopic evaluation, at least one image with white light - evaluated using the Mayo Endoscopic Score (MES), one image with NBI, one image with NBI plus NF, and a biopsy were obtained in each colonic tract (cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum). All the stored images were evaluated by three endoscopists separately and compared with the results of the histological evaluation.

A total of 31 UC patients were included. The inter-rater reliability concerning the different scores used (MES, NBI score, and NBI plus NF score), which was evaluated with Cohen's kappa coefficient, was good for the MES, good to excellent for the NBI score, and good for the NBI plus NF score. The concordance between histological evaluation (using the Nancy Index) and the MES was unsatisfactory for all the endoscopists, while the concordance between the NBI evaluation score and the Nancy Index was good to excellent.

The reported results demonstrated both the inter-rater reliability and diagnostic accuracy of NBI in assessing endoscopic disease activity. The high inter-operator agreement, ranging from good to excellent, further supports the feasibility and consistency of NBI as a practical tool.

The results in the present study suggest that the new endoscopic technologies could be useful to better define disease activity in Inflammatory Bowel Disease (IBD) patients driving better therapeutic strategy.

Lifestyle interventions have been increasingly studied for their potential to improve health outcomes in breast cancer survivors. However, the relative effectiveness of these interventions remains unclear. This study aimed to evaluate the impact of various lifestyle changes on the health outcomes of breast cancer survivors.

A comprehensive analysis of randomized controlled trials (RCTs) involving breast cancer survivors was conducted across major databases, including PubMed, Scopus, Embase, CINAHL, Cochrane Library, and ClinicalTrials.gov. Studies were selected based on their evaluation of lifestyle interventions aimed at reducing breast cancer risk and its recurrence and or improving survival. Non-RCTs and studies focusing solely on pharmacological or genetic interventions were excluded. The risk of bias in included randomized controlled trials was assessed using the Cochrane Risk of Bias 2 (RoB 2). The results of the included studies were presented in tabulated form.

Physical activity emerged as the most effective intervention, significantly enhancing metabolic health, body composition, and cardiorespiratory fitness. Dietary changes and weight management programs provided secondary health benefits, such as modest improvements in diet quality, metabolic markers, and quality of life. The combined intervention of diet and exercise further improved these outcomes although it did not significantly reduce cancer recurrence. The digital support system (EMPOWER-SMS) was feasible and acceptable, offering minor improvements in medication adherence and self-efficacy, though its effects on BMI and quality of life were less pronounced.

Among the various lifestyle interventions explored for breast cancer survivors, physical activity consistently emerged as the most effective in improving health outcomes. While dietary changes, weight management, and combined interventions also offered health benefits, their direct impact on key outcomes like cancer recurrence and survival was less clear. However, when integrated with regular exercise, these interventions contributed to holistic improvements in quality of life, making a combined approach potentially the most comprehensive for supporting breast cancer survivors. This systematic review's limitations include intervention heterogeneity, varied follow-up durations, inconsistent outcome measures, small sample sizes, lack of control over confounding variables, limited participant diversity, potential publication bias, and a focus on short-term outcomes.

Physical activity emerged as the most beneficial lifestyle intervention for breast cancer survivors, particularly when combined with dietary modifications and weight management. A holistic approach that integrates physical activity, dietary changes, and digital support may provide the most comprehensive benefits for breast cancer survivors.

Accurate mortality prediction in intensive care units (ICUs) is essential for enhancing patient outcomes and optimizing healthcare resource allocation. Traditional scoring systems, such as APACHE, APACHE II, and SAPS, have limitations in handling complex, high-dimensional ICU data. In this study, multiple machine learning models were compared to establish an efficacious predictive model for mortality tailored explicitly to the Jordanian population and to explicate factors strongly associated with mortality.

This study was conducted as a single-center, retrospective cohort investigation, and the XGBoost machine learning algorithm was used to develop a novel ICU mortality prediction model. The model aimed to achieve superior prediction accuracy using a diverse set of readily available clinical data, including demographics, comorbidities, laboratory results, and medication groups. Model performance was evaluated against alternative machine learning algorithms, including logistic regression, conventionally employed in traditional scoring systems.

Comparative analysis revealed that the XGBoost model performed better than other scoring systems, manifesting heightened accuracy (87.91%), sensitivity (92.88%), and Area Under the Receiver-Operating Characteristic Curve (AUC-ROC) Score/Curve (94.29%). Notably, the patient's length of hospital stays, albumin levels, and urea levels emerged as the most substantial predictors for ICU mortality, each exhibiting respective SHAP values of 0.5, 0.41, and 0.37.

A locally adapted ICU mortality prediction model was developed, underscoring the pivotal role of predictors such as hospital stay duration, albumin, and urea levels in predicting patient outcomes.

The heightened accuracy and sensitivity of the XGBoost model signify its potential as an invaluable tool in the critical task of mortality prediction within the Jordanian ICU context.

Anti-melanoma Differentiation-associated Gene 5 (aMDA5) antibody-associated Rapidly Progressive Interstitial Lung Disease (RP-ILD) is a rare and potentially fatal condition.

This case report describes a 78-year-old male who presented with a 10-day history of fever, cough, and asthenia.

Despite initial treatment for suspected atypical pneumonia, the clinical condition of the patient rapidly deteriorated, necessitating intensive care and mechanical ventilation. High-resolution CT scans revealed a progressive interstitial lung disease with pneumomediastinum. Autoimmunity blood tests revealed high-titer anti-MDA5 antibodies, leading to a diagnosis of anti-MDA5 RP-ILD. Despite aggressive immunosuppressive therapy, the patient's condition continued to worsen, resulting in death.

Our case underlines the importance of early recognition and diagnosis of anti-MDA5 RP-ILD, as it can present without typical dermatomyositis skin manifestations. The report also includes a comprehensive literature review covering the pathogenesis, clinical manifestations, diagnosis, and treatment options for anti-MDA5-associated disease.

This case underscores the need for increased awareness of this condition among clinicians to improve early diagnosis and treatment outcomes.

The quality of methodological reporting in randomized controlled trials (RCTs) is crucial for guiding healthcare decisions. This study compares the methodological reporting of RCT articles published in Iranian nursing and midwifery journals indexed in Scopus with those published in international nursing and midwifery journals also indexed in Scopus.

This comparative cross-sectional study reviewed RCT articles from eight Iranian Scopus-indexed journals (381 articles) and three journals with the highest CiteScore index (204 articles) from 2017 to 2021. Data were collected using the methodology section of the CONSORT checklist. SPSS 19 software was used for data analysis.

The average percentages of methodological reporting in the top three Iranian journals were 76.4% and 84.4%. The mean quality score of methodological reporting in Iranian nursing and midwifery journals was significantly lower than that in international journals published from 2017-2021 (P <0.001). Underreporting was observed in both groups, particularly regarding randomization and blinding.

Our findings align with previous studies indicating that adherence to reporting standards, such as CONSORT guidelines, is more common in higher-impact journals. Deficiencies in reporting elements, such as randomization and blinding, undermine confidence in study results.

The average quality of methodological reporting in Iranian journals is lower than that in the top three Scopus-indexed journals. Journals with lower reporting quality, like Iranian journals, can enhance article quality by adhering to reporting guidelines for all article types, including RCTs.

Understanding the public perception of colorectal cancer screening is crucial since early diagnosis lowers mortality rates associated with this type of cancer.

The purpose of this study was to determine the most popular technique for colorectal cancer screening in Saudi Arabia. From September 2021 to February 2022, a cross-sectional study on adult Saudi population was undertaken. Data were collected through a self-created survey distributed via an online platform.

Out of 10,781 participants analyzed, 5,612 were found suitable for evaluating preferences between colonoscopy and fecal immunochemical test (FIT) as screening modalities. It was found that gender, employment, and age were important predictors for the preferred screening modality.

The patient’s perspective on screening modalities is crucial to consider in national colorectal cancer screening programs. The future outlook for home-based fecal immunochemical Tests (FIT) may provide superior research regarding cost-effectiveness and adherence among patients compared to colonoscopy or medical facilities in FIT investigations.

More attention should be paid to the population’s preferred method of colorectal cancer screening, which could increase the success of the screening effort. Cultural and socioeconomic status might affect the generalizability of the study.

Chronic liver diseases have been reported to be associated with altered sexual function. The existing gap in understanding the pathophysiological mechanisms linking sexual disorders and chronic liver diseases may explain the lack of attention given to sexual health in this cohort of patients. We, therefore, aimed at reviewing the available evidence linking chronic liver diseases and sexual dysfunction in both sexes.

A search of the PubMed database was conducted for the period between January 1995 and July 2024 using the following terms: “chronic liver disease”, “liver cirrhosis”, “viral hepatitis B”, “viral hepatitis C”, “non-alcoholic fatty liver disease”, “metabolic dysfunction associated steatotic liver disease” “alcoholic liver disease” and “erectile dysfunction,” “hypogonadism”, “infertility”.

A total of 96 articles were reviewed, including preclinical original research articles, human observational and clinical studies, systematic reviews, and meta-analyses. We found that sexual dysfunctions are often associated with chronic liver diseases and that this depends on the degree of the underlying liver damage and etiology. Contributing factors may include hormonal imbalances, psychological disturbances, and endothelial dysfunction.

The degree of liver function impairment, the specific etiology, particularly metabolic dysfunction associated steatotic liver disease, and drugs used in the management of chronic liver diseases all contribute to sexual dysfunction in this clinical setting.

Chronic liver diseases are associated with a wide range of sexual dysfunctions in both sexes, causing an altered quality of life. This suggests that sexual function should be assessed in this clinical setting in order to reach a prompt diagnosis and start appropriate treatment.

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.

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.

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.

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.