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.