Systematic Review Of Clinical Trials Research Articles

Advancements in Virtual Bioequivalence: A Systematic Review of Computational Methods and Regulatory Perspectives in the Pharmaceutical Industry

Background/Objectives: The rise of virtual bioequivalence studies has transformed the pharmaceutical landscape, enabling more efficient drug development processes. This systematic review aims to explore advancements in physiologically based pharmacokinetic (PBPK) modeling, its regulatory implications, and its role in achieving virtual bioequivalence, particularly for complex drug formulations. Methods: We conducted a systematic review of clinical trials using computational methods, particularly PBPK modeling, to carry out bioequivalence assessments. Eligibility criteria are emphasized during in silico modeling and pharmacokinetic simulations. Comprehensive literature searches were performed across databases such as PubMed, Scopus, and the Cochrane Library. A search strategy using key terms and Boolean operators ensured that extensive coverage was achieved. We adhered to the PRISMA guidelines in regard to the study selection, data extraction, and quality assessment, focusing on key characteristics, methodologies, outcomes, and regulatory perspectives from the FDA and EMA. Results: Our findings indicate that PBPK modeling significantly enhances the prediction of pharmacokinetic profiles, optimizing dosing regimens, while minimizing the need for extensive clinical trials. Regulatory agencies have recognized this utility, with the FDA and EMA developing frameworks to integrate in silico methods into drug evaluations. However, challenges such as study heterogeneity and publication bias may limit the generalizability of the results. Conclusions: This review highlights the critical need for standardized protocols and robust regulatory guidelines to facilitate the integration of virtual bioequivalence methodologies into pharmaceutical practices. By embracing these advancements, the pharmaceutical industry can improve drug development efficiency and patient outcomes, paving the way for innovative therapeutic solutions. Continued research and adaptive regulatory frameworks will be essential in navigating this evolving field.

Sacituzumab Govitecan in Triple Negative Breast Cancer: A Systematic Review of Clinical Trials.

Triple-negative breast cancer is difficult to treat due to the absence of hormone receptors and Her2neu. Sacituzumab govitecan is a new therapeutic approach that uses an antibody directed against the Trop-2 antigen present in solid epithelial tumors, linked to the active metabolite SN-38, similar to irinotecan, to specifically target cancer cells while minimizing damage to healthy cells. The objective of the present review was to evaluate the efficacy and safety of sacituzumab govitecan as a single treatment in patients with triple-negative breast cancer and to compare its results with the standard conventional chemotherapy regimen currently used in this disease. A systematic review of randomized clinical trials of sacituzumab govitecan was performed. The search was performed in Medline (PubMed), Web of Science, and Cochrane from September 2022 to January 2024. Thirty-eight articles are included and evaluated according to inclusion and exclusion criteria corresponding to the two most relevant clinical trials, including specific analyses of cohorts and subgroup study arms within these trials. Data from more recent clinical trials are also reviewed. The efficacy results showed a significantly greater clinical benefit with sacituzumab govitecan compared to standard chemotherapy in patients with triple-negative breast cancer. This drug will become a treatment of substantial impact in future treatment guidelines for this type of cancer.

Safety and efficacy of fecal microbiota transplantation for viral diseases: A systematic review of clinical trials.

Gut microbiota play important roles in several diseases like viral infections. In this systematic review, our objective was to assess the efficacy and safety of fecal microbiota transplantation (FMT) in treating various viral diseases. We conducted searches on databases including PubMed, Web of Science, Scopus, and Google Scholar until November 2023. Clinical trials reported outcomes related to safety of FMT or its efficacy in patients with viral diseases were included. We excluded other types of studies that enrolled healthy individuals or patients with other disorders and did not use FMT. The assessment of bias risk was conducted using the National Institutes of Health (NIH) study quality evaluation tool. Eight studies with total 196 participants were included. Viral diseases were human immunodeficiency virus (HIV), hepatitis B, COVID-19 and Clostridioides difficile coinfection, and cytomegalovirus colitis. In hepatitis B cases, HBeAg clearance was significant in those received FMT (p<0.01), while it was not significant in another one (p = 0.19). A clinical response was noted in 37.5% of patients with cytomegalovirus colitis, with an equal percentage achieving clinical remission post-FMT. There was a significant reduction in Clostridioides difficile relapse rate in FMT group than controls in coinfection of Clostridioides difficile and COVID-19 (2.17% vs. 42.5%, p<0.05). In patients with HIV, partial engraftment of the donor microbiome and increases in alpha diversity were observed after FMT. No severe adverse events were reported. Most studies had fair or good qualities. Our findings revealed FMT as a promising, safe treatment for some viral diseases. It improved viral clearance, clinical outcomes, and inflammation. However, the varying responses and small sample sizes call for more trials on FMT in viral diseases.

Short-term safety and tolerability profile of 5-methoxy-N,N-dimethyltryptamine in human subjects: a systematic review of clinical trials.

Psychedelic agents have regained the attention of pharmaceutical companies as promising treatments for depressive episodes. 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT), an atypical psychedelic, is emerging as a potentially effective, novel rapid-acting antidepressant. In this systematic review, we analyze the safety and tolerability evidence from clinical trials. Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, electronic databases (PubMed, SCOPUS, Web of Science, EMBASE, and EBSCO) were searched from inception until 15 May 2024 to identify clinical trials (regardless of phase) reporting on short-term safety and tolerability profile of 5-MeO-DMT using the following keywords in various combinations: 5-methoxy-N, N-dimethyltryptamine, 5-MeO-DMT, safety, adverse, adverse reaction, side effects, tolerability, dropout, healthy volunteer, healthy participant, depression, major depressive disorder. Only studies written in English were considered. Initial search yielded 100 records, out of which 3 met the inclusion criteria. These studies reported on the results from clinical trial phases I and I/II, with a total of 78 participants included; two studies involved healthy volunteers, and one included patients with treatment-resistant depression. Although the data is limited, it confirms a good short-term safety and tolerability profile for 5-MeO-DMT, with no serious adverse events (SAEs) reported. Furthermore, no drop-outs were reported. 5-MeO-DMT administration in human subjects presents favorable short-term safety and tolerability profile. Importantly, no SAEs have been documented, and no adverse events led to participant withdrawal from the studies There is a need for future randomized, double-blind, placebo-controlled trials with larger samples and follow-up to assess potential chronic adverse events.

Comparative Outcomes of Transcatheter Versus Surgical Aortic Valve Replacement in Moderate-Risk Patients With Aortic Stenosis: A Systematic Review of Clinical Trials.

Aortic stenosis (AS) is a prevalent condition among the elderly, characterized by the narrowing of the aortic valve, which, if untreated, can lead to heart failure and decreased quality of life in terms of reduced activity and high mortality in one to two years. Surgical aortic valve replacement (SAVR) has long been the standard treatment for AS. However, it poses significant risks, particularly in older patients with comorbidities. In recent years, transcatheter aortic valve replacement (TAVR) has emerged as a less invasive alternative and is increasingly used in low- and moderate-risk patients. This review seeks to assess the comparative outcomes of TAVR and SAVR in patients with moderate-risk AS. A systematic review was conducted in accordance with PRISMA guidelines, focusing on randomized controlled trials (RCTs) that compared TAVR and SAVR in this patient population. Also, the review included three major RCTs: PARTNER 2, UK TAVI, and DEDICATE. We analyzed the key outcomes of TAVR and SAVR, such as mortality, reintervention rates, complications (such as myocardial infarction, prosthetic valve endocarditis, and pacemaker implantation), and reintervention rates, to evaluate the relative efficacy and safety of TAVR and SAVR. The analysis included data from 4,359 patients across the three trials. TAVR demonstrated a lower all-cause mortality in two of the three trials, with an overall trend favoring TAVR in terms of survival. However, TAVR was associated with a higher incidence of prosthetic valve endocarditis, a greater need for pacemaker implantation, and more frequent reinterventions compared to SAVR. In conclusion, the findings suggest that TAVR may be a better option for moderate-risk AS patients, offering higher survival rates and a less invasive recovery process. While TAVR carries increased risks of endocarditis and pacemaker dependency, its overall benefits, particularly in terms of lower mortality and improved patient outcomes, make it a preferable option over SAVR for many patients. However, acknowledging potential limitations such as variations in trial design and differences in patient populations would indeed provide a more comprehensive perspective. Further research and long-term follow-up are essential to confirm these findings and refine patient selection criteria.

Safety and Efficacy of Fixed-Dose Combination of Adapalene and Benzoyl Peroxide in Acne Vulgaris Treatment: A Systematic Review of Clinical Trials.

The Global Burden of Disease Study 2020 ranked acne vulgaris as the eighth most common skin condition, with a global estimated prevalence of 9.4%. The clinical presentation of acne vulgaris ranges from comedones to nodules and cysts. The main treatment options for acne are retinoids, antibiotics, and benzoyl peroxide (BPO). This study aimed to evaluate the reported efficacy and safety of the combination treatment with retinoid and benzoyl peroxide. Three databases (ScienceDirect, Google Scholar, and PubMed) were searched using keywords such as acne, adapalene/benzoyl peroxide, and randomized controlled trial, and specific search moods such as "Title and abstract" for PubMed and "Title, abstract, and keywords" for ScienceDirect. On Google Scholar, the "allintitle" option was utilized. The articles were searched for the years between 2003 and 2023. The eight trials selected for systematic review reported randomized controlled trials in 4,596 individuals with the first trials being conducted in February 2007 and the last one in May 2022. There were 52.8% females in the trials, and the trials reported a primary reduction of acne lesions (efficacy) from 27.5% to 70.2%.The occurrence of adverse effects was also variable (ranging from 2.7% to 57.9%), but these effects were mild and vanished with time. The results showed that the combination of adapalene and benzoyl peroxide is a safe and effective treatment.

The Effects of Epigallocatechin-3-Gallate Nutritional Supplementation in the Management of Multiple Sclerosis: A Systematic Review of Clinical Trials.

Multiple sclerosis (MS) is a chronic, debilitating neurological condition for which current treatments often focus on managing symptoms without curing the underlying disease. Recent studies have suggested that dietary supplements could potentially modify disease progression and enhance quality of life. This systematic review aims to evaluate the efficacy and safety of epigallocatechin-3-gallate (EGCG) as a dietary supplement in patients with MS, with a specific focus on its impact on disease progression, symptom management, and overall quality of life. We conducted a comprehensive systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, utilizing an exhaustive search across the databases PubMed, Scopus, and Web of Science up to 23 February 2024. Eligible studies were randomized controlled trials. Nine clinical trials involving 318 participants were analyzed, with dosages ranging from 600 mg to 1200 mg of EGCG daily, although most studies had only a 4-month follow-up period. Results indicated that EGCG supplementation, particularly when combined with coconut oil, led to significant improvements in metabolic health markers and functional abilities such as gait speed and balance. One trial observed significant improvements in the Berg balance scale score from an average of 49 to 52 after four months of treatment with 800 mg of EGCG daily. Additionally, interleukin-6 levels significantly decreased, suggesting anti-inflammatory effects. Measures of quality of life such as the Beck Depression Inventory (BDI) scale showed significant improvements after EGCG supplementation. However, primary outcomes like disease progression measured by the Expanded Disability Status Scale (EDSS) and Magnetic Resonance Imaging (MRI) of lesion activities showed minimal or no significant changes across most studies. EGCG supplementation appears to provide certain symptomatic and functional benefits in MS patients, particularly in terms of metabolic health and physical functionality. However, it does not significantly impact the primary disease progression markers such as EDSS scores and MRI lesions. These findings underscore the potential of EGCG as a supportive treatment in MS management, though its role in altering disease progression remains unclear. Future research should focus on long-term effects and optimal dosing to further elucidate its therapeutic potential.

The effect of virtual reality on perioperative pain management in patients undergoing gastrointestinal procedures and surgeries: a systematic review of clinical trials

BackgroundVirtual reality (VR) is an advanced technology that transports users into a virtual world. It has been proven to be effective in pain management via distraction and alteration of pain perception. However, the impact of VR on treating perioperative pain is inconclusive. This systematic review aimed to evaluate the effect of VR on perioperative pain after a gastrointestinal (GI) procedure or surgery. MethodsA systematic review of randomized controlled trials was conducted from inception to January 31, 2024, following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The updated Cochrane risk of bias (RoB 2) assessment tool was used to evaluate the risk of bias. ResultsOf 724 articles screened, 8 studies with 678 participants were included in the systematic review. Four studies evaluated the effect of VR on perioperative pain during GI procedure (eg, colonoscopy) focused on its use after GI surgeries (eg, abdominal surgeries). Some studies reported a reduction in pain scores after the procedure; however, the findings of pain difference in before or during vs after the procedure in the VR vs control groups were mixed. ConclusionVR is a promising tool to control perioperative pain after a GI procedure or surgery. Differences in study protocols, pain assessment scales, and pain therapy used were limitations in performing a comprehensive meta-analysis. Further studies are needed to better evaluate the effects of VR on perioperative pain compared with standard of care.

Exploring Resveratrol Intervention in Managing Menopausal Symptoms: A Comprehensive Systematic Review of Clinical Trials

Introduction: Menopause, a significant event in a woman's reproductive lifespan, entails hormonal changes and a range of symptoms affecting various bodily systems. Conventional treatments like hormone replacement therapy (HRT) have limitations and associated risks, prompting interest in alternative therapies such as resveratrol. Materials/Methods: The literature search was conducted in six databases. The outcome of interest measures the mean changes in bone mineral density (BMD), Quality of Life (QoL), bone biomarkers, menopause symptoms, and cognitive and mood functions pre- and post-interventions. Resveratrol was administered in various forms and doses, including trans-resveratrol 75 mg twice or once daily, 250/500/1000 mg resveratrol tablets, and a combination of fermented soy containing 10 mg equol and 25 mg resveratrol. Quality appraisal was done using the Cochrane Risk of Bias Tool 2. Results: Resveratrol supplementation in post-menopausal women, involving 745 participants across various studies, has shown remarkable health benefits. These include improved cerebral vasoreactivity (CVR) to hypercapnia, a 10% decrease in overall pain, and enhanced quality of life. Additionally, resveratrol boosts flow-mediated dilation (FMD) by 23% and increases serum sex hormone-binding globulin (SHBG) concentrations by 10%, benefiting bone mineral density (BMD). Over the long term, it leads to a significant 35% increase in FMD and a substantial 33% enhancement in overall cognitive performance, highlighting its diverse benefits. Conclusion: For women in the post-menopausal stage, resveratrol supplementation shows potential for improving cardiovascular health, relieving pain, enhancing quality of life, supporting bone health, boosting cognitive function, and promoting overall mental well-being.

Adverse Events with Hypoglossal Nerve Stimulation in the Treatment of Obstructive Sleep Apnea-A Systematic Review of Clinical Trials and Real-World Data.

Background/Objectives: Hypoglossal nerve stimulation (HNS) emerged as an alternative treatment for patients with obstructive sleep apnea (OSA) a decade ago. Long-term clinical trials and real-world data show that HNS treatment provides significant and sustained improvements in both OSA disease control and quality-of-life measures over time. Given the nature of HNS treatment, with the requirement of using an implantable neurostimulation system, patient safety is a critical domain in the assessment of this technology. The objective of this review was to evaluate adverse events (AEs) and complications with HNS therapy in a systematic review of published evidence. Methods: Medline, Cochrane, and Web of Science were systematically searched to identify randomized controlled and real-world observational studies reporting relevant outcomes with HNS therapy for treatment of OSA that included procedure-, device-, and treatment-related AEs. Results: Out of 418 articles screened, 27 were reviewed for eligibility, and 17 studies, the majority found to have low-to-moderate risk of bias, with data on 1962 patients were included for further analysis. Across included studies, reporting of AEs was heterogeneous with regard to the classifications used and the extent of reporting. Over an average follow-up duration of 17.5 ± 16.9 months, the pooled mortality rate was 0.01% (95% CI = 0.0 to 0.2%), with all reported deaths being unrelated to HNS treatment. The HNS system survival probability over the follow-up time of 60 months was 0.9834 (95% CI = 0.9768 to 0.9882), with infections and request for removal by patients being the most common indications. The pooled surgical revision rate was 0.08% (95% CI 0.0 to 0.2%). Most reported treatment-related side effects were transient stimulation-related discomfort (0.08%, 95% CI = 0.0 to 0.2%) and tongue abrasions (0.07%, 95% CI = 0.0 to 0.2%). Based on the systematic review, a standardized set of endpoints was defined, aiming to harmonize safety data relevant to HNS therapy. Conclusions: In this systematic review, HNS therapy for treatment of OSA is associated with a positive patient safety profile. AEs occur mainly at device implantation and during the treatment acclimatization period. Due to a lack of available evidence, partially implantable HNS systems are underrepresented in this review, which limits the generalizability of the results. Significant heterogeneity was found for adverse event reporting. A framework for reporting HNS outcomes that includes AEs and side effects is proposed to facilitate comparability of the reported data.

Examining nutrition strategies to influence DNA methylation and epigenetic clocks: a systematic review of clinical trials.

Nutrition has powerful impacts on our health and longevity. One of the mechanisms by which nutrition might influence our health is by inducing epigenetic modifications, modulating the molecular mechanisms that regulate aging. Observational studies have provided evidence of a relationship between nutrition and differences in DNA methylation. However, these studies are limited in that they might not provide an accurate control of the interactions between different nutrients, or between nutrition and other lifestyle behaviors. Here we systematically reviewed clinical studies examining the impact of nutrition strategies on DNA methylation. We examined clinical studies in community-dwelling adults testing the effects of nutrition interventions on i) global DNA methylation and its proxies, and ii) epigenetic clocks. We included 21 intervention studies that focused on the effects of healthy nutrition patterns, specific foods or nutrients, as well as the effect of multivitamin or multimineral supplements. In four studies on the methylation effects of healthy dietary patterns, as defined by being rich in vegetables, fruits, whole-grains, and nuts and reduced in the intake of added sugars, saturated fat, and alcohol, two of them suggested that a healthy diet, is associated with lower epigenetic age acceleration, one of them reported increases in global DNA methylation, while another one found no diet effects. Studies examining epigenetic effects of specific foods, nutrients, or mixtures of nutrients were scarce. For both folic acid and polyunsaturated fatty acids, the available independent studies produced conflicting findings. Although more evidence is still needed to draw firm conclusions, results begin to suggest that healthy dietary patterns have positive effects on DNA methylation. Additional evidence from large randomized-controlled clinical trials is needed to support the effects of healthy nutrition on the DNA methylome.

Examining the Impact of Ertugliflozin on Cardiovascular Outcomes in Patients with Diabetes and Metabolic Syndrome: A Systematic Review of Clinical Trials.

Cardiovascular diseases (CVDs) constitute a significant cause of morbidity and mortality globally, particularly among individuals with type 2 diabetes mellitus (T2DM). Ertugliflozin, a Sodium-Glucose Co-transporter-2 (SGLT2) inhibitor, is hypothesized to confer cardiovascular protection; however, long-term follow-up studies are necessary to support the hypothesis. This systematic review was conducted to evaluate the cardiovascular effects of ertugliflozin in diabetic versus non-diabetic cohorts, focusing on major adverse cardiovascular events (MACEs), hospitalizations for heart failure, and cardiovascular mortality. Adhering to PRISMA guidelines, the review encompassed studies indexed in PubMed, Scopus, and Web of Science up to March 2024. Eligibility was restricted to studies involving T2DM patients undergoing ertugliflozin treatment with reported outcomes relevant to cardiovascular health. Out of 767 initially identified articles, 6 met the inclusion criteria. Data concerning hazard ratios (HR) and confidence intervals (CI) were extracted to compare the effects of ertugliflozin with those of a placebo or other standard therapies. The collective sample size across these studies was 8246 participants. Ertugliflozin was associated with a significant reduction in hospitalizations for heart failure relative to a placebo (HR 0.70, 95% CI 0.54-0.90, p < 0.05). Furthermore, when combined with metformin, ertugliflozin potentially reduced MACEs (HR 0.92, 95% CI 0.79-1.07), although this finding did not reach statistical significance. Importantly, for patients with pre-existing heart failure, ertugliflozin significantly decreased the exacerbations of heart failure (HR 0.53, 95% CI 0.33-0.84, p < 0.01). Overall, ertugliflozin markedly reduces hospitalizations due to heart failure in T2DM patients and may improve additional cardiovascular outcomes. These results endorse the integration of ertugliflozin into therapeutic protocols for T2DM patients at elevated cardiovascular risk and substantiate its efficacy among SGLT2 inhibitors. Continued investigations are recommended to delineate its long-term cardiovascular benefits in diverse patient populations, including the potential impact on arrhythmias.

Assessment of the Efficacy in Athletes and Non-Athletes of the Use of Creatine Monohydrate in Physical Exercise: A Systematic Review

Background: Considering the growing awareness of the population regarding the importance of engaging in physical activity, the utilization of supplements, such as creatine monohydrate, is also expanding in search of the attributed benefits of these substances. This study describes and analyzes the relationship between supplementation with creatine monohydrate and the improvement in the athletic performance of athletes from various disciplines and training levels, as well as non-athletes. Material and methods: A systematic review of clinical trials that address the use of creatine monohydrate in various sports contexts was conducted, followed by an analysis of the results based on body composition, jump capacity, and strength performance to determine points of correlation between the data presented in each publication. Results: A significant improvement in body composition, jump capacity, and strength performance was observed among participants who used supplementation, although in many cases, the results were heterogeneous. Conclusion: Creatine monohydrate supplementation positively influences body composition and physical performance, but further research is needed to understand its effects in specific populations.

Radiofrequency of suprascapular nerve as an analgesic strategy for chronic pain management. Systematic review and meta-analysis

IntroductionChronic shoulder pain is highly prevalent in the general population. Many different analgesic strategies have been described, including radiofrequency treatment to the suprascapular nerve (RFS); however, the effectiveness this approach remains unclear, and no strong recommendation can be made. The aim of this systematic review is to analyse the latest clinical trials evaluating the effectiveness of RFS techniques applied to the suprascapular nerve in terms of management of chronic shoulder pain, post-procedural functionality, and adverse effects. MethodsWe performed a systematic review of clinical trials retrieved from Medline, Embase and the CENTRAL databases. We included trials comparing RFS with other strategies, including placebo, that had as their primary outcome measures pain rated on a visual analogue scale, functionality rated on a shoulder pain and disability index (SPADI), and the incidence of adverse events. Risk of bias was analysed using the Cochrane RoB2 tool. Evidence was analysed using a random effects model and heterogeneity was quantified using the I2 test. ResultsWe identified 3030 trials, of which 8 met the inclusion criteria (n = 408). Seven had a high risk of bias. Pain intensity at 1 and 3 months was lower in patients receiving RFS, with a standardised mean difference (SMD) of −0.9 (95% CI [−1.1, 0.33], p = 0.29; I2 88%, p < 0.001) and −1.17 (95% CI [−2.49, 0.14], p = 0.08; I2 97%, p < 0.001), respectively. Functional compromise at 1 and 3 months decreased in patients receiving RFS, with an SMD of −0.31 (95% CI [−0.91, 0.29], p = 0.31; I2 80%, p < 0.001) and −1.54 (95% CI [−3.26, 0.19], p = 0.08; I2 98%, p < 0.001), respectively. No RFS-related adverse events were described. ConclusionThe evidence suggests that RFS reduces pain and improves functionality. However, the certainty of the evidence is low.

Effectiveness of mouth antiseptics in reducing the viral load of SARS-CoV-2 load in saliva? A systematic review of clinical trials

This systematic review assessed the effect of mouthwashes on reducing the SARS-CoV-2 viral load in the saliva of infected patients. Fifteen electronic databases were searched using the terms "Mouthwash", "Viral Load", and "COVID-19". Only clinical trials were considered, with no language or publication year restrictions. Bias risk was assessed using the Cochrane tool (Rob 2.0) for randomized clinical trials and non-randomized trials (ROBINS-I). The quality of evidence was evaluated using the GRADE system. After the search, 1,102 references were identified and assessed for eligibility criteria. Among these, 34 were selected, and after a thorough analysis, only six were included. The mouthwashes evaluated included 1% hydrogen peroxide, iodopovidone, cetylpyridinium chloride, and chlorhexidine. The results indicated that iodopovidone, chlorhexidine, and cetylpyridinium chloride performed better compared to other options. In conclusion, the use of mouthwashes appears to be effective in reducing the SARS-CoV-2 viral load in saliva.

Effect of Sunitinib in the Management of Lung Cancer: A Systematic Review of Clinical Trials

Introduction Lung cancer is the most common cancer in terms of both incidence and mortality. Although usually managed with surgery, novel immunotherapies are gradually becoming more popular. The effect of sunitinib with and without erlotinib in the management of lung cancer is reviewed. Methods Eligible search engines and databases were screened to identify studies published in English. Any randomized clinical trials studying the effect of sunitinib, either alone or in combination with erlotinib, were included. Results Thirteen studies with a total sample size of 1,062 cases were included. Males (59.5%) were more common than females (40.5%), and the average age of patients was 64 ± 5.03. Most of the patients (71.5%) had a positive smoking status, and non-small cell carcinoma was the most common lung cancer type (95.4%). Almost all of the adverse events, such as headache (100%), weight loss (100%), constipation (100%), leukocytopenia (96%), pain (92.3%), hypertension (90%), dyspnea (88.7%), cough (84.3%), fatigue (81.6%), fever/chills (77.3%), thrombocytopenia (75%), nausea (73.8%), neutropenia (72%), anorexia (71.4%), vomiting (65.1%), anemia (61.3%), and diarrhea (54.5%) were more common in the sunitinib-only group. The mean overall survival for patients receiving sunitinib alone was 213 days, whereas, for patients receiving sunitinib combined with erlotinib, it was 270 days. Conclusion Adverse events may be encountered more frequently in treatment with sunitinib alone compared to the combination of sunitinib and erlotinib. However, sunitinib alone may result in higher disease stability and lower disease progression. Nevertheless, combination therapy may yield a longer median overall survival.

Mesenchymal Stem Cell Injections for the Treatment of Osteoarthritis: A Systematic Review of Clinical Trials.

Osteoarthritis is a prevalent degenerative disease that affects many people worldwide. The use of mesenchymal stem cells (MSCs) in the setting of osteoarthritis has been explored by many clinical trials in the literature. Exploring these clinical trials is important for assessing the benefit of this modality in the setting of osteoarthritis. On November 9, 2022, a search was conducted on PubMed/MEDLINE databases to explore clinical trials involving MSC injections for osteoarthritis. Only articles that were clinical trials, explored the use of MSC injections in osteoarthritis, involved human subjects, and written in English language, were included. Relevant data was extracted from the included trials. A total of 43 trials were included (N=43). The knee was most the commonly explored joint (95.4%), and adipose tissue was the most commonly utilized MSC source (49%). All but one trial (97.7%) reported clinical improvement in the MSC group on follow up, and 33 trials (76.7%) reported better clinical outcomes in the MSC groups when compared to control groups. Twenty-three trials (53.5%) used imaging to evaluate outcomes following MSC injections, out of which twenty (46.5%) reported improvements in the affected joint. Similarly, four trials (9.3%) used second look arthroscopy, out of which three (7%) reported better outcomes on follow up. While published trials show good therapeutic potential for MSC injections in the setting of osteoarthritis, several discrepancies render the efficiency and reliability of this modality equivocal. The adoption of standardized protocols, employment of comprehensive evaluation tools, and reporting negative results is essential in order to appropriately assess the utility of MSC injections for the treatment of osteoarthritis.

Efficacy and safety of mosunetuzumab-based regimens as first-line therapy in non-Hodgkin lymphomas: A systematic review of clinical trials.

e19013 Background: Bispecific antibodies (BsAbs) are emerging as a promising new immunotherapy modality in patients with lymphoma. Mosunetuzumab is a CD20xCD3 T-cell engaging bispecific monoclonal antibody that redirects T cells to eliminate malignant B cells, was first to receive approval for relapsed or refractory follicular lymphoma. Here, we report the safety and efficacy of Mosunetuzumab as a first line therapy in combination or monotherapy regimen in non-hodgkin lymphoma. Methods: A literature search was performed on PubMed with keywords for “Mosunetuzumab” AND “lymphoma”. The search was performed from the inception of data till 1/1/2024. A total of 237 articles were screened and three non-randomized clinical trials (nRCTs, N=124) were included. PRISMA guidelines were followed while conducting this systematic review. Results: In 3 clinical trials, 54 patients were treated with mosunetuzumab monotherapy, 40 with mosunetuzumab + cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), and 30 with subcutaneous mosunetuzumab. 94 patients had diffuse large B-cell lymphoma (DLBCL), and 30 patients had follicular lymphoma. ORR, CR, and PR were reported in 56%, 43%, and 13% patients, respectively, treated with mosunetuzumab monotherapy in DLBCL. ORR, CR, and PR were reported in 87.5%, 85%, and 2.5% patients, respectively, treated with mosunetuzumab + CHOP in DLBCL. ORR, CR, and PR were reported in 96%, 83%, and 12.5% patients, respectively, treated with subcutaneous mosunetuzumab in follicular lymphoma. Neutropenia, thrombocytopenia, infections, and fatigue were common adverse effects given in the table. Conclusions: Mosunetuzumab with CHOP showed higher efficacy results and was well tolerated by most of the patients and can be an option to achieve high response rates in DLBCL. Subcutaneous mosunetuzumab was active in follicular lymphoma with manageable toxicity in follicular lymphoma. However, long-term results are needed to determine the durability of responses and long-term safety and survival rates with these regimens. [Table: see text]

Physical exercise intervention for gaming disorder: a systematic review of clinical trials

Gaming disorder (GD) is continuously rising in prevalence with no specific treatment modalities proven most effective yet. Physical exercise (PE) has been used as an additional modality in treating addiction. Our study explores the outcome of PE intervention in treating GD. A structured search of the literature was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement guideline, with a pre-determined search strategy starting from study identification, title and abstract screening, eligibility assessment, and inclusion of relevant study. PubMed, ProQuest, and EBSCO databases were searched in February 2024 with additional manual exploration, using “exercise” and “gaming disorder” as keywords. Three studies were included in the final systematic review, all of which are randomized controlled trials (RCTs). PE interventions were found to be effective in diminishing the score of gaming addiction scale. Improvement of gaming duration and mood were also reported. This study supports PE intervention as a favorable method of adjunctive treatment in GD, especially in reducing GD severity in adolescent and young adult.

Intradialytic parenteral nutrition in malnourished patients with chronic kidney disease: a systematic review

Introduction: Malnutrition is a prevalent condition among patients with chronic kidney disease (CKD). Objective: To answer the question of the effect of intradialytic parenteral nutrition (IPN) on malnourished CKD patients undergoing dialysis, a systematic review of clinical trials was performed. Methods: The systematic review was performed according with PRISMA. The review was carried out between September and October 2022. The search strategy included PubMed, Web of Science and LILACS databases. The selection of articles was carried out using the Rayyan platform and to assess the chance of bias, the Rob2 instrument recommended by Cochrane was employed. Results and Conclusions: From 762 article retrieved in the initial strategy only 4 articles were included in the review. In a general view, the use of IPN increased the levels of prealbumin and albumin in the participants. Studies evaluating this topic are sparse. More studies are needed to recommend the use of IPN universally in the context of malnourished patients with CKD.