Preparations, Applications, Patents, and Marketed Formulations of Nanoemulsions - A Comprehensive Review.

Nanoemulsions have emerged as versatile colloidal dispersions with promising applications in various fields, including pharmaceuticals, food, and cosmetics. These nano-sized emulsions, stabilized by surfactants, offer unique advantages such as enhanced ingredient penetration efficacy and versatile dosage forms. This article provides an extensive overview of nanoemulsions, covering their composition, methods of preparation, and applications in drug delivery, the food industry, and cosmetics. Various high-energy and low-energy methods for nanoemulsion preparation are discussed, along with their advantages and limitations. Additionally, the article highlights the potential of nanoemulsions in improving drug bioavailability, stability, and therapeutic efficacy, especially in oral, topical, parenteral, intranasal, ocular, and pulmonary drug delivery. Furthermore, nanoemulsions are explored as carriers for encapsulating flavoring agents, nutraceuticals, and natural preservatives in the food industry, as well as their use in cosmetic formulations. Current clinical trials involving nanoemulsions and recent patents in the field are also summarized, providing insights into ongoing research and development efforts. Lastly, a selection of marketed nanoemulsion formulations is presented, showcasing their practical applications and commercial availability. Overall, nanoemulsions hold great promise as effective delivery systems with broad applications across various industries.

Comparison of Ultrathin- Versus Thin-Strut Stents in Patients With High Bleeding Risk PCI: Results From the COMPARE 60/80 HBR Trial: An Open-Label, Randomized, Controlled Trial.

BACKGROUND: No randomized data exist on ultrathin-strut stents in patients at high bleeding risk (HBR) undergoing an abbreviated dual antiplatelet therapy after coronary stenting. The aim of this study was to compare the safety and effectiveness of the ultrathin-strut biodegradable-polymer sirolimus-eluting Supraflex Cruz stent with the thin-strut biodegradable-polymer sirolimus-eluting Ultimaster Tansei stent in patients at HBR with abbreviated dual antiplatelet therapy after stenting. METHODS: In the investigator-initiated, randomized, open-label COMPARE 60/80 HBR trial (Comparison of the Supraflex Cruz 60 Micron Stent Strut Versus the Ultimaster Tansei 80 Micron Stent Strut in HBR Percutaneous Coronary Intervention Population), 741 patients at HBR according to the Academic Research Consortium HBR criteria were randomized to receive either the ultrathin-strut biodegradable-polymer sirolimus-eluting Supraflex Cruz stent or thin-strut biodegradable-polymer sirolimus-eluting Ultimaster Tansei stent. Dual antiplatelet therapy was recommended according to the applicable guidelines and trial data for patients at HBR. The primary outcome was net adverse clinical events, the composite of cardiovascular death, myocardial infarction, target vessel revascularization, stroke, and major bleeding, and was powered for noninferiority with an absolute margin of 4.0% at 1-sided 2.5% alpha. RESULTS: Between September 2020 and August 2022, 371 patients were randomized to the ultrathin-strut biodegradable-polymer sirolimus-eluting Supraflex Cruz stent and 370 patients to the thin-strut biodegradable-polymer sirolimus-eluting Ultimaster Tansei stent at 11 sites in the Netherlands. At 1 year, the primary outcome was observed in 56 (15.4%) patients in the ultrathin-strut biodegradable-polymer sirolimus-eluting Supraflex Cruz stent group and 61 (17.1%) in the thin-strut biodegradable-polymer sirolimus-eluting Ultimaster Tansei stent group (risk difference, -1.65%; upper boundary of the 1-sided 95% CI, 3.74; P=0.02 for noninferiority at a 0.025 significance level and P=0.55 for 2-sided superiority at a 0.05 significance level). CONCLUSIONS: Among patients at HBR with abbreviated dual antiplatelet therapy post-stenting, the use of an ultrathin-strut biodegradable-polymer sirolimus-eluting Supraflex Cruz stent was noninferior compared with the use of a thin-strut biodegradable-polymer sirolimus-eluting Ultimaster Tansei stent. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04500912.

Treatment of the blood cancer polycythemia vera with ruxolitinib in the MAJIC-PV study: a plain language summary.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of an article describing the main results of the MAJIC-PV study. This study looked at using the cancer drug ruxolitinib to treat a type of blood cancer called polycythemia vera. People with polycythemia vera make too many red blood cells in their body. This can make their blood thicker and can increase the chances of blood clots forming in their blood vessels.Researchers wanted to find out how well ruxolitinib worked compared with the best available therapy as a treatment for people with polycythemia vera who were at risk of developing blood clots that could lead to a heart attack or stroke. Specifically, the study looked at people who had already taken the chemotherapy hydroxycarbamide (also known as hydroxyurea) for their polycythemia vera, but it either didn't work for them or gave them side effects that they could not tolerate. WHAT WERE THE RESULTS?: In the study, researchers divided 180 adults with polycythemia vera who were at high risk of developing blood clots that could lead to a stroke into two groups: 93 people who took ruxolitinib twice a day, and 87 people who took the best available therapy. 43% of people who took ruxolitinib and 26% of people who had the best available therapy had normal blood counts and spleen size within 1 year of treatment. 84% of people who took ruxolitinib and 75% of people who had the best available therapy lived for at least 3 years without their polycythemia vera becoming a more advanced type of blood cancer. The most common side effects were disorders of the digestive system (stomach and gut), disorders of the blood vessels, and infections. This is similar to the side effects that doctors know about for ruxolitinib. WHAT DO THE RESULTS MEAN?: Compared with people who had the best available therapy for their polycythemia vera, people who took ruxolitinib were more likely to have normal blood counts and spleen size within 1 year of treatment, and were more likely to live longer without their polycythemia vera becoming a more advanced type of blood cancer.

Estimating Socio-Economic Status for Alzheimer's Disease Trials.

INTRODUCTION: Metrics of a participant's socioeconomic status (SES) are not routinely collected or standardized in clinical trials. This omission limits the ability to evaluate the generalizability of trial results and restricts clinicians from confidently interpreting the efficacy of new treatments across important sub-populations. METHODS: We adapted an SES measure of social disparity; the Hollingshead Two Factor Index of Social Position, which combines education and occupation into a single metric. We modernized the 1965 occupations to reflect the 2017 careers tabulated by the US Bureau of Labor Statistics. We currently use this adapted measure in Alzheimer's Clinical Trials Consortium studies. RESULTS: We present the revised table of occupations. We found that the collection of SES data using the modified Hollingshead was feasible in a multi-site clinical trial and scores were distributed across all SES strata. DISCUSSION: The modified Hollingshead provides a standardized method for collecting SES information, enabling data aggregation, monitoring, and reporting.

Research protocol for bridging research, accurate information and dialogue (BRAID)-clinical trials: a mixed-methods study of a community-based intervention to improve trust and diversify participation in clinical trials.

Cultural beliefs, personal experiences, and historic abuses within the healthcare system-rooted in structural racism-all contribute to community distrust in science and medicine. This lack of trust, particularly within underserved communities, contributes to decreased participation in clinical trials and a lack of representation in the data. Open dialogue about community concerns and experiences related to research participation and medical care processes can help build trust and change attitudes and behaviors that affect community health. This protocol outlines an approach to increase trust in science and clinical trials among communities in the Bronx, New York that are typically underrepresented in research data. Bridging Research, Accurate Information and Dialogue (BRAID) is a two-phased, evidence-based community engagement model that creates safe spaces for bilateral dialogues between trusted community messengers, and clinicians and scientists. The team will conduct a series of BRAID Conversation Circles on the topic of clinical trials with local trusted community messengers. Participants will be members of the community who are perceived as "trusted messengers" and can represent the community's voice because they have insight into "what matters" locally. Conversation Circles will be audiotaped, transcribed, and analyzed to identify emergent challenges and opportunities surrounding clinical trial participation. These key themes will subsequently inform the codesign and co-creation of tailored messages and outreach efforts that community participants can disseminate downstream to their social networks. Surveys will be administered to all participants before and after each Conversation Circle to understand participants experience and evaluate changes in knowledge and attitudes about clinical trials, including protections for research participants the advantages of having diverse representation. Changes in motivation and readiness to share accurate clinical trial information downstream will also be assessed. Lastly, we will measure participants dissemination of codesigned science messages through their social networks by tracking participant specific resource URLs of materials and videos posted on a BRAID website. This protocol will assess the effectiveness and adoptability of an innovative CBPR model that can be applied to a wide range of public health issues and has the potential to navigate the ever-changing needs of the communities that surround health systems.

Efficacy and safety of chemoradiotherapy plus immune checkpoint inhibitors for the treatment of locally advanced cervical cancer: a systematic review and meta-analysis.

Background: Radiotherapy plus concurrent chemotherapy is a standard method for treating locally advanced cervical cancer (LACC). Immune checkpoint inhibitors (ICIs) are widely applied in the treatment of recurrent cervical cancer, metastatic cervical cancer or LACC. The efficacy and safety of radiotherapy plus immunotherapy for LACC require further investigation. The objective of this review and meta-analysis was to analyze the efficacy and safety of concurrent chemoradiotherapy (CCRT) combined with ICIs for treating LACC on the basis of the results of randomized controlled trials (RCTs). Methods: We comprehensively searched electronic databases to identify RCTs that focused on CCRT plus ICIs for LACC treatment. The outcomes included the objective response rate (ORR) and progression-free survival (PFS), overall survival (OS) and adverse events (AEs). A standard method for systematic review and meta-analysis was used. Review Manager 5.4 was used for data combination and analyses. Results: Three RCTs involving 1882 participants with LACC were identified and included in the systematic review and meta-analysis. CCRT plus ICIs improved the rates of PFS (hazard ratio [HR]: 0.76, 95% confidence interval [CI]: CI: 0.64, 0.91, P = 0.002) and OS (HR: 0.7695% CI (95% CI 0.58-0.99, P = 0.04) in patients with LACC. Compared with the control group, the CCRT plus immunotherapy group had an increased ORR (OR: 1.37, 95% CI: 1.02,1.85, P=0.04). The two methods had similar rates (HR=1.99, 95% CI: 0.99, 1.43; P=0.07) of treatment-related grade 3 or higher AEs. The CCRT plus immunotherapy group had a higher rate than did the control group (HR: 2.68, 95% CI: 1.38, 5.21; P=0.004) in terms of any grade immunotherapy-related AEs. Conclusions: CCRT plus ICIs is efficacious and safe for the management of LACC. The addition of ICIs to CCRT improved the rates of PFS and OS in patients with LACC. The adverse effects of immunotherapy-related AEs should be strictly examined and managed in a timely manner.

Medical Ozone as a Therapeutic Option in Musculoskeletal Pain Control: A Critical Review of Clinical Trials Considering Safety and Quality Indicators for Procedures and Devices.

Background: Drug therapies have been widely applied for pain management, however, there are important side effects such as those related to corticosteroids and opioids. Recent studies demonstrated promising results using medical ozone as a safe, effective, and low-cost intervention for pain control. Objective: to review and critically analyze clinical studies that used ozone therapy for musculoskeletal pain. Methods: a literature search of various databases was performed to identify relevant studies. From a total of 249 records, 27 studies were included. Quality indicators, human and device factors that strongly influence the generation of evidence were considered, such as study design and device safety. We also mitigated biases, considering the safety and efficacy of the intervention itself. Results: Regarding safety, 77 (8%) of studies reported no adverse effects; concerning efficacy outcomes, medical ozone shows to be an effective intervention on musculoskeletal pain control. Important information about used devices were missing. Conclusions: medical ozone shows to be safe and effective; qualification of health professionals as well as the device safety are mandatory. However, there is a lack of requirements to identify the best therapeutic scheme; further longer, clinical and rigorous trials are needed.

Design of a multicenter randomized controlled trial of a post-discharge suicide prevention intervention for high-risk psychiatric inpatients: The Veterans Coordinated Community Care Study.

BACKGROUND: The period after psychiatric hospital discharge is one of elevated risk for suicide-related behaviors (SRBs). Post-discharge clinical outreach, although potentially effective in preventing SRBs, would be more cost-effective if targeted at high-risk patients. To this end, a machine learning model was developed to predict post-discharge suicides among Veterans Health Administration (VHA) psychiatric inpatients and target a high-risk preventive intervention. METHODS: The Veterans Coordinated Community Care (3C) Study is a multicenter randomized controlled trial using this model to identify high-risk VHA psychiatric inpatients (n = 850) randomized with equal allocation to either the Coping Long Term with Active Suicide Program (CLASP) post-discharge clinical outreach intervention or treatment-as-usual (TAU). The primary outcome is SRBs over a 6-month follow-up. We will estimate average treatment effects adjusted for loss to follow-up and investigate the possibility of heterogeneity of treatment effects. RESULTS: Recruitment is underway and will end September 2024. Six-month follow-up will end and analysis will begin in Summer 2025. CONCLUSION: Results will provide information about the effectiveness of CLASP versus TAU in reducing post-discharge SRBs and provide guidance to VHA clinicians and policymakers about the implications of targeted use of CLASP among high-risk psychiatric inpatients in the months after hospital discharge. CLINICAL TRIALS REGISTRATION: ClinicalTrials.Gov identifier: NCT05272176 (https://www. CLINICALTRIALS: gov/ct2/show/NCT05272176).

The evolution of small-molecule Akt inhibitors from hit to clinical candidate.

Akt, a key regulator of cell survival, proliferation, and metabolism, has become a prominent target for treatment of cancer and inflammatory diseases. The journey of small-molecule Akt inhibitors from discovery to the clinic has faced numerous challenges, with a significant emphasis on optimization throughout the development process. Early discovery efforts identified various classes of inhibitors, including ATP-competitive and allosteric modulators. However, during preclinical and clinical development, several issues arose, including poor specificity, limited bioavailability, and toxicity. Optimization efforts have been central to overcoming these hurdles. Researchers focused on enhancing the selectivity of inhibitors to target Akt isoforms more precisely, reducing off-target effects, and improving pharmacokinetic properties to ensure better bioavailability and distribution. Structural modifications and the design of prodrugs have played a crucial role in refining the efficacy and safety profile of these inhibitors. Additionally, efforts have been made to optimize the therapeutic window, balancing effective dosing with minimal adverse effects. The review highlights how these optimization strategies have been key in advancing small-molecule Akt inhibitors toward clinical success and underscores the importance of continued refinement in their development.

Clinical trials involving rare gynaecological cancers.

Clinical trials that investigate therapies for rare gynaecological cancers (RGC) are essential to provide evidence-based data towards new effective and safe treatments, however, they present unique challenges. The main objective of this narrative review is to summarize completed phase III clinical trials investigating therapies for RGC and to discuss the outcomes of these trials. PRISMA guidelines were used to report the steps of the review. We searched the WHO's International Clinical Trials Registry Platform, clinicaltrials.gov and PubMed/Medline for publications reporting results from clinical trials on RGC including at least one medication. From 31 identified phase III clinical trials, 13 were still ongoing, four were terminated and just eight (25.8 %) had posted results and/or publications. The latter completed trials were mostly multi-center and located in at least two continents, participants were mainly adults, and the recruitment period varied from about 2.5 to 10.5 years. Allocation was randomized with parallel assignment in 7 out of 8 trials, while only one trial had double masking. The most common primary outcome measure was progression-free survival (PFS), followed by overall survival (OS). Patient-reported outcomes were secondary outcome measures in four completed trials, assessing quality of life by various questionnaires. Most of the trials did not meet their primary endpoints. By highlighting the scarcity of clinical trials on RGC, our findings further emphasize the need for designing, conducting and sustaining phase III clinical trials to investigate innovative therapies for these conditions and report meaningful outcome measures.

Clinical research vehicles as a modality for medical research education and conduct of decentralized trials, supporting justice, equity, and diversity in research.

Current clinical research lacks diversity in those that participate. This lack of diversity is concerning given its importance for successful drug development. The frequency and severity of many diseases, along with the pharmacological properties of therapies, can display significant differences based on patient diversity. A clinical trial population that is more reflective of these differences will help researchers better understand the therapeutic profile of the treatment and provide generalizable knowledge to the medical community. The advent of decentralized clinical trial designs is meant to help address this lack of diversity by using portable digital health technologies and virtual interactions to enhance clinical trial access and broaden participation. By leveraging these technologies, trial conduct can occur at locations other than traditional research sites. This shift in trial location may help address some of the logistical, educational, engagement, and trust barriers that have historically prevented enrollment of diverse populations. However, these types of trials still have limitations. Ethical concerns around justice, equity, and diversity will still exist with decentralized clinical trials, which could be mediated using clinical research vehicles. When utilized, this modality may enhance the scientific design and conduct of clinical trials and better follow these ethical principles. These enhancements and improved ethical direction could be accomplished through increasing community involvement, improving health literacy, supporting more diverse trial sites, creating community-based research footholds, fostering connections with researchers, limiting technical challenges, and preventing data security issues.

Role of EYP-1901 in neovascular age-related macular degeneration and diabetic eye diseases: review of Phase I/II trials.

EYP-1901 (Duravyu) has demonstrated promising outcomes in Phases I and II clinical trials for the treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME)/diabetic retinopathy. This innovative treatment capitalizes on the potent anti-angiogenic properties of vorolanib, an inhibitor that targets all isoforms of VEGF, effectively mitigating the pathological neovascularization and vascular permeability that underpin these retinal conditions. EYP-1901 is integrated with the Durasert drug delivery system to administer a sustained release of vorolanib directly to the posterior segment of the eye. This delivery system ensures a consistent therapeutic effect over an extended period and significantly reduces the frequency of clinical interventions required, offering a more convenient treatment regimen while maintaining patient safety.

Neovascular age-related macular degeneration (nAMD) and diabetic retinopathy (DR) are eye problems that can make you lose your sight. These eye problems happen when blood vessels in the eye do not work right. Right now, people need lots of shots in their eyes to treat it. EYP-1901 (Duravyu) is a new medicine that helps people with fewer shots in their eyes. It has two parts: one that helps the medicine last longer, and another that helps stop the problem in the eye. Early tests show it works well and helps people keep their sight with fewer treatments.

Past Trends and Future Directions of Cardiac Regenerative Medicine - A Systematic Analysis of Clinical Trial Registries.

Cell therapy, gene therapy, and tissue engineering have been explored as potential strategies to repair or regenerate damaged cardiac tissue. Despite the presence of encouraging preclinical data, clinical trials of regenerative cardiac therapies have yielded mixed results. Our study aimed to investigate the fate of all registered clinical trials within regenerative cardiac medicine, with the purpose of exploring the potential role of publication bias (or trial-completion bias), how published and unpublished research affects the field, and to draw lessons and recommendations for future clinical trials. In this analysis, we show that only a third of all registered trials has yielded results and that a significant number of trials are not completed. Furthermore, we identified significant heterogeneity in study design, study phase, funding, specific therapies used, primary outcome measures and methods of outcome assessment. These observations might hinder the successful translation of cardiac regenerative therapies into clinical practice.

Incidence of aortic valve reintervention in patients with aortic stenosis undergoing transcatheter aortic valve implantation versus surgical aortic valve replacement: a systematic review and updated meta-analysis of randomized studies.

INTRODUCTION: Transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) are established interventions for alleviating symptoms and enhancing survival in individuals with severe aortic stenosis (AS). However, the long-term outcomes and incidence of reintervention associated with TAVI and SAVR remain uncertain. METHODS: We conducted a systematic review and meta-analysis to compare the incidence of reintervention in TAVI versus SAVR. PubMed, Embase, and Cochrane databases were searched for randomized controlled trials (RCTs). Risk ratios (RR) and 95% confidence intervals (CI) were pooled with a random-effects model. A p-value < 0.05 was considered statistically significant. RESULTS: Nine RCTs were included, with 5144 (50.9%) patients randomized to TAVI. Compared with SAVR, TAVI increased reinterventions (RR 1.89; 95% CI 1.29-2.76; p < 0.01) and the need for pacemakers (RR 1.91; 95% CI 1.49-2.45; p < 0.01). In addition, TAVI significantly reduced the incidence of new-onset atrial fibrillation (RR 0.43; 95% CI 0.32- 0.59; p < 0.01). There were no significant differences in all-cause mortality (RR 1.04; 95% CI 0.92-1.16; p = 0.55), cardiovascular mortality (RR 1.04; 95% CI 0.94-1.17; p = 0.44), stroke (RR 0.97; 95% CI 0.80-1.17; p = 0.76), endocarditis (RR 0.96; 95% CI 0.70-1.33; p = 0.82), and myocardial infarction (RR 1.06; 95% CI 0.79-1.41; p = 0.72) between groups. CONCLUSIONS: In patients with severe AS, TAVI significantly increased the incidence of reinterventions and the need for pacemakers as compared with SAVR.

Effect of non-pharmacological interventions in people with cognitive frailty: a systematic review and network meta-analysis.

ABSRTACT: OBJECTIVE: To evaluate the effects of various non-pharmacological interventions on patients with cognitive impairment by systematic search and network meta-analysis, and to rank the effects of the included non-pharmacological interventions. METHODS: The databases of PubMed, Cochrane Library, EMbase, Web of Science, CNKI, VIP, WANFANG, and SinoMed were searched by computer. All randomized controlled trials (RCTs) of non-pharmacological interventions for people with cognitive frailty were collected. The search was conducted from 2000 to February 2024. Two reviewers independently screened the studies, extracted data, and assessed the risk of bias of the included studies, and then used Stata15 and R4.3.1 software to conduct network meta-analysis, with physical function and cognitive function as the main outcome indicators. RESULTS: A total of 19 randomized controlled trials involving 1738 patients were included. The results of network meta-analysis showed that among the non-pharmacological interventions, nutritional support had the best effect on improving frailty scores and cognitive function scores in patients with cognitive frailty. Aerobic training combined with resistance training is best for improving grip strength. For improving the patient's motor status, cognitive training had the best effect on improving TUG test scores. High-speed resistance training is best for improving walking speed. CONCLUSION: This review analyses the current study of non-pharmacological interventions to improve physical performance in patients with cognitive frailty. Current evidence suggests that nutritional support is most effective at improving physical frailty and cognitive decline in patients with cognitive frailty, and that exercise and cognitive training interventions significantly improve grip strength and motor ability. TRIAL REGISTRATION: This meta-analysis was prospectively registered with PROSPERO (registration number: CRD42023486881).

Traditional Chinese medicine for the treatment of cancers of hepatobiliary system: from clinical evidence to drug discovery.

Hepatic, biliary, and pancreatic cancer pose significant challenges in the field of digestive system diseases due to their highly malignant nature. Traditional Chinese medicine (TCM) has gained attention as a potential therapeutic approach with long-standing use in China and well-recognized clinical benefits. In this review, we systematically summarized the clinical applications of TCM that have shown promising results in clinical trials in treating hepatic, biliary, and pancreatic cancer. We highlighted several commonly used TCM therapeutics with validated efficacy through rigorous clinical trials, including Huaier Granule, Huachansu, and Icaritin. The active compounds and their potential targets have been thoroughly elucidated to offer valuable insights into the potential of TCM for anti-cancer drug discovery. We emphasized the importance of further research to bridge the gap between TCM and modern oncology, facilitating the development of evidence-based TCM treatment for these challenging malignancies.

Efficacy of vitamin D supplementation in the treatment of patients with COVID-19: a systematic review and meta-analysis of randomized controlled trials.

Context: COVID-19 has substantial effects on respiratory health and overall well-being. Recent studies suggest vitamin D as a potential treatment, but the results are inconclusive. Objective: The authors conducted a systematic review of randomized controlled trials (RCTs) to examine the link between vitamin D and patients with COVID-19. Data sources: The authors searched electronic databases PubMed, Cochrane, CINAHL, EMBASE and Google Scholar from their inception till August 2023. Study selection: Inclusion criteria used in our systematic review include: (1) patients who tested positive for COVID-19, (2) intervention was vitamin D supplementation, (3) the comparator was either a placebo, standard care of treatment, or, no treatment, (4) at least one of the clinical outcomes of interest were investigated, (5) study design being RCTs. Data extraction: Two independent reviewers manually extracted information from selected articles, including study characteristics, patient characteristics, and the primary outcomes: all-cause mortality, ICU and hospital stay length and secondary outcomes: mechanical ventilation, supplemental oxygen, ICU admission, and adverse events. Risk ratios or mean differences and 95% CIs were calculated using a random-effects model. Data synthesis: The authors' analysis included 14 RCTs with 2165 patients. Vitamin D significantly reduced ICU admissions and lowered the need for mechanical ventilation compared to placebo. However, it did not significantly affect hospital stay length, ICU stay length, mechanical ventilation duration, mortality, or the need for supplemental oxygen. Conclusion: Vitamin D does not significantly improve certain clinical outcomes, such as hospital and ICU stay length, for patients with COVID-19. However, it still may be significantly beneficial in decreasing the burden on intensive care services.

Exploring the clinical effectiveness of glucagon-like peptide-1 receptor agonists in managing cardiovascular complications: an updated comprehensive review and future directives.

The possible cardiovascular advantages of glucagon-like peptide-1 receptor agonists (GLP-1RAs), a class of drugs predominantly used to treat type 2 diabetes (T2D), have garnered increasing attention in recent years. Clinical trials have looked into the possibility that GLP-1RAs have extra cardioprotective benefits in addition to their ability to manage T2D, demonstrating significant major adverse cardiovascular events (MACE) reduction and a favorable safety profile. GLP-1 RAs improve cardiovascular outcomes, especially in those with existing cardiovascular disease. MACE has been steadily declining with this class of drugs, which results in a noticeable rise in cardiovascular outcome trials (CVOTs). GLP-1 RAs have a variety of impacts on the cardiovascular system beyond their function in glycemic control. They offer direct cardioprotection, vasodilation, promotion of salt excretion, reduction of weight, improved lipid profile, and anti-inflammatory qualities through a variety of mechanisms. Thus, this review focuses on GLP-1RAs, its mechanism of action, its clinical effectiveness in CVOTs, the mechanism behind its cardiovascular benefits, its potential role in heart failure, cardiovascular outcomes, its underutilization, and future directives. In conclusion, GLP-1 RAs shows potential in controlling T2D while also lowering cardiovascular risk, but warrants further study into long-term results and real-world data to optimize treatment regimens, ultimately increasing patient outcomes and lowering the burden of cardiovascular disease in T2D populations.

eConsent administered by Community Health Workers in a study using the Trials within Cohorts (TwiCs) design-Experiences from the Community-Based chronic Care Lesotho (ComBaCaL) project.

Improving access to essential health services requires the development of innovative health service delivery models and their scientific assessment in often large-scale pragmatic trials. In many low- and middle-income countries, lay Community Health Workers (CHWs) play an important role in delivering essential health services. As trusted members of their communities with basic medical training, they may also contribute to health data collection. Digital clinical decision support applications may facilitate the involvement of CHWs in service delivery and data collection. Electronic consent (eConsent) can streamline the consent process that is required if the collected data is used for the scientific purposes. Here, we describe the experiences of using eConsent in the Community-Based chronic Care Lesotho (ComBaCaL) cohort study and multiple nested pragmatic cluster-randomized trials assessing CHW-led care delivery models for type 2 diabetes and arterial hypertension using the Trials within Cohorts (TwiCs) design. More than a hundred CHWs, acting both as service providers and data collectors in remote villages of Lesotho utilize an eConsent application that is linked to a tailored clinical decision support and data collection application. The eConsent application presents simplified consent information and generates personalized consent forms that are signed electronically on a tablet and then uploaded to the database of the clinical decision support application. This significantly streamlines the consent process and allows for quality consent documentation through timely central monitoring, facilitating the CHW-led management of a large-scale population-based cohort in a remote low-resource area with continuous enrollment-currently at more than 16,000 participants.