Thousands Of Clinical Trials Research Articles

Acceptance and Commitment Therapy as a Conceptual Treatment Model for Obsessive-Compulsive Personality Disorder

Acceptance and commitment therapy (ACT) has demonstrated efficacy in thousands of clinical trials for eating disorders, depression, anxiety, personality disorders, and more. However, ACT has not established efficacy as a treatment for obsessive compulsive personality disorder (OCPD) in a clinical trial. The prevalence of OCPD is one of the highest among personality disorders, yet there is a dearth of research regarding empirically supported treatments and the disorder in general. Aspects of OCPD, including perfectionism, mood intolerance, experiential avoidance, and impaired psychosocial functioning, make it particularly suitable for research involving ACT, which aims to increase psychological flexibility. The purpose of this paper is to elucidate a conceptual model for the treatment of OCPD using ACT. Specific strategies and techniques will be discussed. Future research avenues include exploring ACT as a viable treatment for OCPD, as well as the constructs of experiential avoidance and psychological flexibility related to OCPD functioning.

Advances in Genetic Reprogramming: Prospects from Developmental Biology to Regenerative Medicine.

The foundations of cell reprogramming were laid by Yamanaka and co-workers, who showed that somatic cells can be reprogrammed into pluripotent cells (induced pluripotency). Since this discovery, the field of regenerative medicine has seen advancements. For example, because they can differentiate into multiple cell types, pluripotent stem cells are considered vital components in regenerative medicine aimed at the functional restoration of damaged tissue. Despite years of research, both replacement and restoration of failed organs/ tissues have remained elusive scientific feats. However, with the inception of cell engineering and nuclear reprogramming, useful solutions have been identified to counter the need for compatible and sustainable organs. By combining the science underlying genetic engineering and nuclear reprogramming with regenerative medicine, scientists have engineered cells to make gene and stem cell therapies applicable and effective. These approaches have enabled the targeting of various pathways to reprogramme cells, i.e., make them behave in beneficial ways in a patient-specific manner. Technological advancements have clearly supported the concept and realization of regenerative medicine. Genetic engineering is used for tissue engineering and nuclear reprogramming and has led to advances in regenerative medicine. Targeted therapies and replacement of traumatized , damaged, or aged organs can be realized through genetic engineering. Furthermore, the success of these therapies has been validated through thousands of clinical trials. Scientists are currently evaluating induced tissue-specific stem cells (iTSCs), which may lead to tumour-free applications of pluripotency induction. In this review, we present state-of-the-art genetic engineering that has been used in regenerative medicine. We also focus on ways that genetic engineering and nuclear reprogramming have transformed regenerative medicine and have become unique therapeutic niches.

Comparison of treatment of COVID-19 with inhaled bromhexine, higher doses of colchicine and hymecromone with WHO-recommended paxlovid, molnupiravir, remdesivir, anti-IL-6 receptor antibodies and baricitinib

Millions of publications and thousands of clinical trials have not led to the discovery of an effective treatment for COVID-19. We believe that the reason for this is the inaccurate strategy of inhibiting target molecules involved in the pathogenesis of the disease. The leading cause of death in COVID-19 is the cytokine storm, which is caused by an NLRP3 inflammasome hyperreaction. WHO recommends for the outpatients treatment drugs blocking the replication of SARS-CoV-2. However, viral load and replication are not directly related to NLRP3 inflammasome hyperreactivity. This also explains the partial success of the WHO favorite paxlovid to reduce hospitalizations (51%). For hospital treatment, WHO suggests antibodies against the interleukin-6 receptor and Janus kinase (JAK) inhibition. Although important, IL-6 is one of dozens of cytokines elevated as a consequence of cytokine storm. The JAK inhibitor baricitinib inhibited the effect of not only IL-6 but also other elevated cytokines. But if the NLRP3 inflammasome is inhibited, the cytokines will not be elevated, and there will be no need for baricitinib. All medicines recommended by the WHO are distinguished by their very high prices. Our therapeutic strategy is based on inhibition of SARS-CoV-2 entry into the cell and inhibition of the NLRP3 inflammasome. We offer two readily available, cheap and well-known medications - bromhexine hydrochloride and colchicine. The many studies on the treatment of COVID-19 so far have not produced the expected result. The devil is buried in the details. For bromhexine, the reason is the way and its late application. Bromhexine is most effective when given prophylactically or started by inhalation after contact with a person with COVID-19. Its earliest possible application is crucial for its effect. Increased doses of colchicine are necessary for COVID-19 treatment due to the fact that it accumulates in leukocytes, and this leads to inhibition of NLRP3. The high doses we administer have been given widely in the past and are completely safe. Our highest dose is about 5 times lower per kg of weight than the lowest severe toxic dose of colchicine described. Our results show about a 5-fold decrease in hospital mortality and almost complete prevention of hospitalizations if outpatients are treated with inhaled bromhexine and colchicine.

An Adaptive Information Borrowing Platform Design for Testing Drug Candidates of COVID-19.

Background There have been thousands of clinical trials for COVID-19 to target effective treatments. However, quite a few of them are traditional randomized controlled trials with low efficiency. Considering the three particularities of pandemic disease: timeliness, repurposing, and case spike, new trial designs need to be developed to accelerate drug discovery. Methods We propose an adaptive information borrowing platform design that can sequentially test drug candidates under a unified framework with early efficacy/futility stopping. Power prior is used to borrow information from previous stages and the time trend calibration method deals with the baseline effectiveness drift. Two drug development strategies are applied: the comprehensive screening strategy and the optimal screening strategy. At the same time, we adopt adaptive randomization to set a higher allocation ratio to the experimental arms for ethical considerations, which can help more patients to receive the latest treatments and shorten the trial duration. Results Simulation shows that in general, our method has great operating characteristics with type I error controlled and power increased, which can select effective/optimal drugs with a high probability. The early stopping rules can be successfully triggered to stop the trial when drugs are either truly effective or not optimal, and the time trend calibration performs consistently well with regard to different baseline drifts. Compared with the nonborrowing method, borrowing information in the design substantially improves the probability of screening promising drugs and saves the sample size. Sensitivity analysis shows that our design is robust to different design parameters. Conclusions Our proposed design achieves the goal of gaining efficiency, saving sample size, meeting ethical requirements, and speeding up the trial process and is suitable and well performed for COVID-19 clinical trials to screen promising treatments or target optimal therapies.

Alloreactivity of Allogeneic Mesenchymal Stem/Stromal Cells and Other Cellular Therapies: A Concise Review.

Cellular therapies, deemed live medicine, have brought a wave of new generation biological therapies to treat previously untreatable diseases such as cancers and degenerative diseases like osteoarthritis. These cellular therapies have gained significant recognition in clinical research. The area has been further strengthened with the approval of Chimeric Antigen Receptor added on T cells (CAR-T) therapies by the regulatory authorities USA's Food and Drugs Administration (FDA), European Medical Agency (EMA), the Australian Therapeutic Goods Administration (TGA), and in many countries in 2017 to treat hematological cancers. Another milestone was achieved when allogeneic Mesenchymal Stem Cell- (MSC-) based therapy was approved by the EMA to treat Chrohn's disease in 2018. Allogeneic donor-derived MSC therapies in particular hold great promise and real hope because of their ‘off-the shelf' availability and accessibility for patients in need of urgent treatment. So far, thousands of clinical trials have explored the safety and efficacy of both autologous and allogeneic cell therapies, deeming them safe, however with varying degrees of efficacy. In the current pandemic, clinical trials have begun in many parts of the world to treat severe cases of COVID with MSCs. However, the risk of tissue rejection and the development of undesirable effects due to alloreactivity of allogeneic cells are currently not adequately addressed. Therefore, this warrants careful investigation and detailed reporting of such events by clinical researchers. This review aims at discussing the current landscape of approved allogeneic MSCs along with a few other cellular therapies. We explore any possible reactivity reported to inform the readers of any safety concern and on the efficacy of such therapies.

Research of Natural Health Products is Lacking – Right?

In May 1994, while working in marketing for BASF Pharmaceuticals in Germany, I was prescribed a product called Sinupret® for chronic sinusitis by my family physician. The product was behind the counter in the local pharmacy and was reimbursed by my health insurance. After some months, my sinusitis was gone and I was intrigued about the product, its regulation and most particularly the research behind it. In reading the Sinupret® packet I discovered to my surprise that it was a herbal medicine. Convinced, with my pharma background, that there would be little evidence for such a product I asked our medical information department to conduct a literature review of all clinical trials for herbal medicines in all languages. A week later I received 4 thick lever arch files of abstracts of tens of thousands of clinical trials on hundreds of products. This delivery changed my life!

Mesenchymal stromal cells: what have we learned so far about their therapeutic potential and mechanisms of action?

Mesenchymal stromal cells (MSCs) have been found to be safe and effective in a wide range of animal models of human disease. MSCs have been tested in thousands of clinical trials, but results show that while these cells appear to be safe, they tend to lack efficacy. This has raised questions about whether animal models are useful for predicting efficacy in patients. However, a problem with animal studies is that there is a lack of standardisation in the models and MSC therapy regimes used; there appears to be publication bias towards studies reporting positive outcomes; and the reproducibility of results from animal experiments tends not to be confirmed prior to clinical translation. A further problem is that while some progress has been made towards investigating the mechanisms of action (MoA) of MSCs, we still fail to understand how they work. To make progress, it is important to ensure that prior to clinical translation, the beneficial effects of MSCs in animal studies are real and can be repeated by independent research groups. We also need to understand the MoA of MSCs to assess whether their effects are likely to be beneficial across different species. In this review, we give an overview of the current clinical picture of MSC therapies and discuss what we have learned from animal studies. We also give a comprehensive update of what we know about the MoA of MSCs, particularly in relation to their role in immunomodulation.

How the COVID-19 pandemic is changing clinical trial conduct and driving innovation in bioanalysis.

Thousands of clinical trials all over the world were stopped, disrupted or delayed while countries grappled to contain the pandemic and research resources were redeployed. The long-term effects of the turbulence caused by the pandemic have yet to be fully understood, but it should already be clear that the increased focus on participant needs and on the logistical challenges of current models are not likely to fade away quickly. This disruption is opening doors for rethinking traditional approaches to clinical trial conduct – including decentralizing site visits, introducing new methods of sample collection, rethinking matrix selection, reducing sample volumes and collaborating on device development. These approaches reduce participant burden while improving critical trial data.

The Multifaceted Role of Th1, Th9, and Th17 Cells in Immune Checkpoint Inhibition Therapy.

During the last decade, immune checkpoint inhibition (ICI) has become a pillar of cancer therapy. Antibodies targeting CTLA-4 or PD-1/PD-L1 have been approved in several malignancies, with thousands of clinical trials currently underway. While the majority of cancer immunotherapies have traditionally focused on enhancing cytotoxic responses by CD8+ or NK cells, there are clear evidences that CD4+ T cell responses can modulate the immune response against tumors and influence the efficacy of ICI therapy. CD4+ T cells can differentiate into several subsets of helper T cells (Th) or regulatory T cells (Treg), with a wide range of effector and/or regulatory functions. Importantly, different Th subsets may have different and sometimes contrasting roles in the clinical response to ICI therapy, which in addition may vary depending on the organ and tumor niche. In this review, we discuss recent evidence that highlights how ICI therapy impacts Th1, Th9, and Th17 cells and vice versa. These data might be important designing better interventions that unleash the full potential of immune response against cancer.

Technologies and Applications Toward Preservation of Cells in a Dry State for Therapies.

Cell-based therapeutics promise to transform the treatment of a wide range of diseases, many of which, up to this point, are incurable. During the past decade, an increasing number of cell therapies have been approved by government regulatory agencies in the United States, Europe, and Japan. Thousands of clinical trials based on live cell therapies are now taking place around the world. But most of these live cell therapies face temporal and/or spatial distances between manufacture and administration, posing a risk of degradation in potency. Cryopreservation has become the predominant biobanking approach to maintain the product's safety and efficacy during transportation and storage. However, the necessity of cryogenic shipment and storage could limit patient access to these emerging therapies and increase the costs of logistics. In the (bio)pharmaceutical industries, freeze-drying and desiccation are established preservation procedures for manufacturing small molecule drugs, liposomes, and monoclonal antibodies. Over the past two decades, there has been a growing body of research exploring the freeze-drying or drying of mammalian cells, with varying degrees of success. This article provides an overview of the technologies that were adopted or developed in these pioneering studies, paving the road toward the preservation of cell-based therapeutics in a dry state for biomanufacturing.

Clinical trials in urological oncology: COVID-19 and the potential need for a new perspective.

The COVID-19 pandemic has led to the suspension, termination or alteration of thousands of clinical trials as the health emergency escalated globally. Whilst the rapid suspension of certain clinical trials was necessary to ensure the safety of high-risk or vulnerable trial participants as well as healthcare workers, the long-term ramifications that this delay will have on the field of urologic oncology is unknown. The COVID-19 pandemic has highlighted the need to plan for and implement new strategies to advance our understanding of unmet areas of need in urologic oncology. The COVID-19 pandemic has led to the suspension, termination or alteration of thousands of clinical trials as the health emergency escalated globally. Whilst the rapid suspension of certain clinical trials was necessary to ensure the safety of high-risk or vulnerable trial participants as well as healthcare workers, the long-term ramifications that this delay will have on the field of urologic oncology is unknown. The COVID-19 pandemic has highlighted the need to plan for and implement new strategies to advance our understanding of unmet areas of need in urologic oncology.

Curative gene therapies for rare diseases

Diseases caused by alterations in the DNA can be overcome by providing the cells or tissues with a functional copy of the mutated gene. The most common form of gene therapy implies adding an extra genetic unit into the cell. However, new genome engineering techniques also allow the modification or correction of the existing allele, providing new possibilities, especially for dominant diseases. Gene therapies have been tested for 30 years in thousands of clinical trials, but presently, we have only three authorised gene therapy products for the treatment of inherited diseases in European Union. Here, we describe the gene therapy alternatives already on the market in the European Union and expand the scope to some clinical trials. Additionally, we discuss the ethical and regulatory issues raised by the development of these new kinds of therapies.

Severe Acute Respiratory Syndrome Coronavirus 2 and Coronavirus Disease 2019: A Clinical Overview and Primer.

Following its emergence in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused what rapidly became a global pandemic. The precise origin and subsequent path of transmission have not yet been established-but like the other novel coronaviruses that it closely resembles, it appears to have evolved naturally in a bat host. The disease caused by SARS-CoV-2 infection, designated as coronavirus disease 2019 (COVID-19), ranges from asymptomatic, to mild self-limited illness, to progressive pneumonia, respiratory compromise, multiorgan failure, and death. In addition, a hyperinflammatory disease state occurs in a subset of patients, and may be seen either during acute infection or following recovery. The search for effective pharmacological management of COVID-19 continues, but several promising candidates have been identified, including the viral nucleoside analog remdesivir. However, despite the existence of literally thousands of clinical trials, the management of COVID-19 remains challenging, and the development of an optimal, evidence-based therapeutic approach is ongoing. The impact of SARS-CoV-2 and COVID-19 on the biobanking world is evolving and profound-in particular, it is likely that many of mysteries surrounding COVID-19 will be solved via the availability of high-quality, large-scale collection, storage, and analysis of patient specimens. The purpose of this review article is therefore to provide a rapid, comprehensive, and relevant overview and primer on SARS-CoV-2 and COVID-19, with attention to the epidemiology, virology, transmission, clinical features, and major therapeutic options currently existent.

A truly 'HANDI' resource.

GPs and patients have an increasing interest in the use of non-drug interventions to treat common conditions seen in primary care. Nearly half the thousands of clinical trials conducted each year are for evaluating non-drug treatments, such as diet, exercise, procedures, and devices. Advances in such treatments in the past few decades have been substantial and diverse — for example, exercise for heart failure and COPD, the Epley manoeuvre for benign paroxysmal positional vertigo, and CBT for depression. However, effective non-drug methods are less well known, less promoted, and less used than their pharmaceutical cousins. There are well-established drugs/medications formularies such as the British National Formulary . However, no such formulary or resource for non-drug treatments (interventions) currently exists in the UK. The Handbook of Non-Drug Interventions — HANDI — project was launched by the Royal Australian College of General Practitioners (RACGP) in 2013 to promote effective non-drug treatments. HANDI is an online formulary of …

The Looming Success in Cancer Vaccination

<p align="justify">Cancer vaccination projects are on trial worldwide and the results are far-off being a remarkable success. Albeit, thousands of clinical trials are taking place, only a several of those are producing a significant result to increase the survival rate of the patients. Four vaccines (Human papillomavirus - HPV vaccines, Hepatitis B virus - HBV vaccines, Sipuleucel-T and Oncophage) are approved for market in the United States and Russia so far. Most of the prototype vaccines are yielding at phase III clinical trials after being successful at phase I and II. Apparently, new visions and approaches are required to guide these projects to harvest better results.<strong></strong></p>

Online portal of thousands of clinical trials could aid disease research

Online portal of thousands of clinical trials could aid disease research

From a Patient Advocate's Perspective: Does Cancer Immunotherapy Represent a Paradigm Shift?

In 2016, the American Society of Clinical Oncology (ASCO) announced immunotherapy as the year's top cancer advance in its "Clinical Cancer Advances 2016: ASCO's Annual Report on Progress Against Cancer." Further, ASCO again named "Immunotherapy 2.0" as the 2017 advance of the year, emphasizing the recent, rapid pace of research into new agents that harness and enhance the innate abilities of the immune system to recognize and fight cancers-and stressing that such agents have extended the lives of many patients with late-stage cancers for which there have been few treatment options. This article discusses the history of cancer immunotherapy and the recent promising advances, yet also presents a note of caution on limitations of immunotherapies, their potential harms, and the critical need for oncologists to appropriately engage with and educate patients to effectively manage their expectations. Learning how to effectively harness the immune system to treat cancer represents an investigative journey of more than 100years. However, after many failures and disappointments, this decade has seen several important successes. In 2011, the Food and Drug Administration (FDA) approved the first immunotherapy agent known as a "checkpoint inhibitor." Beginning in 2014, several additional checkpoint blockage drugs have been FDA-approved, and new indications and drug combinations have emerged. Further, on August 30, 2017, the FDA announced its first approval of a new form of immunotherapy known as CAR T cell therapy. Since the 2011 approval of the first checkpoint inhibitor, cancer immunotherapy research among the pharmaceutical industry and research institutions has exploded, with thousands of clinical trials currently taking place. The current "cancer immunotherapy revolution" is in the headlines daily and is also the primary topic of conversation among major cancer research conferences and symposia attendees. However, a once quiet voice has begun to emerge, where an increasing number of scientists, clinicians, and patient advocates are stressing the need for caution concerning the limitations and potential harms associated with cancer immunotherapy. Many oncologists, scientists, medical professional associations, and advocates agree that no recent cancer advance has been as successful, transformative, and potentially paradigm-shifting as immunotherapy. With this decade, we have seen the approval of several immunotherapy agents that have successfully treated a percentage of patients with notoriously resistant cancers, an increasing number of combination immunotherapy treatments, and new indications for approved agents. However, patients need to be aware that much of the popular media has breathlessly inflated positive outcomes of cancer immunotherapies, while neglecting to stress that just a small percentage of patients actually benefit from such treatments. Further, they often completely overlook the unique, potentially life-threatening harms that may be associated with these agents and fail to cover negative findings where immunotherapies have appeared to paradoxically accelerate cancer growth. Fortunately, the majority of journal articles presenting trial results and comprehensive review articles appropriately discuss the important limitations associated with immunotherapies, the unique spectrum of adverse effects, and the need for further research to improve our ability to identify those patients who are most likely to benefit from specific agents, sparing other patients from exposure to agents that will not be effective, yet may carry potentially life-threatening toxicities.

Immunotherapy of cancer.

Background For 50 years, cancer physicians have relied on just three primary treatment modalities: surgery, radiation therapy and chemotherapy. Over that time, enormous progress has been made in understanding cancer biology, targeted anti-cancer drugs have emerged, and thousands of clinical trials have taught us how best to craft treatment combinations that improve clinical outcomes. Only five years ago, a fourth and radically different form of therapy finally emerged: immune‑based cancer therapies. Objective This review briefly outlines the history and theoretical framework underpinning cancer immunotherapy, and recent progress on several immunotherapeutic approaches. Discussion Immune-based cancer therapies are already revolutionising the management of several types of hitherto intractable cancer, while offering immense hope that the burden of personal suffering and community cost due to cancer will diminish appreciably over the coming decades. At least two immunotherapeutic approaches, checkpoint inhibition and cellular therapy with autologous ('self') chimeric antigen receptor T cells (CAR T cells), now show indisputable evidence of efficacy in several cancer types, and promise yet more rapid progress as they are refined and we learn to combine them with existing conventional therapies and each other.

To Enroll or Not to Enroll?: A Researcher Struggles with the Decision to Involve Study Participants in a Clinical Trial That Could Save Their Lives.

Hundreds of thousands of clinical trials are conducted annually around the world, working to further scientific knowledge and expand medical treatment. At the same time, clinical trials also present novel challenges to researchers who have access to large pools of research participants and are routinely approached by pharmaceutical companies seeking to recruit subjects for clinical trials. This case study discusses the ethical dilemmas faced by a community health investigator who received an invitation to enroll people who inject drugs (PWID) into a clinical trial of a drug that promised a new treatment option for Hepatitis C. The author elaborates on the ethical tensions that he confronted between "doing good" and "avoiding harm. The paper suggests that issues of distributive justice should also be considered, particularly when the drugs being tested might eventually command prices that place them out of reach of the population enrolled in the trial. This case does not attempt to provide an ethical road map to assist researchers in similar circumstances, but rather to illustrate some of the considerations involved in making a decision about whether or not to participate in clinical trials research.

A discussion on adult mesenchymal stem cells for drug delivery: pros and cons.

Mesenchymal stem cells (MSCs) are emerging as candidates for drug delivery to treat numerous diseases. Their ease of isolation, expansion and reduced ethical concern, coupled with their 'plastic' immune functions and homing abilities make MSCs an appealing choice as cellular vehicle for drug delivery, including the delivery of RNA. However, while MSCs are currently listed for thousands of clinical trials, there are many confounding factors that have yet to be elucidated. In this review, we address many of the benefits of MSCs as therapeutic agents, and discuss confounding factors that require further scientific exploration.