Prudent Precaution in Clinical Trials of Nanomedicines

2012 ◽  
Vol 40 (4) ◽  
pp. 831-840 ◽  
Author(s):  
Gary E. Marchant ◽  
Rachel A. Lindor

Medical technologies, including nanomedicine products, are intended to improve health but in many cases may also create their own health risks. Medical products that create their own health risks differ from most other risk-creating technologies in that the very purpose of the medical technology is to prevent or treat health risks. This paradox of technologies intended to reduce existing risks that may have the effect of creating new risks has two conflicting implications. On one hand, we may be more tolerant of health risks from medical technologies because these products are intended to, and often (but not always) do, reduce overall health risks and improve our health. The health benefits of a medical technology may outweigh the unavoidable adverse effects of that same technology in an individual patient or in the overall treated population.

2021 ◽  
Vol 3 (2) ◽  
Author(s):  
Avisek Dutta ◽  
Avisek Dutta ◽  
Avisek Dutta

The objectives of the research are to percolate knowledge which can improve health and improve understanding of human physiology. Pervasive exclusion of children and elderly in clinical trials as is happening today is not justified. Children have different physiology and pharmacology from adults; often adverse effects are also different and specific. Diseases like neonatal hyperbilirubinemia, infantile spasms are very age specific. Elderly too, have age specific issues like dementias, malignancies, weakened systems and polypharmacy that make them a special cohort. Clinical trials in these age groups are essential so as to gather comprehensive data about a medication across all age groups. Informed consent is a challenge in both these groups. It can be remedied by obtaining consent from parents, or legally acceptable representative in case of children and care givers and/or LARs in case of the elderly. Oral assent from 7 to 11 years, and written assent from 12 to 18 years and in the elderly, along with consent from the LAR, parents, care givers as the case may be, forms the bedrock of good clinical trial ethics.


Heart ◽  
2018 ◽  
Vol 104 (22) ◽  
pp. 1817-1822 ◽  
Author(s):  
Peter H Groves ◽  
Chris Pomfrett ◽  
Mirella Marlow

The National Institute for Health and Care Excellence (NICE) Medical Technologies Evaluation Programme (MTEP) promotes the adoption of innovative diagnostic and therapeutic technologies into National Health Service (NHS) clinical practice through the publication of guidance and briefing documents. Since the inception of the programme in 2009, there have been 7 medical technologiesguidance, 3 diagnostics guidance and 23 medtechinnovation briefing documents published that are relevant to the heart and circulation. Medical technologies guidance is published by NICE for selected single technologies if they offer plausible additional benefits to patients and the healthcare system. Diagnostic guidance is published for diagnostic technologies if they have the potential to improve health outcomes, but if their introduction may be associated with an increase in overall cost to the NHS. Medtechinnovation briefings provide evidence-based advice to those considering the implementation of new medical devices or diagnostic technologies. This review provides reference to all of the guidance and briefing medical technology documents that NICE has published that are relevant to the heart and circulation and reflect on their diverse recommendations. The interaction of MTEP with other NICE programmes is integral to its effectiveness and the means by which consistency is ensured across the different NICE programmes is described. The importance of the input of clinical experts from the cardiovascular professional community and the engagement by NICE with cardiovascular professional societies is highlighted as being fundamental to ensuring the quality of guidance outputs as well as to promoting their implementation and adoption.


2020 ◽  
Vol 21 (2) ◽  
pp. 79-88 ◽  
Author(s):  
Pankaj Mandpe ◽  
Bala Prabhakar ◽  
Pravin Shende

Background: Overactive bladder syndrome is a broadly occurring urological disorder with a distressing impact on the quality of life. The commonly used antimuscarinic drugs show poor patient compliance because of unsatisfactory potency, tolerability and high occurrence of adverse effects such as dry mouth, blurred vision, constipation, dizziness etc. Mirabegron is the first approved β3-adrenoreceptor agonist, used as mono or in combination therapies for overactive bladder syndrome. Objective: The present review provides an insight into the mechanism, pharmacokinetics, toxicokinetics, clinical trials and the development of various conventional and modified-release dosage forms of mirabegron for the treatment of overactive bladder syndrome. Results: The clinical trials of phase II and phase III of mirabegron demonstrated symptomatic relief from the overactive bladder without disturbing the micturition cycle. To date, mirabegron showed promising results for safety, tolerability and efficacy in patients with overactive bladder syndrome. The modified-release tablet dosage form of mirabegron appear to be a proficient and suitable replacement for antimuscarinics and revealed the tremendous potential to overcome the adverse effects of conventional antimuscarinic drugs like Oxybutyline chloride ER, Detrol LA, VESIcare, etc. Conclusion: Mirabegron shows a distinct mode of action, i.e., targeting β3-adrenoreceptors and improving bladder storage without altering void contractions. The limited side effects, high safety, efficacy and tolerability of mirabegron present an adequate substitute to antimuscarinics. However, long-term analysis and clinical studies are prerequisites for assessing the safety, tolerability and efficacy profile of mirabegron.


2019 ◽  
Vol 15 (2) ◽  
pp. 130-139
Author(s):  
Ehsan T. Moghaddam ◽  
Ali Tafazoli

Background: Excessive consumption of cola beverages is accompanied by numerous public health risks. But besides these well-known adverse effects, recently, several medical articles have been published that show some indications for cola beverages in clinical practice like resolution of gastrointestinal or feeding tube obstructions, increasing bioavailability and palatability of other medications, rehydration and other uses in healthcare settings. These approaches are not without shortcomings and complications. Methods: In this systematic review we tried to explore these new uses for practitioners and also reemphasize on the most evidence-based complications of cola consumption like bone loss and metabolic and cardiovascular adverse effects in cases of misuse and overuse from both clinical and nutritional points of view via searching the PubMed database. Results: We chose 145 journal articles from the most relevant ones plus 30 extra references and categorized their topics in two classes of medical uses and adverse effects. Conclusion: It could be stated that cola beverages have demonstrated interesting uses and benefits in medicine but their use should be regulated as strict as possible.


2020 ◽  
Vol 15 (3) ◽  
pp. 216-233 ◽  
Author(s):  
Maliha Naseer ◽  
Shiva Poola ◽  
Syed Ali ◽  
Sami Samiullah ◽  
Veysel Tahan

The incidence, prevalence, and cost of care associated with diagnosis and management of inflammatory bowel disease are on the rise. The role of gut microbiota in the causation of Crohn's disease and ulcerative colitis has not been established yet. Nevertheless, several animal models and human studies point towards the association. Targeting intestinal dysbiosis for remission induction, maintenance, and relapse prevention is an attractive treatment approach with minimal adverse effects. However, the data is still conflicting. The purpose of this article is to provide the most comprehensive and updated review on the utility of prebiotics and probiotics in the management of active Crohn’s disease and ulcerative colitis/pouchitis and their role in the remission induction, maintenance, and relapse prevention. A thorough literature review was performed on PubMed, Ovid Medline, and EMBASE using the terms “prebiotics AND ulcerative colitis”, “probiotics AND ulcerative colitis”, “prebiotics AND Crohn's disease”, “probiotics AND Crohn's disease”, “probiotics AND acute pouchitis”, “probiotics AND chronic pouchitis” and “prebiotics AND pouchitis”. Observational studies and clinical trials conducted on humans and published in the English language were included. A total of 71 clinical trials evaluating the utility of prebiotics and probiotics in the management of inflammatory bowel disease were reviewed and the findings were summarized. Most of these studies on probiotics evaluated lactobacillus, De Simone Formulation or Escherichia coli Nissle 1917 and there is some evidence supporting these agents for induction and maintenance of remission in ulcerative colitis and prevention of pouchitis relapse with minimal adverse effects. The efficacy of prebiotics such as fructooligosaccharides and Plantago ovata seeds in ulcerative colitis are inconclusive and the data regarding the utility of prebiotics in pouchitis is limited. The results of the clinical trials for remission induction and maintenance in active Crohn's disease or post-operative relapse with probiotics and prebiotics are inadequate and not very convincing. Prebiotics and probiotics are safe, effective and have great therapeutic potential. However, better designed clinical trials in the multicenter setting with a large sample and long duration of intervention are needed to identify the specific strain or combination of probiotics and prebiotics which will be more beneficial and effective in patients with inflammatory bowel disease.


1985 ◽  
Vol 19 (5) ◽  
pp. 349-358 ◽  
Author(s):  
Peter W. Letendre ◽  
Douglas J. DeJong ◽  
Donald R. Miller

The use of methotrexate in rheumatoid arthritis is reviewed. Methotrexate, a folic acid antagonist, is sometimes employed in an attempt to symptomatically control patients whose disease does not respond adequately to conventional therapies. Systemic administration of 7.5–15 mg/wk in a “pulse” fashion appears to be effective without precipitating severe adverse effects. However, concern over potentially serious side effects and a lack of well-controlled clinical trials have limited its use to severe, refractory disease. Further studies are needed before its role in rheumatoid arthritis can justifiably be expanded.


2021 ◽  
Vol 71 (1) ◽  
Author(s):  
Trishala Gopikrishna ◽  
Harini Keerthana Suresh Kumar ◽  
Kumar Perumal ◽  
Elavarashi Elangovan

Abstract Purpose Fermented soybean foods (FSF) is popularly consumed in the South-East Asian countries. Bacillus species, a predominant microorganism present in these foods, have demonstrated beneficial and deleterious impacts on human health. These microorganisms produce bioactive compounds during fermentation that have beneficial impacts in improving human health. However, the health risks associated with FSF, food pathogens, biogenic amines (BAs) production, and late-onset anaphylaxis, remain a concern. The purpose of this review is to present an in-depth analysis of positive and negative impacts as a result of consumption of FSF along with the measures to alleviate health risks for human consumption. Methods This review was composed by scrutinizing contemporary literature of peer-reviewed publications related to Bacillus and FSF. Based on the results from academic journals, this review paper was categorized into FSF, role of Bacillus species in these foods, process of fermentation, beneficial, and adverse influence of these foods along with methods to improve food safety. Special emphasis was given to the potential benefits of bioactive compounds released during fermentation of soybean by Bacillus species. Results The nutritional and functional properties of FSF are well-appreciated, due to the release of peptides and mucilage, which have shown health benefits: in managing cardiac disease, gastric disease, cancer, allergies, hepatic disease, obesity, immune disorders, and especially microbial infections due to the presence of probiotic property, which is a potential alternative to antibiotics. Efficient interventions were established to mitigate pitfalls like the techniques to reduce BAs and food pathogens and by using a defined starter culture to improve the safety and quality of these foods. Conclusion Despite some of the detrimental effects produced by these foods, potential health benefits have been observed. Therefore, soybean foods fermented by Bacillus can be a promising food by integrating effective measures for maintaining safety and quality for human consumption. Further, in vivo analysis on the activity and dietary interventions of bioactive compounds among animal models and human volunteers are yet to be achieved which is essential to commercialize them for safe consumption by humans, especially immunocompromised patients.


2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Daria Kim ◽  
Joerg Hasford

Abstract The problem of wasteful clinical trials has been debated relentlessly in the medical community. To a significant extent, it is attributed to redundant trials – studies that are carried out to address questions, which can be answered satisfactorily on the basis of existing knowledge and accessible evidence from prior research. This article presents the first evaluation of the potential of the EU Clinical Trials Regulation 536/2014, which entered into force in 2014 but is expected to become applicable at the end of 2021, to prevent such trials. Having reviewed provisions related to the trial authorisation, we propose how certain regulatory requirements for the assessment of trial applications can and should be interpreted and applied by national research ethics committees and other relevant authorities in order to avoid redundant trials and, most importantly, preclude the unnecessary recruitment of trial participants and their unjustified exposure to health risks.


Author(s):  
David Rojas-Rueda

Background: Bicycling has been associated with health benefits. Local and national authorities have been promoting bicycling as a tool to improve public health and the environment. Mexico is one of the largest Latin American countries, with high levels of sedentarism and non-communicable diseases. No previous studies have estimated the health impacts of Mexico’s national bicycling scenarios. Aim: Quantify the health impacts of Mexico urban bicycling scenarios. Methodology: Quantitative Health Impact Assessment, estimating health risks and benefits of bicycling scenarios in 51,718,756 adult urban inhabitants in Mexico (between 20 and 64 years old). Five bike scenarios were created based on current bike trends in Mexico. The number of premature deaths (increased or reduced) was estimated in relation to physical activity, road traffic fatalities, and air pollution. Input data were collected from national publicly available data sources from transport, environment, health and population reports, and surveys, in addition to scientific literature. Results: We estimated that nine premature deaths are prevented each year among urban populations in Mexico on the current car-bike substitution and trip levels (1% of bike trips), with an annual health economic benefit of US $1,897,920. If Mexico achieves similar trip levels to those reported in The Netherlands (27% of bike trips), 217 premature deaths could be saved annually, with an economic impact of US $45,760,960. In all bicycling scenarios assessed in Mexico, physical activity’s health benefits outweighed the health risks related to traffic fatalities and air pollution exposure. Conclusion: The study found that bicycling promotion in Mexico would provide important health benefits. The benefits of physical activity outweigh the risk from traffic fatalities and air pollution exposure in bicyclists. At the national level, Mexico could consider using sustainable transport policies as a tool to promote public health. Specifically, the support of active transportation through bicycling and urban design improvements could encourage physical activity and its health co-benefits.


Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2159
Author(s):  
Charalampos Aktypis ◽  
Maria-Eleni Spei ◽  
Maria Yavropoulou ◽  
Göran Wallin ◽  
Anna Koumarianou ◽  
...  

A broad spectrum of novel targeted therapies with prime antitumor activity and/or ample control of hormonal symptoms together with an overall acceptable safety profile have emerged for patients with metastatic neuroendocrine neoplasms (NENs). In this systematic review and quantitative meta-analysis, the PubMed, EMBASE, Cochrane Central Register of Controlled Trials and clinicaltrials.gov databases were searched to assess and compare the safety profile of NEN treatments with special focus on the cardiovascular adverse effects of biotherapy and molecular targeted therapies (MTTs). Quality/risk of bias were assessed using GRADE criteria. Placebo-controlled randomized clinical trials (RCTs) in patients with metastatic NENs, including medullary thyroid cancer (MTC) were included. A total of 3695 articles and 122 clinical trials registered in clinicaltrials.gov were screened. We included sixteen relevant RCTs comprising 3408 unique patients assigned to different treatments compared with placebo. All the included studies had a low risk of bias. We identified four drug therapies for NENs with eligible placebo-controlled RCTs: somatostatin analogs (SSAs), tryptophan hydroxylase (TPH) inhibitors, mTOR inhibitors and tyrosine kinase inhibitors (TKI). Grade 3 and 4 adverse effects (AE) were more often encountered in patients treated with mTOR inhibitors and TKI (odds ratio [OR]: 2.42, 95% CI: 1.87–3.12 and OR: 3.41, 95% CI: 1.46–7.96, respectively) as compared to SSAs (OR:0.77, 95% CI: 0.47–1.27) and TPH inhibitors (OR:0.77, 95% CI: 0.35–1.69). MTOR inhibitors had the highest risk for serious cardiac AE (OR:3.28, 95% CI: 1.66–6.48) followed by TKIs (OR:1.51, 95% CI: 0.59–3.83). Serious vascular AE were more often encountered in NEN patients treated with mTOR inhibitors (OR: 1.72, 95% CI: 0.64–4.64) and TKIs (OR:1.64, 95% CI: 0.35–7.78). Finally, patients on TKIs were at higher risk for new-onset or exacerbation of pre-existing hypertension (OR:3.31, 95% CI: 1.87–5.86). In conclusion, SSAs and TPH inhibitors appear to be safer as compared to mTOR inhibitors and TKIs with regards to their overall toxicity profile, and cardiovascular toxicities in particular. Special consideration should be given to a patient-tailored approach with anticipated toxicities of targeted NEN treatments together with assessment of cardiovascular comorbidities, assisting clinicians in treatment selection and early recognition/management of cardiovascular toxicities. This approach could improve patient compliance and preserve cardiovascular health and overall quality of life.


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