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ClinicalTrials.gov (CT.gov) is the most comprehensive internet-based register of different types of clinical studies. Expanded access is the use of unapproved drugs, biologics, or medical devices outside of clinical trials. One of the key problems in expanded access is the availability to both health care providers and patients of information about unapproved treatments. We aimed to evaluate CT.gov as a potential source of information about expanded access programs. We assessed the completeness of information in the records of 228 expanded access programs registered with CT.gov from February 2017 through May 2020. Moreover, we examined what percentage of published expanded access studies has been registered with CT.gov. Logistic regression (univariate and multivariate) and mediation analyses were used to identify the predictors of the absence of some information and a study's nonregistration. We found that some important data were missing from the records of many programs. Information that was missing most often included a detailed study description, facility information, central contact person, and eligibility criteria (55.3%, 54.0%, 41.7%, and 17.5% of the programs, respectively). Multivariate analysis showed that information about central contact person was more likely to be missing from records of studies registered in 2017 (adjusted OR 21.93; 95% CI 4.42-172.29; P<.001). This finding was confirmed by mediation analysis (P=.02). Furthermore, 14% of the programs were registered retrospectively. We also showed that only 33 of 77 (42.9%) expanded access studies performed in the United States and published from 2014 through 2019 were registered with CT.gov. However, multivariate logistic regression analysis showed no significant association between any of the variables related to the studies and the odds of study nonregistration (P>.01). Currently, CT.gov is a quite fragmentary source of data on expanded access programs. This problem is important because CT.gov is the only publicly available primary source of information about specific programs. We suggest the actions that should be taken by different stakeholders to fully exploit this register as a source of information about expanded access.

While phage therapy carried out as compassionate use (experimental therapy) has recently flourished, providing numerous case reports of supposedly healed patients, clinical trials aiming to formally prove their value in accord with current regulatory requirements have failed. In light of the current issue of increasing antibiotic resistance, the need for a final say regarding the place of phage therapy in modern medicine is evident. We analyze the possible factors that may favor success or lead to the failure of phage therapy: quality of phage preparations, their titer and dosage, as well as external factors that could also contribute to the outcome of phage therapy. Hopefully, better control of these factors may eventually bring about long-awaited positive results.

The current problems with increasing bacterial resistance to antibacterial therapies, resulting in a growing frequency of incurable bacterial infections, necessitates the acceleration of studies on antibacterials of a new generation that could offer an alternative to antibiotics or support their action. Bacteriophages (phages) can kill antibiotic-sensitive as well as antibiotic-resistant bacteria, and thus are a major subject of such studies. Their efficacy in curing bacterial infections has been demonstrated in in vivo experiments and in the clinic. Unlike antibiotics, phages have a narrow range of specificity, which makes them safe for commensal microbiota. However, targeting even only the most clinically relevant strains of pathogenic bacteria requires large collections of well characterized phages, whose specificity would cover all such strains. The environment is a rich source of diverse phages, but due to their complex relationships with bacteria and safety concerns, only some naturally occurring phages can be considered for therapeutic applications. Still, their number and diversity make a detailed characterization of all potentially promising phages virtually impossible. Moreover, no single phage combines all the features required of an ideal therapeutic agent. Additionally, the rapid acquisition of phage resistance by bacteria may make phages already approved for therapy ineffective and turn the search for environmental phages of better efficacy and new specificity into an endless race. An alternative strategy for acquiring phages with desired properties in a short time with minimal cost regarding their acquisition, characterization, and approval for therapy could be based on targeted genome modifications of phage isolates with known properties. The first example demonstrating the potential of this strategy in curing bacterial diseases resistant to traditional therapy is the recent successful treatment of a progressing disseminated Mycobacterium abscessus infection in a teenage patient with the use of an engineered phage. In this review, we briefly present current methods of phage genetic engineering, highlighting their advantages and disadvantages, and provide examples of genetically engineered phages with a modified host range, improved safety or antibacterial activity, and proven therapeutic efficacy. We also summarize novel uses of engineered phages not only for killing pathogenic bacteria, but also for in situ modification of human microbiota to attenuate symptoms of certain bacterial diseases and metabolic, immune, or mental disorders.

Phages are viruses which can specifically infect bacteria, resulting in their destruction. Bacterial infections are a common complication of wound healing, and experimental evidence from animal models demonstrates promising potential for phage-dependent eradication of wound-associated infections. The studies discussed suggest that phage therapy may be an effective treatment, with important advantages over some current antibacterial treatments. Phage cocktails, as well as co-administration of phages and antibiotics, have been reported to minimise bacterial resistance. Further, phage-antibiotic synergism has been reported in some studies. The ideal dose of phages is still subject to debate, with evidence for both high and low doses to yield therapeutic effects. Novel delivery methods, such as hydrogels, are being explored for their advantages in topical wound healing. There are more and more Good Manufacturing Practice facilities dedicated to manufacturing phage products and phage therapy units across the world, showing the changing perception of phages which is occurring. However, further research is needed to secure the place of phages in modern medicine, with some scientists calling upon the World Health Organisation to help promote phage therapy.

The increasing consumer demand for minimally processed foods (MPFs) has highlighted the need for innovative preservation methods that ensure both safety and quality. Among promising biocontrol tools, bacteriophages—viruses that selectively destroy bacteria—have gained significant attention. This review explores the dual role of bacteriophages in the food industry. On one hand, they offer a natural, highly specific, and environmentally friendly means of controlling both pathogenic and spoilage bacteria in MPFs, contributing to improved food safety, extended shelf life, and reduced reliance on antibiotics and chemical preservatives. Their use spans primary production, bio-sanitization, and biopreservation. On the other hand, phages pose significant risks in fermentation-based industries such as dairy, where they can disrupt starter cultures and impair production. This review also examines the regulatory, technological, and safety challenges involved in phage application, including concerns about antibiotic resistance gene transfer, the presence of endotoxins, and scale-up limitations. Ultimately, this paper argues that with proper strain selection and regulation, bacteriophages can become valuable allies in sustainable food systems, despite their potential drawbacks. The application of strictly virulent bacteriophages as part of “green biotechnology” could enhance food quality and improve consumer health safety. By implementing the “farm to fork” strategy, bacteriophages may contribute to the production of health-promoting and sustainable food.

Acinetobacter baumannii is currently a serious threat to human health, especially to people with immunodeficiency as well as patients with prolonged hospital stays and those undergoing invasive medical procedures. The ever-increasing percentage of strains characterized by multidrug resistance to widely used antibiotics and their ability to form biofilms make it difficult to fight infections with traditional antibiotic therapy. In view of the above, phage therapy seems to be extremely attractive. Therefore, phages with good storage stability are recommended for therapeutic purposes. In this work, we present the results of studies on the stability of 12 phages specific for A. baumannii under different conditions (including temperature, different pH values, commercially available disinfectants, essential oils, and surfactants) and in the urine of patients with urinary tract infections (UTIs). Based on our long-term stability studies, the most optimal storage method for the A. baumannii phage turned out to be − 70 °C. In contrast, 60 °C caused a significant decrease in phage activity after 1 h of incubation. The tested phages were the most stable at a pH from 7.0 to 9.0, with the most inactivating pH being strongly acidic. Interestingly, ethanol-based disinfectants caused a significant decrease in phage titers even after 30 s of incubation. Moreover, copper and silver nanoparticle solutions also caused a decrease in phage titers (which was statistically significant, except for the Acba_3 phage incubated in silver solution), but to a much lesser extent than disinfectants. However, bacteriophages incubated for 24 h in essential oils (cinnamon and eucalyptus) can be considered stable.

Background Expanded access is the use of investigational drugs (IDs) outside of clinical trials. Generally it is performed in patients with serious and life-threatening diseases who cannot be treated satisfactorily with authorized drugs. Legal regulations of expanded access to IDs have been introduced among others in the USA, the European Union (EU), Canada and Australia. In addition, in the USA an alternative to expanded access is treatment under the Right-to-Try law. However, the treatment use of IDs is inherently associated with a number of ethically relevant problems. Main text The objective of this article is to present a coherent framework made up of eight requirements which have to be met for any treatment use of an ID to be ethical. These include a justified need for the use of an ID, no threat to clinical development of the ID, adequate scientific evidence to support the treatment, patient’s benefit as the primary goal of the use of an ID, informed decision of a patient, fair access of patients to IDs, independent review, as well as the dissemination of treatment results. Conclusions While this framework is essentially consistent with the legal regulations of expanded access of the USA, the EU, Canada and Australia, it is substantially wider in scope because it addresses some important issues that are not covered by the regulations. Overall, the framework that we developed minimizes the risks and threats, and maximizes potential benefits to each of the four key stakeholders involved in the treatment use of IDs including patients, doctors, drug manufacturers, and society at large.

Background Compassionate use is the use of unapproved drugs outside of clinical trials. So far, compassionate use regulations have been introduced in the US, Canada, many European countries, Australia and Brazil, and treatment on a compassionate use basis may be performed in Japan and China. However, there are important differences between relevant regulations in individual countries, particularly that approval by a research ethics committee (institutional review board) is a requirement for compassionate use in some countries (e.g. the US, Spain, and Italy), but not in others (e.g. Canada, the UK, France, and Germany). Discussion The main objective of this article is to present aspects of compassionate use that are important for the discussion of the role of research ethics committees in the review of compassionate use. These aspects include the nature of compassionate use, potential risks to patients associated with the use of drugs with unproven safety and efficacy, informed consent, physicians’ qualifications, and patient selection criteria. Our analysis indicates that the arguments for mandatory review substantially outweigh the arguments to the contrary. Conclusions Approval by a research ethics committee should be obligatory for compassionate use. The principal argument against mandatory ethical review of compassionate use is that it is primarily a kind of treatment rather than biomedical research. Nonetheless, compassionate use is different from standard clinical care and should be subject to review by research ethics committees. First, in practice, compassionate use often involves significant research aspects. Second, it is based on unapproved drugs with unproven safety and efficacy. Obtaining informed consent from patients seeking access to unapproved drugs on a compassionate use basis may also be difficult. Other important problems include the qualifications of the physician who is to perform treatment, and patient selection criteria.

In an era of antibiotic therapy crisis caused by spreading antimicrobial resistance, and when recurrent urinary tract infections constitute a serious social and medical problem, the isolation and complex characterization of phages with a potential therapeutic application represents a promising solution. It is an inevitable, and even a necessary direction in the development of current phage research. In this paper, we present two newly isolated myoviruses that show lytic activity against multidrug-resistant clinical isolates of Enterobacter spp. (E. cloacae, E. hormaechei, and E. kobei), the genomes of which belong to a poorly represented phage group. Both phages were classified as part of the Tevenvirinae subfamily (Entb_43 was recognized as Karamvirus and Entb_45 as Kanagawavirus). Phage lytic spectra ranging from 40 to 60% were obtained. The most effective phage-to-bacteria ratios (MOI = 0.01 and MOI = 0.001) for both the phage amplification and their lytic activity against planktonic bacteria were also estimated. Complete adsorption to host cells were obtained after about 20 min for Entb_43 and 10 min for Entb_45. The phage lysates retained their initial titers even during six months of storage at both −70 °C and 4 °C, whereas storage at 37 °C caused a complete loss in their activity. We showed that phages retained their activity after incubation with solutions of silver and copper nanoparticles, which may indicate possible synergistic antibacterial activity. Moreover, a significant reduction in phage titers was observed after incubation with a disinfectant containing octenidinum dihydrochloridum and phenoxyethanol, as well as with 70% ethanol. The observed maintenance of phage activity during incubation in a urine sample, along with other described properties, may suggest a therapeutic potential of phages at the infection site after intravesical administration.

Background Breast cancer (BC) is the most common cancer type in women. The purpose of this study was to assess the eligibility criteria in recent clinical trials in BC, especially those that can limit the enrollment of older patients as well as those with comorbidities and poor performance status. Methods Data on clinical trials in BC were extracted from ClinicalTrials.gov. Co-primary outcomes were proportions of trials with different types of the eligibility criteria. Associations between trial characteristics and the presence of certain types of these criteria (binary variable) were determined with univariate and multivariate logistic regression. Results Our analysis included 522 trials of systemic anticancer treatments started between 2020 and 2022. Upper age limits, strict exclusion criteria pertaining to comorbidities, and those referring to inadequate performance status of the patient were used in 204 (39%), 404 (77%), and 360 (69%) trials, respectively. Overall, 493 trials (94%) had at least one of these criteria. The odds of the presence of each type of the exclusion criteria were significantly associated with investigational site location and trial phase. We also showed that the odds of the upper age limits and the exclusion criteria involving the performance status were significantly higher in the cohort of recent trials compared with cohort of 309 trials started between 2010 and 2012 (39% vs 19% and 69% vs 46%, respectively; p  < 0.001 for univariate and multivariate analysis in both comparisons). The proportion of trials with strict exclusion criteria was comparable between the two cohorts ( p  > 0.05). Only three of recent trials (1%) enrolled solely patients aged 65 or 70 and older. Conclusions Many recent clinical trials in BC exclude large groups of patients, especially older adults, individuals with different comorbidities, and those with poor performance status. Careful modification of some of the eligibility criteria in these trials should be considered to allow investigators to assess the benefits and harms of investigational treatments in participants with characteristics typically encountered in clinical practice.