Isolation and molecular characterization of multidrug­resistant Escherichia coli from chicken meat.

Antibiotics in animal farms play a significant role in the proliferation and spread of antibiotic-resistant genes (ARGs) and antibiotic-resistant bacteria (ARB). The dissemination of antibiotic resistance from animal facilities to the nearby environment has become an emerging concern. The present study was focused on the isolation and molecular identification of Escherichia coli (E. coli) isolates from broiler chicken meat and further access their antibiotic-resistant profile against different antibiotics. Broiler chicken meat samples were collected from 44 retail poultry slaughter shops in Prayagraj district, Uttar Pradesh, India. Standard bacteriological protocols were followed to first isolate the E. coli, and molecular characterization was performed with genus-specific PCR. Phenotypic and genotypic antibiotic-resistant profiles of all confirmed 154 E. coli isolates were screened against 09 antibiotics using the disc diffusion and PCR-based method for selected resistance genes. In antibiotic sensitivity testing, the isolates have shown maximum resistance potential against tetracycline (78%), ciprofloxacin (57.8%), trimethoprim (54.00%) and erythromycin (49.35%). E. coli bacterial isolates have shown relative resistant to amoxicillin-clavulanic acid (43.00%) and against ampicillin (44.15%). Notably, 64.28% E. coli bacteria were found to be multidrug resistant. The results of PCR assays exposed that tetA and blaTEM genes were the most abundant genes harboured by 83 (84.0%) and 82 (82.0%) out of all 99 targeted E. coli isolates, followed by 48.0% for AmpC (CITM) gene and cmlA (23.00%) for chloramphenicol resistance. It is notable that most of the isolates collected from chicken meat samples were multidrug resistant (> 3 antibiotics), with more than 80% of them carrying tetracycline (tetA) and beta-lactam gene (blaTEM). This study highlights the high risk associated with poultry products due to MDR-E. coli and promote the limited use of antibiotics in poultry farms. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-03950-7.

Framework for Adoption of Next-Generation Sequencing (NGS) Globally in the Oncology Area.

Radical new possibilities of improved treatment of cancer are on offer from an advanced medical technology already demonstrating its significance: next-generation sequencing (NGS). This refined testing provides unprecedentedly precise diagnoses and permits the use of focused and highly personalized treatments. However, across regions globally, many cancer patients will continue to be denied the benefits of NGS as long as some of the yawning gaps in its implementation remain unattended. The challenges at the regional and national levels are linked because putting the solutions into effect is highly dependent on cooperation between regional- and national-level cooperation, which could be hindered by shortfalls in interpretation or understanding. The aim of the paper was to define and explore the necessary conditions for NGS and make recommendations for effective implementation based on extensive exchanges with policy makers and stakeholders. As a result, the European Alliance for Personalised Medicine (EAPM) developed a maturity framework structured around demand-side and supply-side issues to enable interested stakeholders in different countries to self-evaluate according to a common matrix. A questionnaire was designed to identify the current status of NGS implementation, and it was submitted to different experts in different institutions globally. This revealed significant variability in the different aspects of NGS uptake. Within different regions globally, to ensure those conditions are right, this can be improved by linking efforts made at the national level, where patients have needs and where care is delivered, and at the global level, where major policy initiatives in the health field are underway or in preparation, many of which offer direct or indirect pathways for building those conditions. In addition, in a period when consensus is still incomplete and catching up is needed at a political level to ensure rational allocation of resources-even within individual countries-to enable the best ways to make the necessary provisions for NGS, a key recommendation is to examine where closer links between national and regional actions could complement, support, and mutually reinforce efforts to improve the situation for patients.

The gaps between the new EU legislation on in vitro diagnostics and the on-the-ground reality.

The background to this debate is now well-known: an EU policy decision to tighten controls on the devices and diagnostics sector led to the adoption of a regulation in 2017 with a schedule for implementation over coming years - a timetable extended still further by last-minute legislation in early 2022, to provide the sector and regulators with more time to adapt to the changes. Discussions among experts organised in April by the European Alliance for Personalized Medicine (EAPM) exposed continuing challenges that cannot be fully resolved by the recent deferral of implementation deadlines. One salient problem is that there is little awareness of the In Vitro Diagnostic Regulation (IVDR) across Europe, and only limited awareness of the different structures of national systems involved in implementing IVDR, with consequent risks for patient and consumer access to in vitro diagnostics (IVDs). The tentative conclusion from these consultations is that despite a will across the sector to seek workable solutions, the obstacles remain formidable, and the potential solutions so far proposed remain more a matter of aspirations than of clear pathways.

Empowering quality data - the Gordian knot of bringing real innovation into healthcare system.

OBJECTIVES: The introduction of Personalised Medicine (PM) into healthcare systems could benefit from a clearer understanding of the distinct national and regional frameworks around the world. Recent engagement by international regulators on maximising the use of real-world evidence (RWE) has highlighted the scope for improving the exploitation of the treasure-trove of health data that is currently largely neglected in many countries. The European Alliance for Personalised Medicine (EAPM) led an international study aimed at identifying the current status of conditions. METHODS: A literature review examined how far such frameworks exist, with a view to identifying conducive factors - and crucial gaps. This extensive review of key factors across 22 countries and 5 regions revealed a wide variety of attitudes, approaches, provisions and conditions, and permitted the construction of a comprehensive overview of the current status of PM. Based on seven key pillars identified from the literature review and expert panels, the data was quantified, and on the basis of further analysis, an index was developed to allow comparison country by country and region by region. RESULTS: The results show that United States of America is leading according to overall outcome whereas Kenya scored the least in the overall outcome. CONCLUSIONS: Still, common approaches exist that could help accelerate take-up of opportunities even in the less prosperous parts of the world.

Fighting Cancer around the World: A Framework for Action.

Tackling cancer is a major challenge right on the global level. Europe is only the tip of an iceberg of cancer around the world. Prosperous developed countries share the same problems besetting Europe-and the countries and regions with fewer resources and less propitious conditions are in many cases struggling often heroically against a growing tide of disease. This paper offers a view on these geographically wider, but essentially similar, challenges, and on the prospects for and barriers to better results in this ceaseless battle. A series of panels have been organized by the European Alliance for Personalised Medicine (EAPM) to identify different aspects of cancer care around the globe. There is significant diversity in key issues such as NGS, RWE, molecular diagnostics, and reimbursement in different regions. In all, it leads to disparities in access and diagnostics, patients' engagement, and efforts for a better understanding of cancer.

Making Sure That Orphan Incentives Tip the Right Way in Europe.

The delicate balance of funding research and development of treatments for rare disease is only imperfectly achieved in Europe, and even the current provisional equilibrium is under a new threat from well-intentioned policy changes now in prospect that could-in addition to the intrinsic complexities of research-reduce the incentives on which commercial activity in this area is dependent. The European Union review of its pharmaceutical legislation, for which proposals are scheduled to appear before the end of 2022, envisages adjusting the decade-old incentives to meet objectives that are more precisely targeted. However, researchers, physicians, patients and industry have expressed concerns that ill-considered modifications could have unintended consequences in disrupting the current balance and could reduce rather than increase the flow of innovative treatments for rare diseases.

How Can the EU Beating Cancer Plan Help in Tackling Lung Cancer, Colorectal Cancer, Breast Cancer and Melanoma?

Cancer is the second leading cause of mortality in EU countries, and the needs to tackle cancer are obvious. New scientific understanding, techniques and methodologies are opening up horizons for significant improvements in diagnosis and care. However, take-up is uneven, research needs and potential outstrip currently available resources, manifestly beneficial practices-such as population-level screening for lung cancer-are still not generalised, and the quality of life of patients and survivors is only beginning to be given attention it merits. This paper, mainly based on a series of multistakeholder expert workshops organised by the European Alliance for Personalised Medicine (EAPM), looks at some of those specifics in the interest of planning a way forward. Part of this exercise also involves taking account of the specific nature of Europe and its constituent countries, where the complexities of planning a way forward are redoubled by the wide variations in national and regional approaches to cancer, local epidemiology and the wide disparities in health systems. Despite all the differences between cancers and national and regional resources and approaches to cancer care, there is a common objective in pursuing broader and more equal access to the best available care for all European citizens.

European Health Data Space-An Opportunity Now to Grasp the Future of Data-Driven Healthcare.

The May 2022 proposal from the European commission for a 'European health data space' envisages advantages for health from exploiting the growing mass of health data in Europe. However, key stakeholders have identified aspects that demand clarification to ensure success. Data will need to be freed from traditional silos to flow more easily and to cross artificial borders. Wide engagement will be necessary among healthcare professionals, researchers, and the patients and citizens that stand to gain the most but whose trust must be won if they are to allow use or transfer of their data. This paper aims to alert the wider scientific community to the impact the ongoing discussions among lawmakers will have. Based on the literature and the consensus findings of an expert multistakeholder panel organised by the European Alliance for Personalised Medicine (EAPM) in June 2022, it highlights the key issues at the intersection of science and policy, and the potential implications for health research for years, perhaps decades, to come.

Accelerating the Development and Validation of Liquid Biopsy for Early Cancer Screening and Treatment Tailoring.

Liquid biopsy (LB) is a minimally invasive method which aims to detect circulating tumor-derived components in body fluids. It provides an alternative to current cancer screening methods that use tissue biopsies for the confirmation of diagnosis. This paper attempts to determine how far the regulatory, policy, and governance framework provide support to LB implementation into healthcare systems and how the situation can be improved. For that reason, the European Alliance for Personalised Medicine (EAPM) organized series of expert panels including different key stakeholders to identify different steps, challenges, and opportunities that need to be taken to effectively implement LB technology at the country level across Europe. To accomplish a change of patient care with an LB approach, it is required to establish collaboration between multiple stakeholders, including payers, policymakers, the medical and scientific community, and patient organizations, both at the national and international level. Regulators, pharma companies, and payers could have a major impact in their own domain. Linking national efforts to EU efforts and vice versa could help in implementation of LB across Europe, while patients, scientists, physicians, and kit manufacturers can generate a pull by undertaking more research into biomarkers.

Meeting the Need for a Discussion of Unmet Medical Need.

As Europe and the world continue to battle against COVID, the customary complacency of society over future threats is clearly on display. Just 30 months ago, such a massive disruption to global lives, livelihoods and quality of life seemed unimaginable. Some remedial European Union action is now emerging, and more is proposed, including in relation to tackling "unmet medical need" (UMN). This initiative-directing attention to the future of treating disease and contemplating incentives to stimulate research and development-is welcome in principle. But the current approach being considered by EU officials merits further discussion, because it may prove counter-productive, impeding rather than promoting innovation. This paper aims to feed into these ongoing policy discussions, and rather than presenting research in the classical sense, it discusses the key elements from a multistakeholder perspective. Its central concern is over the risk that the envisaged support will fail to generate valuable new treatments if the legislation is phrased in a rigidly linear manner that does not reflect the serpentine realities of the innovation process, or if the definition placed on unmet medical need is too restrictive. It cautions that such an approach presumes that "unmet need" can be precisely and comprehensively defined in advance on the basis of the past. It cautions that such an approach can reinforce the comfortable delusion that the future is totally predictable-the delusion that left the world as easy prey to COVID. Instead, the paper urges reflection on how the legislation that will shortly enter the pipeline can be phrased so as to allow for the flourishing of a culture capable of rapid adaptation to the unexpected.

Towards Better Pharmaceutical Provision in Europe-Who Decides the Future?

Significant progress has been achieved in human health in the European Union in recent years. New medicines, vaccines, and treatments have been developed to tackle some of the leading causes of disease and life-threatening illnesses. It is clear that investment in research and development (R&D) for innovative medicines and treatments is essential for making progress in preventing and treating diseases. Ahead of the legislative process, which should begin by the end of 2022, discussions focus on how Europe can best promote the huge potential benefits of new science and technology within the regulatory framework. The challenges in European healthcare were spelled out by the panellists at the roundtable organised by European Alliance for Personalised Medicine (EAPM). Outcomes from panellists' discussions have been summarized and re-arranged in this paper under five headings: innovation, unmet medical need, access, security of supply, adapting to progress, and efficiency. Some of the conclusions that emerged from the panel are a call for a better overall holistic vision of the future of pharmaceuticals and health in Europe and a collaborative effort among all stakeholders, seeing the delivery of medicines as part of a broader picture of healthcare.

Novel CRISPR-Cas Systems: An Updated Review of the Current Achievements, Applications, and Future Research Perspectives.

According to Darwin's theory, endless evolution leads to a revolution. One such example is the Clustered Regularly Interspaced Palindromic Repeats (CRISPR)-Cas system, an adaptive immunity system in most archaea and many bacteria. Gene editing technology possesses a crucial potential to dramatically impact miscellaneous areas of life, and CRISPR-Cas represents the most suitable strategy. The system has ignited a revolution in the field of genetic engineering. The ease, precision, affordability of this system is akin to a Midas touch for researchers editing genomes. Undoubtedly, the applications of this system are endless. The CRISPR-Cas system is extensively employed in the treatment of infectious and genetic diseases, in metabolic disorders, in curing cancer, in developing sustainable methods for fuel production and chemicals, in improving the quality and quantity of food crops, and thus in catering to global food demands. Future applications of CRISPR-Cas will provide benefits for everyone and will save countless lives. The technology is evolving rapidly; therefore, an overview of continuous improvement is important. In this review, we aim to elucidate the current state of the CRISPR-Cas revolution in a tailor-made format from its discovery to exciting breakthroughs at the application level and further upcoming trends related to opportunities and challenges including ethical concerns.

Digitalisation and COVID-19: The Perfect Storm.

"A ship in the harbour is safe, but that is not what ships are built for," observed that sage 19th century philosopher William Shedd. In other words, technology of high potential is of little value if the potential is not exploited. As the shape of 2020 is increasingly defined by the coronavirus pandemic, digitalisation is like a ship loaded with technology that has a huge capacity for transforming mankind's combat against infectious disease. But it is still moored safely in harbour. Instead of sailing bravely into battle, it remains at the dockside, cowering from the storm beyond the breakwaters. Engineers and fitters constantly fine-tune it, and its officers and deckhands perfect their operating procedures, but that promise is unfulfilled, restrained by the hesitancy and indecision of officialdom. Out there, the seas of the pandemic are turbulent and uncharted, and it is impossible to know in advance everything of the other dangers that may lurk beyond those cloudy horizons. However, the more noble course is for orders to be given to complete the preparations, to cast off and set sail, and to join other vessels crewed by valiant healthcare workers and tireless researchers, already deeply engaged in a rescue mission for the whole of the human race. It is the destiny of digitalisation to navigate those oceans alongside other members of that task force, and the hour of destiny has arrived. This article focuses on the potential enablers and recommendation to maximise learnings during the era of COVID-19.

Sexually Transmitted Infections and Behavioral Determinants of Sexual and Reproductive Health in the Allahabad District (India) Based on Data from the ChlamIndia Study.

BACKGROUND: Sexually transmitted infections (STIs), like Chlamydia trachomatis and Neisseria gonorrhoeae (CT and NG, respectively) are linked to an important sexual and reproductive health (SRH) burden worldwide. Behavior is an important predictor for SRH, as it dictates the risk for STIs. Assessing the behavior of a population helps to assess its risk profile. METHODS: Study participants were recruited at a gynecology outpatient department (OPD) in the Allahabad district in Uttar Pradesh India, and a questionnaire was used to assess demographics, SRH, and obstetric history. Patients provided three samples (urine, vaginal swab, and whole blood). These samples were used to identify CT and NG using PCR/NAAT and CT IgG ELISA. RESULTS: A total of 296 women were included for testing; mean age was 29 years. No positive cases of CT and NG were observed using PCR/NAAT. A 7% (22/296) positivity rate for CT was observed using IgG ELISA. No positive association was found between serology and symptoms (vaginal discharge, abdominal pain, dysuria, and dyspareunia) or adverse pregnancy outcomes (miscarriage and stillbirth). Positive relations with CT could be observed with consumption of alcohol, illiteracy, and tenesmus (p-value 0.02-0.03). DISCUSSION: STI prevalence in this study was low, but a high burden of SRH morbidity was observed, with a high symptomatic load. High rates of miscarriage (31%) and stillbirth (8%) were also observed among study subjects. No associations could be found between these ailments and CT infection. These rates are high even for low- and middle-income country standards. CONCLUSION: This study puts forward high rates of SRH morbidity, and instances of adverse reproductive health outcomes are highlighted in this study, although no associations with CT infection could be found. This warrants more investigation into the causes leading to these complaints in the Indian scenario and potential biases to NAAT testing, such as consumption of over-the-counter antimicrobials.

Next-Generation Sequencing: An Emerging Tool for Drug Designing.

BACKGROUND: With the outbreak of high throughput next-generation sequencing (NGS), the biological research of drug discovery has been directed towards the oncology and infectious disease therapeutic areas, with extensive use in biopharmaceutical development and vaccine production. METHOD: In this review, an effort was made to address the basic background of NGS technologies, potential applications of NGS in drug designing. Our purpose is also to provide a brief introduction of various Nextgeneration sequencing techniques. DISCUSSIONS: The high-throughput methods execute Large-scale Unbiased Sequencing (LUS) which comprises of Massively Parallel Sequencing (MPS) or NGS technologies. The Next geneinvolved necessarily executes Largescale Unbiased Sequencing (LUS) which comprises of MPS or NGS technologies. These are related terms that describe a DNA sequencing technology which has revolutionized genomic research. Using NGS, an entire human genome can be sequenced within a single day. CONCLUSION: Analysis of NGS data unravels important clues in the quest for the treatment of various lifethreatening diseases and other related scientific problems related to human welfare.

An Integrated Care Model With Implementation Roadmap to Improve Chlamydia trachomatis Management and Control in India.

Chlamydia trachomatis is the world's most prevalent bacterial Sexually Transmitted infection (STI). It is associated with a wide range of health consequences and sequelae in both the short and long term. Enhanced control of urogenital C. trachomatis infection is particularly important in low- and middle-income countries such as India, where most of the burden goes unnoticed and where limited systematic data is available to gauge the current situation. The World Health Organization (WHO) recently issued its latest strategy on STIs, which is aligned with the achievement of the Sustainable Development Goals (SDGs). Taking the WHO framework into account; this paper puts forward an integrated care model to strengthen the management and control of C. trachomatis in India. The model is compiled of five key components of STI management (awareness, prevention diagnosis, treatment and follow-up). The model considers barriers to effective C. trachomatis control into account. The barriers are discussed and compiled into different categories. A roadmap for the implementation of other similar models to enhance C. trachomatis control in the future is provided.

Making the Most of Innovation in Personalised Medicine: An EU Strategy for a Faster Bench to Bedside and Beyond Process.

Personalised medicine promises to revolutionise healthcare, with its key goal of providing the right treatment to the right patient at the right time, and thus the potential of improving quality of life and helping to bring down healthcare costs. However, a major problem with broader implementation of personalised medicine is patient access to new drugs, devices and treatments. The fact that a new medicine or innovative product can sometimes take as long as 20 years to get from bench to bedside is not only clearly undesirable but is arguably unacceptable in the 21st century. This paper looks in detail at the issues surrounding development, continued investment, risk factors, testing and approval from both the industry perspective as well as that of the assessor and the decision maker/payer. It becomes clear that there is a lack of working in tandem that results in a double time frame (two times 10 years). This is simply because the key stakeholders, surprisingly, do not synergise their assessments of a new product. As well as causing delays in patient access, this can also affect investment confidence as industry waits too long for approval for its product to reach the market and its subsequent implementation into healthcare. Such a slow process undermines continued investment and contributes to a risk-averse environment, which in turn can have an impact on innovation. The solution appears to be uncomplicated, involving better coordination and collaboration between the different stakeholders working at various stages within the bench-to-bedside timeframe. We take the example of the network of the European Alliance for Personalised Medicine (EAPM) to demonstrate possible solutions using an innovative approach.

Burden of Chlamydia trachomatis in India: a systematic literature review.

Chlamydia trachomatis (hereafter CT) is Gram-negative, obligate intracellular pathogen. It causes the world's most common non-viral sexually transmitted disease. India is home to the world's greatest burden of infectious diseases, yet information on prevalence rates of CT is scarce. This article systematically reviews the literature for the prevalence rates and testing methods in India. A total of 27 studies were included. Four main patients groups (symptomatic women, infertile women, pregnant women and asymptomatic population groups) could be identified with varying rates of CT (0.1%-32% using PCR, 2.4%-75% using ELISA serology). Most of the studies originated from urban settings, 11 of them from New Delhi. In-house PCR was the most common diagnostic technique used generating the following ranges in prevalence for the four group studies: symptomatic women 10%-50%, pregnant women 0.1%-2.5% and asymptomatic populations 0.9%-24.5%. The rates among infertile women were 9%-68% based on serology results. The prevalence rates featured in this paper are in line with other locations across the Indian subcontinent. This review highlights the extreme heterogeneity in the limited studies available in India on CT and the need for standardized guidelines for diagnosis and management of CT in India. The availability of resources should be considered in the formulation of recommendations.

Decision support systems for personalized and participative radiation oncology.

A paradigm shift from current population based medicine to personalized and participative medicine is underway. This transition is being supported by the development of clinical decision support systems based on prediction models of treatment outcome. In radiation oncology, these models 'learn' using advanced and innovative information technologies (ideally in a distributed fashion - please watch the animation: http://youtu.be/ZDJFOxpwqEA) from all available/appropriate medical data (clinical, treatment, imaging, biological/genetic, etc.) to achieve the highest possible accuracy with respect to prediction of tumor response and normal tissue toxicity. In this position paper, we deliver an overview of the factors that are associated with outcome in radiation oncology and discuss the methodology behind the development of accurate prediction models, which is a multi-faceted process. Subsequent to initial development/validation and clinical introduction, decision support systems should be constantly re-evaluated (through quality assurance procedures) in different patient datasets in order to refine and re-optimize the models, ensuring the continuous utility of the models. In the reasonably near future, decision support systems will be fully integrated within the clinic, with data and knowledge being shared in a standardized, dynamic, and potentially global manner enabling truly personalized and participative medicine.

An index of barriers for the implementation of personalised medicine and pharmacogenomics in Europe.

BACKGROUND: Personalised medicine (PM) is an innovative way to produce better patient outcomes by using an individualised or stratified approach to disease and treatment rather than a collective treatment approach for patients. Despite its tangible advantages, the complex process to translate PM into the member states and European healthcare systems has delayed its uptake. The aim of this study is to identify relevant barriers represented by an index to summarise challenging areas for the implementation of PM in Europe. METHODS: A systematic literature review was conducted, and a gaps-and-needs assessment together with a strengths-weaknesses-opportunities-and-threats analysis were applied to review strategic reports and conduct interviews with key stakeholders. Furthermore, surveys were sent out to representatives of stakeholder groups. The index was constructed based on the priorisation of relevant factors by stakeholders. RESULTS: A need for stakeholder-agreed standards at all levels of implementation of PM exists, from validating biomarkers to definitions of 'informed consent'. The barriers to implement PM are identified in 7 areas, namely, stakeholder involvement, standardisation, interoperable infrastructure, European-level policy making, funding, data and research, and healthcare systems. CONCLUSIONS: Challenges in the above-mentioned areas can and must be successfully tackled if we are to create a healthier Europe through PM. In order to create an environment in which PM can thrive for the patients' best outcomes, there is an urgent need for systematic actions to remove as many barriers as possible.