Antimicrobial resistance is a public health threat. Because antimicrobial consumption in food-producing animals contributes to the problem, policies restricting the inappropriate or unnecessary ...agricultural use of antimicrobial drugs are important. However, this link between agricultural antibiotic use and antibiotic resistance has remained contested by some, with potentially disruptive effects on efforts to move towards the judicious or prudent use of these drugs.
The goal of this review is to systematically evaluate the types of evidence available for each step in the causal pathway from antimicrobial use on farms to human public health risk, and to evaluate the strength of evidence within a 'Grades of Recommendations Assessment, Development and Evaluation'(GRADE) framework. The review clearly demonstrates that there is compelling scientific evidence available to support each step in the causal pathway, from antimicrobial use on farms to a public health burden caused by infections with resistant pathogens. Importantly, the pathogen, antimicrobial drug and treatment regimen, and general setting (e.g., feed type) can have significant impacts on how quickly resistance emerges or spreads, for how long resistance may persist after antimicrobial exposures cease, and what public health impacts may be associated with antimicrobial use on farms. Therefore an exact quantification of the public health burden attributable to antimicrobial drug use in animal agriculture compared to other sources remains challenging.
Even though more research is needed to close existing data gaps, obtain a better understanding of how antimicrobial drugs are actually used on farms or feedlots, and quantify the risk associated with antimicrobial use in animal agriculture, these findings reinforce the need to act now and restrict antibiotic use in animal agriculture to those instances necessary to ensure the health and well-being of the animals.
Summary
We report the proceedings of the First International new‐onset refractory status epilepticus (NORSE) and febrile infection‐related epilepsy syndrome (FIRES) Symposium. To promote awareness of ...this condition and foster research efforts, we conveyed the First International new‐onset refractory status epilepticus (NORSE) and febrile infection‐related epilepsy syndrome (FIRES) Symposium. The conference was supported by The NORSE Institute (http://www.norseinstitute.org). This article summarizes the discussions that were held during the Symposium and presents our strategy to unravel the cause of these disorders and to improve patient care. The standardized definitions for these disorders that have been developed, are required to improve communication and facilitate the development of multicenter registries and biobanks. A distinction between childhood‐ and adult‐onset forms of the syndrome is not supported by strong scientific evidence and it is argued that both should be studied together. Although the pathophysiology remains elusive, nascent evidence suggests a role for a postinfectious cytokine‐mediated mechanism, which should be further investigated. It also appears important to develop tools for their early recognition and prompt treatment. Recent evidence suggests that specific electroencephalography (EEG) features might be helpful. The optimal treatment options remain to be determined; immune therapies are usually disappointing, but the ketogenic diet has proved effective in uncontrolled trials. NORSE and FIRES represent a very delicate clinical situation with specific communication issues between physicians and with patients and families. Standardized consensus definitions and a multidisciplinary multicenter strategy will help research efforts and improve clinical care for patients with NORSE and FIRES.
Vaccines and other alternative products can help minimize the need for antibiotics by preventing and controlling infectious diseases in animal populations, and are central to the future success of ...animal agriculture. To assess scientific advancements related to alternatives to antibiotics and provide actionable strategies to support their development, the United States Department of Agriculture, with support from the World Organisation for Animal Health, organized the second International Symposium on Alternatives to Antibiotics. It focused on six key areas: vaccines; microbial-derived products; non-nutritive phytochemicals; immune-related products; chemicals, enzymes, and innovative drugs; and regulatory pathways to enable the development and licensure of alternatives to antibiotics. This article, part of a two-part series, synthesizes and expands on the expert panel discussions regarding opportunities, challenges and needs for the development of vaccines that may reduce the need for use of antibiotics in animals; new approaches and potential solutions will be discussed in part 2 of this series. Vaccines are widely used to prevent infections in food animals. Various studies have demonstrated that their animal agricultural use can lead to significant reductions in antibiotic consumption, making them promising alternatives to antibiotics. To be widely used in food producing animals, vaccines have to be safe, effective, easy to use, and cost-effective. Many current vaccines fall short in one or more of these respects. Scientific advancements may allow many of these limitations to be overcome, but progress is funding-dependent. Research will have to be prioritized to ensure scarce public resources are dedicated to areas of potentially greatest impact first, and private investments into vaccine development constantly compete with other investment opportunities. Although vaccines have the potential to improve animal health, safeguard agricultural productivity, and reduce antibiotic consumption and resulting resistance risks, targeted research and development investments and concerted efforts by all affected are needed to realize that potential.
Manure from poultry operations is typically applied to nearby cropland and may affect nutrient loading and the spread of antibiotic resistance (ABR). We analyzed the concentrations of nitrogen and ...phosphorus and the occurrence of ABR in Escherichia coli (E. coli) and extra-intestinal pathogenic E. coli isolates from streams draining 15 small (<19 km2) watersheds of the Chesapeake Bay with contrasting levels of concentrated poultry operations. Total nitrogen and nitrate plus nitrite concentrations increased with poultry barn density with concentrations two and three times higher, respectively, in watersheds with the highest poultry barn densities compared to those without poultry barns. Analysis of N and O isotopes in nitrate by mass spectrometry showed an increase in the proportion of 15N associated with an increase in barn density, suggesting that the nitrate associated with poultry barns originated from manure. Phosphorus concentrations were not correlated with barn density. Antibiotic susceptibility testing of putative E. coli isolates was conducted using the disk diffusion method for twelve clinically important antibiotics. Of the isolates tested, most were completely susceptible (67%); 33% were resistant to at least one antibiotic, 24% were resistant to ampicillin, 13% were resistant to cefazolin, and 8% were multi-drug resistant. Resistance to three cephalosporin drugs was positively associated with an index of manure exposure estimated from poultry barn density and proportion of cropland in a watershed. The proportion of E. coli isolates resistant to cefoxitin, cefazolin, and ceftriaxone, broad-spectrum antibiotics important in human medicine, increased by 18.9%, 16.9%, and 6.2%, respectively, at the highest estimated level of manure exposure compared to watersheds without manure exposure. Our results suggest that comparisons of small watersheds could be used to identify geographic areas where remedial actions may be needed to reduce nutrient pollution and the public health risks of ABR bacteria.
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•Nitrogen concentrations in watersheds increased with numbers of poultry barns in and around the watershed.•Cephalosporin-resistant E. coli in streams was positively correlated with the estimated poultry manure exposure.•Studying small watersheds has the potential to reveal sources of antibiotic resistant bacteria and nutrient pollution.
Vaccines and other alternative products are central to the future success of animal agriculture because they can help minimize the need for antibiotics by preventing and controlling infectious ...diseases in animal populations. To assess scientific advancements related to alternatives to antibiotics and provide actionable strategies to support their development, the United States Department of Agriculture, with support from the World Organisation for Animal Health, organized the second International Symposium on Alternatives to Antibiotics. It focused on six key areas: vaccines; microbial-derived products; non-nutritive phytochemicals; immune-related products; chemicals, enzymes, and innovative drugs; and regulatory pathways to enable the development and licensure of alternatives to antibiotics. This article, the second part in a two-part series, highlights new approaches and potential solutions for the development of vaccines as alternatives to antibiotics in food producing animals; opportunities, challenges and needs for the development of such vaccines are discussed in the first part of this series. As discussed in part 1 of this manuscript, many current vaccines fall short of ideal vaccines in one or more respects. Promising breakthroughs to overcome these limitations include new biotechnology techniques, new oral vaccine approaches, novel adjuvants, new delivery strategies based on bacterial spores, and live recombinant vectors; they also include new vaccination strategies in-ovo, and strategies that simultaneously protect against multiple pathogens. However, translating this research into commercial vaccines that effectively reduce the need for antibiotics will require close collaboration among stakeholders, for instance through public-private partnerships. Targeted research and development investments and concerted efforts by all affected are needed to realize the potential of vaccines to improve animal health, safeguard agricultural productivity, and reduce antibiotic consumption and resulting resistance risks.
Awareness of the long-term outcomes of status epilepticus is key to understanding the condition overall. Maintaining ties with patients' families is vital to both obtaining better long-term patient ...outcomes and obtaining that elusive data on long-term conditions. Common language and linked infrastructure support these ties. This position is posed within the context of NORSE (new-onset refractory status epilepticus) and FIRES (febrile infection-related epilepsy syndrome). This paper was presented at the 8th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures held in September 2022.
This article addresses whether physicians' close ties to their patients might play an unexamined role in their reluctance to initiate palliative care. In cases characterized by uncertainty, ...physicians' emotional investment in their patients and patients' families might unduly promote decisions to continue aggressive treatment rather than transition to comfort care. Continued evaluation and communication of patient status, including scheduled objective consultations, can align compassionate actions with patients' best interests. This argument and analysis are based on a case of new onset refractory status epilepticus (NORSE).
Forward with Dementia is a co-designed campaign to improve communication of dementia diagnosis and post-diagnostic support.
Webinars, a website, social and traditional media, and promotions through ...project partners were used to disseminate campaign messages to health and social care professionals (primary audience) and people with dementia and carers (secondary audience). The campaign ran between October 2021 and June 2022, with 3-months follow-up. The RE-AIM framework was used for process evaluation. Measurements included surveys and interviews, a log of activities (e.g. webinars, social media posts) and engagements (e.g. attendees, reactions to posts), and Google Analytics.
There were 29,053 interactions with campaign activities. More than three-quarters of professionals (n = 63/81) thought webinars were very or extremely helpful. Professionals and people with dementia and carers reported that the website provided appropriate content, an approachable tone, and was easy to use. Following campaign engagement, professionals planned to (n = 77/80) or had modified (n = 29/44) how they communicated the diagnosis and/or provided post-diagnostic information and referrals. Qualitative data suggested that the campaign may have led to benefits for some people with dementia and carers.
Forward with Dementia was successful in terms of reach, appropriateness, adoption and maintenance for professionals, however flow-through impacts on people with dementia are not clear. Targeted campaigns can potentially change health professionals' communication and support around chronic diseases such as dementia.
To describe the prevalence and characteristics of comorbidities in persons with rare epilepsies.
Persons with rare epilepsies and caregivers of those affected were recruited through the Epilepsy ...Foundation and more than 30 rare epilepsy advocacy organizations affiliated with the Rare Epilepsy Network (REN). A web-based survey was conducted using a questionnaire consisting of core sections to collect data from affected persons on various aspects, including comorbidities. Comorbidity information was grouped into 15 classes, 12 of which had a stem question followed by detailed branch questions and 3 that were created from a combination of related questions.
Of 795 persons with more than 30 different rare epilepsy diagnosis groups, one-half had ≥5 comorbidity classes and 97% were classified as complex chronic disease (C-CD). The highest number of comorbidity classes reported per person were persons with Aicardi syndrome, Phelan-McDermid syndrome (median, 7.0; IQR, 5.0-9.0), and tuberous sclerosis complex (median, 6.0; IQR, 4.0-8.0). The most common comorbidity classes were learning/developmental disability (71%), mental health issues (71%), sleep disorders (60%), brain abnormalities (52%), oral issues (49%), bone-joint issues (42%), hyper/hypotonia (42%), and eye-vision disorders (38%). The prevalence of brain abnormalities, hyper/hypotonia, eye, and cardiac disorders was significantly higher in persons first diagnosed with epilepsy at a younger age (<9 months) than in those first diagnosed at an older age (P < .05 for trend).
Nearly all persons with rare epilepsies are medically complex, with a high prevalence of multiple comorbidities, especially those who were diagnosed with epilepsy in the first year of life. Comorbidities should be carefully considered in the diagnosis and management of persons with rare epilepsies.
Previous studies have shown that BRCA1-related breast cancers are often high-grade tumors that do not express estrogen receptors, HER2, p27(Kip1), or cyclin D1, but do express p53 and cyclin E. In ...addition, the expression of cytokeratin 5/6 (CK5/6), indicating a basal epithelial phenotype, is frequent in BRCA1-related breast cancer. Here, in a series of 247 breast cancers, we demonstrate that CK5/6 expression was associated with nearly all of the features of BRCA1-related breast cancer and was also associated with a poor prognosis. In a parsimonious multivariable proportional hazards model, protein levels of cyclin E, p27(Kip1), p53, and the presence of glomeruloid microvascular proliferation all independently predicted outcome after breast cancer. In this model, only cyclin E and p27(Kip1) levels were independent predictors in lymph node-negative cancers, whereas glomeruloid microvascular proliferation and tumor size independently predicted outcome in node-positive disease. The molecular determinants of the basal epithelial phenotype encapsulate many of the key features of breast cancers occurring in germ-line BRCA1 mutation carriers and have independent prognostic value. Basal breast cancer deserves recognition as an important subtype of breast cancer.
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