Search

Antibiotic treatments have detrimental effects on the microbiome and lead to antibiotic resistance. To develop a phage therapy against a diverse range of clinically relevant Escherichia coli, we screened a library of 162 wild-type (WT) phages, identifying eight phages with broad coverage of E. coli, complementary binding to bacterial surface receptors, and the capability to stably carry inserted cargo. Selected phages were engineered with tail fibers and CRISPR-Cas machinery to specifically target E. coli. We show that engineered phages target bacteria in biofilms, reduce the emergence of phage-tolerant E. coli and out-compete their ancestral WT phages in coculture experiments. A combination of the four most complementary bacteriophages, called SNIPR001, is well tolerated in both mouse models and minipigs and reduces E. coli load in the mouse gut better than its constituent components separately. SNIPR001 is in clinical development to selectively kill E. coli, which may cause fatal infections in hematological cancer patients., (© 2023. The Author(s).)

Background: Faecal microbiota transplantation (FMT) is effective for recurrent Clostridioides difficile infection (rCDI), but its effect varies inexplicably., Aims: To optimise the effectiveness of FMT for rCDI and validate determinants for effect METHODS: We conducted a cohort study, including all patients treated with FMT for rCDI between October 2018 and June 2020. Statistical process control was used to evaluate the impact of prospective quality improvement on the effect of single FMT treatments per 10-11 patients. Targeting an 80% effect, optimisations included changes to processing procedures, preparation and clinical application of FMT. The primary outcome was the resolution of Clostridioides difficile-associated diarrhoea at week 8. If CDI recurred, FMT was repeated. All patients were followed for 8 weeks after their latest FMT., Results: 183 patients with rCDI received 290 FMT treatments. A single FMT achieved resolution at week 8 in 127 (69%, 95% CI: 62%-76%), while repeated FMT cumulatively achieved resolution in 167/183 (91%, 95% CI: 86%-95%). The single FMT effect varied between 36% and 100% over time. In a mixed-effect model, patient age above 65 years, non-rCDI antibiotics at week 1 post-FMT, and donor were associated with effect. Neither increasing the dosages of faecal microbes nor standardising the processing improved outcomes., Conclusion: FMT has a high cumulative effectiveness in patients with rCDI following multiple administrations, but the single FMT effect is variable and may be optimised using statistical process control. Optimising FMT by considering patient age, post-FMT antibiotics, donor and multiple administrations may improve the treatment outcomes., Clinicaltrials: gov (Study identifier: NCT03712722)., (© 2023 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Background: Nutrition support teams (NST) may improve parenteral nutrition (PN) outcomes. No previous systematic review has provided conclusive data on catheter-related infection (CRI) occurrence after NST introduction, nor have previous studies performed meta-analysis or graded the evidence., Aims: To systematically evaluate the effects of implementing an NST for hospitalised adults on PN and compare these with standard care., Methods: This was a systematic review and meta-analysis, pre-registered in PROSPERO (CRD42020218094). On November 24, 2020, PubMed, Web of science, Scopus, Embase, Cochrane Library, and Clinical Key were searched. Clinical trials and observational studies with a standard care comparator were included. Primary outcome was relative reduction in CRI rate. A random-effects meta-analysis was used to estimate effects, and evidence was rated using Cochrane and GRADE methodologies., Results: Twenty-seven studies with 8166 patients were included. Across 10 studies, NST introduction reduced the CRI rate (IRR = 0.32, 95% CI: 0.19-0.53) with -8 (95% CI: -12 to -5) episodes per 1000 catheter days compared with standard care. Hypophosphataemia occurred less frequently (IRD = -12%, 95% CI: -24% to -1%) and 30-day mortality decreased (IRD = -6%, 95% CI: -11% to -1%). Inappropriate PN use decreased, both judged by indication (IRD = -18%, 95% CI: -28% to -9%) and duration (IRD = -21%, 95% CI: -33% to -9%). Evidence was rated very low to moderate., Conclusions: This study documents the clinical impact of introducing an NST, with moderate-grade evidence for the reduction of CRI occurrence compared with standard care. Further, NST introduction significantly reduced metabolic complications, mortality, and inappropriate PN use., (© 2021 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Background: Patients with intestinal failure (IF) are prone to hypophosphatemia and shifts in magnesium and potassium levels. Although these shifts are often attributed to refeeding syndrome (RFS), the incidence of electrolyte shifts among patients with IF is unknown. We evaluated the occurrence of hypophosphatemia and other electrolyte shifts according to the functional and pathophysiological IF classifications., Methods: We consecutively included all patients' first admission to an IF unit from 2013 to 2017. Electrolyte shifts were defined as severe hypophosphatemia <0.6 mmol/L (mM) or any 2 other shifts below reference range, comprising hypomagnesemia <0.75 mM, hypophosphatemia <0.8 mM, or hypokalemia <3.5 mM. Outcomes included length of stay, central line-associated bloodstream infection, and other infections. Mortality was evaluated 6 months after discharge., Results: Of 236 patients with IF, electrolyte shifts occurred in 99 (42%), and 127 (54%) of these patients received intravenous supplementation with either phosphate, magnesium, or potassium. In patients who started parenteral nutrition, up to 62% of early-onset shifts (<5 days) related to refeeding, and up to 63% of late-onset shifts (≥5 days) could be ascribed to infections. Derangements occurred in 7 (18%) with type 1 IF, 53 (43%) with type 2 IF, and 39 (53%) readmitted patients with type 3 IF. Of 133 patients with IF secondary to short-bowel syndrome, 65 (49%) developed shifts., Conclusion: In patients with IF, electrolyte shifts are frequent but not always due to RFS. Electrolyte shifts are common in patients with type 2 and those readmitted with type 3 IF., (© 2020 American Society for Parenteral and Enteral Nutrition.)

This study evaluates the potential circularity of PET, PE, and PP flows in Europe based on dynamic material flow analysis (MFA), considering product lifetimes, demand growth rates, and quality reductions of recycled plastic (downcycling). The circularity was evaluated on a baseline scenario, representing 2016 conditions, and on prospective scenarios representing key circularity enhancing initiatives, including (i) maintaining constant plastic consumption, (ii) managing waste plastic exports in the EU, (iii) design-for-recycling initiatives, (iv) improved collection, and (v) improved recovery and reprocessing. Low recycling rates ( RR , 13-20%) and dependence on virgin plastic, representing 85-90% of the annual plastic demand, were demonstrated after 50 years in the baseline. Limited improvements were related to the individual scenarios, insufficient to meet existing recycling targets. However, by combining initiatives, RRs above 55%, where 75-90% was recycled in a closed loop, were demonstrated. Moreover, 40-65% of the annual demand could potentially be covered by recycled plastic. Maintaining a constant plastic demand over time was crucial in order to reduce the absolute dependence on virgin plastic, which was not reflected by the RR . Thus, focusing strictly on RRs and even whether and to which extent virgin material is substituted, is insufficient for evaluating the transition toward circularity, which cannot be achieved by technology improvements alone-the demand must also be stabilized.

Background & Aims: Systemic sclerosis (SSc) commonly affects the gastrointestinal (GI) tract and predisposes to malnutrition. Few studies assessed body composition in outpatients with SSc or used more than one method for comparison over time. The aim of this study was to describe markers of nutrition and body composition in patients with SSc and to identify predictors of unintentional weight loss., Methods: We consecutively included outpatients with SSc and performed a one-year follow-up. Gastrointestinal (GI) involvement was evaluated from clinical investigations. Patients completed questionnaires for organ involvement and functional status. Clinical assessment included body mass index (BMI), the malnutrition universal screening tool (MUST), inter-incisor distance, anthropometry, and bio-electrical impedance analysis (BIA)., Results: In total, 168 consecutive patients with SSc were included, and 127 (76%) completed one-year follow-up. Thirteen (8%) died before follow-up. Based on MUST scores, 12% of patients were at high and 14% at medium risk of malnutrition. A low BMI was associated with small intestinal involvement (p < 0.0001). Percentage body fat correlated with BMI, both when using four-site anthropometry (r = 0.65, p < 0.01) and BIA (r = 0.49, p < 0.01). Nine (7%) patients had >5% unintentional weight loss at follow-up. Independent baseline predictors of unintentional weight loss included upper GI involvement and disease severity estimated by Health Assessment Questionnaire Disability Index score., Conclusions: Nutritional risk and GI involvement are frequent and closely correlated in patients with SSc. BIA and four-site anthropometry are comparable in the clinical assessment of patients with SSc. Unintentional weight loss is discrete and related to disease-specific characteristics., Competing Interests: Declaration of competing interest EH was funded by the Raynaud's and Scleroderma Association. All other authors declare no conflicts of interest., (Copyright © 2020 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Background: Faecal microbiota transplantation (FMT) is effective for recurrent Clostridioides difficile infection (CDI), but inconsistent effect rates and uncertain evidence levels have warranted caution. To clarify, we aimed to establish the evidence of FMT for recurrent CDI, updated across different delivery methods, treatment regimens, and in comparison with standard antibiotics., Methods: In this updated systematic review and meta-analysis, we searched PubMed, Scopus, Embase, Web of Science, Clinical Key, and Svemed+ for FMT literature published in English until November 11, 2019. We included observational and clinical trials with or without antibiotic comparators and excluded studies with below 8 weeks follow-up and fewer than 15 patients. The primary outcome was clinical outcome by week 8. We comprehensively extracted patient and procedural data. In a random-effects meta-analysis, we estimated the clinical effect for repeat or single FMT, different delivery methods, and versus antibiotics. We rated the evidence according to the Cochrane and GRADE methods. The PROSPERO preregistration number is CRD42020158112., Findings: Of 1816 studies assessed, 45 studies were included. The overall clinical effect week 8 following repeat FMT (24 studies, 1855 patients) was 91% (95% CI: 89-94%, I 2 =53%) and 84% (80-88%, I 2 =86%) following single FMT (43 studies, 2937 patients). Delivery by lower gastrointestinal endoscopy was superior to all other delivery methods, and repeat FMT significantly increased the treatment effect week 8 ( P <0·001). Compared with vancomycin, the number needed to treat (NNT) for repeat FMT was 1·5 (1·3-1·9, P <0·001) and 2.9 (1·5-37·1, P =0·03) for single FMT. Repeat FMT had high quality of evidence., Interpretation: High-quality evidence supports FMT is effective for recurrent CDI, but its effect varies with the delivery method and the number of administrations. The superior NNT for FMT compared with antibiotics suggests that patients may benefit from advancing FMT to all instances of recurrent CDI., Funding: Innovation Fund Denmark (j.no. 8056-00006B)., Competing Interests: BHM receives consultancy fees from Finch Therapeutics Group. All other authors declare no conflicts of interest., (© 2020 The Authors.)

Background: Intestinal failure (IF) is defined by a need for intravenous (IV) supplementation. Patients may present with multiple morbidities, and IV treatments carry a risk for catheter-related complications. Few studies described patient characteristics and clinical outcomes according to type of IF., Methods: We consecutively included patients who were admitted to a newly established inpatient IF unit (IFU) from 2013 through 2017. We evaluated patient characteristics and clinical outcomes of all patients' first admission. Outcomes included IF classification, length of stay, central line-associated blood stream infection (CLABSI), and discharge on home parenteral support (HPS). Follow-up was conducted six months after discharge for mortality and the continued need for HPS., Results: A total of 236 patients were evaluated, including 39 (17%) with type 1 IF, 123 (52%) with type 2 IF, and 74 (31%) with type 3 IF. Of 91 who had a central venous catheter (CVC) on admission, CLABSI was present in 11 (12%). The CLABSI occurrence during admission was 2 (1%) of 173 patients with a CVC. Mean length of stay declined from mean 33 days (95% confidence interval (CI): 26.2-42.5) in 2013 to 15 days (95% CI: 12.2-17.7) in 2017 (p < 0.0001). Undiagnosed comorbidity was revealed in 165 patients (70%) with unchanged frequency during the study period (p = 0.8). Sixty-seven (28%) patients were discharged with HPS., Conclusions: Inpatients with IF present with multiple morbidities. CLABSI should be investigated on admission. A low inpatient CLABSI rate may be achieved through the implementation of a specialised IFU., Competing Interests: Declaration of Competing Interest All the authors declared no conflict of interest., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Recycling of plastic is an important step towards circular economy. However, plastic from household waste (HHW) is a heterogeneous and contaminated resource, leading to recycled plastic with reduced quality, limiting the potential for closed-loop recycling. In addition to regulatory requirements for the chemical composition of recycled plastic, reduced physical and mechanical properties may limit the potential for closed-loop recycling. Consequently, this study analyses the thermal degradation, processability and mechanical properties of a range of reprocessed PET, PE and PP samples from source-separated plastic in HHW. On this basis, the potential for closed-loop recycling is evaluated. The study demonstrated that PET, PE and PP recycling represent different challenges. Potential degradation of the PET polymer can be reversed in a decontamination process, making PET waste well-suited for closed-loop, multiple times recycling, even when the degree of heterogeneity in the waste is high. The processability of different kinds of PE and PP packaging types varied considerably, especially for PP. Consequently, current recycling of mixed PP waste and even separate recycling of individual PP waste packaging types, will not technically facilitate recycling into new packaging products. This highlights the importance of PE and PP waste homogeneity when sent to reprocessing. Such homogeneity may be achieved through additional plastic sorting and regulatory harmonisation of product design, accounting for polymer properties and recyclability. Degradation of PP during recycling was shown to be substantial, representing another important limitation for PP recycling, necessary to address in the future., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Recycling of plastic from household waste (HHW) is crucial in the transition towards a circular plastic economy. Plastic from HHW consists of numerous immiscible polymers, product types and product designs (e.g. colour, polymer separability), which often lead to considerable physical losses during sorting, and low-quality recycled plastic. Consequently, recycling initiatives have been proposed to enhance the quantity and quality of plastic recycling from HHW. To quantify the potential effects of such initiatives, a detailed composition of plastic waste is necessary. The aim was to provide such detailed composition of Danish source-separated rigid plastic waste, including information regarding the polymer of the main product component, product type, polymer design and separability as well as colour. The potential effects on recycled quantity and quality from implementing selected recycling initiatives were quantified and recommendations provided. PET, PE and PP made up >90% of the source-separated plastic and both food- and non-food packaging existed in all three polymers. In total, 10-11% of the plastic was black, and around 44% consisted of multiple polymers, of which one-third was non-separable. Initiatives improving product design for recycling will likely result in increased quantity of recycled plastic. By effectively separating food from non-food packaging, e.g. by introducing two bins in the households or politically aligning polymers and product types (all food packaging in PET and PP, all non-food packaging in PE), 39-63% of the waste could potentially be recycled in a closed loop into food-grade quality packaging. The overall highest benefits were reached by combining initiatives., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The global consumption of plastic continues to increase, and plastic recycling is highlighted as crucial for saving fossil resources and closing material loops. Plastic can be made from different polymers and contains a variety of substances, added intentionally to enhance the plastic's properties (metals added as fillers, colourants, etc.). Moreover, plastic can be contaminated during use and subsequent waste management. Consequently, if substances and contaminants are not removed during recycling, potentially problematic substances might be recycled with the targeted polymers, hence the need for quantitative data about the nature and presence of these substances in plastic. Samples of selected polymers (PET, PE, PP, PS) were collected from different origins; plastic household waste, flakes/pellets of reprocessed plastic from households and industry, and virgin plastic. Fifteen selected metals (Al, As, Cd, Co, Cr, Cu, Fe, Hg, Li, Mn, Ni, Pb, Sb, Ti, Zn) were quantified and the statistical analysis showed that both the polymer and origin influenced the metal concentration. Sb and Zn were potentially related to the production stage of PET and PS, respectively. Household plastic samples (waste and reprocessed) were found to contain significantly higher Al, Pb, Ti and Zn concentrations when compared to virgin samples. Only the concentration of Mn was reduced during washing, suggesting that parts of it was present as physical contamination. While most of the metals were below legal limit values, elevated concentrations in reprocessed plastic from households, aligned with increasing recycling rates, may lead to higher metal concentrations in the future., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The current waste management system, handling around 500,000 t of household, commercial, and institutional waste annually in the Irkutsk region, Siberia, is based on landfilling in an old landfill with no controls of leachate and gas. Life-cycle assessment modelling of the current system shows that it is a major load on the environment, while the simulation of seven alternative systems results in large savings in many impact categories. With respect to climate change, it is estimated that a saving of about 1200 kg CO 2 equivalents is possible per year, per inhabitant, which is a significant reduction in greenhouse gas emissions. The best alternatives involve efficient energy recovery from waste and recycling by source separation for commercial and institutional waste, the major waste type in the Irkutsk region. Recycling of household waste seems less attractive, and it is therefore recommended only to consider this option after experience has been gained with the commercial and institutional waste. Sensitivity analysis shows that recovery of energy - in particular electricity, heat, and steam - from waste is crucial to the environmental performance of the waste management system. This relates to the efficiencies of energy recovery as well as what the recovered energy substitutes, that is, the 'dirtier' the off-set energy, the higher the environmental savings for the waste management system. Since recovered energy may be utilised by only a few energy grids or industrial users, it is recommended to perform additional local assessments of the integration of the waste energy into existing systems and facilities.

Plastics recycling has the potential to substitute virgin plastics partially as a source of raw materials in plastic product manufacturing. Plastic as a material may contain a variety of chemicals, some potentially hazardous. Phthalates, for instance, are a group of chemicals produced in large volumes and are commonly used as plasticisers in plastics manufacturing. Potential impacts on human health require restricted use in selected applications and a need for the closer monitoring of potential sources of human exposure. Although the presence of phthalates in a variety of plastics has been recognised, the influence of plastic recycling on phthalate content has been hypothesised but not well documented. In the present work we analysed selected phthalates (DMP, DEP, DPP, DiBP, DBP, BBzP, DEHP, DCHP and DnOP) in samples of waste plastics as well as recycled and virgin plastics. DBP, DiBP and DEHP had the highest frequency of detection in the samples analysed, with 360μg/g, 460μg/g and 2700μg/g as the maximum measured concentrations, respectively. Among other, statistical analysis of the analytical results suggested that phthalates were potentially added in the later stages of plastic product manufacturing (labelling, gluing, etc.) and were not removed following recycling of household waste plastics. Furthermore, DEHP was identified as a potential indicator for phthalate contamination of plastics. Close monitoring of plastics intended for phthalates-sensitive applications is recommended if recycled plastics are to be used as raw material in production., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

To supplement the traditional ICHD-2 diagnosis for migraine with aura (MA) we developed a diagnostic scale for migraine aura that quantifies the importance of the cardinal characteristics of MA. Since more than 99% of MA patients have visual aura, we developed for simplicity a Visual Aura Rating Scale (VARS). In total 427 patients with MA (ICHD-2) or nonaura visual disturbances were diagnosed in a validated semistructured interview by a trained physician. The patients were separated into a derivation sample and a validation sample. By regression analysis we identified the visual aura characteristics associated with MA in the derivation sample. Based on the identified characteristics we developed VARS and derived a predictive VARS score which was tested in the validation sample. The VARS score is the weighted sum of the presence of five visual symptom characteristics: duration 5-60 min (3 points), develops gradually > or = 5 min (2 points), scotoma (2 points), zig-zag lines (2 points), and unilateral (1 point). The maximum score is 10 points. A VARS score of 5 or more diagnosed MA with a sensitivity of 96% (95% CI 92-99%) and a specificity of 98%(95% CI 95-100%) in the derivation sample, and a sensitivity of 91% (95% CI 86-95%) and a specificity of 96% (95% CI 91-100%) in the validation sample. VARS adds evidence based weights to a number of clearly specified characteristics; it is easy to learn, apply and teach and may therefore be a valuable addition to traditional ICHD-2 diagnosis.

Objectives: Since 1998, migraine with aura (MA) has been diagnosed according to the operational diagnostic criteria of the International Headache Society (ICHD-1). Here we present the data underlying the new criteria for MA in the ICHD-2 classification., Methods: Sensitivity of the new criteria was tested in patients with MA and specificity in patients with reversible non-aura visual disturbances. The diagnoses in both groups of patients were made in a validated semistructured physician-conducted interview. We tested five sets of criteria for sensitivity and specificity comparing with the diagnosis according to the ICHD-1 in 200 patients and the selected set of criteria in 274 additional patients., Results: Four sets of criteria had sensitivity/specificity of 46%/100%, 71%/100%, 62%/95%, and 99%/76%. Sensitivity of the selected set of criteria was 84% (95% CI 79% to 90%) and specificity 97% (95% CI 95% to 99%). According to these criteria at least two of the following should be fulfilled: homonymous visual or unilateral sensory symptoms; at least one aura symptom develops gradually over > or =5 minutes and/or different symptoms occur in succession over > or =5 minutes; each symptom lasts > or =5 and < or =60 minutes. In the additional sample sensitivity of the selected criteria was 90% (95% CI 86% to 94%) and specificity 96% (95% CI 91% to 100%)., Conclusions: The diagnostic criteria for MA selected for ICHD-2 had high sensitivity and specificity. The ICHD-2 criteria are more operational and probably delineate a more homogeneous sample of patients than the ICHD-1. The ICHD-2 for MA is intended equally for research and clinical practice and can be used at different levels of specialisation.

The present study is a 16-year follow-up study assessing the long-term outcome of migraine with aura (MA). Additionally possible predictive factors in the prognosis of MA were evaluated. Patients were recruited from the files of Danish headache clinics. A total of 53 patients (11M:42F) with MA (IHS criteria) participated in a follow-up interview. At follow-up attacks had ceased (no MA for 2 years) in 36% of patients. Attacks had ceased in 55% of males and 31% of females (P = 0.17). Attacks had ceased in 41% of patients with visual aura without other aura symptoms and in 25% of those with sensory or aphasic aura besides their visual aura (P = 0.36). Among those with attacks of MA at follow-up frequency of attacks and headache intensity was improved in 44% and 41% of the patients, respectively. The results point to a favourable evolution of MA and suggest possible predictive factors.

In order to better understand sporadic hemiplegic migraine (SHM) and particularly its relation to familial hemiplegic migraine (FHM), migraine without aura (MO) and typical migraine with aura (typical MA), we investigated the occurrence of MO and typical MA among probands with SHM and their first-degree relatives. The pattern of familial aggregation of MO and typical MA was assessed by population relative risk calculations. A total of 105 SHM probands and 483 first-degree relatives were identified in the Danish population. Compared with the general population, SHM probands had no increased risk of MO, but a highly increased risk of typical MA. First-degree relatives of all SHM probands had an increased risk of both MO and typical MA, whereas first-degree relatives of probands with exclusively SHM had no increased risk of MO but an increased risk of typical MA. Our data suggest that SHM is a genetically heterogeneous disorder.