Borrelia bacteria and their transfer to humans, thus causing Lyme disease. It is a unique advantage that the progress of an antibiotic therapy can be examined until the emission of hydrogen is finished. The described technique cannot identify the related bacteria but enables bacterial contamination by hydrogen emitting anaerobes to be recognized. The samples are incubated with the proper culture broth in closed septum vials which remain closed during the whole process. The personnel in the lab never come into contact with pathogens and thus safety regulations are guaranteed.A novel straightforward analytical technique was developed to monitor the emission of hydrogen from anaerobic bacteria cultured in sealed headspace vials using a specific hydrogen sensor. The results were compared with headspace gas chromatography carried out in parallel. This technique was also applied to investigate the efficacy of chemical antibiotics and of natural compounds with antimicrobial properties. Antibiotics added to the sample cultures are apparently effective if the emission of hydrogen is suppressed, or if not, are either ineffective or the related bacteria are even resistant. The sensor approach was applied to prove bacterial contamination in food, animals, medical specimens and in ticks infected by  Although the single analysis of emitted H2 is not sufficient to identify the relevant bacterium on the genus or species level, it can classify its type: obligate anaerobes emit hydrogen together with a mixture of VOCs, but need an oxygen free condition which can be achieved by replacing the ambient air in the vial by flushing with nitrogen. As such, a headspace vial under nitrogen is thus used as a mini-anaerobic chamber in which the bacteria can thrive. Obligate aerobes generate carbon dioxide and water, but no hydrogen, and the emission of CO2 with the lack of hydrogen indicates the presence of such an obligate aerobe. Facultative anaerobes emit H2 and CO2 and some organic compounds, e.g., ethanol. The proof of emitted H2, therefore, was taken in this work to recognize bacterial contamination in food and medical specimens and can be applied particularly to screening applications without the ambition to identify the relevant bacteria which may then be performed subsequently with proven methods. Such an application by HS-GC for proving bacterial contamination in vegetables, animal food and medical specimens has been described [Borrelia and their transfer to humans causing Lyme disease [2 as the leading volatile emission for all of the anaerobic bacteria that are responsible for the bacterial contamination. The proof of H2 comprises all anaerobes: obligate anaerobic, facultative anaerobic and microaerophilic bacteria. The potential of the new sensor approach is presented in this work by comparing it with the result of the HS-GC analysis carried out in parallel.Infections by pathogenic microbes are a growing threat to public healthcare today. Bacterial infections of humans may be caused by contaminated food of animal or vegetable origin, by contact with infected animals or through the bite of an insect. Bacteria emit volatile compounds which can be analyzed by various techniques of gas analysis, preferably gas chromatography. Bacteria specimens are usually cultured by the common plate-based assays technique. The analysis of emitted volatiles requires closed containers, however, and the technique of static headspace gas chromatography (HS-GC) is therefore the preferred technique since the samples are cultured in closed crimp capped headspace vials. This technique was originally applied in 1965 for examining the growth of bacteria in milk . The uni disease  has been disease . In this2 sensor approach described in this study is the proof of bacterial infection in ticks, and the following diagnosis and therapy of the resulting tick-borne Lyme disease of an infected individual. Again, the H2 sensor approach does not enable the identification of a single species, such as the responsible Borrelia burgdorferi and the various Borrelia species and subspecies, but has the advantage that the H2 response comprises the whole complex of co-infection by microbes with similar pathogenic characteristics, because Lyme disease is always associated with multiple microbes [Borreliella [Borrelia+. The list of possible coinfections includes Chlamydia, Bartonella, Mycoplasma, Babesia, Anaplasma, Ehrlichia, Rickettsia and several more. These co-infections have important clinical, diagnostic, and therapeutic implications since co-infected humans tend to display a more severe manifestation of Lyme disease. The proof of H2 therefore enables a broad range of diagnosis and therapy of the most important known or putative tick-borne pathogens, not only in vitro but more importantly even in the blood of an infected patient. Such an in vivo diagnosis is also presented in this article. Here, it is important to note that not only can bacterial infection be recognized by the H2 sensor approach but, moreover, the effect of antibiotics against the responsible microbes, if added to the samples in the vials, is also detected. Antimicrobial resistance is a serious and current issue in medicine. Infections caused by pathogenic microbes are a growing threat to public healthcare today if treated by an ineffective therapy due to resistance against antibiotics [2 approach to prove bacterial contamination in food, in animals and medical specimens, and to test the efficacy of natural and chemical antibiotics.Another application of the Hmicrobes . The comreliella ,10, but reliella  this comibiotics . For thi2 consumption and CO2 generation, but move to fermentation with H2 emission due to declining O2 concentration in the vial, and a CO2 peak at the end of the chromatograms is thus generated. Such a negative CO2 peak may also be generated by aerobes in the sample, since obligate aerobes produce CO2 and water, and O2 from the air in the headspace is thus transferred to CO2. The headspace gas therefore is enriched with nitrogen and due to the lower heat conductivity, compared with the carrier gas, the air causes the small negative peak at the rear of the positive H2 peak. An additional source of such a negative CO2 peak is caused by blood samples in the headspace vials because blood is still active and converts the oxygen of the air in the vials to CO2. These negative CO2 peaks are therefore not unambiguously significant for bacterial activity contrary to H2, which is used here as the leading compound for all active anaerobic bacteria. The negative peak from the O2 deficit is often hidden beneath the hydrogen peak with the Silicagel column while a column with Chromosorb 102 separates it better but has a longer retention time for CO2. Both column types are used for the various examples presented here. Since the gas chromatography (GC) columns with the cheap GC student instrument are operated always at varying room temperatures the retention times of the peaks may vary slightly too  from the fingertip was sucked into a sterile cotton ball from a cotton bud in such a way that the cotton ball did not come into contact with the skin. The blood-soaked cotton ball was then inserted into the sterile culture broth in the vial which was closed immediately by a crimp closure. Blood samples were collected exclusively from the author B.K. and from member of his family. All subjects gave their consent before they participated in this study.The samples are placed into headspace vials, which are then sealed by a crimp closure. The 6 mL vials already contain 2.5 mL of sterile culture broth. Solid samples are cut into small pieces. The ball of cotton wool taken from the cotton bud used to collect a blood or smear sample is also inserted into the liquid culture broth. 2 peak can be obtained [2 sensor. The presence of H2 is indicated with that particular sensor by a red light, though in addition to this optical response, the electrical signal can also be traced by measuring the voltage output (mV). Several chemical and natural antibiotics were tested and a few milligrams of solid antibiotics are added to the culture broth or one microliter for liquid antibiotics. In the following examples, the GC analysis is compared with the response from the H2 sensor and the result is included in the chromatograms either by the positive (+) or the missing (−) H2 red light response.Bulky samples, such as the salad samples cf. a, were pobtained . Some baHydrogen released from bacteria was analyzed by a specific hydrogen sensor and the results compared with those from static HS-GC. The procedure is shown in Salmonella bacteria, generated by the wet juice from the chopped salad and this apparently was also the case here as shown by the H2 peak in the chromatogram. The H2 sensor confirmed this result by the red light and also by measuring the voltage output of 230 mV. The other salad sample, no. 2 in 2 peak in the chromatogram nor a sensor signal. The two negative peaks of CO2 in this chromatogram apparently are generated by obligate aerobes. The determination of obligate anaerobes is shown in Clostridia, Escherichia coli. Small pieces from the feces from a cat were cultivated in the culture medium in 6 mL headspace vials and the air was replaced by flushing with nitrogen to provide the necessary oxygen-free gas phase. The resulting H2 peak in the chromatogram no. 1 corresponded with the positive sensor signal (+). This example shows also the possibility to test the efficacy of antibiotics. A few milligrams of added amoxicillin to the charged vial had no effect, as shown by the same H2 peak (no. 2) and the positive H2 sensor signal (+), while a small droplet from the oil of the clove apparently killed the anaerobes (no. 3), as shown by the missing H2 peak and the negative sensor signal (−). Oil of cloves was already found as a very effective natural antibiotic [2 by obligate anaerobes due to the presence of oxygen (no. 4).tibiotic ,12. Norm2 peak and also by aerobes by the CO2 peak. The addition of penicillin . A freshly caught trout from a clean river generated no H2 emission and was thus not contaminated by anaerobes, but still contained some aerobes as shown by the CO2 peak (no. 2). The chromatogram from the blank sample (no. 3) showed neither H2 nor CO2 peaks.Food poisoning can occur when disease-causing bacteria spread to food and are consumed. Food producing animals from fish and poultry farming are often contaminated by microbes and are therefore treated by antibiotics, but an excess application can cause antibacterial resistance. There is serious concern regarding the increasing number of multi-resistant chemical antibiotics, and the search for natural antibiotics as an alternative to chemical antibiotics is of increasing interest. Two such examples are shown in no. 2 in a to the no. 3 in a has era. Salmon b from an2 emission compared with the fresh quality (no. 1). The example in The next example in Borrelia burgdorferi and its subspecies but can also carry further co-infected pathogens with similar characteristics. Emitted H2 is the common metabolite from this tick-borne mixture comprising all facultative anaerobic subspecies and similar pathogens. Such a single guarding compound simplifies diagnosis and the search for a suitable therapy. However, not all ticks in an infected area are contaminated, therefore, after a tick bite the removed tick should be tested prior to medical treatment. The chromatograms in 2 peak from the infected tick (no. 1) corresponds with the positive sensor signal (+) and also the missing H2 peak (no. 2) with the negative sensor signal (−).People may not only be infected by food-borne microorganisms, but also through contact with animals carrying pathogenic parasites. People who spend time in grassy and wooded environments are at an increased risk of exposure to catching ticks which can cause Lyme disease. Ticks are not only contaminated by Borrelia sensu lato. However, even after 3 weeks treatment the patient still complained about typical pains and a blood sample analyzed now by the HS-GC technique shows in fact still a remarkable H2 peak (no. 1 in +) present. The doxycyclin therapy, with a daily dose of 200 mg, apparently was not sufficient since most experts recommend at least 400 mg/day. Since the patient could not endure this antibiotic, the therapy was continued by a daily dose of 900 mg garlic powder from garlic capsules. After 4 weeks treatment, the blood no longer developed H2  and oil of cloves (Eugenia caryophyllus) have emerged as universally applicable natural antibiotics [A new method is presented to prove bacterial infection in food, animals and humans using the emission of hydrogen. Bacterial contamination was detected in food  and in the meat of animals . Food, particularly offered in supermarkets, is often contaminated by microbes and requires careful control to protect the consumers from food-borne diseases. The Hibiotics ,7 and twBorrelia+ in infected ticks and in the blood of patients suffering from tick-borne Lyme disease. The antibacterial effect of garlic had already been found by Louis Pasteur and also described in detail [Borrelia burgdorferi together with many other essential oils [Borrelia bacteria in ticks and their transfer to the blood of a bitten human causing Lyme disease is of particular interest, since Lyme disease is a potentially fatal illness spread through the bite of ticks that carry infected bacteria, predominantly Borrelia species, including Borrelia burgdorferi and transmitted to the bloodstream of humans. This tick-borne illness comprises serious health effects such as joint malfunctions and neurological or cardiac disorders and many others. If, in its early stages, pathological skin lesions (namely erythema migrans) appear, such an infection is obvious, but often these lesions are not visible and so the infection is therefore ignored with fatal consequences. Even if the erythema migrans appears late, sometimes after weeks or months, this may be too late to start an effective therapy because Lyme disease patients can be cured successfully only in the early stage of infection with the common 2–4 weeks antibiotic treatment. If, however, an infection is not recognized due to missing skin lesions, Lyme disease progresses, and the patient continues to suffer from chronic symptoms described as post-treatment Lyme disease syndrome and this persistent borreliosis is no longer accessible by the common antibiotics. It is therefore important to start the antibiotic therapy in due time and this requires a reliable diagnosis as soon as possible after a tick bite. The available techniques of diagnosis, such as ELISA and Western Blot are not always sufficiently reliable to make a definite diagnosis. This is because these serological assays are indirect tests since they measure an antibody’s response to the infection, not the infection itself, and these need 2 to 6 weeks after infection while the efficacy of antibiotic treatment declines already after 4 weeks [2 sensor technique. The emission of H2 from an infected blood sample is a direct proof of the bacterial infection. As Lyme disease is always associated with the complex mixture of co-infections, it is particularly interesting for a patient that monitoring the H2 emission allows the progress of a suitable therapy to be controlled until those pathogenic microbes are eradicated altogether, as indicated by the disappearance of the H2 signal. Finally, a patient is less interested in knowing the exact composition of the responsible pathogenic mixture, if an efficient therapy eradicates them all, together with the accompanying pain. However, a natural compound with a biocide property found by an in vitro test of a blood sample in a headspace vial may not necessarily be as effective if administered in vivo to a patient suffering from borreliosis, since such an in vivo trial is hardly to be executed as a patient will certainly prefer to rely on proven chemical antibiotics, e.g., doxcycyclin rather than to act as an experimental volunteer for suspected antibiotics. Despite this problem, such an in vivo result is presented in this work, where garlic was found to be effective in curing Lyme disease even after an insufficient doxycyclin therapy.The other antibiotic favorite was garlic, administered as capsules for this study, which are more convenient and above all less unpleasant than rough garlic . Garlic n detail . The Swen detail . The oilial oils ,16. The  4 weeks . All dia 4 weeks . Moreove2 approach has the unique advantage that the whole procedure is carried out in hermetically closed vials, starting with sample preparation. When the samples are inserted into the culture broth, the headspace vials are capped with PTFE-lined septa and sealed with a crimped closure. The septum remains tight and several gas samples can be analyzed at given time intervals, thus enabling kinetic measurements. After analysis, the closed vials with their contents can be sterilized at the necessary high temperature and then safely discarded. Thus, the personnel in a lab never come into contact with the pathogens. Both techniques, HS-GC and the H2 sensor approach, may have different advantages and applications. HS-GC can be carried out with commercially available automated instruments and, thus, up to 100 samples can be processed unattended. It is therefore ideal for a broad range of screening purposes. The H2 sensor approach on the other hand is a simple technique and since such a H2 sensor is a very cheap device it is feasible that the necessary analyses to determine Lyme disease, including controlling the progress of a therapy, may be carried out in the office of a physician or even in a pharmacy since no strict safety requirements are afforded.The H2 sensor approach are perfectly suited for quantitative analysis since the resulting peak area of an HS-GC analysis and the electrical output (mV) of an H2 sensor lend themselves to computer calculation. The real problem for quantitative determination, however, is the preparation of certified calibration standards and this aspect needs further research efforts. Finally, it should be admitted that all examples presented in this article should only be taken as suggestions to encourage more detailed research in the future, specifically to evaluate the proposed method of H2 emission, because our research project is finished now and we have no further possibility to continue.Both techniques of HS-GC and the HGas chromatograph GC-AK 11, Aug. Hedinger GmbH & Co KG, Stuttgart, Germany; GC-columns: 0.8 m × 6 mm polyamide tube, packed with Silicagel 60/80 mesh and 0.8 m × 6 mm polyamide tube, packed with Chromosorb 102, 60/80 mesh. Headspace vials: 6 mL and 20 mL crimp-capped with PTFE-laminated butyl rubber septa from PerkinElmer LAS (Germany) GmbH, Rodgau, Germany. Culture broth: CASO-Bouillon, Merck Life Science GmbH, Darmstadt, Germany; vendor: Mibius e.K. Düsseldorf, Germany, tryptic soy broth acc EP+USP 3080r-20p; composition: pancreatic digest of casein, 17 g; papaic digest of soya bean meal, 3 g; sodium chloride, 5 g; dipotassium hydrogen phosphate, 2.5 g; glucose monohydrate. Garlic capsules with pulverized garlic, 500 mg/tablet, 1 mg Allicin, Hirundo Products, FL-9493 Mauren. Hydrogen sensor: Keyes MQ-8 Hydrogen gas sensor, Modul KS-046, fluxworkshop, purchased from eBay.


Elderly patients discharged from hospital experience fragmented care, repeated and lengthy emergency department (ED) visits, relapse into their earlier condition, and rapid cognitive and functional decline. The Acute Care for Elders (ACE) program at Mount Sinai Hospital in Toronto, Canada uses innovative strategies, such as transition coaches, to improve the care transition experiences of frail elderly patients. The ACE program reduced the lengths of hospital stay and readmission for elderly patients, increased patient satisfaction, and saved the health care system over Can $4.2 million (US $2.6 million) in 2014. In 2016, a context-adapted ACE program was implemented at one hospital in the Centre intégré de santé et de services sociaux de Chaudière-Appalaches (CISSS-CA) with a focus on improving transitions between hospitals and the community. The quality improvement project used an intervention strategy based on iterative user-centered design prototyping and a “Wiki-suite” (free web-based database containing evidence-based knowledge tools) to engage multiple stakeholders.The objectives of this study are to (1) implement a context-adapted CISSS-CA ACE program in four hospitals in the CISSS-CA and measure its impact on patient-, caregiver-, clinical-, and hospital-level outcomes; (2) identify underlying mechanisms by which our context-adapted CISSS-CA ACE program improves care transitions for the elderly; and (3) identify underlying mechanisms by which the Wiki-suite contributes to context-adaptation and local uptake of knowledge tools.Objective 1 will involve staggered implementation of the context-adapted CISSS-CA ACE program across the four CISSS-CA sites and interrupted time series to measure the impact on hospital-, patient-, and caregiver-level outcomes. Objectives 2 and 3 will involve a parallel mixed-methods process evaluation study to understand the mechanisms by which our context-adapted CISSS-CA ACE program improves care transitions for the elderly and by which our Wiki-suite contributes to adaptation, implementation, and scaling up of geriatric knowledge tools.Data collection started in January 2019. As of January 2020, we enrolled 1635 patients and 529 caregivers from the four participating hospitals. Data collection is projected to be completed in January 2022. Data analysis has not yet begun. Results are expected to be published in 2022. Expected results will be presented to different key internal stakeholders to better support the effort and resources deployed in the transition of seniors. Through key interventions focused on seniors, we are expecting to increase patient satisfaction and quality of care and reduce readmission and ED revisit.This study will provide evidence on effective knowledge translation strategies to adapt best practices to the local context in the transition of care for elderly people. The knowledge generated through this project will support future scale-up of the ACE program and our wiki methodology in other settings in Canada.ClinicalTrials.gov NCT04093245; https://clinicaltrials.gov/ct2/show/NCT04093245.DERR1-10.2196/17363 In 2019, more than one in six Canadians were aged 65 years or older. These aging Canadians will account for 20% of the population by 2024 -7. SenioImproving care transitions for seniors requires a multifaceted integrated approach based upon best practices ,38, suchUnfortunately, the ACE best practice guidelines have only been implemented in a few dozen acute care organizations around the world . A majorCentre intégré de santé et de services sociaux de Chaudière-Appalaches (CISSS-CA) was selected by the Canadian Foundation for Healthcare Improvement (CFHI), the Canadian Frailty Network, and Mount Sinai Hospital to implement and adapt the ACE program in the local context. This adaptation also had to be performed in synergy with Quebec’s provincial elder-friendly best practices, the Approche adaptée à la personne âgée en milieu hospitalier  ) to engage knowledge users in adapting the ACE program in the local context at the Hôtel-Dieu de Lévis, one of the four acute care hospitals within the CISSS-CA. WikiTrauma  is a knoThe goal of this study is to improve transition care for seniors within the CISSS-CA. Specifically, it aims to (1) implement a context-adapted CISSS-CA ACE program in its four EDs and measure the impact on patient-, caregiver-, clinical-, and hospital-level outcomes; (2) identify underlying mechanisms by which our context-adapted CISSS-CA ACE program improves care transitions for elderly people; and (3) identify underlying mechanisms by which the Wiki-suite contributes to context adaptation and local uptake of knowledge tools.Our study will have two main parts . Part 1 2)  tool)  tool) ; (2) a g7] tool) ; (4) com7] tool) ,79  , will beIn parallel with these interventions, we will also offer audit and feedback for health professionals and decision-makers in order to support organizational learning that will allow for real-time adjustment of interventions that are implemented. Feedback will take the form of monthly newsletters for the CISSS-CA covering patient-, clinician-, and hospital-level quality indicators. Moreover, our research team will be embedded within the CISSS-CA elder-friendly hospital committee, which plays an active role in supporting quality improvement initiatives and program implementation. This will ensure that results generated by our research team will benefit our population and ensure timely integrated knowledge translation.Results from the centers will be compared with their own results in the preintervention period using data collected for the ITS study.Our primary outcome will be a hospital-level composite outcome of 30-day hospital readmission and ED visit rate. Our secondary outcomes will be hospital-, clinical-, and patient- or caregiver-level outcomes .Régie de l’assurance maladie du Québec (RAMQ) physician billing database and Maintenance et exploitation des données pour l'étude de la clientèle hospitalière (Med-ECHO) database  in addition to databases available at the INESSS in order to identify all public health services used prior to and after the implementation of the CISSS-CA ACE program.Hospital administrative databases  will be used to calculate monthly hospital-level outcomes. Monthly data will then be analyzed to form points in time. Data will be extracted from the Patient and caregiver baseline sociodemographic data will include age, sex, race, language, education level, family income, prehospital living situation , geography of residence , andIn order to measure the change in care processes, we will measure process outcomes such as the proportion of patients seen by the GEM nurse, proportion of patients having a medication reconciliation list, and proportion of patients receiving telemonitoring services .After receiving ethics approval, we will start recruitment for our patient-level outcomes at least 3 months before the implementation of phase 1A at each site. Due to the pragmatic nature of our study, some sites will have longer periods of patient-level outcomes collected before phase 1A than others. Patient recruitment will continue throughout our study and up to a maximum of 24 months after the intervention. We will recruit consecutive eligible ED patients aged 65 years or older, as well as one caregiver whenever possible. We will recruit 38 patients or caregivers per month for each of the four hospitals based on a precision estimate of the CTM-3 measured for the study point of each month.With authorization from the Director of Nursing and the Professional Services Director, a member of our embedded research team will contact by telephone a randomly selected daily sample of patients who visited the ED in the last 24 hours and up to a maximum of 7 days after their ED visit. This research assistant will administer the CTM-3 questionnaire to patients for quality improvement purposes. The research assistant will then ask the patients if they agree to be contacted a second time by a member of the research team to answer additional questions for the purpose of our study. Consenting patients will then be contacted within 7 days to obtain their verbal consent to participate in the study and consent to access their medical charts. We will ensure patients’ understanding by asking them to summarize in their own words the objectives of the study and what their participation involves using the Nova Scotia criteria . The teaWe will use segmented regression statistics to measure the changes in the level and slope in the postintervention period compared with the preintervention period in each center for each of our primary and secondary outcomes . Thus, wWe have calculated the sample size for our patient cohort, which will be based on the smallest clinically significant difference  that the CTM-3 can capture on a maximum score of 100. To detect a difference of 11% with a type I error of 5% and a type II error of 20%, 38 patients per month are needed to calculate a monthly CTM-3 estimate, based on a previous study in which CTM-3 was measured in 21 patients at Hôtel-Dieu Hospital in Lévis and showed an average of 75% and a standard deviation of 23%. Considering a call rejection rate of 70%, the number of people to be contacted in total will be 127 patients per month for each ED. We will therefore contact 5 patients per day in each of the four participating centers to obtain our targeted sample size of 38 patients at the end of the month. To ensure the creation of a random and representative sample of our population of elderly patients being discharged from the ED, a randomization table based on all patients discharged in the previous 24 hours from the ED will be provided every day to select which patients to call.Part II aims to identify the underlying mechanisms  by which our context-adapted CISSS-CA ACE intervention improves care transitions for elderly people and, more specifically, how the Wiki-suite contributes to context-adaptation and local uptake of knowledge tools. Contextual elements affecting the implementation of the ACE program at the four hospital sites and use of our Wiki-suite cannot be addressed using ITS methodology, yet they can have a relevant impact on the use . To scalAlongside phases IB and IC, we will conduct a theory-based process evaluation. All Wiki101 participants will be invited to answer a validated Theory of Planned Behavior questionnaire  at baselWe will conduct at least 32 45-minute individual interviews with purposefully selected key informants  to identify the contextual elements influencing the successful (or failed) implementation of the ACE program for improving care transitions and understand how our Wiki-suite facilitated this. These interviews will take place at least 9 months after first implementing the ACE program at each hospital. A pool of eligible health professionals working in the ED and administrators or decision makers will be created by direct solicitation during departmental or staff meetings (upon invitation from department chiefs) or by direct solicitation by department chiefs. Our study’s goals and procedures will be briefly explained, including eventual solicitation to participate in individual interviews. All eligible and consenting individuals will be asked to provide their contact information for eventual solicitation. Participants will be identified from the pool described above, using purposeful sampling, with an emphasis on maximum variation to obtain a wide range of different points of view and opinions. Each selected individual will be solicited via the contact information provided at initial solicitation. A consent form will be completed over the internet prior to the phone interview. These interviews will be confidential, and no information allowing the identification of individuals will be provided to the administration of the CISSS-CA.A PhD student guided by experienced qualitative researchers will perform the interviews and process evaluation of our intervention. For this analysis, we will perform a mixed inductive and deductive qualitative content analysis of the verbatim transcripts and field notes taken during these interviews, as well as key implementation project documents such as executive committee and local team meeting minutes ,96. The We will also use the National Health Service (NHS) Sustainability Model to guide our process evaluation analysis . The NHSWe will analyze the impact of our intervention within the context of Quebec’s health reform aiming at better integration of care within the health system . This wiThis study was funded by the Canadian Institutes for Health Research in May 2017. The project was approved by the CISSS-CA ethics committee in May 2018. Data collection started in January 2019. As of January 2020, we enrolled 1635 patients and 529 caregivers from the four participating hospitals. Data collection is projected to be completed in January 2022. Data analysis has not yet begun. Results are expected to be published in 2022. Expected results will be presented to different key internal stakeholders to better support efforts and resources deployed in the transitions of seniors. Through key interventions focused on seniors, we are expecting to increase patient satisfaction and quality of care and reduce readmission and ED revisit.Our study will produce a new partnership among patients, clinicians, and decision makers, engaging and empowering them to improve care for elderly people by implementing the CISSS-CA ACE program in four hospitals within the CISSS-CA. This study will also provide qualitative and quantitative evidence on effective strategies for improved transition care for elderly people. This study specifically aims at decreasing CISSS-CA’s 30-day rate of readmission for elderly patients, which has been increasing since 2014 (13% in 2014 and 16% in 2016), and its high 30-day ED visit rate (21% in 2014 and 22% in 2016). Our team will generate real-time quality improvement data that will guide decision-making by the CISSS-CA and help adjust resource allocation and policy-making that will positively influence future care transitions for elderly people.Our study will also identify the human, organizational, and technical factors that support the local adaptation of knowledge and the scale-up of our intervention in other care settings within the CISSS-CA and elsewhere in Canada ,102. ThiOur study is measuring the impact of a complex intervention, which is a common problem in health services research. The ability to measure and evaluate the effect of complex interventions remains underdeveloped -106. TheAnother challenge to complex interventions is the lack of local adoption. In the design of our intervention, we have incorporated best practices from the field of implementation science to design a standardized intervention comprising local barrier identification , multidiThis study will provide much needed evidence on effective KT strategies to adapt best practices to the local context in the transition of care for elderly people. It will contribute to adapting geriatric knowledge to the local context. The knowledge generated through this study will support future scale-up of ACE programs and our Wiki methodology in other settings in Canada.


The specimens will be derived from native explanted cirrhotic livers, liver grafts excluded from donation because of severe steatosis, and primary pancreatic tumours. Magnetic resonance imaging (MRI) examinations will be performed within 24 h from liver or pancreatic lesion surgical removal. The MRI protocol will include morphological sequences, quantitative T1, T2, and fat-, water-fraction maps with Cartesian k-space acquisition, and multiparametric methods based on a transient-state “MRI fingerprinting”. Finally, the specimen will be fixed by formalin. Qualitative imaging analysis will be performed by two independent blinded radiologists to assess image consistency score. Quantitative analysis will be performed by drawing regions of interest on different tissue zones to measure T1 and T2 relaxation times as well as fat- and water-fraction. The same tissue areas will be analysed by the pathologists. This study will provide the possibility to improve our knowledge about qualitative and quantitative abdominal imaging assessment at 7 T, by correlating imaging characteristics and the corresponding histological composition of ex vivo specimens, in order to identify imaging biomarkers. Trial registration: ClinicalTrials.gov: 13646. Registered 9 July 2019—retrospectively registeredThe study focuses on radiological-pathological correlation between imaging of  Explanted livers and pancreatic specimens will be investigated by 7-T magnetic resonance imaging (MRI).Morphological findings and quantitative data will be compared with specimen histology.Quantitative MRI will be explored for liver and pancreatic lesion characterisation.MRI fingerprinting will be used to estimate quantitative maps in a shorter time.Magnetic resonance imaging (MRI) provides information on tissue structure and function by means of measurements of intrinsic differences in relaxation times of hydrogen (as well as other) nuclei following radiofrequency excitation. By increasing the magnetic field of the equipment, an intrinsic increase of the signal-to-noise ratio can be achieved , 2. As aex vivo samples and their histological examination, to assess the correlation between tissue imaging characteristics and pathological features. The examined samples will be native cirrhotic livers explanted during orthotopic liver transplantation (group A), liver grafts excluded from donation because of severe steatosis (group B), and surgical specimens of primary pancreatic tumours, which underwent upfront pancreaticoduodenectomy or total pancreatectomy (group C). To obtain the information on tissue structure and function, this study will include conventional methods and novel multiparametric quantitative evaluation. The novel multiparametric methods are based on a transient-state magnetic resonance fingerprinting (MRF) [k-space acquisitions in two or three dimensions. While conventional imaging for quantitative mapping usually needs multiple acquisitions to obtain the measurements of the different parameters, MRF can provide multiple quantitative information with a single acquisition. This technique compares the variable signal acquired per each pixel during the acquisition with a predefined dictionary of signal evolution, allowing the recognition and the measurement of the different parameters based on the match of their signal evolution. Using MRF to evaluate the upper abdomen, including the liver and pancreas, Chen et al. [This study focuses on the comparison between 7-T MRI of ng (MRF)  sequencen et al.  succeedeThe radiological-pathological correlation may improve the knowledge of the changes that occur in cirrhotic liver and their focal lesions , in non-alcoholic steatotic liver disease, which represents one of the main cause of unsuitability for liver transplant liver graft, and pancreatic ductal adenocarcinoma . More in detail, the T1 and T2 relaxation time values and the fat fraction will be assessed on targeted tissues, consisting of focal pancreatic/hepatic lesions or liver parenchyma (for the excluded liver grafts) and of parenchymal tissues different from the targeted one such as non-neoplastic surrounding parenchyma (non-targeted tissues).We assume that statistically significant differences in relaxation time values between the lesions and non-targeted tissue will be observed.In fact, as already explored in different clinical fields, T1 and T2 relaxation time estimation provided promising results in oncologic and non-oncologic tissue characterisation and evaluation of neoplastic tissue changes after treatment . Among t90Y transarterial radioembolisation), when applied as a “bridge treatment” [The rationale behind the group A of native livers explanted from patients undergoing orthotopic liver transplantation derives from the possibility of investigating focal lesions focusing on hepatocellular carcinoma , 12 and eatment” . All thiGroup B will include grafts that are excluded from liver transplantation due to severe macrovesicular steatosis , 15. Duein vivo applications. These considerations guide the aim of the study for group C: the study of ex vivo pancreatic surgical specimens by 7-T MRI should provide a reference framework to define proper acquisition protocols and imaging biomarkers for future clinical applications.Finally, regarding PDAC, despite significant improvements in surgical and nonsurgical treatment modalities, including new possible therapeutic targets , 19, 5-yex vivo specimens.The main aim is to evaluate the correlation between the characteristics detected by the 7-T equipment and the histological composition of Radiological-pathological correlation of focal lesions affecting the cirrhotic liver and of fibrotic/regenerative characteristics of the liver tissue, free from focal lesions; comparisons will include morphological matching as well as correlations between T1 and T2 relaxation time values and differential diagnosis between lesions and pseudolesions or histological classification of the fibrosis degree;Radiological-histological correlation of hepatic lesions treated by locoregional “bridge” treatments, in particular by evaluating the T1 or T2 relaxation time value difference between lesion histologically classified as complete responders and as partial responder after treatment;The degree of steatosis and to correlate this radiological grading with the well-established histological classification of the steatosis distribution ;The primary study aims for groups A and B are to identify useful imaging biomarkers based on the evaluation of:Radiological-pathological correlation of pancreatic lesions; comparisons will include morphological matching between macroscopic histological evaluation and MRI as well as the correlations between T1 and T2 relaxation time values with the lesion extracellular microenvironment and lesion aggressiveness, respectively.The study aim for group C is the following:Secondary study aim is to standardise and validate new 7-T MRI protocols, including quantitative sequences, to be possibly implemented also on 3-T clinical scanners.ex vivo specimens from liver and pancreatic tissues.This research protocol is a prospective experimental correlational no-profit study on human Before starting the study, every participant of A and C groups will be accurately informed about the management of the resected specimen (whole native liver explanted during orthotopic liver transplantation or pancreatic specimens resected due to the presence of a PDAC lesion) and will be given the informative letter for them and for their general practitioner, the forms of the informed consent, and the one for the treatment of their data for research purposes. All participants will be registered after signing the informed consent. The patients’ eligibility criteria, based on the study group of enrolment, are summarised in Table The study will be performed in agreement with the dictates of the Helsinki Declaration and the rules of Good Clinical Practice ). The approval of regional Ethical Committee to conduct this “single-centre prospective study” was obtained .The enrolment stage, as well as the analysis duration, will last 3 years.ex vivo and in vivo biological tissues is the one caused by fixation [It is well established by the literature that an unavoidable signal difference between fixation , 22. In During the MRI study, the specimen will be placed in a dedicated single-use plastic box previously disinfected by a 90% alcohol solution and dried by a sterile towel  equipped with an autonomously customised 8-channel transmit/receive knee coil.They will include a three-dimensional CUBE T2-weighted fast turbo spin-echo sequence as anatomical reference, as well as T1- and T2-weighted water-only sequences using the “iterative decomposition of water and fat with echo asymmetry and least-squares estimation” (IDEAL) technique  and two-Quantitative mapping will include the following series of techniques and methods.T1 values will be obtained using a modified magnetisation-prepared rapid gradient echo acquisition, named MP2RAGE. Briefly, it consists of the combination of two low-flip angle images with different inversion times (TI). These images are combined according to the following equation1, 2 are the two images with different TIs (TI1 and TI2). This combined image, due to the low flip angle, results to be bias corrected. Moreover, exploiting the knowledge of the acquisition parameters, the T1 values can be uniquely determined from the intensity values as previously described [where TIescribed .T2 values will be obtained by multi-echo spin-echo acquisition. Images for the individual echoes are used to obtain the T2 map using the following signal model:S(TE) represents the voxel-wise signal magnitude for the echo time (TE).where Fat fraction values will be obtained from an IDEAL fast gradient-echo acquisition. To avoid T1-weighting and obtain a proton density-weighted fat fraction, a low flip angle is used. Output water and fat images are combined to obtain fat fraction map, as follows:F and W represent the signal of fat and water, respectively.where  will be included in the protocol. Two different MRF acquisitions will be performed: a three-dimensional acquisition based on spiral projections, which will provide T1, T2, and B1+ transmit field maps, and a spiral two-dimensional acquisition, which will provide T1, FF, B0, and B1+ transmit field maps. In both cases, the parametric maps will be obtained by matching the acquired data to a precomputed dictionary of signal evolutions obtained by means of numerical simulations. For two-dimensional MRF, parameter inference will be performed in two steps [0 values are estimated in the first step and used as input parameter for the second step, where FF, water T1, and B1+ are obtained. Variation of flip angle and other technical parameters are shown in Fig. Multiparametric acquisitions in the transient state wo steps , where BQualitative and quantitative analyses of all collected images will be performed at dedicated workstations .Two independent blinded readers  will assess an image consistency score on a 4-point scale depending on different factors , as follows: 1 = poor, insufficient image quality ; 2 = sufficient ; 3 = good ; 4 = excellent .It will require previously defined regions of interest (ROIs) and cannot be assessed in the whole organ/specimen—will be performed on different areas: (a) “targeted tissue” (group B) or “targeted lesion” (groups A and C); (b) tissue close to the targeted ones but above 5-mm distance from the target (non-target tissue). The non-target tissue refers to a parenchymal area not involved in focal alteration/lesion, but with tissue changes related to other systemic diseases such as fibrosis in cirrhotic livers. In groups A and C, the targeted lesion will be measured including the whole focal lesion, by drawing a hand-made ROI along lesion edges and  on the lesion central and peripheral zones by circular ROIs. In the latter cases, the area of each ROI will include more than 100 voxels. In order to reduce measurement error, the measurement will be repeated three times, and both single and mean values will be analysed.The same tissue areas will be analysed by the pathologists, thanks to the presence of the anatomical landmarks identified by the radiologist during the MRI examination and referred to the pathologist. She/he will be able to recognise by using the same section plan defined for imaging and histological analysis. In fact, the section of the two-dimensional acquisition plane will be defined together with the pathologists in order to perform the subsequent histological analysis of the same section of the tissue. Unfortunately, the MRI slice thickness will not be the same of the histological slice; as a consequence, the difference in slice thickness will remain a limit of our study. The expected outcomes of radiological-pathological correlation are summarised in Table After the MRI study, two pathologists with 20- and 5-year experience in hepatobiliopancreatic pathologies will analyse all specimens. First, the pathologists will evaluate the whole specimen; then, they will focus on specific tissue slices corresponding to the ones on which the radiologists will provide their diagnosis and diagnostic confidence score.< 3 mm) or macronodular (> 3 cm). Subsequently, the liver will be dissected; colour and consistency of liver parenchyma will be described as well as any suspect nodule. Representative samples will be taken for microscopic examination. Main histological features will be reported, and liver neoplasms, when present, will be reported and described according to the 2019 World Health Organization classification of digestive system tumours [For group A, gross examination of the liver will be performed reporting on the size and weight of the specimen as well as the appearance of its external surface. In particular, cirrhosis will be described according to the dimension of single nodules as micronodular  will be reported.For group C, before sampling the specimen, a multicoloured inking of all the pancreatic circumferential margins will be performed. The pancreatic head will be sliced along the axial plane, perpendicularly to the descending part of the duodenum, with a dissection plane similar to that of MRI. Dissection will include the entire head of the pancreas and any adherent structures such as duodenal wall, distal common bile duct, and vascular resection, when present. All main histological features of the tumour and collateral tissue will be reported during the microscopic examination. Margins will be defined negative when no tumour cells are found within 1 mm from inked margins .ex vivo human liver and pancreatic specimens. As a consequence, the sample size calculation cannot be based on previous published experiences. Thus, this preliminary study will start by including at least ten ex vivo specimens per group, a sample size considered as appropriate in terms of feasibility assessment.To the best of our knowledge, the EXLIPSE study could be the first study on quantitative 7-T MRI of r or Spearman ρ will be applied, according to data distribution. When the ANOVA test includes several groups and the analysis results are significant, a post hoc analysis will be performed applying the Bonferroni correctionBefore performing inferential tests, Kolmogorov-Smirnov’s test will be used to evaluate data distribution. In the case of normal distribution, the quantitative T1 and T2 values inside the ROIs obtained will be compared with the different degree assigned to the examined histological tissue characteristics  using a mixed effects ANOVA model. By this statistics, it will be possible to identify differences among the different groups. In the case of not normal distribution, they will be compared by using the Kruskal-Wallis test. To assess the correlation between the relaxation time values and histological measurements Pearson p values will be calculated using the Chi-square distribution for nominal variables. Thus, the correlation between the morphological MRI data and the information provided by the macroscopic and microscopic histological examination of the specimens will be performed. Specimen characteristics will be summarised using descriptive statistics: mean and standard deviation, or median and range for continuous variables, in the case of normal or not normal distribution, respectively, absolute and percentage frequencies for categorical variables.The p value lower than 0.05 will be considered statistically significant, with exception of cases when Bonferroni correction will be appropriate.A ex vivo specimens investigated by 7-T MRI allow a reliable comparison between radiological images and histology. Moreover, 7-T MRI has already been demonstrated as a useful tool able to provide information on surgical margins after surgery. In particular, 7-T MRI showed a good correlation with pathology in the evaluation of negative surgical margins after partial nephrectomy with and sensitivity and specificity for MR assessment of negative surgical margins of 100% and 75%, respectively. With a mandatory protocol optimisation to minimise the scan time, the authors proposed the 7-T MRI specimen evaluation as a promising intraoperative tool to improve the surgical outcomes about margins and parenchymal sparing [The use of specimens allows a high spatial resolution without motion artefacts to guarantee a precise comparison between the information obtained by image analysis and the specimen macroscopic and microscopic pathological examinations. The effort made to build this study protocol was driven by the belief that  sparing . As alreex vivo sample and on an in vivo population.Due to the small study sample per group, the identified imaging biomarkers and morphological tissue changes will have to be validated by future dedicated studies, which will be conducted both on a larger This research protocol had to overcome some difficulties in its design. First, specimen storage: the pathologist responsible for the analysis of liver and pancreas specimens was asked to evaluate how to store the specimens before histological analysis. The specimens should not be treated with formalin before 7-T MRI because a decrease in magnetic resonance tissue characteristics including T1 and T2 relaxation times have been demonstrated after fixation , 29–31.ex vivo specimens were available. As a consequence, before starting the EXLIPSE study, an acquisition protocol had to be set-up.Thus, the pathologists assessed that no tissue damage occurs if the time length from surgical resection to MRI exam and to delivery to the pathologist is less than 24 h. During these 24 h, the specimen should be maintained at a temperature of 4 °C, with the exception of the time spent in the MRI magnet when the specimen temperature will arise above 15 °C. This temperature will be controlled during the exam so that the heating related to radiofrequency exposure does not damage the tissue. The exam will be interrupted if the temperature exceeds 25 °C. Second, the logistics: the lab where the 7-T device is located is about 15 km from the surgical suites and from pathology department. For this reason, the transportation of the specimens required dedicated medical vehicles. Finally, the lack of previous similar experiences in the literature: the 7-T knee coil has been predominantly used and optimised for knee investigations; thus, no examples of technical parameters to study This study will provide the possibility to improve our knowledge about the quantitative abdominal imaging assessment. In fact, the EXLIPSE study could represent an important step to further develop MRF sequences on 3-T MRI. The advantage of using 7-T radiological-pathological correlation to optimise MRF consists in the opportunity of employing the tissue morphologic and quantitative characteristics discovered by the ultrahigh field and confirmed by histology as a reference standard for constructing the signal on the similar sequences for 3-T systems. We expect that the higher 7-T signal in the quantitative maps could provide a useful information, even if for relatively small samples. The higher resolution could provide a more suitable correlation with micron-size histology evaluation.Studies at lower field strengths could benefit from larger samples to achieve further results. Once imaging biomarkers are identified, the next step will be to exploit this knowledge for application on 3-T device, to create a more widespread demonstration and application of their clinical utility, due to the remarkably larger availability of the 3-T scanner. Protocol and sequence optimisation process will be mandatory at 3 T due to the different contrast (increased T1 and decreased T2 at 7 T than at 3 T), potential artefacts observed on the images obtained at different static magnetic fields, and the different availability of dedicated coils. However, the presence of well-optimised dedicated coils for abdominal imaging at 3 T may lead to a more rapid optimisation of sequences and protocols.Additional file 1.