To develop guidelines describing a standardised approach to patient preparation and acquisition protocols for magnetic resonance imaging (MRI), computed tomography (CT) and ultrasound (US) of the small bowel and colon, with an emphasis on imaging inflammatory bowel disease.An expert consensus committee of 13 members from the European Society of Gastrointestinal and Abdominal Radiology (ESGAR) and European Society of Paediatric Radiology (ESPR) undertook a six-stage modified Delphi process, including a detailed literature review, to create a series of consensus statements concerning patient preparation, imaging hardware and image acquisition protocols.One hundred and fifty-seven statements were scored for agreement by the panel of which 129 statements (82 %) achieved immediate consensus with a further 19 (12 %) achieving consensus after appropriate modification. Nine (6 %) statements were rejected as consensus could not be reached.These expert consensus recommendations can be used to help guide cross-sectional radiological practice for imaging the small bowel and colon.Cross-sectional imaging is increasingly used to evaluate the bowel• Image quality is paramount to achieving high diagnostic accuracy• Guidelines concerning patient preparation and image acquisition protocols are provided•  Increased utilisation of cross-sectional techniques to image the bowel has occurred in recent years, particularly in the context of inflammatory bowel disease. A large body of evidence now supports the use of computed tomography (CT), magnetic resonance imaging (MRI) and ultrasound (US) in this context, and recent expert guidelines recommend cross-sectional imaging as first line in the diagnosis, staging and follow up of inflammatory bowel disease . In commA call for expressions of interest to take part in the process was circulated to all ESGAR members. From those expressing interest, a panel of ten members (including the chair) were invited based on publication record in the field and geographical location to ensure, as far as possible, appropriate representation across the ESGAR membership. The committee was then supplemented by three members chosen by the ESPR for all paediatric considerations, to give a total of 13 individuals. Two research fellows were added to help with the literature review and document construction, but they did not take part in committee consensus voting.A modified Delphi approach based on the RAND-UCLA appropriateness method was utilised , encompaThe consensus committee met for a face to face discussion to define the scope and aims of the process (11 June 2015), and an initial questionnaire including 185 items was drafted by the chair and then circulated electronically to all committee members. Each item consisted of a specific question with an appropriate range of possible responses, including an option for free text. The questionnaire was split into four broad topics: (1) patient preparation for MRE/MR enteroclysis/CTE/CT enteroclysis, (2) MRE/ MR enteroclysis technique and sequence selection, (3) CTE/CT enteroclysis technique, and (4) enteric US patient preparation and technique. Items were duplicated for both adult and paediatric populations as appropriate. The questionnaire was then modified based on feedback from committee members and a final version agreed upon, which defined individual topics requiring consensus statements. The consensus committee was split into four subgroups matching the four broad topics. Members of ESPR formed a fifth subgroup for paediatric considerations throughout the questionnaire.The agreed questionnaire was circulated electronically to committee members who completed their responses to each item in order to document initial expert opinion. The responses were summarised centrally.A radiology research fellow performed a detailed literature search based on the strategy used by Puylaert et al. . Full deWithin their working groups, committee members drafted consensus statements for each item listed in the questionnaire based on the available literature and expert opinion as appropriate (using the summarised committee responses to the questionnaire). Members were instructed to always base their statements on the retrieved literature wherever possible, and to this end graded the strength of retrieved relevant publications from I (high) to V (low) using the criteria of the Oxford Centre for Evidence Based Medicine  during tAll committee members graded their agreement with each draft consensus statement from 1 to 5 according to the following definitions; 1, strongly disagree; 2, somewhat disagree; 3, undecided; 4, somewhat agree; 5, strongly agree. The responses were summarised centrally.Those statements achieving a score of 4 or 5 by at least 80 % of committee members in step 5 were accepted into the final set of consensus statements. Those not achieving this were re-discussed at a face to face meeting of the committee (6 March 2016) attended by seven members. Those members who were unable to attend contributed via electronic submissions, which were presented by the chair. Statements not achieving consensus were reviewed with reference to the literature summaries produced by each working group, and committee member opinions were sought. The statement was then either modified or deleted if it was clear consensus could not be reached. The list of revised statements was recirculated to the whole committee who graded agreement from 1 to 5 as in step 5. Those statements achieving a score of 4 or 5 by at least 80 % of committee members were added to the final set of consensus statements.The current clinical practice of the panel members is summarised in Table The final agreed upon questionnaire consisted of 157 items generating individual consensus statements. At the first round of committee voting, 129 statements achieved consensus according to the a priori definition. The remaining 28 statements did not achieve consensus and were modified to produce a set of 19 statements, all of which achieved consensus agreement in the second round of voting. Those statements which could not be modified to reach consensus were deleted and are shown in Table The committee considered four main topics as the basis for the consensus statements, with an additional section for specific paediatric considerations.There is little evidence on optimal patient preparation prior to MRI or CT, and recommendations with regard to periods of nil by mouth for solids and fluids were based mainly on expert opinion. Ingestion of sparkling water is not recommended due to the risk of producing intraluminal gas artefacts, particularly during MRI. There is good evidence that the accuracy of MRI is improved by administration of oral contrast, in comparison to unprepared MRI . Many orThe recommended choice of enteric contrast agents for enteroclysis examinations in general mirrors those recommended for enterography. However, the use of water during CT enteroclysis was included given the speed of CT acquisition, minimising the detrimental effects of gut absorption seen with longer examination times. The optimal volume of contrast agent for both CT enteroclysis and MR enteroclysis should be based on real time on table monitoring.The routine use of bowel laxatives and rectal enema is not recommended, although there is good evidence that detection of colonic inflammation with MRI is improved with administration of a water enema in comparison to evaluating the unprepared colon , 18. If The use of an automated pump for oral contrast administration during enteroclysis is recommended, although hand injection is an acceptable alternative.Although there is some data suggesting superior bowel distension is achieved in the prone position , there iThe use of phased array coils at either 1.5 T or 3 T is recommended. There was no consensus for which field strength was optimal for enteric MRI, with data suggesting high image quality is routinely possible on 3 T as well as good quality 1.5 T , 24.There is some evidence that MRE can achieve high diagnostic accuracy without use of a spasmolytic , althougThere was no consensus as to the optimal timing of spasmolytic administration or whether the dose should be split in an attempt to maintain aperistalsis throughout the duration of the MR examination. It is therefore recommended that spasmolytics should be administered before motion sensitive sequences  and either a single or a split dose are acceptable.There is no available evidence informing the optimal combination of T2-weighted and steady state free precession gradient echo (SSFP GE) sequences, although nearly all studies in the literature utilise both sequence types. Recommendations were therefore mainly based on expert opinion. The use of post-gadolinium T1-weighted images are recommended with data suggesting increased diagnostic accuracy with their use , 30, andThere is increasing evidence in support of quantified small bowel motility to improve diagnostic accuracy , 34, assThere is little evidence for the optimal CT platform for performing CTE and CT enteroclysis, but based on expert opinion it is recommended that 16-slice CT is a minimum and 64+ slices is optimal. The use of spasmolytic is optional given the speed of CT image acquisition compared with MRI, and the lack of data demonstrating a benefit of spasmolytic. As for MRI, hyoscine butylbromide is the recommended first line agent if a spasmolytic is used. There was no consensus as to the need for a second-line agent if hyoscine butylbromide cannot be administered, but glucagon may used.CT scan acquisition in either the enteric phase , 51 or pRecurrent exposure of young patients to ionising radiation from CT is a significant concern. Numerous studies have documented high radiation exposure in the IBD patient population, principally from CT –61. TherThere is little evidence on optimal patient preparation prior to US, and recommendations with regard to the period of nil by mouth for food and liquids were based on mainly on expert opinion. There is no evidence supporting the use of bowel laxatives before US or hydroUS and use is not recommend. Detailed assessment of the colon does not require additional preparation.Similar to MRE and CTE, a range of oral contrast agents for hydosonography is described in the literature –73, withThere is no evidence of benefit from spasmolytic administration prior to enteric US, and diminishing the ability of the practitioner to evaluate real time peristaltic activity in the bowel detracts from the examination. Its use is, therefore, not recommended.There is good evidence supporting the routine use of colour or power Doppler for disease detection and activity assessment during enteric US and hydosonography –79.The routine use of contrast-enhanced US (CEUS) is currently not recommended. However there are increasing reports describing the utility of qualitative evaluation of bowel wall vascularity patterns in CD using CEUS , 81, as However, there are no defined optimal thresholds for quantitative CEUS that differentiate active from inactive disease, and there are differences in perfusion metrics between US manufacturers. The precise role for CEUS in clinical practice is likely to evolve as the evidence base grows.If CEUS is performed the recommendations on dosage are made on the most widely reported agent (sulphur hexafluoride), although other agents are available. These are based on manufacturer recommendations in the absence of other evidence.It is recommended that the practitioner specifically reports if the extra enteric solid organs have been evaluated as part of an US examination focused on the bowel. In some clinical practices, it is expected the examination should evaluate the whole abdomen and pelvis, including solid organs, although targeted enteric US (e.g. for treatment follow-up) is also widely practiced.Although in general, paediatric practice follows that of adults , 91, theThe use of CT is actively discouraged in the paediatric population given the radiation exposure and should be reserved for situations when neither MRI nor US can resolve the clinical question.Younger children do not tolerate prolonged fluid and food restriction prior to examinations, and recommendations are made according to the age of the patient, mainly based on expert opinion.Unlike adult practice, the use of spasmolytic prior to MRE is considered optional in paediatric patients and use is likely dependent on the age of the patient, with older children more likely to tolerate spasmolytic injection. There are data supporting the benefits of glucagon on image quality, at the expense of prolonged imaging time and precipitation of nausea in just under half of paediatric patients , 93. HowRecommendations for oral contrast volume and spasmolytic/gadolinium dose are based on weight. There are no specific recommendations as to the use of hydroUS in the paediatric patient as practice is not well developed. If oral contrast is given prior to US, it would seem sensible to follow the recommendations for MRE in the paediatric population.The modified Delphi process utilised in this document is well established, although for the second face to face meeting, not all committee members could attend, with contributions made electronically. However a representative from each working group was present and all committee members subsequently scored their agreement with each modified statement produced. Wherever possible, recommendations were based on the detailed literature review. However, in many areas there was no available evidence, so recommendations were made based on the combined expert opinion of the panel. This will be influenced by the experience and knowledge of the panel members. To mitigate against potential bias, committee members were selected based on publication record and geographical location, and it was ensured that there was experience in all modalities under consideration across the consensus group. Discussions were moderated by the committee chair who was independent of the working groups within the committee members. Finally, these recommendations are relevant at the time of the consensus process (2015/16). The literature in this field is rapidly expanding, and it is anticipated revised guidelines will be required in the future.In summary, a modified Delphi approach was successfully utilised to produce set of guidelines to help inform current best clinical practice in cross-sectional small bowel and colonic imaging. For only a small number of topics could an agreed consensus statement not be produced by the committee. Whilst there is a clearly a convergence in the literature as to basic techniques, for many specific questions there is no clear evidence base and statements were based on expert opinion, with an emphasis on clinical practicability. Based on the findings of the committee, particular topics can be viewed as research priorities given their potential impact on clinical practice. Examples include the role of DWI and motility imaging as part of MRI protocols, and more detailed guidance on i.v. gadolinium contrast administration given the generally young age of the imaged patient population, frequent repeat imaging and increasing evidence of possible neuronal retention of gadolinium for some contrast agent classes . The cli


Background: Medical treatment requires the implementation of existing evidence in the decision making process in order to be able to find the best possible diagnostic, therapeutic or prognostic measure for the individual patient based on the physician’s own expertise. Clinical trials form the evidence base and ideally, their results are assembled, analyzed, summarized, and made available in systematic review articles. Beside planning, conducting, and evaluating clinical trials in conformity with GCP , it is essential that all results of conducted studies are publicly available in order to avoid publication bias. This includes also the public registration of planned and cancelled trials. History: During the last 25 years, evidence-based medicine became increasingly important in medical care and research. It is closely associated with the names of Archibald Cochrane and David Sackett. About 15 years ago, the Deutsche Cochrane Zentrum (Cochrane Germany) and the Deutsche Netzwerk Evidenzbasierte Medizin e.V.  were founded in Germany. In the International Cochrane Collaboration, clinicians and methodologists come together on an interdisciplinary level to further develop methods of evidence-based medicine and to discuss the topics of evidence generation and processing as well as knowledge transfer.Problem: Evidence is particularly important for physicians in the process of decision making, however, at the same time it is the base of a scientific proof of benefit for the patient and finally for the payers in health care. The closure of evidence gaps requires enormously high staff and financial resources, significant organizational efforts, and it is only successful when clinical and methodical expertise as well as specific knowledge in the field of clinical research are included. On the other hand, the knowledge has to be transferred into practice. For this purpose, practice guidelines, meetings, databases, information portals with processed evidence as well as specific journals and finally teaching are appropriate vehicles. One problem is the multitude of information so that knowledge gaps may affect the clinical routine despite actually existing evidence. Generally, it still takes several years until new knowledge is implemented in daily routine.Tasks: The German Society of Oto-Rhino-Laryngology, Head and Neck Surgery  and the Professional Association of Otolaryngologists  have fundamental interest in supporting their members in generating, processing, and providing evidence as well as accompanying knowledge transfer. It encompasses the fields of diagnostics, therapy, and prognosis in the same way as prevention and applies to medicinal products as well as to medical devices or surgical procedures. The base for this is the regular assessment of evidence gaps, also in the area of established procedures, that has to be followed by a prioritization of research questions and the subsequent initiation of clinical research. In addition, large trials verifying therapies and diagnostics, for example in the context of daily conditions after approval, can only be conducted combining all resources in the ENT community.Method, results, and outlook: Together, the executive committees of the DGHNOKHC and the BVHNO founded the German Study Center of Oto-Rhino-Laryngology, Head and Neck Surgery . First projects have been initiated, among those a clinical trial on the therapy of sudden hearing loss supported by the BMBF and a survey on evidence gaps in oto-rhino-laryngology. It seems to be both reasonable and feasible to make available methodological expertise via such an infrastructure of a study center for physicians in hospitals and private practices in order to support clinical research and to implement the principles of evidence-based medicine in daily routine. It is certainly unique to focus on the lack of knowledge and missing research, besides presenting new knowledge, results of basic and clinical research. At the same time, these journal articles concentrate on a discipline, the evidence-based medicine, that has indeed reached medical care but is not yet “at home” there, as it was described by Baethge in an article in the Deutsche Ärzteblatt ..25].The further processing of existing evidence, the prioritization of research questions and the subsequent closing of evidence gaps require a long and stable cooperation of all disciplines and staff in hospitals and private practices so that this knowledge is implemented in clinical routine afterwards. Missing knowledge and missing evidence are harmful for patients in the same way as missing therapeutic options when risk and benefit cannot be estimated reliably. Patients can only come to an informed decision if they know the existing evidence and in single cases might for example even prefer a higher quality of life instead of a marginal prolonged life.Trials on patient-oriented endpoints are essential and the contact to patients and clinicians represents the basic condition for clinical research. In this context, the structure of the DSZ-HNO under the guidance of the scientific society and the professional association offers the best conditions. With coordinated, evidence-based research including all sectors, a contribution can be made in the sense of the Lancet series entitled “Research: Increasing Value, Reducing Waste” . The whoThe authors declare that they have no competing interests.


Patients with limited health literacy have poorer surgical outcomes. However, current studies assessing the prevalence of limited health literacy in patients expecting surgery are small scale. We aimed to provide insight into the health literacy level of patients undergoing planned surgery.Patients aged ≥18 years visiting the preoperative screening department were approached in the waiting area and invited to participate in a brief interview including the Functional Communicative Critical Health Literacy (FCCHL).In total, 225 patients (84.9% response) were studied. Based on the FCCHL, 37.3% of the patients were classified as having limited health literacy. The mean score in the critical domain (2.7 ± 0.9) was lower than scores in the functional (3.3 ± 0.6) and communicative (3.3 ± 0.6) domains.More than one third of the patients admitted to the hospital for surgery had limited health literacy. Healthcare professionals should be aware of the different health literacy levels and tailor their information provision strategies accordingly. Health literacy, defined as the ability to obtain, understand and use information in health-related decisions, can be described in terms of functional, communicative and critical skills Nutbeam , 2009. FSeveral studies have shown that patients with limited health literacy have poorer health outcomes  in Nieuwegein, The Netherlands. Before planned hospital admission, patients visit this department and receive information about the surgical procedure, anesthesia and the general procedure for hospital admission including preoperative instructions .The study protocol was approved by the Institutional Review Board of the Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht University, and the local review committee of St. Antonius Hospital, Nieuwegein.Patients aged ≥18 years who were scheduled for surgery and visiting the preoperative screening department were invited to participate in the study. Patients insufficiently proficient in the Dutch language and patients with dementia were excluded from the study. Patients who signed the informed consent form were interviewed to assess their health literacy level. A master pharmacy student of the Utrecht School of Pharmacy performed the interviews.Data were collected from September–November 2015. The Dutch version of the Functional Communicative Critical Health Literacy (FCCHL) instrument, a validated questionnaire to assess health literacy skills Nutbeam , was useDescriptive statistics were used to calculate health literacy in total and for the three different sub-scales . We presented the proportion of patients with an FCCHL mean total and sub-scale score ≤3 (see above). Logistic regression analysis controlling for age, gender, educational level and ethnic background was used to calculate odds ratios and their corresponding 95% confidence intervals (CIs) for the association between health literacy and patient characteristics. The possibility for a predictive model for limited health literacy was also investigated. All analyses show the odds ratios for limited health literacy compared with adequate health literacy. Data were analyzed using IBM SPSS version 23.0  for Windows.In total, 225 patients (84.9%) out of 262 invited patients agreed to participate. The most common reasons for non-willingness to participate were lack of interest in the study  and lack of time . Table Overall mean scores ≤3 were found in 84 patients (37.3%), indicating limited health literacy. For the three different sub-scales, 30.7% (n = 69), 31.6% (n = 71) and 54.7% (n = 123) scored below the threshold of three in the functional, communicative and critical domains, respectively. Mean FCCHL scores were lowest for critical health literacy (mean score: 2.7 ± 0.9) compared to functional and communicative health literacy (mean score: 3.3 ± 0.6 for both domains) , which showed a good fit (Hosmer and Lemeshow test p = 0.74); however, the predictive power of the model was poor (area under the curve: 0.68).More than one third of patients scheduled for elective surgery were classified as having limited health literacy. The prevalence of limited health literacy found in our study is in line with other studies  background. This is in line with findings reported in the literature . Many previous studies have used health literacy measurement instruments that focus solely on functional skills, e.g., reading comprehension, while the FCCHL we used in this study also includes assessment of communicative and critical skills and thus gives insight into the broader range of health literacy skills. However, as the FCCHL is a subjective instrument based on self-reporting, it may lead to observations that differ from actual patient behavior. In real-life situations people may experience even more difficulties with certain tasks, in which case our results underestimate the problem of limited health literacy.Low health literacy has previously been associated with poorer surgical outcomes and misunderstanding of information  written information or providing information in another language (Taggart et al. In conclusion, this study shows that a considerable proportion of patients scheduled for surgery have limited health literacy. Patients scored lowest in the critical domain, which may have consequences for self-management. Healthcare providers involved in preoperative screening should actively identify patients with poor health literacy and should adapt their information and instructions for these patients.


The characterization of focal splenic lesions by ultrasound can be quitechallenging. The recent introduction of contrast-enhanced ultrasound (CEUS) hascome to play a valuable role in the field of imaging splenic pathologies,offering the possibility of an ionizing radiation-free investigation. BecauseCEUS has been incorporated into everyday clinical practice, malignant diseasessuch as focal lymphomatous infiltration, metastatic deposits, benign cysts,traumatic fractures, and hemangiomas can now be accurately depicted andcharacterized without the need for further imaging. More specifically, splenictraumatic fractures do not require additional imaging by computed tomography(with ionizing radiation exposure) for follow-up, because splenic fractures andtheir complications are safely imaged with CEUS. In the new era of CEUS, morepatients benefit from radiation-free investigation of splenic pathologies withhigh diagnostic accuracy. Its use forthe examination of the spleen has been established in guidelines ,2 and documented in specific studies -5. Thecombination of microbubble contrast and ultrasound minimizes three challenges facedin imaging: the deleterious effects of the ionizing radiation employed in computedtomography (CT); the possibility of nephrotoxicity caused by the iodinated contrastagents used in CT and magnetic resonance imaging (MRI); and the relatively highcosts of CT and MRI. Here, we present a pictorial review of the CEUS presentationsof a variety of splenic lesions, in comparison with those visible on B-modeultrasound, CT, and MRI.The search for efficient and less expensive imaging techniques is an ongoingchallenge worldwide, ultrasound being ideally positioned to provide comprehensiveimaging in a cost-effective manner. Ultrasound is a valuable tool in the study ofthe spleen, with the ability to determine and monitor alterations in the size,presence, and character of focal lesions, as well as diffuse alterations in the echopattern. In the last 20 years, contrast-enhanced ultrasound (CEUS) has seen advancesin several aspects . These microbubbles are small enough to pass through thelung capillaries but much larger than the molecules and particles used in CT and MRIcontrast agents. Therefore, these microbubbles do not cross the endothelium and cellmembrane, remaining exclusively in the intravascular space. The microbubbleultrasound contrast agent in current use is not nephrotoxic, and its excretion isessentially pulmonary, the inert gas (sulfur hexafluoride) being excreted via therespiratory tract and the phospholipid shell being metabolized in the liver.The contrast agents used in ultrasound are composed of small (3-5 µm)microbubbles, with low solubility in blood, covered by a membrane-typically a lipid,although proteins and polymers are also used . In a large review ofthe use of microbubble contrast in over 23,000 abdominal studies, there were nodeaths and only two anaphylactic reactions occurred, the incidence of serious eventsbeing less than 1 event/10,000 examinations . The authors reported that the most common adverse effectswere cough and back pain. Other possible effects are headache, nausea, andventricular extrasystole, the last possibly being relevant only in cardiacexaminations.Severe adverse events related to the use of microbubble contrast agents, anaphylacticshock being the worst possible event, are rare, with an estimated prevalence of0.0086%, considerably lower than that reported for the use of iodinated contrastagents and comparable to those reported for most antibiotics and analgesics. At ourinstitution, a Siemens Acuson S2000 ultrasound system  is used with the Lumason/SonoVue microbubble contrast agent. The microbubble contrast agent is injected intravenously viaa cannula inserted into the left antecubital fossa, at a dose of 1.2-2.4 mL; thedose recommended by the manufacturer is 4.8 mL, which is now rarely needed. With theimprovements in the quality of the ultrasound systems, transducers, and imageprocessing, 1.2 mL of microbubble contrast is sufficient for examination of thespleen, particularly in smaller patients. If necessary, the procedure can safely berepeated after a 5-min interval.Only after the spleen has been examined with B-mode and Doppler ultrasound should aCEUS examination be performed. The operator must choose the best patient position toallow visualization during respiration, taking both patient and operator comfortinto account. To improve visualization of the deep pole and subphrenic areas of thespleen, for example, the patient can be placed in the lateral decubitus position orimaged during inspiration . For better image definition, weuse the highest frequency possible, tailored to the depth of the target area.Although it is normal practice to use a 3.5-5.0 MHz transducer, resolution isimproved with a 7.5 MHz transducer, albeit at the expense of the detection of lessobvious microbubbles . During CEUS, a digital video clipis recorded and still images are acquired as necessary.In all of the cases illustrated here, a low-mechanical-index technique-cadencecontrast pulse sequencing -was used, themechanical index being set at or below 0.10, with split-screen imaging, which allowsthe targeting of focal lesions. The mechanical index is a measure of the power ofthe ultrasound beam, and a low mechanical index results in minimal microbubbledestruction, thus allowing enhanced imaging for a prolonged period The spleen is a solid organ, the superficial location of which makes it well suitedfor CEUS examination. On CEUS, the perfusion dynamics of the spleen differ fromthose of the liver, in which there is a dual blood supply, and mirrors the perfusioncharacteristics seen on a contrast-enhanced CT scan, although with better definitionof the vascular components. In the early phase, microbubble contrast is seen withinthe splenic artery and its branches, usually within the first 20 s after microbubblecontrast injection. Subsequently, the opacification becomes inhomogeneous, producingthe so-called "zebra" pattern, which mimics what is seen in the arterial phase of CT. The spl. Secondary cystshave no cellular lining and typically occur after trauma. Cysts can haveinternal debris, the echogenicity of which makes them difficult to evaluate onB-mode ultrasound, although primary congenital cysts are usually well defined,with posterior acoustic enhancement. Following microbubble contrastadministration, the definition of the cyst is enhanced, no internal vascularityis observed, and any internal debris is not enhanced.Splenic cysts  can be p.The most common primary sources of such infection are the following: theendocardium (endocarditis); the urinary tract; a surgical or traumatic wound;and the appendix (appendicitis). Splenic abscesses are typically cystic, with athick, irregular wall, and contain debris and septations . CEUS appearances can varydepending on the number of internal septations. Generally, there ishyperenhancement of the wall and enhancement of the internal septations . The CEUS imagingfindings are those of a rounded well-defined lesion usually lying within thefracture plane (when post-traumatic) and demonstrate vascular enhancementsimilar to that seen on contrast-enhanced CT, CEUS having the advantage ofreal-time dynamic imaging , as illustrated in Splenic artery pseudoaneurysm is a rare entity that usually results from trauma,pancreatitis, or surgery. If left untreated, a splenic pseudoaneurysm has a riskof rupture of up to 37% and, if ruptured, a mortality rate of up to 90%; whendetected, the appropriate treatment can be endovascular or surgical, dependingon the size of the pseudoaneurysm, although its size is not predictive of therisk of hemorrhage . On imaging, splenunculitypically present adjacent to the splenic hilum; they can be single or multipleand are usually ≤ 2 cm in diameter. Splenunculi can be ectopic and canoccur in a variety of locations, including the pancreas and scrotal sac. On CTand ultrasound, splenunculi appear as well-defined nodules, with density similarto that of the spleen itself (.Splenunculi are variants of normality, identified in 30% of autopsies n itself .On B-moCEUS is a powerful, accessible tool for the study of the spleen. Comparing CEUS withB-mode ultrasound, the addition of microbubble contrast increases the conspicuity ofthe majority of incidentally identified splenic lesions and can be used withconfidence to determine the nature of cysts, hemangiomas, infarctions, andabscesses, as well as to facilitate the differentiation between benign and malignantlesions. CEUS improves trauma imaging of the spleen, making it a practical tool forincreasing diagnostic reliability. The estimation of the extent of traumatic lesionswith CEUS is far more accurate than that achieved with B-mode ultrasound and similarto that achieved with contrast-enhanced CT. CEUS of the spleen can also be used infollow-up evaluations to identify complications associated with traumatic lacerationof the spleen, including pseudoaneurysm formation, and allows ionizingradiation-free assessment of resolution of the injury.


Dirofilaria immitis is an important filarial nematode in dogs. In this study, age and sex distribution of this zoonotic nematode among dogs were investigated in northwest of Iran in Meshkin-Shahr city. Molecular characteristics of the isolates, based on cytochrome oxidase subunit 1 (COX1) gene were compared to the isolates from other areas of the world.Blood samples were collected from 91 dogs which were selected by simple classified accidental sampling. Thin and thick blood smear examinations were used to find out infectivity with D. immitis. DNA extraction was performed from adult D. immitis recovered from heart of infected dogs. The COX1 gene was amplified and sequenced. Phylogenetic analysis was carried out using sequences obtained in this study along with relevant sequences deposited in the GenBank. Phylogenetic analysis and sequence variation was performed using MEGA software in comparison with those COX1 sequences deposited in GenBank. Out of 91 dogs, 19 (20.87%) were found positive for infection with D. immitis. There was no statistically significant difference between males and females of dogs in terms of D. immitis infection. However, the rate of infection in dogs more than 2 years old was significantly higher than those with lower age. Both sequences analyzed in this study showed 100% homology to each other. Intra-species variation of these isolates with those from other areas of the world amounted to 0 to 0.50%. Phylogenetic analysis of the COX1 gene suggested that it is conserved, and can be used for study on genetic diversity and classification of filarial nematodes. Dirofilaria immitis is a mosquito born filarial nematode and a wide range of carnivores especially dogs and cats are the known definitive hosts.1 It is transmitted by several mosquito species of Culicidae family as vector.2 Adult worms live in right ventricle, pulmonary artery and posterior vena cava.3 Microfilariae circulate in the peripheral vasculatures in dogs while amicrofilaremic infections are common in felines.11,4 In human, D. immitis causes pulmonary dirofilariasis and is usually asymptomatic. In symptomatic dirofilariasis cough, chest pain, fever, and pleural effusion are present.1,5Dirofilariosis often has no clinical signs in mild infection, however, may cause clinical signs as cough, congestive heart failure, intravascular haemolysis and pulmonary thromboembolism, and even death in dogs.Dirofilaria immitis is widespread in the tropics, subtropics and temperate zones.1,6,7 Canine D. immitis infection is reported in different areas of Iran. Epidemiological studies have indicated that the prevalence of D. immitis in dogs from different parts of Iran ranges from 1.40% to 51.40%.8-17 Meshkin-Shahr is an endemic area for this parasite. There are four reports of human D. immitis infection in Iran in which two pulmonary cases were related to Meshkin-Shahr district.16,18-20 Regarding high prevalence of dirofilariasis in dogs in this area and their medical importance, the current study was designed to understand age and sex distribution of D. immitis in infected dogs and molecular analysis of D. immitis based on partial mitochondrial cytochrome oxidase subunit 1 (COX1) sequence and their phylogenetic relationships compared to the isolates from other areas of the world.Study area. Meshkin-Shahr is a city located in the central northern part of the Ardabil Province, northwest of Iran. It is situated at an altitude of 1490 m above sea level between longitudes 47° 190ˊ and 48° 170ˊ East and latitudes 38° 570ˊ and 38° 130ˊ North  ethanol until extraction of genomic DNA.D. immitis adult worms were thoroughly washed in distilled water to remove ethanol. Total genomic DNA was extracted using Bioneer DNA extraction kit  according to the manufacturer's instructions and stored at – 20 ˚C until polymerase chain reaction (PCR) amplification.At the time of extraction, 2 ; 10 pmol of each primer and 3 μL of DNA sample. Primers COIintF (5-TGATTGGTGGTTTTGGTAA-3) and COIintR (5-ATAAGTAC GAGTATCAATATC-3) amplify a 689 bp target of COX1 gene.23 The temperature profile was an initial denaturation step at 94 ˚C for 5 min, followed by 30 cycles of denaturation at 94 ˚C for 30 sec, annealing at 52 ˚C for 45 sec, extension at 72 ˚C for 60 sec, followed by a final extension at 72 ˚C for 7 min.The PCR was carried out in a final reaction volume of 30 μL using 15 μL of PCR mix containing 1.25 U Taq DNA polymerase, 200 μM of dNTPs and 1.5 mM MgClThe PCR products were electrophoresed on a 1.5% of agarose gel  and visualized using ethidium bromide in UV transilluminator . Next, The PCR products were purified with a commercial purification kit (Bioneer), according to the manufacturer’s instructions. Purified products were sequenced in one direction using the forward primer.24 Phylogenetic analysis was carried out using maximum likelihood method based on Tamura-Nei model.25 Pairwise comparisons were determined as as the level of sequence differences using MEGA software .25 Bootstrap analysis was carried out with 1000 replications.Sequence results were edited and analyzed by Geneious software . The sequences were compared GenBank references sequences by BLAST program.Statistical analysis. Chi-square (X2) test was used to compare infection with D. immitis in the infected dogs in association with their gender and age. Statistical analyses were performed using SPSS , with a p value less than 0.05 as statistically significant.D. immitis. The rate of infection in male and female dogs were 15 (16.40%) and 4 (12.00%), respectively. No statistically significant difference was found between D. immitis infection and gender (p = 0.70). However, the rate of infection in dogs more than 2 years old (17/60) was significantly higher than those with lower age (2/31) . Out of 91 dogs examined in the current study, using direct blood smears, 75 (82.40%) were male and 16 (17.60%) were female. All of the dogs were in mixed breed, keeping as guard dogs and sheep-dogs. Overall, 19 dogs (20.87%) were found infected with D. immitis were collected from heart of two necropsied dogs (D. immitis GenBank references sequences. The COX1 sequences of the isolates obtained in this study were submitted to GenBank database (accession numbers: KT318126 and KT960976). The BLAST analysis indicated that the sequences of the isolates of D. immitis from this study were identical and presented 100% homology with D. immitis isolated from jackal (KT351852) in northeast Iran,26 dog (EU159111) and red panda (EU169124) in China, dog (KC107805) in Bangladesh and cat (AM749227), dog (AM749228) and wolf (DQ358815) in Italy and was 99.40% similar in that of D. immitis isolated from dog in Italy .Adult worms of ied dogs . The twoied dogs . The seqAscaris lumbricoides (Accession no. AB591801) as out-group were included in a big branch tree. Phylogenetic analysis showed that D. immitis and D. repens were sister species.All the taxa besides D. immitis was 0 to 0.50%; meanwhile, inter-species sequence differences among the seven nematodes of onchocercidae family were significantly higher, being 10.70 to22.50% , depending on the environmental and climatic conditions, distribution of the vector and diagnostic methods.8-14,16,17 The gold standard technique for canine dirofilariasis considered to be Knott’s test,27 thus, the real infection rate in the study area might be higher.In the current study, based on the thin and thick blood smears examination, microfilariae of D. immitis than that of females (16.40% versus 12.00%), however, similar to some previous studies,13,16,17,28 this difference was not statistically significant. This was in part probably due to sample size of the present study. Some other researchers, however, reported that rate of infection in males was higher than female dogs.23,29The results of this study showed that male dogs were more infected with D. immitis was increased with age of the dogs and it was in agreement with some previous studies.16,30 Statistical analysis revealed greater infection rate in older dogs (more than two years old) than younger dogs (28.30% versus 6.40%) and it was possibly due to the longer exposure of older dogs to the mosquito bites.31Our findings indicated that the chance of infection with 32-34 However, only a few studies have analyzed molecular characterization of D. immitis.35,36 This study is the first phylogenetic analysis of D. immitis from Iran. As mentioned earlier, the isolates of D. immitis collected from dogs in Meshkin-Shahr had 100% homology with the isolates of D. immitis collected from dog, red panda, cat, jackal and wolf from different areas of the world except for one isolate of D. immitis from Italy (Accession no. AM749228) with 99.40% similarity.Sequence-based phylogenetic analysis is a useful tool to get information from organism evolutionary relationships. The existence of genetic variation among nematodes has been confirmed previously.Therefore, phylogenetic analysis reveals that variation of the host was not associated with sequence variation of the parasite isolates.D. immitis were classified close to the cluster containing D. repens isolate. These results suggested the existence of polymorphic variation in the COX1 sequence in Dirofilaria species that could be suitable for species identification of the genus Dirofilaria. According to Huang et al. phylogeny analysis of the family Onchocercidae based on COX1 gene is in agreement with the classification of filarial nematodes using morphological and biological characters and could be helpful for distinguishing intra- and interspecies genetic variation.35In the present study, the isolates of Dirofilaria nematodes. For an intensive understanding of genetic variation among populations of D. immitis, analysis of more isolates from other geographical areas, different hosts and genetic markers is recommended.In conclusion, this study demonstrated that COX1 gene sequences were suitable markers for phylogenetic analysis of


Despite ongoing consumer demand and an emerging scientific evidence-base for traditional and complementary medicine (T&CM), there remains a paucity of reliable information in standard clinical guidelines about their use. Often T&CM interventions are not mentioned, or the recommendations arising from these guidelines are unhelpful to end-users . Insufficient evidence of efficacy may be a contributing factor; however, often informative recommendations could still be made by drawing on relevant information from other avenues. In light of this, the aim of this research was to review national and internationally endorsed consensus statements for clinical guideline developers, and to interpret how to apply these methods when making recommendations regarding the use of T&CM.The critical interpretive review method was used to identify and appraise relevant consensus statements published between 1995 and 2015. The statements were identified using a purposive sampling technique until data saturation was reached. The most recent edition of a statement was included in the analysis. The content, scope and themes of the statements were compared and interpreted within the context of the T&CM setting; including history, regulation, use, emerging scientific evidence-base and existing guidelines.Eight consensus statements were included in the interpretive review. Searching stopped at this stage as no new major themes were identified. The five themes relevant to the challenges of developing T&CM guidelines were: (1) framing the question; (2) the limitations of using an evidence hierarchy; (3) strategies for dealing with insufficient, high quality evidence; (4) the importance of qualifying a recommendation; and (5) the need for structured consensus development.Evidence regarding safety, efficacy and cost effectiveness are not the only information required to make recommendations for clinical guidelines. Modifying factors such as burden of disease, magnitude of effect, current use, demand, equity and ease of integration should also be considered. Uptake of the recommendations arising from this review are expected to result in the development of higher quality clinical guidelines that offer greater assistance to those seeking answers about the appropriate use of T&CM. Traditional and complementary medicine (T&CM) refers to a conglomerate of health-related interventions and therapies not usually considered mainstream by the Western medical system. T&CM includes (but is not limited to) naturopathy, traditional Chinese medicine, Ayurvedic medicine, homeopathy, chiropractic, osteopathy, massage therapy, yoga and meditation. In such a multifarious field with divergent training requirements, different models of regulation, and myriad treatment options informed by varying (and sometimes inconsistent) evidence, it is not surprising there is considerable diversity in clinical practice . The imp“systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances” [Clinical guidelines are stances”  that aimstances” –6. The lstances” . Increasstances” –10. Despstances” .The quality of clinical guidelines continues to be a matter of concern, hence the development of various guideline appraisal tools such as the AGREE II , 13. In Given the aforementioned findings, clinical guidelines of higher quality are urgently required to guide the safe and rational use of T&CM in practice . Indeed,“Decision makers do not have the luxury of waiting for certain evidence. Even though evidence is insufficient, the clinician must still provide advice, patients must make choices, and policy makers must establish policies” [olicies” .Insufficient evidence about any intervention or practice poses significant challenges for guideline developers. In the case of T&CM, failure to evaluate the field or even make a recommendation when there is insufficient evidence of efficacy may simply widen the gap between what practitioners and users of T&CM are doing, and what is considered best practice. Guideline developers should always attempt to make specific, informative recommendations about the use of T&CM –20. As PFurther guidance on how to use all available information and evidence for clinical decision making will help improve the utility of clinical guidelines that consider T&CM. Debate continues in the T&CM field and more generally around the appropriate use of evidence for evaluating interventions –24. The A critical interpretive review of consensus statements for guideline developers was undertaken , 26. TheThe consensus statements for guideline developers were identified using a similar approach to that used in the interpretive synthesis outlined by Dixon-Woods et.al . The litThe authors defined a consensus statement as a document or similar resource (e.g. website) developed by an independent panel of experts that provided systematic guidance. In this instance, the guidance was on methodologies for formulating clinical guidelines or related health policies. Only statements endorsed by national or international authorities and published in English were included. Consensus statements on health policy making were also included since clinical guidelines are used not only to inform clinical decision making but to inform health service delivery and public health policies. Consensus statements describing how to appraise the quality of clinical guidelines were excluded as no new themes could be identified that were not already addressed in detail, including the rationale, in the statements on guideline development. Statements published from 1995 until the end of the search date in 2015 were included. For those with multiple iterations, only the most recent edition of a statement was included in the analysis. and contradictions . Lines-of-arguments (synthesising arguments) were generated by integrating the content and themes identified in the individual statements. The aim was to identify overarching themes and constructs, and then interpret how they apply to T&CM.An interpretive approach was used to appraise and synthesise the information , 26. ThiEight consensus statements for guideline developers met the inclusion criteria for in-depth review; this was the point at which data saturation was reached and no new major themes emerged. Three of the statements were international , 32–63; The primary focus of the first seven statements  was often recommended to help formulate clinically relevant questions and patient-important outcomes were increasingly emphasised , 68, 72.“The effects of complementary and alternative therapies may be addressed in the guideline if such therapies are commonly used in the clinical area of interest. If commonly used complementary and alternative therapies are not to be covered in the guideline, this should be stated clearly in the scope.” [ scope.” .Little guidance was provided however about methods for systematically identify potentially relevant interventions and selecting interventions for further in-depth systematic reviews. The WHO and NICE both provided guidance around choosing priority topics and interventions , 72. ThiAs the various recommendations for developing guidelines have been updated, there has been a move away from using a ‘hierarchy of evidence’ or ‘levels of evidence’ towards the GRADE approach to making recommendations. This is due to ongoing concerns that a hierarchy can inappropriately encourage guideline developers and policy makers to directly link study design to recommendation strength, or ignore lower levels of evidence that should also be included when grading the strength of the recommendation . NICE ceThe Australian National Health and Medical Research Council (NHMRC) guideline was the only included consensus statement that continued to use an evidence hierarchy as a direct constrainer on the strength of the recommendations . AccordiGRADE and the USPSTF statements provided the most specific advice on how to manage the challenges of insufficient, high quality evidence. The SUPPORT statement most clearly emphasised that inconclusive results or lack of research should not be misinterpreted as evidence of no effect. Despite insufficient evidence about effectiveness, informed decisions can still be made about interventions that are potentially harmful or when the potential benefits are not worth the cost .In situations of low quality evidence for an intervention and a lack of confidence in the effect estimates of the risks and benefits, the GRADE statements outlined five instances when a strong recommendation could still be made . Table 4In the case of inconclusive or absent evidence from randomised controlled trials (RCTs) and meta-analyses, the USPSTF proposed several instances where the assemblage of non-RCT evidence would be admissible in clinical guidelines. The first is where an intervention is potentially effective, there is a large burden of disease and there is no research investigating the direct effects of the intervention on the health outcome . In thisThe second instance proposed by the USPSTF for the assemblage of non-RCT evidence is when the intervention is not amenable to being evaluated under RCT conditions . ExampleBurden of suffering – the incidence and prevalence of a condition; the degree of personal, family and community suffering; and the burden to families, society and health care systems.Potential harm – the immediate and long-term harms to individuals and patients from delivering an intervention or service and from alternatives, including the potential harms associated with doing nothing.Cost – the direct monetary costs of a service or intervention; the opportunity costs, such as the time, money and resources that would be diverted to provide an intervention with less evidence or acceptability to patients; and the costs of decommissioning the intervention should it then prove to be ineffective.Current practice – the potential negative consequences  of providing a novel, less widely used service or intervention compared to those commonly in place; and the extra resources that will be needed to change ingrained practice .  is effective for managing menopausal symptoms; however, there is also high quality evidence about the risks of HRT. , 85 By cThe inconsistencies regarding the inclusion of T&CM and recommendations made about their use in clinical guidelines calls for a more transparent and systematic approach to guideline development. Even formal methods for consensus development such as those outlined in AWMF  will be This interpretive review has considered, for the first time, the usefulness of directives for developing guidelines and recommendations regarding T&CM practice and policy. Like many areas of healthcare, insufficient evidence about efficacy poses significant challenges to guideline developers, which in the field of T&CM has contributed towards insufficient and inconsistent recommendations. The emerging and heterogeneous evidence-base for many T&CM interventions necessitates a range of methodologies to ensure the systematic selection of interventions and consideration of modifying factors when formulating and qualifying recommendations. In light of these issues and the high demand for T&CM, we behove guideline developers to consider T&CM from a number of perspectives when appraising the evidence, and to make clinically useful and specific recommendations regarding their use.Specifically, guideline developers should cease endorsing an evidence hierarchy as a direct constrainer of recommendations. Strict use of the levels of evidence runs the risk of inappropriately linking the quality of the evidence for efficacy directly to the strength of the recommendation, whilst ignoring admissible non-RCT evidence and important modifying factors. In instances of very low quality or equivocal evidence of efficacy, guideline developers must consider the paradigmatic situations where nonetheless a strong recommendation can be made. Failing this, broader contextual information is often available for T&CM even when there is low quality scientific evidence regarding efficacy. Information about modifying factors should be presented to facilitate informed decision making and improve clinical relevance. Finally, greater attention must be given to adopting a systematic and transparent approach to the entire development process, including the selection of comparative interventions and patient relevant outcomes. The uptake of these recommendations is expected to result in higher quality clinical guidelines that offer greater assistance to those seeking answers about the appropriate use of T&CM.


Therefore, healthcare guidelines and their appropriate implementation are of interest to nationalorganizations, professional societies, health care providers, policy-makers, patients,and the public.Clinical practice guidelines are useful tools to improve delivery of the best care, basedon the best available evidence, for our patients. They help practitioners to makeclinical decisions and might help to ensure the proper allocation of resources in publichealth policy.Guidelines must be grounded on the evidence-based medicine paradigm, which is comprisedof four fundamental aspects: recognition of the patient's problem and the constructionof a structured clinical question, effective and extensive search of the medicalliterature to obtain the best available evidence, critical appraisal of the evidence,and, finally, integration of the evidence in patient decision making to determine thebest clinical care for the patient.Associação de Medicina Intensiva Brasileira (AMIB) hassettled on a project called "Diretrizes AMIB" to develop evidence-basedlocal medicine guidelines in several areas of critical care. In this issue of ourJournal, the first clinical guidelines resulting from this initiative are published.AMIB and the Associação Brasileira de Transplante deÓrgãos (ABTO) have developed guidelines for the recognition, evaluation,and validation of potential donors for organ transplantation. This is a crucial aspect,as organ transplantation is the last resource available for several health conditionsand availability of organs is limited and expensive, with high costs associated.Therefore, these guidelines aim to improve our ability to recognize and diagnose braindeath and to assess eligibility for organ donation.The  and the level ofevidence according to the Projeto Diretrizes daAssociação Médica Brasileira (AMB) e doConselho Federal de Medicina (CFM). The authors then built a set of recommendations aimingto establish more protocolled care of the potential donor, as well as identifying andselecting patients, and optimizing the use of resources. The authors made a substantialeffort to summarize the best evidence available, especially in a subject such as this,in which few high quality studies are published. Certainly, this project will provideguidance on the most effective management methods to screen, identify, and select adonor in Brazil, thus improving organ availability and transplantation.The authors divide the guidelines into four subgroups: screening of potential donors;brain death diagnosis; criteria for the selection of potential donor; and organ-specificcontraindications. The authors defined the strength of recommendation according to theGRADE methodology  Based on AGREE II, any guideline shouldbe evaluated according to six domains, and this methodology will be used during thewhole process in the project Diretrizes AMIB.These guidelines were evaluated by members of the editorial board of the Journal whoconsidered qualitative aspects of its methodology. Every clinical recommendation andguideline should be assessed to ensure that potential biases of guideline developmenthave been adequately addressed and that the recommendations are both internally andexternally valid and are feasible for practice. This is a complex process, and sometools are available in the literature . The assessment includesjudgments about the methods used for developing the guidelines, the components of thefinal recommendations, and the factors that are linked to their uptake.The first domain refers to the "Scope and purpose" of the guideline. Here, reviewers willevaluate whether objectives, research questions, and study populations are well definedand declare the expected health benefit specific to the clinical problem or healthtopic. Then, the second domain assesses "Stakeholder involvement." The guideline will beassessed regarding authors' involvement in the process and to ensure that all groupspotentially interested in the results are represented and that targets are well defined.Undeclared conflicts of interest may be discovered when assessing these points andshould be considered in guideline quality analysis as along with editorial independence.The next domain is "Rigor of development," in which all methodologies of guidelinebuilding will be evaluated. The domain will address search criteria, how evidence wasselected and graded, the strength of recommendations and how were they stated, and howwell these aspects were described. Next, the fourth domain will assess "Clarity ofpresentation." This refers to how specific and unambiguous the recommendations providedare, what options for management are offered, and how to handle uncertainty about thebest care option when evidence is not definite. The fifth domain is "Applicability." Aproper guideline should describe facilitators and barriers to its implementation as wellas discuss resources and tools for monitoring or auditing its implementation. The lastdomain refers to "Editorial independence" and aims to assure that the views of thefunding body have not influenced the guideline content and recommendations.Diretrizes AMIB project aimed to improve thequality of critical care in Brazil by delivering the best available care based on thebest available evidence. Evidence-based practice brings pertinent, trustworthyinformation into clinical management and policy arenas by systematically acquiring,analyzing, and transferring research findings. Evaluating our documents based on the described aspects forquality assessment will ensure liability, scientific rigor, and the confidence ofdoctors, families, and health policy makers in our recommendations, as well ascontribute to the rational use of resources to provide the best management available forcritical care patients in Brazil.We at the Revista Brasileira de Terapia Intensiva look forward to the next initiativesand guidelines from the


The objective of this work was to provide easy access to reliable health information based on good quality research that will help health care professionals to learn what works best for seniors to stay as healthy as possible, manage health conditions and build supportive health systems. This will help meet the demands of our aging population that clinicians provide high quality care for older adults, that public health professionals deliver disease prevention and health promotion strategies across the life span, and that policymakers address the economic and social need to create a robust health system and a healthy society for all ages.The McMaster Optimal Aging Portal’s  professional bibliographic database contains high quality scientific evidence about optimal aging specifically targeted to clinicians, public health professionals and policymakers. The database content comes from three information services: McMaster Premium LiteratUre Service (MacPLUS™), Health Evidence™ and Health Systems Evidence. The Portal is continually updated, freely accessible online, easily searchable, and provides email-based alerts when new records are added. The database is being continually assessed for value, usability and use. A number of improvements are planned, including French language translation of content, increased linkages between related records within the Portal database, and inclusion of additional types of content. While this article focuses on the professional database, the Portal also houses resources for patients, caregivers and the general public, which may also be of interest to geriatric practitioners and researchers. As the population in many countries steadily ages and individuals get older , 2, therThe shift in population demographics has implications for professionals working in the health care field. While geriatricians and other clinicians will be required to continue providing high quality care for unhealthy older adults, there is a growing expectation for public health professionals to deliver disease prevention and health promotion strategies focused on older adults and for policymakers to address the economic and social need to create a healthy society for all ages . Easy acThere is widespread acceptance that health care practices and policies should be based on research evidence . HoweverThe McMaster Optimal Aging Portal’s professional bibliographic database contains high quality scientific evidence about optimal aging specifically targeted to clinicians, public health professionals and policymakers. The search engine allows users to quickly examine synthesized evidence on the available research, be alerted to new evidence as it is published, and get direct access to updated information that can be used to help geriatric patients, communities and jurisdictions to be as healthy as possible. The database is freely accessible via the McMaster Optimal Aging Portal , which was officially launched on October 1, 2014. The Portal also houses resources for patients, caregivers and the general public, which may also be of interest to geriatric practitioners and researchers, and is described elsewhere . This arThe Portal database content comes from three information services: McMaster Premium LiteratUre Service (MacPLUS™) –14, Healhttps://www.healthsystemsevidence.org/about). To be included in the Portal database, the content from each service is filtered for its application to adults 60 years of age and older. The database is continually being expanded with new records/publications, and includes original studies and systematic reviews and select single studies  with older adults and research on health promotion, disease prevention or the management of health conditions. As of September 15, 2015, the Portal database contained 29,247 bibliographic records .MacPLUS™ was created in 1991 and continuously updated since. The intellectual property for the process of critical appraisal and clinical ratings belongs to McMaster University, a not-for-profit, public university in Hamilton, Ontario, Canada. MacPLUS™ is supported by research funds and licensing contracts with academic, professional and commercial publishers which collectively cover the production costs and research dedicated to improving the service –14. DeveWe used HTML5, CSS3, and Javascript jQuery components incorporating, but not limited to, KendoUI. We leveraged the extensibility of the Telerik Sitefinity ASP.NET web content management system to enhance the existing components/widgets, and create our own model-view-controller (MVC)-based ones. Communication between the presentation layer of the website and the database is handled in the backend using a custom C# application programming interface (API) to query the remote databases; and is delivered locally through a RESTful API to the site through the ServiceStack platform. This allows us to prevent cross-origin JavaScript object notation (JSON) issues, and restrict access using the native permissions in the web content management system.The system is built on the Microsoft ASP.NET 4.5 framework, using a SQL 2008 R2 database for both the evidence articles and web content management system. We also use a social integration Software-as-a-Service model to ensure all pages, posts, resources and links are shareable; as well as incorporating a Twitter widget on the site, where appropriate.http://www.sitefinity.com/multilingual-content) were used, aiming for a fully bilingual site in English and French. This multilingual framework provides the potential for additional languages in the future.The Sitefinity content management system’s multilingual content and translation management features (http://en.wikipedia.org/wiki/Agile_software_development). This approach encompasses the overall design, including the website interface, architecture, registration functionality and database integration. The Portal is built using a mobile first approach to ensure a stable responsive design that scales to any size phone, tablet or desktop . The Portal database was developed with a primary goal of easy navigation and searchability. The results that best match the users’ identified professional role are displayed most prominently in the central portion of the webpage. The relevant content from the different disciplinary services is also retrieved following the search. The related records from the other professional (and citizen) content available on the Portal are available on the right side of the page Fig. . For allThe content of the Portal database is not static; rather it is constantly updated. The Portal provides an easy way to access high quality, rated research evidence from the huge and ever growing health sciences literature. The information contained in the database can provide support for evidence-based practice, evidence-based public health, and evidence-informed policy. It can facilitate a number of research endeavors such as bibliometric, scientometric and knowledge-based informatics research, user and role search preferences, and information needs analysis.The database was pilot-tested with 20 professional users  and eight non-professional users. Overall, the Portal was perceived as a useful resource for professionals. Based on specific feedback, we implemented a number of changes to improve display, usability, functionality, navigation, and address any technical glitches.While other bibliographic databases exist, the Portal database bring together a wide range of features by including all of the characteristics listed in Table Global Health  and UpToDate (http://www.uptodate.com).The Portal content has been independently rated for quality by MacPLUS™, Health Evidence or Health Systems Evidence before being included in the database Table , with adWe strive to continue improving the value and usability of the Portal’s database content for professionals. A number of improvements are planned for the near future Table .Table 3PWe present fictional case studies to demonstrate three possible uses of the Portal database. The individuals depicted below are not real people; rather, they were invented for illustrative purposes only. The case studies are based on a combination of use cases with scenarios and personas that were created during the development and testing phases , feedbacDr. Seow is visited by an 80-year old healthy patient who mentions a study that appeared on the evening news and attracted her attention. The study claimed that vitamin D can prevent cancer. However, her friend was taking vitamins and she was only 70 years old when she died of cancer. The patient is wondering whether she should start taking vitamin D. The physician logs on to the Portal using the clinic computer. By searching for “vitamin D and cancer” he finds 25 high quality systematic reviews in the clinician service on the topic Fig. . He narrDiana is developing a new initiative on injury and falls prevention. She is interested in what the evidence says about community-wide falls prevention strategies. A search on “fall prevention” brings up 77 public health articles. To be certain that she reviews the best quality evidence, she selects “Strong” under the “Review quality rating” filter which reduces the results set to 40. She directs a member of her team to review the 40 articles, while she also examines the clinician and policymaker records. Based on a number of high quality systematic reviews, the team decides to start a program offering group exercise sessions and instructional training for home exercises focused on improving balance.The news has recently been focusing on patient safety and adverse drug reactions in long-term care/nursing homes. Joseph, a policymaker, wants to know where to invest time and resources. He logs onto the Portal to look for a systematic review on the topic. A search for “long term care” retrieves 30 policymaker records. Joseph is pleased to find a 2015 article entitled “Computerised clinical decision support systems to improve medication safety in long-term care homes: A systematic review.” He is able to link to the freely available full-text report, and shares the structured abstract with his colleagues. At the next team meeting, they discuss the finding of the systematic review; i.e., that computerized clinical decision support systems may improve the quality of prescribing decisions in long-term care, better detect potential adverse drug reactions, and show potential to reduce injury risk among older adults. Together, they plan to implement a pilot study in collaboration with a long-term care facility. Joseph also signs up to receive monthly email alerts containing links to newly identified research evidence on the topic of delivery arrangements and home care and long-term care sectors.one place the highest quality available research evidence on geriatrics. By having a single evidence database to access, professionals no longer have to remember which database to go to depending on their query and do not have to visit individual databases for different professional perspectives on a health topic. Health professionals and researchers can access research evidence about healthy aging that has been synthesized on a single topic. The database contains only research evidence in which users can have confidence or it provides a quality rating that allows users to adjust their confidence level.The Portal database puts in The limitations of the Portal professional database include those related to the individual methodology of the three information sources Table . Only sp


In the first decades of the 20th century, scientific papers were published suggesting the presence of Tick-Borne Relapsing Fever in Colombia. As a contribution, we present some historical aspects referring to this topic. Dear Editor,We have read with great interest the review made by Lopez JE, et al., in which several aspects related to Tick-Borne Relapsing Fever (TBRF) in the Americas are addressed . In thisOrnithodoros turicata is the possible vector of the disease in the municipality of Muzo, Department of Boyacá [Borrelia  as etiological agents of TBRF in the neotropical region comprised between southern Central America and northern South America, related with O. talaje and O. venezuelensis as their vectors, respectively [O. venezuelensis were captured, of which 2483 (61 pools) were evaluated for the presence and infection by Borrelia through the murine model, with 17 pools being positive (27.86%) [O. venezuelensis, mainly in the departments of the Colombian Pacific region, suggesting an appropriate environment for TBRF in human population, easily confused with Malaria in that geographical region [In Colombia, the first approaches to the local epidemiology of TBRF were published by Franco R, et al. in 1911, suggesting that the tick f Boyacá . Subsequectively ,4,5. In ectively . This siich 2483 1 pools wich 2483 1 pools wO. venezuelensis by Brumpt in 1921 [O. talaje and O. turicata, related to the transmission of TBRF in Colombia, Venezuela and Panamá before 1923, actually belonged to the species O. venezuelensis [O. venezuelensis and O. talaje (classified at that time as competent vectors for Borrelia spp.) in such Latin American countries, describing the former as a common tick in households, whose main host was the human, and the latter, that, despite being present in households (in a lesser extent), mainly fed upon rodents of the genus Rattus and rarely humans [O. venezuelensis is the main vector related to the epidemiology of TBRF in northern South America.Interestingly, in 1927, based on his own investigation, and those from other authors, especially in the previous taxonomic description of uelensis . Additioy humans . Thus, iOn the other hand, as Dunn, Emilio J. Pampana described in the 1920s the clinical context of the TBRF in Colombia after the observation of human cases in the department of Chocó (Colombian Pacific region) . Thus, iO. rudis Karsch, 1880 (previously O. venezuelensis) [O. talaje, the distribution of which remained unclear [O. rudis was also recognized as a vector of TBRF in the south of Central America and in Venezuela in the border region with Colombia [B. venezuelensis was the probable etiologic agent [Years later, with the research work of Osorno-Mesa in 1940, elensis)  was cons unclear . In relaColombia , and B. ic agent .Ornithodoros in Central and South America, the related Borrelias that cause TBRF and possible underdiagnosed human cases or confusion with other causes of acute febrile syndrome [With this review, we have presented the, even now very little, scientific evidence that suggests the presence of TBRF in Colombia. This could be the initial point for starting new investigations, hand-in-hand with tools such as molecular biology, in order to determine the current distribution of ticks of the genus syndrome , as was syndrome .


Informed consent (IC) is an ethical and legal prerequisite for trial participation, yet current approaches evaluating participant understanding for IC during recruitment lack consistency. No validated measure has been identified that evaluates participant understanding for IC based on their contributions during consent interactions. This paper outlines the development and formative evaluation of the Participatory and Informed Consent (PIC) measure for application to recorded recruitment appointments. The PIC allows the evaluation of recruiter information provision and evidence of participant understanding.Published guidelines for IC were reviewed to identify potential items for inclusion. Seventeen purposively sampled trial recruitment appointments from three diverse trials were reviewed to identify the presence of items relevant to IC. A developmental version of the measure (DevPICv1) was drafted and applied to six further recruitment appointments from three further diverse trials to evaluate feasibility, validity, stability and inter-rater reliability. Findings guided revision of the measure (DevPICv2) which was applied to six further recruitment appointments as above.DevPICv1 assessed recruiter information provision (detail and clarity assessed separately) and participant talk (detail and understanding assessed separately) over 20 parameters . Initial application of the measure to six diverse recruitment appointments demonstrated promising stability and inter-rater reliability but a need to simplify the measure to shorten time for completion. The revised measure (DevPICv2) combined assessment of detail and clarity of recruiter information and detail and evidence of participant understanding into two single scales for application to 22 parameters or 25 parameters for three-arm trials. Application of DevPICv2 to six further diverse recruitment appointments showed considerable improvements in feasibility (e.g. time to complete) with good levels of stability (i.e. test-retest reliability) and inter-rater reliability maintained.The DevPICv2 provides a measure for application to trial recruitment appointments to evaluate quality of recruiter information provision and evidence of patient understanding and participation during IC discussions. Initial evaluation shows promising feasibility, validity, reliability and ability to discriminate across a range of recruiter practice and evidence of participant understanding. More validation work is needed in new clinical trials to evaluate and refine the measure further.The online version of this article (doi:10.1186/s13063-017-2048-7) contains supplementary material, which is available to authorized users. Informed consent (IC) is a legally and ethically established prerequisite for trial participation that is enshrined in international and national guidelines –3. IC isExisting methods for assessing participant understanding for IC for research participation include participant self-report via questionnaires –13 or stThese frameworks evaluate the content and manner in which recruiters provide information, but make no attempt to measure participant understanding as demonstrated in the interaction or extent of participation in the conversation , 21. EviWe set out to develop a measure of IC that could be applied to consent interactions taking place during recruitment appointments (or recordings of these) to evaluate the breadth and clarity of information provision on key issues required for IC and also, more innovatively, to assess evidence of patient understanding and participation during the interaction. The ultimate aim of this work is to optimise participant understanding during trial recruitment by improving recruiter practice during informed consent discussions. This paper outlines the development and formative evaluation of the Participatory and Informed Consent (PIC) measure.There were two stages in the development and formative evaluation of the PIC measure: first, determining items for inclusion; and second a two-phase formative evaluation.The following academic literature was reviewed to identify potential concepts for inclusion: published international and national guidelines on what information should be understood by potential participants for IC to be achieved –3, 5–7; A purposive sample of 17 audio-recorded recruitment appointments involving recruiters with a range of specialties and backgrounds  from three trials –41 canc.Table 2CTwo researchers with expertise in recruitment to trials (JW and SP) analysed all 17 appointments independently to identify the presence or absence of concepts identified in Table Combining evidence from the academic literature review and subsequent assessment of the practicability and feasibility of evaluating audio-recordings of trial recruitment appointments, a developmental version of the measure was drawn up  or 23 parameters  of the new measure was assessed by evaluating changes in item responses when the measure was applied to a single appointment by the same researcher, with an interval of at least 14 days. Rating procedure was as described for inter-rater reliability.In interpreting both reliability and stability, a discrepancy of 1 point or less was deemed acceptable on the grounds that this might represent the difference between the presence and absence of information and between ‘mostly clear’ and ‘very clear’ on the scale. Larger discrepancies were noted.Qualitative evaluation: free-text comments recorded by raters on the content and interaction in the recruitment appointment and the application of the measure were collated. Thematic analysis [analysis  was usedFindings from phase 1 were reviewed by a panel  convened to revise and shorten the measure to produce DevPICv2. In phase 2, it was then applied by the same two researchers (JW and DE) to six new appointments, purposively sampled as before from three trials , 43, 46,The DevPICv1  as described in phase 1 above.Each rater was required to rate each of 22 parameters  or 25 parameters  twice, first evaluating the presence and clarity of recruiter information and second evidence of understanding shown in patient talk about each parameter. This gave a total of 138 comparisons evaluating recruiter information and 138 comparisons evaluating evidence of patient understanding respectively. As in phase one, a discrepancy of 1 point or less was deemed acceptable on the grounds that this might represent the difference between the presence and absence of information and between ‘mostly clear’ and ‘very clear’ on the scale. Larger discrepancies were noted.Free-text or narrative comments made during application of the measure were collated and analysed thematically as described above. In addition, concurrent validity was assessed by applying another measure of recruiter information provision for informed consent, the Process and Quality of Informed Consent Instrument (P-QIC) , to the Analysis of the initial 17 recruitment appointments revealed wide variation in both whether and how concepts identified within guidelines as a pre-requisite for the IC process were presented and discussed during appointments. Guidelines identified concepts to be covered but did not provide sufficient detail to enable consistency in presentation during recruitment to trials in practice. The broad stipulation that participants should understand trial procedures , 3 was tConcepts and items in the measure were revised to reflect these issues and particularly to include patient priorities during the information exchange as identified in these appointments and previous studies , 25, 47.Table Completion of the measure took a mean of 117 min per appointment, and varied from 75 to 169 min for those lasting between 17 min and 40 min. Although raters felt that the time commitment decreased as familiarity with the measure increased this was longer than the hour limit set; therefore, the measure needed to be reduced.Analysis of missing data for individual items showed no missing data in first application of the measure by either rater, indicating good acceptability of included items. Free-text comments provided by raters reported difficulty rating levels of patient understanding.Levels of inter-rater agreement are shown in Table Rates of test-retest or intra-rater agreement are shown in Table per se on the basis of evidence emerging from the interaction. It was argued that a more realistic option would be to rate only evidence of understanding or misunderstanding. Recruiters who were most successful in allowing evidence of understanding to emerge during the discussion facilitated substantive patient contributions to the discussion. They also framed equipoise as providing the rationale for both the trial and the random allocation of treatment to take place.Free-text comments noted on application of the measure during phase 1 of the evaluation highlighted a number of issues. Time taken to complete the measure needed to be reduced and it was questioned whether a rater was able to judge levels of patient understanding Levels of recruiter detail and clarity of detail were combined into a single scale so that raters were able to rate presence/absence of information and the level of clarity of that information within a single 4-point scale .evidence of understanding. The revised scale required a judgement about levels of evidence of understanding .The two scales rating the level of detail found in patient talk and levels of patient understanding were also merged into a single 4-point scale. Feedback from the qualitative evaluation was that raters could not be expected to make a judgement on participants’ levels of understanding but only to judge levels of Key content relevant for setting the trial in the context of the patient’s diagnosis and decision-making regarding treatments were brought together in Section 2i, items 1–8 of the measure  what the recruiter said, (2) how it was said and (3) how it appeared to be understood by the participant .Analysis of missing data for individual items showed no missing data in the first application of the measure by either rater, indicating good acceptability of included items. Spearman’s rank correlation between P-QIC and the total score for DevPICv2 recruiter information provision was 0.80  are shown in Table nt Figs.  and 2 thComments in this section noted that at times a brief summary of key information  appeared more beneficial to patient understanding than extensive detail about treatment arms . Raters observed that evidence of understanding as created during conversation could be distinguished from evidence of understanding brought by patients and present from the outset. Evidence for this could be detected in patient comments showing awareness of issues that had not yet been discussed or showing evidence of understanding emerging during discussion.This study describes the development and formative evaluation of a measure of participatory and informed consent (PIC) for application to trial recruitment appointments to evaluate consent interactions for the content and clarity of recruiter information provision and also the extent to which evidence of patient understanding emerges. Initial work identified concepts for inclusion in the measure. This was followed by a two-phase evaluation: phase 1 highlighted a need to shorten the measure to improve feasibility, validity and reliability; and phase 2 showed considerable improvements in feasibility (e.g. time to complete) stability (i.e. test-retest reliability) and inter-rater reliability, suggesting that the measure is now ready for a more comprehensive evaluation. The measure’s novelty and value lie in its evaluation of evidence of patient understanding to place this at the forefront and as the key variable for evaluating the immediate outcomes of an IC discussion. It is now available for further validation in the context of new clinical trials.The ultimate goal of this work is to optimise information provision by trial recruiters so that they are able to attend to and maximise participant understanding during consent interactions during recruitment. Participant understanding is an ethical prerequisite for recruiters taking consent for trial participation and it should, therefore, be in evidence during the IC discussion prior to consent or refusal being given . By evalPrevious measures of informed consent for research have mainly used methods of participant reporting via questionnaires or telephone interviews –15. SuchThis study describes the development and formative evaluation of the PIC; further evaluation is ongoing. Mean time to complete the measure remained at just under an hour per appointment during phase-2 evaluation: for the measure to be feasible for application in busy clinics it will benefit from further reduction in rater burden. Evaluation to date has been small scale and data on stability and reliability have been reported as percentage agreements rather than performing formal calculations (e.g. kappa statistics). Future evaluation should include sociodemographic data on patients involved in the recruitment appointments. However, the PIC evaluates understanding for IC in a way that has not previously been attempted and an iterative developmental process was most appropriate at this stage. There are methodological challenges in attempting to measure evidence of participant understanding (or misunderstanding) based on their contributions to a discussion, e.g. assuming understanding on the basis of a minimal response (e.g. ‘mm’ or ‘uhuh’) from the participant to information presented by the recruiter when they may have been functioning as continuers, signalling ‘passive recipiency’ .Insights from conversation analysis (CA) on achieving understanding in interaction show that repeat utterances or even statements such as ‘I understand’ are often treated as only claiming, as opposed to evidencing understanding . FurtherFuture development of the measure will include the creation of a detailed coding manual with the aim of increasing inter-rater reliability and evaluation of the measure’s performance in additional trial contexts in a full psychometric evaluation. Promising agreement was shown in DevPICv2 between evaluation using Section 2i-iii and Section 3 and it may be that the measure can be reduced further using Section 3 as a model; more data are needed to determine relative validity of these two sections. The measure currently incorporates a qualitative narrative describing the interaction, adding to the rater burden but providing useful insights into issues that are highly relevant to optimizing patient understanding. Future work will examine whether these areas can be quantified. Preliminary evaluation reported here showed variation in the extent to which recruiter information provision conformed to standards identified in our measure and assumed to be requisite for the IC process, indicating promising discriminative validity and showing consistency with other study findings . It alsoThe PIC was conceived as a formative measure of informed consent, i.e. application of the measure will inform on areas of recruiter practice that can be modified in order to benefit participant understanding for informed consent. The measure provides a rapid method of evaluating the breadth and clarity of information provided by recruiters in order to highlight areas where information is lacking or unclear with a view to feed this information into training of recruiters. It was designed to be applicable across trials and diseases so as to be maximally generalizable . Our appThe DevPICv2 provides a novel measure of IC that can be applied directly to recruitment appointments where trial participation is discussed in order to evaluate the quality of recruiter information provision and, most importantly for consent interactions, evidence of patient understanding. Initial evaluation shows promising feasibility, validity and reliability and evidence that the measure is able to discriminate across a range of recruiter practice and evidence of participant understanding. Further validation work is needed in new clinical trials to evaluate and refine the measure further.