Our retrospective collection from the database registry of the Hematology Unit of the Federico II University Medical School of Naples  of all patients referring to our center (from 1 January 2009 to 31 January 2019) for lymph node biopsy-proven lymphoma and one or more distinct splenic lesions, visible at baseline ultrasonographic scans and submitted to CEUS, could be a great asset in the diagnostic approach for splenic lymphoma. For the first time, based on a robust sample size of 260 nodules  we showed that CEUS can achieve the diagnosis of splenic malignant lymphoma with excellent accuracy.n = 44) or Hodgkin lymphoma  at staging (n = 56) or follow-up (n = 21) were collected in a hematology Italian center and retrospectively analyzed. Nodules were classified as malignant lymphoma if ≥0.5 cm (long axis) with arterial phase isoen-hancement and early (onset <60 s after contrast agent injection) wash-out of marked (≤120 s after contrast agent injection) degree. Other perfusional combinations at CEUS scans qualified lesions as benign or inconclusive. Diagnostic reference standard was clinical laboratory imaging monitoring for 230 nodules, and/or histology for 30 nodules. The median nodule size was 1.5 cm (range 0.5–7 cm). According to the reference standard, 204 (78%) nodules were lymphomas (aggressive-NHL (a-NHL), 122; classic-HL (c-HL), 65; indolent (i)-NHL, 17) and 56 (22%) were benign  lesions. Sensitivity, specificity, positive predictive value, negative predictive value, and overall diagnostic accuracy of CEUS for detecting lymphoma in the spleen were 95%, 100%, 100%, 85%, and 96%, respectively. Marked wash-out range of 55–90 s , 92–120 s , and 101–120 s  was 100%, 96.6%, and 77% predictive of a-NHL, c-HL, and i-NHL splenic nodular infiltration, respectively. The CEUS perfusional pattern of arterial phase isoenhancement with early wash-out of marked degree was highly accurate for the detection of lymphomatous invasion of spleen in patients at risk, enabling its use for a confident non-invasive diagnosis.Contrast-enhanced ultrasonography (CEUS) use for detecting lymphoma in the spleen was questioned because of the risk of its inadequate diagnostic accuracy. The aim of the present study was to validate CEUS exam for the identification of spleen involvement by lymphoma in patients at risk. A total of 260 nodules from the spleens of 77 patients with lymph node biopsy-proven non-Hodgkin lymphoma (NHL;  Spleen invasion in lymphoproliferative malignancies occurs in a significant proportion of patients: involvement is reported in up to 40% of patients with non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL), and this increases to 70% at postmortem . AlthougThe American College of Radiology has recently released a very useful system (Contrast-Enhanced Ultrasonography (CEUS)/Liver Imaging Reporting and Data System (LI-RADS)) to classify nodules at risk of hepatocellular carcinoma (HCC) investigated by CEUS . The LI-The aim of this study was to test the accuracy of intravenous microbubble-based microvasculature ultrasonographic assessment of sulfur exafluoride for diagnosing lymphoma nodular infiltration of the spleen. In addition, we explored the CEUS perfusional patterns of the three principal clinical categories of lymphomas, i.e., aggressive NHL (a-NHL), classic (c)-HL, and indolent NHL (i-NHL), affecting the spleen. Finally, we examined how CEUS results impacted the diagnostic flow-chart of spleen status in patients with lymphoma at risk of splenic involvement. In our Institution, CEUS is held as a routine imaging practice for all significant lesions detected in the spleen at risk for lymphomatous invasion ,13. HereAll necessary approvals were obtained from the Ethic Committee of the Federico II University Medical School of Naples . Given the retrospective design, the acquisition of all individual informed consents was waived (except for performing microbubble intravenous infusion at CEUS time).Inclusion criteria were: (i) histological diagnosis of lymphoma , which was managed and/or treated according to the National Comprehensive Cancer Network guidelines ,16,17,18The definitive diagnoses of the subtypes of lymphomatous nodules affecting the spleen were established based on histologic results of superficial or deep-seated lymph node biopsies plus clinical/laboratory/imaging follow-up (lasting at least six months after the CEUS examinations (monitoring after therapy)), or whenever available, splenectomy or radiologically guided CNB . The defThis retrospective study was conducted in the Hematology Unit of the Federico II University of Naples .The patients included in the study underwent CEUS examinations of the spleen from 1 January 2009 to 31 January 2019.Ultrasonographic investigation of the spleen was obtained by hematologists with extensive expertise in lymphomas management and spleen CEUS  ,13, usinArterial phase isoenhancement was defined as a lesion becoming globally isoechoic compared to the surrounding parenchyma, in the arterial phase of the study. Arterial phase hypoenhancement was defined as a lesion becoming globally hypoechoic compared to the surrounding parenchyma, in the arterial phase of the study.Arterial phase hyperenhancement was defined as a lesion becoming globally or partially hyperechoic  compared to the surrounding parenchyma, in the arterial phase of the study.A rim enhancement pattern  was defined as increased enhancement mainly concentrated at the periphery of the nodule in the arterial phase of the study, followed by late wash-out.A peripheral discontinuous globular pattern was defined as peripheral enhancement in the arterial phase with progressive centripetal partial or complete fill-in.In the arterial phase of the study, a reverse rim sign describes relative hypoenhancement of the periphery of the nodule and normal enhancement in the remaining portion of the lesion.Wash-out was defined when the lesion became hypoechoic compared to the surrounding parenchyma in the portal-venous phase. When such wash-out occurred, it was further classified according to its timing: as “early” if it appeared before 60 s following contrast injection or as “late” if it occurred after 60 s, and according to its intensity, as “marked” when the lesion become hypoenhanced or dark within 2 min (otherwise defined as “mild”) following contrast injection [NHL- and HL-diagnostic criteria (DC) at CEUS were defined as nodules ≥0.5 cm with hypoenhancement in the parenchymal phase, depicted as a progressive increase of nodule-to-parenchyma contrast gradient  while moving from the arterial phase to the late phase of parenchymal opacification . Benign findings (BF)-DC at CEUS comprised nodules ≥0.5 cm with: (i) hypoenhancement in the arterial phase without late wash-out , (ii) isoenhancement in the arterial phase with or without late wash-out of mild degree intensity (capillary hemangiomas), (iii) discontinuous globular peripheral enhancement followed by progressive centripetal fill-in or very late (>3 min) wash-out of mild degree  a thin rim enhancement pattern in the arterial phase followed by wash-out in the venous phase (abscess), (v) reverse rim sign (granulocyte colony-stimulating factors (G-CSF)-related myeloid metaplasia), and (vi) hyperenhancement in the arterial phase without later wash-out (hamartomas) ,21.In a post hoc assessment, we analyzed the microvessel density (MVD) by immunohistochemical and morphometric evaluations of vascular endothelial growth factor-A (VEGF-A), VEGF receptor (Flk-1), and cyclooxygenase 2 (COX2) expression, as already described by others . This asSensitivity (probability that a CEUS result will be positive when the disease is present (true-positive rate)), specificity (probability that a CEUS result will be negative when the disease is not present (true-negative rate)), positive predictive value , negative predictive value , and, lastly, the diagnostic accuracy )  were repp < 0.05. Analysis of the data was performed using SPSS statistical analysis software .Continuous variables were reported with their median and range. A descriptive analysis was carried out, reporting rates in absolute numbers and percentages. Comparisons among groups were calculated using nonparametric (Mann–Whitney and Wilcoxon) tests. Categorical variables were considered significant at Data from a total of 264 spleen nodules were collected in 78 patients. One patient with four nodules was excluded for equivocal histologic results regarding specimens obtained by using imaging-guided CNB. Thus, the final analysis was performed on 260 nodules in 77 patients receiving the scheduled dose of contrast agent. The average time required for the complete ultrasonographic assessment was 30 min (range 25–45 min); the perfusional examinations were well-tolerated without complications. All ultrasonographic scans were assessable for the final classification. A consolidated standard for reporting of diagnostic accuracy study (STARD) diagram summarizes the flow of nodules through the study in Patient and splenic nodule characteristics are reported in n = 14 cases), CHOP (n = 4 cases), and ABVD (n = 3 cases)).The median age of analyzed patients was 48 years (range 22–72 years). Males were 57% of the cases. Fifty-six patients were found to have 198 (76%) nodules in the spleen at the time of the staging process of lymphomas. They were scheduled to receive front-line therapy  in 30 cases; Rituximab, Cyclophosphamide, Hydroxydaunorubicin, Vincristine, and Prednisone (R-CHOP) in 23 cases; and Rituximab and Bendamustin (R-Benda) in three cases) . Twenty-The median size of nodules was 1.5 cm (range 0.5–7.0 cm). Two or more nodules occurred in 47 patients , while a single nodule occurred in 30 patients. After clinical and whole-body imaging evaluations, 230 splenic nodules were accompanied by superficial and/or deep-seated lymphadenopathies, whereas the remaining 30 nodules occurred in the absence of other sites of involvement by disease.According to the reference standard, a total of 204 (in 55 patients) of 260 nodules were classified as lymphomas: a-NHL for 122 nodules ; 10, T-rich B-cell lymphoma (TRBCL); four, anaplastic T-cell lymphoma (ATCL)); c-HL for 65 nodules ; and i-NHL for 17 nodules  were found to be of benign etiology acording to the reference standard , four G-CSF-related myeloid metaplasias, one hamartoma, and one infarction; A total of 194 nodules had CEUS test positivity for lymphoma. The enhancement pattern characterized by the iso -hypo (in the venous phase), i.e., isoenhancement in the arterial phase followed by wash-out appearance that had early onset and marked degree, occurred in 100% of these lesions. In particular, the wash-out onset occurred at a median of 43 s (range 20–60 s), and the median timing of the marked wash-out was 74 s (range 55–120 s). The dynamic patterns of the 56 nodules classified as benign according to the CEUS are reported in CEUS examinations of the remaining 10 nodules were classified as inconclusive. The median size of such nodules was 1 cm (range 0.8–1.5 cm). All inconclusive nodules appeared with a pattern characterized by arterial phase isoenhancement followed by mild and late wash-out of contrast agent. There was excellent concordance in the classification of positive findings for malignancy between the reference standard and CEUS scans. The sensitivity rate of spleen lymphomatous malignant status was 95% : 91% to 98%), i.e., 194 of 204 nodules positive for lymphomas were identified by CEUS, with a false negative rate of 5%  of 204 nodules positive for lymphoma were not identified). Noteworthy was the specificity rate of 100% (95% CI: 94% to 100%), PPV rate was 100% (95% CI: 98% to 100%), and NPV rate was 85% (95% CI: 74% to 92%), confirming the value of CEUS for detecting lymphoma in the spleen. Additionally, the concordance in the classification of positive findings for benignity between the reference standard and CEUS scans was excellent: 100% of agreement on the spleen benign status . FinallyTo classify the lymphomatous lesions of the spleen within further three DC, i.e., a-NHL-DC, c-HL-DC, and i-NHL-DC, we compared the findings of the wash-out patterns among the 122 a-NHL nodules, 60 c-HL nodules, and 12 i-NHL nodules which were detected at CEUS examinations.a-NHL nodules displayed isoenhancement in the arterial phase followed by wash-out appearance that had early onset and marked degree within <90 s following contrast agent injection, in a total of 122/122 (100%) nodules . The wasC-HL nodules showed isoenhancement in the arterial phase followed by early wash-out onset appearance and marked in degree between 90 and 110 s following contrast agent injection, in a total of 57/60 (95%) nodules . The 60 Finally, i-NHL nodules displayed isoenhancement in the arterial phase followed by wash-out appearance that was early in onset and marked in degree between >110 and ≤120 s following contrast agent injection, in a total of 10/12 (83%) nodules . The wasp < 0.0001), as well as being significantly shorter for c-HL-DC than for i-NHL-DC  or radiologically guided CNB. By immunohistochemical and morphometric evaluations, the MVD was investigated in 15 splenic nodules of a-NHL , c-HL (five lesions), and i-NHL (three lesions). Overall, in our post hoc analysis, the grade of MVD was higher for a-NHL nodules, and MVD seemed to be higher also in c-HL nodules. In fact, MVD decreased in the nodules in the following order: mean microvessel count of 30/0.5 mmThe clinical importance of diagnosing splenic involvement by lymphoma has been underlined in several reports: infiltration is considered an adverse prognostic factor ,4,5,6,7.For the first time, based on a robust sample size of 260 nodules  we showed that CEUS was able to achieve the diagnosis of splenic malignant lymphoma with excellent accuracy. The hallmark sign of lymphomatous nodular infiltration of spleen consisted of arterial phase isoehnacement followed by early (<60 s) and marked (≤120 s) wash-out appearance of sulfur exafluoride microbubbles. This finding validated the effectiveness of temporal CEUS enhancement and wash-out criteria to establish the diagnosis of involvement by lymphoma. The three principal clinical subtypes of lymphomas analyzed in the study, i.e., a-NHL, c-HL, and i-NHL, were differentiated on the basis of the degree of wash-out intensity (from contrast injection) of nodules. The totality of a-NHL nodules was categorized according to the typical wash-out appearance of very marked degree, i.e., within <90 s following contrast agent injection A–C resul2 for a-NHL, 26/0.5 mm2 for c-HL, and 20/0.5 mm2 for i-NHL. Abundant angiogenesis such as vessel proliferation  and abnormal vascularization  is recognized as being critical for lymphoma pathogenesis [In our post hoc analysis regarding tumoral neoangiogenesis evaluation, MVD decreased in the nodules in the following order: mean microvessel count of 30/0.5 mmogenesis . CEUS feIn our hands, CEUS allowed a correct assessment of spleen status providing prompt characterization of nodule(s) in most cases. Our study provides important information on the patients who may benefit most from CEUS exam in the real-life. Out of 260 nodules at risk of lymphoma, 56 (21%) were finally found to be benign and these were all correctly identified by CEUS. This leads to three main considerations. First, in patients with a diagnosis of lymphoma (on lymph node specimen) and splenic nodular lesions suspected, about a quarter of nodules are nonmalignant. Second, the spleens of the subjects  who carried such nodules were most likely not involved by disease. Finally, in such instances, CEUS can accurately define the benignity status of spleen avoiding more invasive, complex, and dangerous imaging procedures.However, our study suffers from four major limitations. First, this trial was conducted in a single center; therefore, studies from other institutions are needed to assess (i) interobserver and interequipment ultrasonographic finding variability; and (ii) reproducibility quality of the CEUS reporting a-NHL, c-HL, and i-NHL diagnostic categories, i.e., concordance among sonographers in diagnosing and subtyping spleen lymphomas. Second, a bias error could have been committed due to the retrospective analysis of the study. For example, the small number of nodules due to i-NHL does not allow to draw a conclusion in this subsetting of lymphoma. Thus, it is desirable to conduct prospective studies from multiple institutions. Third, this study does not shed more light on the involvement of spleen by lymphoma, without nodules, because this category was not included in the study. Lastly, this study does not include findings on the metastatic invasion of spleen by solid cancers, i.e., CEUS behaviors of non-hematologic malignant lesions, such as colorectal adenocarcinoma or melanoma. In conclusion, modern ultrasonographic technology is cost-effective as part of the diagnostic work-up of spleen status in patients with lymphomas. We present important indications of CEUS for assessing the spleen at risk of lymphomatous invasion. CEUS can be used as a prompt, harmless, and simple first-step to better characterize nodule(s) detected on routine imaging surveillance at the time of the staging process following lymph node biopsy-proven lymphomas, and during follow-up of previously treated lymphoma. New guidelines could therefore reconsider the most appropriate position of CEUS in the diagnostic flow chart of spleen status in patients at risk of lymphomas.


Expert evidence plays a central role in establishing the relevant standard of care in medical litigation. In Australia, little is known about the expert witnesses who provide evidence about the standard of care provided in ED. A sample of recent published case law suggests that a proportion of expert evidence about breach of the standard of reasonable care in ED is provided by medical practitioners who are not emergency physicians and/or have no recent practice experience in an ED. This may potentially distort the identification of the relevant standard of care. In the United States, the American College of Emergency Physicians has attempted to address this issue by developing and promulgating expert witness guidelines. Is there a case for the Australasian College for Emergency Medicine to assume an advocacy role and/or develop standards in this area? Expert evidence plays a central role in informing legal decision‐makers about the relevant standard of care in medical litigation. Expert evidence about care provided in ED is sought by coroners, the Australian Health Practitioner Regulation Agency or other disciplinary bodies, by solicitors in cases of alleged medical negligence and (less commonly) in criminal cases. By definition, expert witnesses provide opinion evidence, using specialised knowledge arising from their training, study and/or experience.Expert evidence assists in defining the relevant standard of care in civil liability claims and, where it is considered that the care fails to meet the standard of a reasonable clinician, whether that failure was causative of the outcome.We were unable to identify any published information about the characteristics of experts in ED‐related litigation in Australia. Data from other medical litigation contexts suggest that medical expert witnesses in Australia are commonly older, Caucasian, male sex and working in metropolitan and/or academic centres.There is no publicly accessible record of Australian ED expert witnesses, and the Australasian College for Emergency Medicine (ACEM) does not maintain an expert witness register. However, some information about ED expert witnesses may be gleaned from reviewing published reports of judicial decisions.Boxell,LazareskiGouldBoxell, six of 10 expert witnesses were emergency physicians with current ED practice experience. In Lazareski, only one of five experts met this definition. In Gould, the number was one in four. The other experts included infectious disease physicians, radiologists, cardiologists and thoracic surgeons. This is not to imply criticism of the experts who were not emergency physicians, who were no doubt providing their opinions in good faith and may have been addressing causation or damages issues rather than standard of care issues. However, in the context of evidence of the standard of care in the ED, a lack of direct and recent experience of the ED context and its challenges could, at least theoretically, result in the identification of a standard that is not consistent with contemporaneous ED practice in Australia.The recent Australian cases of Given this, relevant literature highlights the importance of ‘true’ peers and like circumstances being used to establish the standard of care, and the negative impacts on justice for all parties if inappropriate standards are applied.Good Medical Practice: A code of conduct for doctors in Australia for medical practitioners providing evidence to be clear about the limits of their knowledge and expertise and not to provide an opinion beyond those limits.There is a clear requirement in the Medical Board of Australia's One risk may be that non‐emergency physician experts may not appreciate where the extent of their expertise ends with respect to an undifferentiated patient in an ED or the broader ED context. Some may assume that their prior experience working in an ED some years ago equips them with sufficient knowledge of the ED practice context, without appreciating intervening changes in practice or ED‐specific scientific evidence. Another risk may be the application of a diagnosis‐based lens, assuming that because (e.g.) the witness is a cardiologist who treats heart attacks, they may safely comment on assessment of undifferentiated chest pain in ED of which heart disease makes up only a small proportion.If these risks are accepted, does ACEM have a role in advocacy and education with courts, regulators, insurers and lawyers about the special characteristics of ED practice and the importance of evidence about standard of care being provided by experts with appropriate qualifications and experience? If so, what might be the scope of that role?Expert Witness Guidelines for the Specialty of Emergency Medicine.The American College for Emergency Medicine (ACEP) first addressed this issue in 1990 in its policy titled Hold current registration as a medical practitioner;Have a recognised qualification in Emergency Medicine. ;Be in active clinical practice in Emergency Medicine for at least 3 years (exclusive of training) immediately preceding the events in question; andAbide by professional ethical guidelines.Key points in ACEP's guideline are that expert witnesses providing evidence with respect to the appropriate standard of care should:The current version of the ACEP policy also includes a requirement that the expert witness should be willing to submit the transcripts of depositions and testimony to peer review. The policy then goes on to state that misconduct as an expert, including the provision of false, fraudulent, or misleading testimony, may expose the physician to disciplinary action by the College.This policy has influenced the US legal system. Several US states now have local requirements (either in State statutes or evidence codes) that specify evidence about the applicable standard of care is limited to the standard of care for the specific specialty of the defendant provider.Arguably there is some equivalence in Australia in the peer professional practice provisions contained in civil liability legislation. For example, the NSW legislation states that a professional does not incur a liability in negligence arising from the provision of a professional service if it is established that the professional acted in a manner that (at the time the service was provided) was widely accepted in Australia by peer professional opinion as competent professional practice.It should be recognised that in the United States, some courts have found similar policies to cast a shadow on the standing of the professional College. For example, one judgement stated that Colleges had, through their guidelines, ‘moved away from disinterested scientific inquiry and into litigation policy to serve their members interests’.If ACEM was to develop a policy, the question arises whether it should go further than recommending basic qualifications and ethical standards with respect to providing expert evidence. As a professional body with a focus on quality and safety for the benefit of society, these altruistic values should also be applied to the provision of expert evidence by emergency physicians. Ways of achieving this might include recommending that emergency physicians providing expert opinions have training in legal systems and undertake relevant continuing professional education. However this goes beyond the remit of a specialist medical College, whose purpose is education and training, to accredit experts. In any event, an exclusionary accreditation process may not be accepted by the Courts.Available evidence suggests that expert opinion about standard of care in ED is sometimes provided by medical practitioners without specific training or recent experience in emergency medicine. This, at least theoretically, has the potential to distort standard of care assessments by legal decision‐makers. An ACEM policy on expert evidence in medical litigation of ED‐related cases could go some way to addressing this issue.


Neurogenic lower urinary tract dysfunction (NLUTD), the abnormal function of the lower urinary tract in the context of neurological pathology, has been the subject of multiple efforts worldwide for the development of clinical practice guidelines. These guidelines are based on the same body of evidence, and are therefore subject to the same gaps. For example, sexual and bowel dysfunction in the context of NLUTD, optimal renal function assessment in those who are non-ambulatory or with low muscle mass, optimal upper tract surveillance timing, and modification of diagnostic and treatment modalities for low-resource nations and communities are inadequately addressed. In addition, many aspects of the conclusions and final recommendations of the guidelines are similar. This duplicative work represents a large expenditure of time and effort, which we believe could be focused instead on evidence gaps. Here, we call for a global unified approach to create a single, resource-independent, comprehensive guidance on NLUTD, neurogenic sexual, and neurogenic bowel dysfunction. Targeted research addressing the evidence gaps should be called for and pursued. This will allow for focus to shift to filling the gaps in the evidence for future guidelines. Neuro-urology is a dynamic and rapidly developing subspeciality bridging the fields of neurology and urology  1,2]. A,2. A1,2]Clinical practice guidelines are statements that include recommendations to optimize patient care and are based on systematic evidence reviews and assessments of the benefits and harms of alternative management options . NLUTD gThe various NLUTD guidelines are devoid of guidance on several practical and important unaddressed topics germane to the practicing clinician, such as those listed in Another major guidance gap is the lack of detailed discussion of the associated sexual or bowel dysfunction which is frequently present with NLUTD. While management of these conditions often has fallen outside the scopes of NLUTD guidelines, the conditions should be considered in parallel with NLUTD because tailored treatments may benefit (or worsen) these other conditions. Data demonstrate that those with worse lower urinary tract symptoms have more severe bowel dysfunction, that stool impaction in the rectum may mechanically impede bladder emptying in neurological patients, and that type of lower urinary tract management correlates with severity of bowel symptoms ,9,10. CoExisting guidance also generally does not address the optimal process by which a patient with NLUTD is transitioned from pediatric to adult urological clinics. Evidence on this subject is evolving, and some studies suggest that at the time of transition, patients are at risk of declining health ,13. ThusIn some cases, specialized guidance documents have been introduced in order to fill in the gaps in the neuro-urology guidance. For example, the Spina Bifida Association provides guidance on the transition of patients with spina bifida from pediatric to adult urological clinics . The intA final area where there is variability in the guidelines is the surveillance protocols for NLUTD. Initially, many guidelines on NLUTD surveillance were written for patients with SCI or spina bifida, where there is a known and significant risk of silent renal deterioration due to lower urinary tract pathologies such as neurogenic detrusor overactivity, detrusor sphincter dyssynergia, low bladder compliance, and vesico-uretero-renal reflux. However, in many cases these guidelines did not represent reality, as few patients receive any degree of surveillance in the real-world setting ,20,21. NThe issues of redundancy, gaps, and variability are not specific to neuro-urology. Other fields have addressed these issues through successfully developing and implementing global consensus guidance. Notably, in 2016 the International Consensus Guidance for Management of Myasthenia Gravis (MG) was released . The guiWe suggest a unified approach to create a single comprehensive guidance on neuro-urology, including NLUTD, but also neurogenic sexual and bowel dysfunction. Endorsement by the major urological societies would be essential. Guidance for both high-income and low-income countries should be included, and great care must be taken to identify and include guideline panel representatives from diverse geographical locations. Targeted research addressing the evidence gaps should be called for and pursued. The guidance panel should include neuro-urologists and neurologists, but also consultants with expertise in diverse areas including gastroenterology, nutrition, infection, pediatrics, gynecology, and sexual medicine. The guideline should be applicable to all of those who care for neuro-urological patients—urologists, neurologists, primary care providers, specialized nurses, physiatrists, and infectious disease specialists—while recognizing that other specialties may require their own guidance documents to address specific issues within their disciplines. We do not need more summaries of the evidence for treatments that are accepted and have been studied with high-quality randomized controlled trials, nor do we need a weighty textbook that tries to summarize every study in neuro-urology. Well-written, concise, and internationally agreed-upon standards for the management and follow-up of neuro-urological patients will allow focus to shift to filling the gaps in the evidence for future guidelines.


We are experiencing an evolutionary phase in the teaching of orthopaedic surgery. The model of apprenticeship, which has been the foundation for most professions where both knowledge and technical skills need to be taught, continues still. Within this model, the trainer imparts not just the surgical skills of the operating room but the decision-making algorithms that have been formulated through learning, experience, reflection and self-critique. The apprentice learns by emulation and through a cycle of observation – recall – practise under the tutelage of experts. This expertbased training is entrenched in surgery.1. The 1980’s saw a new wave in medicine. David Sackett – amongst others – encouraged a re-look of how we make decisions and challenged the established norms and prevalent wisdom in medical practice. His personal journey to this end is worth a read2. There was a push to appraise the quality of the published literature and to adopt the conclusions only if well-founded by the science within. There was emphasis on good scientific rigour and, for clinical studies, ways to amalgamate the best into summary analyses. This was a departure from the primacy given to the ‘wisdom’ of experts and, to some, a challenge to expertbased medicine4.Medicine and surgery are, however, sciences and embedded within is the scientific method – the idea leading to a question which is tested through experiment and proof5. Secondly, in the era of expert-based medicine, clinical practice and decision-making algorithms were referenced to experts, often with little questioning of the rationale, science or proof behind.The subsequent four decades have seen evidence-based medicine (EBM) established as a cornerstone of modern medical and surgical practice. In my role as a trainer and teacher, this has been a welcome change. However, evidence-based medicine may have become so pervasive that I sense a danger of the same problems that emerged with expert-based medicine happening again. What do I mean by this? Firstly, expert-based medicine has been subject to influence from the industry. This too is happening in EBM as major trials often have sponsors from the industryToday the same clinical practice and decisions are referenced to published evidence. Whilst this is, in a scientific sense, more robust than the previous era based on experts, much depends on the quality of evidence referenced. Editors and reviewers of the journals sift the submitted material and challenge methodologies, analyses and inferences made before publication. Here in lies a quality-dependent process. Whilst it is true that the impact factor of journals may lend some weight and gravitas to the published evidence, there is a problem in that those journals – especially in orthopaedic surgery – tend to favour only the highest level of evidence and these studies, in turn, often cover a similar area most of the time. The subspecialist areas of orthopaedic surgery are not always represented and this is partly because randomised controlled trials are either difficult to design or fund here. As such, studies with lesser levels of evidence are more common from these subspecialties and often gain publication in smaller journals. So there is variation in ‘qualities’ of the levels of published evidence and quoting evidence without the ability to assess the strength of that evidence independently is the same danger that occurred when practice was expert-based; quoting one expert without the ability to question or understand the rationale or science behind it.This problem has been compounded by another change in the 21st century - the digital information age. Access to published material in medicine and surgery has never been easier. With all the evidence available through a few taps and swipes of fingers on phones, any clinician can pick and choose a published paper to support a particular point of view. Add to this is the flood of narrative and systematic reviews as well as meta-analyses, many of which are based on historical studies, some poorly done, others serving vested interests, and many leading to a conclusion that “more research is needed”. Are we really better off today?6. And this will, in turn, allow the surgeon to make independent assessments of what he or she reads, instead of just relying on the designated level of evidence as declared by the publishing journal.I believe the answer to this question is a qualified “YES”. The reason it is qualified is because we have yet to teach the skill of assessing the strength of published evidence. This skill is about understanding uncertainty. Good science and good surgery are related to the science of probability. The ability to be explicit about the uncertainty over certain decisions or interventions is at its core. And so what must lie at the heart of training the future orthopaedic surgeon is education on uncertainty and probability that is relevant to clinical work. The surgeon needs to be familiar with the methodologies behind clinical studies as well as statistical entities like odds ratios, likelihood ratios, relative risks, and forest plots. How can one judge the quality of evidence (and not just the level of evidence it is supposed to represent) unless one is educated in understanding the structure of the experiment that was designed to find the answer? It is this skill and ability that will give future surgeons the ability to sort the “wheat from the chaff” in the mountain of published literature7. The top positions held by meta-analyses and randomised controlled trials – a scenario fostered by the EBM movement – have seen their worth being questioned as a consequence of industry involvement9. Additionally, there are circumstances where the quality of evidence presented in one tier (for instance Level 3) can be better than the adjacent one above (Level 2) Similarly, some tiers have poorer evidence than ones from the adjacent level below. This blurring of the boundaries is a welcome perspective as it breaks down what has been a very rigid hierarchy. Furthermore, the gold standard experiment in clinical medicine – the randomised controlled trial (RCT) – has also been subject to scrutiny10. In surgery, the pragmatic RCT has been touted to be surgery’s answer to the double blind RCT in medicine, is an attempt to bring the ‘real world’ into the experiment. It aims to use the typical group of patients for whom the treatment is meant and for these patients to be treated by a range of surgeons who would normally encounter such patients11. This contrasts against an experiment in a single centre seeing a much smaller subset of patients and treated by a smaller group of surgeons for which the conclusions reached may not apply to other centres with different circumstances. At first sight, this seems a good approach. However, there can be procedures in surgery which possess longer and more difficult learning curves which may, if subject to a pragmatic design of RCT, show to produce no difference in outcomes over standard methods.There is an increasing appreciation that the delineation between the tiers in the pyramid of levels of evidence should be blurredet al citing the possibility of certain techniques being effective under better circumstances; in short, there are some procedures which require surgeons to attain a level of ability beyond the average level of the majority and may well prove effective after this level of skill had been attained12. Such circumstances depict a situation where an expert surgeon operating in optimum conditions may achieve different results. In view of this possibility, a recommendation was made for new procedures to be trialled first under such circumstances (by experts in optimum scenarios) before being subject to pragmatic RCTs. Simply, expert-based surgery is not dead.This danger of the pragmatic RCT was raised by Simpson 13. Expertise can influence decisions; the different levels of clinician knowledge, experience and skill is just another description for expertise. So for each decision we make in clinical care, there are multiple influencing variables. Relying on the results of a RCT or a meta-analysis may not suffice. We need to move a little beyond and adopt a system where all the influencing variables are accounted for. It is probable that some experts were achieving this in the past through the amalgam of knowledge, experience and skill and this may have been borne out through a high number of positive outcomes for their patients, whether as assessed clinically or through patient-reported measures. But is there a way to enable this ability to be taught or even computed? There is some hope that the system of Bayesian networks as used in medicine and surgery may provide an answer15. These systems will enable the ability to compute the probability of an outcome where the best available evidence is added to expert knowledge, patient influences, causal factors and even the surgeon’s past results. These probabilities can be computed for past data and updated for new and changing data on these variables with time.David Sackett was a strong proponent of an evidence-based practice but what is often forgotten is the emphasis he gave to including clinician knowledge, experience, skill, patient values and their preferences together with the best available evidence for the decision-making processIt has taken a generation for evidence-based practice to become entrenched in modern clinical life. It brought with it – for orthopaedic surgeons at least – new terminology, new concepts and demands for a better understanding of the structure and quality of clinical experiments. It may take another generation for the blend between expertise, patient characteristics and best available evidence to become a default process in clinical work. This return to appreciating the value of expertise in clinical care is not a case of back to expert-based medicine but a real step forward in as much as modern computing abilities and artificial intelligence will allow us to simplify that collation of information for making individualised decisions for individuals, and not adopt a “one size fits all” approach in treatment.


Purpose: The aim of this study lies in articulating the relationship between digital literacy and private concern as a predictor of intention to use digital therapeutics. Materials and Methods: An online survey was conducted through a research company among 600 panels. The survey questionnaire consists of items of digital literacy, privacy concern, perceptions, and intention to use digital therapeutics, and the participants were asked to fill out the questions online. A structural equation model was established, and the difference in paths between the MZ generation and the baby boomers were examined. Results: Public perception of digital therapeutics was categorized into seven factors and the dimension of digital literacy as categorized into three factors. For the MZ generation, digital literacy and privacy concern both directly and indirectly affect the digital therapeutics use intention, in that higher the level of digital literacy and the lower the privacy concern, digital therapeutics perception and digital therapeutics use intention becomes intensified. For the baby boomers, digital literacy and privacy concern positively affect digital therapeutics perception, and as digital therapeutics perception becomes more positive, digital therapeutics use intention also increases. Direct effects of digital literacy and privacy concern to digital therapeutics use intention were not found for the baby boomers. Conclusion: In order to promote the use of digital therapeutics, it is common for the MZ generation and baby boomers to develop a positive perception toward digital therapeutics by cultivating digital literacy. For the MZ generation, privacy concerns need to be cautiously considered as they negatively affect the intention to use digital therapeutics. First introduced in 2000 by Seth Frank, digital health, largely encompassing media and internet-focused applications for the Internet, performs a few critical functions . The excDigital health care is a multidisciplinary umbrella term that includes concepts from an intersection between information technology and healthcare. Digital health care was born by the convergence of advanced information and communication technology and medical technology. As such, the core technologies of the fourth industrial revolution, such as artificial intelligence and big data, and the development of a digitally transformed society, are applied to the field of health care . In digiDigital health care has a very high potential for development according to the growing interest in health care and the need for chronic disease management as an aging society deepens. Efforts to develop digital health care at the government level include the telemedicine service pilot project that started in 1988, the establishment of a national health computer network, and policies related to medical informatization such as dissemination of electronic medical records to medical institutions . RecentlSince artificial intelligence relies on digitized personal health data, the importance of data in digital health care is emerging in relation to the securing and utilization of these data . In thisSince individuals using digital health care have to utilize cutting-edge digital technology, digital literacy, which indicates how well they can handle digital technologies and acceptability of new digital technologies, is expected to affect the spread and utilization of digital health care. Digital healthcare has evolved, along with the development of digital technology. In this respect, it can be seen that individuals using digital health care presuppose the use of digital technology. Therefore, it can be assumed that digital literacy, which indicates how well you can handle digital technologies, will affect the dissemination and utilization of digital health care.In this regard, it is necessary to pay attention to digital literacy related to the ability to handle digital health care. Digital literacy also affects health literacy, which accesses, understands, and utilizes health information, and can be measured by digital communication ability and creative production capacity using digital devices. Adoption of new digital technologies varies by age group . In KoreAccording to previous studies related to digital health acceptance, health interest, functional excellence and innovation, compatibility with other devices, design aesthetics, cost effectiveness, information quality, reliability of data security, and ease of use were related to the intention to accept digital health care services . AccordiSince digital health care utilizes various data generated in an individual’s life, it is inevitable to avoid being connected to personal privacy. Depending on how much you care about privacy in a digital health care setting, it is necessary to review whether it affects access to and use of digital health care. However, there is still a lack of research on how concerns about privacy, such as security management of health care data, differ by generation and how this affects the acceptability of digital health care. Privacy issues such as data reliability and information security are considered to be important drivers for the development of digital health care, so research on them is very necessary. In addition, there are few studies showing how digital literacy, which plays an important role in understanding and applying digital technologies, is related to situations where people need to operate and utilize devices or services on their own, such as digital health care.Therefore, in this study, we would like to examine how digital literacy and privacy concerns are related to the acceptance of digital technology. Specifically, we presented digital therapeutics as a typical digital health care, a technology that is expected to grow and attract attention in fields such as mental health, chronic disease, and pain control among digital health care. Digital therapeutics can be defined as a regulatory approved digital system or application that is prescribed to treat medical conditions, similar to that of new drug molecules or medical devices ,14,15,16Studies have shown individuals of higher socioeconomic and education status tend to be healthier and have healthier behaviors ,18,19 AgDigital therapeutics are not yet popularized. Therefore, in this study, we first examine how the perception of digital therapeutics appears in Korea, and the effect of digital literacy and privacy concern on the perception and intention of using digital therapeutics.Anonymous online surveys were conducted to collect data via a professional online research firm. The online research panel was recruited by random quota sampling, and the quota represented a general demographic composition similar to the most recent Korean Census Data . The surThe measuring items for digital literacy were adopted and modified from conceptualization of digital literacy in the work of Eshet-Alkalai and Eshet-Alkalai and Chajut ,24. A toα = 0.77). Awareness of privacy practices dimension was measured using 3 items, including “a good consumer online privacy policy should have a clear and conspicuous disclosure”, etc. (α = 0.87). Collection dimension was measured using 4 items, including “it usually bothers me when online companies ask me for personal information” etc. (α = 0.79). The respondents were asked to answer on a 5-point Likert scale ranging from 5 (strongly agree) to 1 . The coefficient α for 10 items of privacy concern was 0.89.Privacy concern was measured by the items adopted and modified from the internet user’s information privacy concerns, which consist of three subdimensions of control, awareness of privacy practices, and collections . Controlhttp://www.bigkinds.or.kr). Of these, two are conservative, two are progressive, and the other is an industry-specialized newspaper. This method of newspaper selection has been used in other analyses of media reports to select a broad sample of newspapers with various readership profiles and political orientations [A media content analysis was conducted as a pretest to develop items for public perception. We selected five Korean daily newspapers with high circulation and a range of readership profiles .Statistical analyses were performed in three stages. In the first stage, exploratory factor analyses were employed to identify the underlying relationships between measured variables  to extract their common dimensions. In the second stage, a reliability test was performed to assess the stability and consistency of the measured items, including descriptive statistics. In the third stage, a structural equation model was established to examine the relationship between latent variables, and moderation effect analysis was conducted to examine the difference between the millennials and baby boomers.α test was conducted several times. First, Cronbach’s α test was conducted for all items of the constructs. The variables from the latent constructs used summated rating scales composed of many measurement items extracted from the exploratory factor analysis. All the items consisting of observable variables reported Cronbach’s α coefficients of over 0.60.The means, standard deviation, and Pearson correlations of the observed variables are presented in As a result of an exploratory factor analysis for the items extracted from Eshet-Alkalai and Eshet-Alkalai and Chajut’s studies ,24, 16 iThe first factor, named as information utilization ability, was found to explain 30.79% of the total variance. This factor represented one’s ability to use the Internet. The second factor, named as creative producing ability, was found to explain 19.87% of the total variance. This factor was related to one’s creative ability to produce and manage one’s Internet space and to show oneself on the Internet. The third factor, named as digital communication ability, was found to explain 18.12% of the total variance. This factor represented one’s communication ability to send messages online by email and use the Internet to know other people. Specific items consisting of each factor are shown in As a result of an exploratory factor analysis for the items extracted from media content analysis, public perceptions of digital therapeutics were categorized into seven factors. The EFA showed 32 factors, explaining 60.54% of total variance .The first factor, named as regulation need, was found to explain 16.35% of the total variance. This factor represented the public’s legal requirements related to the use of digital therapeutics. The second factor, named as cost efficiency, was found to explain 10.72% of the total variance. This factor was related to public tendency to judge the efficiency of the digital therapeutics. The third factor, named as health benefit, was found to explain 9.60% of the total variance. This factor represented whether the use of digital therapeutics can benefit one’s own health. The fourth factor, named as medical concern, was found to explain 7.53% of the total variance. This factor represented public thought on how medical staff related to digital therapeutics think of digital therapeutics use in medical encounters. The fifth factor, named as device credibility, was found to explain 6.00% of the total variance. This factor is related to one’s favorability toward direct communication with doctors and represents trustworthiness of doctor’s medical device. The sixth factor, named as health inequality, was found to explain 5.73% of the total variance. This factor represented one’s concern that using digital therapeutics would result in any inequality related to health. The last factor was named uncertain literacy, in that it represented one’s idea that understanding and utilizing digital therapeutics is not an easy matter.After the reliability and validity test, the group analysis between the MZ generation and the baby boomers was completed. The MZ generation showed a higher mean value in health literacy, while baby boomers showed a relatively higher mean value in privacy concern. For digital therapeutics perception, the MZ generation showed a higher mean value in cost efficiency, device credibility, health inequality, and uncertain literacy, while baby boomers showed a higher mean value in regulation need and health benefit. For medical concern, the MZ generation and baby boomers showed the same mean value, and there were almost no differences in the mean value of digital therapeutics use intention in two groups .2 = 582.885, df = 107, p = 0.000; and the other fit index indicated a good fit within the accepted exhortation level .To find out the relationship between digital literacy, privacy concern, digital therapeutics perception, and digital therapeutics use intention, we proposed a structural equation model. We evaluated the goodness-of-fit indices for the proposed structural equation model and the model generated χß = 0.250, p < 0.001), in that as digital literacy increases, digital therapeutics perception intensifies. However, the direct effect of digital literacy to digital therapeutics use intention was not found.The result of path analysis showed that digital literacy positively affected digital therapeutics perception , in that as privacy concern increases, digital therapeutics perception also intensifies. In the case of digital therapeutics use intention, the negative effect of privacy concern was found to be statistically significant . Thus, as privacy concern increases, the intention of digital therapeutics use decreases.Moreover, the direct effect of privacy concern to digital therapeutics perception was found to be statistically significant .In the main research model, digital literacy did not affect DTx use intention. To compare the MZ generation and baby boomers, a moderation model analysis was performed. We again evaluated the goodness-of-fit indices for the proposed structural equation model for the moderation analysis, and the moderation model generated χIn the moderation model where the comparative analysis of the MZ generation and baby boomers was carried out, all the paths turned out to be statistically significant in the MZ generation.ß = 0.156, p < 0.01). In the MZ generation, digital literacy not only directly affected digital therapeutics use intention, but also mediated digital therapeutics perception  and affected digital therapeutics use intention significantly .First of all, the direct effect of digital literacy toward digital therapeutics use intention was found to be statistically significant in the MZ generation  and negatively affected DTX use intention   .ß = 0.267, p < 0.05) and affected digital therapeutics use intention .In baby boomers, direct effects of digital literacy and privacy concern to digital therapeutics use intention were not found to be statistically significant. A mediated effect of digital therapeutics perception was found, in that digital literacy mediated digital therapeutics perception , and digital therapeutics perception affected digital therapeutics use intention (In baby boomers, a mediation effect also appeared, in that as privacy concern increased, digital therapeutics perception intensified (ntention .This study was conducted to investigate how digital literacy and privacy concerns affect digital healthcare acceptance. In particular, we tried to predict the acceptability of digital healthcare by examining the characteristics of digital literacy and people’s perceptions of digital therapeutics, which are a part of digital healthcare.The main findings of this study are summarized as follows. First, it is necessary to positively change the perception of digital health care in order to increase the acceptance of digital health care. According to the results of this study, perceptions of digital therapeutics were divided into seven categories, including legal dimensions, cost effectiveness dimensions, health dimensions, device dimensions, and so on. Therefore, taking these individual dimensions into account, it is not easy to convert and reinforce all perceptions positively. Nevertheless, efforts such as adding technical supplementation to the digital treatment machine to increase credibility in the device is sufficiently possible. The device credibility is the part where the perception gap of MZ generation and the baby boomers existed, so it can be said that it is a part that needs to be strategically paid special attention to in order to increase the acceptance of digital healthcare.A second interesting finding is related to privacy concerns. In the MZ generation, it was found that the greater the concern about personal information, the lower the DTx use intention. On the other hand, in baby boomers, privacy concerns did not appear to affect the DTx use intension. These results do not appear because the MZ generation is more concerned about privacy than the baby boomers in digital healthcare. Rather, privacy concerns are higher among baby boomers than the MZ generation. However, it can be inferred from the result that baby boomers are relatively vulnerable to disease situations because they are older than the MZ generation, and therefore have a high degree of involvement in digital health care.In the case of the MZ generation, there are various ways to increase the intention to use DTx. By cultivating digital literacy and devising ways to overcome privacy concerns, the perceptions of digital therapeutics can be positively reinforced, thereby increasing the intention to use DTx. However, as privacy concerns increase, the intention to use DTx decreases, so this is an area that needs to be carefully reviewed.In the case of baby boomers, the pathways to increase the intention to use digital therapeutics are not as diverse as the MZ generation. The intention to use DTx can be increased only by positively reinforcing the awareness of digital therapeutics through measures to cultivate digital literacy and overcome privacy concerns. Therefore, it is important to cultivate the literacy necessary for the digital environment and to understand privacy-related matters through education.The limitations of this study are as follows. First, though the explanation of DTx was provided in the survey, the interpretation and understanding of DTx may differ for each respondent. Second, the items measuring DTx perception in this study were extracted from media analysis. In the future, it is necessary to increase the acceptance of digital healthcare by specifying and diversifying the perception of digital therapeutics through an expert group interview.Although this study reviewed the relationship between perception of digital therapeutics, digital literacy, and privacy concerns in the intention to use digital therapeutics, future research should consider the relationship of various variables that can influence this process. For example, illness experience or the need for face-to-face treatment may affect perceptions of digital therapeutics. Cultural variables may also be a factor influencing perceptions and intention to use digital therapeutics.Depending on how the perception of digital therapeutics is formed, the intention to use digital therapeutics may vary. According to the results of this study, perceptions of digital therapeutics were divided into seven categories, including legal requirements related to digital therapeutics, cost efficiency, health benefit, medical concern, device credibility, health inequality, and uncertain literacy. These dimensions contain both positive expectations and concerns, and ultimately affects the intention to use digital therapeutics.In addition, factors affecting the perception of digital therapeutics across generations are digital literacy and privacy concerns. In this point, it is necessary to cultivate digital literacy for a better understanding of digital therapeutics. At the same time, it is necessary to increase accessibility to digital therapeutics by strengthening the legal and institutional environment for privacy concerns, such as personal information protection.In fact, discussing how digital therapeutics might affect human lives is beyond the scope of this study. However, understanding people’s perceptions of digital therapeutics is a necessary part of understanding our lives where many of which are already digitalized. Ultimately, understanding people’s perceptions of digital therapeutics can be a starting point for disease treatment and health promotion.


To summarize the relevant evidence for nondrug nursing programs in neonatal operational pain management.  Computer search for the literature on neonatal procedural pain from 2015 to 2020 in Up To Date, JBI, NICE, SIGN, RNAO, NGC, PubMed, Cochrane Library, CNKI, and Wanfang database was conducted. All literature works that may meet the inclusion criteria were independently evaluated by two researchers to determine the quality grade of the articles.  Finally, 9 literature works were extracted, including 4 guidelines, 3 systematic reviews, and 2 evidence summaries. The relevant contents of the literature were extracted and summarized, and 20 pieces of the best evidence were obtained.  Breast feeding, sweetener, Kangaroo mother care, sensory stimulation, nonnutritive sucking, and other nondrug nursing programs can reduce the neonatal operational pain, which has guiding significance in neonatal operational pain management. Since the development of the neonatal pain conduction pathway is not perfect and the inhibition of pain is also lacking, the neonate often produces relatively strong pain response . The pai1  and O2 ; ⑤ S (setting): pediatric ward; ⑥T (type of evidence): guideline, systematic reviews, and evidence summary.According to PIPOST tools, clinical problems are transformed into evidence-based problems: ① P (population): neonates whose birth age is ≤28 days; ② I (intervention): intervention measures to relieve pain; ③ P : pediatric nurses, physicians, and family members of neonates; ④ O (outcome): OWith “procedural pain, pain, analgesia, non-drug analgesia, neonate, neonatology department” as the English keywords, the retrieved databases include the following: Up To Date, JBI Evidence-Based Health Care Center database, National Institute for Clinical Excellence (NICE), Scottish Interhospital Guide Network (SIGN), Registered Nurses' Association of Ontario (RNAO), National Guideline Clearinghouse (NGC), PubMed, Cochrane Library, CNKI, and Wanfang database. The retrieval period was from 2015 to 2020.Inclusion criteria are as follows: the research object includes clinical guidelines, evidence summary, and systematic reviews of neonates with operational pain. Exclusion criteria are as follows: Studies that involve nondrug nursing programs but do not indicate specific interventions, summary, abstract, draft, interpretation of evidence, research proposal, research with no clear conclusion, and duplicate evidence.① Appraisal of Guidelines Research and Evaluation in Europe II (AGREE II) was used to evaluate the clinical guideline . The eva② Assessment of multiple systematic reviews (AMSTAR) was used to evaluate the systematic reviews . It incl③ All the literature potentially meeting the inclusion criteria was independently evaluated by 2 researchers trained through a national evidence-based nursing curriculum to determine the quality grade of the articles. For literature works that are difficult to reach consensus, the third researcher trained through a national evidence-based nursing curriculum will participate in the discussion to reach consensus. The inclusion principle of literature evidence included the following: evidence-based evidence, high-quality evidence, and newly published evidence should be given priority.④ The JBI evidence recommendation level system was used for evidence summary . The levA total of 402 literature works were obtained in the initial examination. After reading the title, abstract, and full text, the unqualified literature works were eliminated. Finally, 9 literature works were extracted, including 4 guidelines, 3 systematic reviews, and 2 evidence summaries. The basic characteristics of the included literature works are shown in The total quality scores of the 4 guidelines are ≥5 points, so it is recommended to use these 4 guidelines as shown in The problems of the 3 systematic reviews are as follows: the grey literature is not considered in the inclusion criteria, and the possibility of publication bias has not been fully assessed. The 3 systematic reviews are all of high quality, can clearly put forward relevant evidence-based questions, and are scientific and authentic as shown in In the process of evidence summary, the 2 evidence summaries included in this study both adopt the original evidence level and recommendation level. The relevant contents of the literature were extracted and summarized, and 20 pieces of the best evidence were obtained. The summary of evidence is shown in Breast feeding can be divided into direct breast feeding and indirect breast feeding. The method can promote the mother-infant contact, it can provide physical and psychological comfort for neonates, and it does not increase any medical cost. Ponce-Garcia's team believed that breast feeding can reduce the probability of sleep and breathing disorder in children and significantly shorten the duration of crying in children . Peng's Sweetener has become a commonly used analgesic measure for neonates, and its possible mechanism is that it stimulates an oral sense of taste, stimulates oral tactile receptors, and triggers the release of endogenous opioids. The opioid receptor is a part of the endorphin system, and activating the receptor can reduce the pain sensation of the HPA axis of neonates . GeneralKMC refers to the nursing method of placing the newborn's whole body naked on the mother's chest for maximum skin-to-skin contact . KMC relβ-endorphin in the pituitary gland increased significantly [Sensory stimulation is the primary way of nondrug intervention for neonatal pain. Individualized dependence on sensory intervention can control the programmed change of the HPA axis to a certain extent. Sensory stimulation mainly include touch (stroking the face and back of neonates), taste , hearing , and vision (looking at the neonates) . Qiu's tficantly . Massageficantly . van derficantly . Kurdahificantly . Evidencficantly .NNS is a method of increasing the sucking action of a neonate by gently placing a pacifier into the mouth of neonates. During the NNS intervention, no breast milk or formula was inhaled . CarbajaTo sum up, breast feeding, sweetener, KMC, sensory stimulation, NNS, and other nondrug nursing programs can reduce the operational pain of neonates, which is characterized by low-risk, simple, and easy implementation. Most of the evidence in this study is Grade A recommendation, which has guiding significance in neonatal operational pain management. In clinical work, it is necessary to increase the attention of nurses to neonatal procedural pain and to adopt a variety of methods to implement comprehensive pain nursing interventions for neonates. In addition, in the process of using evidence, medical staff should fully consider the own situation of neonates, department environment, and other factors, and they should use high-quality evidence-based evidence to improve clinical practice.


Evidence-based medicine (EBM) originated from the new science that resulted from combining the methods of epidemiology and clinical research. At a time when clinicians and epidemiologists were beset by rivalry, Archibald Cochrane integrated knowledge from these two fields and created what came to be known as clinical epidemiology. With help from his collaborators, including Professor Kerr L. White, he set out his clamor for efficacy, effectiveness and efficiency in clinical teaching, practice and research.EBM crowns the fundamental concepts of medicine and healthcare through requiring evidence of effectiveness, efficiency and safety to guide decision-making such that there will be greater likelihood of making correct decisions. The concept of EBM was introduced at the beginning of the 1990s and was followed by establishment of the Cochrane Collaboration in 1992,by Professor Iain Chalmers in Oxford.Cochrane Brazil was founded in 1996 , one year after I was first elected as Scientific Director of the São Paulo Medical Association . In the same year, the postgraduate course that today is named the Postgraduate Program on Evidence-Based Healthcare was founded at the São Paulo Medical School (Escola Paulista de Medicina), Federal University of São Paulo .th century and was followed by publication of the first controlled clinical trial by James Lind.,Supporting medical practices on the basis of the best evidence, coming from rigorous methodologies that give this evidence comparative validity, is a civilizing process. This process was started by René Descartes at the beginning of the 18In 1948, Bradford Hill and Archibald Cochrane conducted the first blinded randomized controlled clinical trial, to test use of streptomycin for treating tuberculosis.The entire new methodology that was proposed had the objective of rationalizing how studies were conducted, with the aim of supplanting the bias caused through fantasies, emotions, beliefs and interests. In particular, it aimed to combat financial interests: not only among individuals but also among major corporations that seek to make profits. Few attitudes can lead to so much efficiency and avoid so much suffering and waste of money and lives as the use of evidence for making decisions, not only in relation to human health and the right to healthcare but also in relation to education, agriculture, veterinary science, social science and so on.Deviation from this civilizing path is unthinkable. To recommend treatments without any scientific basis would be equivalent to regressing to the year 1650. It would throw back medical care by centuries, waste money, opportunities and lives and represent choosing irresponsible management of all these values.In the postgraduate program at UNIFESP, more than 300 master’s and doctoral students have now graduated, to become involved in teaching and research. The Cochrane Library has now published more than 8,000 systematic reviews that map out important subjects relating to prevention, diagnosis and treatment of greater efficiency and safety for human health. Moreover, it has published the references of almost one million randomized clinical trials, which it has made available to everyone.With support from the APM and from the Coordination Office for Improvement of Higher-Education Personnel ,Cochrane Brazil has been placing all this information at the disposal of all Brazilians since 2001. This information is available simply by accessing the website of Cochrane Brazil (www.cochranebrazil.org.br).We will be returning to this topic with further details.


Recently, two major medical journals, The Lancet and New England Journal of Medicine, each withdrew an article on coronavirus from their databasesAnnouncements of cures for COVID-19 are appearing frequently. However, there is a clear simultaneous association between such news and the share values of drug-manufacturing laboratories that are promising miraculous cures on the basis of just a few cases that were poorly or barely documented.It seems that the virus is also affecting the health sciences, the reputations of renowned journals, the state of political debate and the institutions responsible for preserving the population’s state of physical, mental and social wellbeing, i.e. people’s health.All of this is easy to understand given the gravity of the tragic context. Moreover, it has occurred because clinical research not only requires clinical competence but also needs great detachment, time, impartiality and good evidence (proof) coming from other careful research.Healthcare practices and evidence-based medicine require the use of reasoning. However, we need to be prepared not only to use rational thinking but also to avoid situations in which interests, emotions, fantasies, charlatanism and so on might get in the way of rationality and free scientific thought. Through this, professional practice can be based on good evidence, i.e. valid scientific proof, that interventions will have a higher chance of providing more benefit than harm.For more than 30 years, together with many colleagues, we have striven to improve research, teaching and application of evidence-based medicine in Brazil and internationally. The results have been satisfying, because teaching and research within evidence-based medicine has had clear scientific, didactic, economic and juridical impacts, both in Brazil and around the world, over these last decades.The thirst and respect for scientific evidence seen among many journalists in Brazil during this pandemic has been remarkable. It shows that our continuous collective work over this 35-year period has been worthwhile.The charlatans who always appear at times of despair have had short lives with their vested-interest fake news, thanks to the now-established cultural foundation of demand for valid scientific evidence, coming from many different sectors of society.Judicialization of healthcare in Brazil, in which judges have been asked to make rulings in cases based on emotional blackmail, for expensive treatments without proof of effectiveness to be released, under the justification that “without this, the patient will die”, has largely been rationalized, with major savings of public expenditure. This has occurred through requirements for good evidence of effectiveness, efficiency and safety to be presented before permission for these therapies to be released through judicial petitions is granted. In this manner, the groundbreaking concept of evidence-based rights to healthcare has been created in Brazil. In this regard, we have trained around 3,000 judges, prosecutors and attorneys through distance-learning courses sponsored by the Brazilian Ministry of Health.Unfortunately, for a variety of understandable reasons, the great pioneering experience of doctors in Wuhan, China, regarding COVID-19 could not be properly followed up with enough adequate clinical research methodologies, to generate valid proof, given the lack of time.There was no time for good orchestration of scientific production that would properly take into account the basic principles for obtaining and evaluating valid evidence. It also has to be recognized that entire impact of this pandemic has been felt within a period of only six months. Most of the data have been retrospective.A good clinical trial, with more than 1000 cases, would require several years of intense dedicated work. Cochrane systematic reviews take two to four years to be published. The Cochrane Collaboration is now promoting rapid reviews of lower sophistication on matters of urgent interest, within the fight against COVID-19.If a new disease emerges, there is a need to know the following, for example:How to diagnose the diseaseWhat the clinical condition and its diagnostic tests are, and what usefulness and credibility the results from these tests haveWhat the risk factors for individuals to become infected areWhat the risk factors for occurrences of severe outcomes are: for example, shock and kidney failureWhat the risk factors signaling severe forms of the disease and death areHow to minimize complications of the disease, such as thromboembolism, cytokine storms, inflammatory reactions, acute respiratory insufficiency or kidney failureHow to deal with the causes and consequence of the various complicationsIn all of this, the methodology of clinical epidemiology, which is the tool that generates the notions of evidence-based medicine and evidence-based health, is fundamental. Thus, to evaluate various risk factors, observational studies are extremely useful. These may include case-control studies, which can be applied to ascertain whether age, medications, profession or attitudes might have an association with becoming ill with the disease. These studies have the great advantage of enabling assessment of several risk factors in a single study and can be conducted quickly. A very good case-control study was published recently.On the other hand, because these studies are retrospective, they have the disadvantage of depending on the patients’ memory. Moreover, they are not of much use for evaluating treatments and diagnostic tests because the proportions of cases and controls to be compared are established in an artificial manner.For prospective evaluation of patients’ evolution and what the risk factors associated with their evolution are, prospective cohort studies are fundamental. For example, it might be asked whether COVID-19 has outcomes of greater severity in patients whose laboratory assay results are more inclined to the left or to the right. In such cases, prospective studies that have been suitably designed beforehand will supply data and evidence that are much more trustworthy than those from retrospective analyses on cases that have already occurred but were not followed up in a planned manner. Prospective studies will thus avoid data losses.It might be asked whether patients with higher C-reactive protein levels in blood analyses are at greater risk of mortality. Prospective cohort studies frequently have the disadvantage of requiring very long and laborious follow-ups. However, this does not occur significantly with COVID-19, given that this disease only lasts for two to four weeks. Thus, within a short time, large numbers of cases within this pandemic can be evaluated prospectively.,A variety of associations of risk factors for worsening of COVID-19, obtained through retrospective studies, have now been reported.After hypotheses have been raised retrospectively, knowledge can be improved through prospective studies, so as to have a much more realistic vision of what is happening with each marker. Thus, therapeutic interventions aimed towards each desirable outcome and/or a set of outcomes of interest can be planned.Therapeutic interventions cannot be securely assessed through case series without a protocol for a controlled clinical trial. Furthermore, such trials should preferably be double-blind, and these are necessarily prospective. Even though many people are greatly attracted towards cases series, these should generally serve only to generate questions that later on need to be answered using clinical trials. Hypotheses are then tested so that treatments can be put into practice based on evidence. This is very different from conduct based only on hypotheses.Retrospective studies or studies without control groups may show that a series of patients received a benefit, or even some harm. However, these studies always leave a trail of continuing uncertainties if they are not followed by adequate prospective studies. This is so even in situations of the best of intentions, such as in cases of compassionate treatment. We end up not knowing whether the treatment was beneficial or harmful because we did not have a comparison group that was chosen randomly and impartially.On the other hand, a clinical trial that is conducted with the competence and seriousness that this merits will, independent of the result, bring great benefits for all of humanity. In other words: if the intervention was beneficial, it can be used; but if it was ineffective, resources and sometimes lives will not be wasted, and the way forward may then be to explore new possibilities.Among the sources of great confusion in the literature on this subject, both in academic settings and in the lay press, lack of verification of the application of basic scientific fundaments of knowledge has generated confusion, conflict and commotion that can only be resolved through good-quality evidence.For example, since the expected average mortality rate from symptomatic cases of COVID-19 is around 5%, it can be expected therefore that out of every 100 cases, around 95 should survive purely through the action of nature. Hence, even if only placebo is administered , 95% of the patients will be saved and will be computed as cases of successful treatment and the other 5% will not be able to come back to complain, in the remote hypothesis that all the cases are well documented.Thus, in the absence of an adequate control group, masking for the researcher and patients, randomization, a good study protocol and a good way of conducting the study, large quantities of useless data end up supporting spurious opinions of well-intentioned people who are unaware of the appropriate methods for obtaining trustworthy data. This also supports the opinions of ill-intentioned people whose interest lies in deceiving others and promoting themselves professionally to gain financial advantages. Good scientific products are the fruit of a continuous struggle against possible confounding factors, systematic errors and random effects that might falsify the conclusions and mislead the researcher.Although evidence-based medicine has led to great achievements so far, both in Brazil and around the world, there is still much to be done. The current pandemic has certainly helped to improve social awareness of the role of well-prepared scientists as essential actors in the war against this extremely dangerous invisible enemy. This is a war in which the lives of hundreds of millions of people depend on the outcome, and definitively it is not for just any healthcare professional to engage in.On the websites of clinical trial registers, more than one hundred trials on treatments for COVID-19 are currently in progress. One of the best of these, Recovery, conducted by Oxford University,One of these clinical trials has compared use of oral or intravenous dexamethasone in patients hospitalized with COVID-19 who require noninvasive oxygenation or mechanical ventilation. Given the high quality of this project and the adequate sample size, there is little doubt that this trial provides the first evidence of drug treatment with real benefit for treating patients with COVID-19 who require supplementary oxygenation, with significant reduction in mortality. However, this finding does not apply to milder cases.Other studies with similar objectives are underway and, if their quality is good, their results may have an important role in reducing the remaining uncertainties, when added carefully to the current results in a conservative statistical process and through a properly done meta-analysis. In this manner, the best level of evidence for basing healthcare decisions on will be achieved through systematic reviews, and these trials will then enter history. The Cochrane Collaboration has the role of doing analyses of this nature in an impartial and live manner, i.e. continuously and explicitly, in all important fields of healthcare, and publishing them in the Cochrane Library.Consulting good sources of evidence is essential for patients, students, doctors, other healthcare professionals, researchers, managers, journalists and lawyers. Free access to the Cochrane Library has been available in Brazil since 2001.https://brazil.cochrane.org/).The Cochrane Center of Brazil has been in operation within the Federal University of São Paulo  since 1996 (


Academic literacy, as a representation of required skills in the academic community, has gained increasing prominence and attention over the past decade. It has been the focal point of many studies in different contexts drawing on different perspectives. However, the way academic literacy development is researched and practiced in multilingual and multicultural settings is limitedly clarified and dealt with in second/foreign language contexts. Moreover, the role of different developmental trends of this research strand on EFL teachers in multilingual milieus has been overlooked, to date. To shed more light on the construct of academic literacy development in multilingual and EFL contexts, the present review article takes a global vision and explicates the past, present, and future trends in researching and practicing this significant construct. In so doing, it defines the concepts and presents the dimensions of academic literacy and academic literacy development. Then the role of academic literacy in multilingualism has been elaborated on using empirical evidence. Finally, the study provides and explains some implications for EFL teachers, teacher educators, curriculum designers, and scholars, who can update their information about academic literacy development in multilingual contexts with particular nuances. Academic literacy; Academic literacy development; EFL teacher; Multilingualism; Multiculturalism; Second/foreign language education. AcademiGiven its social nature, literacy is now positioned in the context of power relations and macro-societal factors like race, justice, identity, gender, emotion, and access that significantly influence one’s academic literacy development . With thAlthough researching academic literacy development is not totally uncharted in L2 contexts, its role and significance in multilingual and multicultural contexts have been limitedly investigated. Moreover, most of the current studies in this domain have focused on the academic literacy development of EFL students, while teachers' perspectives and status have remained under-explored. To fill these gaps, the present theoretical review aimed to present a global view of EFL teachers' academic literacy development, which is, in turn, crucial for students' academic literacy development teachers' academic literacy plays an important role in learners' academic literacy development .22.1In the pertinent literature, different definitions and explanations exist for the concept of academic literacy. However, the most widely used and comprehensive one is that the term has to do with a gamut of literacy skills associated with content learning and an individual’s higher-order thinking . It comp“Genre” approach is the next theoretical underpinning on academic literacy, which regards it as a person’s ongoing achievement of common cultural values and communicative practices in a community or field of study . Accordi2.2Given the significance of academic literacy and literacies in different academic contexts and programs, educators and practitioners paid a special attention to the development of this pivotal construct. This surge of interest led to the emergence of ‘academic literacy development’, which refers to the process of acquiring an understanding of disciplinary practices and requirements and one’s capacity to interpret the relationship between text, context, and social actions of different genres . In this2.3After establishing itself in the literature, academic literacy development captured scholarly attention that proved its nature to be multidimensional rather than a single construct . AccordiThese dimensions reveal that the construct of academic literacy development is complex and multi-layered and may demand more research in different contexts to unravel more possible dimensions . A proba2.4With the rise and prominence of the sociocultural approach to academic literacy development, strong premises have been held seeing it as situated and complex. Another emerging feature in this domain is the increasing attention paid to multilingualism and multiculturalism, especially among international students . This prAnother area that requires more attention is the research literacy skills that multilingual and multicultural students and teachers need in the globalization era . In orde2.5Academic literacy and its development have been an important aspect of higher education in different fields for decades . After eMoreover, a large body of existing studies on academic literacy has focused on different language skills and sub-skills that students can improve in light of receiving literacy training . With moLiteracy + Numeracy Intervention Process” on the research abilities of researchers in New Zealand.Some other studies on academic literacy have focused on the impact of specific approaches and practices in improving teachers' and students' academic literacy. For example, Others, however, shifted their attention to teachers' academic literacy as a precondition for learners' academic literacy to occur. For instance, In the context of English for specific purposes (ESP), the construct of teacher academic literacy development has also been sought out by researchers. As a single landmark research, In spite of the prominence of all these previously conducted studies, teachers' perceptions and practices of academic literacy development in multilingual and multicultural contexts have mostly remained under-researched, to date. In an influential study, 2.6Research and practice of academic literacy development have gone through different changes and theoretical trends . TraditiLater, the language-based trend was criticized by cognitivists, who argued that academic literacy development goes beyond a simple acquisition of rhetorical structures and it is a tool for content learning and scientific reasoning . This psNow, the developmental path has come into the sociocultural stance that places academic literacy within larger societal and cultural structures and norms rather than discrete linguistic or cognitive skills . During Another trend that grew out of sociocultural perspectives is ‘The New Literacy Studies’ or NLS, which has provided an ideological model of literacy that reconciled between literacy and orality . This trAlthough these trends have been insightful enough to move the field forward, future trends may also appear given the development and changes in human knowledge and disciplinary requirement. Previous trends limitedly (if any) consider the role of emotions and affect in the academic literacy development of multilingual and multicultural students, who are experiencing many challenges in learning content and language in L2 contexts. Therefore, a future trend in this domain can be emotion-based as students from international/global contexts require care, love, and devotion on the part of their teachers. Particularly, the role of positive psychology constructs and interpersonal communication factors  can be inspected in multilingual settings, as well . Moreove3In this review article, it was contended that EFL teachers and even students are now requiring different academic literacies in comparison to the decade’s ago. Previously, training courses and research trends on academic literacy and its development were confined to linguistic and cognitive aspects. However, with the globalization of English and the internationalization of higher education, many international students and teachers are now working in multilingual contexts that demand different academic literacies than mainstream educators. In multilingual contexts, teachers may face various challenges in teaching English to students who come from different cultural contexts and speak non-English languages. They need to cultivate multiliteracies in students so that they have an authorial voice in academia and position themselves within their community of practice that adheres to specific academic literacies and rhetorical patterns. Instead of sticking to linguistic aspects of English and the content of education, teachers must focus more on communicative functions and norms that are pivotal in a specific discipline. Since multilingual contexts, especially those in which English is considered as a foreign language, are full of challenges for both teachers and students, educators must strike a balance between language learning and content learning.By paying attention to these propositions and contentions, EFL teachers can benefit from this theoretical review in that they understand the common trends in teaching English in multilingual and multicultural contexts and propose suitable practices to raise their students' academic literacies. By knowing the requirements of their discipline at the moment, EFL teachers can highlight academic literacies such as academic writing, communicative competence, and digital academic literacies in remote education. They can also improve their mentality about academic literacy development courses in light of the information provided by different trends explained in this article. They may become cognizant that academic literacy development is no longer seen as an isolated construct, but as a social practice sensitive to cultural values and norms.Moreover, curriculum planners and designers can use this study to modify their current practices and make suggestions to integrate new academic literacies into their curricula at both micro and macro levels in multilingual and multicultural contexts. Teacher trainers in multilingual contexts can use this study as a guide and try to offer professional development courses to L2 teachers with different experiences in which the complexities, challenges, and common academic literacies and norms of their disciplines are highlighted. The trainers must shift from exclusive linguistic aspects of teaching at the multilingual context and capitalize on the social, cultural, emotional, and digital needs of the given discipline. They have to practically instruct the teachers on how to work at multilingual and multicultural milieus so that their pupils can benefit from their knowledge and survive in the globalized world with many academic pressures on non-English speaking students.Researchers may also find this review insightful in that it extends the literature on academic literacy development in multilingual and multicultural contexts, especially those in which English is spoken and taught as a foreign language. The existing literature on this topic is scan regarding the impact of academic literacy development on L2 education, especially in terms of cultural disparity among students. Furthermore, the current body of knowledge on academic literacy is mostly limited to theoretical studies that intended to explicate what the concept of academic literacy development means, case studies on the development of academic literacies of particular stakeholders in particular educational contexts, one-shot surveys, and quantitative studies on the underlying components of academic literacy development in contexts other that multilingualism and multiculturalism. This is where the present article can be significant and pave the way for future studies that take advantage of other research designs and instruments to present a more vivid picture of academic literacy development in multilingual settings. Additionally, further research can be done on the possible trends like affective trends and digitalized trends to academic literacy development to move the field forward. Needs analysis studies can also be carried out to disclose the literacies that teachers and students of specific fields perceive essential to be covered in training courses. Cross-cultural studies on academic literacies of similar disciplines are also an interesting line of research for future researchers.All authors listed have significantly contributed to the development and the writing of this article.Foundation of Henan Educational Committee [2022-JSJYYB-027].This work was supported by No data was used for the research described in the article.The authors declare no conflict of interest.No additional information is available for this paper.