Level Of Evidence For Use Research Articles

Oral anticoagulant safety in family practice: prognostic accuracy of Bleeding Risk Scores (from the CACAO study).

To assess bleeding risk of patients treated by oral anticoagulants, several scores have been constructed to assist physicians in the evaluation of the benefit risk. Most of these scores lack a strong enough level of evidence for use in family practice. To assess the predictive prognostic accuracy of 13 scores designed to assess the risk of major or clinically relevant non-major (CRNM) bleeding events in a French ambulatory cohort receiving Vitamin-K antagonists (VKA) or direct oral anticoagulants (DOACs) in a family practice setting. CACAO (Comparison of Accidents and their Circumstances with Oral Anticoagulants) was a multicentre prospective cohort of ambulatory patients prescribed oral anticoagulants. We selected patients from the cohort who had received an oral anticoagulant because of non-valvular atrial fibrillation (NVAF) and/or venous thromboembolism (VTE) to be followed during one year by their GP. The following scores were calculated: mOBRI, Shireman, Kuijer, HEMORR2HAGES, ATRIA, HAS-BLED, RIETE, VTE-BLEED, ACCP score, Rutherford, ABH-Score, GARFIEL-AF, and Outcomes Registry for Better InformedTreatment of Atrial Fibrillation (ORBIT). Prognostic accuracy was assessed by using receiver operating characteristic curves and c-statistics. During 1 year, 3,082 patients were followed. All of the scores demonstrated only poor to moderate ability to predict major bleeding or CRNM in NVAF patients on DOACs (c-statistic: 0.41-0.66 and 0.45-0.58), respectively. The results were only slightly better for patients prescribed VKA (0.47-0.66 and 0.5-0.55, respectively) in this indication. The results were also unsatisfactory in patients treated for VTE. None of the scores demonstrated satisfactory discriminatory ability when used in family practice. ClinicalTrials.gov NCT02376777.

Effect of 5-Aminolevulinic Acid and Sodium Fluorescein on the Extent of Resection in High-Grade Gliomas and Brain Metastasis.

Simple SummaryComplete surgical removal of high-grade gliomas (HGG) is known to increase the overall survival and progression-free survival. Several studies have shown that fluorescence-guided surgery with 5-aminolevulinic acid (5-ALA) increases gross total resection considerably compared to white light surgery (65% vs. 36%). Recently, an off-label fluorophore, sodium fluorescein (SF), has become popular in fluorescence-guided surgery due to numerous utility benefits compared to 5-ALA, including lower cost, non-toxicity, easy administration during surgery and a wide indication for other CNS tumors. However, the level of evidence is inferior compared to 5-ALA. We reviewed the latest literature on fluorescence-guided surgery with 5-ALA and SF for brain tumors with emphasis on fluorescence-guided surgery in HGG and brain metastases. Further, we assessed the advantages and disadvantages of both fluorophores and discussed their future perspectives.Surgery is essential in the treatment of high-grade gliomas (HGG) and gross total resection (GTR) is known to increase the overall survival and progression-free survival. Several studies have shown that fluorescence-guided surgery with 5-aminolevulinic acid (5-ALA) increases GTR considerably compared to white light surgery (65% vs. 36%). In recent years, sodium fluorescein (SF) has become an increasingly popular agent for fluorescence-guided surgery due to numerous utility benefits compared to 5-ALA, including lower cost, non-toxicity, easy administration during surgery and a wide indication range covering all contrast-enhancing lesions with disruption of the blood–brain barrier in the CNS. However, currently, SF is an off-label agent and the level of evidence for use in HGG surgery is inferior compared to 5-ALA. Here, we give an update and review the latest literature on fluorescence-guided surgery with 5-ALA and SF for brain tumors with emphasis on fluorescence-guided surgery in HGG and brain metastases. Further, we assess the advantages and disadvantages of both fluorophores and discuss their future perspectives.

Use of Bone Marrow Concentrate to Treat Pain and Musculoskeletal Disorders: An Academic Delphi Investigation

Acute and degenerative musculoskeletal disorders are among the most common etiologies of disability worldwide. Recently, there has been interest in the field of regenerative medicine to bridge the gap between conservative and surgical management of these conditions. Autologous bone marrow concentrate is one type of injectate that has increased in popularity over the last few decades. Though there is promising evidence supporting its efficacy, standard of care practice guidelines to govern the appropriate use and implementation of such technology are currently lacking. The aim of this article is to report findings from a survey administered using the Delphi technique to a group of physicians using bone marrow concentrate in practice to determine best practice consensus regarding optimization of patient safety and education. Delphi panel technique. The study was first announced at a national meeting and continued remotely across the United States via 4 rounds of online surveys. An initial panel of 30 expert members was convened and a 5-member steering committee was established. Four rounds of consensus questionnaires totaling 11 unique questions were distributed. Ten questions included a 5-point Likert scale from "Strongly Agree" to "Strongly Disagree," and one question had a selection of 5 options regarding minimum level of evidence required. The anonymized aggregate results of each round were shared with the group prior to voting in the subsequent round in accordance with the Delphi process. Consensus was defined as 80% agreement of the statements indicating either "Strongly Agree" or "Agree" for the 10 questions with the Likert Scale and 80% agreement among 2 of 5 choices in the question regarding levels of evidence. Three invited participants were excluded by the second round of questions due to lack of response in a timely manner, leaving 27 physicians queried. Nine of the 11 questions met criteria for > 80% consensus. Areas of agreement included importance of a treatment registry, candidacy grading, expanded informed consent, scientific accuracy in advertising, institutional review board approval for novel uses, performance of procedures by only licensed physicians or mid-level providers with direct physician oversight, use of image guidance for injections, data submission for publication in peer reviewed literature, and a minimum requirement of case-series level of evidence for use of bone marrow concentrate in musculoskeletal medicine. The 2 areas that did not meet criteria for consensus included online publishing of individual clinic data and standards around cell counting for dosing. The Delphi panel of experts was convened on a voluntary basis rather than a nomination process. Our panel of experts were all physicians who use bone marrow concentrate in practice, therefore it is possible that a different panel of experts within other disciplines would reach different conclusions. There is significant consensus among a panel of physicians performing bone marrow concentrate injections regarding best practice guidelines for musculoskeletal conditions.

Plasma exchange in patients with acute and acute-on-chronic liver failure: A systematic review.

BACKGROUNDAcute liver failure (ALF) and acute-on-chronic liver (ACLF) carry high short-term mortality rate, and may result from a wide variety of causes. Plasma exchange has been shown in a randomized control trial to improve survival in ALF especially in patients who did not receive a liver transplant. Other cohort studies demonstrated potential improvement in survival in patients with ACLF.AIMTo assess utility of plasma exchange in liver failure and its effect on mortality in patients who do not undergo liver transplantation.METHODSDatabases MEDLINE via PubMed, and EMBASE were searched and relevant publications up to 30 March, 2019 were assessed. Studies were included if they involved human participants diagnosed with liver failure who underwent plasma exchange, with or without another alternative non-bioartificial liver assist device.RESULTSThree hundred twenty four records were reviewed, of which 62 studies were found to be duplicates. Of the 262 records screened, 211 studies were excluded. Fifty-one articles were assessed for eligibility, for which 7 were excluded. Twenty-nine studies were included for ALF only, and 9 studies for ACLF only. Six studies included both ALF and ACLF patients. A total of 44 publications were included. Of the included publications, 2 were randomized controlled trials, 14 cohort studies, 12 case series, 16 case reports. All of three ALF studies which looked at survival rate or survival days reported improvement in outcome with plasma exchange. In two out of four studies where plasma exchange-based liver support systems were compared to standard medical treatment (SMT) for ACLF, a biochemical improvement was seen. Survival in the non-transplanted patients was improved in all four studies in patients with ACLF comparing plasma exchange vs SMT. Using the aforementioned studies, plasma exchange based therapy in ACLF compared to SMT improved survival in non-transplanted patients at 30 and 90-d with a pooled OR of 0.60 (95%CI 0.46-0.77, P < 0.01).CONCLUSIONThe level of evidence for use of high volume plasma exchange in selected ALF cases is high. Plasma exchange in ACLF improves survival at 30-and 90-d in non-transplanted patients. Further well-designed randomized control trials will need to be carried out to ascertain the optimal duration and amount of plasma exchange required and assess if the use of high volume plasma exchange can be extrapolated to patients with ACLF.

Operationalization of Next-Generation Sequencing and Decision Support for Precision Oncology.

Genomic testing has become a part of routine oncology care and plays critical roles in diagnosis, prognostic assessment, and treatment selection. Thus, in parallel, the variety of genomic testing providers and sequencing platforms has grown exponentially. Selection of the best-fit panel for each case can be daunting, with many factors to consider. Among them is whether alteration interpretation and therapy/clinical trial matching are included and/or sufficient. In this article, we review some common commercially available sequencing platforms for the genes and types of alterations tested, samples needed, and reporting content provided. We review publicly available resources for a do-it-yourself approach to alteration interpretation when it is not provided or when supplemental research is needed, along with resources to identify genomically matched treatment options that are approved and/or investigational. However, with both commercially provided interpretation and publicly available resources, there are still caveats and limitations that can stem from insufficient or ambiguous nomenclature as well as from the presentation of information. Use cases in which clinical decision making was affected are discussed. After treatment options are identified, it is important to assess the level of evidence for use within the patient's tumor type and molecular profile. However, numerous level-of-evidence scales have been published in recent years, so we provide a publicly available tool to facilitate interoperability. The level of evidence, along with other factors, such as allelic frequency and copy number, can be used to prioritize treatment options when multiple are identified.

THE APPLICATION OF VIRTUAL REALITY IN GERIATRIC MENTAL HEALTH: THE STATE OF THE EVIDENCE

Introduction In recent years, there has been a rise in the prevalence of cognitive and affective disorders in the ageing population. This has led to an impetus on innovative, scalable and engaging interventions for these disorders, and technology has proved to be a promising frontier. In the past decade, virtual reality (VR) technology has seen a shift from two-dimensional non-immersive projections to three-dimensional fully immersive experiences, allowing for the development of more sophisticated simulations. There have been successful applications of VR in clinical settings with children and teens, including social cognition training for autism, sustained attention in attention-deficit hyperactivity disorder (ADHD), exposure-based therapies for anxiety disorders, and depression pathology. However, VR has been less studied in the geriatric population. The purpose of this study is to determine the existing levels of evidence for use of VR in clinical settings and identify areas where more evidence may guide translation of existing VR interventions for older adults. Methods This study is a systematic review. We conducted a search on PubMed in December 2018 for peer-reviewed journal articles published in English within the last 10 years. We narrowed the search to VR technology and its applications in older adults, as well as studies of VR in normal aged adults for comparative value. We rejected articles if the title and abstract did not meet inclusion criteria and authors LM, AR and MS agreed by consensus on which articles were relevant. We also used the bibliographies of selected articles to find additional articles that we may have missed in the initial search. We then reviewed article content to classify the articles into appropriate domains of geriatric mental health (content domains) and research objectives (research domains). Results Based on our review, a total number of 426 articles were found, and 49 met our inclusion criteria related to older adults. We conducted a yearly count for the number of search results to identify if there has been an increase in research in the field. The number of search results by year are positively correlated (see Figure 1). We also identified 5 additional articles which focused on younger adults which we opted to include in the review based on internal consensus amongst all authors that they reflected VR application in domains of mental health that are known to apply to older adults as well. We found that the articles fell across several content domains: Cognition, conditions along the mood spectrum, anxiety, post-traumatic stress disorder (PTSD), and caregiver burden. The research domain with the highest number of articles was VR validity testing (26), followed by cognitive training (18), indicating that these are the VR applications for which the best evidence exists currently. Conclusions Currently, existing evidence offers clear support for the use of VR as a screening tool for cognitive impairment in older adults, and as a training tool to improve cognitive skills. VR-based tasks demonstrated validity comparable to some traditional paper-based assessments of cognition. Furthermore, there are indications that VR can play a role in delaying the onset of Alzheimer's Disease (AD), mild cognitive impairment (MCI), and other forms of dementia. More work is needed to refine VR screening capabilities for more specific diagnoses, but the potential for innovation in VR environments and tasks makes VR a promising medium to achieve this specificity. Additionally, there were many different VR environments used across studies, which may show a need for standardization of environments before comparisons can be made between VR simulations. Given the robust evidence of VR as a treatment in affective disorders in younger adults, we see potential for the same intervention in older adult mood spectrum disorders and other psychiatric conditions. Finally, future studies should address key issues surrounding VR use in clinical settings, such as usability, data privacy, and confidentiality. This research was funded by Anonymous philanthropic donation to McLean Hospital.

Evidence in focus: Nusinersen use in spinal muscular atrophy: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology.

To identify the level of evidence for use of nusinersen to treat spinal muscular atrophy (SMA) and review clinical considerations regarding use. The author panel systematically reviewed nusinersen clinical trials for patients with SMA and assigned level of evidence statements based on the American Academy of Neurology's 2017 therapeutic classification of evidence scheme. Safety information, regulatory decisions, and clinical context were also reviewed. Four published clinical trials were identified, 3 of which were rated above Class IV. There is Class III evidence that in infants with homozygous deletions or mutations of SMN1, nusinersen improves the probability of permanent ventilation-free survival at 24 months vs a well-defined historical cohort. There is Class I evidence that in term infants with SMA and 2 copies of SMN2, treatment with nusinersen started in individuals younger than 7 months results in a better motor milestone response and higher rates of event-free survival than sham control. There is Class I evidence that in children aged 2-12 years with SMA symptom onset after 6 months of age, nusinersen results in greater improvement in motor function at 15 months than sham control. Nusinersen was safe and well-tolerated. Evidence of efficacy is currently highest for treatment of infantile- and childhood-onset SMA in the early and middle symptomatic phases. While approved indications for nusinersen use in North America and Europe are broad, payer coverage for populations outside those in clinical trials remain variable. Evidence, availability, cost, and patient preferences all influence decision-making regarding nusinersen use.

Evidence on botulinum toxin in selected disorders

Botulinum toxin (BoNT) is a neurotoxin produced by the bacteria Clostridium botulinum that has become widely used for various neurologic indications. The four toxin formulations currently available for use in the United States (approved by the Food and Drug Administration) are onabotulinumtoxinA (Botox®), abobotulinumtoxinA (Dysport®), incobotulinumtoxinA (Xeomin®), and rimabotulinumtoxinB (Myobloc®). While the FDA-approved labels indicate that potency conversions should not be done, literature supports relative dose equivalents of approximately 1:1:2–4:50-100, respectively. The aim of this paper is to review the evidence on the use of BoNT formulations available in the United States for specific neurologic disorders, including blepharospasm, cervical dystonia (CD), upper and lower extremity spasticity and chronic migraine. Data from the updated 2016 American Academy of Neurology (AAN) guidelines are presented and the level of evidence for use of the four available preparations of BoNT are discussed (Table 2 in appendix).For the management of blepharospasm, the recommendations are for use of onaBoNT-A and incoBoNT-A injections with level B evidence. For the management of CD, the recommendations are for use of aboBoNT-A and rimaBoNT-B with level A evidence. For the management of upper extremity spasticity, the recommendations are for use of aboBoNT-A, incoBoNT-A and onaBoNT-A with level A evidence. For the management of lower extremity spasticity, the recommendations are for use of onaBoNT-A and aboBoNT-A with level A evidence. For the management of chronic migraines, the recommendations are for use of onaBoNT-A to help improve headache-free days, with level A evidence. It is important for the clinician to understand that BoNT is for use in symptomatic control for the underlying neurologic disorder and, at present, has not shown a role in disease modification.

Evidence for the use of "medical marijuana" in psychiatric and neurologic disorders.

Cannabis is listed as a Schedule I substance under the Controlled Substances Act of 1970, meaning the US federal government defines it as an illegal drug that has high potential for abuse and no established medical use; however, half of the states in the nation have enacted "medical marijuana" (MM) laws. Clinicians must be aware of the evidence for and against the use of MM in their patients who may consider using this substance. A PubMed database search was performed using the text string: "Cannabis"[Mesh] OR "Marijuana Abuse"[Mesh] OR "Medical Marijuana"[Mesh] OR "Marijuana Smoking"[Mesh] OR "cannabi*" OR "tetrahydrocannabinol." The search was further limited to randomized clinical trial publications in English on human subjects to identify articles regarding the therapeutic use of phytocannabinoids for psychiatric and neurologic disorders. Commercially available products (ie, dronabinol, nabilone, nabiximols) and synthetic cannabinoids were excluded from the review. Publications were identified that included patients with dementia, multiple sclerosis, Parkinson disease, Huntington disease, schizophrenia, social anxiety disorder, depression, tobacco use disorder, and neuropathic pain. There is great variety concerning which medical conditions are approved for treatment with MM for either palliative or therapeutic benefit, depending on the state law. It is important to keep an evidence-based approach in mind, even with substances considered to be illegal under US federal law. Clinicians must weigh risks and benefits of the use of MM in their patients and should ensure that patients have tried other treatment modalities with higher levels of evidence for use when available and appropriate.

Hand hygiene techniques: still a requirement for evidence for practice?

Introduction Two hand hygiene techniques are promoted internationally: the World Health Organisation’s 6 step and the Centre for Disease Control’s 3 step techniques; both of which may be considered to have suboptimum levels of empirical evidence for use with alcohol based hand rub (ABHR). Objectives The aim of the study was to compare the effectiveness of the two techniques in clinical practice. Methods A prospective parallel group randomised controlled trial (RCT) was conducted with 1:1 allocation of 6 step versus the 3 step ABHR hand hygiene technique in a clinical setting. The primary outcome was residual microbiological load. Secondary outcomes were hand surface coverage and duration. The participants were medical and nursing participants (n=120) in a large teaching hospital. Results The 6 step technique was statistically more effective at reducing the bacterial count 1900cfu/ml (95% CI 1300, 2400cfu/ml) to 380cfu/ml (95% CI 150, 860 cfu/ml) than the 3 step 1200cfu/ml (95% CI 940, 1850cfu/ml) to 750cfu/ml (95% CI 380, 1400cfu/ml) (p=0.016) but even with direct observation by two researchers and use of an instruction card demonstrating the technique, compliance with the 6 step technique was only 65%, compared to 100% compliance with 3 step technique. Further those participants with 100% compliance with 6 step technique had a significantly greater log reduction in bacterial load with no additional time or difference in coverage compared to those with 65% compliance with 6 step technique (p=0.01). Conclusion To our knowledge this is the first published RCT to demonstrate the 6 step technique is superior to the 3 step technique in reducing the residual bacterial load after hand hygiene using alcohol based hand rub in clinical practice. What remains unknown is whether the residual bacterial load after the 3 step technique is low enough to reduce risk of transmission from the hands and whether the 6 step technique can be adapted to enhance compliance in order to maximise reduction in residual bacterial load and reduce duration.

EHealth in Wound Care: from conception to implementation.

Executive summary Purpose This document aims to provide wound care clinicians with a rapid and structured overview of the key issues related to use of eHealth applications (telemedicine and telehealth) within wound care. This includes: An overview of terminology and available literature Guidance on the methodology for evaluation of eHealth solutions An introduction to and discussion of the potential benefits of eHealth technologies in wound care, and the possible barriers to their implementation Recommendations for ensuring a good implementation process and supporting involvement of wound care professionals in safeguarding that eHealth solutions meet the needs of the patients. Methodology The document sections lean on the structure and focus areas of the Model for ASsessment of Telemedicine (MAST) which defines crucial items to evaluate an eHealth application. The content of the document is developed on the basis of a literature review, identifying available documentation for use of eHealth solutions in wound care. Furthermore, it draws on various key documents recently published on the general development, evaluation and implementation of eHealth solutions. These include valuable up-to-date information relevant for any group of clinicians wishing to follow and influence the way eHealth solutions are integrated into clinical practice. Findings and conclusions The literature review revealed that the amount and level of evidence for use of eHealth applications in wound care is still limited. Some MAST domains are not examined in any of the available studies. Thus, more research is required to identify the potential benefits and harms to patients, and the possible challenges related to implementation of eHealth solutions in wound care. Potential barriers and facilitators for the implementation of eHealth applications into wound care practice are identified in the document, and these may all either enhance or impede the process. However, the available research does demonstrate patient satisfaction, improved access to health services for all client cohorts, and increased job satisfaction for clinicians. The document recommends that wound management clinicians, considering the use of eHealth applications in their clinical practice, consult widely and conduct regular evaluation of the outcomes to ensure efficient implementation of these services. To support this approach, steps to ensure a good implementation process within a given organisation have been proposed. These are synthesised into a three circle model.

The State of the Evidence: ASHA Develops Levels of Evidence for Communication Sciences and Disorders

The State of the Evidence: ASHA Develops Levels of Evidence for Communication Sciences and Disorders