Appropriate Level Of Evidence Research Articles

A Regenerative Interventional Approach to the Management of Degenerative Low Back Pain

Objective: Low back pain has been strongly related to the degenerative process of the spine, especially the degeneration of the intervertebral disc and facet joints. The main procedures for the management of low back pain are no intended to slow down or reverse the degenerative process. Platelet Rich Plasma (PRP), an orthobiologic product, has been the subject of several studies in the management of low back pain. Methods: A prospective case series study presenting the clinical results of 23 patients treated with PRP injections performed following clinical a interventionist protocol called PerMuTIS – Personalized Multi Target Biologic Injection of the Spine. The method to obtain the platelet concentrate was the Simple Double Spin technique, a low-cost double spin that produces Leucocyte Rich PRP. Baseline scores of pain and disability using the Visual Analog Scale (VAS) and Roland-Morris Disability Questionnaire (RMDQ) were recorded. Results: Mean VAS pain score across the cohort decreased by approximately 62%, while the Roland-Morris disability score decreased by about 60% at 52 weeks. There was no report of adverse events. The Leucocite and Monocite Rich PRP product showed concentration of 4.3X above baseline, with monocites concentration of 3.2X baseline. Conclusion: The concept of application in multiple targets using a simple and low-cost preparation technique proved to be feasible and without reports of serious side effects that compromise its indication. The PerMuTIS – Personalized Multi Target Biologic Injection in the Spine Technique using Simple Double Spin protocol demonstrated safety and feasibility in this prospective study of patients with low back pain who failed conservative treatments. Large scale, multicenter randomized clinical trial will provide an appropriate level of evidence to assist in clinical practice.

Cross-validation of predictive models for functional recovery after post-stroke rehabilitation

BackgroundRehabilitation treatments and services are essential for the recovery of post-stroke patients’ functions; however, the increasing number of available therapies and the lack of consensus among outcome measures compromises the possibility to determine an appropriate level of evidence. Machine learning techniques for prognostic applications offer accurate and interpretable predictions, supporting the clinical decision for personalised treatment. The aim of this study is to develop and cross-validate predictive models for the functional prognosis of patients, highlighting the contributions of each predictor.MethodsA dataset of 278 post-stroke patients was used for the prediction of the class transition, obtained from the modified Barthel Index. Four classification algorithms were cross-validated and compared. On the best performing model on the validation set, an analysis of predictors contribution was conducted.ResultsThe Random Forest obtained the best overall results on the accuracy (76.2%), balanced accuracy (74.3%), sensitivity (0.80), and specificity (0.68). The combination of all the classification results on the test set, by weighted voting, reached 80.2% accuracy. The predictors analysis applied on the Support Vector Machine, showed that a good trunk control and communication level, and the absence of bedsores retain the major contribution in the prediction of a good functional outcome.ConclusionsDespite a more comprehensive assessment of the patients is needed, this work paves the way for the implementation of solutions for clinical decision support in the rehabilitation of post-stroke patients. Indeed, offering good prognostic accuracies for class transition and patient-wise view of the predictors contributions, it might help in a personalised optimisation of the patients’ rehabilitation path.

Exploring the misalignment on the value of further research between payers and manufacturers. A case study on a novel total artificial heart.

Payers and manufacturers can disagree on the appropriate level of evidence that is required for new medical devices, resulting in high societal costs due to decisions taken with sub‐optimal information. A cost‐effectiveness model of a hypothetical total artificial heart was built using data from the literature and the (simulated) results of a pivotal study. The expected value of perfect information (EVPI) was calculated from both the payer and manufacturer perspectives, using net monetary benefit and the company's return on investment respectively. A function was also defined, linking effectiveness to market shares. Additional constraints such as a minimum clinical difference or maximum budget impact were introduced into the company's decisions to simulate additional barriers to adoption. The difference in the EVPI between manufacturers and payers varied greatly depending on the underlying decision rules and constraints. The manufacturer's EVPI depends on the probability of being reimbursed, the uncertainty on the (cost‐)effectiveness of the technology, as well as other parameters relating to initial investments, operating costs and market dynamics. The use of Value of information for both perspectives can outline potential misalignments and can be particularly useful to inform early dialogs between manufacturers and payers, or negotiations on conditional reimbursement schemes.

POSB52 Exploring the Misalignment on the Value of Further Research between Payers and Manufacturers: A Case Study on a Novel Total Artificial Heart

Payers and manufacturers may disagree on what is the appropriate level of evidence for novel medical devices. Payers need to balance the benefits of immediate reimbursement with the benefits of waiting until more evidence becomes available. In fact, optimal decisions depend upon the type and amount of the existing uncertainty, the utility-function used to estimate the value of research (e.g., minimum clinical difference, or cost-effectiveness), and the reimbursement options in their policy toolbox.

Digital health care in China and access for older people

Digital health care in China and access for older people

Parkinson's Patients' Tolerance for Risk and Willingness to Wait for Potential Benefits of Novel Neurostimulation Devices: A Patient-Centered Threshold Technique Study.

Background. Parkinson’s disease (PD) is neurodegenerative, causing motor, cognitive, psychological, somatic, and autonomic symptoms. Understanding PD patients’ preferences for novel neurostimulation devices may help ensure that devices are delivered in a timely manner with the appropriate level of evidence. Our objective was to elicit preferences and willingness-to-wait for novel neurostimulation devices among PD patients to inform a model of optimal trial design. Methods. We developed and administered a survey to PD patients to quantify the maximum levels of risks that patients would accept to achieve potential benefits of a neurostimulation device. Threshold technique was used to quantify patients’ risk thresholds for new or worsening depression or anxiety, brain bleed, or death in exchange for improvements in “on-time,” motor symptoms, pain, cognition, and pill burden. The survey elicited patients’ willingness to wait to receive treatment benefit. Patients were recruited through Fox Insight, an online PD observational study. Results. A total of 2740 patients were included and a majority were White (94.6%) and had a 4-year college degree (69.8%). Risk thresholds increased as benefits increased. Threshold for depression or anxiety was substantially higher than threshold for brain bleed or death. Patient age, ambulation, and prior neurostimulation experience influenced risk tolerance. Patients were willing to wait an average of 4 to 13 years for devices that provide different levels of benefit. Conclusions. PD patients are willing to accept substantial risks to improve symptoms. Preferences are heterogeneous and depend on treatment benefit and patient characteristics. The results of this study may be useful in informing review of device applications and other regulatory decisions and will be input into a model of optimal trial design for neurostimulation devices.

What is an appropriate level of evidence for a digital health intervention?

What is an appropriate level of evidence for a digital health intervention?

On the benefits and challenges of using kanban in software engineering: a structured synthesis study

ContextKanban is increasingly being used in diverse software organizations. There is extensive research regarding its benefits and challenges in Software Engineering, reported in both primary and secondary studies. However, these results have not been synthesized yet.Goalto investigate and identify the actual benefits and challenges of using Kanban in Software Engineering to support practitioners in understanding and analyzing the benefits and challenges of adopting Kanban in their software projects.Methodto use the Structured Synthesis Method to aggregate existing empirically-grounded evidence in the published primary studies regarding using Kanban in Software Engineering.Resultsfrom the 20 selected primary studies in which over 16 benefits were identified, four had the most robust results in the aggregation, i.e., with the most confidence associated, namely: ‘work visibility,’ ‘control of project activities and tasks,’ ‘flow of work,’ and ‘time-to-market.’ Furthermore, the ‘organizational culture’ was identified as the most dominant challenge in Kanban implementations.ConclusionsSyntheses studies represent a fundamental step in organizing the body of evidence as an empirically-grounded reference for decision-making in practice. The benefits with most confidence indeed appear to be the ones intrinsically linked to the Lean thinking and the Kanban approach. As Kanban originated in the manufacturing, it is interesting to observe this kind of confirmation in the software domain. Still, there are several benefits and challenges which still lacks the appropriate level of evidence. We also noticed the absence of negative results reported in the technical literature. These aspects need the additional attention of the research community.

Evidence Synthesis of Diagnostics: GRADE and How It Can Be Used for Veterinary Evidence

<p>While textbooks on evidence-based medicine still mainly focus on accuracy studies as most appropriate level of evidence for diagnostic questions, the guideline developers have moved forward to patient important outcomes. In other words, a perfect test may still be useless if it does not change clinical decisions and outcomes for patients. What is the current state of evidence-based diagnostics and how can this be translated to different veterinary situations?</p><br /> <img src="https://www.veterinaryevidence.org/rcvskmod/icons/oa-icon.jpg" alt="Open Access" />

Evidence Synthesis of Diagnostics: GRADE and How It Can Be Used for Veterinary Evidence

While textbooks on evidence-based medicine still mainly focus on accuracy studies as most appropriate level of evidence for diagnostic questions, the guideline developers have moved forward to patient important outcomes. In other words, a perfect test may still be useless if it does not change clinical decisions and outcomes for patients. What is the current state of evidence-based diagnostics and how can this be translated to different veterinary situations?

Radiographic Diagnosis of Pincer-Type Femoroacetabular Impingement: A Systematic Review.

Background:Femoroacetabular impingement (FAI) is a well-recognized condition that causes hip pain and can lead to early osteoarthritis if not managed properly. With the increasing awareness and efficacy of operative treatments for pincer-type FAI, there is a need for consensus on the standardized radiographic diagnosis.Purpose:To perform a systematic review of the evidence regarding imaging modalities and radiographic signs for diagnosing pincer-type FAI.Study Design:Systematic review; Level of evidence, 4.Methods:A literature review was performed in 2016 using the Cochrane, PubMed, and Embase search engines. All articles focusing on a radiographic diagnosis of pincer-type FAI were reviewed. Each of the included 44 articles was assigned the appropriate level of evidence, and the particular radiographic marker and/or type of imaging were also summarized.Results:There were 44 studies included in the final review. Most of the articles were level 4 evidence (26 articles), and there were 12 level 3 and 6 level 2 articles. The crossover sign was the most commonly used radiographic sign (27/44) followed by the lateral center-edge angle (22/44). Anteroposterior (AP) pelvis plain radiographs were the most commonly used imaging modality (33 studies). Poor-quality evidence exists in support of most currently used radiographic markers, including the crossover sign, lateral center-edge angle, posterior wall sign, ischial spine sign, coxa profunda, acetabular protrusion, and acetabular index. There is poor-quality conflicting evidence regarding the use of the herniation pit to diagnose pincer-type FAI. Some novel measurements, such as β-angle, acetabular roof ratio, and acetabular retroversion index, have been proposed, but they also lack support from the literature.Conclusion:No strong evidence exists to support a single best set of current radiographic markers for the diagnosis of pincer-type FAI, largely due to the lack of better quality trials (levels 1 and 2) that compare conventional radiographic findings with the gold standard, which is the intraoperative findings. More sophisticated imaging modalities such as computed tomography and magnetic resonance arthrography are often needed to diagnose pincer-type FAI, and these investigations are relatively accurate in assessing labral pathology or cartilage damage.

Clinical studies in lysosomal storage diseases: Past, present, and future.

Lysosomal storage disorders (LSDs) consist of over 40 diseases, some of which are amenable to treatment. In this review, we consider the regulatory context in which LSDs studies are performed, highlight design specificities and explore operational challenges.Orphan drug legislations, both in Europe and US, were effective to stimulate LSDs drug development. However, regulators flexibilities toward approval vary leading to global discrepancies in access to treatments.Study designs are constrained because few patients can be studied. This implies LSDs treatments need to demonstrate large levels of clinical efficacy. If not, an appropriate level of evidence is difficult to achieve. While biomarkers could address this issue, none have been truly accepted as primary outcome.Enrichment of study population can increase the chance of success, especially with clinical outcomes. Adaptive designs are operationally challenging. Innovative methods of analysis can be used, notably using a patient as his/her own control and responder analysis. The use of extension phases and patient registries as a source of historical comparison can facilitate data interpretation.Operationally, few patients are available per centers and multiple centers need to be initiated in multiple countries. This impacts time-lines and budget.In the future, regulators flexibility will be essential to provide patients access to innovative treatments.

Building the evidentiary framework for pharmacogenetic testing: is it time to move beyond randomized controlled trials?

There is a rapidly expanding evidentiary gap between new molecular markers predictive of drug response and data that supports using such molecular markers (e.g., DNA, RNA or smallmolecule-based tests) in clinical practice. This evidence gap is a barrier to realizing the promise of personalized medicine where treatments are tailored to a patient’s individual characteristics. Randomized controlled trials (RCTs) are the ‘gold-standard’ metric for establishing the evidence that a particular intervention is superior to the current standard of care. However, the RCT is not without limitations and may not be the appropriate level of evidence required to support the clinical use of pharmacogenomic testing. We live in an environment where it is impractical to expect a RCT for each new marker. We should not abandon evidence-based practices when deciding to use a new pharmaco genomic marker; instead, clinicians and researchers must decide the appropriate level of evidence, short of the RCT, that supports the use of a novel pharmacogenomic marker in clinical care.

Frontal fibrosing alopecia: a review of eleven patients

Frontal fibrosing alopecia (FFA) is a primary lymphocytic cicatricial alopecia with a distinctive clinical pattern of progressive frontotemporal hairline recession. Our purpose was to describe the clinical and histopathological features as well as the response to treatment of eleven cases of FFA diagnosed at the Trichology Consultation, over three years. A retrospective case note review was performed of eleven adult patients with FFA. The clinical data as well the histopathologic findings and laboratory tests were accessed. The patients were treated with different drugs, depending on the stage of the disease. The age of onset of the alopecia ranged from 45 to 80 years. Ten patients (90.9%) were postmenopausal women. All patients had progressive and symmetrical alopecia localized to the frontal and temporal hairline. Seven patients (63.6%) had marked decreased to complete loss of eyebrows and in four patients axillar alopecia was also evident. Laboratory investigations were normal. Scalp biopsy specimens from the anterior hairline showed similar findings. No significant improvement was observed in the majority of cases. Differential diagnosis should take into account several other conditions. It seems there is no effective treatment proven with an appropriate level of evidence in the management of FFA.

An Overview of Mood Disorders in the DSM-5

The process of revising the DSM, which is based on new findings in the literature and experience with the current classification, is initiated every 12-18years. The process for the revision of DSM-IV to the DSM-5 began in 2006-after a series of meeting proceedings and monographs were published during the previous 3years-with the appointment of diagnostic group chairs by Director Dr. David Kupfer and Vice Director Dr. Darrel Regier. Members were recruited for workgroups to review the existing DSM-IV, to decide what worked well and which areas needed change, to review the available literature and data, and to propose changes based on an appropriate level of evidence in the literature proportional to the significance of the change. At the halfway point in this process, the Mood Disorders Workgroup has made tentative recommendations to be tested in field trials. These recommendations and some of the basis for them are discussed in this review. Final decisions await the data from field trials, possible revisions by the workgroups, and action by the task force. This article describes some of the recommendations made by the Mood Disorders Workgroup at this point in the process.

Frontal Fibrosing Alopecia: To Treat or Not to Treat?

published studies have evaluated a variety of therapeutic agents in frontal fibrosing alopecia (FFA); however, data on whether fibrosis is already established when the patients initially present are scarce. to identify the prevalence of active disease in patients initially diagnosed with FFA and to evaluate the efficacy of therapeutic agents suggested in the medical literature. eighteen postmenopausal women with FFA presented at the outpatient clinic of our hospital from June 2003 to August 2007. Five patients who also presented with androgenetic alopecia were treated with finasteride 2.5 mg/d plus minoxidil 5% for 12 months. One patient with a rapidly regressing disease received systemic corticosteroids. The remaining 12 patients were divided into two groups: 6 patients received topical clobetasol 0.05% solution once daily for 6 months and the rest received no treatment. thirteen of 18 patients presented with stable disease. No significant improvement was observed in any of the patients. to date, there is no effective treatment proven with an appropriate level of evidence in the management of FFA. Exclusion criteria in future clinical studies should take into account patients presenting with stable disease. What needs to be established is whether treatment can halt or slow the progression of active disease.

Does the Evidence Support Use of the Baha Implant System (Baha) in Patients with Congenital Unilateral Aural Atresia?

To determine if the evidence supports the recommendation of Baha implant systems (Bahas) over unaided conditions in persons with conductive hearing loss due to congenital unilateral aural atresia (CUAA), and if laboratory measures predict patient benefit and satisfaction. A systematic review. The authors constructed and submitted search strings to PubMed and other electronic databases to identify studies in peer-reviewed journals that were at an appropriate level of evidence (systematic reviews, randomized controlled trials, or nonrandomized intervention studies); used outcome measures assessing audibility, localization, or speech-recognition in noise; included patients with CUAA using Bahas; and had intrepretable data. References of all retrieved articles were also hand searched for relevant studies. Evaluation forms were completed by the authors for each of the included studies at all phases of the review including quality assessment and data extraction. The authors reviewed 88 retrieved titles and excluded four that had no relevance to the topic and 67 that were duplicates. Abstracts were reviewed for the remaining 17, and six nonrelevant studies were excluded. The remaining 11 articles were retrieved for full-text review; only three studies met inclusion criteria and were analyzed further. The three studies were not appropriate for a meta-analysis due to limited data, too few participants, and insufficient presentations of results. Qualitative analysis revealed inconsistent findings across audiometric measures, and few significant differences were noted with and without Bahas, yet most participants believed that Bahas improved their quality of life. Laboratory measures did not always predict patient benefit and satisfaction with Bahas. Results were limited for this narrow population having CUAA and the specific criteria used for this review. Audiologic measures generally failed to predict patients' success and/or satisfaction with their Bahas, but most of the included studies showed that patients perceived some benefits. Ideally, clinical decision making should include the highest levels of scientific evidence. However, when evidence is unavailable or does not support a clear-cut recommendation for a particular treatment across patients, as seems to be the case for the use of Bahas with CUAA, then clinicians must rely more heavily on clinical expertise and individual patient preferences in guiding clinical decision making.

Evidence-Based Medicine Analysis of Isthmic Spondylolisthesis Treatment Including Reduction Versus Fusion In Situ for High-Grade Slips

: Literature review. : The purpose of this article is to review the available literature and to attempt to formulate evidence-based recommendations for the surgical treatment of high-grade spondylolisthesis in the pediatric population. : The surgical management of high-grade spondylolisthesis remains controversial due to the lack of high level evidence. Prospective randomized studies have not been completed. : Through an electronic database search and published literature cross-reference, appropriate studies were identified and assigned the appropriate level of evidence. : There were no Level I or II evidence on this topic with our search. The best level of evidence that we have on this topic is retrospective comparative studies. We found 5 such articles which compared fusion in situ to reduction and fusion for high-grade spondylolisthesis. Pseudarthrosis rates are decreased by performing an instrumented reduction with a fusion. However, there is no significant difference in a clinical outcome of patients treated in situ versus reduction. : Because of the paucity of high levels of evidence, we are not able to formulate clear guidelines for treatment of high-grade spondylolisthesis based on the best evidence available in the published literature.

Adjuvant analgesic therapy for cancer-related pain: Does the evidence support the practice?

8032 Background: Adjuvant analgesic treatments have primary indications for uses other than the treatment of pain but demonstrate analgesic activity in some conditions. Although there is high level evidence to support the use of adjuvant analgesics in the chronic pain setting (eg antidepressants and anticonvulsants for benign neuropathic pain) the evidence relevant to the cancer pain setting has never been reviewed. Methods: This study examined the literature assessing adjuvant analgesic treatments specifically for publications restricted to patients with cancer pain, where pain relief was the primary outcome. Relevant studies were identified following searches of MEDLINE, EMBASE and the Cochrane Library (including up to December 2003). An appropriate level of evidence (NHMRC Australia designation) was applied for each treatment. Results: Significant variation in the extent and quality of research was noted across treatments. Level I or II evidence existed to support analgesic efficacy for NSAIDs, intravenous bisphosphonates and radiation treatment for painful bone metastases. Treatments employed for relief of cancer-related neuropathic pain were associated with a low evidence for analgesic efficacy, including anticonvulsants (Level III), systemic local anaesthetics (Level III), ketamine (Level II) and antidepressants (no evidence). Conclusions: Recruitment of patients with cancer-related pain to studies assessing adjuvant analgesic treatments is difficult, but clearly there is an important need for further clinical trials in this area. No significant financial relationships to disclose.

The Clinical Significance of Quality-of-Life Results: Practical Considerations for Specific Audiences

This is the sixth article in a series intended to summarize the state of the science for assessing the clinical significance of quality-of-life (QOL) assessments. The previous 5 articles dealt with specific methodological issues, whereas this article addresses practical considerations in implementing the methods and presenting the results to various audiences with differing perspectives. Proposals for how to interpret the "clinical significance" or "clinical meaningfulness" of changes in QOL scores were addressed in previous articles within this series. Within this article, 4 audiences-patients and physicians, clinical researchers, health policymakers, and private- and public-sector employees who work in health-related fields-are examined because each is a unique stakeholder with a distinct vantage point and each can interpret QOL outcomes differently. A clinician may attempt to explain to a patient potential treatment alternatives for his or her QOL; a health policymaker may try to describe to elected officials the financial impact on a patient population with reduced QOL; a researcher may try to obtain the vital messages from a clinical trial that included QOL end points; and a regulatory agency and/or pharmaceutical company may try to ascertain the appropriate level of evidence required for a successful research study. For each of the 4 audiences, concrete examples and practical guidelines are offered by which changes in QOL outcomes can be interpreted meaningfully. Ultimately, both determining and disseminating the meaning of clinical significance are functions of the outlook of the audience because the perspective of the audience determines its ability to comprehend, evaluate, and convey the context within which such outcomes appear meaningful. Among the audiences described within this article, a commonality of interests exist that mandates a careful exposition of the scientific rigor involved in describing the clinical significance of QOL assessments. Collectively, this series attempts to provide methods and means for making such determinations.