Evidence-based Medicine Guidelines Research Articles

EPID-03. BRAIN CANCER IN AFRICA: UNCOVERING THE HIDDEN EPIDEMIC THROUGH A SYSTEMATIC REVIEW

Abstract BACKGROUND Cancer poses a significant public health threat globally, leading to substantial morbidity. While malignancies were previously thought to predominantly affect high-income countries, numerous studies indicate an increasing burden on resource-limited nations. Brain cancer, in particular, can be devastating due to treatment challenges and high mortality rates. Africa, with its resource-limited countries, must establish proper healthcare infrastructure to reduce cancer incidence and enhance patient survival. Additionally, the scarcity of data in this area in Africa presents a challenge to effective management. This study aims to explore the available evidence on the epidemiology and etiology of brain cancer in resource-limited African countries, highlighting the growing burden and advocating for further research. MATERIALS AND METHODS We conducted a systematic review by searching PubMed and Scopus using a predefined approach. Additionally, we utilized the Global Cancer Observatory and Global Burden of Disease databases. Studies reporting on brain cancer epidemiology, etiology, and impact in Africa were included, with the level of evidence assessed according to Centre for Evidence-Based Medicine guidelines. RESULTS Brain cancer presents a significant healthcare challenge in many African developing nations due to poor survival rates, inadequate funding and resources for reporting, identification, and treatment, as well as limited comprehensive research. CONCLUSION This study underscores the urgent need to address brain cancer as a major public health crisis in Africa. Improved treatment options and access to screening are essential to mitigate the disease burden. Thus, substantial and comprehensive research on brain cancer within Africa is crucial for effective management and reducing associated morbidity and mortality.

Worldwide availability of medications for migraine and tension-type headache: A survey of the International Headache Society

Background In this study, we aimed to evaluate the differing global access to acute and preventive medications for migraine and tension-type headache. Methods A custom-built questionnaire created by members of the International Headache Society Juniors Group was sent to International Headache Society members worldwide, including a list of acute and preventive treatments for migraine and tension-type headache. This list was based on evidence-based medicine guidelines. For each treatment, participants were asked about availability, type of reimbursement and variability of access within their country. Results Eighty-four members completed the questionnaire providing data for 84 countries. The majority were neurologists (88%) and worked at an academic/university hospital (62%). Of participants, 36% were located in high-income economy countries and 13% were located in low-income economies. Common preventive treatments such as propranolol and topiramate were available in most countries (respectively in 99% and 92% of responding countries). Sumatriptan was available in most countries (95%), whereas other triptan availability was lower. Novel migraine treatments such as rimegepant and erenumab were only available in 14% and 46% of the assessed countries, respectively. Conclusions Availability of headache medications, ranging from simple analgesics to novel therapies migraine-specific drugs, varied greatly across the world. Actions are needed to improve effective drug availability in many countries to ensure an adequate management of people living with headache.

Uncovering Oral Health Concerns: Exploring dental anxiety within Transgender community- A systematic review

Dental fear and anxiety (DFA) have substantial implications for oral health, often resulting in the avoidance of dental care and negative consequences. Despite facing unique health challenges and discrimination, there is a lack of research on the prevalence of DFA among transgender individuals. This paper seeks to synthesize evidence regarding the prevalence of DFA within this population. We searched multiple databases, including PubMed, Google Scholar, Cochrane Database, Web of Science, and LILACS, for studies published up to May 2024. We included observational studies, cross-sectional studies, surveys, and cohort studies that provided data on DFA prevalence among transgender individuals. Eligible studies were screened, and data extraction was performed according to predefined criteria. The risk of bias was evaluated using the ROBINS-E tool, while the level of evidence and quality were assessed following the Oxford Centre for Evidence-Based Medicine guidelines. Among the 20 studies assessed for eligibility, only 2 met the inclusion criteria and were thus included in the review. These studies reported varying prevalence rates of DFA among transgender individuals, with both exhibiting a moderate risk of bias. However, the quality of evidence was deemed low due to the limited number of studies and their observational nature. The available evidence indicates that transgender individuals experience notable levels of dental fear and anxiety, which contribute to disparities in accessing oral health care and achieving positive outcomes. This review underscores the imperative for further high-quality research to comprehensively understand and address the oral health needs of transgender individuals, ensuring equitable and effective dental care.

Evaluating the Adherence of Large Language Models to Surgical Guidelines: A Comparative Analysis of Chatbot Recommendations and North American Spine Society (NASS) Coverage Criteria.

Background There has been a significant increase in cervical fusion procedures, both anterior and posterior, across the United States. Despite this upward trend, limited research exists on adherence to evidence-based medicine (EBM) guidelines for cervical fusion, highlighting a gap between recommended practices and surgeon preferences. Additionally, patients are increasingly utilizing large language models (LLMs) to aid in decision-making. Methodology This observational study evaluated the capacity of four LLMs, namely, Bard, BingAI, ChatGPT-3.5, and ChatGPT-4, to adhere to EBM guidelines, specifically the 2023 North American Spine Society (NASS) cervical fusion guidelines. Ten clinical vignettes were created based on NASS recommendations to determine when fusion was indicated. This novel approach assessed LLM performance in a clinical decision-making context without requiring institutional review board approval, as no human subjects were involved. Results No LLM achieved complete concordance with NASS guidelines, though ChatGPT-4 and Bing Chat exhibited the highest adherence at 60%. Discrepancies were notably observed in scenarios involving head-drop syndrome and pseudoarthrosis, where all LLMs failed to align with NASS recommendations. Additionally, only 25% of LLMs agreed with NASS guidelines for fusion in cases of cervical radiculopathy and as an adjunct to facet cyst resection. Conclusions The study underscores the need for improved LLM training on clinical guidelines and emphasizes the importance of considering the nuances of individual patient cases. While LLMs hold promise for enhancing guideline adherence in cervical fusion decision-making, their current performance indicates a need for further refinement and integration with clinical expertise to ensure optimal patient care. This study contributes to understanding the role of AI in healthcare, advocating for a balanced approach that leverages technological advancements while acknowledging the complexities of surgical decision-making.

Uncovering Oral Health Concerns: Exploring Dental Anxiety within Transgender Community: A Systematic Review

Dental fear and anxiety (DFA) have substantial implications for oral health, often resulting in the avoidance of dental care and negative consequences. Despite facing unique health challenges and discrimination, there is a lack of research on the prevalence of DFA among transgender individuals. This paper seeks to synthesize evidence regarding the prevalence of DFA within this population. We searched multiple databases, including PubMed, Google Scholar, Cochrane Database, Web of Science, and LILACS, for studies published up to May 2024. We included observational studies, cross-sectional studies, surveys, and cohort studies that provided data on DFA prevalence among transgender individuals. Eligible studies were screened, and data extraction was performed according to predefined criteria. The risk of bias was evaluated using the ROBINS-E tool, while the level of evidence and quality were assessed following the Oxford Centre for Evidence-Based Medicine guidelines. Among the 20 studies assessed for eligibility, only 2 met the inclusion criteria and were thus included in the review. These studies reported varying prevalence rates of DFA among transgender individuals, with both exhibiting a moderate risk of bias. However, the quality of evidence was deemed low due to the limited number of studies and their observational nature. The available evidence indicates that transgender individuals experience notable levels of dental fear and anxiety, which contribute to disparities in accessing oral health care and achieving positive outcomes. This review underscores the imperative for further high-quality research to comprehensively understand and address the oral health needs of transgender individuals, ensuring equitable and effective dental care.

Systematic review of topical, laser, and oral treatments in acanthosis nigricans clinical trials.

Acanthosis nigricans(AN), with an estimated prevalence of 19.4% in the U.S., presents as hyperpigmented, velvety plaques in intertriginous regions. Acanthosis Nigricans negatively affects psychological well-being and particularly impacts skin of color individuals. Addressing the underlying cause of acanthosis nigricans, as current guidelines recommend, is often challenging. This highlights the importance of skin directed treatment for acanthosis nigricans. This systematic review evaluated topical, laser, and oral treatments for acanthosis nigricans and provides evidence-based recommendations for clinical use. Adhering to PRISMA guidelines, we evaluated 19 clinical trials investigating topical, oral, and laser interventions for acanthosis nigricans. Oxford Centre for Evidence-Based Medicine guidelines were used to make clinical recommendations. We strongly recommend topical tretinoin (grade A) and endorse the appropriate use of adapalene gel, urea cream, and fractional carbon dioxide laser therapy (grade B). Further research is essential to enhance our understanding of alternative treatments to determine additional evidence-based recommendations. This review aims to guide clinicians in managing acanthosis nigricans, especially when direct treatment of underlying conditions is impractical.

Do we really apply evidence-based-recommendations to spine surgery? Results of an international survey

ObjectiveThis international survey investigated Evidence-Based Medicine (EBM) in spine surgery by measuring its acceptance among spine surgeons. It assessed their understanding of EBM and how they apply it in practice by analyzing responses to various clinical scenarios..Materials and methodsFollowing the CHERRIES guidelines, an e-survey was distributed to multiple social media forums for neurosurgeons and orthopedic surgeons on Facebook, LinkedIn, and Telegram and circulated further through email via the authors’ network. Three hundred participants from Africa, Asia, Europe, North America, and Oceania completed the survey.ResultsOur study revealed that 67.7% (n = 203) of respondents used EBM in their practice, and 97.3% (n = 292) believed training in research methodology and EBM was necessary for the practice of spine surgery. Despite this endorsement of using EBM in spine surgery, we observed varied responses to how EBM is applied in practice based on example scenarios. The responders who had additional training tended to obey EBM guidelines more than those who had no additional training. Most surgeons responded as always or sometimes prescribing methylprednisolone to patients with acute spinal cord injury. Other significant differences were identified between geographical regions, training, practice settings, and other factors.ConclusionsMost respondents used EBM in practice and believed training in research methodology and EBM is necessary for spine surgery; however, there were significant variations on how to use them per case. Thus, the appropriate application of EBM in clinical settings for spinal surgery must be further studied.

Cosmeceuticals for antiaging: a systematic review of safety and efficacy.

Cosmeceuticals, the bridge between pharmaceuticals and cosmetics, contain biologically active ingredients that may improve the skin's overall appearance. As the market, accessibility, and popularity of cosmeceuticals increase, it is essential to understand the safety and efficacy of such products. This systematic review aims to examine published clinical studies involving the use of cosmeceuticals for antiaging to provide evidence-based recommendations based on available efficacy and safety data. PubMed, Embase, and Cochrane were systematically searched on January 1, 2023 using PRISMA guidelines. Strength of evidence was graded using the Oxford Centre for Evidence-Based Medicine guidelines. Clinical recommendations were made based on the quality of the existing literature. A total of 153 articles regarding the use of cosmeceuticals for treatment of antiaging were identified. After screening of titles, abstracts, and full text, 32 studies involving 1236 patients met inclusion criteria, including 20 randomized controlled trials (RCTs) and 12 non-randomized open-label clinical trials for Vitamin C, Retinol, Bakuchiol, Tetrahydrojasmonic acid, Growth Factors, Methyl Estradiolpropanoate, Timosaponin A-III (TA-III), Protocatechuic acid, Grammatophyllum speciosum, and Jasmine rice panicle extract. Retinol and vitamin C for antiaging received a Grade A for recommendation. Methyl estradiolpropanoate, bakuchiol, tetrahydrojasmonic acid, and growth factors received a recommendation grade of C. The remaining ingredients were assigned an inconclusive grade of recommendation due to lack of evidence. Cosmeceuticals included in the review had favorable safety profiles with few significant adverse events. The review analyzes numerous different ingredients to provide an evidence-based approach to decision-making for consumers and physicians on the use of cosmeceuticals for antiaging. Limitations to our review include a limited number of randomized controlled trials and a need for long-term data on each cosmeceutical's efficacy and safety. Future research is needed to establish the long-term effectiveness and safety of cosmeceuticals.

Benefits of Citicoline in Ischemic Stroke Management

Background: Stroke is the third most common disease after heart disease and cancer and the main cause of disability worldwide. The most common type of stroke, which accounts for around 85%-87% of cases, is ischemic stroke (IS). This report is to examine the benefits of citicoline for IS patients. Case: A 63-year-old male was admitted with a diagnosis of IS and electrolyte disturbances. General treatment is semi-Fowler’s position, oxygen, and maintaining fluid and nutritional intake. Specific management is RL infusion 20 gtt/minute, candesartan 1x16 mg, clopidogrel 1x75 mg, omeprazole 40 mg/24 h intravenous (IV), and citicoline 500 mg/12 h IV. The patient showed clinical improvement. Method: Articles in PubMed, Cochrane, and Google Scholar in February-April 2022 were searched to find relevant studies to be evaluated with inclusion and exclusion criteria. The full text was obtained and critically reviewed with the evidence-based medicine guidelines. The results are limited to systematic reviews and meta-analyses. Results: Five studies were deemed valid, important, and applicable. However, the quality of these studies varies. Conclusion: All studies show that citicoline use could potentially improve clinical outcomes in IS patients.

277 Clinical Outcome With and Without Adherence to Evidence-based Medicine Guidelines for Lumbar Degenerative Spondylolisthesis Fusion Patients

INTRODUCTION: Degenerative lumbar spondylolisthesis (DS) patients are treated with instrumented fusion, following EBM guidelines, and typically have excellent clinical outcomes. However, not all lumbar fusion procedures adhere to EBM guidelines, typically due to a lack of prospective data. METHODS: This study compared outcomes of lumbar fusion procedures for degenerative spondylolisthesis in two groups: 125 patients treated according to EBM guidelines and 21 patients without EBM literature support. ODI scores were collected pre- and post-surgery and categorized into SCB, MCID, no MCID, or no change/worsening. Statistical analysis included χ2, Fisher exact, and t-student tests. Multivariate logistic regression analyzed the odds of achieving MCID after six months of follow-up. RESULTS: The study included a total of 146 lumbar fusion patients, with the majority (125/146) adhering to EBM guidelines (EBM concordant) while a smaller proportion (21/146) did not (EBM discordant). The EBM concordant group demonstrated a statistically significant improvement in ODI scores compared to the EBM discordant group (p = 0.02). Compliance with EBM guidelines was associated with higher odds of achieving MCID, with an odds ratio of 2.93 and a confidence interval of 1.128-7.58 (p = 0.027). In the EBM concordant group, 42% of patients achieved SCB, and 64.8% showed MCID, whereas in the EBM discordant group, only 14% achieved SCB, and 38.1% showed MCID. These findings suggest that adherence to EBM guidelines in lumbar fusion procedures may lead to better clinical outcomes for patients. CONCLUSIONS: Patients whose lumbar fusions met the EBM criteria exhibited better self-reported outcomes at six months compared to those who did not meet the requirements. In order to strengthen EBM-guided patient care, an expanded knowledge base is needed.

Expert consensus on the clinical application of narrow-band intense pulsed light (2024 edition)

The continuous innovation of medical cosmetology technology promotes the rapid development of aesthetic medicine. Narrow-band intense pulsed light (NB-IPL), which is developed based on conventional intense pulsed light, is a more accurate, efficient, and safer technique on clinical application. In order to promote more professionalization and standardization of the clinical application of NB-IPL, a panel of clinical experts in plastic surgery, dermatology and other fields developed the consensus based on the evidence-based medicine, clinical practice, and authoritative guidelines of other disciplines. The consensus panel discussed the indications, treatment parameters, contraindications, and precautions for the clinical application of NB-IPL and would serve as a reference for clinicians, nurses, teaching and research personnels engaged in plastic and cosmetics related work.

Evaluation of Decision-to-Delivery Interval and Its Effect on Maternal and Neonatal Outcomes in Category-1 and Category-2 Emergency Caesarean Section Deliveries: A Systematic Review

Emergency cesarean section is a surgery delivery through the abdomen that must be carried out immediately within a decision-to-delivery interval (DDI) <30 minutes because it threatens the maternal and neonatal. This study prevents prolonged DDI response time for emergency cesarean section categories 1 and 2. This study aims to determine the causes of prolonged DDI for maternal and neonatal outcomes so that hospital management becomes standardized with the standard of care for emergency cesarean sections and the quality of care for patients increases. A literature search was conducted through four databases, SpringerLink, ScienceDirect, Google Scholar, and PubMed, using keywords that matched the clinical questions. Article selection was carried out based on exclusion and inclusion criteria. The selected literature was reviewed and assessed for validity, importance, and applicability based on the Oxford Center of Evidence-Based Medicine guidelines. Nineteen (19) studies examined category 1 or category 2 emergency cesarean sections from publications from 2018 to 2022. Of the 19 studies, only 3 achieved a response time of 30 minutes for emergency cesarean section category 1 and 75 minutes for category 2. However, 17 studies explained that DDI did not affect maternal and neonatal outcomes. Factors that influence not achieving the DDI target are the unavailability of operating rooms, anesthesiologists, pediatricians, and insufficient nurses. On the other hand, lack of special training, no standard emergency cesarean section service, and limited places and facilities impact maternal and neonatal outcomes.

Safety and Effectiveness of Limited Incision Facelifts: A Systematic Review and Meta-analysis

Abstract Goals/Purpose Limited incision facelifts offer a less invasive approach compared to a standard facelift and allow for the procedure to be completed under local anesthesia. While there have been various types of limited incision facelifts described, there have been no systematic reviews of their evidence. The purpose of this study is to systematically review the limited incision facelift literature, describe the various surgical approaches and their indications, and summarize their safety and effectiveness. Methods/Technique A systematic review of the literature was performed following the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines and registered with the PROSPERO international prospective register of systematic reviews. The MEDLINE (Pubmed), EMBASE, and Cochrane Central Register of Trials were queried. Screening and full-text review of studies was conducted by two independent evaluators using predetermined inclusion and exclusion criteria. Data obtained from each eligible study included information on author specialty, Oxford Centre for Evidence-Based Medicine level of evidence, and patient demographics. Operative data included anesthetic approach, operative duration, incisional pattern, SMAS technique, concomitant procedures, and drain or tissue sealant use. Complication frequencies were calculated from those studies that specifically described complication data and included the prevalence of hematoma, wounds or skin necrosis, infection, nerve injuries, and revision surgery. Data on patient- and provider-reported outcomes were also collected. Meta-analyses were performed using aggregated data. Proportions are provided with the corresponding 95% confidence interval. A Random-effects model was used to summarize complications data and meta-regressions were conducted to analyze associations with operative variables. Results/Complications A total of 1137 articles were retrieved using the pre-specified search criteria. Following the removal of duplicates, 758 studies were screened using titles and/or abstracts, and 144 articles underwent full-text review. Review yielded twenty articles that met inclusion criteria. Using the Oxford Centre for Evidence-Based Medicine guidelines, 17 (85%) articles provided level IV evidence while three (15%) provided level III evidence. Articles included a total of 4451 patients with an average age of 56 years. Ninety-four percent were women while 6% were men. Forty-two percent of patients underwent surgery awake under local anesthesia, 24% under IV sedation, 18% under intramuscular sedation, and 16% under general anesthesia. Incisional patterns varied but were categorized as limited to pre-auricular (5%), pre-and retro-auricular (10%), pre-auricular with horizontal sideburn extension (30%), pre-auricular with temporal extension (35%), and pre- plus retro-auricular with temporal extension (20%) (Figure). SMAS technique included plication (33%), purse-string suspension (28%), plication plus SMASectomy (11%), plication plus SMASectomy and purse-string suspension (11%), SMASectomy only (6%), or other (18%). Forty-five percent of articles described using drains and 10% described using a tissue sealant. The overall complication frequency was 4.0% (95% CI 2.8-5.2%). The use of a drain or sealant was associated with a decreased complication frequency of 2.6% (95%CI 1.0-4.2%) compared to 5.0% (95% CI 3.4-6.6%) in studies using no drain or sealant (p=0.04). There were no associations found between complications and incision type or anesthetic approach. Eighteen studies described hematoma frequencies. Among these articles, there was a 2.3% hematoma frequency (95% CI 1.5-3.0%). Twenty-seven patients (1.5%) had hematomas that were treated with conservative management like needle aspiration while eight (0.4%) required a return to the operating room. The next most common complication described was temporary nerve injury or neuropraxia with a rate of 0.2% (95% CI 0.1%-0.4%­­­). The frequency of skin necrosis or non-healing wounds was 0.2% (95% CI 0.1%-0.04%). No permanent nerve injuries were described. Other less commonly described complications included widening or hypertrophic scars, dog ear deformities (all within patients undergoing pre-auricular limited incisions), skin dimpling, three cases of parotid fistula, and a DVT in a patient undergoing multiple concomitant body procedures. Seven articles (35%) provided data on patient-reported outcomes while three (15%) provided data on provider-based outcomes, such as ratings of postoperative results. Conclusion To our knowledge, this is the first systematic review and meta-analysis of limited incision facelifts. This surgical approach offers an alternative to traditional rhytidectomy for the properly selected candidate. Meta-analysis demonstrates a low postoperative complication rate which is further reduced in studies using a drain or tissue sealant. This meta-analysis provides plastic surgeons and their patients with an evidence-based reference for complication data and can improve the preoperative counseling process. Future studies should focus on incorporating validated patient-reported outcome measures and comparing surgical approaches.

Efficacy of Fascia Iliaca Compartment Blocks in Proximal Femoral Fractures in the Prehospital Setting: A Systematic Review and Meta-Analysis.

Proximal femoral fractures are characterized as one of the most common and most painful injuries sustained by patients of all ages and are associated with high rates of oligoanalgesia in the prehospital setting. Current treatments include oral and parenteral opiates and sedative agents, however regional anesthesia techniques for pain relief may provide superior analgesia with lower risk of side effects during patient transportation. The fascia iliaca compartment block (FICB) is an inexpensive treatment which is performed with minimal additional equipment, ultimately making it suitable in prehospital settings. In adult patients sustaining proximal femoral fractures in the prehospital setting, what is the effect of the FICB on non-verbal pain scores (NVPS), patient satisfaction, success rate, and adverse events compared to traditional analgesic techniques? A librarian-assisted literature search was conducted of the Cochrane Database, Ovid MEDLINE, PubMed, Ovid EMBASE, Scopus, and Web of Science indexes. Additionally, reference lists for potential review articles from the British Journal of Anesthesia, the College of Anesthetists of Ireland, the Journal of Prehospital Emergency Care, Annales Francaises d'Anesthesie et Réanimation, and the Scandinavian Journal of Trauma, Resuscitation, and Emergency Medicine were reviewed. Databases and journals were searched during the period from January 1, 1980 through July 1, 2022. Each study was scrutinized for quality and validity and was assigned a level of evidence as per Oxford Center for Evidence-Based Medicine guidelines. Five studies involving 340 patients were included (ie, two randomized control trials [RCTs], two observational studies, and one prospective observational study). Pain scores decreased after prehospital FICB across all included studies by a mean of 6.65 points (5.25 - 7.5) on the NVPS. Out of the total 257 FICBs conducted, there was a success rate of 230 (89.3%). Of these, only two serious adverse events were recorded, both of which related to local analgesia toxicity. Neither resulted in long-term sequelae and only one required treatment. Use of FICBs results in a significant decrease in NVPS in the prehospital setting, and they are ultimately suitable as regional analgesic techniques for proximal femur fractures. It carries a low risk of adverse events and may be performed by health care practitioners of various backgrounds with suitable training. The results suggest that FICBs are more effective for pain management than parenteral or oral opiates and sedative agents alone and can be used as an appropriate adjunct to pain management.

Clinical Outcomes with and without Adherence to Evidence-Based Medicine Guidelines for Lumbar Degenerative Spondylolisthesis Fusion Patients.

Degenerative lumbar spondylolisthesis (DS) patients are treated with instrumented fusion, following EBM guidelines, and typically have excellent clinical outcomes. However, not all lumbar fusion procedures adhere to EBM guidelines, typically due to a lack of prospective data. This retrospective study compared outcomes of DS lumbar fusion patients treated according to EBM guidelines (EBM concordant) to lumbar fused patients with procedures that did not have clear EBM literature that supported this treatment, the goal being to examine the value of present EBM to guide clinical care. A total of 125 DS patients were considered EBM concordant, while 21 patients were EBM discordant. Pre- and postsurgical ODI scores were collected. Clinical outcomes were stratified into substantial clinical benefit (SCB ΔODI >10 points), minimal clinical importance benefit (MCID ΔODI ≥ 5 points), no MCID (ΔODI < 5 points), and a group that showed no change or worsening ODI. Fisher's exact and χ2 tests for categorical variables, Student's t-test for continuous variables, and descriptive statistics were used. Statistical tests were computed at the 95% level of confidence. Analysis of 125 degenerative spondylolisthesis patients was performed comparing preoperative and postoperative (6 months) ODI scores. ODI improved by 8 points in the EBM concordant group vs. 2.1 points in the EBM discordant group (p = 0.002). Compliance with EBM guidelines was associated with an odds ratio (OR) of 2.93 for achieving MCID ([CI]: 1.12-7.58, p = 0.027). Patients whose lumbar fusions met EBM criteria had better self-reported outcomes at six months than those who did not meet the requirements. A greater knowledge set is needed to help further support EBM-guided patient care.

Thrombin generation assays to personalize treatment in bleeding and thrombotic diseases.

Treatment of bleeding and thrombotic disorders is highly standardized and based on evidence-based medicine guidelines. These evidence-based treatment schemes are well accepted but may lead to either insufficient treatment or over-dosing, because the individuals' hemostatic properties are not taken into account. This can potentially introduce bleeding or thrombotic complications in individual patients. With the incorporation of pharmacokinetic (PK) and pharmacodynamic (PK-PD) parameters, based on global assays such as thrombin generation assays (TGAs), a more personalized approach can be applied to treat either bleeding or thrombotic disorders. In this review, we will discuss the recent literature about the technical aspects of TGAs and the relation to diagnosis and management of bleeding and thrombotic disorders. In patients with bleeding disorders, such as hemophilia A or factor VII deficiency, TGAs can be used to identify patients with a more severe bleeding phenotype and also in the management with non-replacement therapy and/or bypassing therapy. These assays have also a role in patients with venous thrombo-embolism, but the usage of TGAs in patients with arterial thrombosis is less clear. However, there is a potential role for TGAs in the monitoring of (long-term) antithrombotic therapy, for example with the use of direct oral anticoagulants. Finally this review will discuss controversies, limitations and knowledge gaps in relation to the introduction of TGAs to personalize medicine in daily medical practice.

Adaptations in models of urological regulation and their application to sub-Saharan Africa.

Regulation of medical care is something that has grown from humble roots in professional craft groups to huge establishment in well-resourced, high-income countries. Self-regulation was the preferred method of determining appropriate behaviour initially, but a lack of public trust in this, and the desire of patients to contribute to the establishment of the standard of care that they receive, has meant that most Anglophone countries have adopted some form of independent regulation. Regulators are responsible for the registration of doctor's qualifications, licensing them to practise, accrediting institutions to provide undergraduate and postgraduate education and certifying the attainment of accepted standards of achievement by some form of assessment process. Regulators also have powers to sanction individuals whose practice falls outside expected levels of competence. Both centralized and devolved models of regulation have evolved. Much of the accreditation for postgraduate education and training has been handed down to collegiate bodies, or non-governmental organizations, who can also certify completion of training. Evidence-based medicine and clinical practice guidelines have enforced an informal tier of regulation in high-income countries; guideline-derived practice is now widely regarded as an accepted standard of care. In low- and middle-income countries in sub-Saharan Africa the governmental and legislative structures and finance available to provide the regulation espoused in more privileged environments is rarely available. The workforce is structured in a completely different way and some care groups are totally unregulated. Medical councils in sub-Saharan Africa fulfil a registration and licensing function but surgical collegiate bodies provide the structure for postgraduate training. The East and West African Colleges of Surgeons have developed into robust organizations, who have verifiable, quality-assured, accreditation systems that have helped improve standards of care for the large populations for which their member surgeons are responsible. Formal regulation of continuing practice and sanctions are challenges that are, at present, largely unaddressed.

MicroRNA biomarkers of type 2 diabetes: evidence synthesis from meta-analyses and pathway modelling

Aims/hypothesisMicroRNAs are being sought as biomarkers for the early identification of type 2 diabetes. This study aimed to synthesise the evidence from microRNA–type 2 diabetes association studies and microRNA-regulated type 2 diabetes pathway delineation studies that met stringent quality criteria to identify and validate microRNAs of both statistical and biological significance as type 2 diabetes biomarkers.MethodsEligible controlled studies on microRNA expression profiling of type 2 diabetes were retrieved from PubMed, ScienceDirect and Web of Science. MicroRNA-regulated type 2 diabetes pathway delineation studies were conducted by integrating and cross-verifying the data from miRTarBase, TransmiR, miRecords, TargetScanHuman, the Kyoto Encyclopedia of Genes and Genomes (KEGG) and the Retraction Watch database. Before meta-analysis, quality assessment was performed according to the corresponding reporting guidelines for evidence-based medicine. To select the most statistically significant microRNAs, we conducted extensive meta-analyses according to the latest methodology. Subgroup and sensitivity analyses were carried out to further examine the microRNA candidates for their tissue specificity and blood fraction specificity and the robustness of the evidence. Signalling pathway impact analysis of dysregulated microRNAs identified from meta-analyses was performed to select biologically significant microRNAs that were enriched in our newly built microRNA-regulated pathways.ResultsOf the 404 differentially expressed microRNAs identified in the 156 controlled profiling studies with a combined sample size of >15,000, only 60 were both consistently and significantly dysregulated in human type 2 diabetes. No microRNAs were both consistently and significantly dysregulated in multiple tissues according to subgroup analyses. In total, 58 microRNAs were found to be robust in sensitivity analyses. A total of 1966 pathway delineation studies were identified, including 3290 microRNA–target interactions, which were further combined with KEGG pathways, producing 225 microRNA-regulated pathways. Impact analysis found that 16 dysregulated microRNAs identified from extensive meta-analyses were statistically significantly enriched in the augmented KEGG type 2 diabetes pathway.Conclusions/interpretationSixteen microRNAs met the criteria for biomarker selection. In terms of both significance and relevance, the order of priority for verification of these microRNAs is as follows: miR-29a-3p, miR-221-3p, miR-126-3p, miR-26a-5p, miR-503-5p, miR-100-5p, miR-101-3p, mIR-103a-3p, miR-122-5p, miR-199a-3p, miR-30b-5p, miR-130a-3p, miR-143-3p, miR-145-5p, miR-19a-3p and miR-311-3p.RegistrationPROSPERO registration number CRD42017081659.Graphical abstract

Breaking new frontiers: Assessment and re-evaluation of clinical trial design for nutraceuticals.

Despite sophisticated study designs and measurement tools, we have yet to create an innovative space for diet and dietary supplements in the health care system. The path is challenging due to current hierarchies of scientific evidence and regulatory affairs. The role of the randomized, double-blind, placebo-controlled clinical trial (RCT) as a research approach functions well to characterize the benefits and risks of drugs but lacks the sensitivity to capture the efficacy and safety of nutraceuticals. While some facets of RCTs can be relevant and useful when applied to nutraceuticals, other aspects are limiting and potentially misleading when taken in their entirety. A differentiation between guidelines for evidence-based medicine and the evidence required for nutrition spotlight the need to reconceptualize constituents of the RCT and their applicability with relevance to health promotion. This perspective identifies the limitations of the traditional RCT to capture the complexities of nutraceuticals and proposes the N-of-1 as Level 1 evidence better suited for the proof of efficacy of nutraceuticals.

O095 Cell-based therapies in surgery: a systematic review of the yield and composition of freshly isolated cells obtained from point-of-care devices which mechanically dissociate lipoaspirate

Abstract Introduction Cell-based therapies using lipoaspirate are gaining popularity within surgical fields due to their hypothesised regenerative potential. Several point-of-care lipoaspirate-processing devices have become available to isolate cells for therapeutic use, with published evidence reporting their clinical relevance. However, few studies have analysed the composition of their minimally manipulated cellular products, information that is vital to understand the mechanisms by which these therapies may be efficacious. This review aimed to identify devices using mechanical-only processing of lipoaspirate, their cell yields, viability, phenotype and where available clinical outcomes. Methods MEDLINE, Embase and PubMed databases were systematically searched on 01/09/21 using relevant keywords. PRISMA guidelines were followed (PROSPERO#CRD42021282041), and level of evidence was assessed using the Oxford Centre for Evidence-Based Medicine guidelines. Information was extracted and analysed to summarise the cellular composition derived from these devices and their clinical outcomes. Results 2895 studies were screened and a total of 15 articles (11=Level 5 evidence) fulfilled the inclusion criteria. Overall, 13 devices were identified. All the studies reported cell yield for their devices (range 0.005–21×106). 10 reported viability (range 60–98%), 11 performed immuno-phenotypic analysis of the cell-subtypes and 4 investigated clinical outcomes of their cellular products. Only 2 studies reported all four parameters. Conclusion Although many devices are available to mechanically process lipoaspirate, few have published peer-reviewed literature of their products’ composition. Significant heterogeneity in the reporting of these studies makes it difficult to summarise their clinical potential. This review is unable to make any recommendations on the clinical use of these devices. Take-home message Many point-of-care devices have become available to mechanically process lipoaspirate to form a cellular product for therapeutic use in surgery. However, few have publications on their products’ composition which is information required to understand the mechanisms by which these therapies may be efficacious.