Standards Of Evidence-based Medicine Research Articles

Dermatologic manifestations of hereditary hemochromatosis: A systematic review.

Hereditary hemochromatosis (HH) is a genetic disorder leading to excessive iron absorption, impacting multiple organs, notably the skin, nails and mucosae. The objective of this study is to elucidate the dermatologic manifestations, associated symptoms, pathophysiology and management recommendations of HH. We searched five primary databases (PubMed, Embase, Cochrane Library, Scopus and Web of Science) up to April 2023. Non-English articles were included to minimize language bias. The studies were evaluated using Oxford Centre for Evidence-based Medicine standards, with adherence to PRISMA guidelines. Inaccessible articles were directly sourced from authors. Out of the initial 1582 publications from 1904 to 2023, 22 studies (19 in English, 2 in French and 1 in German) were selected. Most reports were from the USA, UK and France and were predominantly case reports, covering 148 patients with skin symptoms related to hereditary hemochromatosis. We collected data on the cutaneous findings and, when available, their histopathological features. The current study highlights the scope, variety and traits of dermatologic symptoms in hereditary hemochromatosis, pinpointing research gaps and areas for future exploration. Our review accentuates the diverse dermatological manifestations of hereditary hemochromatosis, notably hyperpigmentation, hypertrichosis and resistant pruritus, often linked to excessive iron deposition and subsequent impairment of skin cell function. We also found controversial evidence indicating that skin cancers seem to be associated with hereditary hemochromatosis. Porphyria cutanea tarda and hereditary hemochromatosis were frequently reported together. Given hereditary hemochromatosis's genetic nature, early identification in one individual can substantially guide familial care and preemptive interventions. Clinicians should prioritize hereditary hemochromatosis as a differential when patients present with specific dermatological symptoms, especially in sun-exposed regions. A rigorous assessment ensures accurate diagnosis, facilitating optimal management for both the patient and their family.

Medical Misinformation in Polish on the World Wide Web During the COVID-19 Pandemic Period: Infodemiology Study.

Although researchers extensively study the rapid generation and spread of misinformation about the novel coronavirus during the pandemic, numerous other health-related topics are contaminating the internet with misinformation that have not received as much attention. This study aims to gauge the reach of the most popular medical content on the World Wide Web, extending beyond the confines of the pandemic. We conducted evaluations of subject matter and credibility for the years 2021 and 2022, following the principles of evidence-based medicine with assessments performed by experienced clinicians. We used 274 keywords to conduct web page searches through the BuzzSumo Enterprise Application. These keywords were chosen based on medical topics derived from surveys administered to medical practitioners. The search parameters were confined to 2 distinct date ranges: (1) January 1, 2021, to December 31, 2021; (2) January 1, 2022, to December 31, 2022. Our searches were specifically limited to web pages in the Polish language and filtered by the specified date ranges. The analysis encompassed 161 web pages retrieved in 2021 and 105 retrieved in 2022. Each web page underwent scrutiny by a seasoned doctor to assess its credibility, aligning with evidence-based medicine standards. Furthermore, we gathered data on social media engagements associated with the web pages, considering platforms such as Facebook, Pinterest, Reddit, and Twitter. In 2022, the prevalence of unreliable information related to COVID-19 saw a noteworthy decline compared to 2021. Specifically, the percentage of noncredible web pages discussing COVID-19 and general vaccinations decreased from 57% (43/76) to 24% (6/25) and 42% (10/25) to 30% (3/10), respectively. However, during the same period, there was a considerable uptick in the dissemination of untrustworthy content on social media pertaining to other medical topics. The percentage of noncredible web pages covering cholesterol, statins, and cardiology rose from 11% (3/28) to 26% (9/35) and from 18% (5/28) to 26% (6/23), respectively. Efforts undertaken during the COVID-19 pandemic to curb the dissemination of misinformation seem to have yielded positive results. Nevertheless, our analysis suggests that these interventions need to be consistently implemented across both established and emerging medical subjects. It appears that as interest in the pandemic waned, other topics gained prominence, essentially "filling the vacuum" and necessitating ongoing measures to address misinformation across a broader spectrum of health-related subjects.

Artificial-intelligence-based risk prediction and mechanism discovery for atrial fibrillation using heart beat-to-beat intervals

Early diagnosis of atrial fibrillation (AF) is important for preventing stroke and other complications. Predicting AF risk in advance can improve early diagnostic efficiency. Deep learning hasbeen used for disease risk prediction; however, it lacks adherenceto evidence-based medicine standards. Identifying the underlyingmechanisms behind disease risk prediction is important and required. We developed an explainable deep learning model called HBBI-AI to predict AF risk using only heart beat-to-beat intervals (HBBIs) during sinus rhythm. We proposed a possible AF mechanism based on the model's explainability and verified this conjecture using confirmed AF risk factors while also examining new AF risk factors. Finally, we investigated the changes in clinicians' ability to predict AF risk using only HBBIs before and after learning the model's explainability. HBBI-AI consistently performed well across large in-house and external public datasets. HBBIs with large changes or extreme stability were critical predictors for increased AF risk, and the underlying cause was autonomic imbalance. We verified various AF risk factors and discovered that autonomic imbalance was associated with all these factors. Finally, cardiologists effectively understood and learned from these findings to improve their abilities in AF risk prediction. HBBI-AI effectively predicted AF risk using only HBBI information through evaluating autonomic imbalance. Autonomic imbalance may play an important role in many risk factors of AF rather than in a limited number of risk factors. This study was supported in part by the National Key R&D Program and the National Natural Science Foundation of China.

Observational studies as a tool for introducing innovative oncology approaches into clinical practice: A review

Randomized clinical trials (RCTs) are the gold standard of evidence-based medicine. However, it is no less evident that real practice presents many new and important questions that are difficult to answer in the RCT. To what extent does the real patient meet the criteria for inclusion in the study? What are the efficacy and safety of the drug in comorbid and elderly patients? How deviations from the treatment regimen affect safety, etc. The introduction of innovative oncology approaches is disproportionately faster than in other fields. That is why a balanced analysis of the effects of innovation in real-world practice is relevant. Regulatory authorities are aware of this and demonstrate a willingness to consider and actively support real-world evidence research as part of drug applications, which is a powerful incentive for developing this area. The purpose of the article is to analyze the regulatory approaches in the United States and Europe to real-world studies when considering drug applications and to discuss the experience of organizing an observational study of the effectiveness of individual drugs for the treatment of oncological diseases in Moscow as a unique example of interaction between regulatory authorities and the expert community of oncologists.

Evidence-based medicine: new in the search for evidence

The review is focused on discussing new trends in DM, rethinking the evidence base medicine with an emphasis on demonstrating the efficacy and safety of new therapeutic agents and medical technologies, from gene editing to AI algorithms. At the same time, clinical trials of drugs are also not standing still, there is active development, new approaches, methods and designs are being developed. The process of drug development, registration and market launch of any drug takes a significant period of time, requires high financial costs and human resources. The gold standard of evidence-based medicine was initially considered to be RCTs, but at the same time, they have objective disadvantages: limited sample, inability to control all factors; insufficient follow-up time,negative impact on participants, inability to determine cause-and-effect relationships; limited measurement methods, limited budget and others. This review discusses the trends in the methodology of clinical research. The active implementation of new designs such as Adaptive Clinical Trials, "Master" protocols including Umbrella Study, Basket Study, Platform Studies, Master Observational Trials and the increased use of Single Patient Trials (N-of-1 trials) are allowing studies to become more efficient, relevant and applicable to real-life health care practice settings and patient-centered. In the review, we also look at both the pros and cons of the expanded use of biomarkers and Digital Endpoints in clinical trials and virtual clinical trials, which use mathematical models to study patient heterogeneity and its impact on various therapeutic questions. The process of expertise and regulatory approval continues to slow down the entry of drugs into the pharmaceutical market. The review considers changes in the approaches of regulators (FDA, EMEA and Russian Ministry of Health) to the drug registration procedure. The COVID-19 pandemic and sanctions have led to the need to expand the list of drugs with authorized accelerated registration. However, accelerated registration raises many questions regarding the sufficiency of the level of evidence and safety. As we can see a deep synthesis and integration of all available data is needed to achieve the next generation of evidence-based medicine. The major challenge in the next two decades will be to exploit the potential of multidimensional evidence generation by extracting, collating and generating large data sets of natural course of disease, genomics and all other omics analyses, all published clinical trials, RWD to provide next generation evidence.

Use of progestagens to preserve pregnancy: modern approaches

Review objectives: to summarize current and clinical data on the role of progesterone support in women at risk of miscarriage and premature pregnancy according to the standards of evidence-based medicine. Control of plasma progesterone levels is a fundamental tool for managing the effectiveness of assisted reproductive technologies. The association of a low level of serum progesterone with lower rates of current pregnancy and live birth in cycles of assisted reproductive technologies was revealed. Patients with low serum progesterone on the day of embryo transfer need individualized support of the luteal phase, which involves adding additional doses of progesterone to standard regimens.
 Vaginal micronized progesterone is currently believed to be the only progestogen that increases the likelihood of a live birth in women with bleeding in early pregnancy which has one or more miscarriages.
 Vaginal progesterone can be considered for patients with a high risk of miscarriage in the following modes: with vaginal bleeding and a history of one or more miscarriages (threatened miscarriage) – 400 mg twice a day, starting with the detection of vaginal bleeding up to 16 full weeks of pregnancy; with a history of three or more pregnancy losses of unknown etiology (habitual miscarriage) – asymptomatic patients — 200 mg twice a day up to 12 full weeks of pregnancy; patients with vaginal bleeding – 400 mg 2 times a day up to 16 weeks of pregnancy. Currently, there is no evidence of the effectiveness other forms of progesterone and other doses.
 Conclusions. Vaginal micronized progesterone demonstrated: high efficiency as a standard of luteal phase support; increasing the chance of a live birth in women with a double risk factor for miscarriage (vaginal bleeding in the 1st trimester and ≥1 previous miscarriage); the absence of safety problems for the fetus and the health of newborns when used in the early and late stages of pregnancy.

Autologous Blood Injections in Temporomandibular Hypermobility: A Systematic Review.

The injection of autologous blood (AB) is one of the methods of treatment of recurrent dislocations in the temporomandibular joints (TMJs). Due to the low invasiveness of this technique, it is reasonable to evaluate it in accordance with the standards of evidence-based medicine. The purpose of this systematic review is to identify primary studies on AB injection for the treatment of TMJ hypermobility and assess the therapy for effectiveness. This systematic review was conducted in accordance with the current "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" guidelines. Controlled randomized trials comparing dislocation episode rates, range of motion in the TMJ, or articular pain intensity were adopted as the eligibility criteria. Final searches were conducted on 11 June 2023 using Bielefeld Academic Search Engine, Elsevier Scopus, and the National Library of Medicine: PubMed. Trials were assessed using the "Oxford Center for Evidence-Based Medicine 2011 Levels of Evidence" scale and "A revised Cochrane risk-of-bias tool for randomized trials". The results of the individual studies were tabulated, syntheses were illustrated in graphs. Twenty two studies involving 982 patients were included in the qualitative analysis, of which seven studies involving 390 patients were subject to quantitative analysis. None of the included randomized controlled trials presented a high risk of bias, 75% of them raised some concerns. In a three-month observation, administration of AB was more efficient in limiting temporomandibular dislocations than hypertonic dextrose (1 study, 32 patients, relative risk = 0.33, odds ratio = 0.29) and no difference in outcomes was observed between intracavitary and pericapsular administration compared to pericapsular injection alone (2 studies, 70 patients, relative risk = 1.00, odds ratio = 1.00). Injections of AB into the temporomandibular joints are effective in preventing further TMJ dislocation episodes in 75-94% of patients. This study received no funding.

Retinodural haemorrhage of infancy, abusive head trauma, shaken baby syndrome: The continuing quest for evidence.

The shaken baby syndrome was originally proposed in the 1970s without any formal scientific basis. Once data generated by scientific research was available, the hypothesis became controversial. There developed essentially two sides in the debate. One side claimed that the clinical triad of subdural haemorrhage, retinal haemorrhage, and encephalopathy, or its components, is evidence that an infant has been shaken. The other side stated this is not a scientifically valid proposal and that alternative causes, such as low falls and natural diseases, should be considered. The controversy continues, but the contours have shifted. During the last 15 years, research has shown that the triad is not sufficient to infer shaking or abuse and the shaking hypothesis does not meet the standards of evidence-based medicine. This raises the issue of whether it is fit for either clinical practice or for the courtroom; evidence presented to the courts must be unassailable. WHAT THIS PAPER ADDS: There is insufficient scientific evidence to assume that an infant with the triad of subdural haemorrhage (SDH), retinal haemorrhage, and encephalopathy must have been shaken. Biomechanical and animal studies have failed to support the hypothesis that shaking can cause SDH and retinal haemorrhage. Patterns of retinal haemorrhage cannot distinguish abuse. Retinal haemorrhages are commonly associated with extracerebral fluid collections (including SDH) but not with shaking. Infants can develop SDH, retinal haemorrhage, and encephalopathy from natural diseases and falls as low as 1 foot. The shaking hypothesis and the literature on which it depends do not meet the standards of evidence-based medicine.

The quest for diffusible community health worker projects and the pitfalls of scaling culture

ABSTRACT Researchers of community health worker (CHW) models in many countries are looking for ways to scale without losing one of their main advantages, their context-sensitivity. This paper looks at one research strategy to make CHW projects scalable, namely by developing a generic notion of culture-sensitivity. Based on in-depth qualitative analysis, we reconstruct how ‘culture’ has been enshrined in a US-based CHW project and specifically in the artefact of a binder with teaching materials for vulnerable mothers. The inscription of generalized, culture-sensitive spaces into the binder did allow the Project to comply with standards of evidence-based medicine while respecting community self-determination and made space for creative and competent CHW practices. Yet at the same time, it took away from more substantive conceptions of community engagement and from community empowerment through CHWs. Our analysis highlights how the focus on culture can invisibilise and displace the importance of competent CHW practice and processes of community engagement.

Comparative analysis of efficacy of different combination therapies of α-receptor blockers and traditional Chinese medicine external therapy in the treatment of chronic prostatitis/chronic pelvic pain syndrome: Bayesian network meta-analysis.

Combination therapy of α-receptor blockers (α-RBs) and traditional Chinese medicine external therapy can serve as a treatment of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). α-RBs includes tamsulosin, terazosin and so on and the traditional Chinese medicine external therapy includes needling, moxibustion, acupoint catgut embedding, acupoint application, auricular point sticking and hot medicated compress and so forth. Currently, there is no study in which Bayesian network meta-analysis is applied to making a comparative analysis of efficacy of different combination therapies of α-RBs and traditional Chinese medicine external therapy in the treatment of CP/CPPS. Therefore, based on Bayesian algorithm, a network meta-analysis was conducted by us to make a comparison between different combination therapies of α-RBs and traditional Chinese medicine external therapy. A document retrieval was conducted in the databases PubMed, Cochrane Library, Embase, Web of science, China National Knowledge Infrastructure, WanFang Data Dissertations of China database, VIP China Science and Technology Journal Database, SinoMed. Literatures were searched for published in biomedical journals concerning clinical study on α-RBs combined with various traditional Chinese medicine external therapies in the treatment of CP/CPPS from inception of database to July 2022. Newest version risks of bias assessment tool (RoB2) was used to assess the risks of bias of studies included in this analysis. Stata 16.0 software and R4.1.3 software were used to make a Bayesian network meta-analysis and charts. 19 literatures were included involving 1739 patients concerning 12 interventions which were used in the treatment of CP/CPPS. With respect to the total effective rate, α-RBs+ needling was most likely to be the optimal treatment. Concerning National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) total score, α-RBs+ moxibustion+ auricular point sticking was most likely to be optimal treatment, the therapy ranking second was α-RBs+ needling, and the therapy ranking third was α-RBs+ moxibustion. Pain score, voiding score and quality-of-life score are subdomains of the NIH-CPSI total score. With regard to pain score, α-RBs+ moxibustion was most likely to be optimal treatment. In reference to voiding and quality-of-life score, there was no statistically significant difference between the efficacy of various interventions. α-RBs+ needling, α-RBs+ moxibustion and α-RBs+ moxibustion+ auricular point sticking provided relatively good efficacy in the treatment of CP/CPPS. In these treatments, attention should be paid on α-RBs+ needling and α-RBs+ moxibustion which ranked higher many times in the evaluation of various outcome indicators. However, there still were certain limitations in this study, so large-sample clinical randomized control trials with a rigor design following the evidence-based medicine standards need to be conducted to justify the results of this study. [https://www.crd.york.ac.uk/prospero/], identifier: [CRD42022341824].

Real-world evidence of biological agents in dermatology: A review of its applications, advantages, and limitations.

Randomized controlled trials (RCTs) are regarded as the gold standard of evidence-based medicine. However, the disadvantages of RCTs have been well-documented for a lengthy period of time. Due to the carefully controlled conditions, a small group of patients is studied, resulting in a lack of external validity and generalizability. To address this issue, real-world evidence (RWE) has grown in importance as a complement to randomized controlled trials (RCTs). We introduce and describe the databases used by RWE in this post. Applications of RWE are described in following aspects with examples of patients in the use of biological agents with skin diseases: (1) support the safety and efficacy outcomes of RCTs; (2) reveal real-world situations of adverse event management; (3) optimal treatment plans; (4) treatment's real-world cost burden. We also focus on its superiority of generalizability, external validity, and time and economic efficiencies as well as its deficiencies in data resources, study design, and statistical methodologies.

Key barriers against racial and ethnic minority participation in U.S. clinical trials

<p class="abstract">Despite the United States’ (U.S.) longstanding history of promoting a melting pot nation of people from diverse racial and ethnic backgrounds all capable of achieving the American Dream, it is argued that the U.S. is failing to deliver high quality healthcare to all of its constituents equally. The widely seen health disparities of ethnic minority groups endure has extended into the parallel field of clinical research and clinical trials. There is a staggering gap between the percentage of White clinical trial participants compared to clinical trial participants of racially and ethnically diverse minority groups in U.S. clinical trials. Underrepresentation of minority groups in clinical trials dismisses opportunities to identify potential serious sub-group safety or efficacy signals, open doors to access life-saving treatments, and ultimately improve the standard of evidence-based medicine in the United States. Current literature on this issue frequently reiterates the following five key barriers underrepresented minority groups face against clinical trial participation: mistrust, lack of awareness and access, cultural and language barriers, investigator and provider bias, and financial burdens. A deeper dive into understanding each barrier will be critical in implementing changes with actions and in perspectives in order to address the issue of poor racial and ethnic representation in clinical trial populations.</p>

AIRO Breast Cancer Group Best Clinical Practice 2022 Update.

Breast cancer is the most common tumor in women and represents the leading cause of cancer death. Radiation therapy plays a key-role in the treatment of all breast cancer stages. Therefore, the adoption of evidence-based treatments is warranted, to ensure equity of access and standardization of care in clinical practice. This national document on the highest evidence-based available data was developed and endorsed by the Italian Association of Radiation and Clinical Oncology (AIRO) Breast Cancer Group.We analyzed literature data regarding breast radiation therapy, using the SIGN (Scottish Intercollegiate Guidelines Network) methodology (www.sign.ac.uk). Updated findings from the literature were examined, including the highest levels of evidence (meta-analyses, randomized trials, and international guidelines) with a significant impact on clinical practice. The document deals with the role of radiation therapy in the treatment of primary breast cancer, local relapse, and metastatic disease, with focus on diagnosis, staging, local and systemic therapies, and follow up. Information is given on indications, techniques, total doses, and fractionations. An extensive literature review from 2013 to 2021 was performed. The work was organized according to a general index of different topics and most chapters included individual questions and, when possible, synoptic and summary tables. Indications for radiation therapy in breast cancer were examined and integrated with other oncological treatments. A total of 50 questions were analyzed and answered.Four large areas of interest were investigated: (1) general strategy (multidisciplinary approach, contraindications, preliminary assessments, staging and management of patients with electronic devices); (2) systemic therapy (primary, adjuvant, in metastatic setting); (3) clinical aspects (invasive, non-invasive and micro-invasive carcinoma; particular situations such as young and elderly patients, breast cancer in males and cancer during pregnancy; follow up with possible acute and late toxicities; loco-regional relapse and metastatic disease); (4) technical aspects (radiation after conservative surgery or mastectomy, indications for boost, lymph node radiotherapy and partial breast irradiation).Appendixes about tumor bed boost and breast and lymph nodes contouring were implemented, including a dedicated web application. The scientific work was reviewed and validated by an expert group of breast cancer key-opinion leaders. Optimal breast cancer management requires a multidisciplinary approach sharing therapeutic strategies with the other involved specialists and the patient, within a coordinated and dedicated clinical path. In recent years, the high-level quality radiation therapy has shown a significant impact on local control and survival of breast cancer patients. Therefore, it is necessary to offer and guarantee accurate treatments according to the best standards of evidence-based medicine.

Overview of systematic reviews of acupuncture clinical research published in international journals

The systematic reviews (SRs) of acupuncture published before December 31 of 2020 in PubMed, Cochrane and EMbase databases were searched, and the publication overview of international acupuncture SRs were analyzed. As a result, a total of 717 SRs were included, and the overall number of published SRs showed a fluctuating upward trend. A total of 15 categories of diseases were involved, of which 113 SRs suggested that acupuncture was effective, and 12 SRs did not support acupuncture, and the remaining SRs showed uncertain conclusions. It is suggested that the standard of evidence-based medicine should be adopted to standardize the design of acupuncture trial and improve the level of clinical research; SRs should include high-quality literature that met the standards according to the principles and methods of PRISMA, so as to provide reliable clinical evidence for acupuncture.

What's New in Spine Surgery.

What's New in Spine Surgery.

Spontaneous Coronary Artery Dissection and Evidence-Based Medicine

Spontaneous coronary artery dissection (SCAD) is a relatively newly diagnosed area, and evidence-based medicine (EBM) standards are emerging and currently include an aspirin, β blocker, clopidogrel, angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker for patients with hypertension, vascular abnormality imaging, and cardiac rehabilitation. Because SCAD is an uncommon condition, many providers are unfamiliar with EBM treatment standards which could affect the implementation of recommended treatment. This study documented the frequency of failure to meet EBM SCAD treatment standards and factors contributing to conformance failure. Patients who presented to a tertiary referral hospital from January 1, 2005, to July 6, 2020, were included. The electronic medical record was reviewed for EBM treatment. Patients who did not meet the criteria of EBM were contacted by phone for a phone interview. The study period included 118 patients with SCAD, 3 of whom (2.5%) died and were not eligible for this study. In the final cohort of 115 patients, the average age was 55 years, female gender (97%) and EBM standards were met in 30%. Of patients who participated in the phone interview, 38 (33%) reported frustration with SCAD misdiagnosis (39%), inadequate mental health resources (37%), and communication failure regarding the need for cardiologist follow-up (26%). Cardiac rehabilitation use was impacted by location, time of day, availability, and cost. The most common medication-limiting factor for β-blocker usage was fatigue (15%). Most (59%) patients did not undergo fibromuscular dysplasia imaging. In conclusion, in this 15-year SCAD study from a single tertiary care hospital SCAD registry, only 30% met the current EBM for SCAD. Unique solutions that are both patient-informed and evidence-driven are needed to achieve the best clinical outcomes.

Did the Scientific Innovations in the Management of Non-Muscle Invasive Bladder Cancer Patients Improve the Outcome during the Last 2 Decades?

Objectives: Previous reviews reported the outcome of each scientific modality in the management of T1 high-grade bladder cancer. The objective of this review is to assess and evaluate the available scientific modalities used during the last two decades and determine whether they were able to improve the clinical outcome. Literature Search Methodology: A systematic literature review was conducted from 2000-2020 using PubMed, Medline, Embase, and other database sites looking at randomized controlled trials (RCTs), clinical trials, research, review articles, and original articles addressing the different scientific modalities used to diagnose and manage patients with non-muscle invasive Bladder cancer (NMIBC)during the last 2 decades. More than 573 studies were retrieved following the preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and PICOS criteria (Population, Intervention, Comparators, Outcomes, and Study design). Only 85 articles were selected for review including 19 prospective trials, 44 RCTs, original articles, research articles, one review article, and clinical trials—Retrospective studies were excluded to limit bias as much as possible in the analysis. Results: Randomized controlled trials (RCTs) have become the gold standard for evaluating the efficacy of new treatments. They are considered the highest standard of evidence-based medicine and are the method of choice. Overall, we selected 85 studies for review, among them 63 prospective trials and RCTs, with a total of 21,895 patients, published between 2000 and 2020. Previously conducted studies have shown that identifying rare histological types with poor prognoses can help improve outcomes, mainly the plasmacytoid type. Many articles addressed the role of biomarkers in the early identification of patients with NMIBC for recurrence and progression—P-cadherin expression and others were used to predict recurrence and/or progression with promising results. Despite the need for modifications, risk stratification is an important tool that should be used to improve the outcome of patients with NMIBC. Some found that fluorescence diagnostic cystoscopy (FDC) and Photodynamic diagnosis (PDD) improved recurrence-free survival but not progression and outcome. All authors agree that intravesical BCG is the most effective therapy that changes the course of high-grade T1 mainly progression. Re-TURBT has become one of the recommendations of international societies, but its potential effect on survival improvement is debatable. Most of the articles showed the advantages of early cystectomy in NMIBC but all agree that the selection criteria must be clearly defined. Conclusions: This review analyzed the outcomes provided by the scientific advances in the field of management of NMIBC patients in the last two decades. Patients with T1 bladder cancer have variable outcomes because of tumor heterogeneity and clinical staging. Despite the great development in the field of diagnosis, risk stratification, and management, further large studies are mostly needed to better elucidate this subset of patients and avoid over and under-treatment.

"Closing the chasm" - guidelines bridge the gap from evidence to implementation.

"Closing the chasm" - guidelines bridge the gap from evidence to implementation.

Computer analysis of the emotional modality of 20 million publications in PUBMED database indicates ways to increase the effectiveness of pharmacotherapy by identifying pseudoscientific publications aimed at negative emotional "pumping" of doctors

The search for original publications on fundamental and clinical medicine that would produce results of the highest scientific quality represents an urgent need for every medical researcher. Such publications are essential, in particular, for the development of reliable treatment standards. The Englishlanguage resources PUBMED and EMBASE are essential to help in solving this problem. However, there is an obvious problem in assessing the quality of the studies found. The paper formulates a method for analyzing the texts of biomedical publications, which is based on an algorithmic assessment of the emotional modality of medical texts (so-called sentiment analysis). The use of the topological theory of data analysis made it possible to develop a set of high-precision algorithms for identifying 16 types of sentiments (manipulative turns of speech, research without positive results, propaganda, falsification of results, negative personal attitude, aggressiveness of the text, negative emotional background, etc.). On the basis of the developed algorithms, a point scale for assessing the sentiment quality of research was obtained, which we called the "β-score": the higher the β-score, the less the evaluated text contains manipulative language constructions. As a result, the ANTIFAKE system (http://antifake-news.ru) was developed to analyze the sentiment-quality of Englishlanguage scientific texts. An analysis of ~ 20 million abstracts from PUBMED showed that publications with low sentiment quality (β-score <0, that is, that the prevalence of manipulative constructions over meaningful ones) is only 19 %. In the overwhelming majority of thematic headings (27,090 out of 27,840 headings of the MESH system PUBMED), a positive dynamics of sentiment quality of the texts of publications is shown by years). At the same time, as a result of the study, 249 headings were identified with sharply negative dynamics of sentiment quality and with a pronounced increase in manipulative sentiments characteristic of the "yellow" English-language press. These headings include tens of thousands of publications in peer-reviewed journals, which are aimed at (1) legalizing ethically unacceptable practices (euthanasia, perversions, so-called "population control", etc.), (2) discrediting psychiatry as a science, (3) media the war against micronutrients and (4) discrediting evidence-based medicine under the guise of developing the so-called "international standards of evidence-based medicine". In general, the developed system of artificial intelligence allows researchers to filter out pseudoscientific publications, the text of which is overloaded with emotional manipulation and which are published under the guise of "evidence-based standards".

Influence of Dietary Supplementation With a Powder Containing A.N. ProDen™ (Ascophyllum Nodosum) Algae on Dog Saliva Metabolome.

The objective of this placebo-controlled, double-blind, randomized study (designed according to evidence-based medicine standards) was to determine the effect of 30-day administration of powdered brown algae, Ascophyllum nodosum (ProDen PlaqueOff, SwedenCare AB, Sweden), on saliva metabolomes in dogs. Sixty client-owned dogs underwent professional dental cleaning and were randomly subdivided into two groups receiving daily powdered brown algae A. nodosum, or a placebo (microcrystalline cellulose in powder), adjusted to their bodyweight. After a comprehensive oral health assessment and professional dental cleaning, which were both performed under general anesthesia, clinical assessments for gingivitis, plaque, and calculus were conducted. Saliva samples were collected at Day 0 and Day 30 of supplementation. Whole saliva is a mixed fluid that is derived predominantly from the major salivary glands but it also contains numerous other constituents. Additionally, its composition varies on whether salivary secretion is basal or stimulated. Authors put efforts to avoid contamination of saliva by other constituents and character of saliva was basal. Quadrupole time-of-flight (QTOF) mass spectrometer was used to conduct analysis of the saliva samples. Metabolomic analyses identified clear changes after 30 days of supplementation, and the direction of these changes was completely different than in dogs that received a placebo treatment during the same period. The positive clinical effect of 30 days of A. nodosum supplementation on oral health status in dogs described in previous publication combined with the absence of some metabolites in the saliva of dogs on day 30 of supplementation suggest that brown algae inhibit or turn off some pathways that could enhance plaque or calculus development. The exact mechanism of A. nodosum is still unclear and warrants further study.