Trustworthy evidence-based versus untrustworthy guidelines: detecting the difference.

Guidelines are essential tools in healthcare decision-making. Trustworthy guidelines inform clinicians not only on the direction (against or in favour) and strength (strong or weak/conditional) of recommendations but also on the certainty of the underlying evidence. Developing trustworthy guidelines requires panellists with clinical and methodological expertise who consider patients' values and preferences. Adherence to trustworthiness standards remains variable; clinicians should, therefore, be able to distinguish trustworthy from untrustworthy guidelines. In this paper, we offer eight domains of disparities between trustworthy evidence-based guidelines and less trustworthy guidelines.

Treatment of Infected Pseudarthrosis of the Tibia Using the Ilizarov Method and the Orr Dressing.

Objective This study aims to analyze outcomes and clinical and epidemiological data of infected tibial pseudarthrosis using the Ilizarov method and the Orr dressing. Methods Data from n = 43 patients diagnosed with infected tibial pseudarthrosis were analyzed by descriptive and inferential statistical methods. In addition, Paley's assessment criteria evaluated bone and functional outcomes. Qualitative variables were presented as the distribution of absolute and relative frequencies. The presentation of quantitative variables followed the D'Agostino-Pearson test. Results Thirty-seven (86.04%) subjects were males, and six (13.95%) were females. The most frequent age group among patients was 50 to 59 years old (25.6%), with a p-value = 0.8610. The treatment time was longer for the trifocal treatment (23.8 months) when compared to the bifocal treatment (15.6 months), with a p-value = 0.0010* (highly significant). Excellent bone outcomes represented 72.09% of the sample; 23.25% of outcomes were good. Functional outcomes were excellent in 55.81%, good in 6.97%, and regular in 27.90% of subjects. The Orr dressing (using Vaseline gauze) proved effective, achieving wound healing with soft tissue coverage in all patients evaluated. Conclusions The Ilizarov method resulted in a substantial change in the treatment of bone infections, especially infected pseudarthrosis. The versatility of this method has turned it into an effective tool, allowing the healing of the infectious process and the correction of potential deformities and shortening.

Certainty of evidence, why?

Optimal clinical decision-making requires understanding of evidence regarding benefits, harms, and burdens of alternative management options. Rigorously conducted systematic reviews and meta-analyses offer accurate summaries of the evidence. However, such summaries may review only low-certainty evidence, in the process highlighting that no single decision is likely to be best for all patients. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach offers a systematic and transparent method for rating certainty of evidence in systematic reviews. In this paper, we will address the importance of assessing the certainty associated with bodies of evidence; explain how the GRADE system rates the certainty of evidence from systematic reviews; and present the GRADE evidence to decision framework for moving from evidence to strong or weak recommendations in clinical practice guidelines.

Treatment of Infected Pseudarthrosis of the Tibia Using the Ilizarov Method and the Orr Dressing / Tratamento das pseudoartroses infectadas da tÍbia pelo mÉtodo de Ilizarov associado ao curativo de Orr

Abstract Objective This study aims to analyze outcomes and clinical and epidemiological data of infected tibial pseudarthrosis using the Ilizarov method and the Orr dressing. Methods Data from n = 43 patients diagnosed with infected tibial pseudarthrosis were analyzed by descriptive and inferential statistical methods. In addition, Paley's assessment criteria evaluated bone and functional outcomes. Qualitative variables were presented as the distribution of absolute and relative frequencies. The presentation of quantitative variables followed the D'Agostino-Pearson test. Results Thirty-seven (86.04%) subjects were males, and six (13.95%) were females. The most frequent age group among patients was 50 to 59 years old (25.6%), with a p-value = 0.8610. The treatment time was longer for the trifocal treatment (23.8 months) when compared to the bifocal treatment (15.6 months), with a p-value = 0.0010* (highly significant). Excellent bone outcomes represented 72.09% of the sample; 23.25% of outcomes were good. Functional outcomes were excellent in 55.81%, good in 6.97%, and regular in 27.90% of subjects. The Orr dressing (using Vaseline gauze) proved effective, achieving wound healing with soft tissue coverage in all patients evaluated. Conclusions The Ilizarov method resulted in a substantial change in the treatment of bone infections, especially infected pseudarthrosis. The versatility of this method has turned it into an effective tool, allowing the healing of the infectious process and the correction of potential deformities and shortening.

Resumo Objetivo Analisar os resultados e os dados clínicos e epidemiológicos do tratamento das pseudoartroses infectadas da tíbia pelo método de Ilizarov associado ao curativo de Orr. Métodos Para analisar os dados de n = 43 pacientes com diagnóstico de pseudoartrose infectada da tíbia foram aplicados métodos estatísticos descritivos e inferenciais e os resultados ósseos e funcionais foram avaliados de acordo com os critérios de avaliação de Paley. As variáveis qualitativas foram apresentadas por distribuição de frequências absolutas e relativas. As variáveis quantitativas foram apresentadas pelo teste de DAgostino-Pearson. Resultados Foi encontrado que 37 (86,04%) eram do sexo masculino, 6 (13,95%) femininos. A faixa etária mais frequente entre os pacientes foi de 50 a 59 anos (25.6%), p-valor = 0.8610. O tempo de tratamento é maior no tratamento trifocal (23.8 meses) quando comparado com o Bifocal (15.6 meses), p-valor =0.0010* (altamente significante). Os resultados ósseos excelentes representaram 72,09%, 23,25% foram de resultados considerados bons. Os resultados funcionais considerados excelentes foram 55,81%, os resultados bons foram 6,97%, resultados regulares foram 27,90. O curativo com gaze vaselinada (curativo de Orr) mostrou-se eficaz, alcançando assim a cicatrização das feridas com cobertura de partes moles em todos os pacientes avaliados. Conclusões O método de Ilizarov proporcionou uma mudança substancial no tratamentos das infecções ósseas, especialmente das pseudoartroses infectadas. A versatilidade deste método se transformou em uma ferramenta eficaz, permitindo a cura do processo infeccioso, bem como correção das possíveis deformidades e do encurtamento.

Could Low-dose Cone-beam CT be Used for Endodontic Intraoperative Diagnosis?

INTRODUCTION: Cone-beam computed tomography (CBCT) allows three-dimensional evaluation and has high diagnostic accuracy of endodontic conditions. Considering that the most indicated protocol for endodontics should have smaller field-of-view and higher spatial resolution, a higher radiation dose may be associated. Thus, this study evaluated the accuracy of an optimized CBCT protocol for the detection of intraoperative endodontic complications. METHODS: An image phantom was custom-made with a human mandible covered with Mix-D and forty mandibular first molars. The teeth were subdivided into 4 groups of endodontic complications which were simulated. All teeth were individually inserted into the left second molar socket of the phantom and CBCT images were acquired with OP 300 unit adjusted to a field-of-view of 6 × 4 cm, 90kVp, and 2 dose protocols: low and high. Furthermore, a titanium implant, a tooth with endodontic treatment, and a cobalt-chromium post were inserted into the empty sockets adjacent to the teeth of interest and additional images were acquired. Four endodontists evaluated the images and indicated the presence of endodontic complications on a 5-point scale. Sensitivity, specificity, and area under the receiver operating characteristic curve were obtained. The different groups were compared by ANOVA and Tukey tests (α = 0.05). RESULTS: In most conditions, irrespective of the presence of metallic materials, the values of accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve did not differ significantly (P > .05) between the dose protocols. CONCLUSIONS: Optimized CBCT protocols should be considered for the detection of intraoperative endodontic Diagnostic complications.

How to recognize a trustworthy clinical practice guideline.

Trustworthy clinical practice guidelines represent a fundamental tool to summarize relevant evidence regarding a set of clinical choices and provide guidance for making optimal clinical decisions. Clinicians must differentiate between guidelines that provide trustworthy evidence guidance and those that do not. We present six questions clinicians should ask when evaluating a guideline's trustworthiness. (1) Are the recommendations clear?; (2) Have the panelists considered all alternatives?; (3) Have the panelists considered all patient-important outcomes?; (4) Is the recommendation based on an up-to-date systematic review?; (5) Is the strength of the recommendation compatible with the certainty of the evidence?; (6) Might conflicts of interest influence the recommendations? If yes, were they managed? Once the conclude they are dealing with a trustworthy guideline, clinicians must gain an understanding of the transparent evidence summary that the guideline will offer, and judge the applicability of trustworthy recommendations to their patients and settings. Consideration of the circumstances and values and preferences of patients will be crucial for all weak or conditional recommendations.

Benefits and harms of drug treatment for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials.

OBJECTIVE: To compare the benefits and harms of drug treatments for adults with type 2 diabetes, adding non-steroidal mineralocorticoid receptor antagonists (including finerenone) and tirzepatide (a dual glucose dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonist) to previously existing treatment options. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Ovid Medline, Embase, and Cochrane Central up to 14 October 2022. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Eligible randomised controlled trials compared drugs of interest in adults with type 2 diabetes. Eligible trials had a follow-up of 24 weeks or longer. Trials systematically comparing combinations of more than one drug treatment class with no drug, subgroup analyses of randomised controlled trials, and non-English language studies were deemed ineligible. Certainty of evidence was assessed following the GRADE (grading of recommendations, assessment, development and evaluation) approach. RESULTS: The analysis identified 816 trials with 471 038 patients, together evaluating 13 different drug classes; all subsequent estimates refer to the comparison with standard treatments. Sodium glucose cotransporter-2 (SGLT-2) inhibitors (odds ratio 0.88, 95% confidence interval 0.83 to 0.94; high certainty) and GLP-1 receptor agonists (0.88, 0.82 to 0.93; high certainty) reduce all cause death; non-steroidal mineralocorticoid receptor antagonists, so far tested only with finerenone in patients with chronic kidney disease, probably reduce mortality (0.89, 0.79 to 1.00; moderate certainty); other drugs may not. The study confirmed the benefits of SGLT-2 inhibitors and GLP-1 receptor agonists in reducing cardiovascular death, non-fatal myocardial infarction, admission to hospital for heart failure, and end stage kidney disease. Finerenone probably reduces admissions to hospital for heart failure and end stage kidney disease, and possibly cardiovascular death. Only GLP-1 receptor agonists reduce non-fatal stroke; SGLT-2 inhibitors are superior to other drugs in reducing end stage kidney disease. GLP-1 receptor agonists and probably SGLT-2 inhibitors and tirzepatide improve quality of life. Reported harms were largely specific to drug class (eg, genital infections with SGLT-2 inhibitors, severe gastrointestinal adverse events with tirzepatide and GLP-1 receptor agonists, hyperkalaemia leading to admission to hospital with finerenone). Tirzepatide probably results in the largest reduction in body weight (mean difference -8.57 kg; moderate certainty). Basal insulin (mean difference 2.15 kg; moderate certainty) and thiazolidinediones (mean difference 2.81 kg; moderate certainty) probably result in the largest increases in body weight. Absolute benefits of SGLT-2 inhibitors, GLP-1 receptor agonists, and finerenone vary in people with type 2 diabetes, depending on baseline risks for cardiovascular and kidney outcomes (https://matchit.magicevidence.org/230125dist-diabetes). CONCLUSIONS: This network meta-analysis extends knowledge beyond confirming the substantial benefits with the use of SGLT-2 inhibitors and GLP-1 receptor agonists in reducing adverse cardiovascular and kidney outcomes and death by adding information on finerenone and tirzepatide. These findings highlight the need for continuous assessment of scientific progress to introduce cutting edge updates in clinical practice guidelines for people with type 2 diabetes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022325948.

Introducing the Library of Guidance for Health Scientists (LIGHTS): A Living Database for Methods Guidance.

Importance: Improving methodological quality is a priority in the health research community. Finding appropriate methods guidance can be challenging due to heterogeneous terminology, poor indexing in medical databases, and variation in formats. The Library of Guidance for Health Scientists (LIGHTS) is a new searchable database for methods guidance articles. Observations: Journal articles that aim to provide guidance for performing (including planning, design, conduct, analysis, and interpretation), reporting, and assessing the quality of health-related research involving humans or human populations (ie, excluding basic and animal research) are eligible for LIGHTS. A team of health researchers, information specialists, and methodologists continuously identifies and manually indexes eligible guidance documents. The search strategy includes focused searches of specific journals, specialized databases, and suggestions from researchers. A current limitation is that a keyword-based search of MEDLINE (and other general databases) and manual screening of records were not feasible because of the large number of hits (n = 915 523). As of September 20, 2022, LIGHTS included 1246 articles (336 reporting guidelines, 80 quality assessment tools, and 830 other methods guidance articles). The LIGHTS website provides a user-oriented search interface including filters for study type, specific methodological topic, research context, guidance type, and development process of the guidance. Automated matching of alternative methodological expressions (eg, enter loss to follow-up and find articles indexed with missing data) enhances search queries. Conclusions and Relevance: LIGHTS is a peer-supported initiative that is intended to increase access to and use of methods guidance relevant to health researchers, statisticians, methods consultants, methods developers, ethics boards, peer reviewers, journal editors, and funding bodies.

Certainty of evidence, why? / Certeza das evidências, por quê?

ABSTRACT Optimal clinical decision-making requires understanding of evidence regarding benefits, harms, and burdens of alternative management options. Rigorously conducted systematic reviews and meta-analyses offer accurate summaries of the evidence. However, such summaries may review only low-certainty evidence, in the process highlighting that no single decision is likely to be best for all patients. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach offers a systematic and transparent method for rating certainty of evidence in systematic reviews. In this paper, we will address the importance of assessing the certainty associated with bodies of evidence; explain how the GRADE system rates the certainty of evidence from systematic reviews; and present the GRADE evidence to decision framework for moving from evidence to strong or weak recommendations in clinical practice guidelines.

RESUMO Para tomar a melhor decisão clínica, é preciso compreender as evidências a respeito dos benefícios, malefícios e ônus das alternativas de manejo. Revisões sistemáticas e meta-análises que sejam realizadas com rigor oferecem resumos precisos das evidências. No entanto, é possível que esses resumos avaliem apenas as evidências cujo grau de certeza é baixo e, ao fazê-lo, ressaltem que provavelmente não existe uma decisão única que será a melhor para todos os pacientes. O Grading of Recommendations Assessment, Development, and Evaluation (GRADE) é um método sistemático e transparente para avaliar o grau de certeza das evidências em revisões sistemáticas. Neste artigo, abordaremos a importância de avaliar o grau de certeza das evidências; explicaremos como o sistema GRADE classifica o grau de certeza das evidências provenientes de revisões sistemáticas e apresentaremos o evidence to decision framework (quadro para a avaliação de evidências) do GRADE para decidir se as evidências se traduzem em recomendações fortes ou fracas nas diretrizes de prática clínica.

Functional and morphologic dysfunctions in the airways of rats submitted to an experimental model of obesity-exacerbated asthma.

The obesity-exacerbated asthma phenotype is characterized by more severe asthma symptoms and glucocorticoid resistance. The aim of this study was to standardize an obesity-exacerbated asthma model by a high glycemic level index (HGLI) diet and ovalbumin (OVA) sensitization and challenges in Wistar rats. Animals were divided into groups: control (Ctrl), obese (Ob), asthmatic (Asth), obese asthmatic (Ob + Asth) and obese asthmatic treated with dexamethasone (Ob + Asth + Dexa), and in vivo and in vitro functional and morphological parameters were measured. After HGLI consumption, there was an increase in body weight, fasting blood glucose, abdominal circumferences, body mass index and adiposity index. Respiratory function showed a reduction in pulmonary tidal volume and ventilation. In isolated tracheas, carbachol showed an increase in contractile efficacy in the Ob, Ob + Asth and Ob + Asth + Dexa, but mostly on Ob + Asth. Histological analysis of lungs showed peribronchovascular inflammation and smooth muscle hypertrophy and extracellular remodeling on Ob + Asth and Ob + Asth + Dexa. An obesity-exacerbated asthma model was successfully established. Therefore, this model allows further molecular investigations and the search for new therapies for the treatment and relief of symptoms of patients with obesity-induced resistant asthma.

Integrated review of resource recovery on aerobic granular sludge systems: Possibilities and challenges for the application of the biorefinery concept.

Aerobic Granular Sludge (AGS) is a biological treatment technology that has been extensively studied in the last decade. The possibility of resource recovery has always been highlighted in these systems, but real-scale applications are still scarce. Therefore, this paper aimed to present a systematic review of resources recovery such as water, energy, chemicals, raw materials, and nutrients from AGS systems, also analyzing aspects of engineering and economic viability. In the solid phase, sludge application in agriculture is an interesting possibility. However, the biosolids' metal concentration (the granules have high adsorption capacity due to the high concentration of extracellular polymeric substances, EPS) may be an issue. Another possibility is the recovery of Polyhydroxyalkanoates (PHAs) and Alginate-like exopolymers (bio-ALE) in the solid phase, emphasizing the last one, which has already been made in some Wastewater Treatment Plants (WWTPs), named and patented as Kaumera® process. The Operational Expenditure (OPEX) can be reduced by 50% in the WWTP when recovery of ALE is made. The ALE recovery reduced sludge yield by up to 35%, less CO2 emissions, and energy saving. Finally, the discharged sludge can also be evaluated to be used for energetic purposes via anaerobic digestion (AD) or combustion. However, the AD route has faced difficulties due to the low biodegradability of aerobic granules.

Cerium-zirconium mixed oxide nanostructures for diesel soot oxidation: synthesis and effect of structure.

Nanostructured materials have been used in several branches of science and technology. Particulate matter is one of the major air pollution concerns. In this work, nanorods and nanoparticles of Ce0.8Zr0.2O2 (CZ) mixed oxides were prepared by different routes, and the use of an organic template was evaluated in diesel soot oxidation. The catalysts were characterized by several techniques including structural analysis (XRD, TEM, N2 adsorption-desorption) and activity (TPR/MS, TPO/MS). A fast TPR/MS method is proposed to calculate hydrogen consumption that can be correlated to the oxygen storage capacity (OSC). It was demonstrated that CZ-nanorods with twice the amount of template in the syntheses (CZ-NRs-2X) were very active for soot oxidation with T 50% at 351 °C, and CO2 and H2O were the only oxidation products from Printex®-U (Evonik). This catalyst, reported for the first time, was subjected to up to three cycles and it showed fair activity, proving that this morphology is one of the best mixed oxides of CZ for oxidation.