What is the probability that higher versus lower quality of evidence represents true effects estimates?

RATIONALE, AIMS, AND OBJECTIVES: The previous studies demonstrated that the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, a leading method for evaluating the certainty (quality) of scientific evidence (CoE), cannot reliably differentiate between various levels of CoE when the objective is to accurately assess the magnitude of the treatment effect. An estimated effect size is a function of multiple factors, including the true underlying treatment effect, biases, and other nonlinear factors that affect the estimate in different directions. We postulate that non-weighted, simple linear tallying can provide more accurate estimates of the probability of a true estimate of treatment effects as a function of CoE. METHODS: We reasoned that stable treatment effect estimates over time indicate truthfulness. We compared odds ratios (ORs) from meta-analyses (MAs) before and after updates, hypothesising that a ratio of odds ratios (ROR) equal to 1 will be more commonly observed in higher versus lower CoE. We used a subset of a previously analysed data set consisting of 82 Cochrane pairs of MAs in which CoE has not changed with the updated MA. If the linear model is valid, we would expect a decrease in the number of ROR = 1 cases as we move from high to moderate, low, and very low CoE. RESULTS: We found a linear relationship between the probability of a potentially 'true' estimate of treatment effects as a function of CoE (assuming a 10% ROR error margin) (R2 = 1; p = 0.001). The probability of potentially 'true' estimates decreases by 21% (95% CI: 18%-24%) for each drop in the rating of CoE. A linear relationship with a 5% ROR error margin was less clear, likely due to a smaller sample size. Still, higher CoE showed a significantly greater probability of 'true' effects (53%) compared to non-high (i.e., moderate, low, or very low) CoE (25%); p = 0.032. CONCLUSION: This study confirmed linear relationship between CoE and the probability of potentially 'true' estimates. We found that the probability of potentially "true" estimates decreases by about 20% for each drop in CoE (from about 80% for high to 55% for moderate to 35% to low and 15% to very low CoE).

A pragmatic approach to selecting a grading system for clinical practice recommendations in palliative care.

BACKGROUND: The limited palliative care evidence base is poorly amenable to existing grading schemes utilized in guidelines. Many recommendations are based on expert consensus or clinical practice standards, which are often considered 'low-quality' evidence. Reinforcing provider hesitancy in translating recommendations to practice has implications for patient care. AIM: To rationalize the selection of an appropriate grading system for rating evidence to support recommendations made in palliative care clinical practice guidelines. DESIGN: Review of the methodology sections of international palliative care guidelines published in English identified five grading systems comparison: Grading of Recommendations, Assessment, Development and Evaluations (GRADE); the Scottish Intercollegiate Guidelines Network (SIGN); Infectious Diseases Society of America-European Society for Medical Oncology (IDSA-ESMO); Confidence in the Evidence from Reviews of Qualitative research (CERQual) and the National Service Framework for Long Term Conditions (NSF-LTC). RESULTS: There is heterogeneity among grading systems used in published palliative care or terminal symptom management guidelines. GRADE has been increasingly adopted for its methodological rigour and inter-guideline consistency with other medical associations. CERQual has the potential to support recommendations informed by qualitative evidence, but its role in clinical guidelines is less defined. The IDSA-ESMO system has an intuitive typology with the ability to categorize tiers of lower-quality evidence. CONCLUSIONS: It is challenging to apply commonly used grading systems to the palliative care evidence base, which often lacks robust randomized controlled trials (RCTs). Adoption of IDSA-ESMO offers a feasible and practical alternative for lower-resourced guideline developers and palliative clinicians without a prerequisite for methodological expertise.

Cannabinoids as a Natural Alternative for the Management of Neuropathic Pain: A Systematic Review of Randomized Placebo-Controlled Trials.

Dysfunction or damage to the nervous system may develop into and result in a chronic pain condition known as neuropathic pain. Neuropathic pain is defined as the structural and functional alteration of the somatosensory component of the nervous system. The treatment of neuropathic pain is a complex endeavor, which often requires specialist care and intensive drug therapy. Recently, cannabinoids have emerged as an alternative and natural option for the treatment of chronic pain, with tetrahydrocannabinol (THC) and cannabidiol (CBD) being the most extensively studied neuroactive components. The therapeutic potential of cannabis remains largely underexplored, primarily due to its social stigma and the restrictions that are in place on its cultivation. The primary aim of this systematic review was to explore the therapeutic value of cannabinoids in the management of chronic pain and thus achieve an improved quality of life for those patients. A systematic review of the literature published over the last two decades was performed using the following databases: PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Turning research into practice (Trip), and Google Scholar. Studies that were completed and published between January 01, 2000 and August 31, 2024, in English language, were extracted and appraised. A combination of keywords and Boolean operators Cannabis OR Chronic Pain OR End of life OR Pain Management AND Drug therapy was employed for data extraction. The Cochrane risk-of-bias tool for randomized trials (RoB 2) was used for risk-of-bias assessment. The initial search resulted in 125282 articles; 86,781 of the articles were identified as duplicates and were removed from the primary analysis, and 38,501 abstracts were thus screened. Abstracts, case studies, reports, editorials, viewpoints, cross-sectional studies, cohort studies, case-control studies, case series, and letters to the editor/correspondence manuscripts (n =38,492) were furthermore excluded. Nine full-text articles were critically assessed and tested against the inclusion and exclusion criteria, and a further four articles were excluded with a total of five placebo-controlled randomized control studies being ultimately included in the final systematic review. Compared to placebo, cannabinoids provided significant relief from chronic pain (33% vs 15%) as measured by the visual analog scale. The transdermal application of CBD led to a more pronounced reduction in sharp pain, according to the neuropathic pain scale. Minimal to no side effects were recorded, further highlighting the potential benefits of cannabinoids.

Use and impact of clinical pathways across various healthcare settings: A protocol for an umbrella review of global evidence.

AIM: The proposed umbrella review aims to assess the use and impact of clinical pathways on professional practice, patient outcomes, length of hospital stay, hospital costs, patient satisfaction, and hospital staff satisfaction through a synthesis of existing systematic reviews and meta-analyses. METHODS: Following PRIOR guidelines, a systematic search will be conducted in MEDLINE, Epistemonikos, and the Cochrane Library to identify relevant systematic reviews and meta-analyses, from inception till March 2024. Two reviewers will independently screen titles and abstracts, with a third resolving any disagreements. Full-text articles considered potentially relevant will be assessed for eligibility by the same process. The data extraction form will cover information about the review methods, characteristics of the included primary studies, the types of interventions evaluated, and the reported outcomes. This standardized data extraction form will be piloted by the review team on five to ten articles to ensure all relevant information is recorded. The quality of included systematic reviews and meta-analyses will be evaluated using AMSTAR 2. PROSPERO registration number is CRD42024529371. RESULTS: The study will present a narrative synthesis of the findings, addressing the clinical and methodological heterogeneity and assessing the impact of clinical pathways on various healthcare outcomes. CONCLUSION AND IMPLICATIONS: This umbrella review will provide evidence-based insights into the effectiveness, challenges, and best practices of clinical pathways, guiding healthcare decision-making and identifying areas for future research. Results will be disseminated widely to inform policy and improve healthcare service delivery. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution, as this paper is a protocol of an umbrella review.

International Society for Diseases of the Esophagus consensus on management of the failed fundoplication.

Fundoplication is a durable, effective, and well-accepted treatment for gastroesophageal reflux disease. Nonetheless, troublesome postoperative symptoms do occasionally occur with management varying widely among centers. In an attempt to standardize definition and management of postfundoplication symptoms, a panel of international experts convened by the Guidelines Committee of the International Society for Diseases of the Esophagus devised a list of 33 statements across 5 domains through a Delphi approach, with at least 80% agreement to establish consensus. Eight statements were endorsed for the domain of Definitions, four for the domain of Investigations, nine for Dysphagia, nine for Heartburn, and four for Revisional surgery. This consensus defined as the treatment goal of fundoplication the resolution of symptoms rather than normalization of physiology or anatomy. Required investigations of all symptomatic postfundoplication patients were outlined. Further management was standardized by patients' symptomatology. The appropriateness of revisional fundoplication and the techniques thereof were described and the role of revisional surgery for therapies other than fundoplication were assessed. Fundoplication remains a frequently-performed operation, and this is the first international consensus on the management of various postfundoplication problems.

A comparison of drug information question responses by a drug information center and by ChatGPT.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: A study was conducted to assess the accuracy and ability of Chat Generative Pre-trained Transformer (ChatGPT) to systematically respond to drug information inquiries relative to responses of a drug information center (DIC). METHODS: Ten drug information questions answered by the DIC in 2022 or 2023 were selected for analysis. Three pharmacists created new ChatGPT accounts and submitted each question to ChatGPT at the same time. Each question was submitted twice to identify consistency in responses. Two days later, the same process was conducted by a fourth pharmacist. Phase 1 of data analysis consisted of a drug information pharmacist assessing all 84 ChatGPT responses for accuracy relative to the DIC responses. In phase 2, 10 ChatGPT responses were selected to be assessed by 3 blinded reviewers. Reviewers utilized an 8-question predetermined rubric to evaluate the ChatGPT and DIC responses. RESULTS: When comparing the ChatGPT responses (n = 84) to the DIC responses, ChatGPT had an overall accuracy rate of 50%. Accuracy across the different question types varied. In regards to the overall blinded score, ChatGPT responses scored higher than the responses by the DIC according to the rubric (overall scores of 67.5% and 55.0%, respectively). The DIC responses scored higher in the categories of references mentioned and references identified. CONCLUSION: Responses generated by ChatGPT have been found to be better than those created by a DIC in clarity and readability; however, the accuracy of ChatGPT responses was lacking. ChatGPT responses to drug information questions would need to be carefully reviewed for accuracy and completeness.

V Brazilian Consensus on Rhinitis - 2024.

Since we published the "IV Brazilian Consensus on Rhinitis", in2017, several advances have been achieved and have enabled a further understanding of the different aspects of "Rhinitis". This new guideline, developed jointly by ASBAI, SBP and SBORL, represents a relevant milestone in the updated and integrated management of the different forms of the disease, and it aims to unify evidence-based approaches to improve the diagnosis and treatment of this common and often underestimated condition. The document covers a wide range of topics, including clear definitions of the different phenotypes and endotypes of rhinitis, risk factors, updated diagnostic criteria, and recommended methods for clinical and laboratory investigation. We stress the importance of detailed clinical history and objective assessment, as well as tools for control and assessing severity tools an accurate diagnostic approach to the disease. Regarding treatment, it emphasizes the treatment customization, considering the severity of symptoms, the presence of comorbidities and the impact on the patient's quality of life. We discuss different drug treatment, in addition to non-pharmacological measures, such as environmental control and specific immunotherapy; and the possible role of immunobiological agents. Furthermore, the consensus addresses issues related to patient education, prevention and management of special situations, such as rhinitis in children, in pregnant women and in the elderly. In short, the "V Brazilian Consensus on Rhinitis" represents a comprehensive and updated guide for healthcare professionals involved in the diagnosis and management of rhinitis, aiming to improve patients' quality of life through an integrated and evidence-based approach.

Uptake of health economic evaluations alongside clinical trials in Australia: an observational study.

BACKGROUND: Australia's clinical trials sector is highly productive with continued sector investment needed to enhance research impact. Generating economic evidence alongside trials has the potential to facilitate the implementation of trial results into practice. Ascertaining the use of health economic evaluations alongside clinical trials can assist in determining whether clinical trials fully realize and operationalize their potential to change policy and practice. The aims of this study were to ascertain the uptake of health economic evaluations alongside Australian-led clinical trials and explore associations between uptake and trial characteristics. METHODS: This observational study comprised a descriptive analysis of clinical trials registries, a cross-sectional survey of Australian Clinical Trials Alliance (ACTA) networks, and a subgroup analysis of completed acute care trials. Descriptive analyses of trial registrations were conducted, with logistic regressions used to identify predictors of proposing and subsequently publishing a health economic evaluation alongside acute care trials. RESULTS: Few randomized Australian-led clinical trials (11% of 9251) and ACTA network trials (43% of 227) proposed a health economic evaluation. In the subgroup analysis, 22% of the 324 acute care trials and 53% of the 38 ACTA network acute care trials proposed a health economic evaluation. Acute care trials funded by government bodies were significantly more likely to propose and publish a health economic evaluation than those funded by hospitals, universities, and other funders, after adjusting for phase, registration year, primary sponsor type, and comparator. CONCLUSIONS: Current uptake of health economic evaluations alongside Australian-led clinical trials is low, with uptake higher among the subset of ACTA network trials. This is despite economic evidence playing an increasingly prominent role in health system management, as well as rising health expenditure, limited budgets, and competing demands. There is significant opportunity to embed health economic evaluations alongside clinical trials, particularly phase 3 trials, to increase research outputs and optimize research translation. Investing in clinical trial networks that support funding for a health economist or a health economic evaluation may be an effective strategy to increase the uptake of health economic evaluations alongside trials.

Applying Implementation Science to Advance Electronic Health Record-Driven Learning Health Systems: Case Studies, Challenges, and Recommendations.

With the widespread implementation of electronic health records (EHRs), there has been significant progress in developing learning health systems (LHSs) aimed at improving health and health care delivery through rapid and continuous knowledge generation and translation. To support LHSs in achieving these goals, implementation science (IS) and its frameworks are increasingly being leveraged to ensure that LHSs are feasible, rapid, iterative, reliable, reproducible, equitable, and sustainable. However, 6 key challenges limit the application of IS to EHR-driven LHSs: barriers to team science, limited IS experience, data and technology limitations, time and resource constraints, the appropriateness of certain IS approaches, and equity considerations. Using 3 case studies from diverse health settings and 1 IS framework, we illustrate these challenges faced by LHSs and offer solutions to overcome the bottlenecks in applying IS and utilizing EHRs, which often stymie LHS progress. We discuss the lessons learned and provide recommendations for future research and practice, including the need for more guidance on the practical application of IS methods and a renewed emphasis on generating and accessing inclusive data.

Teprotumumab for the Treatment of Thyroid Eye Disease: Why Should We Keep Our Eyes "Wide Open"?-A Clinical and Pharmacovigilance Point of View.

Objectives: Thyroid eye disease (TED) treatment has been recently revolutionized with the approval of teprotumumab, a targeted insulin growth factor 1 receptor (IGF1R) inhibitor. To date, teprotumumab is the only FDA-approved drug for treating TED. In this article, we would like to temper the current enthusiasm around IGF1R inhibitors. Methods: critical review of the literature by independent academic practitioners. Results: several questions should be raised. First, "how an orphan drug has become a blockbuster with annual sales exceeding $1 billion?" Teprotumumab infusions are expensive, costing about USD 45,000 for one infusion and USD 360,000 for eight infusions in a 75 kg patient. Teprotumumab approval was based on two randomized clinical trials investigating active (clinical activity score ≥ 4) TED patients. Despite this, teprotumumab was approved by the FDA for "the treatment of TED" without distinguishing between active and inactive forms. The second question is as follows: "how can a new drug, compared only to a placebo, become the new standard without being compared to historically established gold standard medical or surgical treatments?" Teprotumumab has never been compared to other medical treatments in active TED nor to surgery in chronic TED. Up to 75% of patients may experience proptosis regression after treatment discontinuation. Finally, ototoxicity has emerged as a potentially devastating side effect requiring frequent monitoring. Investigation into the long-term side effects, especially in women of childbearing age, is also warranted. Conclusions: Teprotumumab is undoubtedly a major treatment option in TED. However, before prescribing a drug, practitioners should assess its benefit/risk ratio based on the following: (i) evidence-based medicine; (ii) their empirical experience; (iii) the cost/benefit analysis; (iv) the long-term outcomes and safety profile.

Over-the-Counter Hearing Aids Versus Traditional Hearing Aids in Patients With Mild-to-Moderate Hearing Loss: Protocol for a Noninferiority Randomized Controlled Trial.

BACKGROUND: With the aging of society, the prevalence of hearing loss (HL) is increasing. Currently, approximately 5% of the global population has HL, and this number is projected to reach 7 million by 2050. Although hearing aids (HAs) are the primary treatment for HL, their use is limited by barriers such as high costs and social stigma. To address these limitations, over-the-counter (OTC) HAs have been introduced, but their effectiveness and drawbacks require further investigation. OBJECTIVE: This study aims to conduct a noninferiority randomized controlled trial comparing OTC HAs with traditional HAs to assess the clinical effectiveness of OTC HAs. METHODS: We designed a noninferiority randomized controlled trial comparing OTC HAs and traditional HAs in adults with mild-to-moderate HL. A total of 64 participants (32 per group) will be recruited. Randomization will be performed using block randomization (block sizes of 2 or 4) with an equal allocation ratio. The study will include 2 types of HAs: an OTC HA (Jabra Enhance Pro) and a traditional HA (LiNX Quattro LE561-DRW) by GN ReSound A/S. OTC HAs will be self-fitted using a smartphone app, while traditional HAs will be fitted by a licensed audiologist using the National Acoustics Laboratories-Non-Linear Prescription, second generation. Assessments, including functional gain, real-ear measurement, speech audiometry, and questionnaires, will be conducted at 6-month intervals over the course of 3 visits. Statistical analysis will compare the 2 outcomes, focusing on functional gain, to determine noninferiority. RESULTS: This study is scheduled to begin in August 2024 and has not yet recruited any participants. The study will be conducted over 2 years, from August 2024 to July 2026. Each participant will have 2 follow-up visits at 6-month intervals, making the total follow-up period 1 year. CONCLUSIONS: Since 2022, the introduction of OTC HAs has revolutionized access to these devices. Researchers, clinicians, and the general public are keen to evaluate the clinical effectiveness of OTC HAs, as more individuals will likely use them for HL. This increased usage will provide valuable real-world data to understand the benefits and limitations of OTC HAs. Monitoring the outcomes and user feedback will provide insights into their effectiveness and impact on hearing rehabilitation. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/59894.

Be SMART About Asthma Management: Single Maintenance and Reliever Therapy.

Single maintenance and reliever therapy (SMART) is an asthma treatment approach that utilizes combined inhaled corticosteroids and long-acting ß-agonists for maintenance and quick relief therapy. Despite the evidence for its benefits in asthma treatment and its adoption into American and international asthma guidelines and recommendations, SMART remains a practice of some debate. This article reviews the available evidence for SMART and offers guidance for its integration into comprehensive asthma management. Overall, short-acting ß-agonist-only asthma therapy regimens should be avoided, regardless of condition severity (SOR A Recommendation). Family medicine clinicians should start SMART for patients requiring either GINA Step 3 or 4 therapy, especially if they have signs of poor adherence (SOR B Recommendation). Finally, use budesonide-formoterol over other inhaled corticosteroid/long-acting ß-agonist combinations when implementing SMART (SOR B Recommendation).

Predicting the sample size of randomized controlled trials using natural language processing.

Objectives: Extracting the sample size from randomized controlled trials (RCTs) remains a challenge to developing better search functionalities or automating systematic reviews. Most current approaches rely on the sample size being explicitly mentioned in the abstract. The objective of this study was, therefore, to develop and validate additional approaches. Materials and Methods: 847 RCTs from high-impact medical journals were tagged with 6 different entities that could indicate the sample size. A named entity recognition (NER) model was trained to extract the entities and then deployed on a test set of 150 RCTs. The entities' performance in predicting the actual number of trial participants who were randomized was assessed and possible combinations of the entities were evaluated to create predictive models. The test set was also used to evaluate the performance of GPT-4o on the same task. Results: The most accurate model could make predictions for 64.7% of trials in the test set, and the resulting predictions were equal to the ground truth in 93.8%. GPT-4o was able to make a prediction on 94.7% of trials and the resulting predictions were equal to the ground truth in 90.8%. Discussion: This study presents an NER model that can extract different entities that can be used to predict the sample size from the abstract of an RCT. The entities can be combined in different ways to obtain models with different characteristics. Conclusion: Training an NER model to predict the sample size from RCTs is feasible. Large language models can deliver similar performance without the need for prior training on the task although at a higher cost due to proprietary technology and/or required computational power.

12. Vascular pain: Ischemic pain in the extremities and Raynaud's syndrome

INTRODUCTION: Peripheral artery diseases (PAD) and Raynaud's syndrome are associated with substantial morbidity. PAD, through the restriction of blood flow to the extremities, may lead to critical limb ischemia with symptoms of pain at rest which may eventually progress to severe limb ischemia with gangrene. This serious and painful clinical condition requires extensive medical care, is limb-threatening and, in case of delayed or unsuccessful treatment, is associated with a high mortality rate. In Raynaud's syndrome, the blood supply to certain parts of the body, usually the fingers and toes and less frequently the nose or ears, is restricted because of vasculopathy of the smaller vessels at acral sites. Under certain circumstances, with cold as the most well-known provoking factor, blood flow restriction occurs, leading to demarcated color changes and symptoms such as pain, paresthesia, and numbness. In severe cases of Raynaud syndrome tissue ischemia may lead to necrosis and the need for amputation of the affected area. METHODS: In this narrative review, the literature on the diagnosis and interventional pain treatment of PAD and Raynaud's syndrome was updated and summarized. OBJECTIVES: This review focused on interventional pain treatment. In PAD, the effects of the intervention on limb salvage, ulcer healing, and ischemic pain were summarized. Additionally, results with respect to skin microcirculation and quality of life were reported if available. In Raynaud's syndrome, we focused on the effect of the intervention on peripheral blood flow metrics and pain intensity during attacks. RESULTS: In PAD, prevention and treatment of risk factors are important. Initially, conservative treatment and pharmacological therapy are preferred first-line therapies. However, when disease progression occurs, interventional management may be considered. The literature search yielded conflicting evidence for sympathectomy as a treatment for PAD. Spinal cord stimulation (SCS) as a treatment modality for advanced PAD had high-quality evidence for limb salvage in subgroups of patients but conflicting evidence for other outcome measures such as pain, wound healing, and quality of life. The literature search for interventional pain management in Raynaud's syndrome was limited to only one randomized controlled trial (RCT) studying the effect of thoracic sympathectomy. This study had several limitations and hence the level of evidence for this interventional treatment is very low. No RCTs studying SCS in patients with Raynaud's syndrome were found. CONCLUSIONS: In both PAD and Raynaud's syndrome, additional RCTs are needed to substantiate interventional (pain) management and bolster the evidence base for sympathectomy and SCS as treatment options.