Canadian Network for Mood and Anxiety Treatments (CANMAT) 2023 Update on Clinical Guidelines for Management of Major Depressive Disorder in Adults: Réseau canadien pour les traitements de l'humeur et de l'anxiété (CANMAT) 2023 : Mise à jour des lignes directrices cliniques pour la prise en charge du trouble dépressif majeur chez les adultes.

BACKGROUND: The Canadian Network for Mood and Anxiety Treatments (CANMAT) last published clinical guidelines for the management of major depressive disorder (MDD) in 2016. Owing to advances in the field, an update was needed to incorporate new evidence and provide new and revised recommendations for the assessment and management of MDD in adults. METHODS: CANMAT convened a guidelines editorial group comprised of academic clinicians and patient partners. A systematic literature review was conducted, focusing on systematic reviews and meta-analyses published since the 2016 guidelines. Recommendations were organized by lines of treatment, which were informed by CANMAT-defined levels of evidence and supplemented by clinical support (consisting of expert consensus on safety, tolerability, and feasibility). Drafts were revised based on review by patient partners, expert peer review, and a defined expert consensus process. RESULTS: The updated guidelines comprise eight primary topics, in a question-and-answer format, that map a patient care journey from assessment to selection of evidence-based treatments, prevention of recurrence, and strategies for inadequate response. The guidelines adopt a personalized care approach that emphasizes shared decision-making that reflects the values, preferences, and treatment history of the patient with MDD. Tables provide new and updated recommendations for psychological, pharmacological, lifestyle, complementary and alternative medicine, digital health, and neuromodulation treatments. Caveats and limitations of the evidence are highlighted. CONCLUSIONS: The CANMAT 2023 updated guidelines provide evidence-informed recommendations for the management of MDD, in a clinician-friendly format. These updated guidelines emphasize a collaborative, personalized, and systematic management approach that will help optimize outcomes for adults with MDD.

Toward evidence-based communication on overweight body mass index and mortality.

BACKGROUND: Reducing overweight and obesity has been a longstanding focus of public health messaging and physician-patient interactions. Clinical guidelines by major public health organizations describe both overweight and obesity as risk factors for mortality and other health conditions. Accordingly, a majority of primary care physicians believe that overweight BMI (even without obesity) strongly increases mortality risk. MAIN POINTS: The current evidence base suggests that although both obese BMI and underweight BMI are consistently associated with increased all-cause mortality, overweight BMI (without obesity) is not meaningfully associated with increased mortality. In fact, a number of studies suggest modest protective, rather than detrimental, associations of overweight BMI with all-cause mortality. Given this current evidence base, clinical guidelines and physician perceptions substantially overstate all-cause mortality risks associated with the range of BMIs classified as "overweight" but not "obese." Discrepancies between evidence and communication regarding mortality raise the question of whether similar discrepancies exist for other health outcomes. CONCLUSIONS: Health communication that inaccurately conveys current evidence may do more harm than good; this applies to communication from health authorities to health practitioners as well as to communication from health practitioners to individual patients. We give three recommendations to better align health communication with the current evidence. First, recommendations to the public and health practitioners should distinguish overweight from obese BMI and at this time should not describe overweight BMI as a risk factor for all-cause mortality. Second, primary care physicians' widespread misconceptions about overweight BMI should be rectified. Third, the evidence basis for other potential risks or benefits of overweight BMI should be rigorously examined and incorporated appropriately into health communication.

Navigating the uncommon: challenges in applying evidence-based medicine to rare diseases and the prospects of artificial intelligence solutions.

The study of rare diseases has long been an area of challenge for medical researchers, with agonizingly slow movement towards improved understanding of pathophysiology and treatments compared with more common illnesses. The push towards evidence-based medicine (EBM), which prioritizes certain types of evidence over others, poses a particular issue when mapped onto rare diseases, which may not be feasibly investigated using the methodologies endorsed by EBM, due to a number of constraints. While other trial designs have been suggested to overcome these limitations (with varying success), perhaps the most recent and enthusiastically adopted is the application of artificial intelligence to rare disease data. This paper critically examines the pitfalls of EBM (and its trial design offshoots) as it pertains to rare diseases, exploring the current landscape of AI as a potential solution to these challenges. This discussion is also taken a step further, providing philosophical commentary on the weaknesses and dangers of AI algorithms applied to rare disease research. While not proposing a singular solution, this article does provide a thoughtful reminder that no 'one-size-fits-all' approach exists in the complex world of rare diseases. We must balance cautious optimism with critical evaluation of new research paradigms and technology, while at the same time not neglecting the ever-important aspect of patient values and preferences, which may be challenging to incorporate into computer-driven models.

Clinical Physician Assistant Students' Perceptions of Evidence-Based Medicine Resources: A Cross-Sectional Examination.

Evidence-based medicine (EBM) instruction is required for physician assistant (PA) students. As a follow-up to an initial didactic year survey, this study seeks to understand which attributes of EBM resources clinical PA students find most and least useful, their self-efficacy utilizing medical literature, and their usage of EBM tools in the clinic. Results indicate that students preferred UpToDate and PubMed. PA students valued ease of use, which can inform instructors and librarians. Respondents utilized EBM tools daily or a few days a week, underscoring the importance of EBM tools in real-world scenarios. After their clinical year, students felt moderately confident utilizing the medical literature, emphasizing EBM training.

Building the workforce of tomorrow: The weighting of rural exposure in standardised curriculum vitae scoring criteria for entrance into Australian specialty training programs.

OBJECTIVE: To determine the weighting of rural exposure within publicly available standardised curriculum vitae (CV) scoring criteria for trainee medical officer's applying into medical and surgical specialty training programs in Australia and New Zealand. METHODS/DESIGN: An observational analysis of rural exposure point allocations within publicly available standardised CV scoring criteria for entrance into specialty training programs. SETTING: All Australian and New Zealand medical and surgical specialties training programs outlined by the Australian Health Practitioner Regulation Agency (AHPRA) who publish publicly available standardised CV scoring criteria for entrance into specialty training were included. RESULTS: Of the 14 specialty training programs that publish publicly available standardised CV scoring criteria, 8/14 allocate points towards rural exposure. While the allocation of points within this scoring domain varies between the eight training programs, the mean weighting of rural exposure is 13.7%. CONCLUSIONS: The relative weighting of rural exposure varies between the eight specialty training programs who include rural exposure as a CV scoring criteria. The deliberate and strategic construction of CV scoring criteria and inclusion of rural exposure points is important to continue developing the Australian rural specialist workforce. Future development of standardised CV scoring criteria should continue to consider point allocation towards rural exposure and related activities to ensure that the requirements of rural Australian healthcare needs are met across medical and surgical specialties.

Comparative analysis of Cochrane and non-Cochrane reviews over three decades.

BACKGROUND: Systematic reviews are viewed as the best study design to guide clinical decision-making as they are the least biased publications assuming they are well-conducted and include well-designed studies. Cochrane was initiated in 1993 with an aim of conducting high-quality systematic reviews. We aimed to examine the publication rates of non-Cochrane systematic reviews (henceforth referred to simply as "systematic reviews") and Cochrane reviews produced throughout Cochrane's existence and characterize changes throughout the period. METHODS: This observational study collected data on systematic reviews published between 1993 and 2022 in PubMed. Identified Cochrane reviews were linked to data from the Cochrane Database of Systematic Reviews via their Digital Object Identifier. Systematic reviews and Cochrane reviews were analyzed separately. Two authors screened a random sample of records to validate the overall sample, providing a precision of 98%. RESULTS: We identified 231,602 (94%) systematic reviews and 15,038 (6%) Cochrane reviews. Publication of systematic reviews has continuously increased with a median yearly increase rate of 26%, while publication of Cochrane reviews has decreased since 2015. From 1993 to 2002, Cochrane reviews constituted 35% of all systematic reviews in PubMed compared with 3.5% in 2013-2022. Systematic reviews consistently had fewer authors than Cochrane reviews, but the number of authors increased over time for both. Chinese first authors conducted 15% and 4% of systematic reviews published from 2013-2022 and 2003-2012, respectively. Most Cochrane reviews had first authors from the UK (36%). The native English-speaking countries the USA, the UK, Canada, and Australia produced a large share of systematic reviews (42%) and Cochrane reviews (62%). The largest publishers of systematic reviews in the last 10 years were gold open access journals. CONCLUSIONS: Publication of systematic reviews is increasing rapidly, while fewer Cochrane reviews have been published through the last decade. Native English-speaking countries produced a large proportion of both types of systematic reviews. Gold open access journals and Chinese first authors dominated the publication of systematic reviews for the past 10 years. More research is warranted examining why fewer Cochrane reviews are being published. Additionally, examining these systematic reviews for research waste metrics may provide a clearer picture of their utility.

Arthrocentesis versus occlusal coverage splints in the management of disc displacement without reduction: a systematic review and meta-analysis.

Disc displacement without reduction (DDwoR) can cause pain and limitations in mouth opening, with a significant impact on function. The optimal management strategy for DDwoR is unclear. Treatments include conservative management such as mandibular manipulation, occlusal splints, and patient education/self-management, as well as arthrocentesis, which is a minimally invasive procedure. The aim of this systematic review and meta-analysis was to ascertain whether there is a role for arthrocentesis in the management of DDwoR. Studies analysing the outcomes pain and maximum mouth opening (MMO) in patients with DDwoR treated by arthrocentesis or occlusal coverage devices were eligible for inclusion. Following a database search, six studies with a total of 343 participants were found to be eligible for analysis (three prospective observational studies, one retrospective observational study, one non-randomized single-blind clinical trial, and one unblinded randomized clinical trial). When compared to occlusal coverage splints, arthrocentesis demonstrated a slight improvement in pain, although this was statistically non-significant (standardized mean difference (SMD) -0.50, 95% confidence interval (CI) -1.04 to 0.05, P = 0.07; I2 = 81%), and a significant improvement in MMO (SMD 0.79 mm, 95% CI 0.24-1.35 mm, P = 0.005; I2 = 79%). However, due to the significant heterogeneity between studies and the high risk of bias, along with the paucity of double-blind randomized controlled clinical trials, definitive conclusions cannot be drawn for this clinical question.

The fragility index in randomised controlled trials of interventions for aneurysmal subarachnoid haemorrhage: A systematic review.

Background: Fragility analysis supplements the p-value and risk of bias assessment in the interpretation of results of randomised controlled trials. In this systematic review we determine the fragility index (FI) and fragility quotient (FQ) of randomised trials in aneurysmal subarachnoid haemorrhage. Methods: This is a systematic review registered with PROSPERO (ID: CRD42020173604). Randomised controlled trials in adults with aneurysmal subarachnoid haemorrhage were analysed if they reported a statistically significant primary outcome of mortality, function (e.g. modified Rankin Scale), vasospasm or delayed neurological deterioration. Results: We identified 4825 records with 18 randomised trials selected for analysis. The median fragility index was 2.5 (inter-quartile range 0.25-5) and the median fragility quotient was 0.015 (IQR 0.02-0.039). Five of 20 trial outcomes (25%) had a fragility index of 0. In seven trials (39.0%), the number of participants lost to follow-up was greater than or equal to the fragility index. Only 16.7% of trials are at low risk of bias. Conclusion: Randomised controlled trial evidence supporting management of aneurysmal subarachnoid haemorrhage is weaker than indicated by conventional analysis using p-values alone. Increased use of fragility analysis by clinicians and researchers could improve the translation of evidence to practice.

A Comprehensive Narrative Review of Neuropathic Pain: From Pathophysiology to Surgical Treatment.

Neuropathic pain is a challenging condition. Despite the immense progress made in the pathophysiology and treatment of such conditions, so much work still has to be done. New frontiers previously unexplored are now objects of study with exciting results, mainly regarding neuromodulation and optogenetics. This review explores the already known pathophysiology and the clinical and surgical treatment in the light of evidence-based medicine. Additionally, new concepts and insights are discussed, presenting the hope for the development of new paradigms in the treatment of neuropathic pain.

High certainty evidence is stable and trustworthy, whereas evidence of moderate or lower certainty may be equally prone to being unstable.

OBJECTIVE: To assess to what extent the overall quality of evidence indicates changes to observed intervention effect estimates when new data become available. STUDY DESIGN AND SETTING: We conducted a meta- epidemiological study. We obtained evidence from meta-analyses of randomized trials of Cochrane reviews addressing the same healthcare question that was updated with inclusion of additional data between January 2016 and May 2021. METHODS: We extracted the reported effect estimates with 95% confidence intervals from meta-analyses and corresponding GRADE (Grading of Recommendations Assessment, Development, and Evaluation) assessments of any intervention comparison for the primary outcome in the first and the last updated review version. We considered the reported overall quality (certainty) of evidence (CoE) and specific evidence limitations (no, serious or very serious for risk of bias, imprecision, inconsistency, and/or indirectness). We assessed the change in pooled effect estimates between the original and updated evidence using the ratio of odds ratio (ROR), absolute ROR (aROR), ratio of standard errors (RoSE), direction of effects, and level of statistical significance. RESULTS: High CoE without limitations characterized 19.3% (n=29) out of 150 included original Cochrane reviews. The update with additional data did not systematically change the effect estimates (mean ROR 1.00; 95%CI 0.99-1.02), which deviated 1.06-fold from the older estimates (median aROR; IQR: 1.01-1.15), gained precision (median RoSE 0.87; IQR 0.76-1.00), and maintained the same direction with the same level of statistical significance in 93% (27 of 29) of cases. Lower CoE with limitations characterized 121 original reviews and graded as moderate CoE in 30.0% (45 of 150), low CoE in 32.0% (48 of 150), and very low CoE in 18.7% (28 of 150) reviews. Their update had larger absolute deviations (median aROR 1.12 to 1.33) and larger gains in precision (median RoSE 0.78 to 0.86) without clear and consistent differences between these categories of CoE. Changes in effect direction or statistical significance were also more common in the lower quality evidence, again with a similar extent across categories (without change in 75.6%, 64.6%, and 75.0% for moderate, low, very low CoE). As limitations increased, effect estimates deviated more (aROR 1.05 with zero, 1.11 with one, 1.25 with two, 1.24 with three limitations) and changes in direction or significance became more frequent (93.2% stable with no limitations, 74.5% with one, 68.2% with two, and 61.5% with three limitations). CONCLUSIONS: High-quality evidence without methodological deficiencies is trustworthy and stable, providing reliable intervention effect estimates when updated with new data. Evidence of moderate and lower quality may be equally prone to being unstable and cannot indicate if available effect estimates are true, exaggerated, or underestimated.

Rapidly expanding gender-affirming care based on consensus instead of evidence justifies rigorous governance and transparency.

OBJECTIVE: Public services offering gender-affirming care to minors have rapidly expanded across Australia. Despite limited evidence of safety and efficacy, no public information about these services is routinely available. Data from freedom of information requests sent to Australian public gender services for minors is summarised. Gender service numbers increased rapidly in Queensland (2017:190 - 2022:922) and in Victoria (2019:472 - 2023:1290). Limited transparency prevented strong confidence in the number of patients receiving hormone therapy. Staff FTE employed by gender services jumped after 2020 in NSW (to 16.7 across two sites in 2023), Queensland (to 11.4 in 2023), Victoria (to 9.4 in 2022), and WA (to 10.2 in 2023). CONCLUSIONS: Despite low confidence in their safety and efficacy, the number of patients seen by public gender services has expanded rapidly since 2018. Limited transparency makes it difficult to judge the number of patients seen, treatments provided, and outcomes achieved. Safe, effective care of this vulnerable group requires clear treatment goals, and annual reporting.

Insights into the nutritional prevention of macular degeneration based on a comparative topic modeling approach.

Topic modeling and text mining are subsets of natural language processing (NLP) with relevance for conducting meta-analysis (MA) and systematic review (SR). For evidence synthesis, the above NLP methods are conventionally used for topic-specific literature searches or extracting values from reports to automate essential phases of SR and MA. Instead, this work proposes a comparative topic modeling approach to analyze reports of contradictory results on the same general research question. Specifically, the objective is to identify topics exhibiting distinct associations with significant results for an outcome of interest by ranking them according to their proportional occurrence in (and consistency of distribution across) reports of significant effects. Macular degeneration (MD) is a disease that affects millions of people annually, causing vision loss. Augmenting evidence synthesis to provide insight into MD prevention is therefore of central interest in this article. The proposed method was tested on broad-scope studies addressing whether supplemental nutritional compounds significantly benefit macular degeneration. Six compounds were identified as having a particular association with reports of significant results for benefiting MD. Four of these were further supported in terms of effectiveness upon conducting a follow-up literature search for validation (omega-3 fatty acids, copper, zeaxanthin, and nitrates). The two not supported by the follow-up literature search (niacin and molybdenum) also had scores in the lowest range under the proposed scoring system. Results therefore suggest that the proposed method's score for a given topic may be a viable proxy for its degree of association with the outcome of interest, and can be helpful in the systematic search for potentially causal relationships. Further, the compounds identified by the proposed method were not simultaneously captured as salient topics by state-of-the-art topic models that leverage document and word embeddings (Top2Vec) and transformer models (BERTopic). These results underpin the proposed method's potential to add specificity in understanding effects from broad-scope reports, elucidate topics of interest for future research, and guide evidence synthesis in a scalable way. All of this is accomplished while yielding valuable and actionable insights into the prevention of MD.

Systematic Review of the Impact of Protease Inhibitor-Based Combination Antiretroviral Therapy on Renal Transplant Outcomes in Recipients Living with HIV Infection.

Advances in Human Immunodeficiency Virus (HIV) treatment including combination antiretroviral therapy (cART) have transformed HIV into a chronic condition. Kidney diseases cause morbidity and mortality in patients living with HIV (PLWH), though cART has permitted kidney transplants with acceptable post-transplant graft and patient survival. Risk of allograft rejection remains high, which may be related to interactions between cART, specifically protease inhibitors (PI), and immunosuppressants prescribed post-transplant. This systematic review evaluates renal transplant outcomes in PLWH treated with PI- vs. non-PI-based cART. A search strategy was generated with terms related to renal transplant, HIV, and cART and run on PubMed, Embase, Scopus, and Cochrane. Studies were evaluated using PRISMA guidelines on Covidence by two reviewers, then evaluated for bias. Of 803 studies, 9 were included. Included papers were prospective or retrospective cohort studies or chart reviews of adult patients. Outcome measures included acute graft rejection, graft survival, and patient survival. One study had significant results demonstrating that PI-based therapy was correlated with increased graft rejection rates. Two studies demonstrated significant graft survival benefit to non-PI-based therapy while one demonstrated significant benefit to PI-based therapy. Two studies found significant patient survival benefit to non-PI-based therapy. For each outcome measure, remaining data suggested improved outcomes with non-PI-based therapies without achieving statistical significance. The results demonstrate superior outcomes in PLWH taking non-PI-based cART, though the paucity of significant results suggests that PLWH who require PI-based cART for virological control may continue their regimen safely post-kidney transplant.

Integrating training in evidence-based medicine and shared decision-making: a qualitative study of junior doctors and consultants.

BACKGROUND: In the past, evidence-based medicine (EBM) and shared decision-making (SDM) have been taught separately in health sciences and medical education. However, recognition is increasing of the importance of EBM training that includes SDM, whereby practitioners incorporate all steps of EBM, including person-centered decision-making using SDM. However, there are few empirical investigations into the benefits of training that integrates EBM and SDM (EBM-SDM) for junior doctors, and their influencing factors. This study aimed to explore how integrated EBM-SDM training can influence junior doctors' attitudes to and practice of EBM and SDM; to identify the barriers and facilitators associated with junior doctors' EBM-SDM learning and practice; and to examine how supervising consultants' attitudes and authority impact on junior doctors' opportunities for EBM-SDM learning and practice. METHODS: We developed and ran a series of EBM-SDM courses for junior doctors within a private healthcare setting with protected time for educational activities. Using an emergent qualitative design, we first conducted pre- and post-course semi-structured interviews with 12 junior doctors and thematically analysed the influence of an EBM-SDM course on their attitudes and practice of both EBM and SDM, and the barriers and facilitators to the integrated learning and practice of EBM and SDM. Based on the responses of junior doctors, we then conducted interviews with ten of their supervising consultants and used a second thematic analysis to understand the influence of consultants on junior doctors' EBM-SDM learning and practice. RESULTS: Junior doctors appreciated EBM-SDM training that involved patient participation. After the training course, they intended to improve their skills in person-centered decision-making including SDM. However, junior doctors identified medical hierarchy, time factors, and lack of prior training as barriers to the learning and practice of EBM-SDM, whilst the private healthcare setting with protected learning time and supportive consultants were considered facilitators. Consultants had mixed attitudes towards EBM and SDM and varied perceptions of the role of junior doctors in either practice, both of which influenced the practice of junior doctors. CONCLUSIONS: These findings suggested that future medical education and research should include training that integrates EBM and SDM that acknowledges the complex environment in which this training must be put into practice, and considers strategies to overcome barriers to the implementation of EBM-SDM learning in practice.

A Core Outcome Set for Intact Abdominal Aortic Aneurysm Repair.

OBJECTIVE: Technology and advances in clinical care have changed the management of abdominal aortic aneurysms (AAAs) but the clinical effectiveness of continuing advances needs to be assessed. To facilitate rapid synthesis of new evidence and improve stakeholder representation, including patients, the concept of core outcome sets has been developed. Core outcome sets, reflecting the needs of all stakeholders, have been established across several surgical specialties. This study aimed to develop an international core outcome set for intact AAA repair. METHODS: Following COMET methodology, potential outcomes were identified from a systematic review of published outcomes and focus groups involving patients, carers, and nurses. A 38 question Delphi consensus survey in lay language was developed (with translation to local languages); this included 35 themes identified from the findings of the systematic review and three themes from the focus groups. All three of the themes identified by the focus groups (cognitive, physical, and social functioning) can be evaluated from quality of life instruments, with overall quality of life being identified from the systematic review. The survey was completed by patients, carers or family members, vascular nurses, vascular surgeons, trainees, interventional radiologists, anaesthetists, and industry partners from six European countries. After two rounds of the survey, the top outcomes were discussed at a face to face multistakeholder consensus meeting. RESULTS: The 38 item questionnaire was amended after piloting among all stakeholder groups. After the first round of the Delphi survey (98 respondents), 15 questions were eliminated and 11 further questions were eliminated after round two (90 respondents). This left two outcome questions for discussion at the consensus meeting, where the top six outcomes were unanimously endorsed: mortality at 30 days (or in hospital if longer), secondary AAA rupture, overall quality of life and retention of cognitive functioning after recovery, 5 year survival, and continued sac growth. CONCLUSION: Six core outcomes are recommended for use as a minimum framework in all future studies and registries of intact open and endovascular AAA repair. Further work to select instruments for quality of life and define instruments for cognitive functioning is needed.

The efficacy and safety of direct oral anticoagulants in the treatment of the acute phase of heparin-induced thrombocytopenia: A systematic review.

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: To investigate the safety and efficacy of direct oral anticoagulants (DOACs) in the treatment of the acute phase of heparin-induced thrombocytopenia (HIT). SUMMARY: A systematic review of the literature was conducted on PubMed, MEDLINE, Embase, and Web of Science Core Collection through July 2023. Search terms included "heparin-induced thrombocytopenia AND direct-oral-anticoagulants" in addition to a list of oral anticoagulants. Adult patients who used direct oral anticoagulants as the initial treatment for the acute phase of HIT were included. A total of 1,188 articles were initially identified, with 770 articles reviewed following removal of duplicates. Following the application of inclusion and exclusion criteria, 12 articles were ultimately included. Rivaroxaban was the most-utilized DOAC (28 patients), followed by apixaban (7 patients) and dabigatran (1 patient). All patients with thrombocytopenia demonstrated successful platelet recovery, with two patients presenting with normal platelet counts. One patient developed a deep venous thrombosis with no other new or recurrent thromboses. There were no reported clinically significant adverse events in any patient. Obstacles and deterrents to the use of the standards of care in the acute phase of HIT exist. Argatroban and bivalirudin require intravenous infusion and require close aPTT monitoring and dose adjustment. Fondaparinux requires injection and is contraindicated with body weight <50kg. DOACs would offer the novel ability for an oral treatment in the treatment of the acute phase HIT and allow for minimal monitoring and consistent dosing strategies. Therefore, DOACs are an intriguing choice for the treatment of the acute phase of HIT. CONCLUSION: Data from 12 publications and across 36 patients suggests that the use of DOACs in the acute phase of HIT may be a safe and efficacious treatment option with favorable ease of monitoring and management.