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PubMed2026

What do we know about medical invalidation and related concepts? - A scoping review and thematic analysis about the definitions, measurements, causes, consequences and potential solutions for medical invalidation.

BACKGROUND: Medical invalidation, medical gaslighting, and related constructs have gained visibility in public discourse but remain inconsistently defined in scientific literature. Despite growing research-often focused on specific diseases- to date, no single review has comprehensively synthesized their definitions, causes, consequences, or methods of measurement. This scoping review addresses this gap by examining medical invalidation and related constructs. METHODS: Using a preregistered protocol, we systematically searched PubMed, CINAHL, Web of Science, Google Scholar, and ProQuest (dissertations) without year restrictions. Eligible sources included peer-reviewed empirical, theoretical, and conceptual work in English addressing invalidation, gaslighting, or closely related notions within healthcare. A total of 158 studies were identified through database searches and citation tracking. Data extraction followed a standardized schema, and findings were synthesized descriptively and through thematic analysis to clarify terminology, map determinants and outcomes, and identify existing measurement approaches. RESULTS: The results showed substantial inconsistency in how "invalidation," "not being taken seriously," and "gaslighting" were defined. Medical invalidation emerged as a multifactorial phenomenon driven by diagnostic challenges, structural and societal factors, provider and patient characteristics, stigma, misattribution, interactional dynamics, academic knowledge gaps, and disease-related complexity. Invalidation was associated with wide-ranging behavioural, emotional, cognitive, physical, relational, and systemic harms, while validation had consistently beneficial effects. Proposed solutions in the summarized studies included communication improvements, clinician training, patient support, targeted research, and structural and systemic changes. DISCUSSIONS: Medical invalidation represents a complex, systemic issue with significant implications for patient safety. The discussion highlights its multifactorial origins, its potential to cause both psychological and physical harm, and the need for clearer conceptualisation within the field. Advancing research requires validated instruments and longitudinal designs to examine underlying mechanisms and consequences. Addressing medical invalidation will demand multi-level interventions to improve communication, reduce structural barriers, and promote equitable, patient-centred care. OSF PREREGISTRATION: https://doi.org/10.17605/OSF.IO/MPE6U.

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PubMed2026

Associations between smart infusion pump-electronic health record interoperability and healthcare outcomes: A systematic review.

OBJECTIVE: This study synthesized available evidence on the associations between smart infusion pump-electronic health record (EHR) interoperability and healthcare outcomes. METHODS: A systematic review of PubMed, CINAHL, Embase, and Scopus databases identified 901 records, which were imported into Rayyan® for duplicate removal, independent screening by three reviewers, and resolution of discrepancies. Eligible studies were peer-reviewed, data-driven, and reported associations between smart infusion pump-EHR interoperability and healthcare outcomes. Studies focused solely on technical validation or interoperability prototypes were excluded. A backward citation search identified additional studies. Two reviewers independently extracted and cross-validated study characteristics using standardized templates. Methodological quality was assessed with the Joanna Briggs Institute Critical Appraisal Tools. RESULTS: Twenty records of 14 full-text studies and 6 conference proceedings were included. Most records reported positive associations between smart infusion pump-EHR interoperability and outcomes related to safety (e.g., medication administration errors, safety-reported events, pump alerts, and compliance with interoperability and drug library), operational efficiency (e.g., programming and documentation time and technical issues), financial performance (e.g., charges captured, and cost avoided), and user experience domains. Most studies used observational designs, reflecting real-world interoperability implementations, where controlling confounding factors is challenging. Limited reporting of baseline characteristics, pump type, and sample sizes limited comparability across studies. CONCLUSIONS: Smart infusion pump-EHR interoperability was associated with improvements in patient safety, efficiency, charge capture, and user experience, with variable findings across studies. Future research should use rigorous methodologies and standardized measures, examine relationships across outcome domains, assess limitations of pump-EHR interoperability, and evaluate underexplored outcomes, including team communication, cognitive workload, and AI-enabled pumps. IMPLICATIONS FOR CLINICAL PRACTICE: Interoperability should be viewed as a component of a broader sociotechnical system, in which technology, user, workflow, clinical content, and organizational practices collectively determine overall effectiveness.

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PubMed2026

Proteomic characterization of the acquired enamel pellicle under acidic challenges at early and mature formation stages.

OBJECTIVES: This study aimed to characterize acquired enamel pellicle (AEP) proteomic changes after exposure to citric acid (CA) and hydrochloric acid (HCl) under different pellicle formation times (3 and 120 min) in the same volunteers. DESIGN: Nine healthy volunteers participated in this randomized crossover in vivo study. The AEP was allowed to form for 3 or 120 min and subsequently exposed for 10 s to deionized water (control), 1% CA (pH 2.5), or 0.01 M HCl (pH 2.0). Pellicle samples were collected, followed by protein extraction, tryptic digestion, and analysis by nanoliquid chromatography (nanoLC) coupled to mass spectrometry (MS) with MSE (data-independent acquisition; nanoLC-MSᴱ). Label-free quantitative proteomics were performed for relative quantification using t-test (p < 0.05). RESULTS: At 120 min, CA exposure markedly reduced several typical AEP proteins, especially acidic proline-rich proteins (PRPs). Conversely, basic PRPs were upregulated, suggesting acid-resistance protein signature. At 3 min, basal-layer proteins (PRPs, cystatins, histatins and mucins) were more abundant. Hemoglobins increased 6-8-fold (up to 150-fold in 3 min control), suggesting association with early pellicle formation and an acid-resistant protein signature. CA exposures for 120 min also upregulated typical AEP proteins (PRPs, mucins, cystatins, immunoglobulins), while HCl exposure depleted albumins and lactotransferrin. CONCLUSION: Intrinsic and extrinsic acids induce distinct proteomic signatures in the AEP. Hemoglobin and PRPs appear consistently enriched in the early pellicle layer, reflecting an initial acid-resistant protein signature. These findings provide new insights into the molecular remodeling of the AEP following intrinsic and extrinsic acid exposure, highlighting proteins potentially involved in early-stage pellicle formation.

Humans↗

PubMed2026

Incidence and risk factors for malignancy in patients with incidental solitary pulmonary nodules: a systematic review and meta-analysis.

BACKGROUND: The increasing use of chest imaging has led to a higher detection rate of incidental solitary pulmonary nodules (SPNs), often causing patient anxiety. Determining the malignancy rate and associated risk factors is crucial for developing appropriate follow-up strategies to prevent overdiagnosis, overtreatment, or missed diagnoses. This meta-analysis aims to investigate the malignancy rate and risk factors in patients with incidental SPNs. METHODS: A systematic search of PubMed, Embase, Web of Science, and the Cochrane Library was conducted up to June 30, 2025. Data on malignancy rates and potential risk factors were extracted from eligible studies. All pooled analyses were performed using a random-effects model. RESULTS: Fifty-four studies involving 19,985 patients were included. The pooled malignancy rate for incidental SPNs was 56.7% (95% CI: 51.5-62.0), with significant between-study heterogeneity (I2 = 98.5%, p < 0.001). The pooled effect size showed a minimal change after adjustment for potential publication bias using the non-parametric Trim-and-Fill method (54.7%; 95%CI: 50.9-58.8). Risk factor analysis identified that older age, history of cancer, cigarette smoker, larger nodule diameter, spiculation, upper lobe location, lobulation, pleural indentation, vascular convergence, solid nodules, family history of cancer, and irregular or ill-defined margins were significantly associated with an increased risk of malignancy. Conversely, male sex, presence of calcification, and clear borders were significantly associated with a reduced risk of malignancy. CONCLUSION: This meta-analysis provides a comprehensive assessment of malignancy rates and risk factors in incidental SPNs. The high pooled malignancy rate should be interpreted considering the significant heterogeneity and the inclusion of a high proportion of retrospective studies and populations from high-risk regions. Nonetheless, these findings offer essential evidence for clinical risk stratification, supporting optimized follow-up and informed decision-making.

Humans↗

PubMed2026

Future promise, current clinical ambiguity: a systematic review of machine learning algorithm outputs predicting risk of cardiovascular disease.

OBJECTIVE: To examine whether the outputs of machine learning algorithms designed to predict risk of cardiovascular disease (CVD) address known deficiencies of the Framingham Risk Score (FRS) and improve risk estimates. METHODS: For this critical review, Medline, Embase and IEEE were searched from inception to 1 January 2025. Included were studies describing machine learning algorithms designed to specifically compare output of cardiovascular risk assessment with the FRS. Commentaries, letters, unpublished work or non-peer-reviewed papers were excluded.Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, two reviewers screened titles and abstracts independently, then populated a purpose-built data extraction form. A subsequent qualitative thematic analysis focused on algorithms' strengths, added value, potential harms, unintended consequences and equity implications.The main outcome assessed was whether, among healthy adults, the algorithm improved CVD risk prediction relative to the FRS. RESULTS: Of 707 studies retrieved, 29 met inclusion criteria. 23 reported improved predictive ability relative to the FRS. Most datasets and/or medical records used included sociodemographic predictors of CVD not included among FRS inputs. Some added costly diagnostic tests like CT angiography to FRS screening indicators. When they were defined, inputs and outcomes such as hypertension or myocardial infarction did not always adhere to FRS values. Statistical significance was generally taken as a proxy for clinical significance. Some algorithms overestimated the number at risk compared with the FRS without discussing whether that larger proportion might be at risk of overdiagnosis rather than CVD, while a few decreased the proportion found to be at risk. CONCLUSIONS: Use of artificial intelligence to improve accuracy of risk assessment for CVD demonstrates the technological capacity to merge known sociodemographic predictors with biologic variables and examine non-linear interactions among these. Still needed to achieve patient benefit is clinical insight, adherence to screening principles and cost-benefit assessment of inputs selected.

Humans↗

PubMed2026

Complexity in disguise: a systematic review of fractal analysis in psychiatric neuroimaging.

OBJECTIVES: Psychiatric diagnosis and fractal studies are complex processes that extend beyond clinical evaluation and require careful methodological considerations in neuroimaging. Over the years, fractals have helped reduce these complexities in research, but they still cannot grant clinical diagnoses. Thus, the main objective was a systematic review exploring the potential applications of fractal analysis in characterizing psychiatric conditions through neuroimaging techniques-including both functional and structural MRI. MATERIALS AND METHODS: A systematic literature review was conducted on PubMed, identifying thirty-nine original studies that met the inclusion criteria. Areas showing statistical significance (p < 0.05) were reported. These studies were categorized according to DSM-V classification and examined for the description of psychiatric conditions through the fractal analysis. RESULTS: The review primarily focuses on young adults with psychiatric conditions compared to control groups. Schizophrenia and Autism Spectrum Disorder are major areas of investigation, and fractal dimension (FD) is the primary analysis method used to reflect brain patterns. Studies that calculated whole-brain FD may have underestimated local abnormalities due to the inclusion of a high percentage of tissue, potentially resulting in overlooked findings. Notably, abnormalities in the frontal cortex represent a common neurobiological feature across several psychiatric conditions. CONCLUSIONS: The findings from this systematic review shed light on the use of fractal analysis to quantify complex brain patterns in both psychiatric patients and healthy individuals. However, it is essential to recognize the need for further research to elucidate a fractal analysis protocol that allows for optimal extraction of psychiatric insights. KEY POINTS: Question Fractal analysis applied to structural and functional MRI help characterize brain alterations across psychiatric conditions. Findings This review shows consistent fractal patterns across multiple psychiatric disorders, especially in frontal regions. Despite heterogeneous methodologies, results highlight shared structural and functional abnormalities. Clinical relevance Fractal analysis may offer complementary characterization of subtle brain organization across psychiatric disorders. Its potential clinical utility-such as improving diagnostic characterization, earlier detection, among others-remains limited by the current absence of a standardized protocol.

Humans↗

PubMed2026

Diabetic macular edema and GLP-1 receptor agonist use: a systematic review and meta-analysis.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for type II diabetes and obesity because of their cardiometabolic benefits. However, concerns regarding potential ocular adverse effects, particularly diabetic macular edema (DME), have prompted the need to clarify their retinal safety. METHODS: A systematic review and meta-analysis study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis of Observational Studies in Epidemiology statements (PROSPERO registration: CRD420251176164). MEDLINE (Ovid), EMBASE (Ovid), CENTRAL (Ovid), Web of Science, and PubMed were searched from inception to October 24, 2025. Randomized trials and observational cohort or case-control studies, including individuals with diabetes without baseline DME and exposed to GLP-1RAs were eligible. Two reviewers independently screened studies, extracted data, and assessed risk of bias using ROBINS-I. Certainty of evidence was evaluated using Grading of Recommendations, Assessment, Development, and Evaluation. Random-effects models were used to pool incidence proportions and hazard ratios (HRs). RESULTS: Thirteen retrospective cohort studies (2021-2025) using large real-world databases were included. Across 6 studies, the pooled proportion of incident DME among GLP-1RA users was 0.14 (95% CI: 0.07-0.23; I² = 99.8%). Compared with mixed antihyperglycemic therapies, GLP-1RA use was not associated with increased DME risk (pooled HR: 0.81, 95% CI: 0.52-1.26). GLP-1RAs were associated with a higher relative risk of DME compared with sodium-glucose cotransporter-2 inhibitors (HR: 1.50, 95% CI: 1.17-1.94) but not compared with dipeptidyl peptidase-4 inhibitors (HR: 0.90, 95% CI: 0.69-1.19). Evidence certainty was very low. CONCLUSION: Current low-certainty observational evidence does not support an overall increased risk of DME with GLP-1RA use. Prospective studies are needed to clarify comparative retinal safety.

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PubMed2026

Aneurysmal subarachnoid hemorrhage care in a middle-income public healthcare system: A real-world neurocritical care cohort.

BACKGROUND AND PURPOSE: Although aneurysm treatment capacity has expanded worldwide, outcomes after aneurysmal subarachnoid hemorrhage (aSAH) remain strongly influenced by neurocritical care (NCC) delivery, referral pathways, and access to specialized treatment. Contemporary data describing real-world aSAH care in resource-limited healthcare systems remain scarce. We aimed to characterize treatment patterns, NCC delivery, complications, and outcomes in a large Brazilian public referral center. METHODS: This retrospective cohort study included consecutive adults with confirmed aSAH admitted between June 2018 and March 2022 to a high-volume Brazilian tertiary referral center. Only patients admitted within five days of symptom onset were included. Demographic, clinical, radiological, treatment, complication, and outcome data were extracted from institutional records. Primary outcomes were in-hospital mortality and 3-month functional outcome assessed by the modified Rankin Scale (mRS). RESULTS: Seventy-four patients were included. Disease severity was high, with 45% presenting WFNS grades 4-5, 73% modified Fisher grade 4 hemorrhage, and 64% hydrocephalus. Endovascular treatment was performed in 73% of cases, and median time from admission to aneurysm treatment was 1 day. Despite early treatment capability, only 28% of patients were admitted to an ICU within 48 h, while 38% never received ICU care. Delayed cerebral ischemia occurred in 43%, radiologic vasospasm in 58%, ventriculitis in 22%, and infectious complications in 57%. External ventricular drainage was required in 42%, and vasoactive drugs were used in 85%. In-hospital mortality was 42%, and 66% had unfavorable 3-month outcomes (mRS 4-6). CONCLUSIONS: This real-world cohort highlights the substantial neurocritical care burden of aSAH in a middle-income public healthcare system. Despite timely access to definitive aneurysm treatment, patients experienced frequent neurological and systemic complications, emphasizing that contemporary aSAH care extends well beyond aneurysm occlusion.

Humans↗

PubMed2026

Clinicopathological response and survival outcomes of HER2-low versus HER2-zero early breast Cancer: A systematic review and Meta-analysis.

BACKGROUND: Breast cancer is the most common malignant tumor in women. Human epidermal growth factor receptor 2 (HER2) is a key biomarker for classification and treatment. A subgroup with HER2-low expression has been identified, but existing evidence is heterogeneous. This systematic review and meta-analysis compared pathological response and survival outcomes between HER2-low and HER2-zero early-stage breast cancer to clarify prognostic features. METHODS: This study followed PRISMA guidelines and was registered in PROSPERO (CRD420251120506). PubMed, Embase, Web of Science, ClinicalTrials.gov, and major oncology conferences were searched through September 2025. Cohort studies of early-stage breast cancer comparing HER2-low (IHC 1+/2+ and ISH-negative) vs. HER2-zero with extractable pCR, DFS, or OS data were included. Studies involving HER2-positive patients or inconsistent definitions were excluded. Meta-analyses were performed using RevMan 5.3. RESULTS: Twenty-eight studies involving 115,182 patients were included. HER2-low patients showed significantly lower pCR rates (OR = 0.58, 95% CI: 0.52-0.65). DFS favored HER2-low (multivariate HR = 0.75, 95% CI: 0.69-0.83), especially in HR+ tumors, with a weaker effect in HR- cases. OS also favored HER2-low (HR = 0.80, 95% CI: 0.72-0.89), mainly driven by the HR- subgroup; no OS difference was seen in HR+ tumors. Sensitivity analyses and funnel plots indicated robust results with no apparent publication bias. Overall study quality was high (17 high-quality, 11 moderate-quality). CONCLUSION: HER2-low early breast cancer shows lower pCR after neoadjuvant therapy but better long-term survival. These findings support the clinical relevance of HER2-low as a biologically meaningful subgroup within HER2-negative disease, while its status as a stable and independent subtype still requires further validation through prospective studies, standardized testing, and multi-omics investigation.

Humans↗

PubMed2026

Association of galectin-3 in systemic lupus erythematosus: A systematic review and meta-analysis.

BackgroundSystemic lupus erythematosus (SLE) is an autoimmune condition showing persistent profiling of inflammation and damage of organs and immune system. Amongst many biomarkers for such autoimmune diseases, Galectin-3 (Gal-3) a β-galactoside-binding lectin responsible for regulation, inflammation, and fibrosis of immune repsonses, has engrossed researchers for further investigations as a potential biomarker. However, correlation has been studied between circulating Galectin-3 levels and SLE but outcomes still remain inconsistent. Therefore, this systematic review and meta-analysis evaluated the association between circulating galectin-3 levels and SLE.Materials and MethodsPubMed, Scopus, ScienceDirect, Web of Science, and Embase databases are extensively used for literature search. The last database search was conducted on September 6, 2025. Eligible studies included case control studies reporting circulating galectin-3 levels in individuals with SLE and healthy controls. Two independent reviewers performed study selection and data extraction. Study quality was evaluated using the Newcastle-Ottawa Scale. Comprehensive Meta-Analysis software was used for statistical analysis. Pooled effect sizes were calculated as mean differences with 95% confidence intervals. Heterogeneity was assessed using the Cochrane Q test and I2 statistics, and publication bias was evaluated using Begg's funnel plot and Egger's regression analysis.ResultsSeven eligible studies were included in the meta-analysis. The pooled results showed that patients with SLE had significantly higher circulating Galectin-3 levels than healthy controls (mean difference = 8.48; 95% CI: 3.84-13.12; p < 0.0001). Substantial heterogeneity was observed across studies (Tau square: 32.57, Q = 196.03; p < 0.0001, I2 = 96.93%). Sensitivity analysis confirmed the stability of the overall findings. Begg's funnel plot and Egger's regression analysis indicated no publication bias among studies. Subgroup analysis supports the results of the overall analysis.ConclusionThis meta-analysis depicts that galectin-3 may serve as a biomarker associated with SLE pathogenesis and inflammatory activity due to significantly elevated levels of circulating galectin-3 levels in patients with systemic lupus erythematosus.

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PubMed2026

Imaging‑based models for predicting cerebrovascular complications of carotid stenosis.

This is a protocol for a Cochrane review (prognosis). The objectives are as follows: Primary objective To systematically review and critically appraise multivariable prognostic models developed for adults (≥ 18 years) with carotid stenosis in which imaging biomarkers (e.g. plaque characteristics derived from magnetic resonance imaging (MRI), computed tomography (CT), or ultrasound) constitute the core predictors. The primary focus is to evaluate the predictive performance of these models for cerebrovascular complications - specifically ipsilateral ischaemic stroke and transient ischaemic attack (TIA) - which are the clinical outcomes to be predicted. Where feasible, we will summarise and compare the models' discrimination (C‑statistic/area under the curve (AUC)) and calibration (calibration‑in‑the‑large, calibration slope, observed‑to‑expected ratio) across studies, and assess their potential for clinical application and external validation. For the purpose of defining symptomatic carotid stenosis as an eligibility criterion and subgroup variable, we will include studies that also considered retinal ischaemia (e.g. retinal embolism, amaurosis fugax) as a qualifying event. Secondary objectives To describe the combinations of imaging markers, modelling techniques, sample sizes, and variable‑selection strategies used in the development of the included models To evaluate the performance of these models for additional secondary clinical outcomes: plaque progression or regression, incident high‑risk imaging features, and the transition from asymptomatic to symptomatic disease To explore whether predictive performance differs according to imaging modality (MRI versus CT versus contrast‑enhanced ultrasound (CEUS)) or technical protocol (e.g. 3 T versus 1.5 T, spectral CT versus conventional CT) For studies that report both cerebrovascular and broader cardiovascular outcomes (major adverse cardiovascular events, myocardial infarction, etc.), we will only extract the performance metrics relating to cerebrovascular events for the primary analysis. Performance metrics for cardiovascular outcomes will be considered exploratory and will not form part of the main synthesis.

Humans↗

PubMed2026

Artificial intelligence in genitourinary oncology: publication trends and systematic review.

OBJECTIVE: To conduct an analysis of publication trends and a systematic review of randomized controlled trials (RCTs) to characterize the current state of artificial intelligence (AI) use in genitourinary (GU) oncology, as AI has emerged as a transformative tool in healthcare with potential applications in diagnostics, treatment planning, and prognostication. METHODS: We searched the Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica dataBASE (EMBASE; Ovid), and Cumulative Index to Nursing and Allied Health Literature (CINAHL) Ultimate for studies related to AI and GU oncology, excluding non-English papers, non-human studies, review articles, and articles using AI solely for manuscript writing. Publication trends were analysed from 2013 to 2023 and categorized by study design and cancer type. RCTs were evaluated through systematic review using Covidence (Veritas Health Innovation Ltd, Melbourne, Victoria, Australia) for screening and data extraction. Two reviewers independently assessed all studies, with risk of bias (RoB) evaluated using the Cochrane RoB 2.0 tool. RESULTS: Of 2409 articles identified, 1220 met inclusion criteria. These included 962 retrospective articles, 175 prospective studies, 79 studies with combined retrospective/prospective methods, and four RCTs. Studies most commonly addressed prostate (n = 923), renal (n = 274), and urothelial (n = 194) cancers. Publications grew from 14 in 2013 to 362 in 2023, with substantial acceleration in 2019. Four RCTs were identified - one in urothelial cancer and three in prostate cancer. Two RCTs evaluated AI-based diagnostics, demonstrating improved performance over conventional methods; the remaining two RCTs evaluated AI in prognostication and treatment planning, showing improved gains in imaging interpretation and operational efficiency. RoB varied across studies, primarily related to randomisation and deviations from intended interventions. CONCLUSIONS: Artificial intelligence research in GU oncology has grown, although high-level evidence from RCTs remains limited. Existing trials underscore AI's promise in diagnostics, prognostication, and treatment planning, and the rapidly evolving nature of this field warrants continued prospective investigation.

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PubMed2026

Vertical distribution of accessory canals in different tooth types: A systematic review and meta-analysis.

OBJECTIVE: To systematically analyze the vertical distribution of accessory canals and propose potential root-end resection levels in different tooth types. DATA: Proportional distribution of accessory canals (PD-AC) in 1 mm intervals, cumulative proportions within 2 mm and 3 mm (CP-AC0-2 and CP-AC0-3), mean distance from accessory foramen to root apex or main foramen (MD-AF), and prevalence of accessory canals in 2D cross-sections (PR-AC-2D). SOURCES: A systematic search of electronic databases was conducted through December 25, 2025. The review was registered in PROSPERO (CRD420251107855). STUDY SELECTION: Two reviewers independently performed study selection, data extraction, and risk of bias assessment using the AQUA tool. Nineteen studies were included for qualitative synthesis, of which eleven provided sufficient data for meta-analysis. A random-effects model was used, and subgroup analyses were stratified by tooth type, accessory canal type, and country. Within 0-1 mm, 1-2 mm, 2-3 mm, and 3-4 mm from the apex, 41.5%, 34.3%, 9.9%, and 4.4% of accessory canals were located, respectively. Molars had significantly higher proportions than anterior teeth both within 2 mm (90.0% vs. 72.4%) and 3 mm (96.9% vs. 87.5%). Of apical ramifications, 86.4% were within 2 mm. The pooled MD-AF was 1.472 mm. PR-AC-2D decreased from 29.3% at 1 mm to 1.3% at 5 mm. All studies presented moderate to high risk of bias. CONCLUSIONS: A 2 mm root-end resection level may be sufficient for molars, whereas anterior teeth may require a higher level. Further randomized controlled trials are needed. CLINICAL SIGNIFICANCE: A 2 mm resection may adequately expose or remove most accessory canals in molars, potentially preserving more root length while maintaining treatment efficacy. In anterior teeth, a traditional 3 mm resection remains advisable until further evidence becomes available.

Humans↗

PubMed2026

Intramuscular Fat Infiltration and Knee Osteoarthritis: A Systematic Review and Meta-Analysis.

BACKGROUND: Intramuscular fat infiltration (IMFI) is considered to be closely associated with knee osteoarthritis (KOA); however, its overall association, muscle-specific involvement, and clinical relevance remain unclear. OBJECTIVE: To quantify the association between IMFI and KOA, identify affected muscle groups, and evaluate prognostic value. METHODS: We searched PubMed, Web of Science, Scopus, and Embase up to December 2025 for observational studies. Two reviewers independently screened, extracted data, and assessed bias (NOS/JBI). Pooled standardized mean differences (SMDs) were calculated using random-effects models, with subgroup and sensitivity analyses. RESULTS: Seventeen studies were included. IMFI was significantly higher in KOA patients than controls (SMD = 0.63, 95% CI 0.41-0.85, I2 = 84.7%). Anatomically, the anterior thigh muscles (rectus femoris, vastus lateralis, vastus medialis) demonstrated a significant pooled effect (SMD = 0.96, 95% CI 0.66-1.25, I2 = 3.2%) and showed the strongest pooled association, whereas posterior, medial, and composite measures did not demonstrate significant associations. At the individual muscle level, a single study reported a notable association for the semimembranosus (SMD = 1.25, 95% CI 0.57-1.93); however, this finding is based on limited evidence and requires confirmation in future studies. Subgroup by imaging modality: CT demonstrated a significant association (SMD = 0.59, 95% CI 0.28-0.90), while MRI and ultrasound did not show significant associations. Elevated IMFI was also associated with reduced muscle strength, higher KOA incidence, structural progression, and increased knee replacement risk. CONCLUSION: A moderate positive association exists between IMFI and KOA, with notable muscle-specific heterogeneity. Anterior thigh muscles show the strongest pooled association, whereas individual muscle findings require further confirmation. These findings suggest that IMFI may represent a promising potential marker warranting further prospective investigation for risk stratification, though causality and its role in modifying disease progression remain to be established.

Humans↗

PubMed2026

Do adherence-focused interventions in low back pain have an impact on rehabilitation outcomes? A systematic review with meta-analysis.

BACKGROUND: Low back pain (LBP) is the leading cause of disability worldwide. Exercise-based interventions are effective, but adherence remains suboptimal. This systematic review and meta-analysis evaluated the effectiveness of strategies designed to enhance adherence to exercise-based interventions in individuals with LBP in terms of adherence as well as pain and functionality. METHODS: Randomized controlled trials including adults with non-specific LBP were eligible if they compared exercise-based interventions incorporating adherence-enhancing strategies versus exercise alone or usual care. Primary outcome was adherence; secondary outcomes were pain and functionality. Searches were conducted in PubMed, Embase, Web of Science, Cochrane Library, CINAHL, Scopus, and PEDro up to May 2026. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the Cochrane RoB 2 tool. Random-effects meta-analyses were performed using standardized mean differences. Certainty of evidence was evaluated using the GRADE approach. RESULTS: Fourteen randomized controlled trials including 1233 participants were included. Risk of bias was low in six studies, with the remainder showing some concerns or high risk. For adherence outcomes, evidence showed no clear effect of adherence-enhancing strategies on either device-measured physical activity (SMD = 0.21, 95% CI -0.01 to 0.43; 3 trials, 320 participants; moderate-certainty evidence) or questionnaire-based adherence (SMD = 0.33, 95% CI -0.23 to 0.89; 4 trials, 377 participants; very low-certainty evidence). For pain and functionality, moderate certainty of evidence indicated small improvements favoring intervention groups in the medium term. CONCLUSIONS: Strategies to enhance adherence to exercise in LBP show uncertain effects on adherence but may provide small improvements in clinical outcomes in the medium term. Higher-quality trials are needed to strengthen the evidence base.

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PubMed2026

Diagnostic communication in functional neurological disorder: A systematic review and meta-analysis of patient acceptance and clinical outcomes.

OBJECTIVES: Diagnostic disclosure is a key therapeutic moment in Functional Neurological Disorder (FND). This systematic review aimed to evaluate quantitative evidence on diagnostic acceptance, understanding, satisfaction, symptom outcomes, and healthcare utilisation following diagnostic disclosure in FND, and to conduct a meta-analysis of diagnostic acceptance. METHODS: Systematic searches of PubMed, Scopus, PsycINFO, and Web of Science identified quantitative studies in adults with FND. Screening followed predefined inclusion criteria. Data were extracted using a structured template and risk of bias was assessed using the Newcastle-Ottawa Scale. A random-effects meta-analysis of proportions was conducted using the Freeman-Tukey transformation. RESULTS: Fifteen studies were included, four of which contributed to the meta-analysis (n = 481). Reported diagnostic acceptance rates ranged from 38.7% to 90%, although the timing and method of assessment varied across studies. Pooled acceptance was 0.68 (95% CI 0.44-0.88), with substantial heterogeneity. Structured or reinforced communication was frequently associated with improved understanding and satisfaction, although its superiority for diagnostic acceptance was not established. In some studies, diagnostic acceptance was associated with more favourable clinical outcomes, although findings were inconsistent. Some studies reported reductions in healthcare utilisation or costs following satisfactory diagnostic explanation, whereas others found no sustained overall reduction. CONCLUSIONS: Diagnostic communication in FND is associated with differences in acceptance, understanding, and downstream clinical and healthcare outcomes. Approximately two-thirds of patients were reported as accepting the diagnosis following disclosure, although the timing and method of assessment varied substantially across studies. Empathic and evidence-informed communication may enhance understanding and engagement, although its effects on healthcare use and recovery remain uncertain. PRACTICE IMPLICATIONS: Diagnostic disclosure should be delivered clearly, empathically, and with reinforcement over time. Written information, reputable educational resources, and opportunities for follow-up clarification may support patient understanding and engagement, although stronger comparative evidence is needed.

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PubMed2026

Effectiveness of hyperbaric oxygen in traumatic brain injury patients: A systematic review and meta-analysis.

BACKGROUND: Traumatic brain injury (TBI) is the most common neurological disorder and a leading cause of global mortality and disability. Although growing evidence suggests potential benefits of Hyperbaric Oxygen Therapy (HBOT) for TBI, its efficacy remains controversial. METHODS: We systematically searched PubMed, Embase, Cochrane Library, and Web of Science from inception to March 2026. Randomized controlled trials (RCTs) evaluating HBOT versus any comparator including sham, standard care and no treatment in adults with TBI were included. Two independent reviewers screened records, extracted data, and assessed risk of bias using the Cochrane Risk of Bias tool. Heterogeneity was assessed using the I² statistic. Effect sizes were pooled using random/fixed-effects models per heterogeneity results. RESULTS: 8 studies involving 570 participants were included. HBOT significantly improved computerized cognitive performance (SMD = 0.23, 95% CI: 0.07-0.40, p = 0.004, I² = 0%), executive function and processing speed (SMD = -0.59, 95% CI: -0.93 to -0.26, p = 0.0005, I² = 30%), memory function (SMD = 0.33, 95% CI: 0.03-0.63, p = 0.03, I² = 0%), and sleep quality (MD = 1.98, 95% CI: 0.07-3.88, p = 0.04, I² = 65%). No significant benefits were observed for Glasgow Outcome Scale (RR = 1.57, 95% CI: 0.55-4.44, I² = 87%), PTSD symptoms (MD = -3.05, 95% CI: -7.05-0.95, I² = 67%), neurobehavioral symptoms (MD = -9.06, 95% CI: -32.13-14.00, I² = 97%), and emotional distress (SMD = 0.25, 95% CI: -0.32-0.81, I² = 85%). Most adverse events were mild and transient. CONCLUSION: HBOT demonstrates domain‑specific benefits for cognitive function and sleep quality in TBI patients, predominantly those with mild TBI. However, evidence for PTSD, neurobehavioral symptoms, and emotional distress remains uncertain. Furthermore, the applicability of current evidence to moderate-to-severe TBI populations is restricted.

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PubMed2026

Co-location of services: an umbrella review to consider how primary care estates could be better used to support disadvantaged groups.

AIM: To examine how co-located community and health services in primary care could support disadvantaged groups. BACKGROUND: Co-locating services is thought to improve access, collaboration, and patient outcomes. There are thousands of primary care premises across the UK. At a time of stagnating or widening health inequalities, they present an ideal opportunity to support communities, especially in disadvantaged areas. METHOD: We conducted a systematic umbrella review. Articles were retrieved from Ovid MEDLINE and Ovid Embase with supplementary snowball and grey literature searches. Reviews of co-located services supporting disadvantaged groups in primary care between 2010 and February 2024 were included. Quality and risk of bias were assessed using the Joanna Briggs Institute checklist. Two reviewers assessed eligibility, extracted data and assessed quality. Outcomes relating to health, welfare, healthcare utilization, and activity and processes were assessed. Data were narratively synthesized using a convergent integrated approach. FINDINGS: 2626 studies were screened, supplemented by snowball and grey literatures searches. Thirteen reviews were included for synthesis. One review included meta-analysis. Three models of care were identified; legal advice, welfare advice, and complementary health care. Data were synthesized according to themes: access and engagement, quality of care, efficiency, improved health, and improved social factors. We found co-located services can improve access to care, engagement in treatment, and quality of care for disadvantaged groups. Improvements to social determinants of health and mental health and well-being outcomes were reported. Findings were inconsistent when considering the impact of co-location on efficiency. We conclude that co-located services in primary care have the potential to improve identification of people most in need and improve their access to high quality health care and social support. Policy makers and practitioners should maximize the use of primary care estates to support disadvantaged groups and communities.

Humans↗