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The role of artificial intelligence in the diagnosis and prognosis of traumatic brain injury based on brain CT scans: a systematic review.

Traumatic brain injury (TBI) is a leading cause of emergency department visits and a major contributor to injury-related mortality and long-term neurological disability. Non-contrast computed tomography (CT) is the gold-standard imaging modality for the rapid diagnosis of TBI. Clinical outcomes depend strongly on early detection and prompt acute management. Artificial intelligence (AI)-based models may support faster automated identification of traumatic findings and early prediction of patient prognosis. A systematic literature search was conducted in PubMed/MEDLINE, Scopus, IEEE Xplore, ACM Digital Library, and the Cochrane Library in accordance with PRISMA 2020 guidelines to evaluate AI-based models for automated detection of TBI-related findings on CT and for prediction of clinical outcomes. Risk of bias and applicability were assessed using QUADAS-2 for diagnostic accuracy studies and PROBAST + AI for prediction model studies. Twenty-two studies were included. Sixteen studies evaluated diagnostic tasks and 10 evaluated prognostic outcomes, with four studies contributing to both categories. Diagnostic performance was generally high, with many studies reporting AUC values approaching or exceeding 0.90, particularly for larger lesion volumes.Prognostic performance was more variable, with moderate to high discrimination and substantial heterogeneity. Only 9 studies incorporated independent external validation, and performance was frequently lower in external cohorts. All prognostic model studies were judged to be at high overall risk of bias using PROBAST + AI, and most diagnostic accuracy studies also demonstrated high or unclear risk of bias in at least one QUADAS-2 domain, most frequently in patient selection. AI-based models applied to brain CT demonstrate strong technical performance for both diagnostic and prognostic tasks in TBI. However, most studies relied on retrospective designs and lacked independent external validation which limits models generalizability and raises concern for potential overfitting. Prospective, multicenter studies with standardized methodologies and rigorous external validation are required before widespread clinical implementation.

Humans

Vitamin D Supplementation Modulates Base Excision Repair (BER) Machinery in Systemic Sclerosis: A Prospective Longitudinal Study.

Systemic sclerosis (SSc) is a chronic, autoimmune, fibrotic disorder involving immune dysregulation, vascular abnormalities and progressive fibrosis. Although oxidative stress and defective DNA repair have been implicated in its pathogenesis, the impact of vitamin D on DNA repair pathways remains unclear. This study aimed to investigate the expression of DNA repair enzymes in SSc, explore their relationship with vitamin D status and assess the effects of vitamin D supplementation on the transcriptional expression of these enzymes. Peripheral blood samples were collected from 52 female patients with SSc and 31 age-matched healthy controls (HCs). Gene expression levels of base excision repair (BER) enzymes (APE1 and OGG1) and nucleotide excision repair (NER) enzymes (XPA and XPC) were analyzed. Serum vitamin D levels were measured and correlated with disease activity scores. In a prospective arm of the study, patients received six months of vitamin D supplementation and their DNA repair capacity was evaluated pre- and post-intervention. Baseline expression of APE1 and OGG1 was significantly lower in SSc patients than in HCs, whereas expression of the NER genes remained unchanged, indicating selective impairment of the BER pathway. Vitamin D deficiency was prevalent in SSc and inversely correlated with disease severity. Supplementation significantly increased serum vitamin D levels and up-regulated APE1 and OGG1 expression; while NER genes remained unaffected. These findings are consistent with evidence of elevated oxidative DNA lesions in SSc and support a mechanistic link between BER activity and the repair of oxidative DNA damage. SSc patients exhibit reduced transcription of BER-specific enzymes associated with vitamin D deficiency andrestoration of vitamin D levels partially rescues BER enzyme expression. These findingshighlight a potentially modifiable axis linking micronutrient status, genomic stability and disease activity and provide a rationale for investigating vitamin D optimization as an adjunctive strategy to enhance DNA repair and potentially attenuate inflammatory and fibrotic processes in SSc.

Humans

Methylation profiling in CNS tumor diagnostics: a single-centre real-world experience from Central Europe.

Genome-wide DNA methylation profiling has transformed neuro-oncology by providing an objective, machine learning-based taxonomy that mitigates interobserver variability and refines the histo-molecular criteria of the current WHO classification. We evaluate the real-world diagnostic performance and clinical utility of this modality in a prospective, consecutively accrued three-year cohort of 291 central nervous system (CNS) tumors across a mixed adult-pediatric population. Successful profiling was completed in 95.9% of cases. Using the Epignostix classifier, a high-confidence diagnostic match (calibrated score [CS]&#x2009;&#x2265;&#x2009;0.84) was achieved in 70.3% of analyzable samples, while 26.5% returned lower-confidence scores (&#x2265;&#x2009;0.3 to <&#x2009;0.84) and only 3.2% remained completely unclassifiable (CS&#x2009;<&#x2009;0.3). When integrated into a comprehensive diagnostic framework, methylation profiling provided clinically useful results in 81.1% of cases, establishing diagnoses in 70 cases submitted for molecular subclassification and resolving diagnostic uncertainty or prompting major revisions in 149 histologically challenging tumors. Within truly ambiguous lesions, integration of methylome data dictated tumor grade modifications in 38.8% of cases (upgrading in 29.4% and downgrading in 9.4%), shifting patient risk stratification. Crucially, over half (52.7%) of the lower-confidence cases yielded meaningful clinical integration when supported by histomorphology and ancillary genetic or immunohistochemical markers, demonstrating that rigid score cutoffs should not dictate assay failure. Discrepant or misleading classifications occurred in 1.9%. Updating bioinformatic pipelines from version 11b4 to 12.8 rescued multiple ambiguous entries, increasing overall clinical utility to 84.1%. These findings demonstrate that integrating computational epigenomics with classical neuropathology enhances diagnostic precision, while highlighting the ongoing need for careful clinical-pathological correlation.

Central nervous system tumors

Clinical Performance of Bulk-Fill Versus Incremental Composite Placement Approaches in Vital Posterior Teeth: A 24&#x2009;Months Randomized Controlled Trial.

BACKGROUND: Composite resin placement technique may influence marginal integrity, polymerization stress distribution, and long-term clinical performance of posterior restorations. This randomized controlled clinical trial evaluated the 24-month clinical performance of four different placement techniques in Class I posterior composite restorations. METHODS: Fifty patients aged 20-35&#x2009;years presenting with four occlusal carious lesions each were enrolled, resulting in 200 restorations. Cavities (4-5&#x2009;mm depth) were prepared according to caries extension. Restorations were randomly allocated into four equal groups (n&#x2009;=&#x2009;50) according to placement technique: stamp technique, snowplow technique, modified incremental "pizza" technique, and bulk-fill technique. All materials were applied following manufacturers' instructions. Clinical evaluation was performed at baseline and after 6, 12, and 24&#x2009;months using FDI criteria. Functional (fracture/retention, marginal adaptation), esthetic (marginal staining, anatomical form), and biological (postoperative sensitivity, secondary caries) properties were assessed by two calibrated evaluators. Statistical analysis was performed at a significance level of &#x3b1;&#x2009;=&#x2009;0.05. RESULTS: Thirty-eight patients with a total of 152 restorations were evaluated at the end of the 24&#x2009;months in line with FDI at the end of the study with 76% recall rates. No statistically significant differences were observed among groups regarding fracture/retention or secondary caries (p&#x2009;>&#x2009;0.05). Marginal adaptation and marginal staining demonstrated minor deterioration over time across all groups, with statistically significant intergroup differences found (p&#x2009;<&#x2009;0.05). Postoperative sensitivity was minimal and transient in all groups with no significant difference (p&#x2009;=&#x2009;0.181). CONCLUSIONS: Within the limitations of this 24-month follow-up, the four placement techniques demonstrated comparable clinical performance in Class I posterior composite restorations. Selection of technique may therefore be guided by clinical preference and procedural efficiency rather than differences in short-term clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT07415317.

Humans

Efficacy of afoxolaner (NexGard&#xae;) for the treatment of myiasis caused by the zoonotic tumbu fly, Cordylobia anthropophaga, in domestic dogs under field conditions.

Cordylobia anthropophaga is a major cause of furuncular myiasis in dogs and humans in sub-Saharan Africa, yet evidence for pharmacological control remains limited. Current management relies mainly on mechanical larval removal, and no controlled studies have assessed the efficacy of modern antiparasitic agents. This study evaluated the curative and preventive efficacy of a single dose of afoxolaner (NexGard&#xae;) in dogs with naturally acquired C. anthropophaga infestation under field conditions and explored a possible indirect protective effect in puppies after maternal treatment. A randomized, blinded, negative-controlled field study was conducted in Samburu County, Kenya, and included 104 naturally infested dogs allocated to a treated group (n&#x202f;=&#x202f;53) or an untreated control group (n&#x202f;=&#x202f;51). Clinical evaluations were performed on Days 0, 15 (&#xb1;2), 30 (&#xb1;2), and 45 (&#xb1;2). Efficacy was assessed based on the presence of active nodules and clinical scores. Additional observational data were collected from puppies born to or nursing from treated bitches. Compared to the control group, parasiticide efficacy was 94% on Day 15 and 100% on Day 30. The number of parasite-free dogs reached 86.3% on Day 15, 100% on Day 30, and 95.3% on Day 45. Treated dogs showed a significant clinical improvement from the first post-treatment assessment, whereas infestation persisted in controls (nodules: OR = 0.003, 95% CI 0.001-0.017; skin lesions: OR = 0.010, 95% CI 0.002-0.051; lymph node: OR = 0.013, 95% CI 0.002-0.074; body condition: OR = 0.073, 95% CI 0.027-0.195; all p&#x202f;<&#x202f;.001), with large effect sizes at the final visit for all outcomes (r&#x202f;=&#x202f;0.521-0.793). No C. anthropophaga infestations were detected in examined puppies from treated dams, including puppies exposed during pregnancy or lactation, up to 4 weeks after birth and up to 11 weeks of age, respectively. Afoxolaner appears effective to control canine cordylobiosis and may offer indirect protection to puppies, warranting further investigation.

Animals

Clinical Utility of Ultra-Widefield Swept-Source OCT for Intraocular Tumors: Comparison With Ultrasonography, SD-OCT, and MRI.

PURPOSE: To evaluate the clinical performance of ultra-widefield swept-source optical coherence tomography (UWF-OCT) in the assessment of choroidal tumors and to compare it with ultrasonography (US), spectral-domain (SD)-OCT, and magnetic resonance imaging (MRI). DESIGN: Retrospective diagnostic comparison. SUBJECTS: Thirty-nine eyes from 39 patients diagnosed with choroidal tumors at a single tertiary referral center. METHODS: This retrospective diagnostic comparison evaluated patients diagnosed with choroidal tumors at a single tertiary referral center between January 2023 and August 2025. All patients underwent UWF-OCT imaging at diagnosis. Tumor measurements obtained with UWF-OCT were compared with US, SD-OCT, and MRI. Comparative analysis among imaging modalities and predictors affecting UWF-OCT applicability was performed. MAIN OUTCOME MEASURES: Tumor thickness (mm) and largest basal diameter (LBD, mm) measurements, and complete measurability rate across different tumor size categories. RESULTS: Thirty-nine eyes from 39 patients (mean age 59.2 &#xb1; 16.9 years) were analyzed, including 27 choroidal melanomas (69.2%), 5 metastatic tumors (12.8%), 4 hemangiomas (10.3%), 2 osteomas (5.1%), and 1 (2.6%) indeterminate choroidal melanocytic lesion. UWF-OCT successfully measured both tumor thickness and largest basal diameter (LBD) in 100% (31/31) of small and medium choroidal tumors, substantially outperforming SD-OCT (complete measurement achieved in 63.6% of small tumors, and 0% of medium or large tumors). UWF-OCT measurements were systematically smaller than ultrasonography (thickness: -32.3%, P < .01; LBD: -11.1%, P < .01) and MRI (thickness: -29.2%, P < .01). Mushroom-shaped tumor morphology was the strongest negative predictor of UWF-OCT quality (OR = 0.015, 95% CI 0.001-0.196, P < .01). UWF-OCT's complete measurability was limited in large tumors (12.5%, 1/8). CONCLUSIONS: UWF-OCT provides precise, noninvasive, single-scan assessment of small-to-medium choroidal tumors with detailed structural visualization. It may be particularly useful for dome-shaped tumors, while multimodal imaging with US and MRI remains optimal for complex morphologies. Overall, UWF-OCT represents a valuable tool for diagnosis and treatment planning, with potential utility for longitudinal follow-up in choroidal tumor management.

Humans

Antimicrobial resistance in Staphylococcus spp. isolated from sporotrichosis-affected cats in Brazil: Detection of MRSP and MRSA.

Recently, Brazil has experienced a zoonotic emergence of sporotrichosis. The associated cutaneous lesions are often extensive and slow to heal, thereby providing a gateway for opportunistic bacteria belonging to the normal skin microbiota. Among these, Staphylococcus spp. are of particular concern due to their high prevalence and notable levels of antimicrobial resistance. The objective of this study was to identify and characterize Staphylococcus spp. isolated from the cutaneous wounds of domestic cats undergoing treatment for sporotrichosis and exhibiting clinical signs of secondary bacterial infection. A total of 233 samples from 203 cats were analyzed. Staphylococcus spp. was isolated from 156 samples (67%), with S. aureus (42.3%) and S. felis (25.6%) being the most prevalent. Antimicrobial susceptibility testing revealed high levels of resistance to penicillin (51.9%), erythromycin (28.8%), and clindamycin (19.2%). In contrast, most isolates were susceptible to chloramphenicol (98%), ciprofloxacin (96.7%), and nitrofurantoin (93%). Multidrug-resistant strains were identified in 24% (38/156) of the isolates. Overall, 12 isolates (7.7%) were classified as methicillin-resistant staphylococci, including four methicillin-resistant S. pseudintermedius (MRSP) and one methicillin-resistant S. aureus (MRSA). To investigate the genetic profiles and epidemiological relationships of these isolates, all the MRSP and MRSA strains were subjected to whole-genome sequencing. Among the MRSP isolates, four sequence types (STs) were identified, including ST551, the founder of clonal complex (CC)551, which is commonly associated with infection in dogs. The MRSA isolate belonged to ST1176, a member of CC5, which is a globally prevalent lineage and is frequently associated with nosocomial infections in humans. This study demonstrates that Staphylococcus species, including methicillin-resistant isolates, are frequently present in the wounds of sporotrichosis-infected cats exhibiting clinical signs of secondary bacterial infection. The detection of MRSA and MRSP in a cat highlights an additional public health concern associated with feline sporotrichosis and further reinforces the growing concern regarding antimicrobial resistance in companion animals.

Animals

Outcomes and Associated Prognostic Factors for Orthograde Canal Obturation Using Ortho MTA III: A Randomised Prospective Clinical Trial.

AIM: To prospectively compare treatment outcomes for orthograde canal obturation using Ortho MTA III (OMTA) with the continuous wave of compaction (CWC) using gutta-percha (GP) and AH Plus sealer, and to identify associated predictive factors. METHODOLOGY: Informed consent was obtained (110 patients), and single- or two-rooted permanent teeth (n&#x2009;=&#x2009;120) diagnosed with pulp necrosis (or previously treated) and asymptomatic apical periodontitis or chronic apical abscess (periapical index, PAI&#x2009;&#x2265;&#x2009;3) were randomly assigned to two groups (n&#x2009;=&#x2009;60/group). The canals were prepared to a minimal apical size #40 (ISO) based on their initial file size, disinfected and obturated by either CWC or OMTA using an enhanced disinfection protocol (GP disinfected, new gloves after each intraoperative radiograph and before starting obturation). Clinical and periapical radiographic examinations were conducted by two calibrated, independent endodontists during follow-up periods of at least 12&#x2009;months. Success rates and associated predictive factors (tooth-, operator- and patient-related) were analysed statistically using binary and multiple logistic regression (p&#x2009;<&#x2009;0.05). RESULTS: The median recall period was 30&#x2009;months (14-48&#x2009;months), and 104 teeth were finally analysed (recall rate: 86.67%). No significant differences in success rate were observed between the groups (p&#x2009;>&#x2009;0.05) under both loose (OMTA: 88.24%, CWC: 83.02%) and strict criteria (OMTA: 64.71%, CWC: 58.49%). Multivariate analysis revealed that age (OR&#x2009;=&#x2009;5.735, 95% CI: 1.286-25.577, p&#x2009;=&#x2009;0.022), periapical lesion size (OR&#x2009;=&#x2009;6.596, 95% CI: 1.397-31.138, p&#x2009;=&#x2009;0.017) and PAI score (OR&#x2009;=&#x2009;2.081, 95% CI: 1.047-4.136, p&#x2009;=&#x2009;0.036) were significant predictors of treatment failure. CONCLUSIONS: Orthograde obturation of infected canals with Ortho MTA III demonstrated comparable success and treatment outcomes to those filled with GP and sealer by CWC, supporting its potential as a clinically viable alternative for the obturation of infected root canals. TRIAL REGISTRATION: cris.nih.go.kr registration number: KCT00099939.

Humans

Surgical treatment of schwannomas around the tarsal tunnel: a case series of 40 patients and systematic review of the literature.

OBJECTIVE: Schwannomas in the tibial, plantar, or medial calcaneal nerves around the ankle can mimic symptoms of tarsal tunnel syndrome. Outcomes after resection of schwannomas from these nerves have mainly been reported in case reports. The objectives of this study were to investigate the presentation and results for resection of schwannomas around the tarsal tunnel in a large case series and systematically review the currently available literature. METHODS: Data from 40 patients (27 sporadic and 13 schwannomatosis cases) treated at 2 centers were retrospectively analyzed for preoperative type and duration of symptoms, schwannoma size at presentation, and outcome after resection. The following different locations around the ankle were compared: proximal to the tarsal tunnel (PTT), at the tarsal tunnel (ATT), and distal to the tarsal tunnel (DTT). The severity of symptoms was categorized in increasing order for pain only on touch, during load-bearing activities, and symptoms also at rest. Surgical outcome was assessed based on pain relief and occurrence of complications. The systematic literature review was performed using a PubMed and Embase search. RESULTS: All but 1 patient presented with pain, local at the ankle, or neuropathic pain during weight-bearing activities (13/40, 32.5%). More than half of the patients also experienced symptoms at rest (52.5%). In 14 cases, the schwannoma was located PTT, in 17 cases ATT, and in 9 cases DTT in the plantar nerves. There were no significant differences in size and symptom duration at presentation for the different locations. Tumor size did not correlate with symptom severity. Outcomes after resection were excellent, with complete pain relief in all but 1 patient (97.0%). Complications included wound infection (5%) and temporary decreased sensation on the heel (7.5%). A review of 44 previously reported cases also frequently showed complete pain relief after resection. CONCLUSIONS: The results of this study show that schwannomas around the tarsal tunnel often present with severe pain symptoms, even if the lesion is still relatively small. Resection frequently results in excellent pain relief. During surgery, it may not be necessary to open the entire length of the tarsal tunnel, thereby limiting the size of the incision, especially in schwannomas located proximally or distally to the tarsal tunnel.

Humans

Comparative Efficacy of Different AI Systems for Polyp Detection by Size During Colonoscopy: Systematic Review and Network Meta-Analysis.

BACKGROUND: Colorectal cancer remains a leading cause of death despite being largely preventable through polypectomy. AI systems designed to enhance polyp detection during colonoscopy have shown promise, but the extent to which they improve detection of different-sized polyps remains unclear. OBJECTIVE: This study compared the size-stratified efficacy of AI-assisted colonoscopy vs standard colonoscopy using the Hartung-Knapp-Sidik-Jonkman (HKSJ) method, and generated exploratory rankings while acknowledging all cross-platform comparisons are indirect. METHODS: This systematic review and network meta-analysis (NMA) searched PubMed, Embase, Cochrane CENTRAL, and Web of Science from inception to July 25, 2026, supplemented by citation searching. We included randomized controlled trials (RCTs) comparing AI-assisted vs standard colonoscopy in adults (&#x2265;18 years of age), reporting mean polyp detection counts stratified by size (&#x2264;5 mm, 6-9 mm, and &#x2265;10 mm). Two reviewers screened studies, extracted data, and assessed risk of bias using the Cochrane Risk of Bias 2.0. We conducted frequentist NMA using the HKSJ method with restricted maximum likelihood estimation, calculated 95% prediction intervals (PIs), and assessed heterogeneity using I2 and &#x3c4;2. Certainty of evidence was rated using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework. RESULTS: A total of 13 RCTs (4156 participants) compared 8 AI systems to standard colonoscopy, forming a network without direct AI comparisons. For diminutive polyps (&#x2264;5 mm), AI showed a modest advantage (standardized mean difference [SMD] 0.21, 95% CI 0.07 to 0.35, 95% PI -1.12 to 1.54), but substantial heterogeneity (I2=86.6%) and wide PI crossing the null indicated high uncertainty. EndoScreener showed the most consistent evidence (SMD 0.36, 95% CI 0.18-0.54). For small and large polyps, effects were minimal (SMD 0.02, 95% CI -0.02 to 0.06, 95% PI -0.03 to 0.07; SMD 0.01, 95% CI 0.00-0.02, 95% PI -0.01 to 0.03). GRADE certainty was very low for diminutive polyps and low for small and large polyps. Sensitivity analysis excluding Tianjin YuJin did not materially change findings. CONCLUSIONS: AI may modestly enhance diminutive polyp detection, but effects on small and large polyps are minimal, with no platform superiority. Given very low to low certainty, findings are hypothesis-generating. This exploratory NMA provides size-stratified comparisons that can inform future head-to-head trial design. Unlike prior reviews aggregating all polyp sizes, we show the overall AI benefit is driven by diminutive polyp detection, providing a framework for targeted deployment-prioritizing AI for diminutive polyp screening, with limited value for larger lesions. Head-to-head trials are urgently needed. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD420251266932; https://www.crd.york.ac.uk/PROSPERO/view/CRD420251266932.

Colonoscopy

Remotely Supervised, Home-Based Transcranial Direct Current Stimulation for Major Depressive Disorder: Systematic Review and Meta-Analysis.

BACKGROUND: Major depressive disorder affects over 280 million people worldwide, and access to effective treatment remains limited. Transcranial direct current stimulation (tDCS) is a noninvasive option, and portable devices now allow for home-based delivery under varying degrees of remote supervision. OBJECTIVE: This study aimed to systematically review and meta-analyze the efficacy, safety, feasibility, and acceptability of home-based and remotely supervised tDCS for depressive disorders. METHODS: Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 and PRISMA-S (Preferred Reporting Items for Systematic Reviews and Meta-Analyses literature search extension) guidelines, we searched MEDLINE, Embase, Web of Science, the Cochrane databases, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform up to July 2025, with backward and forward citation searching. Two reviewers independently screened records, extracted data, and assessed risk of bias (version 2 of the Cochrane risk-of-bias tool for randomized trials, Newcastle-Ottawa Scale for observational studies, and Critical Appraisal Skills Programme for qualitative studies) and certainty of evidence (Grading of Recommendations Assessment, Development, and Evaluation; GRADE). RESULTS: This review included 12 distinct studies (16 reports), of which 6 (50%) were randomized sham-controlled trials forming the meta-analytic pool. Active home-based tDCS produced a small, statistically significant improvement over sham (pooled Hedges g=0.36, 95% CI 0.06-0.66; P=.03; I2=34.3%). The effect was not robust to removal of the single largest positive trial (omitting the one study from 2025: g=0.39, 95% CI -0.12 to 0.91), and trial-level results were mixed: the 2 largest trials (one unsupervised [n=210] and one self-administered [n=141]) were negative on their primary depression outcomes, whereas the largest real-time supervised trial (n=174) was positive (between-group 95% CI 0.51-4.01; P=.01). This estimate was concordant in direction with an independent peer-reviewed meta-analysis of overlapping trials, which reported a pooled Montgomery-&#xc5;sberg Depression Rating Scale reduction (weighted mean difference -2.74, 95% CI -4.19 to -1.29) and Hamilton Depression Rating Scale reduction (weighted mean difference -2.24, 95% CI -4.16 to -1.49), attenuating to nonsignificance (P>.05) in major depressive disorder without comorbid cognitive impairment. The pooled effect fell at or near the minimal clinically important difference. GRADE certainty was moderate. Adverse events were predominantly mild: one pilot study was terminated early for skin lesions, and one nonfatal suicide attempt occurred in an unsupervised trial. CONCLUSIONS: Home-based and remotely supervised tDCS produces a small, statistically significant but clinically modest antidepressant effect that is sensitive to the inclusion of the largest positive trial, with the 2 largest trials being negative. The available controlled evidence does not establish supervision intensity as a determinant of efficacy. Current data are insufficient to recommend routine clinical adoption; adequately powered trials with standardized supervision and longer follow-up are needed.

Humans