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Background The aim of the current meta‐analysis was to investigate predictors of the durability of the antidepressant effect of high‐frequency (>1 Hz) repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex in the absence of active maintenance treatment. Methods Following a systematic literature search of Medline and PsycInfo, N = 16 double‐blind, parallel‐design, randomized‐controlled trials (RCTs) with high‐frequency rTMS and inactive sham were included in the current meta‐analysis. The effect size (Cohen's d) was the standardized mean difference in depression scores between sham and rTMS groups (baseline –follow‐up). Meta‐analysis was conducted according to a random‐effects model with inverse‐variance weights. Results Most RCTs reported only short follow‐up phases of 2 weeks (range of 1–16 weeks). The antidepressant effect was observed during follow‐up (in the absence of maintenance treatment) compared to baseline (overall mean weighted d = –.48, 95% confidence interval: –.70, –.25, P < .001, N = 16 RCTs with 495 patients). Such an antidepressant effect during follow‐up was higher in RCTs with patients who were less severely ill, unipolar, nonpsychotic, treatment‐resistant, and on antidepressants (either started with rTMS or continued at stable doses during acute treatment phases). The effect sizes were lower in RCTs with longer (8–16 weeks) compared to shorter (1–4 weeks) follow‐up periods. The risk of publication bias was low. Conclusions High‐frequency rTMS has only a small antidepressant effect during follow‐up after short acute treatment (5–15 sessions) in the absence of active maintenance treatment. This effect depends on illness severity, decreases over time, and appears to be enhanced by antidepressants.

Recently, the development of dental materials has increased the availability of various hyperesthesia desensitizers. However, there are no studies on the duration of retreatment in terms of adherence rates. Thus, the adhesion rates of resin-based desensitizers were investigated. We used a conventional desensitizer and a recently developed desensitizer containing calcium salt of 4-methacryloxyethyl trimellitic acid (C-MET) and 10-methacryloyloxydecyl dihydrogen calcium phosphate (MDCP). These colored agents were applied to the surfaces of premolars and molars, and the area was measured from weekly oral photographs. Areas were statistically analyzed and mean values were calculated using 95% confidence intervals. A p-value of <0.05 was considered statistically significant. These rates were significantly higher on the buccal side of the maxilla and lower on the lingual side of the maxilla. In addition, the desensitizer containing C-MET and MDCP displayed significantly higher adhesion rates. It is suggested that this will require monthly follow-ups and reevaluation because both agents cause less than 10% adherence and there is almost no sealing effect after 4 weeks. In addition, the significantly higher adhesion rate of the desensitizer containing C-MET and MDCP indicated that the novel monomer contributed to the improvement in the adhesion ability.

All s are available in Spanish and Mandarin Chinese on Wiley Online Library (http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1545‐5300). Please pass this information on to your international colleagues and students. Systemic therapy is a widely used psychotherapy approach. Yet there exist few systematic reviews on its efficacy. A meta‐content analysis was performed to analyze the efficacy of systemic therapy for the treatment of mental disorders in adulthood. All randomized (or matched) controlled trials (RCT) evaluating systemic/systems oriented therapy in various settings (family, couple, individual, group, multifamily group therapy) with adult index patients suffering from mental disorders were identified by database searches and cross‐references in other reviews. Inclusion criteria were: index patient diagnosed with a DSM or ICD listed mental disorder, trial published in any language up to the end of 2008. The RCTs were content analyzed according to their research methodology, interventions applied, and results. Thirty‐eight trials published in English, German, Spanish, and Chinese were identified, 34 of them showing systemic therapy to be efficacious for the treatment of mood disorders, eating disorders, substance use disorders, mental and social factors related to medical conditions and physical disorders, and schizophrenia. Systemic therapy may also be efficacious for anxiety disorders. Results were stable across follow‐up periods of up to 5 years. There is a sound evidence‐base for the efficacy of systemic therapy for adult index patients with mental disorders in at least five diagnostic groups. RESUMEN Introducción: La terapia sistémica es un enfoque psicoterapéutico muy utilizado, sin embargo, existen pocas evaluaciones sistemáticas sobre su eficacia. Se realizó un análisis de metacontenido a fin de analizar la eficacia de la terapia sistémica para el tratamiento de trastornos mentales en la adultez. Métodos: Mediante búsquedas en bases de datos y remisiones en otras evaluaciones se identificaron todas las pruebas controladas aleatorias (o emparejadas) que evaluaban la terapia sistémica en varios contextos (terapia familiar, de pareja, individual, grupal, multifamiliar) con pacientes índice adultos que padecían trastornos mentales. Los criterios de inclusión fueron: paciente índice diagnosticado con un trastorno mental listado en el “Manual diagnóstico y estadístico de los trastornos mentales” (DSM, por sus siglas en inglés) o en la “Clasificación internacional de enfermedades” (ICD), prueba publicada en cualquier idioma hasta fines de 2008. Se analizó el contenido de las pruebas controladas aleatorias de acuerdo con su metodología de investigación, intervenciones aplicadas y resultados. Resultados: Se identificaron 38 pruebas publicadas en inglés, alemán, español y chino, 34 de las cuales demostraron la eficacia de la terapia sistémica para el tratamiento de trastornos del estado de ánimo, trastornos alimenticios, trastornos de abuso de sustancias, factores mentales y sociales relacionados con problemas de salud y trastornos físicos, y esquizofrenia. La terapia sistémica también puede ser eficaz para los trastornos de la ansiedad. Los resultados fueron estables durante periodos de seguimiento de hasta 5 años. Debate: Existe una base sólida de evidencia en relación con la eficacia de la terapia sistémica para pacientes índice adultos con trastornos mentales en por lo menos cinco grupos diagnósticos. Palabras clave: Terapia sistémica, terapia familiar con orientación sistémica, terapia de parejas, terapia familiar, terapia de grupo multifamiliar, terapia individual, prueba controlada aleatoria, eficacia, investigación sobre terapia.

Dysmenorrhea causes pain and inconvenience during menstruation. In addition to medication, natural compounds are widely used to relieve various types of pain. In this study, we aimed to assess the effects of vitamin D (vit. D) supplementation in relieving the symptoms of primary dysmenorrhea. A comprehensive systematic database search of randomized controlled trials (RCTs) was performed. Oral forms of vit. D supplementation were included and compared with a placebo or standard care. The degree of dysmenorrhea pain was measured with a visual analogue scale or numerical rating scale. Outcomes were compared using the standardized mean difference (SMD) and 95% confidence intervals (CIs) in a meta-analysis. RCTs were assessed using the Cochrane risk-of-bias v2 (RoB 2) tool. The meta-analysis included 8 randomized controlled trials involving 695 participants. The results of the quantitative analysis showed a significantly lower degree of pain in the vit. D versus placebo in those with dysmenorrhea (SMD: −1.404, 95% CI: −2.078 to −0.731). The results of subgroup analysis revealed that pain lessened when the average weekly dose of vit. D was over 50,000 IU, in which dysmenorrhea was relieved regardless of whether vit. D was administered for more or less than 70 days and in any dose interval. The results revealed that vit. D treatment substantially reduced the pain level in the primary dysmenorrhea population. We concluded that vit. D supplementation is an alternative treatment for relieving the pain symptoms of dysmenorrhea.

Recent open-label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression. To test the antidepressant effects of ayahuasca, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 29 patients with treatment-resistant depression. Patients received a single dose of either ayahuasca or placebo. We assessed changes in depression severity with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale at baseline, and at 1 (D1), 2 (D2), and 7 (D7) days after dosing. We observed significant antidepressant effects of ayahuasca when compared with placebo at all-time points. MADRS scores were significantly lower in the ayahuasca group compared with placebo at D1 and D2 (p = 0.04), and at D7 (p < 0.0001). Between-group effect sizes increased from D1 to D7 (D1: Cohen's d = 0.84; D2: Cohen's d = 0.84; D7: Cohen's d = 1.49). Response rates were high for both groups at D1 and D2, and significantly higher in the ayahuasca group at D7 (64% v. 27%; p = 0.04). Remission rate showed a trend toward significance at D7 (36% v. 7%, p = 0.054). To our knowledge, this is the first controlled trial to test a psychedelic substance in treatment-resistant depression. Overall, this study brings new evidence supporting the safety and therapeutic value of ayahuasca, dosed within an appropriate setting, to help treat depression. This study is registered at http://clinicaltrials.gov (NCT02914769).

To evaluate an approach using automation and crowdsourcing to identify and classify randomized controlled trials (RCTs) for rheumatoid arthritis (RA) in a living systematic review (LSR). Records from a database search for RCTs in RA were screened first by machine learning and Cochrane Crowd to exclude non-RCTs, then by trainee reviewers using a Population, Intervention, Comparison, and Outcome (PICO) annotator platform to assess eligibility and classify the trial to the appropriate review. Disagreements were resolved by experts using a custom online tool. We evaluated the efficiency gains, sensitivity, accuracy, and interrater agreement (kappa scores) between reviewers. From 42,452 records, machine learning and Cochrane Crowd excluded 28,777 (68%), trainee reviewers excluded 4,529 (11%), and experts excluded 7,200 (17%). The 1,946 records eligible for our LSR represented 220 RCTs and included 148/149 (99.3%) of known eligible trials from prior reviews. Although excluded from our LSRs, 6,420 records were classified as other RCTs in RA to inform future reviews. False negative rates among trainees were highest for the RCT domain (12%), although only 1.1% of these were for the primary record. Kappa scores for two reviewers ranged from moderate to substantial agreement (0.40–0.69). A screening approach combining machine learning, crowdsourcing, and trainee participation substantially reduced the screening burden for expert reviewers and was highly sensitive.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint pain, swelling, and stiffness, affecting approximately 1% of the adult population. Tocilizumab (TCZ), a monoclonal antibody targeting the IL-6 receptor, has emerged as an effective treatment for RA. This narrative review provides an update on TCZ’s efficacy and safety based on data from randomized controlled trials (RCTs) and real-world evidence (RWE). TCZ, available in subcutaneous (SC) and intravenous (IV) formulations, has shown significant benefits in RA management. Key clinical trials, including SAMURAI, OPTION, RADIATE, and TOWARD, have demonstrated TCZ’s efficacy as monotherapy and in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), particularly in patients with inadequate responses to methotrexate or TNF inhibitors. Long-term studies, such as STREAM, have highlighted TCZ’s sustained efficacy and favorable safety profile over 5 years. The impact of TCZ on cardiovascular health, lipid profiles, and the risk of infections has been a focal point, with findings suggesting no significant increase in cardiovascular disease risk compared to other RA therapies. RWE further highlights the effectiveness of TCZ, identifying predictors of response, such as age, and emphasizes its suitability for biologic-naïve and overweight patients. Special considerations include TCZ use in RA-associated interstitial lung disease and amyloidosis. Overall, TCZ remains a pivotal option in RA treatment, with a well-established safety and efficacy profile supported by extensive clinical and real-world data.

Older adults are more susceptible to severe health outcomes for coronavirus disease 2019 (COVID-19). Universal vaccination has become a trend, but there are still doubts and research gaps regarding the COVID-19 vaccination in the elderly. This study aimed to investigate the efficacy, immunogenicity, and safety of COVID-19 vaccines in older people aged ≥ 55 years and their influencing factors. Randomized controlled trials from inception to April 9, 2022, were systematically searched in PubMed, EMBASE, the Cochrane Library, and Web of Science. We estimated summary relative risk (RR), rates, or standardized mean difference (SMD) with 95% confidence interval (CI) using random-effects meta-analysis. This study was registered with PROSPERO (CRD42022314456). Of the 32 eligible studies, 9, 21, and 25 were analyzed for efficacy, immunogenicity, and safety, respectively. In older adults, vaccination was efficacious against COVID-19 (79.49%, 95% CI: 60.55-89.34), with excellent seroconversion rate (92.64%, 95% CI: 86.77-96.91) and geometric mean titer (GMT) (SMD 3.56, 95% CI: 2.80-4.31) of neutralizing antibodies, and provided a significant protection rate against severe disease (87.01%, 50.80-96.57). Subgroup and meta-regression analyses consistently found vaccine types and the number of doses to be primary influencing factors for efficacy and immunogenicity. Specifically, mRNA vaccines showed the best efficacy (90.72%, 95% CI: 86.82-93.46), consistent with its highest seroconversion rate (98.52%, 95% CI: 93.45-99.98) and GMT (SMD 6.20, 95% CI: 2.02-10.39). Compared to the control groups, vaccination significantly increased the incidence of total adverse events (AEs) (RR 1.59, 95% CI: 1.38-1.83), including most local and systemic AEs, such as pain, fever, chill, etc. For inactivated and DNA vaccines, the incidence of any AEs was similar between vaccination and control groups ( > 0.1), while mRNA vaccines had the highest risk of most AEs (RR range from 1.74 to 7.22). COVID-19 vaccines showed acceptable efficacy, immunogenicity and safety in older people, especially providing a high protection rate against severe disease. The mRNA vaccine was the most efficacious, but it is worth surveillance for some AEs it caused. Increased booster coverage in older adults is warranted, and additional studies are urgently required for longer follow-up periods and variant strains.

Trial emulation, also known as target trial emulation, has significantly advanced epidemiology and causal inference by providing a robust framework for deriving causal relationships from observational data. This approach aims to reduce biases and confounding factors inherent in observational studies, thereby improving the validity of causal inferences. By designing observational studies to mimic randomized controlled trials (RCTs) as closely as possible, researchers can better control for confounding and bias. Key components of trial emulation include defining a clear time-zero, simulating random assignment using techniques like propensity score matching and inverse probability treatment weighting, assessing group comparability by standardized mean differences and establishing a clear comparison strategy. The increasing availability of large-scale real-world databases, such as research cohorts, patient registries, and hospital records, has driven the popularity of target trial emulation. These data sources offer information on patient outcomes, treatment patterns, and disease progression in real-world settings. By applying the principles of target trial emulation to these rich data sources, researchers can design studies that provide robust causal inferences about the effects of interventions, informing clinical guidelines and regulatory decisions. Despite its advantages, trial emulation faces challenges like data quality, unmeasured confounding, and implementation complexity. Future directions include integrating trial emulation with machine learning techniques and developing methods to address unmeasured confounding. Overall, trial emulation represents a significant advancement in epidemiology, offering a valuable tool for deriving accurate and reliable causal inferences from observational data, ultimately improving public health outcomes. Graphical abstract

Background: Cold atmospheric plasma (CAP) therapy has emerged as a novel nonthermal modality for managing chronic wounds. However, its clinical efficacy relative to standard wound care remains uncertain. This systematic review and meta‐analysis aimed to evaluate the effectiveness of CAP in promoting complete wound healing. Method: An extensive literature search was performed across major databases for randomized controlled trials (RCTs) published between January 2005 and January 2025. Eligible studies included adult patients with chronic wounds treated with CAP compared to standard care or placebo. The primary outcome was complete wound healing. Risk ratios (RRs) with 95% confidence intervals (CIs) were synthesized using a random‐effects model in RStudio with the metafor package. Results: Three RCTs comprising 149 participants (CAP group: 76; control group: 73) were included. The fixed‐effects meta‐analysis demonstrated that CAP therapy radically improved wound healing outcomes compared to standard care, with a pooled RR of 3.53 (95% CI: 2.12–5.89; p < 0.001). However, the random‐effects model yielded a nonsignificant result (RR = 3.31; 95% CI: 0.35–31.59; p = 0.150) and revealed substantial heterogeneity ( I 2  = 68.9%, Q  = 6.44, p = 0.040). Random‐effects analysis was nonsignificant; findings are suggestive and require confirmation through larger, rigorous randomized trials. Conclusions: CAP therapy significantly enhances complete wound healing in patients with chronic wounds and demonstrates a favorable safety and efficacy profile. These findings support CAP as a promising adjunct to standard wound care.