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Examining Behavioral Interventions for Infancy and Early Toddlerhood: A Systematic Review of Intervention Effects, Parameters, and Participants.

Rapid advancement is paving the way to identify children who would likely benefit from early intervention during the first years of life, prior to the onset of significant delays in development. With the widely acknowledged benefits of early intervention, key questions arise: Does behavioral intervention targeted to infancy and early toddlerhood improve developmental outcomes? What procedures might be used, and under what circumstances? Who do these interventions work for? The current review comprehensively examined the literature on behavioral interventions based in operant learning, focused on key developmental areas with children in the first two years of life. We located and synthesized 69 studies with unique participant cohorts that included 1735 children. The search revealed many studies focused on the first year of life, of which a large proportion investigated approaches to increase communication. We provide implications, limitations, and future directions on how behavioral interventions for infants and young toddlers can inform current practice and future intervention research this population.

Humans

Clinical Performance of Bulk-Fill Versus Incremental Composite Placement Approaches in Vital Posterior Teeth: A 24 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

Mobile health apps improve Health-Related Quality of Life in Type 2 Diabetes Mellitus by enhancing medication adherence: A multicentre randomised controlled trial with mediation analysis.

AIMS: This study evaluated whether a gamified mHealth application (CareAide&#xae;) improves Health-Related Quality of Life (HRQoL) in Type 2 Diabetes Mellitus (T2DM) and whether this effect is mediated by medication adherence. METHODS: Prespecified secondary analysis of the T2DM cohort from a 6-month multicentre RCT (NCT06068309; N&#x202f;=&#x202f;663; three Malaysian hospitals). Participants were randomised 1:1 to standard care or CareAide&#xae;. Adherence (MMAS-8), EQ-5D-5L utility (Malaysian value set), and AQoL-6D were assessed at baseline and 6 months. Simple mediation analysis (PROCESS Model 4; 5000 bootstraps) adjusted for baseline HRQoL. RESULTS: CareAide&#xae; significantly predicted higher MMAS-8 scores (mean difference +1.756; d = 1.638; p&#x202f;<&#x202f;0.001). Higher MMAS-8 scores significantly predicted improved AQoL-6D utility (b = 0.024; p&#x202f;<&#x202f;0.001). The direct effect on AQoL-6D was non-significant (p&#x202f;=&#x202f;0.248). Bootstrapped indirect effect confirmed full mediation via AQoL-6D (0.042; 95% CI [0.024, 0.060]). A sensitivity analysis adjusting for baseline HbA1c confirmed full mediation (indirect = 0.034; 95% CI [0.015, 0.052]; n&#x202f;=&#x202f;563). EQ-5D-5L utility showed a significant direct between-group difference at 6 months (p&#x202f;=&#x202f;0.012) but did not operate as a mediation outcome. CONCLUSIONS: Medication adherence fully mediates the AQoL-6D HRQoL benefit of a gamified mHealth intervention in T2DM, as confirmed by both the primary and HbA1c-adjusted sensitivity analyses. These findings support integration of behaviourally informed digital adjuncts into routine primary diabetes care.

Humans

Predicting training outcomes for developmental dyslexia from EEG data.

Developmental dyslexia (DD) is characterised by lower-than-average reading abilities and is diagnosed in approximately 10% of individuals. The societal barriers may limit professional fulfilment and psychological wellbeing of individuals with DD, calling for the development of effective interventions to counteract them. As DD is associated with challenges in both phonological and visuo-attentional domains, different longitudinal training approaches were developed to strengthen them. However, they require a considerable amount of personal, social and economic resources and the outcomes may vary depending on individual differences in behavioural and neurophysiological functionality. Hence, predicting training outcomes might help in developing personalised treatment protocols and optimising the use of resources. In the present work we applied machine learning to resting-state EEG to predict longitudinal training outcomes in adults with DD enrolled in a randomized clinical trial. In particular, one group received a visuo-attentional training combined with transcranial alternating current stimulation (tACS), another group received visuo-attentional training with sham/placebo stimulation, and the third group received a phonological training with sham/placebo stimulation. The improvement in text reading speed was associated with spectral power in low-beta and individual frequencies in the alpha (IAF) and beta (IBF) bands, while the improvement in pseudoword reading was associated with IBF. The findings highlight the potential of capturing neural markers of treatment responsiveness in DD. Future studies should focus on the generalisability of predictive models to real-world settings, while investigating whether specific EEG markers predict responsiveness to distinct remediation protocols, thus supporting the development of personalised interventions.

Humans

Relationship between participant-reported outcomes, residual beta cell function and metabolic parameters in youth with newly diagnosed type 1 diabetes.

AIMS/HYPOTHESIS: Clinical trials of interventions to preserve beta cell function in new-onset type 1 diabetes frequently employ participant-reported outcome measures (PROMs). However, the expected changes in PROMs scores immediately following diagnosis and their association with residual beta cell function, metabolic markers and continuous glucose monitoring (CGM) are unclear. METHODS: Repeated PROMs including Paediatric Quality of Life Inventory diabetes module (PedsQL) and hypoglycaemia fear survey (HFS) were recorded from participants aged 10-18 years with newly diagnosed type 1 diabetes and their parents in two clinical trials: CLOuD (N=97, hybrid closed loop [HCL] vs multiple daily injections [MDI]) and USTEKID (N=72, ustekinumab immunotherapy vs placebo). Scores were compared with serial mixed meal-stimulated C-peptide levels (AUC C-peptide), HbA1c and CGM data. RESULTS: PedsQL and HFS scores for children/adolescents and their parents showed wide variation between individuals but did not change substantially within individuals over the first 48 months from diagnosis. Baseline scores were highly predictive of scores at 12-48 months (p<0.001). PedsQL scores were higher (better) in those reported by children/adolescents than by their parents (p<0.01). In contrast, HFS scores were higher in parents than children (p<0.001), indicating more fear. Strong correlations were observed between child and parent scores (p<0.001). No significant improvement in these scores was detected following intervention (ustekinumab or HCL). Meta-analysis revealed modest but statistically significant associations between HbA1c and PedsQL (&#x3b2;(std)=-0.11; 95% CI -0.20, -0.03) and HFS (&#x3b2;(std)=0.11; 95% CI 0.00, 0.21), and between CGM time in range and PedsQL (&#x3b2;(std)=0.14; 95% CI 0.03, 0.26) but not HFS (&#x3b2;(std)=-0.05; 95% CI -0.16, 0.06). Beta cell function (AUC C-peptide) was strongly associated with HbA1c (&#x3b2;(std)=-0.29; 95% CI -0.39, -0.20) and CGM time in range (&#x3b2;(std)=0.41; 95% CI 0.30, 0.52). Higher beta cell function showed a trend towards better PedsQL (&#x3b2;(std)=0.11; 95% CI -0.03, 0.25) and lower HFS (&#x3b2;(std)=-0.05; 95% CI -0.17, 0.07) but this did not reach statistical significance. CONCLUSIONS/INTERPRETATION: PedsQL and HFS scores changed little during the first 48 months after diagnosis of type 1 diabetes. These scores showed modest but statistically significant associations with measures of glucose management (HbA1c and CGM time in range), whereas the relationships with residual beta cell function (C-peptide) were weaker and did not reach significance. The modest size of these effects suggests current PROMs capture only limited aspects of the clinical benefit associated with beta cell preservation. Future research should incorporate psychometric instruments that are specifically adapted for young people using modern diabetes technologies and undergoing disease-modifying therapy, to ensure outcomes are meaningfully represented in early-stage type 1 diabetes trials.

Adolescent

Comparative effects of 12-week resistance training on unstable and stable surfaces on muscle stiffness, muscle co-activation, and balance in older patients with knee osteoarthritis.

OBJECTIVE: This randomized trial compared the effects of unstable resistance training (URT), involving resistance exercises on unstable surfaces, and stable resistance training (SRT), performed on stable surfaces, on muscle stiffness, co-activation, and balance in older adults with knee osteoarthritis (KOA). We hypothesized that URT would yield greater improvements by enhancing neuromuscular adaptability. METHODS: Fifty patients with KOA were randomly assigned to the URT group (n&#x202f;=&#x202f;25) or the SRT group (n&#x202f;=&#x202f;25). After attrition, 46 participants (URT: n&#x202f;=&#x202f;23; SRT: n&#x202f;=&#x202f;23) completed the intervention and were included in the final analysis. Both groups completed a 12-week supervised lower-limb resistance training program (3 sessions/week) consisting of 10 exercises performed under either unstable or stable support conditions. RESULTS: After 12 weeks of intervention, both groups showed significant reductions in pain intensity (p&#x202f;<&#x202f;0.001). However, compared with the SRT group, the URT group demonstrated significantly greater reductions in quadriceps stiffness (p&#x202f;<&#x202f;0.05), selected hamstring stiffness outcomes (p&#x202f;<&#x202f;0.05), and quadriceps-hamstring co-activation (p&#x202f;<&#x202f;0.001), alongside superior improvements in both dynamic balance and static balance (all p&#x202f;<&#x202f;0.05). CONCLUSION: While both training modalities are effective for pain relief, URT elicited greater improvements in balance-related performance and neuromuscular-mechanical outcomes than SRT in older adults with KOA. These findings suggest that incorporating unstable support conditions into resistance training may provide additional rehabilitation benefits for this population.

Humans

Vaginal Hysterectomy Versus Vaginal Assisted Natural Orifice Transluminal Endoscopic Surgery Hysterectomy; Results of a Randomised Controlled Trial.

OBJECTIVE: To compare Vaginal Hysterectomy (VH) with Vaginal Assisted Natural Orifice Transluminal Endoscopic Surgery (NOTES) hysterectomy (VANH) as a day-care procedure. DESIGN: Single-blind, multicentre randomised controlled trial. SETTING: Two Dutch non-academic teaching hospitals. POPULATION: Women aged &#x2265;&#x2009;18&#x2009;years undergoing hysterectomy for benign indications. METHODS: Women were randomised 1:2 (VH or VANH). Primary outcome was SDD. Secondary outcomes included operative time, rate of elective salpingectomies, intraoperative blood loss, complications (Clavien-Dindo), pain scores (NRS) and analgesic use, post-operative recovery (RI-10), and quality of life (EQ-5D-5L). Analyses were performed on an intention-to-treat basis. RESULTS: A total of 113 patients were included in the analyses (n&#x2009;=&#x2009;42 VH, and n&#x2009;=&#x2009;71 VANH). SDD occurred significantly more frequently in the VANH group (87.3%) than VH group (71.4%; OR 2.76, 95% CI 1.04-7.25; p&#x2009;=&#x2009;0.04). VANH was associated with a significantly shorter operative time (median 55&#x2009;min versus 65&#x2009;min; p&#x2009;=&#x2009;0.005), less blood loss (median 50&#x2009;mL vs. 150&#x2009;mL; p&#x2009;<&#x2009;0.001) and more often elective opportunistic salpingectomy compared to VH (100% vs. 77.4%; p&#x2009;=&#x2009;0.008). NRS were significantly lower in the VANH group the first hour post-operative (3 vs. 1, p&#x2009;<&#x2009;0.001). Post-operative complications (VH 9.5% vs. VANH 15.5%; p&#x2009;=&#x2009;0.34), readmission (VH 4.8% vs. VANH 8.5%; p&#x2009;=&#x2009;0.47), analgesic use, recovery, and quality of life were not statistically significant. CONCLUSIONS: VANH is a safe and effective alternative to VH, offering a higher likelihood of SDD, shorter operative time, reduced blood loss, and more often an elective salpingectomy, without increased complications or differences in pain, recovery, or quality of life.

Humans

Insulin, Semaglutide and Dapagliflozin in Adults With Type 1 Diabetes: Design and Methods of Triple Therapy for Type 1 Diabetes (TTT1)-An International Phase 3 Clinical Trial.

AIMS: Attaining target glycaemia can be a challenge in Type 1 Diabetes (T1D) due to insulin-induced weight gain. Adjunct therapy with modern glucose-lowering agents developed for type 2 diabetes (T2D) has great potential but may be insufficiently efficacious and carries risks of hypoglycaemia and ketosis. We designed the first Phase 3 clinical trial to assess the efficacy and safety of adding a Glucagon-Like Peptide 1 receptor agonist (GLP-1RA) and a Sodium-Glucose Co-transporter (SGLT2) Inhibitor to insulin therapy in overweight and obese adults with T1D and glycaemia above target (HbA1c 7.5%-11.0% inclusive) (NCT03899402). MATERIALS AND METHODS: In Period 1, participants are randomized 2:1 (open label) for 26&#x2009;weeks to semaglutide and insulin (uptitrated to 1.0&#x2009;mg weekly) or standard insulin therapy. In Period 2, those randomized to semaglutide and insulin in Period 1 are further randomized (double-blind) for 26&#x2009;weeks to dapagliflozin (10&#x2009;mg daily) or placebo, in addition to semaglutide. The primary objective is to compare change in HbA1c on 'triple therapy' (dapagliflozin, semaglutide and insulin) with 'dual therapy' (placebo, semaglutide and insulin). Secondary objectives include comparisons of triple therapy with standard insulin therapy and dual therapy (semaglutide and insulin) with standard insulin therapy. Safety outcomes include hypoglycaemia and ketosis. A sample size recalculation during the trial based on analysis of masked data revised the original recruitment target from 114 to 82 participants. CONCLUSION: The TTT1 trial will provide clinically useful information on combination adjunct therapy in the treatment of T1D.

Humans

Impact of oliceridine versus sufentanil on postoperative nausea and vomiting in patients undergoing thyroid surgery: a prospective, double-blind, randomized controlled trial.

PURPOSE: Postoperative nausea and vomiting (PONV) is a common complication following thyroid surgery, often exacerbated by opioid use. Oliceridine, a novel G protein-biased &#x3bc;-opioid receptor agonist, may reduce opioid-related adverse events. This study aimed to compare the impact of oliceridine versus sufentanil on the incidence and severity of PONV in patients undergoing thyroid surgery. PATIENTS AND METHODS: In this prospective, double-blind, randomised controlled trial conducted between May 2025 and February 2026, 232 patients scheduled for thyroid surgery were randomly assigned to receive either oliceridine or sufentanil for intraoperative analgesia. The primary outcome was the incidence of PONV during the first 48&#x2009;h postoperatively. Secondary outcomes included PONV severity, need for rescue anti-emetics, postoperative pain scores, recovery quality, and other adverse events. RESULTS: The incidence of PONV within 48&#x2009;h postoperatively was significantly lower in the oliceridine group [13/107 (12%)] compared with the sufentanil group [31/110 (28%)] (OR = 0.35, 95% CI: 0.17-0.72, p&#x2009;=&#x2009;0.006). Postoperative pain scores, rescue analgesia requirements, and Quality of Recovery-15 scores were comparable between the two groups (p&#x2009;>&#x2009;0.05). Besides, exploratory unadjusted analyses revealed fewer rescue anti-emetics: O group 8/107 (8%) vs S group 25/110 (23%) (OR = 0.27, 95% CI: 0.12-0.64, p&#x2009;=&#x2009;0.002); and less abdominal distension: O group 4/107 (4%) vs S group 19/110 (17%) (OR = 0.19, 95% CI: 0.06-0.57, p&#x2009;=&#x2009;0.001). CONCLUSION: For young ASA I-II patients undergoing thyroid surgery, oliceridine yields adequate postoperative analgesia and lower PONV rates versus sufentanil. Additional trials involving high-intensity surgical procedures are needed to confirm consistent equivalence.

Humans

Long-term safety of oral orforglipron in Japanese participants with type 2 diabetes (ACHIEVE-J): a multicentre, randomised, open-label, parallel-group phase 3 trial.

BACKGROUND: Orforglipron, an oral GLP-1 receptor agonist, requires further evaluation in east Asian populations with type 2 diabetes, given this group's distinct pathophysiological characteristics. This study aimed to assess orforglipron as add-on treatment to diet and exercise alone or to oral antihyperglycaemic medications in Japanese participants with type 2 diabetes. METHODS: This multicentre, randomised, open-label phase 3 study was conducted in 40 medical research centres and hospitals in Japan. Adults with type 2 diabetes and elevated glucose levels managing their condition with diet and exercise alone or with one or two oral antihyperglycaemic medications were assigned (1:1:1) via computer-generated random sequence to receive once-daily oral orforglipron (3 mg, 12 mg, or 36 mg). Randomisation was stratified by background therapy, baseline HbA1c (&#x2264;8&#xb7;5% or >8&#xb7;5%), and metformin use (yes vs no; applied only to &#x3b1;-glucosidase inhibitors, thiazolidinedione, and glinides). Investigators, participants, and site staff were not masked to treatment. The primary endpoint was safety for 52 weeks, assessed in all randomly assigned participants who received at least one dose of orforglipron. This study is registered with ClinicalTrials.gov, NCT06010004 (ACHIEVE-J). FINDINGS: Between Sept 28, 2023, and June 5, 2025, 450 participants were screened and 401 were randomly assigned to three groups (3 mg, n=132; 12 mg, n=135; and 36 mg, n=134). 352 (88%) completed study treatment. 339 participants (85%, 95% CI 80&#xb7;7-87&#xb7;8) had at least one treatment-emergent adverse event (TEAE), more frequently in the 36-mg group (118 [88%, 95% CI 81&#xb7;5-92&#xb7;5]) than in the 3-mg (107 [81%, 73&#xb7;5-86&#xb7;8]) and 12-mg (114 [84%, 77&#xb7;4-89&#xb7;6]) groups. Most TEAEs were of mild (267 [67%, 61&#xb7;8-71&#xb7;0]) or moderate (63 [16%, 12&#xb7;5-19&#xb7;6]) severity. Discontinuations due to an adverse event occurred in 19 of 134 participants (14%, 95% CI 9&#xb7;3-21&#xb7;1) in the 36-mg group compared with seven of 132 (5%, 2&#xb7;6-10&#xb7;5) in the 3-mg group and 11 of 135 (8%, 4&#xb7;6-14&#xb7;0) in the 12-mg group. Across treatment groups, gastrointestinal symptoms were the most common TEAEs leading to study treatment discontinuation (3 mg: 5 [3&#xb7;8%, 1&#xb7;6-8&#xb7;6]; 12 mg: 8 [5&#xb7;9%, 3&#xb7;0-11&#xb7;3]; and 36 mg: 11 [8&#xb7;2%, 4&#xb7;7-14&#xb7;1]). Level 2 (blood glucose <54 mg/dL) hypoglycaemia events occurred in three of 135 participants in the 12-mg group (2%, 0&#xb7;8-6&#xb7;3) and in three of 134 in the 36-mg group (2%, 0&#xb7;8-6&#xb7;4) groups. No level 3 (severe) hypoglycaemia events occurred. Outcomes were generally similar across background therapies. INTERPRETATION: Treatment with orforglipron in combination with diet and exercise alone or one or two oral antihyperglycaemic medications for 52 weeks demonstrated an acceptable safety profile in Japanese adults with type 2 diabetes. FUNDING: Eli Lilly. TRANSLATION: For the Japanese translation of the abstract see Supplementary Materials section.

Aged

Associations Between Routine Vaccinations and the Risk of New-Onset Idiopathic Uveitis.

OBJECTIVE: To evaluate the association between vaccination and the risk of new-onset idiopathic uveitis (NIU). DESIGN: Retrospective cohort study of aggregated electronic health records from multiple health systems across the United States. SUBJECTS: Subjects who received the coronavirus disease 2019 (COVID-19), human papillomavirus (HPV), varicella, recombinant herpes zoster, or live herpes zoster vaccinations from 2006 to 2025 and propensity-score matched controls. INTERVENTION: Vaccines against COVID-19, HPV, varicella, recombinant herpes zoster, or live herpes zoster. MAIN OUTCOMES AND MEASURES: The main outcome was the incidence of NIU at 3, 6, and 12 months following vaccination. Vaccinated patients were compared with matched controls who did not receive the respective vaccines. Analyses were repeated, excluding patients with previous diagnosis of the respective viral infection. Risk ratios (RR) with 95% confidence intervals (CIs) were calculated for overall NIU and constituent subtypes (anterior, intermediate, posterior, and panuveitis). RESULTS: All tested vaccinations were associated with reduced risk of NIU through 12 months compared with matched controls. Relative risk reductions were 65% for COVID-19 (RR, 0.35; CI, 0.33-0.37), 56% for HPV (RR, 0.44; CI, 0.35-0.54), 71% for varicella (RR, 0.29; CI, 0.25-0.33), 68% for live zoster (RR, 0.32; CI, 0.23-0.43), and 69% for recombinant zoster vaccination (RR, 0.31; CI, 0.26-0.37). Similar reductions were observed after excluding patients with prior diagnoses of the respective viral infections. CONCLUSIONS: Vaccination was associated with a lower risk of idiopathic uveitis, representing the complex interplay between immune modulation and the development of NIU.

Humans

A randomized trial of viral vector and adjuvanted protein HBV therapeutic vaccine in people with chronic hepatitis B on nucleos(t)ide analogs.

BACKGROUND: This study assessed the safety, efficacy, and immunogenicity of a therapeutic immunization strategy aimed at reaching a functional cure for chronic hepatitis B (CHB), relying on a heterologous prime-boost with viral vectors ChAd155-hIi-HBV and MVA-HBV, combined with sequential or concomitant administration of adjuvanted recombinant HBV proteins (HBc-HBs/AS01B). METHODS: This single-blind, randomized, controlled, first-in-human, phase 1/2 trial enrolled adults aged 18-65 years with HBeAg-negative CHB, virally suppressed on nucleos(t)ide analogs (NAs), with HBsAg >50&#xa0;IU/mL. Participants received NAs and the following regimens of 4 doses (8-week intervals): sequential administration of ChAd155-hIi-HBV, MVA-HBV, and 2 HBc-HBs/AS01B doses; co-administration of ChAd155-hIi-HBV+HBc-HBs/AS01B, followed by 3 co-administered MVA-HBV+HBc-HBs/AS01B doses; 4 HBc-HBs/AS01B doses; 2 placebo doses followed by ChAd155-hIi-HBV and MVA-HBV administered alone or with HBc-HBs/AS01B; or 4 placebo doses. Safety, efficacy (&#x2265;1-log decrease in quantitative (q)HBsAg or HBsAg loss 24 weeks post-dose 4 [day (D)337]), antibody, and T-cell responses were evaluated. RESULTS: In all, 134 participants were vaccinated. Grade 3 solicited adverse events (AEs) (median duration: 2-3 days) were more frequent after co-administration (systemic: 59.3%; administration-site: 33.3%) than sequential administration (systemic: 10.3%; administration-site: 12.8%) of high-dose viral vectors and proteins. No vaccine-related or fatal serious AEs were reported. After 4 doses, no participant had HBsAg loss or &#x2265;1-log decrease in qHBsAg (D337 vs. D1). Co-administration induced the strongest anti-HBs response (73.7% achieved anti-HBs &#x2265;10&#xa0;mIU/mL 2 weeks post-dose 4 vs. 40.0% after sequential administration). Both sequential and co-administration induced HBc-specific CD4+ and CD8+ T-cell responses, with a prime-boost effect of the viral vectors. CONCLUSIONS: Heterologous prime-boost with ChAd155-hIi-HBV and MVA-HBV, combined with sequential or co-administration of HBc-HBs/AS01B, had an acceptable safety profile, were moderately immunogenic, but no participants showed the expected efficacy outcome.

Humans

Effects of Adding Incentive Spirometry to Hospital-Based Cardiovascular Rehabilitation on Pulmonary Complications, Hospital Length of Stay, and Clinical-Functional Recovery After Cardiac Surgery: A Randomized Controlled Trial.

BACKGROUND AND PURPOSE: This study investigated the effects of combining incentive spirometry with cardiac rehabilitation compared with cardiac rehabilitation alone on postoperative pulmonary complications, clinical-functional recovery, and hospital length of stay in patients undergoing cardiac surgery. METHODS: Randomized controlled trial was conducted from May 2019 to October 2023 in two hospitals, including 46 inpatients undergoing cardiac surgery. Participants were assigned to incentive spirometry plus cardiac rehabilitation or cardiac rehabilitation alone. Both interventions were performed twice daily; spirometry used a volume-oriented device, and rehabilitation followed a seven-step protocol (2-4 METs). Outcomes included postoperative pulmonary complications, functional capacity (6-min walk test), handgrip strength, respiratory muscle function, and length of hospital stay. RESULTS: The incentive spirometry associated with cardiac rehabilitation group had a longer extracorporeal circulation time (98&#xa0;&#xb1;&#xa0;26&#xa0;min) than the cardiac rehabilitation group (76&#xa0;&#xb1;&#xa0;1; p&#xa0;=&#xa0;0.008). Both groups showed a postoperative decline in respiratory muscle strength, and walking distance (MD: -64.37&#xa0;m; 95% CI: [-24.1; -104.6]; d&#xa0;=&#xa0;0.71), with no difference in postoperative pulmonary complications and handgrip strength. The incentive spirometry associated with cardiac rehabilitation group did not significantly differ on postoperative hospital stay compared with the cardiac rehabilitation group (MD: -1&#xa0;day; 95% CI: [-4.71; 2.71]; d&#xa0;=&#xa0;-0.19). CONCLUSIONS: In this study, no additional benefit was observed with the addition of incentive spirometry to cardiac rehabilitation compared with cardiac rehabilitation alone. No significant differences were detected between groups in postoperative pulmonary complications, hospital length of stay, or clinical-functional recovery among individuals undergoing cardiac surgery. TRIAL REGISTRATION: Brazilian Registry of Clinical Trials (REBEC) under the number RBR-8tsjf97.

Aged

E-cigarette product characteristics and packaging features and interest in e-cigarette use: Results from a randomized within-person trial nested in three prospective cohorts.

BACKGROUND: Product characteristics and packaging may be key targets for regulation to reduce e-cigarette use among youth, but existing data are limited. METHODS: Data are from an experimental study (2018-2020) nested within three prospective cohorts (age 14-26) in southern California (N&#x2009;=&#x2009;3565). Participants were shown five e-cigarette (e-liquid) packages in a random order that varied in flavor (sweet vs. tobacco), flavor name (descriptive ["blueberry cheesecake"] vs. concept ["smurf cake"] vs. none [number only]), and cartoon image on package (yes/no). For each stimuli, survey items assessed the following outcomes: product appeal (self-enjoyment, others' enjoyment; Likert scale [1-5]), susceptibility to use (use if friends offered, curiosity; 4 ordered responses [definitely not-definitely yes]), peer acceptability (definitely not-definitely yes), and perceived harm (definitely not-definitely yes). Mixed effects proportional odds models evaluated within-person effects of each factor (flavor, flavor name, cartoon) with each outcome. RESULTS: Participants reported greater appeal, susceptibility, and peer acceptability (OR range=3.7-16.9; ps<0.05), and lower perceived harm (OR=0.61; 95%CI=0.53, 0.70) for sweet (vs. tobacco-flavored) e-cigarettes; effects were progressively stronger for younger cohorts. The descriptive flavor name rated higher than the concept flavor (OR range=1.13-2.02; ps<0.05) or number only (OR range=1.18-1.69; ps<0.05) for appeal and susceptibility measures; no differences for concept vs. number were found. The cartoon image rated higher for appeal, curiosity, and peer acceptability (OR range=1.24-1.51; ps<0.05). CONCLUSIONS: Sweet flavors, descriptive flavor names, and cartoon images may increase the appeal of e-cigarettes among youth and young adults with no history of e-cigarette use, and are key targets for regulation.

Humans

Outcomes at rapid diagnostic centres and the association between non-specific symptoms and cancer: A systematic review and meta-analyses of up to 21,392 patients.

INTRODUCTION: Cancer remains a leading cause of mortality and poses a significant public health challenge. Several non-specific symptoms (NSSs) often indicate non-serious disease but can also accompany malignancy even in the absence of organ-specific signs. Therefore, the aim of the study was to comprehensively delineate the association between the most common NSSs (weight loss, fatigue, pain and nausea/appetite loss) and cancer or non-cancer diagnoses. METHODS: Database searches of PubMed and Embase were conducted applying search criteria to identify studies that investigated common NSSs in cancer patients diagnosed through rapid diagnostic centres (RDCs). The quality of the included studies was assessed using a modified Newcastle-Ottawa Scale (NOS). For each symptom, pooled relative risks (RRs) with 95% confidence intervals were derived using random-effects meta-analysis. RESULTS: Eleven studies met the inclusion criteria. All studies were considered to be of high methodological quality. The most frequent disease locations for cancer entities included hematologic, lung and lower gastrointestinal. Together with miscellaneous, rheumatic, and musculoskeletal conditions, these were the most common for non-cancer diagnoses. Nausea/appetite loss showed a statistically significant association with cancer (RR=1.20, 95%-CI 1.07-1.35). Pain showed a non-significant association (RR=1.07, 95%-CI 0.75-1.53) with substantial between-study heterogeneity, and weight loss showed a non-significant inverse trend (RR=0.92, 95%-CI 0.84-1.02). Fatigue showed no association with cancer (RR=1.00, 95%-CI 0.85-1.18). DISCUSSION/CONCLUSION: NSSs may be valuable for cancer risk assessment, but the associations remain modest. The complexity of patients' clinical presentations suggests that additional factors likely influence the cancer risk. Future research should examine symptom combinations and, where data allow, perform subgroup analyses.

Humans

Age at menopause and subjective cognitive symptoms predict digital cognitive outcomes at the gynecological Well-Woman visit.

INTRODUCTION: Women are at increased risk for Alzheimer's Disease (AD). Growing evidence suggests that the menopausal transition may represent a vulnerable window for development of AD-related pathology. Yet, women are diagnosed with AD later than men. Conducting routine cognitive screenings and integrating information about both cognitive symptoms and age at menopause may help address sex-based disparities in detection and prevention. This study investigated whether subjective cognitive symptoms, in combination with age at menopause, were associated with performance on a digital cognitive task in postmenopausal women. METHODS: 183 postmenopausal women (mean age&#x2009;=&#x2009;63.8, range&#x2009;=&#x2009;45-85) were recruited after their Well-Woman visit. Participants completed the Screener for Cognitive Problems in Everyday Life (SCoPE) to assess subjective cognitive symptoms, followed by a sensitive measure of objective cognition: the Linus Health Digital Clock and Recall (DCR&#x2122;). Information was also collected on age at menopause. We examined associations of subjective cognitive symptoms and age at menopause with digital cognitive performance, adjusting for age, education and depression. Model fit was evaluated using adjusted R2, AIC, and BIC. RESULTS: 48.1% of women reported one or more cognitive symptoms on the SCoPE. On objective testing, 73.2% scored in the normal range, 20.8% in the borderline range, and 6.0% in the impaired range. SCoPE total score was negatively associated with objective cognitive performance in adjusted models (B&#x2009;=&#x2009;-.12, p&#x2009;=&#x2009;.03). Age at menopause showed a significant quadratic association with cognitive performance (B&#x2009;=&#x2009;-0.006, p<.001). SCoPE total was not associated with DCR subtests, while age at menopause predicted both Delayed Recall and Clock Drawing. CONCLUSION: Subjective cognitive symptoms and age at menopause were associated with lower performance on a sensitive, objective cognitive test. Findings support routine cognitive screening and suggest that subjective cognitive symptoms as well as age at menopause are associated with cognitive function.

Humans

Improved donor-site biomechanics and functional recovery with xenogeneic acellular dermal matrix after ALT flap harvest: A prospective randomized controlled study.

BACKGROUND: Donor-site management after anterolateral thigh (ALT) flap harvest is a significant yet underaddressed concern in reconstructive surgery for oral cancer. While xenogeneic acellular dermal matrix (Xeno-ADM) is common in soft-tissue repair, its efficacy for fascia lata reconstruction at the ALT donor site remains insufficiently characterized. This study aimed to assess the efficacy of xeno-ADM in fascia lata repair, focusing on compartment pressure, inflammatory and muscle injury biomarkers, and functional recovery. METHODS: In this prospective, randomized, single-blind trial, 200 patients undergoing ALT flap reconstruction were allocated to Xeno-ADM repair (n&#x202f;=&#x202f;100) or primary closure (n&#x202f;=&#x202f;100). Primary endpoints included compartment pressure, inflammatory markers in drainage fluid, serum muscle injury biomarkers, and functional outcomes. RESULTS: The xeno-ADM group showed significantly lower compartment pressures throughout postoperative days (POD) 1-5. Inflammatory markers in drainage fluid (CRP on POD 3 and 5) and serum muscle injury biomarkers (creatine kinase on POD 1 and 5) were significantly lower in xeno-ADM group. Functional outcomes were superior in the Xeno-ADM group, with faster gait recovery, lower pain scores at POD 7, and better lower-limb function at the 1- and 6-month follow-ups. Drainage duration did not differ between groups. Stratified analyses revealed that the benefits of xeno-ADM were more pronounced in patients with defect width >3&#x202f;cm or a body mass index &#x2265;24&#x202f;kg/m2. CONCLUSION: Xeno-ADM provides a safe and effective approach for fascia lata repair, reducing biomechanical and inflammatory burdens while enhancing functional recovery. These findings support a transition from simple structural closure toward functional donor-site reconstruction.

Humans

Impaired toilet training and bladder and bowel dysfunction in children with developmental coordination disorder - an underreported issue.

BACKGROUND & OBJECTIVE: Children with Developmental Coordination Disorder (DCD) face significant, yet often overlooked, challenges beyond motor impairments, including difficulties with toilet training and bladder and bowel dysfunctions (BBD). This study aims to explore whether children with DCD exhibit greater difficulties in these areas compared to typically developing children (TDC). METHOD: This cross-sectional case-control study included 84 children aged 5-8 years (42 DCD, 42 TDC), matched by school-grade and sex (33 boys and 9 girls per group). Parents completed the Vancouver Symptom Score for Dysfunctional Elimination Syndrome (VSSDES) to assess BBD symptoms, the Dutch DCD-questionnaire (DCD-Q) to evaluate motor coordination, and additional questions regarding toilet training, elimination diagnosis, and co-occurring conditions. Correlations and exploratory group differences were analysed. RESULTS: Parents of children with DCD reported significantly more toilet training difficulties than parents of controls (p < 0.001), including persistent accidents (47.6% vs. 9.5%), prolonged training (45.2% vs. 4.8%), and difficulties recognizing urination urgency (40.5% vs. 2.4%). The parental report of delayed attainment of bowel and bladder control (p < 0.05) and BBD rates (p < 0.001) was also significantly higher in children with DCD. Exploratory analyses indicated that the prevalence of these outcomes was not significantly different between children with DCD with and without co-occurring ADHD or autism, suggesting a possible primary association with DCD. Additionally, across both children with DCD and TDC, poorer motor skills were associated with more BBD symptoms (r = -0.474, p < 0.001). CONCLUSION: Children with DCD have a higher prevalence of toilet training difficulties and BBD compared to TDC, potentially affecting their psychosocial well-being. Greater awareness is crucial for timely and targeted care. Notably, the study's design, directly comparing children diagnosed with DCD to matched TDC, provides new insights into the prevalence of elimination difficulties in this population.

Humans