Mean Difference Research Articles

Neurodevelopmental outcome at two years of age and predictive value of General Movement Assessment in infants exposed to alcohol and/or drugs during pregnancy: a prospective cohort study

BackgroundExposure to alcohol and/or other addictive drugs in pregnancy is a documented risk factor for neurological impairment. We aimed to assess neurodevelopmental outcome at two years of age in infants exposed to prenatal alcohol and/or other addictive drugs and to examine the predictive value of early motor assessment.MethodsThis was a follow-up at two years of age in the prospective cohort study Children Exposed to Alcohol and/or Drugs in Intrauterine Life (CEADIL). The exposed group comprised 73 infants recruited from primary health care and included in a hospital follow-up programme at St. Olavs Hospital, Trondheim University Hospital, Norway. The control group comprised 93 healthy, unexposed infants recruited from the maternity ward at the same hospital. All children had been assessed by physiotherapists using the General Movement Assessment (GMA) at three months of age. Presence of fidgety movements, movement character and the Motor Optimality Score – Revised (MOS-R) were used. At two years of age, the children were assessed by trained examiners using the Bayley Scales of Infant and Toddler Development – Third Edition (BSID-III), Ages & Stages Questionnaires: Social-Emotional (ASQ:SE) and the Hollingshead Two-Factor Index of Social Position (SES).ResultsThe cognitive, language and motor composite scores of BSID-III were considerably lower in the exposed group than in the control group. Mean differences adjusted for age and parental SES ranged from − 13.3 (95% confidence interval, CI: -18.6 to -8.0) to -17.7 (95% CI: -23.3 to -12.2). Suboptimal fidgety movements and monotonous movement character had high sensitivity (0.94 to 0.74), but low specificity (0.10 to 0.32), while sensitivity and specificity of the MOS-R was around 50 and 60%, respectively.ConclusionsNeurodevelopmental outcome at two years of age was poorer in a group of children exposed to alcohol and/or drugs in pregnancy compared with a control group of healthy, unexposed children. Sensitivity of suboptimal fidgety movements and monotonous movement character at three months of age for later neurodevelopmental outcome was high to acceptable, but the MOS-R had limited sensitivity.

Sociocultural features of lifestyle modifications among TB–diabetes comorbid patients in Satara, India and its implications for planning self-management interventions for TB–diabetes comorbid patients

BackgroundLifestyle modifications (LM) are crucial in managing comorbid Tuberculosis (TB) and Diabetes Mellitus (DM) patients, significantly impacting treatment outcomes and overall health. In view of this, a study was conducted to clarify sociocultural features associated with LM among TB–diabetes comorbid patients.MethodsA cross-sectional descriptive study among randomly selected 180 adult TB–diabetes-comorbid-patients was conducted using a semi-structured interview schedule. Mann–Whitney-U-test was used to examine differences in means between patterns of distress (PDs) and perceived causes (PCs) regarding TB and Diabetes for two identified LM strategies among comorbid patients. Stepwise logistic regression was used to study factors associated with these LM strategies.ResultsTB–diabetes-comorbid-patients reporting physical symptoms as PDs preferred to follow the LM-1 strategy for TB and LM-2 for Diabetes. In contrast, patients reporting health-illness-injury-related causes follow LM-2 for TB and LM-1 for Diabetes. Further patients reporting hypertension for Diabetes (AOR = 2.916, 95% CI 0.9262–9.1788) and concerns-about-the-course-of-TB-illness (AOR = 3.746, 95% CI 1.4683–9.5593) as PDs were 3–4 times more likely to follow LM-1. While those reporting prior illnesses (AOR = 4.255, 95% CI 1.3941–12.9837) and sanitation (AOR = 5.242, 95% CI 1.2028–22.8446) as PCs for TB were 4–5 times follow LM-2. Patients who perceived consumption of alcohol as PCs of Diabetes were 10 times more likely to stop addictions (AOR = 9.680, 95% CI 2.5555–36.6639) and follow the LM-2 strategy.ConclusionGiven significant associations of sociocultural features with LM strategies, consideration of sociocultural features vis-à-vis these strategies is indispensable for managing TBDM comorbidity, emphasizing the need for developing comprehensive, patient-centred self-management interventions to enhance adherence and improve health outcomes.

Effect of electronic alerts on the care and outcomes in patients with acute kidney injury: a meta-analysis and trial sequential analysis

BackgroundAlthough electronic alerts are being increasingly implemented in patients with acute kidney injury (AKI), their effect remains unclear. Therefore, we conducted this meta-analysis aiming at investigating their impact on the care and outcomes of AKI patients.MethodsPubMed, Embase, Cochrane Library, and Clinical Trial Registries databases were systematically searched for relevant studies from inception to March 2024. Randomized controlled trials comparing electronic alerts with usual care in patients with AKI were selected.ResultsSix studies including 40,146 patients met the inclusion criteria. The pooled results showed that electronic alerts did not improve mortality rates (relative risk (RR) = 1.02, 95% confidence interval (CI) = 0.97–1.08, P = 0.44) or reduce creatinine levels (mean difference (MD) = − 0.21, 95% CI = − 1.60–1.18, P = 0.77) and AKI progression (RR = 0.97, 95% CI = 0.90–1.04, P = 0.40). Instead, electronic alerts increased the odds of dialysis and AKI documentation (RR = 1.14, 95% CI = 1.05–1.25, P = 0.002; RR = 1.21, 95% CI = 1.01–1.44, P = 0.04, respectively), but the trial sequential analysis (TSA) could not confirm these results. No differences were observed in other care-centered outcomes including renal consults and investigations between the alert and usual care groups.ConclusionsElectronic alerts increased the incidence of AKI and dialysis in AKI patients, which likely reflected improved recognition and early intervention. However, these changes did not improve the survival or kidney function of AKI patients. The findings warrant further research to comprehensively evaluate the impact of electronic alerts.

The correlation between serum vitamin D status and the occurrence of diabetic foot ulcers: a comprehensive systematic review and meta‐analysis

The association between vitamin D concentrations and the occurrence of diabetic foot ulcers (DFUs) remains a topic of ongoing debate. In order to provide a comprehensive and updated review, we conducted this meta‐analysis to further investigate the relationship between vitamin D concentrations and DFUs occurrence. The following databases, including Cochrane Library, EMBASE, Web of Science, PubMed, CBM, CNKI, WANFANG DATA and VIP Database, were systematically searched for studies published up to Dec. 20th, 2023. The combined estimation was calculated using both fixed-effects and random‐effects models. The overall effect size was reported as a weighted mean difference (WMD) with a corresponding 95% confidence interval (95%CI). Data analysis was performed utilizing Review Manager 5.4 and Stata 14. The Protocol has been registered in PROSPERO CRD42024503468. This updated meta-analysis, incorporating thirty-six studies encompassing 11,298 individuals with or without DFUs, demonstrated a significant association between vitamin D deficiency/insufficiency and an elevated risk of DFUs occurrence (< 25 nmol/L, OR 3.28, P < 0.00001; < 50 nmol/L, OR 2.25, P < 0.00001; < 75 nmol/L, OR 1.67, P = 0.0003). Vitamin D concentrations were significantly lower in individuals with DFUs compared to those without DFUs (P < 0.00001). Subgroup analyses consistently demonstrated this trend among the older population (> 50 years, P < 0.00001), individuals with long duration of diabetes (> 10 years, P < 0.00001), and those with poor glycemic control (mean HbA1c 8%-9% and > 9%, P < 0.00001).

Impact of work pace on cardiorespiratory outcomes, perceived effort and carried load in industrial workers: a randomised cross-over trial

ObjectivesThis study investigates the impact of different work paces on cardiorespiratory outcomes, perceived effort and carried load (CL) in industrial workers.MethodsA randomised cross-over trial was conducted at a mid-sized steel...

The Diagnosis and Treatment of Chronic Rhinosinusitis.

Chronic rhinosinusitis (CRS) is a heterogeneous condition characterized by local chronic inflammation of the mucous membranes of the nose and paranasal sinuses. It affects approximately 5% of the population. This review is based on relevant publications retrieved by a selective search of the literature, with particular attention to current national and international guidelines. CRS is defined by, and diagnosed on the basis of, a combination of symptoms and objective findings of nasal endoscopy and imaging studies. It markedly impairs quality of life and gives rise to both direct and indirect health care costs. In 20-45% of cases, CRS is associated with comorbid bronchial asthma and a significantly elevated risk of further diseases (e.g., COPD, OR 1.73; depression, HR 1.50; obstructive sleep apnea, OR 1.91; carcinoma, OR 1.14-5.30). CRS is primarily treated medically with topical steroids (standardized mean difference of nasal symptoms, -0.63 (95% confidence interval [-0.89; -0.37]; standardized mean difference of quality of life as measured by SNOT -22, -5.46 [-8.08; -2.84]), as well as with nasal lavage and, as an option, systemic steroids (and antibiotics where appropriate). If appropriate medical treatment fails to bring about adequate and sustained improvement, endoscopic surgery on the paranasal sinuses is indicated. This improves the individual symptoms, the overall symptom score, and patients' quality of life. Severe refractory CRS with nasal polyposis can be treated with biological agents. CRS calls for individually adapted medical and/or surgical treatment.

Cemented versus cementless Oxford unicompartmental knee arthroplasty for the treatment of medial knee osteoarthritis: an updated systematic review and meta-analysis.

This meta-analysis sought to compare the efficacy of cemented versus cementless Oxford unicompartmental knee arthroplasty(UKA) for the treatment of medial knee osteoarthritis. A comprehensive search of the following databases was conducted: Pubmed, The Cochrane Library, China National Knowledge Infrastructure (CNKI), Embase, the Web of Science, and MEDLINE. The objective was to identify literature comparing cemented versus cementless Oxford unicompartmental knee arthroplasty for the treatment of medial knee osteoarthritis. Duplicate literature, low-quality literature, literature with incompatible observations, and literature for which the full text was not available were excluded. Two independent researchers employed the Cochrane Risk Assessment Tool and the Newcastle-Ottawa Scale (NOS) to evaluate the quality of the included literature. The data then were extracted and subsequently meta-analyzed using RevMan 5.4. A total of 12 papers were included in the analysis, encompassing a cumulative of 2558 cumulative cases. Of these, 1258 were cemented and 1300 were cementless. A meta-analysis was conducted to compare the outcomes of cemented versus cementless Oxford UKA. The Oxford UKA group exhibited a significantly longer surgery time than the cementless Oxford UKA group [mean difference (MD) = 9.91, 95% confidence interval (CI) (7.64,12.17)]. Additionally, the cemented Oxford UKA group demonstrated a significantly lower knee OKS score compared to the cementless Oxford UKA group. The mean difference (MD) was - 1.58 (95% CI: -2.30, -0.86), indicating a significantly lower score for the cemented Oxford UKA group. Similarly, the mean difference (MD) was - 1.8 for the knee KSS clinical score, indicating a significantly lower score for the cemented Oxford UKA group. The results demonstrated that the knee KSS functional score was significantly lower in the cemented Oxford UKA group than in the cementless Oxford UKA group [MD=-1.72, 95% CI (-3.26, -0.37)]. 95% CI (-3.27,-0.17)], the cemented Oxford UKA group exhibited a significantly higher incidence of radiolucent lines around the prosthesis than the cementless Oxford UKA group [ratio of ratios (OR) = 3.62, 95% CI (1.08,12.13)]. The revision rate was significantly higher in the cemented Oxford UKA group than in the cementless Oxford UKA group [OR = 2.22, 95% CI (1.40,3.53)]. However, no significant difference was observed between the two groups in terms of reoperation rate, five-year prosthesis survival rate, and complication rate. The findings indicated that, in comparison to cemented Oxford UKA, cementless Oxford UKA resulted in a reduction in surgical time, an improvement in knee OKS score, KSS clinical score, and KSS functional score, and a decrease in the incidence of periprosthetic radiolucent lines and the rate of revisions.

Pomalidomide for Epistaxis in Hereditary Hemorrhagic Telangiectasia

BackgroundHereditary hemorrhagic telangiectasia (HHT) is characterized by extensive telangiectasias and arteriovenous malformations. The primary clinical manifestation is epistaxis that results in iron-deficiency anemia and reduced health-related quality of life.MethodsWe conducted a randomized, placebo-controlled trial to evaluate the safety and efficacy of pomalidomide for the treatment of HHT. We randomly assigned patients, in a 2:1 ratio, to receive pomalidomide at a dose of 4 mg daily or matching placebo for 24 weeks. The primary outcome was the change from baseline through week 24 in the Epistaxis Severity Score (a validated bleeding score in HHT; range, 0 to 10, with higher scores indicating worse bleeding). A reduction of 0.71 points or more is considered clinically significant. A key secondary outcome was the HHT-specific quality-of-life score (range, 0 to 16, with higher scores indicating more limitations).ResultsThe trial was closed to enrollment in June 2023 after a planned interim analysis met a prespecified threshold for efficacy. A total of 144 patients underwent randomization; 95 patients were assigned to receive pomalidomide and 49 to receive placebo. The baseline mean (±SD) Epistaxis Severity Score was 5.0±1.5, a finding consistent with moderate-to-severe epistaxis. At 24 weeks, the mean difference between the pomalidomide group and the placebo group in the change from baseline in the Epistaxis Severity Score was −0.94 points (95% confidence interval [CI], −1.57 to −0.31; P=0.004). The mean difference in the changes in the HHT-specific quality-of-life score between the groups was −1.4 points (95% CI, −2.6 to −0.3). Adverse events that were more common in the pomalidomide group than in the placebo group included neutropenia, constipation, and rash.ConclusionsAmong patients with HHT, pomalidomide treatment resulted in a significant, clinically relevant reduction in epistaxis severity. No unexpected safety signals were identified. (Funded by the National Heart, Lung, and Blood Institute; PATH-HHT Clinicaltrials.gov number, NCT03910244).

The Battle of Endoscopic Bariatric Therapies for Obesity: Endoscopic Sleeve Gastroplasty Versus Endoscopically Inserted Intragastric Balloon—A Pairwise Meta-Analysis of Comparative Studies and a Call for Randomized Controlled Trials

Background: Endoscopic sleeve gastroplasty (ESG) represents the latest primary endoscopic intervention for managing obesity. Both ESG and intragastric balloons (IGBs) have demonstrated effectiveness and safety for weight loss. However, there is a paucity of high-quality evidence supporting the superiority of one over the other, and no pairwise meta-analysis of comparative studies has been published to date. Our aim was to conduct a pairwise meta-analysis of comparative studies directly comparing ESG and IGB. Methods: We systematically conducted a literature search on PubMed and Google Scholar following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Our search used specific search terms. The Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) Tool was used to evaluate the quality of the included studies. Data were analyzed using Review Manager (RevMan) 5.4.1 software with a random-effects model. The statistical method used was the Mantel-Haenszel method. For dichotomous data, the effect size was represented using odds ratio (OR), while mean difference (MD) was utilized as the effect size for continuous data. Results: After screening 967 records, a total of 9 studies met the inclusion criteria for this meta-analysis (5302 patients). The quality assessment categorized 5 studies as having a moderate risk of bias, while 3 studies were classified as having a low risk of bias. Sufficient information was not available for one study to ascertain its overall quality. A statistically significant increase in total weight loss percentage (TWL%) at 1 and 6 months was observed with ESG compared with IGB. In addition, a statistically insignificant decrease in the incidence of adverse events and readmissions was observed with ESG. Furthermore, a statistically significant decrease in the incidence of reintervention was observed with ESG. Conclusions: While this study suggests a higher TWL% associated with ESG compared with IGB, drawing definitive conclusions is challenging due to limitations identified during a comprehensive quality assessment of the available literature. We advocate for randomized controlled trials (RCTs) directly comparing the newer IGB (with a 12-mo placement duration) with ESG. However, this study consistently reveals higher rates of early reintervention (re-endoscopy) within the IGB group, primarily necessitated by the removal or adjustment of the IGB due to intolerance. Given the additional intervention required at 6 or 12 months to remove the temporarily placed IGB, this trend may imply that IGB is less economically viable than ESG. Cost-effectiveness analyses comparing ESG and IGB are warranted to provide valuable scientific insights.

Diagnostic accuracy of hemodynamic assessment of intracranial atherosclerotic stenosis from a single angiographic view: a validation study

BackgroundThe aim of this study is to assess the feasibility of identifying the hemodynamic status of intracranial atherosclerotic stenosis (ICAS) using angio-based fractional flow (FF) calculated from a single angiographic...

Artificial intelligence improves bronchoscopy performance – a randomized cross-over trial

RationaleFlexible bronchoscopy is an operator dependent procedure. An automatic bronchial identification system based on artificial intelligence (AI) could help bronchoscopists to perform more complete and structured procedures through automatic guidance.Methods101 participants were included from six different continents at the European Respiratory Society annual conference in Milan, 9–13th September 2023. Participants were split into three groups based on experience: Novices (0 bronchoscopies), Intermediates (1-249 bronchoscopies), and Experienced (≥250 bronchoscopies). The participants performed two bronchoscopies on a realistic physical phantom, one with AI (AmbuBronchoSimulatorTrainingGUIDEv.0.0.1, Prototype version, Ambu) and one Standard procedure. The F1-group received AI-guidance for their first procedure, the F2-group for their second. A cross-over randomization controlled for learning by testing. All procedures were automatically rated according to the outcome measures: Inspected segments, Structured Progressions, and Procedure Time.ResultsAI guidance caused the participants to inspect more segments, (mean difference, paired t-test: +6.0 segments, p&lt;0.001), perform more Structured Progressions (+5.2 progressions, p&lt;0.001), and spend more time on the procedure (+72 s, p&lt;0.001) compared to their standard procedures. The effects of AI guidance on inspected segments and structured progression were highest for novices but significant for all experience groups: Novices (+8.2 segments, p=.012 and +6.6 progressions p&lt;0.001), Intermediates (+5.7 segments, p=.006 and +5.1 progressions p&lt;0.001, and Experienced (+4.3 segments, p=.006 and +3.8 progressions p&lt;0.016).ConclusionsAI-guidance helped bronchoscopists of all experience levels to inspect more segments in a more structured order. Clinical implementation of AI guidance could help ensure and document more complete bronchoscopy procedures in the future.

Identification and Characterization of Key Genes Associated with Amelogenesis

Abstract Objectives The identification of key genes associated with amelogenesis would be helpful in finding solutions to genetic disorders in oral biology. The study aimed to use in silico analysis to identify the key genes involved in tooth development associated with preameloblasts (PABs) and secretory ameloblasts (SABs). Material and Methods The data was subjected to quality analysis and uniform manifold approximation and projection analysis. To examine the distribution of the genes and identify important upregulated loci, a p-value histogram, a quantile plot, a mean difference and mean-variance plot, and a volcano plot were generated. Finally, protein-protein interaction and gene enrichment analyses were performed to determine the ontology, relevant biological processes, and molecular functions of selected genes. Results A total of 157 genes were found to be significant in the PAB versus SAB comparison. HIST1H31 revealed strong interaction with HIST1H2BM, and EXO1, ASPM, SPC25, and TTK showed strong interactions with one other. The STRING database revealed that NCAPG, CENPU, NUSAP1, HIST1H2BM, and HIST1H31 are involved in biological processes. NCAPG, CENPU, SPC25, ETV5, TTK, ETV1, FAM9A, NUSAP1, HIST1H2BM, and HIST1H31 are involved in cellular components. Conclusion The TTK, NUSAP1, CENPU, NCAPG, FAM9A, ASPM, SPC25, and HIST1H31 genes demonstrate functions in cell division. These genes might play a role in ameloblast development. These results will be useful in developing new methods to stimulate ameloblast development, which is essential for tooth regeneration and tissue engineering. However, more research is required to validate the functions of these genes and the genes with which they interact. A wide variety of genetic, epigenetic, and exogenous signaling factors regulate these genes and pathways throughout development and differentiation, cell fate, and behavior.

Higher fiber higher carbohydrate diets better than lower carbohydrate lower fiber diets for diabetes management: Rapid review with meta-analyses.

Some dietary recommendations continue to recommend carbohydrate restriction as a cornerstone of dietary advice for people with diabetes. We compared the cardiometabolic effects of diets higher in both fiber and carbohydrate with lower carbohydrate lower fiber diets in type 1 or type 2 diabetes. MEDLINE, Embase, and the Cochrane Database of Systematic Reviews up to June 24, 2024, with additional hand searching. Randomized controlled trials in which both dietary fiber and carbohydrate amount had been modified were identified from source evidence syntheses on carbohydrate amount in people with diabetes. Two reviewers independently. Ten eligible trials including 499 participants with diabetes (98% with T2) were identified from the potentially eligible 828 trials included in existing evidence syntheses. Pooled findings indicate that higher fiber higher carbohydrate diets reduced HbA1c (mean difference [MD] -0.50% [95% confidence interval -0.99 to -0.02]), fasting insulin (MD -0.99 μIU/mL [-1.83 to -0.15]), total cholesterol (MD -0.16 mmol/L [-0.27 to -0.05]) and low-density lipoprotein cholesterol (MD -0.16 mmol/L (-0.31 to -0.01) when compared with lower carbohydrate lower fiber diets. Trials with larger differences in fiber and carbohydrate intakes between interventions reported greater reductions. Certainty of evidence for these outcomes was moderate or high, with most outcomes downgraded due to heterogeneity unexplained by any single variable. Our predefined scope excluded trials with co-interventions such as energy restriction, which may have provided addition information. Findings indicate the greater importance of promoting dietary fiber intakes, and the relative unimportance of carbohydrate amount in recommendations for people with diabetes.

Mandibular Advancement and Skeletal Anchorage in Class II Malocclusion Patients: A Systematic Review with Meta-Analysis

(1) Objectives: The purpose of this review was to compare the effects of combining skeletal anchorage and Class II devices, both from an overall perspective and individually for each type of appliance, considering as main outcomes the vertical dimensions and the inclination of the mandibular and maxillary incisors. (2) Materials and Methods: A search without time restrictions was performed up to February 2024 in PubMed, PubMed Central, Scopus, and Medline for randomized controlled trials, as well as prospective and retrospective cohort studies, considering Class II patients treated with and without skeletal anchorage. The effect measure used for the meta-analytic evaluation was the standardized mean difference (SMD). The SMD calculation was obtained by subtracting the mean values of T1–T0 for each individual treatment and then calculating the SMD between the treatments involved. The meta-analysis was performed using the standardized mean difference of the mean difference of the T1–T0 change in the outcome between the different treatments evaluated as the effect size. (3) Results: A total of 1217 documents were initially retrieved. According to the PRISMA protocol, 18 studies comparing different skeletal anchorage protocols (upper/lower miniscrews and miniplates), combined with four appliances (Herbst, Forsus, Carriere Motion, and elastics), were included in the analysis. No significant difference in skeletal divergence was found between groups from an overall point of view (SMD: 0.19 (−0.48 to 0.83) according to the random-effects model). A statistically significant reduction in IMPA° was found in patients treated with temporary anchorage devices (TADs) (SMD of 5.58 (3.40 to 7.75)), except for the elastics group (SMD: 3.76 (−0.91 to 8.43)). The effect on the upper incisors’ inclination appeared to be strictly dependent on the type of anchorage (TADs in one or both of the arches). Some limitations must be considered when interpreting the results: the small number of studies included and the heterogeneity among them are among the limitations, and the temporal disparity among some studies; the ages of the patients were not always comparable; and, finally, the clinical relevance of the effects of TADs is sometimes questionable. (4) Conclusions: The vertical dimension seems not to be significantly affected by skeletal anchorage; instead, the proclination of mandibular incisors is generally reduced when TADs are used. Skeletal anchorage might be useful if lingual tipping of the upper incisors is required; however, it is influenced by the anchorage protocol.

High-Risk HLA-DQ Mismatches Are Associated With Adverse Outcomes After Lung Transplantation

Human leukocyte antigen (HLA) mismatches (MM) between donor and recipient lead to eplet MM (epMM) in lung transplantation (LTX), which can induce the development of de-novo donor-specific HLA-antibodies (dnDSA), particularly HLA-DQ-dnDSA. Aim of our study was to identify risk factors for HLA-DQ-dnDSA development. We included all patients undergoing LTX between 2012 and 2020. All recipients/donors were typed for HLA 11-loci. Development of dnDSA was monitored 1-year post-LTX. EpMM were calculated using HLAMatchmaker. Differences in proportions and means were compared using Chi2-test and Students’ t-test. We used Kaplan-Meier curves with LogRank test and multivariate Cox regression to compare acute cellular rejection (ACR), chronic lung allograft dysfunction (CLAD) and survival. Out of 183 patients, 22.9% patients developed HLA-DQ-dnDSA. HLA-DQ-homozygous patients were more likely to develop HLA-DQ-dnDSA than HLA-DQ-heterozygous patients (p = 0.03). Patients homozygous for HLA-DQ1 appeared to have a higher risk of developing HLA-DQ-dnDSA if they received a donor with HLA-DQB1*03:01. Several DQ-eplets were significantly associated with HLA-DQ-dnDSA development. In the multivariate analysis HLA-DQ-dnDSA was significantly associated with ACR (p = 0.03) and CLAD (p = 0.01). HLA-DQ-homozygosity, several high-risk DQ combinations and high-risk epMM result in a higher risk for HLA-DQ-dnDSA development which negatively impact clinical outcomes. Implementation in clinical practice could improve immunological compatibility and graft outcomes.

Validation evidence with experimental and clinical data to establish credibility of TAVI patient-specific simulations

PurposeThe objective of this study is to validate a novel workflow for implementing patient-specific finite element (FE) simulations to virtually replicate the Transcatheter Aortic Valve Implantation (TAVI) procedure. MethodsSeven patients undergoing TAVI were enrolled. Patient-specific anatomical models were reconstructed from pre-operative computed tomography (CT) scans and subsequentially discretized, considering the native aortic leaflets and calcifications. Moreover, high-fidelity models of CoreValve Evolut R and Acurate Neo2 valves were built. To determine the most suitable material properties for the two stents, an accurate calibration process was undertaken. This involved conducting crimping simulations and fine-tuning Nitinol parameters to fit experimental force-diameter curves. Subsequently, FE simulations of TAVI procedures were conducted. To validate the reliability of the implemented implantation simulations, qualitative and quantitative comparisons with post-operative clinical data, such as angiographies and CT scans, were performed. ResultsFor both devices, the simulation curves closely matched the experimental data, indicating successful validation of the valves mechanical behaviour. An accurate qualitative superimposition with both angiographies and CTs was evident, proving the reliability of the simulated implantation. Furthermore, a mean percentage difference of 1,79 ± 0,93 % and 3,67 ± 2,73 % between the simulated and segmented final configurations of the stents was calculated in terms of orifice area and eccentricity, respectively. ConclusionThis study shows the successful validation of TAVI simulations in patient-specific anatomies, offering a valuable tool to optimize patients care through personalized pre-operative planning. A systematic approach for the validation is presented, laying the groundwork for enhanced predictive modeling in clinical practice.

The efficacy of mobile applications for reducing depression in adolescents and young adults: A meta-analysis of randomized control trials.

Mobile applications for mental health have the potential to aid people with mental health disorders, especially depression, by providing them with tools and coping mechanisms. Adolescents and young adults, being at risk of depressive symptoms and leading mobile users, are among the main targets of using mobile applications to alleviate symptoms. This study aimed to evaluate the impact of mobile application-based psychological interventions in reducing depression symptoms in adolescents and young adults compared to those not exposed to the intervention. We conducted a meta-analysis focusing on mobile applications for reducing depressive symptoms. We searched two databases: MEDLINE and EMBASE and included randomized controlled trials conducted in English among participants aged 18-35 years old who were assessed for depressive symptoms using a validated screening measure and used mobile applications-based psychological interventions. Two of six independent reviewers conducted study selection, data extraction, and bias assessment. A pooled mean standardized difference (Cohen's d) and 95% CI were calculated using random-effects meta-analysis. Risk of bias was assessed using I2 statistics and forest plot. Egger's test was used for assessing publication bias. After screening 740 references, we identified 12 trials with 1869 participants, with a mean age of participants ranging from 14.70 to 25.1 years. The interventions ranged from cognitive behavioral therapy (CBT)-based mobile apps to interactive story-telling apps and apps delivering a mix of CBT, interpersonal psychotherapy for adolescents, and dialectical behavior therapy elements. Control groups included information-only, waitlist, no intervention, and treatment as usual. Seven studies used Patient Health Questionnaire-9 (PHQ-9) to assess the severity of depressive symptoms, while the other five used different scales. There was no evidence of publication bias (p = 0.325). The mobile applications reduced depression score by 0.08 units of standardized difference more than the control, with a 95% CI of -0.19 to 0.03 (p = 0.294, I2 = 15.4%) using standardized mean difference (SMD) as the effect estimate. In a sensitivity analysis including only studies that used PHQ-9, we found a similar trend, SMD -0.72 (95%CI -1.48 to 0.03). However, both findings were not significant. Current evidence is insufficient to support mobile applications to relieve depression symptoms in adolescents and young adults. Further trials with larger sample size are needed to confirm our findings of a positive trend. With emerging technologies and the high exposure of apps in this population, mobile applications for depression hold promise for the future of treatment and awareness of mental health disorders in this population.

Black Americans with sickle cell disease (SCD) demonstrate accelerated epigenetic pace of aging compared to Black Americans without SCD

Abstract Background Sickle cell disease (SCD) is a chronic medical condition characterized by red blood cell sickling, vaso-occlusion, hemolytic anemia, and subsequently, end-organ damage and reduced survival. Because of this significant pathophysiology and early mortality, we hypothesized that patients with SCD are experiencing accelerated biological aging compared to individuals without SCD. Methods We utilized the DunedinPACE measure to compare the epigenetic pace of aging in 131 Black Americans with SCD to 1391 Black American veterans without SCD. Results SCD patients displayed a significantly accelerated pace of aging (DunedinPACE mean difference of 0.057 points) compared to the veterans without SCD, whereby SCD patients were aging approximately 0.7 months more per year than those without SCD (p=4.49x10-8). This was true, even though the SCD patients were significantly younger according to chronological age than the individuals without SCD, making the epigenetic aging discrepancy even more apparent. This association became stronger when we removed individuals with PTSD from the non-SCD group (p=2.18x10-9), and stronger still when we restricted the SCD patients to those with hemoglobin SS and Sβ0 thalassemia genotypes (p=1.61x10-10). Conclusions These data support our hypothesis that individuals with SCD experience accelerated biological aging as measured by global epigenetic variation. The assessment of epigenetic measures of biological aging may prove useful to identify which SCD patients would most benefit from clinical interventions to reduce mortality.

Effect of factor VIII and FVIII/PC ratio on portal vein thrombosis in liver cirrhosis: a systematic review and meta‑analysis

BackgroundTo date, there is an ongoing debate regarding the ability to predict PVT development using markers of FVIII or FVIII/PC ratio. This study presents evidence-based medical findings on the influence of FVIII activity levels and FVIII/PC values in the formation of PVT in cirrhosis.MethodsThe search for original studies on risk factors for portal vein thrombosis (PVT) associated with cirrhosis was conducted, which primarily focused on comparing circulating FVIII activity levels or FVIII/PC ratio in cirrhotic patients with and without PVT. The quality of evidence from each study was assessed using the Newcastle-Ottawa Scale.ResultsThe meta-analysis included a total of 10 original studies. In total, 2250 cirrhotic patients were included, with 414 having PVT and 1836 without PVT. The pooled analysis using a random-effects model showed no significant difference in standardized mean difference (SMD) for FVIII activity levels in cirrhotic patients with or without PVT (SMD = 0.12, 95% CI=-0.46 to 0.70, P = 0.68), but there was significant heterogeneity (I2 = 95.52%, P = 0.00). Meta-regression analysis indicated that differences in mean FVIII activity levels in the PVT group, the number of cases in the non-PVT group, and the study design methods partially contributed to the heterogeneity (P < 0.05). However, compared to the non-PVT group, the PVT group had higher FVIII/PC ratio with a statistically significant difference (SMD = 0.39, 95% CI: 0.15 to 0.63, P = 0.00), and there was no significant heterogeneity (I2 = 28.62%).ConclusionIn conclusion, the FVIII/PC ratio not only reflects the severity of liver disease, but also can be used as one of the predictors of PVT development.

The Use of Nudge Strategies in Improving Physicians’ Prescribing Behavior: A Systematic Review and Meta-analysis

Background Nudges have been proposed as a method of influencing prescribing decisions. Purpose The purpose of this article is to 1) investigate associations between nudges’ characteristics and effectiveness, 2) assess the quality of the literature, 3) assess cost-effectiveness, and 4) create a synthesis with policy recommendations. Methods We searched health and social science databases. We included studies that targeted prescribing decisions, included a nudge, and used prescribing behavior as the outcome. We recorded study characteristics, effect size of the primary outcomes, and information on cost-effectiveness. We performed a meta-analysis on the standardized mean difference of the studies’ primary outcomes, tested for associations between effect size and key intervention characteristics, and created a funnel plot evaluating publication bias. Synthesis We identified 21 studies containing 25 nudges. In total, 62 of 85 (73%) outcomes showed a statistically significant effect. The average effect size was −0.22 standardized mean difference. No studies included heterogeneity analyses. We found no associations between effects and selected study characteristics. Study quality varied and correlated with study design. A total of 7 of 21 (33%) studies included an evaluation of costs. These studies suggested that the interventions were cost-effective but considered only direct effects. We found evidence of publication bias. Limitations Heterogeneity and few studies limit the possibilities of statistical inference about effectiveness. Conclusions Nudges may be effective at directing prescribing decisions, but effects are small and health effects and cost-effectiveness are unclear. Future nudge studies should contain a rationale for the chosen nudge, prioritize the use of high-quality study designs, and include evaluations of heterogeneity, cost-effectiveness, and health outcomes to inform decision makers. Moreover, preregistration of the protocol is warranted to limit publication bias. Highlights Nudging as a method to improve prescribing decisions has gained popularity during the past decade. We find that nudging can improve prescribing decisions, but effect sizes are mostly small, and the size of derived health outcomes is unclear. Most studies use feedback and error-stopping nudges to target excessive opioid or antibiotic prescribing, making heterogeneity analyses across nudge types difficult. Further research on the cost-effectiveness of nudges and generalizability is needed to guide decision makers considering nudging as a tool to guide prescribing decisions.