Skeletal editing through direct nitrogen deletion of secondary amines.

Synthetic chemistry aims to build up molecular complexity from simple feedstocks1. However, the ability to exert precise changes that manipulate the connectivity of the molecular skeleton itself remains limited, despite possessing substantial potential to expand the accessible chemical space2,3. Here we report a reaction that 'deletes' nitrogen from organic molecules. We show that N-pivaloyloxy-N-alkoxyamides, a subclass of anomeric amides, promote the intermolecular activation of secondary aliphatic amines to yield intramolecular carbon-carbon coupling products. Mechanistic experiments indicate that the reactions proceed via isodiazene intermediates that extrude the nitrogen atom as dinitrogen, producing short-lived diradicals that rapidly couple to form the new carbon-carbon bond. The reaction shows broad functional-group tolerance, which enables the translation of routine amine synthesis protocols into a strategy for carbon-carbon bond constructions and ring syntheses. This is highlighted by the use of this reaction in the syntheses and skeletal editing of bioactive compounds.

MANOCCA: a robust and computationally efficient test of covariance in high-dimension multivariate omics data.

Multivariate analysis is becoming central in studies investigating high-throughput molecular data, yet, some important features of these data are seldom explored. Here, we present MANOCCA (Multivariate Analysis of Conditional CovAriance), a powerful method to test for the effect of a predictor on the covariance matrix of a multivariate outcome. The proposed test is by construction orthogonal to tests based on the mean and variance and is able to capture effects that are missed by both approaches. We first compare the performances of MANOCCA with existing correlation-based methods and show that MANOCCA is the only test correctly calibrated in simulation mimicking omics data. We then investigate the impact of reducing the dimensionality of the data using principal component analysis when the sample size is smaller than the number of pairwise covariance terms analysed. We show that, in many realistic scenarios, the maximum power can be achieved with a limited number of components. Finally, we apply MANOCCA to 1000 healthy individuals from the Milieu Interieur cohort, to assess the effect of health, lifestyle and genetic factors on the covariance of two sets of phenotypes, blood biomarkers and flow cytometry-based immune phenotypes. Our analyses identify significant associations between multiple factors and the covariance of both omics data.

The randomized controlled trial (NAVKIDS2) of a patient navigator program created for children with chronic kidney disease.

Patient navigators enable adult patients to circumnavigate complex health systems, improving access to health care and outcomes. Here, we aimed to evaluate the effects of a patient navigation program in children with chronic kidney disease (CKD). In this multi-center, randomized controlled trial, we randomly assigned children (aged 0-16 years) with CKD stages 1-5 (including children on dialysis or with kidney transplants), from low socioeconomic status backgrounds, and/or residing in remote areas, to receive patient navigation at randomization (immediate) or at six months (waitlist). The primary outcome was self-rated health (SRH) of participating children at six months, using intention to treat analysis. Secondary outcomes included caregivers' SRH and satisfaction with health care, children's quality of life, hospitalizations, and missed school days. Repeated measures of the primary outcome from baseline to six months were analyzed using cumulative logit mixed effects models. Semi-structured interviews were thematically evaluated. Of 398 screened children, 162 were randomized (80 immediate and 82 waitlist); mean age (standard deviation) of 8.8 (4.8) years with 64.8% male. SRH was not significantly different between the immediate and wait-listed groups at six months. There were also no differences across all secondary outcomes between the two groups. Caregivers' perspectives were reflected in seven themes: easing mental strain, facilitating care coordination, strengthening capacity to provide care, reinforcing care collaborations, alleviating family tensions, inability to build rapport and unnecessary support. Thus, in children with CKD, self-rated health may not improve in response to a navigator program, but caregivers gained skills related to providing and accessing care.

Sleep disturbances in children and adolescents after kidney transplantation.

BACKGROUND: Disturbances of sleep are prevalent among children with chronic kidney disease. However, the aetiology of sleep disorders in children particularly after kidney transplantation is not clear. We sought to ascertain the prevalence and type of sleep disturbances in paediatric kidney transplant recipients and to identify predictors of sleep disturbances in this population. METHODS: Caregivers of kidney transplant recipients completed online questionnaires about their child's sleep. The questionnaires utilised were the Sleep Disturbance Scale for Children (SDSC), the Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD), questions about sleep hygiene, and questions about restless leg syndrome. Demographic and clinical details were collected from medical records. RESULTS: Thirty-five children were included in the study, with a median (IQR) age of 14.1 years (9.5-16.1) and median years (IQR) since transplant of 3.7 (0.7-8.7) years, and 72.0% were identified to have at least one category of sleep disturbance according to scores on the SDSC. The most common sleep disturbances reported were disorders of initiating and maintaining sleep (DIMS) (40.0%) and disorders of excessive somnolence (DOES) (31.4%). Statistically significant predictors of sleep disturbances include low estimated glomerular filtration rate and increased age. Among children who screened positive for DIMS and DOES, the majority indicated use of electronic devices in 1 h before bed. CONCLUSIONS: A high prevalence of sleep disturbances has been identified in children after kidney transplants, and some risk factors may be modifiable. Further studies are required to understand whether there are other readily modifiable predictors of sleep disturbances.

The 2022 world health organization reevaluation of human and mammalian toxic equivalency factors for polychlorinated dioxins, dibenzofurans and biphenyls.

In October 2022, the World Health Organization (WHO) convened an expert panel in Lisbon, Portugal in which the 2005 WHO TEFs for chlorinated dioxin-like compounds were reevaluated. In contrast to earlier panels that employed expert judgement and consensus-based assignment of TEF values, the present effort employed an update to the 2006 REP database, a consensus-based weighting scheme, a Bayesian dose response modeling and meta-analysis to derive "Best-Estimate" TEFs. The updated database contains almost double the number of datasets from the earlier version and includes metadata that informs the weighting scheme. The Bayesian analysis of this dataset results in an unbiased quantitative assessment of the congener-specific potencies with uncertainty estimates. The "Best-Estimate" TEF derived from the model was used to assign 2022 WHO-TEFs for almost all congeners and these values were not rounded to half-logs as was done previously. The exception was for the mono-ortho PCBs, for which the panel agreed to retain their 2005 WHO-TEFs due to limited and heterogenous data available for these compounds. Applying these new TEFs to a limited set of dioxin-like chemical concentrations measured in human milk and seafood indicates that the total toxic equivalents will tend to be lower than when using the 2005 TEFs.

Does the Nutritional Intake and Diet Quality of Children With Chronic Kidney Disease Differ From Healthy Controls? A Comprehensive Evaluation.

OBJECTIVE: Children with chronic kidney disease (CKD) experience many obstacles to achieving optimal dietary intake. Dietary intake patterns remain unexplored or poorly described. This study compares nutritional intake and diet quality of Australian children with CKD to controls. METHODS: A food frequency questionnaire captured intake data and was compared to controls. Nutritional intake was determined using individualized nutrient reference values, and diet quality described using the Australian Guide to Healthy Eating and the Australian Child and Adolescent Recommended Food Score. RESULTS: Children with CKD (n = 36) and controls (n = 82) were studied. Children with CKD had lower weight and height z scores, but higher body mass index (P < .0001 for all parameters). Children with CKD had adequate energy intake, and excessive protein and sodium intake (336% and 569%). They were significantly less likely to meet requirements for vitamin A (P < .001), thiamine (P = .006), folate (P = .01), vitamin C (P = .008), calcium (P < .0001), iron (P = .01), magnesium (P = .0009), and potassium (P = .002). No child met recommended vegetable intake; however, less than half of children with CKD met fruit (44%), grains (31%), and dairy serves (31%). They were also less likely to meet recommended fruit and dairy serves (P = .04 and P = .01, respectively). Non-core foods provided 36% of energy, and although comparable to controls, was contributed more by takeaway foods (P = .01). CONCLUSION: Children with CKD have reduced nutritional intake of key nutrients and consume more takeaways than controls. Attention to increasing core foods, limiting sodium intake, and managing restrictions while promoting nutrient density appears necessary.

Are serious games seriously good at preparing students for clinical practice?: A randomized controlled trial.

PURPOSE: Serious games (SGs) have great potential for pediatric medical education. This study evaluated the efficacy of a SG in improving learner satisfaction, knowledge, and behavior. MATERIALS AND METHODS: This was an investigator-blinded randomized controlled trial (RCT) comparing a SG against two controls: (i) adaptive tutorial (AT), and (ii) low-stimulus control (LSC). SG is a highly immersive role-playing game in a virtual hospital. AT delivers interactive web-based lessons. LSC is paper-based clinical practice guidelines. Metropolitan senior medical students at UNSW were eligible. A total of 154 enrolled and were block randomized to one intervention. Participants had access to one intervention for 8 weeks which taught pediatric acute asthma and seizure assessment and management. Satisfaction was assessed with Likert-scale responses to 5 statements and 2 free-text comments. Knowledge was assessed with 10 multiple-choice questions (MCQs). Clinical behavior was assessed during a 30-point simulated clinical management scenario (CMS). Primary analysis was performed on a modified intention-to-treat basis and compared: (1) SG vs. AT; and (2) SG vs. LSC. RESULTS: A total of 118 participants were included in the primary analysis (modified intention-to-treat model). No significant differences in MCQ results between the SG and control groups. SG group outperformed the LSC group in the CMS, with a moderate effect (score out of 30: 20.8 (3.2) vs. 18.7 (3.2), respectively, d = 0.65 (0.2-1.1), p = 0.005). No statistically significant difference between SG and AT groups in the CMS (score: 20.8 (3.2) vs. 19.8 (3.1), respectively, d = 0.31 (-0.1 to 0.8), p = 0.18). A sensitivity analysis (per-protocol model) was performed with similar outcomes. CONCLUSIONS: This is the first investigator-blinded RCT assessing the efficacy of a highly immersive SG on learner attitudes, knowledge acquisition, and performance in simulated pediatric clinical scenarios. The SG demonstrated improved translation of knowledge to a simulated clinical environment, particularly compared to LSC. SGs show promise in pediatric medical education.

Medical student interactions with children in their daily lives.

Learning to communicate effectively with children in clinical interactions can be challenging. This study aimed to determine the extent to which medical students are exposed to children in their daily lives, in order to understand the experience students bring when entering paediatric rotations. METHODS: A cross-sectional survey of medical students entering paediatric rotations from two medical schools was conducted. Students were asked to rate the frequency of their interactions with infants, preschool-aged and school-aged children and their confidence in doing so. RESULTS: 339 out of 476 students participated in this study. Interactions with infants and preschool-aged children were rare, with most students reporting interactions once or two times per year or less (83% and 67%, respectively). Students interacted with school-aged children more frequently (43% most weeks or days). Students who interacted more frequently with children were more confident when entering their paediatric placements. CONCLUSIONS: Medical students have limited exposure to infants and preschool-aged children in their daily lives and this affects their confidence. Supervisors should incorporate activities aimed at building confidence interacting with young children early in clinical attachments.

Vascular Closure Devices For Axillary Artery Access: A Systematic Review and Meta-Analysis.

PURPOSE: To evaluate the technical success and complication rates of vascular closure devices (VCDs) in the axillary artery. MATERIALS AND METHODS: MEDLINE and Embase were searched independently by two reviewers to identify observational studies from inception through October 2021. The following outcomes were meta-analyzed: technical success, hematoma, dissection, pseudoaneurysm, infection, and local neurological complications. Complications were also graded as mild, moderate, and severe. A logistic regression evaluating the influence of sheath size for the outcome of technical success rate was performed using individual patient-level data. RESULTS: Of 1496 unique records, 20 observational studies were included, totaling 915 unique arterial access sites. Pooled estimates were as follows: technical success 84.8% (95% confidence interval [CI]: 78%-89.7%, I2=60.4%), hematoma 7.9% (95% CI: 5.8%-10.6%, I2=0%), dissection 3.1% (95% CI: 1.3%-7.3%, I2=0%), pseudoaneurysm 2.7% (95% CI: 1.3%-5.7%, I2=0%), infection <1% (95% CI: 0%-5.7%, I2=20.5%), and local neurological complications 2.7% (95% CI: 1.7%-4.4%, I2=0%). There was a significant negative association between sheath size and technical success rate (odds ratio [OR]: 0.87 per 1 French (Fr) increase in sheath size, 95% CI: 0.80-0.94, p=0.0005). Larger sheath sizes were associated with a greater number of access-site complications (adjusted odds ratio [aOR]: 1.21 per 1 Fr increase sheath size, 95% CI: 1.04-1.40, p=0.013). CONCLUSIONS: Off-label use of VCDs in the axillary artery provides an 85% successful closure rate and variable complication rate, depending on the primary procedure and sheath size. Larger sheaths were associated with a lower technical success and greater rate of access-related complications. CLINICAL IMPACT: Safe arterial access is the foundation for arterial intervention. While the common femoral artery is a well established access site, alternative arterial access sites capable of larger sheath sizes are needed in the modern endovascular era. This article provides the largest synthesis to date on the use of vascular closure devices for percutaneous axillary artery access in endovascular intervention. It should serve clinicians with added confidence around this approach in terms of providing a reference for technical success and complications. Clinically, this data is relevant for patient consent purposes as well as for practice quality improvement in setting safety standards for this access site.

The Use of Vascular Closure Devices for Brachial Artery Access: A Systematic Review and Meta-Analysis.

PURPOSE: To estimate the rates of technical success and adverse events of vascular closure devices (VCDs) in the brachial artery and compare the rates of adverse events with manual compression. MATERIALS AND METHODS: MEDLINE and Embase were searched for observational studies examining VCDs in the brachial artery. Meta-analyses were performed using random effects for the following outcomes: (a) technical success, (b) hematoma at the access site, (c) pseudoaneurysm, (d) local neurological adverse events, and (e) total number of adverse events. A pairwise meta-analysis compared VCD with manual compression for the outcomes of hematoma and the total number of adverse events. RESULTS: Of 1,761 eligible records, 16 studies including 510 access sites were included. Primary procedures performed were peripheral arterial disease interventions, percutaneous coronary intervention, and endovascular thrombectomy for ischemic stroke. The technical success rate was 93% (95% CI, 87%-96%; I2 = 47%). Data on the following adverse events were obtained via meta-analysis: (a) hematoma, 9% (5%-15%; I2 = 54%); (b) stenosis or occlusion at access site, 3% (1%-14%; I2 = 51%); (c) infection, 0% (0%-5%; I2 = 0%); (d) pseudoaneurysm, 4% (1%-13%; I2 = 61%); (e) local neurological adverse events, 5% (2%-13%; I2 = 54%); and (f) total number of adverse events, 15% (10%-22%; I2 = 51%). Angio-Seal success rate was 96% (93%-98%; I2 = 0%), whereas the ExoSeal success rate was 93% (69%-99%; I2 = 61%). When comparing VCD and manual compression, there was no difference in hematoma formation (relative risk, 0.75; 95% CI, 0.35-1.63; I2 = 0%; P = .47) or the total number of adverse events (relative risk, 0.75; 95% CI, 0.35-1.58; I2 = 76%; P = .45). CONCLUSIONS: Despite being off-label, studies suggest that VCDs in the brachial artery have a high technical success rate. There was no significant difference in adverse events between VCDs and manual compression in the brachial artery.

Baseline characteristics of participants in the NAVKIDS2 trial: a patient navigator program in children with chronic kidney disease.

BACKGROUND: Children with chronic kidney disease (CKD) require multidisciplinary care to meet their complex healthcare needs. Patient navigators are trained non-medical personnel who assist patients and caregivers to overcome barriers to accessing health services through care coordination. This trial aims to determine the effectiveness of a patient navigator program in children with CKD. METHODS: The NAVKIDS2 trial is a multi-center, waitlisted, randomized controlled trial of patient navigators in children with CKD conducted at five sites across Australia. Children (0-16 years) with CKD from low socioeconomic status rural or remote areas were randomized to an intervention group or a waitlisted control group (to receive intervention after 6 months). The study primary and secondary endpoints include the self-rated health (SRH) (primary), and utility-based quality of life, progression of kidney dysfunction of the child, SRH, and satisfaction with healthcare of the caregiver at 6 months post-randomization. RESULTS: The trial completed recruitment in October 2021 with expected completion of follow-up by October 2022. There were 162 patients enrolled with 80 and 82 patients randomized to the immediate intervention and waitlisted groups, respectively. Fifty-eight (36%) participants were from regional/remote areas, with a median (IQR) age of 9.5 (5.0, 13.0) years, 46% were of European Australian ethnicity, and 65% were male. A total of 109 children (67%) had CKD stages 1-5, 42 (26%) were transplant recipients, and 11 (7%) were receiving dialysis. CONCLUSION: The NAVKIDS2 trial is designed to evaluate the effectiveness of patient navigation in children with CKD from families experiencing socioeconomic disadvantage. A higher resolution version of the Graphical abstract is available as Supplementary information.

Return to Sport and Clinical Outcomes Following Osteochondral Autograft Transplantation in Baseball Players and Gymnasts With Unstable Osteochondritis Dissecans: A Critically Appraised Topic.

CLINICAL SCENARIO: Osteochondritis dissecans (OCD) of the capitellum is a condition occurring at the elbow and often seen in both baseball players and gymnasts due to the repetitive loading of the radiocapitellar joint. Treatment options for OCD vary and are dependent on lesion presentation, elbow motion, and growth plate maturity. OCD lesions categorized as unstable can be treated with an osteochondral autograft transplantation surgery (OATS). FOCUSED CLINICAL QUESTION: In an adolescent population, what are the return to sport rates and clinical outcomes following OATS in baseball players and gymnasts with unstable OCD lesions? SUMMARY OF KEY FINDINGS: Three articles met the inclusion criteria for this appraisal, and all indicate an OATS procedure should be considered in the management of unstable OCD lesions. Return to play outcomes were favorable for both baseball players and gymnasts. Self-reported patient function and elbow extension all improved following an OATS. CLINICAL BOTTOM LINE: An OATS procedure is a favorable option for the management of OCD lesions of the elbow in baseball players and gymnasts. STRENGTH OF RECOMMENDATION: There is level B evidence to support return to sport and clinical outcomes in baseball players and gymnasts following an OATS procedure. This score is directly related to the quality of evidence that currently exists on the topic.

Dynamic insights on transcription initiation and RNA processing during bacterial adaptation.

Transcription initiation and RNA processing govern gene expression and enable bacterial adaptation by reshaping the RNA landscape. The aim of this study was to simultaneously observe these two fundamental processes in a transcriptome responding to an environmental signal. A controlled σE system in E. coli was coupled to our previously described tagRNA-seq method to yield process kinetics information. Changes in transcription initiation frequencies (TIF) and RNA processing frequencies (PF) were followed using 5' RNA tags. Changes in TIF showed a binary increased/decreased pattern that alternated between transcriptionally activated and repressed promoters, providing the bacterial population with transcriptional oscillation. PF variation fell into three categories of cleavage activity: (i) constant and independent of RNA levels, (ii) increased once RNA has accumulated, and (iii) positively correlated to changes in TIF. This work provides a comprehensive and dynamic view of major events leading to transcriptomic reshaping during bacterial adaptation. It unveils an interplay between transcription initiation and the activity of specific RNA cleavage sites. This study utilized a well-known genetic system to analyze fundamental processes and can serve as a blueprint for comprehensive studies that exploit the RNA metabolism to decipher and understand bacterial gene expression control.

Percutaneous Transluminal Angioplasty for Below-the-Elbow Critical Hand Ischemia: A Systematic Review.

PURPOSE: To perform a systematic review assessing the safety and efficacy of percutaneous transluminal angioplasty (PTA) for treatment of critical hand ischemia (CHI) due to below-the-elbow (BTE) obstructive arterial disease. MATERIALS AND METHODS: MEDLINE and EMBASE systematic searches were performed from inception to December 2020 to identify studies assessing PTA for management of BTE obstructive arterial disease. Three independent reviewers performed abstract selection, data extraction, and quality assessment. The Newcastle-Ottawa Scale was used to assess individual study bias for non-randomized controlled trials. RESULTS: Eight studies comprising 176 patients with obstructive BTE vessel disease were included. All studies had a score >5 on the Newcastle-Ottawa Scale, indicative of high quality. All studies used low-profile balloons (1.5-4 mm) for PTA of stenotic lesions or chronic total occlusions (CTOs). The weighted average technical success and clinical success rates were 89.3% (range = 82%-100%) and 69.9% (range = 19%-100%), respectively, at a mean follow-up of 29.7 ± 17.1 months. The short-term (<30 days) complication rate was low at 4.7% and most commonly included access site hematomas, pseudoaneurysms, and radial artery perforation or re-thrombosis. Nearly 20% of patients required an amputation, and most (96%) were minor (either distal phalanges or digits). Only 2 patients required above-wrist amputations. The primary and secondary patency rate at 5 years were 38% and 54%, respectively. The cumulative 5-year mortality rate was 33.1%. CONCLUSIONS: PTA for CHI due to BTE obstructive arterial disease is feasible with a high technical success rate and a low short-term complication rate. Additional long-term comparative studies are required to unequivocally establish the clinical benefit of endovascular treatment compared with conservative management or surgical bypass.

Uterine Artery Embolization for Pedunculated Subserosal Fibroids: A Systematic Review and Meta-Analysis.

PURPOSE: To provide a comprehensive overview of the literature assessing the safety and efficacy of uterine artery embolization (UAE) for patients with pedunculated subserosal fibroids. MATERIALS AND METHODS: MEDLINE and Embase databases were searched without language or publication type restrictions for observational studies to estimate safety (adverse events) and efficacy (devascularization, fibroid volume reduction, and uterine volume reduction) outcomes. Case reports were included to qualitatively report adverse events. Meta-analysis was performed for single proportions and mean changes with random-effects modeling. RESULTS: Of 98 eligible articles, 11 studies were included in the final analysis. Of the adverse events detailed in these cases, 5 events were mild, 2 were moderate (torsion of pedunculated fibroid requiring laparoscopic myomectomy and persistent bleeding after embolization requiring hysterectomy), and 1 was severe (fibroid necrosis causing bowel obstruction requiring bowel resection and hysterectomy). There were no deaths reported in the literature. The pooled risk of adverse events was 1.7% (95% confidence interval [CI], 0.29%-9.2%; 4 of 181; I2 = 0%). The pooled devascularization rate was 75.9% (95% CI, 62.4%-85.6%; 140 of 189; I2 = 75%) at 3.91 months of follow-up. The percent volume reduction of the dominant pedunculated fibroid was 38.6% (95% CI, 33.0%-44.2%; I2 = 0%) at 4.3 months of follow-up. The percent uterine volume reduction was 36.7% (95% CI, 30.3%-43.0%; I2 = 47%) at 3.5 months of follow-up. CONCLUSIONS: UAE for pedunculated subserosal fibroids has a low risk of adverse events and effectively reduces fibroid and uterine size.

Arteries of the Lower Limb-Embryology, Variations, and Clinical Significance.

OBJECTIVES: The purpose of this article is to review the embryology of the lower limb arterial anatomy along with common variants and their clinical relevance. DESIGN: Embryologic variations of the lower limb arterial system may be explained by i.) persistence of primordial arterial segments, ii.) abnormal fusion, iii.) segmental hypoplasia/absence, or a combination of both. Persistent sciatic artery, corona mortis, and popliteal entrapment syndrome will also be discussed with associated symptoms, and potential complications. CONCLUSION: Knowledge of these variations is essential for surgical and endovascular management as failure to recognize them can result in complications.

Primary school teachers' contributions to oral health promotion in urban and rural areas of the Gulu District, Northern Uganda: a qualitative study.

BACKGROUND: Dental caries remains the most prevalent non-communicable disease globally affecting 60-90% of children. The World Health Organisation's (WHO) health-promoting school program offers a framework for dental intervention in low- and middle-income countries (LMICs). This study explored teacher contributions to children's oral health in relation to the WHO health-promoting school framework in rural Uganda. METHODS: Semi structured interviews were conducted with a purposive sample of 18 teachers. All interviews were transcribed verbatim and analysed thematically. RESULTS: Many teachers reported preparing children to practise proper oral hygiene care through skills training and demonstrations around proper teeth brushing. Teachers' roles included raising health awareness by providing information on oral health topics using different educational methods. Many teachers mentioned performing oral health examinations on children at the school, first aid, referral for dental treatments and engaging parents, students and health workers in oral health promotion. CONCLUSIONS: Teachers play an essential role in oral health promotion in countries like Uganda. Teachers are implementing key principles of the WHO's health-promoting school framework on the ground and need to be considered as a key public health resource. If improvements in oral health are to be attained in Sub-Saharan Africa and other LMICs, government interventions need to harness teachers' contributions in delivering oral health promotion.

Effectiveness of primary school-based interventions in improving oral health of children in low- and middle-income countries: a systematic review and meta-analysis.

BACKGROUND: Risk factors for oral disease can potentially be ameliorated by school-based interventions. This review evaluates the effectiveness of primary school-based interventions in improving oral health among children in low-and middle-income countries (LMICs). METHODS: Our systematic review was conducted in accordance with the Joanna Briggs Institute methodology for systematic reviews of effectiveness. Medline, Embase, Global Health, CINAHL, Emcare, Scopus, Web of Science, WHO website, Google Advanced and Google Scholar were searched for experimental and observational studies published between 1995 and 2021 in English. Quality assessment and data extraction of the articles were performed by two independent reviewers. The primary outcome was decayed, missing, and filled teeth/surfaces [dmft(s)/DMFT(S)] scores. Seven meta-analyses were conducted. RESULTS: The search yielded 1178 publications and after removing duplicates, 753 remained. A further 648 publications were excluded after screening titles and abstracts. 105 publications were reviewed in full and 34 were included. Narrative synthesis showed school-based interventions had a positive effect on oral health outcomes. Meta-analysis showed a significant positive effect on dental caries measured by DMFT scores (standardised mean difference (SMD) = - 0.33; 95% CI - 0.56 to - 0.10; P = 0.005), net increment in DMFS scores (SMD = - 1.09; 95% CI - 1.91 to - 0.27; P = 0.009), dmft and DMFT/S score > 1 (Risk Ratio = 0.70; 95% CI 0.53 to 0.94; P = 0.02) and plaque scores (SMD = - 0.32; 95% CI - 0.46 to - 0.18; P < 0.00001). Non-significant positive effect was observed for dental caries measured by net increment in DMFT scores (SMD = - 0.34; 95% CI - 0.69 to 0.02; P = 0.06) and DMFS scores (SMD = - 0.26; 95% CI - 0.70 to 0.18; P = 0.24), and gingival health (SMD = 0.12; 95% CI - 0.32 to 0.55; P = 0.60). Certainty of evidence was assessed as very low for all oral health outcomes. CONCLUSION: School-based interventions can be effective in reducing the burden of oral disease among primary school children in LMICs, with skills-based education, teacher training, provision of access to oral health services and parental engagement emerging as particularly promising. Further research is required to provide evidence of effectiveness of primary school-based interventions to improve oral health. Systematic review registration The title of this review was registered with PROSPERO (registration number: CRD42020202599).

Complication rates associated with antegrade use of vascular closure devices: a systematic review and pooled analysis.

BACKGROUND: Vascular closure devices (VCDs) have become a mainstay in endovascular interventions in recent years. On-label use only allows for retrograde interventions originating at the common femoral artery (CFA). However, off-label use in antegrade and/or superficial femoral artery (SFA) access has become more common in the treatment of peripheral arterial disease. Despite this, there is a paucity of comparative literature assessing individual VCD safety profiles and relative complication risks of CFA vs SFA applications. METHODS: MEDLINE and EMBASE systematic searches were performed from inception to October 2019 to identify studies assessing VCD use in antegrade CFA and SFA interventions. Abstract selection and data extraction were performed by two independent reviewers. Primary outcomes included bleeding-related complications, vessel occlusion or stenosis, embolization, pseudoaneurysm formation, or arteriovenous fistula formation. RESULTS: Twenty-four unique studies with 4124 vascular closure events via six unique VCDs were included (Angioseal, Exoseal, Femoseal, Glubran 2, Mynx, Starclose; 3698 CFA, 426 SFA). Pooled occurrence of all complications across closure devices used in the CFA and SFA ranged from 0.9% (Mynx) to 7.4% (Starclose) and 0% (Perclose) to 10.1% (Starclose), respectively, depending on VCD type. Clinically meaningful differences were identified between devices with a trend toward significance (P = .08 CFA, P = .07 SFA). Individual devices demonstrated a range of bleeding complication rates from 0.4% (Mynx) to 7.2% (Femoseal) for the CFA site and from 0% (Perclose) to 6.4% (Starclose) for the SFA site (P = .01 and P = .03, respectively). Significant heterogeneity between studies precludes definitive characterization of the device as cause for variations in bleeding complication rates. Pooled complication rates did not differ between the CFA and SFA arms (4.6% vs 5.8%, P = .56). Bleeding complication rates also did not differ between the CFA and SFA arms (3.6% vs 3.6%, P = .98). CONCLUSIONS: Clinically meaningful differences in overall pooled complications were identified between VCDs with a trend toward significance. Significant differences between VCDs exist with respect to bleeding risk. However, this must be interpreted with caution as these differences could be secondary to interstudy heterogeneity. Finally, no difference was identified between antegrade SFA and CFA VCD use with respect to overall complication and bleeding risks.