Conservative versus liberal oxygenation targets in critically ill children (Oxy-PICU): a UK multicentre, open, parallel-group, randomised clinical trial.

BACKGROUND: The optimal target for systemic oxygenation in critically ill children is unknown. Liberal oxygenation is widely practiced, but has been associated with harm in paediatric patients. We aimed to evaluate whether conservative oxygenation would reduce duration of organ support or incidence of death compared to standard care. METHODS: Oxy-PICU was a pragmatic, multicentre, open-label, randomised controlled trial in 15 UK paediatric intensive care units (PICUs). Children admitted as an emergency, who were older than 38 weeks corrected gestational age and younger than 16 years receiving invasive ventilation and supplemental oxygen were randomly allocated in a 1:1 ratio via a concealed, central, web-based randomisation system to conservative peripheral oxygen saturations ([SpO2] 88-92%) or liberal (SpO2 >94%) targets. The primary outcome was the duration of organ support at 30 days following random allocation, a rank-based endpoint with death either on or before day 30 as the worst outcome (a score equating to 31 days of organ support), with survivors assigned a score between 1 and 30 depending on the number of calendar days of organ support received. The primary effect estimate was the probabilistic index, a value greater than 0·5 indicating more than 50% probability that conservative oxygenation is superior to liberal oxygenation for a randomly selected patient. All participants in whom consent was available were included in the intention-to-treat analysis. The completed study was registered with the ISRCTN registry (ISRCTN92103439). FINDINGS: Between Sept 1, 2020, and May 15, 2022, 2040 children were randomly allocated to conservative or liberal oxygenation groups. Consent was available for 1872 (92%) of 2040 children. The conservative oxygenation group comprised 939 children (528 [57%] of 927 were female and 399 [43%] of 927 were male) and the liberal oxygenation group included 933 children (511 [56%] of 920 were female and 409 [45%] of 920 were male). Duration of organ support or death in the first 30 days was significantly lower in the conservative oxygenation group (probabilistic index 0·53, 95% CI 0·50-0·55; p=0·04 Wilcoxon rank-sum test, adjusted odds ratio 0·84 [95% CI 0·72-0·99]). Prespecified adverse events were reported in 24 (3%) of 939 patients in the conservative oxygenation group and 36 (4%) of 933 patients in the liberal oxygenation group. INTERPRETATION: Among invasively ventilated children who were admitted as an emergency to a PICU receiving supplemental oxygen, a conservative oxygenation target resulted in a small, but significant, greater probability of a better outcome in terms of duration of organ support at 30 days or death when compared with a liberal oxygenation target. Widespread adoption of a conservative oxygenation saturation target (SpO2 88-92%) could help improve outcomes and reduce costs for the sickest children admitted to PICUs. FUNDING: UK National Institute for Health and Care Research Health Technology Assessment Programme.

Targeted long-read sequencing identifies missing disease-causing variation.

Despite widespread clinical genetic testing, many individuals with suspected genetic conditions lack a precise diagnosis, limiting their opportunity to take advantage of state-of-the-art treatments. In some cases, testing reveals difficult-to-evaluate structural differences, candidate variants that do not fully explain the phenotype, single pathogenic variants in recessive disorders, or no variants in genes of interest. Thus, there is a need for better tools to identify a precise genetic diagnosis in individuals when conventional testing approaches have been exhausted. We performed targeted long-read sequencing (T-LRS) using adaptive sampling on the Oxford Nanopore platform on 40 individuals, 10 of whom lacked a complete molecular diagnosis. We computationally targeted up to 151 Mbp of sequence per individual and searched for pathogenic substitutions, structural variants, and methylation differences using a single data source. We detected all genomic aberrations-including single-nucleotide variants, copy number changes, repeat expansions, and methylation differences-identified by prior clinical testing. In 8/8 individuals with complex structural rearrangements, T-LRS enabled more precise resolution of the mutation, leading to changes in clinical management in one case. In ten individuals with suspected Mendelian conditions lacking a precise genetic diagnosis, T-LRS identified pathogenic or likely pathogenic variants in six and variants of uncertain significance in two others. T-LRS accurately identifies pathogenic structural variants, resolves complex rearrangements, and identifies Mendelian variants not detected by other technologies. T-LRS represents an efficient and cost-effective strategy to evaluate high-priority genes and regions or complex clinical testing results.

Frontiers in congenital disorders of glycosylation consortium, a cross-sectional study report at year 5 of 280 individuals in the natural history cohort.

OBJECTIVE: Our report describes clinical, genetic, and biochemical features of participants with a molecularly confirmed congenital disorder of glycosylation (CDG) enrolled in the Frontiers in Congenital Disorders of Glycosylation (FCDGC) Natural History cohort at year 5 of the study. METHODS: We enrolled individuals with a known or suspected CDG into the FCDGC Natural History Study, a multicenter prospective and retrospective natural history study of all genetic causes of CDG. We conducted a cross-sectional analysis of baseline study visit data from participants with confirmed CDG who were consented into the FCDGC Natural History Study (5U54NS115198) from October 2019 to November 2023. RESULTS: Three hundred thirty-three subjects consented to the FCDGC Natural History Study. Of these, 280 unique individuals had genetic data available that was consistent with a diagnosis of CDG. These 280 individuals were enrolled into the study between October 8, 2019 and November 29, 2023. One hundred forty-one (50.4%) were female, and 139 (49.6%) were male. Mean and median age at enrollment was 10.1 and 6.5 years, respectively, with a range of 0.22 to 71.4 years. The cohort encompassed individuals with disorders of N-linked protein glycosylation (57%), glycosylphosphatidylinositol anchor disorder (GPI anchor) (15%), disorders of Golgi homeostasis, trafficking and transport (12%), dolichol metabolism disorders (5%), disorders of multiple pathways (6%), and other (5%). The most frequent presenting symptom(s) leading to diagnosis were developmental delay/disability (77%), followed by hypotonia (56%) and feeding difficulties (42%). Mean and median time between first related symptom and diagnosis was 2.7 and 0.8 years, respectively. One hundred percent of individuals in our cohort had developmental differences/disabilities at the time of their baseline visit, followed by 97% with neurologic involvement, 91% with gastrointestinal (GI)/liver involvement, and 88% with musculoskeletal involvement. Severity of disease in individuals was scored on the Nijmegen Progression CDG Rating Scale (NPCRS) with 27% of scores categorized as mild, 44% moderate, and 29% severe. Of the individuals with N-linked protein glycosylation defects, 83% of those with data showed a type 1 pattern on carbohydrate deficient transferrin (CDT) analysis including 82/84 individuals with PMM2-CDG, 6% a type 2 pattern, 1% both type 1 and type 2 pattern and 10% a normal or nonspecific pattern. One hundred percent of individuals with Golgi homeostasis and trafficking defects with data showed a type 2 pattern on CDT analysis, while Golgi transport defect showed a type II pattern 73% of the time, a type 1 pattern for 7%, and 20% had a normal or nonspecific pattern. Most of the variants documented were classified as pathogenic or likely pathogenic using ACMG criteria. For the majority of the variants, the predicted molecular consequence was missense followed by nonsense and splice site, and the majority of the diagnoses are inherited in an autosomal recessive pattern but with disorders of all major nuclear inheritance included. DISCUSSION: The FCDGC Natural History Study serves as an important resource to build future research studies, improve clinical care, and prepare for clinical trial readiness. Herein is the first overview of CDG participants of the FCDGC Natural History Study.

Elevated oxysterol and N-palmitoyl-O-phosphocholineserine levels in congenital disorders of glycosylation.

Congenital disorders of glycosylation (CDG) and Niemann-Pick type C (NPC) disease are inborn errors of metabolism that can both present with infantile-onset severe liver disease and other multisystemic manifestations. Plasma bile acid and N-palmitoyl-O-phosphocholineserine (PPCS) are screening biomarkers with proposed improved sensitivity and specificity for NPC. We report an infant with ATP6AP1-CDG who presented with cholestatic liver failure and elevated plasma oxysterols and bile acid, mimicking NPC clinically and biochemically. On further investigation, PPCS, but not the bile acid derivative N-(3ß,5α,6ß-trihydroxy-cholan-24-oyl) glycine (TCG), were elevated in plasma samples from individuals with ATP6AP1-, ALG1-, ALG8-, and PMM2-CDG. These findings highlight the importance of keeping CDG within the diagnostic differential when evaluating children with early onset severe liver disease and elevated bile acid or PPCS to prevent delayed diagnosis and treatment.

Fractionated plasma N-glycan profiling of novel cohort of ATP6AP1-CDG subjects identifies phenotypic association.

ATP6AP1-CDG is an X-linked disorder typically characterized by hepatopathy, immunodeficiency, and an abnormal type II transferrin glycosylation pattern. Here, we present 11 new patients and clinical updates with biochemical characterization on one previously reported patient. We also document intrafamilial phenotypic variability and atypical presentations, expanding the symptomatology of ATP6AP1-CDG to include dystonia, hepatocellular carcinoma, and lysosomal abnormalities on hepatic histology. Three of our subjects received successful liver transplantation. We performed N-glycan profiling of total and fractionated plasma proteins for six patients and show associations with varying phenotypes, demonstrating potential diagnostic and prognostic value of fractionated N-glycan profiles. The aberrant N-linked glycosylation in purified transferrin and remaining plasma glycoprotein fractions normalized in one patient post hepatic transplant, while the increases of Man4GlcNAc2 and Man5GlcNAc2 in purified immunoglobulins persisted. Interestingly, in the single patient with isolated immune deficiency phenotype, elevated high-mannose glycans were detected on purified immunoglobulins without glycosylation abnormalities on transferrin or the remaining plasma glycoprotein fractions. Given the diverse and often tissue specific clinical presentations and the need of clinical management post hepatic transplant in ATP6AP1-CDG patients, these results demonstrate that fractionated plasma N-glycan profiling could be a valuable tool in diagnosis and disease monitoring.

Assessing the Effect of Time from Injection of Collagenase to Manipulation on Success Rates in Dupuytren Disease.

PURPOSE: Dupuytren disease can be managed with an injection of collagenase Clostridium histolyticum enzyme followed by manual manipulation. Although the recommended time from injection to manipulation is 24-72 hours, patient and physician schedules may not accommodate this time frame. Therefore, we sought to study the impact of time from injection to manipulation on outcomes and complications of collagenase injection. METHODS: We performed a review of 309 patients who underwent an injection of collagenase Clostridium histolyticum for Dupuytren disease with manipulation at two, five, or seven days after injection. We compared preinjection and postinjection contracture angles as well as frequency of skin tears and tendon ruptures. RESULTS: Of the 309 patients, 207 underwent manipulation at two days, 32 at five days, and 70 at seven days. Patients had similar preinjection contracture angles. All patients demonstrated improvement in contracture after manipulation. Rates of skin tears and tendon ruptures were similar in all three groups. Significant predictors of complications included number of cords injected and history of previous collagenase injection, but not history of previous Dupuytren diagnosis. CONCLUSIONS: Although collagenase injection for Dupuytren disease is typically performed with plans for manipulation at 24-72 hours, postinjection manipulation could be performed as late as seven days without adversely affecting the frequency of skin and tendon complications. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

Frequency, Indications and Intraoperative Dynamics of Repositioning of the Lateral Crura of the Lower Lateral Cartilage: A 35-Year Experience.

BACKGROUND: Lower lateral cartilage repositioning (LLCR) is an effective technique that places the lateral crus in a newly created caudal pocket, and is utilized for a variety of indications including cephalic malposition, alar asymmetries and tip rotation/projection alteration. However, there is a relative sparsity in the literature regarding this procedure and the dynamic changes that it produces. In this study, we report our experience with LLCR in regard to its indications and related interplays. METHODS: Data from our institution were collected from the most recent 100 primary rhinoplasties, most recent 100 secondary rhinoplasties and all LLCRs performed. For each LLCR, patient demographics and concurrent surgical techniques were compiled. A descriptive analysis was performed for all cohorts, while Fischer's exact test was performed to compare the associations of categorical data for the respective sample sizes of the primary and secondary rhinoplasty cohorts. RESULTS: Overall, 127 patients underwent LLCR, with eleven (11%) LLCRs in the primary rhinoplasty cohort and twelve (12%) LLCRs in the secondary rhinoplasty cohort. The most common indication for LLCR was cephalic malposition, followed by over-projection and asymmetry of the lower lateral cartilages. Intraoperative observation of dynamic changes included invariable cephalic rotation of the tip, ability to precisely control the tip projection, drastic narrowing of the domal arch often minimizing the need for the transdomal suture, alar repositioning caudally, correction of alar retraction and more elegant tip definition. However, the external valve lost its strength on majority of LLCR patients, which required almost routine use of Gunter lateral crus strut. CONCLUSION: LLCR is a powerful and versatile tool that can be utilized in either primary or secondary rhinoplasty. Its transposition results in cephalic rotation of the tip, narrowing of the domal arch, caudal reposition of the alar rim and superior tip definition. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266.

The Versatile Role of Fat Injection During Various Genioplasties.

BACKGROUND: Fat injection has become increasingly popular in aesthetic surgery, but there is a sparsity of literature regarding its role during genioplasty. In this study, we present the largest series of patients receiving fat injections to the chin for various indications. METHODS: Data were collected from January 2016 to December 2021 for patients who underwent chin fat injection for a variety of chin refinements. Patients with chin fat injection were divided into isolated genioplasty with fat injection (CF), combined facial and chin fat injection (CFC) and combined chin fat injection and osseous genioplasty (CFG). Complication rates and reoperations were compared using Fischer's exact test between each cohort. RESULTS: 181 patients were included in final analysis, with 14 patients in CF cohort, 130 patients in CFC cohort, 24 patients in CFG cohort, and 13 patients who underwent genioplasty alone. Repeat fat injections were required in 17 (9.4%) patients overall, which included 14 patients (10.8%) of CFC subcohort and three patients (12.5%) of CFG subcohort (p > 0.05). No patients who underwent genioplasty alone or CF required reoperation. There were no significant differences in complications between genioplasty alone group (0%) in comparison to CF (7.1%; p = 1.00), CFC (6.2%; p = .53), or CFG cohorts (7.7%; p = 1.00). CONCLUSION: Fat injection can safely correct minor chin deficiency or asymmetry, as either an isolated procedure or in combination with osteotomies. Additionally, fat injection enables advancement of the caudal segment to achieve superior outcomes by preventing unaesthetic deepening of labiomental groove which will not be advanced during sliding osteotomy. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Common Dorsal Flaws Following Preservation Rhinoplasty: A Systemic Analysis.

BACKGROUND: There has recently been a resurgence of interest in preservation rhinoplasty (PR) for dorsal hump elimination or dorsal projection reduction. However, no studies have scrutinized aesthetic outcomes to identify common pattern of flaws seen in published images to aid those with ardent enthusiasm for this technique to become aware of the frequency of these flaws and find ways to reduce imperfections. METHODS: A systematic literature review was performed using search terms ("preservation" OR "let down", "push down") AND "rhinoplasty" on PubMed, Cochrane, SCOPUS, and EMBASE databases for studies between January 2000 and December 2022. Patient images from these studies were analyzed by three reviewers (MWW, IAC, and BG) for dorsal flaws. Raw interrater agreement percentage and Krippendorff's alpha were calculated to determine interrater reliability. A descriptive and comparative analysis with Fisher's exact test was performed for the aggregate data. RESULTS: There were 59 patient images with 464 views from 24 studies included for final analysis. Optimal dorsal aesthetic lines (DAL) were noted in 12 patients (20.3%), while optimal profile was observed in 15 patients (25.4%) (p = 0.66). Combined ideal front and profile view of dorsum was not observed on any patients. The most common flaws were DAL irregularities (n = 45; 78.0%), dorsal deviation (n = 32, 54.2%), and residual hump (n = 25, 42.4%). There was excellent interrater agreement. CONCLUSIONS: While PR may have some advantages, it has shortcomings in outcomes, particularly dorsal irregularities, dorsal deviation, and residual humps. Awareness of these imperfections may compel those performing this procedure to modify their techniques and improve their results. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The Logical Sequence of Primary Open Rhinoplasty Founded on the Principles of Rhinoplasty Dynamics.

Rhinoplasty is a perplexing procedure due to the variety of complex interplays between anatomical structures of the nose and the maneuvers used to accomplish the intended objective. Although every rhinoplasty is individualized, having a systematic order and an algorithm is crucial to achieve the designed aesthetic goals and a superior outcome, considering the interactions between maneuvers. Otherwise, the accumulated, unanticipated effects will result in displeasing outcomes due to over or under correction. In this report, we describe the sequential steps of rhinoplasty based on knowledge that the senior author has garnered over four decades of experience and having studied the rhinoplasty dynamics continually. Furthermore, we explain the detailed reasoning for each maneuver based on surgical indications and the resulting interplays.Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266.

Exploring the Resurgence of the Preservation Rhinoplasty: A Systematic Literature Review.

INTRODUCTION: The underlying principles of preservation rhinoplasty (PR) center around maintaining the soft tissue envelope, dorsum, and alar cartilage through surgical manipulations and tip suture techniques. In particular, the let-down (LD) and push-down (PD) techniques have been described, although reports of indications and outcomes in the literature are sparse. METHODS: A systematic review of the literature was performed using search terms "preservation" OR "let down" OR "push down" AND "rhinoplasty" on PubMed, Cochrane, SCOPUS, and EMBASE databases. Patient demographic information, operative details, and surgical outcomes were recorded. Sub-cohorts for patients who underwent LD and PD techniques were analyzed utilizing Fischer's exact test for categorical variables and Student's t test for continuous variables. RESULTS: Overall, there were 5967 PR patients in 30 studies in the final analysis, with 307 patients in the PD cohort and 529 patients in the LD cohort. The Rhinoplasty Outcome Evaluation Questionnaire showed a significant increase of patient satisfaction after PR compared to before PR (62.13 vs 91.14; p < 0.001). There was a significantly lower rate of residual dorsal hump or recurrence of 1.3% (n = 4) in the PD when compared to 4.6% (n = 23) in LD cohorts (p = 0.02). The revision rate of PD (0%, n = 0) was also significantly lower than that of LD (5.0%, n = 25) (p < 0.001). CONCLUSION: Based on these published articles, it seems that preservation rhinoplasty is safe and efficacious procedure with improved dorsal aesthetic lines, reduced dorsal contour irregularities, and claimed excellent patient satisfaction. In particular, the PD technique has fewer reported complications and revisions than LD approach, although PD is often indicated in patients with smaller dorsal humps. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Homozygous Mutations in CSF1R Cause a Pediatric-Onset Leukoencephalopathy and Can Result in Congenital Absence of Microglia.

Microglia are CNS-resident macrophages that scavenge debris and regulate immune responses. Proliferation and development of macrophages, including microglia, requires Colony Stimulating Factor 1 Receptor (CSF1R), a gene previously associated with a dominant adult-onset neurological condition (adult-onset leukoencephalopathy with axonal spheroids and pigmented glia). Here, we report two unrelated individuals with homozygous CSF1R mutations whose presentation was distinct from ALSP. Post-mortem examination of an individual with a homozygous splice mutation (c.1754-1G>C) demonstrated several structural brain anomalies, including agenesis of corpus callosum. Immunostaining demonstrated almost complete absence of microglia within this brain, suggesting that it developed in the absence of microglia. The second individual had a homozygous missense mutation (c.1929C>A [p.His643Gln]) and presented with developmental delay and epilepsy in childhood. We analyzed a zebrafish model (csf1rDM) lacking Csf1r function and found that their brains also lacked microglia and had reduced levels of CUX1, a neuronal transcription factor. CUX1+ neurons were also reduced in sections of homozygous CSF1R mutant human brain, identifying an evolutionarily conserved role for CSF1R signaling in production or maintenance of CUX1+ neurons. Since a large fraction of CUX1+ neurons project callosal axons, we speculate that microglia deficiency may contribute to agenesis of the corpus callosum via reduction in CUX1+ neurons. Our results suggest that CSF1R is required for human brain development and establish the csf1rDM fish as a model for microgliopathies. In addition, our results exemplify an under-recognized form of phenotypic expansion, in which genes associated with well-recognized, dominant conditions produce different phenotypes when biallelically mutated.

A rapid and non-invasive proteomic analysis using DBS and buccal swab for multiplexed second-tier screening of Pompe disease and Mucopolysaccharidosis type I.

PURPOSE: Current newborn screening programs for Pompe disease (PD) and mucopolysaccharidosis type I (MPS I) suffer from a high false positive rate and long turnaround time for clinical follow up. This study aimed to develop a novel proteomics-based assay for rapid and accurate second-tier screening of PD and MPS I. A fast turnaround assay would enable the identification of severe cases who need immediate clinical follow up and treatment. METHODS: We developed an immunocapture coupled with mass spectrometry-based proteomics (Immuno-SRM) assay to quantify GAA and IDUA proteins in dried blood spots (DBS) and buccal swabs. Sensitivity, linearity, reproducibility, and protein concentration range in healthy control samples were determined. Clinical performance was evaluated in known PD and MPS I patients as well as pseudodeficiency and carrier cases. RESULTS: Using three 3.2 mm punches (~13.1 µL of blood) of DBS, the assay showed reproducible and sensitive quantification of GAA and IDUA. Both proteins can also be quantified in buccal swabs with high reproducibility and sensitivity. Infantile onset Pompe disease (IOPD) and severe MPS I cases are readily identifiable due to the absence of GAA and IDUA, respectively. In addition, late onset Pompe disease (LOPD) and attenuated MPS I patients showed much reduced levels of the target protein. By contrast, pseudodeficiency and carrier cases exhibited significant higher target protein levels compared to true patients. CONCLUSION: Direct quantification of endogenous GAA and IDUA peptides in DBS by Immuno-SRM can be used for second-tier screening to rapidly identify severe PD and MPS I patients with a turnaround time of <1 week. Such patients could benefit from immediate clinical follow up and possibly earlier treatment.

Personal radiofrequency electromagnetic field exposure of adolescents in the Greater London area in the SCAMP cohort and the association with restrictions on permitted use of mobile communication technologies at school and at home.

Personal measurements of radiofrequency electromagnetic fields (RF-EMF) have been used in several studies to characterise personal exposure in daily life, but such data are limitedly available for adolescents, and not yet for the United Kingdom (UK). In this study, we aimed to characterise personal exposure to RF-EMF in adolescents and to study the association between exposure and rules applied at school and at home to restrict wireless communication use, likely implemented to reduce other effects of mobile technology (e.g. distraction). We measured exposure to RF-EMF for 16 common frequency bands (87.5 MHz-3.5 GHz), using portable measurement devices (ExpoM-RF), in a subsample of adolescents participating in the cohort Study of Cognition, Adolescents and Mobile Phones (SCAMP) from Greater London (UK) (n = 188). School and home rules were assessed by questionnaire and concerned the school's availability of WiFi and mobile phone policy, and parental restrictions on permitted mobile phone use. Adolescents recorded their activities in real time using a diary app on a study smartphone, while characterizing their personal RF-EMF exposure in daily life, during different activities and times of the day. Data analysis was done for 148 adolescents from 29 schools who recorded RF-EMF data for a median duration of 47 h. The majority (74%) of adolescents spent part of their time at school during the measurement period. Median total RF-EMF exposure was 40 µW/m2 at home, 94 µW/m2 at school, and 100 µW/m2 overall. In general, restrictions at school or at home made little difference for adolescents' measured exposure to RF-EMF, except for uplink exposure from mobile phones while at school, which was found to be significantly lower for adolescents attending schools not permitting phone use at all, compared to adolescents attending schools allowing mobile phone use during breaks. This difference was not statistically significant for total personal exposure. Total exposure to RF-EMF in adolescents living in Greater London tended to be higher compared to exposure levels reported in other European countries. This study suggests that school policies and parental restrictions are not associated with a lower RF-EMF exposure in adolescents.

Medical education interventions influencing physician distribution into underserved communities: a scoping review.

BACKGROUND AND OBJECTIVE: Physician maldistribution is a global problem that hinders patients' abilities to access healthcare services. Medical education presents an opportunity to influence physicians towards meeting the healthcare needs of underserved communities when establishing their practice. Understanding the impact of educational interventions designed to offset physician maldistribution is crucial to informing health human resource strategies aimed at ensuring that the disposition of the physician workforce best serves the diverse needs of all patients and communities. METHODS: A scoping review was conducted using a six-stage framework to help map current evidence on educational interventions designed to influence physicians' decisions or intention to establish practice in underserved areas. A search strategy was developed and used to conduct database searches. Data were synthesized according to the types of interventions and the location in the medical education professional development trajectory, that influence physician intention or decision for rural and underserved practice locations. RESULTS: There were 130 articles included in the review, categorized according to four categories: preferential admissions criteria, undergraduate training in underserved areas, postgraduate training in underserved areas, and financial incentives. A fifth category was constructed to reflect initiatives comprised of various combinations of these four interventions. Most studies demonstrated a positive impact on practice location, suggesting that selecting students from underserved or rural areas, requiring them to attend rural campuses, and/or participate in rural clerkships or rotations are influential in distributing physicians in underserved or rural locations. However, these studies may be confounded by various factors including rural origin, pre-existing interest in rural practice, and lifestyle. Articles also had various limitations including self-selection bias, and a lack of standard definition for underservedness. CONCLUSIONS: Various educational interventions can influence physician practice location: preferential admissions criteria, rural experiences during undergraduate and postgraduate medical training, and financial incentives. Educators and policymakers should consider the social identity, preferences, and motivations of aspiring physicians as they have considerable impact on the effectiveness of education initiatives designed to influence physician distribution in underserved locations.

Protocol for a Randomized Multiple Center Trial of Conservative Versus Liberal Oxygenation Targets in Critically Ill Children (Oxy-PICU): Oxygen in Pediatric Intensive Care.

OBJECTIVES: Oxygen administration is a fundamental part of pediatric critical care, with supplemental oxygen offered to nearly every acutely unwell child. However, optimal targets for systemic oxygenation are unknown. Oxy-PICU aims to evaluate the clinical effectiveness and cost-effectiveness of a conservative peripheral oxygen saturation (Sp o2 ) target of 88-92% compared with a liberal target of more than 94%. DESIGN: Pragmatic, open, multiple-center, parallel group randomized control trial with integrated economic evaluation. SETTING: Fifteen PICUs across England, Wales, and Scotland. PATIENTS: Infants and children age more than 38 week-corrected gestational age to 16 years who are accepted to a participating PICU as an unplanned admission and receiving invasive mechanical ventilation with supplemental oxygen for abnormal gas exchange. INTERVENTION: Adjustment of ventilation and inspired oxygen settings to achieve an Sp o2 target of 88-92% during invasive mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Randomization is 1:1 to a liberal Sp o2 target of more than 94% or a conservative Sp o2 target of 88-92% (inclusive), using minimization with a random component. Minimization will be performed on: age, site, primary reason for admission, and severity of abnormality of gas exchange. Due to the emergency nature of the treatment, approaching patients for written informed consent will be deferred to after randomization. The primary clinical outcome is a composite of death and days of organ support at 30 days. Baseline demographics and clinical status will be recorded as well as daily measures of oxygenation and organ support, and discharge outcomes. This trial received Health Research Authority approval on December 23, 2019 (reference: 272768), including a favorable ethical opinion from the East of England-Cambridge South Research Ethics Committee (reference number: 19/EE/0362). Trial findings will be disseminated in national and international conferences and peer-reviewed journals.

Research experiences for Canadian aspiring physicians: a descriptive analysis of medical school admission policies concerning research involvement in Canada.

BACKGROUND: Many aspiring physicians perceive research experience as a way to support their medical school applications; however, the importance of research experiences as articulated in medical school admission policies is unclear. This is significant since policies and other discursive signals about selection processes can influence the behaviour of aspiring physicians. The purpose of this study is to describe the ways through which Canadian medical schools articulate the importance of research experiences in publicly available policy documents. METHODS: From January to June 2021, the authors reviewed publicly available selection criteria, application materials, institutional and research-related web pages associated with the 17 Canadian medical schools alongside high-level Canadian articulations of important competencies for physicians. These materials were analyzed using a qualitative descriptive approach. The authors considered concordance and/or discordance within each school's stance on the importance of research experiences in their selection criteria and application materials. RESULTS: Research experiences are typically not explicitly required for entry into a Canadian Doctor of Medicine (MD) program; however, there are expectations that graduating physicians should understand research. All 17 Canadian medical schools signal an appreciation for the value of research on an institutional level. Review of selection criteria and application materials show that five Canadian medical schools suggest to aspiring physicians that research experiences are important for admission and four do not suggest that research experiences are important for admission. There were both intra-institution and inter-institution discordance concerning the importance of research experiences for medical school applicant selection in one and seven medical schools respectively. CONCLUSIONS: Given the significant variance among the 17 Canadian medical schools, it is worthwhile for medical schools to evaluate their front-facing admission policies with consideration of the potential impact it might have on the behaviour of aspiring physicians, to ensure best selection of future physicians.

Repair Sequence and Management of the Premaxilla in Patients With Bilateral Cleft Lip and Palate: A Systematic Review of the Literature.

BACKGROUND: Bilateral cleft lip and palate (BCLP) remains a difficult surgical problem due to the severely protruding premaxillary segment, with no consensus of optimal treatment sequence in older patients. A systematic review of the literature was performed to assess the current status of BCLP repair based on age. METHODS: A PRISMA systematic review of the PubMed, Web of Science, and Embase databases was performed using a series of search terms related to BCLP. Studies were categorized based on the age of presentation, repair sequence, and technique. RESULTS: The database search identified 381 articles. Of these, 72 manuscripts were ultimately included. The lip was repaired first in 1077 patients (86.0%), palate first in 161 patients (12.9%), and simultaneous lip and palate in 14 patients (1.1%). Patients less than 6 months old received lip repair first (n = 959, 98.6%), with complications of unaesthetic appearance (n = 86, 62.3%) and midface retrusion (n = 41, 34.1%) in younger patients and wound dehiscence (n = 8, 40%) in older patients. Primary lip repair was preceded by presurgical orthopedics (n = 760) or lip adhesion (n = 272) to reduce lip tension with nasoalveolar molding (n = 452, 62.9%) or the Latham device (n = 282, 37.1%). In older patients, the palate was repaired first or premaxillary setback (n = 222) was indicated in protruded premaxillae greater than 10 mm, but carried the risk of premaxilla mobility (n = 20, 37.7%) and midface retrusion (n = 10, 18.9%). CONCLUSION: In younger patients, lip repair is performed first with preoperative orthopedics or lip adhesion. In older patients, the palate is more commonly repaired first compared with the lip; however, there is no difference in complication rate.

Maxillary and Mandibular Healing After Facial Allotransplantation.

INTRODUCTION: Facial transplantation has emerged as a viable option in treating devastating facial injuries.Despite the high healing rate of Le Fort III and bilateral sagittal split osteotomies (BSSO) in nontransplant patients, few studies have reported assessment of maxillary and mandibular healing in face transplant patients compared with nontransplant patients. The aim of this study was to examine differences in bone healing in our patients. PATIENTS AND METHODS: A retrospective chart review was conducted of facial allotransplantation patients at the Cleveland Clinic from December 2008 to inception. Demographics such as age, date of birth, and sex were recorded. Additional variables included procedures, revisions, reoperations, medications, and bone stability and healing. Computed tomography (CT) images assessed the alignment of skeletal components, bony union quality, and stability of fixation. RESULTS: Three patients were included: 2 had Le Fort III segment transplantation, and 1 had transplantation of both a Le Fort III segment and mandibular BSSO. The Le Fort III segment in all patients exhibited mobility and fibrous union at the Le Fort III osteotomy on CT. In contrast, the BSSO healed uneventfully after transplantation and revision surgery, with bony union confirmed by both CT and histology of the fixation area between the donor and recipient mandible bilaterally. No patients with midfacial fibrous union required revision of the nonunion as they were clinically asymptomatic. CONCLUSION: Le Fort osteotomy demonstrates inferior healing in facial transplantation compared with the nontransplant population. In contrast, the successful healing in the mandible is likely owing to the high density of rich cancellous bone.

A Longitudinal, Geographical, and Descriptive Analysis of Political Contributions of Plastic Surgeons.

BACKGROUND: Political contributions from healthcare providers are essential to shaping healthcare policy and allow physicians to expand their influence on a national level. Political Action Committees in particular provide a useful avenue for unifying contributions for the interest of a specific community. This study examined the geographical distribution, temporal pattern, and overall nature of the political contributions made by plastic surgeons. METHODS: The Federal Election Commission was analyzed for political contributions made by plastic surgeons from 2003 to 2021 using the search terms "plastic surgeon," "microsurgeon," and "craniofacial" as well as physician contributions to PlastyPAC. Contributions were categorized based on political parties (Democratic, Republican, and independent parties), and further analyzed based on state distribution and year of contribution. Spatial distribution data were then visualized using heatmaps for each state. RESULTS: The total sum of contributions between 2003 and 2021 from plastic surgeons was $5,306,605, with $1,737,178.51 for the Republican party, $962,773.26 for the Democratic party, and $2,604,149.86 for independent parties. Political funding of PlastyPAC consisted of 47.3% of the overall political contributions. There was no significant trend through the years in the overall contribution amount. The states with the most political contributions were California, New York, Florida, and Texas. CONCLUSIONS: The temporal stagnation of total political contributions and decline in recent PlastyPAC funding from plastic surgeons support an increased political awareness for new plastic surgeons. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .