An international RAND/UCLA expert panel to determine the optimal diagnosis and management of burn inhalation injury.

BACKGROUND: Burn inhalation injury (BII) is a major cause of burn-related mortality and morbidity. Despite published practice guidelines, no consensus exists for the best strategies regarding diagnosis and management of BII. A modified DELPHI study using the RAND/UCLA (University of California, Los Angeles) Appropriateness Method (RAM) systematically analysed the opinions of an expert panel. Expert opinion was combined with available evidence to determine what constitutes appropriate and inappropriate judgement in the diagnosis and management of BII. METHODS: A 15-person multidisciplinary panel comprised anaesthetists, intensivists and plastic surgeons involved in the clinical management of major burn patients adopted a modified Delphi approach using the RAM method. They rated the appropriateness of statements describing diagnostic and management options for BII on a Likert scale. A modified final survey comprising 140 statements was completed, subdivided into history and physical examination (20), investigations (39), airway management (5), systemic toxicity (23), invasive mechanical ventilation (29) and pharmacotherapy (24). Median appropriateness ratings and the disagreement index (DI) were calculated to classify statements as appropriate, uncertain, or inappropriate. RESULTS: Of 140 statements, 74 were rated as appropriate, 40 as uncertain and 26 as inappropriate. Initial intubation with ≥ 8.0 mm endotracheal tubes, lung protective ventilatory strategies, initial bronchoscopic lavage, serial bronchoscopic lavage for severe BII, nebulised heparin and salbutamol administration for moderate-severe BII and N-acetylcysteine for moderate BII were rated appropriate. Non-protective ventilatory strategies, high-frequency oscillatory ventilation, high-frequency percussive ventilation, prophylactic systemic antibiotics and corticosteroids were rated inappropriate. Experts disagreed (DI ≥ 1) on six statements, classified uncertain: the use of flexible fiberoptic bronchoscopy to guide fluid requirements (DI = 1.52), intubation with endotracheal tubes of internal diameter < 8.0 mm (DI = 1.19), use of airway pressure release ventilation modality (DI = 1.19) and nebulised 5000IU heparin, N-acetylcysteine and salbutamol for mild BII (DI = 1.52, 1.70, 1.36, respectively). CONCLUSIONS: Burns experts mostly agreed on appropriate and inappropriate diagnostic and management criteria of BII as in published guidance. Uncertainty exists as to the optimal diagnosis and management of differing grades of severity of BII. Future research should investigate the accuracy of bronchoscopic grading of BII, the value of bronchial lavage in differing severity groups and the effectiveness of nebulised therapies in different severities of BII.

Long-term (180-Day) Outcomes in Critically Ill Patients With COVID-19 in the REMAP-CAP Randomized Clinical Trial.

Importance: The longer-term effects of therapies for the treatment of critically ill patients with COVID-19 are unknown. Objective: To determine the effect of multiple interventions for critically ill adults with COVID-19 on longer-term outcomes. Design, Setting, and Participants: Prespecified secondary analysis of an ongoing adaptive platform trial (REMAP-CAP) testing interventions within multiple therapeutic domains in which 4869 critically ill adult patients with COVID-19 were enrolled between March 9, 2020, and June 22, 2021, from 197 sites in 14 countries. The final 180-day follow-up was completed on March 2, 2022. Interventions: Patients were randomized to receive 1 or more interventions within 6 treatment domains: immune modulators (n = 2274), convalescent plasma (n = 2011), antiplatelet therapy (n = 1557), anticoagulation (n = 1033), antivirals (n = 726), and corticosteroids (n = 401). Main Outcomes and Measures: The main outcome was survival through day 180, analyzed using a bayesian piecewise exponential model. A hazard ratio (HR) less than 1 represented improved survival (superiority), while an HR greater than 1 represented worsened survival (harm); futility was represented by a relative improvement less than 20% in outcome, shown by an HR greater than 0.83. Results: Among 4869 randomized patients (mean age, 59.3 years; 1537 [32.1%] women), 4107 (84.3%) had known vital status and 2590 (63.1%) were alive at day 180. IL-6 receptor antagonists had a greater than 99.9% probability of improving 6-month survival (adjusted HR, 0.74 [95% credible interval {CrI}, 0.61-0.90]) and antiplatelet agents had a 95% probability of improving 6-month survival (adjusted HR, 0.85 [95% CrI, 0.71-1.03]) compared with the control, while the probability of trial-defined statistical futility (HR >0.83) was high for therapeutic anticoagulation (99.9%; HR, 1.13 [95% CrI, 0.93-1.42]), convalescent plasma (99.2%; HR, 0.99 [95% CrI, 0.86-1.14]), and lopinavir-ritonavir (96.6%; HR, 1.06 [95% CrI, 0.82-1.38]) and the probabilities of harm from hydroxychloroquine (96.9%; HR, 1.51 [95% CrI, 0.98-2.29]) and the combination of lopinavir-ritonavir and hydroxychloroquine (96.8%; HR, 1.61 [95% CrI, 0.97-2.67]) were high. The corticosteroid domain was stopped early prior to reaching a predefined statistical trigger; there was a 57.1% to 61.6% probability of improving 6-month survival across varying hydrocortisone dosing strategies. Conclusions and Relevance: Among critically ill patients with COVID-19 randomized to receive 1 or more therapeutic interventions, treatment with an IL-6 receptor antagonist had a greater than 99.9% probability of improved 180-day mortality compared with patients randomized to the control, and treatment with an antiplatelet had a 95.0% probability of improved 180-day mortality compared with patients randomized to the control. Overall, when considered with previously reported short-term results, the findings indicate that initial in-hospital treatment effects were consistent for most therapies through 6 months.

Efficacy and Complications of External and Internal Pediatric Blepharoptosis Repair Techniques: A Systematic Review.

PURPOSE: To review and evaluate the efficacy and complication rates of external and internal blepharoptosis repair techniques in pediatric patients. METHODS: The systematic review protocol was published on PROSPERO (CRD42020197343). Embase, MEDLINE, CENTRAL, and ClinicalTrials.gov were searched without date limitations. Two independent reviewers evaluated the articles for inclusion. Study quality and risk of bias were assessed using GRADE and Cochrane's ROBINS-I tool, respectively. RESULTS: Of 2,228 articles screened, 23 studies involving 730 patients were included. There were 20 case series and 3 retrospective cohort studies, but no randomized controlled studies. Overall study quality was low with serious risk of bias according to the GRADE and ROBINS-I criteria, respectively. External levator resection was the most studied procedure, evaluated in 18 studies. Seven studies investigated internal approaches including the Fasanella-Servat procedure. There was no standardized evaluation of surgical efficacy. Reoperation rates were 16.6% (range 3.6-50.9%) for external levator resection compared with 22.2% (range 0.0-25.8%) for internal approaches. The commonest postoperative complications were not sight-threatening. The most consistently reported complication was undercorrection, occurring at rates of 8.4% (range 2.4-16.7%) and 15.3% (range 2.7-75.0%) for external levator resection and internal approaches, respectively. There were no consistently applied, validated patient-reported outcomes or cosmetic outcomes. CONCLUSIONS: External and internal approaches have been successfully employed in pediatric blepharoptosis repair. However, noncomparative designs and risk-of-bias limit existing studies. Thus, prospectively designed studies with standardized outcome measures are required to minimize reporting bias, facilitate evidence synthesis, and support clinical decision making.

Evidence-Based Blepharoplasty: An Analysis of Highly Cited Research Papers.

PURPOSE: The purpose of the study was to appraise the methodological quality of the highest impact blepharoplasty research and to describe prevalent research themes. METHODS: The 100 most highly cited research papers relevant to blepharoplasty were obtained from Web of Science, with no journal or date limitations applied. Data extraction included the study design, main research topic and specialty, outcome measures, and citation count. Each paper's level of evidence was independently evaluated by 2 authors according to the Oxford Centre for Evidence-Based Medicine system. RESULTS: Overall, the 100 most cited blepharoplasty research papers were cited by 4,194 papers. The mean number of citations for each paper was 73 (range: 42-239). Most of the papers presented level 4 (n = 51) or level 5 (n = 35) evidence, which is consistent with the predominance of case series (n = 47) and expert opinions (n = 18) amongst study designs. No papers achieved level 1 (highest) evidence. Six papers presented level 2 evidence and 8 papers presented level 3. Significant research foci included innovative surgical techniques (n = 65) and anatomical considerations (n = 10), with reconstructive and cosmetic implications. Senior authors were mainly affiliated with centers of plastic (n = 53) or ophthalmic/oculoplastic (n = 34) surgery. Only 3 papers used validated subjective or objective cosmetic outcome measures. CONCLUSIONS: Despite a significant impact on current practice, the level of evidence of the highly cited blepharoplasty research was predominantly low. Robust research methodology, through well-designed studies and standardized outcome measures, is necessary to facilitate evidence synthesis and guide clinical practice.

The effect of smoking on COVID-19 severity: A systematic review and meta-analysis.

Various comorbidities represent risk factors for severe coronavirus disease 2019 (COVID-19). The impact of smoking on COVID-19 severity has been previously reported in several meta-analyses limited by small sample sizes and poor methodology. We aimed to rigorously and definitively quantify the effects of smoking on COVID-19 severity. MEDLINE, Embase, CENTRAL, and Web of Science were searched between 1 December 2019 and 2 June 2020. Studies reporting smoking status of hospitalized patients with different severities of disease and/or at least one clinical endpoint of interest (disease progression, intensive care unit admission, need for mechanical ventilation, and mortality) were included. Data were pooled using a random-effects model. This study was registered on PROSPERO: CRD42020180920. We analyzed 47 eligible studies reporting on 32 849 hospitalized COVID-19 patients, with 8417 (25.6%) reporting a smoking history, comprising 1501 current smokers, 5676 former smokers, and 1240 unspecified smokers. Current smokers had an increased risk of severe COVID-19 (risk ratios [RR]: 1.80; 95% confidence interval [CI]: 1.14-2.85; P = .012), and severe or critical COVID-19 (RR: 1.98; CI: 1.16-3.38; P = .012). Patients with a smoking history had a significantly increased risk of severe COVID-19 (RR: 1.31; CI: 1.12-1.54; P = .001), severe or critical COVID-19 (RR: 1.35; CI: 1.19-1.53; P < .0001), in-hospital mortality (RR: 1.26; CI: 1.20-1.32; P < .0001), disease progression (RR: 2.18; CI: 1.06-4.49; P = .035), and need for mechanical ventilation (RR: 1.20; CI: 1.01-1.42; P = .043). Patients with any smoking history are vulnerable to severe COVID-19 and worse in-hospital outcomes. In the absence of current targeted therapies, preventative, and supportive strategies to reduce morbidity and mortality in current and former smokers are crucial.

The 100 Most-Cited Articles in Liposuction: A Bibliometric Analysis.

BACKGROUND: Liposuction is one of the most common cosmetic surgical procedures performed worldwide. Despite previous citation analyses in plastic surgery, the most-cited works in liposuction have not yet been qualitatively or quantitatively appraised. We hypothesized that use of validated outcome measures and levels of evidence would be low among these articles. Thus, we performed a bibliometric analysis aiming to comprehensively review the most-cited liposuction literature, evaluating characteristics and quality of the top 100 articles. METHODS: The 100 most-cited articles in liposuction were identified on Web of Science, across all available journals and years (1950-2020). Study details, including the citation count, main subject, and outcome measures, were extracted from each article by 2 independent reviewers. The level of evidence of each study was also assessed. RESULTS: The 100 most-cited articles in liposuction were cited by a total of 4809 articles. Citations per article ranged from 602 to 45 (mean, 92). Most articles were level of evidence 4 (n = 33) or 5 (n = 35), representative of the large number of case series, expert-opinion articles, and narrative reviews. Ten articles achieved level of evidence 3, 22 articles achieved level of evidence 2, and none reached level 1. The main subject was operative technique in 63 articles, followed by outcomes in 32 articles. Five articles assessed the metabolic effects of liposuction. Only 1 article used a validated objective cosmetic outcome measure, and none used validated patient-reported outcome measures. CONCLUSIONS: This analysis provides an overview of the top cited liposuction literature. Overall, level of evidence was low, and no articles achieved the highest level of evidence. Improving the quality of literature requires prioritization of better-designed studies and incorporation of validated outcome measures, which will increase patient satisfaction and ensure provision of excellent, reproducible clinical care.

Evaluating the clinical and cost-effectiveness of a conservative approach to oxygen therapy for invasively ventilated adults in intensive care: Protocol for the UK-ROX trial.

Background: In the United Kingdom, around 184,000 adults are admitted to an intensive care unit (ICU) each year with over 30% receiving mechanical ventilation. Oxygen is the commonest therapeutic intervention provided to these patients but it is unclear how much oxygen should be administered for the best clinical outcomes. Methods: The UK-ROX trial will evaluate the clinical and cost-effectiveness of conservative oxygen therapy (the minimum oxygen concentration required to maintain an oxygen saturation of 90% ± 2%) versus usual oxygen therapy in critically ill adults receiving supplemental oxygen when invasively mechanically ventilated in ICUs in England, Wales and Northern Ireland. The trial will recruit 16,500 patients from approximately 100 UK adult ICUs. Using a deferred consent model, enrolled participants will be randomly allocated (1:1) to conservative or usual oxygen therapy until ICU discharge or 90 days after randomisation. Objectives: The primary clinical outcome is all cause mortality at 90 days following randomisation. Discussion: The UK-ROX trial has received ethical approval from the South Central - Oxford C Research Ethics Committee (Reference: 20/SC/0423) and the Confidentiality Advisory Group (Reference: 22/CAG/0154). The trial commenced in May 2021 and, at the time of publication, 95 sites had opened to recruitment.

Comparing the Efficacy and Safety of Combination Triamcinolone Acetonide and 5-Fluorouracil versus Monotherapy Triamcinolone Acetonide or 5-Fluorouracil in the Treatment of Hypertrophic Scars and Keloids: A Systematic Review and Meta-Analysis.

BACKGROUND: Keloids and hypertrophic scars cause physical and psychosocial problems. Combination 5-fluorouracil (5-FU) with triamcinolone acetonide (TAC) may enhance the treatment of pathological scars, although the evidence base is limited. OBJECTIVES: We aimed to evaluate the efficacy and complication rates of combination intralesional TAC and 5-FU in comparison to monotherapy intralesional TAC or 5-FU for the treatment of keloids and hypertrophic scars. METHODS: EMBASE, MEDLINE and CENTRAL were searched by two independent reviewers. The primary outcome was treatment efficacy (51% to 100% improvement). Study quality and risk of bias were assessed using Cochrane's risk of bias tool, respectively. RESULTS: Of 277 articles screened, 13 studies were included comprising 12 randomised control trials (RCT) and 1 non-randomised study. There were six and nine studies comparing combination intralesional therapy versus monotherapy 5-FU and monotherapy TAC, respectively. The combined group demonstrated superior objective treatment efficacy compared to the monotherapy TAC group (OR 3.45, 95% C.I: [2.22-5.35], I 2=0%, P<0.00001) and monotherapy 5-FU group (OR 4.17, 95% C.I: [2.21-7.87], I 2=0%, P<0.0001). Telangiectasia was less frequent in combination therapy (OR 0.24, 95% CI: [0.11-0.52], I 2=0%, P=0.0003) compared to monotherapy TAC. CONCLUSIONS: Combined intralesional TAC and 5-FU administration demonstrated superior treatment efficacy outcomes compared to monotherapy TAC or 5-FU. Patient-reported outcome measures, lacking here, should be incorporated in the design of future research to justify clinical recommendations.

A Bibliometric Analysis of the Highest Cited Rhytidectomy Literature.

In this bibliometric analysis, we investigated the top 100 most cited articles on rhytidectomy, a prevalent cosmetic surgical procedure in the United States of America. Using data from Web of Science spanning from 1900 to 2021, we found these papers collectively cited 7737 times, with individual citation counts ranging from 277 to 37 (mean 77). Notably, the majority of these papers (58 out of 100) were categorized as Level of Evidence 5, indicating a prevalence of expert opinions, anatomical studies, and narrative reviews. Interestingly, none of the papers achieved Level 1 status, underscoring a lack of high-quality research in the field. The primary focus of these papers was on operative techniques (48 papers) and surgical anatomy of the face (20 papers). Only 10 articles incorporated patient-reported outcome measures (PROMs), but none utilized validated scales. This analysis highlights the urgent need for improved research methodologies in rhytidectomy studies, emphasizing the necessity for rigorous, high-quality research, and the implementation of validated rhytidectomy-specific PROMs.

Impact of inhalation injury on outcomes in critically ill burns patients: 12-year experience at a regional burns centre.

INTRODUCTION: Burns inhalation injury increases the attributable mortality of burns related trauma. However, diagnostic uncertainties around bronchoscopically graded severity, and its effect on outcomes, remain. This study evaluated the impact of different bronchoscopic burns inhalation injury grades on outcomes. METHODS: A single-centre cohort study of all patients admitted to the London Burns centre intensive care unit (BICU) over 12 years. Demographic data, burn and burns inhalation injury characteristics, and ICU-related parameters were collected retrospectively. The primary outcome was mortality. Secondary outcomes were hospital and ICU lengths of stay. The impact of pneumonia was determined. Univariate and multivariable Cox's proportional hazards regression analyses informed factors predicting mortality. RESULTS: Burns inhalation injury was diagnosed in 84 of 231 (36%) critically ill burns patients; 20 mild (grade 1), 41 severe (grades 2/3) and 23 unclassified bronchoscopically. Median (IQR) total body surface area burned (TBSA) was 20% (10-40). Mortality was significantly higher in patients with burns inhalation injury vs those without burns inhalation injury (38/84 [45%] vs 35/147 [24%], p < 0.001). Patients with pneumonia had a higher mortality than those without (34/125 [27%] vs 8/71 [11%], p = 0.009). In multivariable analysis, severe burns inhalation injury significantly increased mortality (adjusted HR=2.14, 95%CI: 1.12-4.09, p = 0.022), compared with mild injury (adjusted HR=0.58, 95% CI: 0.18-1.86, p = 0.363). Facial burns (adjusted HR=3.13, 95%CI: 1.69-5.79, p < 0.001), higher TBSA (adjusted HR=1.05, 95%CI: 1.04-1.06, p < 0.001) and older age (adjusted HR=1.04, 95%CI: 1.02-1.07, p < 0.001) also independently predicted mortality, though pneumonia did not. CONCLUSIONS: Severe burns inhalation injury is a significant risk factor for mortality in critically ill burns patients. However, pneumonia did not increase mortality from burns inhalation injury. This work confirms prior implications of bronchoscopically graded burns inhalation injury. Further study is suggested, through registries, into the diagnostic accuracy and reliability of bronchoscopy in burns related lung injury.

The 100 Most-cited Articles in Abdominoplasty: A Bibliometric Analysis.

Abdominoplasty is one of the most common aesthetic procedures performed globally. Research in this field is evolving, with recent emphasis on evidence-based surgery optimizing informed consent. This bibliometric analysis aimed to characterize emerging research trends and to assess the methodological quality of the highest impact abdominoplasty research. METHODS: The 100 most-cited articles in abdominoplasty were identified on Web of Science, across all available journals and years (1950-2019). Study details, including the citation count, main subject, and outcome measures, were extracted from each article by 2 independent reviewers. The level of evidence of each study was also assessed. RESULTS: The 100 most-cited articles in abdominoplasty were cited by a total of 2545 articles. Citations per article ranged from 206 to 34 (mean 65). Overall, 50 articles were assessed to be level of evidence 3, which is representative of the large number of cohort studies (n = 59) on the list. Similar numbers achieved levels 2, 4, and 5 (n = 16, 20, and 14), though none reached level 1. The main subject was operative technique in 50 articles, followed by outcomes in 34 articles. Only 7 articles utilized objective cosmetic outcome measures. Patient-reported outcome measures were employed in 25 articles, though only 5 incorporated validated questionnaires. CONCLUSIONS: The most-cited research in abdominoplasty largely comprised low-to-moderate quality studies, with no article achieving the highest level of evidence. Contemporary high-quality evidence incorporating validated outcome measures is crucial to enhance shared decision-making, particularly in aesthetic procedures.