Use of mathematical modelling to assess respiratory syncytial virus epidemiology and interventions: a literature review.

Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infection worldwide, resulting in approximately sixty thousand annual hospitalizations of< 5-year-olds in the United States alone and three million annual hospitalizations globally. The development of over 40 vaccines and immunoprophylactic interventions targeting RSV has the potential to significantly reduce the disease burden from RSV infection in the near future. In the context of RSV, a highly contagious pathogen, dynamic transmission models (DTMs) are valuable tools in the evaluation and comparison of the effectiveness of different interventions. This review, the first of its kind for RSV DTMs, provides a valuable foundation for future modelling efforts and highlights important gaps in our understanding of RSV epidemics. Specifically, we have searched the literature using Web of Science, Scopus, Embase, and PubMed to identify all published manuscripts reporting the development of DTMs focused on the population transmission of RSV. We reviewed the resulting studies and summarized the structure, parameterization, and results of the models developed therein. We anticipate that future RSV DTMs, combined with cost-effectiveness evaluations, will play a significant role in shaping decision making in the development and implementation of intervention programs.

Differential hysteresis scanning of non-templated monomodal amorphous aerogels.

We perform Differential Hysteresis Scanning (DHS) Porosimetry of amorphous silicon oxycarbide aerogels to quantify hierarchical connectivity in these porous materials. We contrast high-resolution argon sorption scanning isotherms of samples obtained through a non-templated synthesis using different solvents, and characterize respective changes after calcination at 1000 °C. The multi-scan DHS data sets are analyzed through non-negative least-squares deconvolution using a kernel of theoretically derived isotherms for a selection of hierarchical geometries using non-local density functional theory (NL-DFT). We obtain two-dimensional contour plots that characterize mesopores according to the ratio between pore diameter and its connecting window. Combined information from DHS and complementary BET and BJH approaches reveals one system with monomodal distribution both in pore diameters and in window diameters. Hence, this amorphous material exhibits a uniformity usually only observed for crystalline systems. We demonstrate that DHS analysis provides quantitative data analyzing the hierarchical structure of mesoporous materials and unlocks pathways towards tailored materials with control of surface heterogeneity, localization, and sequential accessibility - even for amorphous systems.

Combined Tumor Environment Triggered Self-Assembling Peptide Nanofibers and Inducible Multivalent Ligand Display for Cancer Cell Targeting with Enhanced Sensitivity and Specificity.

Many new technologies, such as cancer microenvironment-induced nanoparticle targeting and multivalent ligand approach for cell surface receptors, are developed for active targeting in cancer therapy. While the principle of each technology is well illustrated, most systems suffer from low targeting specificity and sensitivity. To fill the gap, this work demonstrates a successful attempt to combine both technologies to simultaneously improve cancer cell targeting sensitivity and specificity. Specifically, the main component is a targeting ligand conjugated self-assembling monomer precursor (SAM-P), which, at the tumor site, undergoes tumor-triggered cleavage to release the active form of self-assembling monomer capable of forming supramolecular nanostructures. Biophysical characterization confirms the chemical and physical transformation of SAM-P from unimers or oligomers with low ligand valency to supramolecular assemblies with high ligand valency under a tumor-mimicking reductive microenvironment. The in vitro fluorescence assay shows the importance of supramolecular morphology in mediating ligand-receptor interactions and targeting sensitivity. Enhanced targeting specificity and sensitivity can be achieved via tumor-triggered supramolecular assembly and induces multivalent ligand presentation toward cell surface receptors, respectively. The results support this combined tumor microenvironment-induced cell targeting and multivalent ligand display approach, and have great potential for use as cell-specific molecular imaging and therapeutic agents with high sensitivity and specificity.

Aviation-Style Computerized Surgical Safety Checklist Displayed on a Large Screen and Operated by the Anesthesia Provider Improves Checklist Performance.

BACKGROUND: Many hospitals have implemented surgical safety checklists based on the World Health Organization surgical safety checklist, which was associated with improved outcomes. However, the execution of the checklists is frequently incomplete. We reasoned that aviation-style computerized checklist displayed onto large, centrally located screen and operated by the anesthesia provider would improve the performance of surgical safety checklist. METHODS: We performed a prospective before and after observational study to evaluate the effect of a computerized surgical safety checklist system on checklist performance. We created checklist software and translated our 4-part surgical safety checklist from wall poster into an aviation-style computerized format displayed onto a large, centrally located screen and operated by the anesthesia provider. Direct observers recorded performance of the first part of the surgical safety checklist that was initiated before anesthetic induction, including completion of each checklist item, provider participation and distraction level, resistance to use of the checklist, and the time required for checklist completion before and after checklist system implementation. We compared trends of the proportions of cases with 100% surgical safety checklist completion over time between pre- and postintervention periods and assessed for a jump at the start of intervention using segmented logistic regression model while controlling for potential confounding variables. RESULTS: A total of 671 cases were observed before and 547 cases were observed after implementation of the computerized surgical safety checklist system. The proportion of cases in which all of the items of the surgical safety checklist were completed significantly increased from 2.1% to 86.3% after the computerized checklist system implementation (P < .001). Before computerized checklist system implementation, 488 of 671 (72.7%) cases had <75% of checklist items completed, whereas after a computerized checklist system implementation, only 3 of 547 (0.5%) cases had <75% of checklist items completed. CONCLUSIONS: The implementation of a computerized surgical safety checklist system resulted in an improvement in checklist performance.

Forecasting a Crisis: Machine-Learning Models Predict Occurrence of Intraoperative Bradycardia Associated With Hypotension.

BACKGROUND: Predictive analytics systems may improve perioperative care by enhancing preparation for, recognition of, and response to high-risk clinical events. Bradycardia is a fairly common and unpredictable clinical event with many causes; it may be benign or become associated with hypotension requiring aggressive treatment. Our aim was to build models to predict the occurrence of clinically significant intraoperative bradycardia at 3 time points during an operative course by utilizing available preoperative electronic medical record and intraoperative anesthesia information management system data. METHODS: The analyzed data include 62,182 scheduled noncardiac procedures performed at the University of Washington Medical Center between 2012 and 2017. The clinical event was defined as severe bradycardia (heart rate <50 beats per minute) followed by hypotension (mean arterial pressure <55 mm Hg) within a 10-minute window. We developed models to predict the presence of at least 1 event following 3 time points: induction of anesthesia (TP1), start of the procedure (TP2), and 30 minutes after the start of the procedure (TP3). Predictor variables were based on data available before each time point and included preoperative patient and procedure data (TP1), followed by intraoperative minute-to-minute patient monitor, ventilator, intravenous fluid, infusion, and bolus medication data (TP2 and TP3). Machine-learning and logistic regression models were developed, and their predictive abilities were evaluated using the area under the ROC curve (AUC). The contribution of the input variables to the models were evaluated. RESULTS: The number of events was 3498 (5.6%) after TP1, 2404 (3.9%) after TP2, and 1066 (1.7%) after TP3. Heart rate was the strongest predictor for events after TP1. Occurrence of a previous event, mean heart rate, and mean pulse rates before TP2 were the strongest predictor for events after TP2. Occurrence of a previous event, mean heart rate, mean pulse rates before TP2 (and their interaction), and 15-minute slopes in heart rate and blood pressure before TP2 were the strongest predictors for events after TP3. The best performing machine-learning models including all cases produced an AUC of 0.81 (TP1), 0.87 (TP2), and 0.89 (TP3) with positive predictive values of 0.30, 0.29, and 0.15 at 95% specificity, respectively. CONCLUSIONS: We developed models to predict unstable bradycardia leveraging preoperative and real-time intraoperative data. Our study demonstrates how predictive models may be utilized to predict clinical events across multiple time intervals, with a future goal of developing real-time, intraoperative, decision support.

Immune globulin subcutaneous, human 20% solution (Xembify®), a new high concentration immunoglobulin product for subcutaneous administration.

Immune globulin subcutaneous, human 20% solution (IGSC-C 20%, Xembify®)-a new 20% immunoglobulin (IgG) liquid product for subcutaneous (SC) administration-has been developed by Grifols. The IGSC-C 20% formulation is based on knowledge acquired from the formulation of Immune Globulin Injection (Human),10% Caprylate/Chromatography Purified (IGIV-C 10%, Gamunex®-C). The protein concentration was increased from 10% to 20% to provide a smaller volume for SC administration. The IGSC-C 20% manufacturing process employs the same caprylate/chromatography purification steps as IGIV-C 10%, with the addition of an ultrafiltration step so that the product can be formulated at a higher protein concentration. IGSC-C 20% has been produced at full industrial scale to support clinical studies and licensure. These batches were characterized using a comprehensive panel of analytical testing. The new IGSC-C 20% product maintains the same composition, neutralizing activity, purity, and quality characteristics found in IGIV-C 10%.

Electronic Audit and Feedback With Positive Rewards Improve Anesthesia Provider Compliance With a Barcode-Based Drug Safety System.

BACKGROUND: We implemented a previously described barcode-based drug safety system in all of our anesthetizing locations. Providers were instructed to scan the barcode on syringes using our Anesthesia Information Management System before drug administration, but the rate of provider adherence was low. We studied an implementation intervention intended to increase the rate of scanning. METHODS: Using our Anesthesia Information Management System and Smart Anesthesia Manager software, we quantified syringe drug administrations by anesthesia providers with and without barcode scanning. We use an anesthesia team model in which an attending anesthesiologist is paired with a certified registered nurse anesthetist (CRNA) or a resident. Our system identified the pair of providers associated with a particular drug administration, but did not distinguish which providers actually administered the drug. Therefore, the rate of barcode scanning for a particular case was assigned to both providers equally. A baseline rate of scanning was established over a period of 17 months. An audit and feedback intervention was then performed that consisted of monthly performance reports sent by email to individual providers along with coffee gift card awards for top performers. The coffee gift cards were awarded in only the first 2 months of the intervention, while the email performance reports continued on a monthly basis. The coffee card awards were made public. The monthly emails reported the individual provider's rank order of performance relative to other providers, but was otherwise anonymous. The baseline rate of scanning was compared to the rate of scanning after the intervention for a period of 7 months. RESULTS: From November 2014 to March 2017, we accumulated 60,197 cases performed by 88 attending anesthesiologists, 65 CRNAs, and 148 residents. The total number of syringe drug administrations was 653,355. Average scanning performance improved from 8.7% of syringe barcodes scanned during the baseline period from November 2014 to February 2016 to 64.4% scanned during the period September 2016 to March 2017 (P < .001). Variation in performance among individuals was marked, ranging from 0% to 100% of syringes scanned. The performance of some individuals showed marked oscillation over time. There was greater variation in performance attributable to residents than in performance attributable to CRNAs. CONCLUSIONS: Feedback of individual provider performance data from the anesthesia information system to providers can be used in conjunction with other measures to improve performance. Despite improved average performance, there was marked variation in performance between individuals, and some individuals had marked oscillation of their performance over time.

Shockwave compression and dissociation of ammonia gas.

We performed a series of plate impact experiments on NH3 gas initially at room temperature and at a pressure of ∼100 psi. Shocked states were determined by optical velocimetry and the temperatures by optical pyrometry, yielding compression ratios of ∼5-10 and second shock temperatures in excess of 7500 K. A first-principles statistical mechanical (thermochemical) approach that included chemical dissociation yielded reasonable agreement with experimental results on the principal Hugoniot, even with interparticle interactions neglected. Theoretical analysis of reshocked states, which predicts a significant degree of chemical dissociation, showed reasonable agreement with experimental data for higher temperature shots; however, reshock calculations required the use of interaction potentials. We rationalize the very different shock temperatures obtained, relative to previous results for argon, in terms of atomic versus molecular heat capacities.

Comparison of the liquid and lyophilized formulations of Prolastin®-C for Alpha1-Antitrypsin deficiency: Biochemical characteristics, pharmacokinetics, safety and neoantigenicity in rabbits.

Multiple analytical and preclinical studies were performed to compare the biochemical characteristics, pharmacokinetics (PK), safety and neoantigenicity of a new 5% liquid formulation of Alpha-1 Proteinase Inhibitor (Liquid A1PI, Prolastin®-C Liquid) with the lyophilized version (Lyophilized A1PI, Prolastin®-C). Liquid A1PI and Lyophilized A1PI had similar average mass (~52 kDa), and both forms exhibited glycoform patterns consistent with the known banding pattern of A1PI (dominated by the M6 and M4 bands, including deconvoluted masses). Both Liquid A1PI and Lyophilized A1PI yielded average percent purity values ranging from 96% to 99% and had active content ranging from 53  mg/mL to 59  mg/mL. The PK profile of Liquid A1PI was similar to Lyophilized A1PI. Safety assessments in rabbits showed good tolerability and no test article-related changes in mortality, clinical signs, clinical pathology, body weight, food consumption, or urinalysis parameters. Following immunodepletion of antibodies that recognize Lyophilized A1PI, there were no significant differences in the anti-drug titers among animals immunized with Lyophilized A1PI and Liquid A1PI (p > 0.05), indicating that no antibodies to neoantigens were generated. Liquid A1PI and Lyophilized A1PI have similar profiles with respect to biochemical characteristics, PK, safety and neoantigenicity.

Inhaled nitric oxide: Current clinical concepts.

Nitric oxide (NO) has come far since being discovered serendipitously to relax vascular smooth muscle. Initially, administered to animals to reduce pulmonary artery pressures and improve oxygenation. It now enjoys FDA approval for administration to newborns with pulmonary hypertension but is used common place for other critical cardiopulmonary ailments. While never quite living up to expectations, newer applications show greater promise as a therapy especially in the area of ischemia-reperfusion. The following will give a clinical overview of inhaled nitric oxide as a gas, as applied to the pediatric patient population, and to those adults suffering with cardiopulmonary and hematologic disease. Lastly, due to more recent discoveries, the effects of how NO may be used to treat disorders such as ischemia-reperfusion, will also be reviewed.

The influence of societal individualism on a century of tobacco use: modelling the prevalence of smoking.

BACKGROUND: Smoking of tobacco is estimated to have caused approximately six million deaths worldwide in 2014. Responding effectively to this epidemic requires a thorough understanding of how smoking behaviour is transmitted and modified. METHODS: We present a new mathematical model of the social dynamics that cause cigarette smoking to spread in a population, incorporating aspects of individual and social utility. Model predictions are tested against two independent data sets spanning 25 countries: a newly compiled century-long composite data set on smoking prevalence, and Hofstede's individualism/collectivism measure (IDV). RESULTS: The general model prediction that more individualistic societies will show faster adoption and cessation of smoking is supported by the full 25 country smoking prevalence data set. Calibration of the model to the available smoking prevalence data is possible in a subset of 7 countries. Consistency of fitted model parameters with an additional, independent, data set further supports our model: the fitted value of the country-specific model parameter that determines the relative importance of social and individual factors in the decision of whether or not to smoke, is found to be significantly correlated with Hofstede's IDV for the 25 countries in our data set. CONCLUSIONS: Our model in conjunction with extensive data on smoking prevalence provides evidence for the hypothesis that individualism/collectivism may have an important influence on the dynamics of smoking prevalence at the aggregate, population level. Significant implications for public health interventions are discussed.

Bioavailability of AREDS1 micronutrients from softgel capsules and tablets: a pilot study.

PURPOSE: The benefits of antioxidant micronutrients in slowing progression to advanced stages of age-related macular degeneration (AMD) was supported by the 4/day tablet form investigated in the Age-related Eye Disease Study 1 (AREDS1) and the 2/day softgel form in the Age-related Eye Disease Study 2 (AREDS2). However, the choices of excipient, dosage form, and ingredient chemistry as well as the patient physiologies and pathologies can influence bioavailability and efficacy. The objective of the study was to explore the influence of dosage form on the bioavailability of the five primary AREDS1 and Tier-2 AREDS2 micronutrients: the metals zinc and copper, ß-carotene, and vitamins E and C. The intent was to establish by chemical analysis the relative bioavailabilities of these five micronutrients in plasma, or serum for the metals, as well as to identify any opportunities for improvements. METHODS: A total of 15 healthy men (5) and women (10) were recruited for a controlled, randomized, three-arm, crossover trial of the AREDS1 micronutrients. The study investigated responses in bioabsorption to a single dose of either four tablets or two softgels at the full dose level, or one softgel at the half-dose level. The bioavailability of each micronutrient was based on the pharmacokinetic profiles established through 15 samplings for each ingredient/dosage form in plasma/serum over the course of one week. RESULTS: Bioavailability was estimated using model-independent and model-dependent procedures. A statistical advantage of the dosage form was observed in only two cases from the exaggerated effects using the half-dose softgel and for the tablet dosage form for ß-carotene and vitamin E. An unanticipated complexity was suggested by the bimodal absorption of zinc. For these micronutrients, no disadvantage (though potential advantage) was inferred for the water-soluble components presented in a softgel formulation. Increased fractional absorption was observed for the smaller dose (one capsule versus two), but it was not sufficient to reach the level achieved by the full dose of either four tablets or two softgels. A model-dependent analysis permitted an estimation of the percentage of micronutrients absorbed, with zinc, the single most important ingredient, absorbed at about a 10% level. CONCLUSIONS: The results suggest modestly contradictory requirements in the dosage form for water-soluble and lipid-soluble ingredients, as based on a goal of improved bioavailability. Comparative consistency in bioavailability was observed across dosage forms, and most nutrients between AREDS1 and AREDS2 (full dose) formulations relative to the significant variations observed within this controlled population. The results emphasize the importance of defining the requisite bioavailability of each micronutrient and the influence of the dosage form that provides it. With the recognition of global and population-specific micronutrient deficiencies, notably in the elderly populations afflicted with AMD and their significant metabolic and health consequences, establishing efficient means of supplementation are of continuing epidemiologic interest.

Characterization of Thrombate III®, a pasteurized and nanofiltered therapeutic human antithrombin concentrate.

Thrombate III(®) is a highly purified antithrombin concentrate that has been used by clinicians worldwide for more than two decades for the treatment of hereditary antithrombin deficiency. The manufacturing process is based on heparin-affinity chromatography and pasteurization. To modernize the process and to further enhance the pathogen safety profile of the final product, despite the absence of infectious disease transmission, a nanofiltration step was added. The biochemical characterization and pathogen safety evaluation of Thrombate III(®) manufactured using the modernized process are presented. Bioanalytical data demonstrate that the incorporation of nanofiltration has no impact on the antithrombin content, potency, and purity of the product. Scaledown models of the manufacturing process were used to assess virus and prion clearance under manufacturing setpoint conditions. Additionally, robustness of virus clearance was evaluated at or slightly outside the manufacturing operating limits. The results demonstrate that pasteurization inactivated both enveloped and non-enveloped viruses. The addition of nanofiltration substantially increased clearance capacities for both enveloped and non-enveloped viruses by approximately 4-6 log10. In addition, the process achieves 6.0 log10 ID50 prion infectivity clearance. Thus, the introduction of nanofiltration increased the pathogen safety margin of the manufacturing process without impacting the key biochemical characteristics of the product.

Assessment of using Google Trends for real-time monitoring of infectious disease outbreaks: a measles case study.

Measles remains a significant threat to children worldwide despite the availability of effective vaccines. The COVID-19 pandemic exacerbated the situation by leading to the postponement of supplementary measles immunization activities. Along with this postponement, measles surveillance also deteriorated, with the lowest number of submitted specimens in over a decade. In this study, we focus on measles as a challenging case study due to its high vaccination coverage, which leads to smaller outbreaks and potentially weaker signals on Google Trends. Our research aimed to explore the feasibility of using Google Trends for real-time monitoring of infectious disease outbreaks. We evaluated the correlation between Google Trends searches and clinical case data using the Pearson correlation coefficient and Spearman's rank correlation coefficient across 30 European countries and Japan. The results revealed that Google Trends was most suitable for monitoring acute disease outbreaks at the regional level in high-income countries, even when there are only a few weekly cases. For example, from 2017 to 2019, the Pearson correlation coefficient was 0.86 (p-value< 0.05) at the prefecture level for Okinawa, Japan, versus 0.33 (p-value< 0.05) at the national level for Japan. Furthermore, we found that the Pearson correlation coefficient may be more suitable than Spearman's rank correlation coefficient for evaluating the correlations between Google Trends search data and clinical case data. This study highlighted the potential of utilizing Google Trends as a valuable tool for timely public health interventions to respond to infectious disease outbreaks, even in the context of diseases with high vaccine coverage.

Comparison of a static cohort model and dynamic transmission model for respiratory syncytial virus intervention programs for infants in England and Wales.

BACKGROUND: A recent study comparing results of multiple cost-effectiveness analyses (CEAs) in a hypothetical population found that monoclonal antibody (mAb) immunoprophylaxis for respiratory syncytial virus (RSV) in infants averted fewer medically attended cases when estimated using dynamic transmission models (DTMs) versus static cohort models (SCMs). We aimed to investigate whether model calibration or parameterization could be the primary driver of inconsistencies between SCM and DTM predictions. METHODS: A recently published DTM evaluating the CEA of infant mAb immunoprophylaxis in England and Wales (EW) was selected as the reference model. We adapted our previously published SCM for US infants to EW by utilizing the same data sources used by the DTM. Both models parameterized mAb efficacy from a randomized clinical trial (RCT) that estimated an average efficacy of 74.5% against all medically attended RSV episodes and 62.1% against RSV hospitalizations. To align model assumptions, we modified the SCM to incorporate waning efficacy. Since the estimated indirect effects from the DTM were small (i.e., approximately 100-fold smaller in magnitude than direct effects), we hypothesized that alignment of model parameters should result in alignment of model predictions. Outputs for model comparison comprised averted hospitalizations and averted GP visits, estimated for seasonal (S) and seasonal-with-catchup (SC) immunization strategies. RESULTS: When we aligned the SCM intervention parameters to DTM intervention parameters, significantly more averted hospitalizations were predicted by the SCM (S: 32.3%; SC: 51.3%) than the DTM (S: 17.8%; SC: 28.6%). The SCM most closely replicated the DTM results when the initial efficacy of the mAb intervention was 62.1%, leading to an average efficacy of 39.3%. Under this parameterization the SCM predicted 17.4% (S) and 27.7% (SC) averted hospitalizations. Results were similar for averted GP visits. CONCLUSIONS: Parameterization of the RSV mAb intervention efficacy is a plausible primary driver of differences between SCM versus DTM model predictions.

Public health impact and return on investment of the pediatric National Immunization Program in Italy.

OBJECTIVES: We conducted a cost-benefit analysis of the pediatric National Immunization Program (NIP) in Italy. METHODS: An economic model evaluated the benefit-cost ratio (BCR) of the Italian pediatric NIP, including 10 pathogens for mandatory vaccines and 4 pathogens for recommended vaccines for children aged 0-10 years from the healthcare-sector and societal perspectives. Separate decision trees were used to model each vaccine-preventable disease (VPD). The 2020 birth cohort (n = 420,084) was followed over their lifetime; the model projected and compared discounted disease cases, life-years, quality-adjusted life-years (QALYs), and costs (2021 euros) with and without immunization (based on current and pre - vaccine era disease incidence estimates, respectively). RESULTS: The pediatric NIP was estimated to prevent 1.8 million cases of VPDs and 3,330 deaths, resulting in 45,900 fewer life-years lost and 57,000 fewer QALYs lost. Vaccination costs of €285 million were offset by disease cost savings of €1.6 billion, resulting in a BCR of 5.6 from a societal perspective (BCR = 1.7 from a healthcare-sector perspective). When QALYs gained were valued, the BCR increased to 15.6. CONCLUSIONS: The benefits of the Italian pediatric NIP, including averted disease-related morbidity, mortality, and associated costs, highlight the value of continued investment in pediatric immunization.

Use of a left-sided double-lumen endotracheal tube in a patient with a prior left pneumonectomy.

A 77-year-old man, 7 years after left pneumonectomy, was scheduled for a right upper pulmonary lobectomy. The early identification of a newly developing carcinoma on the right upper pulmonary lobe warranted surgical resection. Right exploratory thoracotomy, pleural lysis, partial pleurectomy, and right upper lobe wedge resection were completed, and the patient was discharged without sequelae. This case report describes the intraoperative anesthetic management of a right upper lobe wedge resection and attributes the uneventful intraoperative outcome to a strategically and skillfully placed left double-lumen endotracheal tube.

A short history of the successes and failures of the international climate change negotiations.

The last 35 years have been a period of intense and continuous international negotiations to deal with climate change. During the same period of time humanity has doubled the amount of anthropogenic carbon dioxide in the atmosphere. There has, however, been progress and some notable successes in the negotiations. In 2015, at COP21 of the United Nations Framework Convention on Climate Change, 196 countries adopted the Paris Agreement stating that they would limit global temperatures to well below 2°C above pre-industrial levels and would pursue efforts to limit the temperature increase to 1.5°C above pre-industrial levels. The first review of the Paris Agreement was at COP26 in Glasgow with many countries pledging to go to net zero emissions by the middle of the century. But currently these pledges, if fulfilled, will only limit the global average temperature to between 2.4°C and 2.8°C. At COP27 in Egypt the core agreements from the Glasgow Climate Pact were maintained and countries finally agreed to set up a loss and damage facility - although details of who will provide the finance and who can claim are still be to be worked out. This article reviews the key moments in the history of international climate change negotiations and discusses what the key objectives are for future COP meetings.

Chondrosarcoma of the thyroid cartilage: surgical management of a rare case.

Laryngeal malignancy encompasses about 1% of all cancers. Chondrosarcoma in the head and neck region represents about 0.1% of head and neck malignancies. Typical presenting symptoms relate to the anatomical location of these tumours and include dysphonia, inspiratory stridor, dysphagia, odynophagia or a neck mass. Benign and malignant cartilaginous cancers of the larynx have been described, and preoperative diagnosis can be difficult. Our report highlights the surgical management of a male patient in his 50s with chondrosarcoma of the thyroid cartilage.

Clinical decision making in paediatric otitis media: A pilot quality improvement study.

OBJECTIVES: This study aimed to improve local management of paediatric otitis media using the 2022 American-Academy of Otolaryngology Head and Neck Surgery (AAO-HNS) Clinical Practice Guideline for Tympanostomy Tubes in Children. METHODS: A SQUIRE 2.0 compliant quality improvement study was carried out within the outpatient department of our otolaryngology tertiary referral centre. Local outpatient management of paediatric otitis media was compared to the AAO-HNS guidelines, specifically focussing on the decision to offer tympanostomy tubes. Following initial audit of practice, an educational session was performed within the otolaryngology department and local practice was subsequently re-evaluated. RESULTS: Overall, 88 children were included (46 pre-intervention and 42 post-intervention) with a mean age of 7.6 years (range 1-12 years). Sixty-four (72.7%) children presented with suspected otitis media with effusion. The remainder presented with recurrent or persistent acute otitis media (24/88, 27.3%). Twenty-six children were offered tympanostomy tubes (29.5%). Initial evaluation of practice identified that the decision to offer tympanostomy tubes was guideline appropriate in 76.1% of children (35/46). This significantly improved following an educational session (40/42, 95.2%, p = 0.02). The reasons for non-guideline compliance included: otitis media with effusion <3 months, no evidence of middle ear fluid and patients meeting criteria for tympanostomy tube insertion not being offered. CONCLUSIONS: A focussed educational intervention may improve local adherence to guidelines in the management of paediatric otitis media. Continued re-evaluation of local practice is essential in order to ensure children are managed in accordance with the guidelines.