Acute otitis externa: Consensus definition, diagnostic criteria and core outcome set development.

OBJECTIVE: Evidence for the management of acute otitis externa (AOE) is limited, with unclear diagnostic criteria and variably reported outcome measures that may not reflect key stakeholder priorities. We aimed to develop 1) a definition, 2) diagnostic criteria and 3) a core outcome set (COS) for AOE. STUDY DESIGN: COS development according to Core Outcome Measures in Effectiveness Trials (COMET) methodology and parallel consensus selection of diagnostic criteria/definition. SETTING: Stakeholders from the United Kingdom. SUBJECTS AND METHODS: Comprehensive literature review identified candidate items for the COS, definition and diagnostic criteria. Nine individuals with past AOE generated further patient-centred candidate items. Candidate items were rated for importance by patient and professional (ENT doctors, general practitioners, microbiologists, nurses, audiologists) stakeholders in a three-round online Delphi exercise. Consensus items were grouped to form the COS, diagnostic criteria, and definition. RESULTS: Candidate COS items from patients (n = 28) and literature (n = 25) were deduplicated and amalgamated to a final candidate list (n = 46). Patients emphasised quality-of-life and the impact on daily activities/work. Via the Delphi process, stakeholders agreed on 31 candidate items. The final COS covered six outcomes: pain; disease severity; impact on quality-of-life and daily activities; patient satisfaction; treatment-related outcome; and microbiology. 14 candidate diagnostic criteria were identified, 8 reaching inclusion consensus. The final definition for AOE was 'diffuse inflammation of the ear canal skin of less than 6 weeks duration'. CONCLUSION: The development and adoption of a consensus definition, diagnostic criteria and a COS will help to standardise future research in AOE, facilitating meta-analysis. Consulting former patients throughout development highlighted deficiencies in the outcomes adopted previously, in particular concerning the impact of AOE on daily life

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Evaluating Exaggerated, Prolonged, or Delayed Postoperative Intraocular Inflammation

To provide a diagnostic approach for the evaluation of patients with exaggerated, prolonged, or delayed postoperative intraocular inflammation. Perspective. Selected articles on normal and abnormal postoperative intraocular inflammation were reviewed and interpreted in the context of the authors' clinical and research experience. In addition to infectious endophthalmitis, a number of noninfectious conditions characterized by exaggerated, prolonged, or delayed postoperative inflammation have been described. Heuristically, increased postsurgical inflammation may be categorized by time from surgery to first recognition using the following general guidelines: as immediate and occurring within 2 days after surgery; as early and occurring after 2 days, but within the first 2 weeks, after surgery; and as delayed and occurring more than 2 weeks after surgery. Although infectious endophthalmitis always must be excluded as a cause of increased postoperative intraocular inflammation, potential noninfectious causes also exist. We review both infectious and noninfectious causes of increased postoperative inflammation and provide a diagnostic framework for evaluating such patients

Pseudocystic foveal cavitation in tamoxifen retinopathy

To present 3 cases of tamoxifen-induced foveal cavitation and review previous prospective and cross-sectional studies. Observational case series. Retrospective analysis of patients presenting to a single institution with evidence of tamoxifen-induced maculopathy. Three patients presented with pseudocystic foveal cavitation similar in appearance to macular telangiectasia type 2 on spectral-domain optical coherence tomography (SD OCT) imaging. Tamoxifen maculopathy is characterized by cavitation in the central macula with or without typical cystoid macular edema. Pathogenesis involves toxicity to retinal Müller cells. It can occur with low daily and cumulative doses of the drug, and in the absence of subjective visual complaints or crystalline retinopathy. Prospective research with SD OCT imaging will be required to gain a more accurate estimate of the incidence of tamoxifen retinopathy

Epiretinal Macular Edema Associated With Thick Epiretinal Membranes

High-resolution imaging with spectral-domain optical coherence tomography has identified an unusual group of epiretinal membranes (ERMs) in the presence of lamellar macular holes. These ERMs are unusually thick. The authors present the case of a patient with age-related macular degeneration who developed edema within a thickened ERM in both eyes after cataract surgery. The edema resolved with anti-vascular endothelial growth factor (VEGF) therapy. The authors propose that the VEGF-responsive fluid within these thick ERMs arose from fibrovascular tissue derived from the retina. Further studies with histopathology will be required to determine whether neovascular tissue is present in all cases of thickened ERMs with epiretinal edema

Invasive Versus Medical Management in Patients With Chronic Kidney Disease and Non–ST‐Segment–Elevation Myocardial Infarction

Background The role of invasive management compared with medical management in patients with non–ST‐segment–elevation myocardial infarction (NSTEMI) and advanced chronic kidney disease (CKD) is uncertain, given the increased risk of procedural complications in patients with CKD. We aimed to compare clinical outcomes of invasive management with medical management in patients with NSTEMI‐CKD. Methods and Results We identified NSTEMI and CKD stages 3, 4, 5, and end‐stage renal disease admissions using International Classification of Diseases, Tenth Revision, Clinical Modification (ICD‐10‐CM) codes from the Nationwide Readmission Database 2016 to 2018. Patients were stratified into invasive and medical management. Primary outcome was mortality (in‐hospital and 6 months after discharge). Secondary outcomes were in‐hospital postprocedural complications (acute kidney injury requiring dialysis, major bleeding) and postdischarge 6‐month safety and major adverse cardiovascular events. Out of 141 052 patients with NSTEMI‐CKD, 85 875 (60.9%) were treated with invasive management, whereas 55 177 (39.1%) patients were managed medically. In propensity‐score matched cohorts, invasive strategy was associated with lower in‐hospital (CKD 3: odds ratio [OR], 0.47 [95% CI, 0.43–0.51]; P<0.001; CKD 4: OR, 0.79 [95% CI, 0.69–0.89]; P<0.001; CKD 5: OR, 0.72 [95% CI, 0.49–1.06]; P=0.096; end‐stage renal disease: OR, 0.51 [95% CI, 0.46–0.56]; P<0.001) and 6‐month mortality. Invasive management was associated with higher in‐hospital postprocedural complications but no difference in postdischarge safety outcomes. Invasive management was associated with a lower hazard of major adverse cardiovascular events at 6 months in all CKD groups compared with medical management. Conclusions Invasive management was associated with lower mortality and major adverse cardiovascular events but minimal increased in‐hospital complications in patients with NSTEMI‐CKD compared with medical management, suggesting patients with NSTEMI‐CKD should be offered invasive management