31064 The Detroit Keloid Scale: A validated tool for rating keloids

Background: No keloid-specific outcome measures exist. Objective: To develop and validate the Detroit Keloid Scale (DKS), a standardized method of keloid assessment to better compare treatments. Methods: Forty-seven physicians were polled to develop the DKS. The scale was validated in 52 patients with keloids against the Vancouver Scar Scale (VSS), Patient and Observer Scar Assessment Scale (POSAS), and Dermatology Life Quality Index (DLQI) by 3 physicians. Results: The interrater reliability was “substantial” for observer component of the DKS and only “moderate” for the VSS and observer POSAS (ICC were 0.80, 0.60, and 0.47, respectively). Pearson’s correlation indicated a “moderate” association between the observer component of DKS with observer component of POSAS (ρ = 0.56, P \u3c.001) and a “substantial” relationship between the observer component of DKS and VSS (ρ = 0.63, P \u3c.001). Pearson’s correlation indicated a “moderate” association between the patient portion of DKS and patient portion of POSAS and the patient portion of the DKS and DLQI (0.61 and 0.60, respectively, P \u3c.05). The DKS total score consistently showed “substantial” relationship with POSAS total score (ρ = 0.65, P \u3c.001). Limitations: Single center study, no intrarater reliability analysis. Conclusions: The substantial interrater reliability of the DKS will allow for improved standardization in future keloid research

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

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

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Skin cancer screening and primary prevention: facts and controversies

Skin cancer is both common and responsible for significant morbidity and mortality. Opportunities for both primary and secondary prevention are available to both dermatologists and non-dermatologists. Counseling selected patients about ultraviolet avoidance and proper use of sunscreens is recommended. Due to technical and financial barriers, no study has conclusively confirmed the benefits of skin cancer screening. Both dermatologists and non-dermatologists often do not perform total body skin examinations during clinical encounters, despite high acceptance rates by patients. Many non-dermatologists would benefit from additional education pertaining to the diagnosis of cutaneous malignancy. Teledermatology may have a role in areas with poor access to dermatologists. There are ample opportunities for more to be learned in the future

Disease Severity and Quality of Life Outcome Measurements in Patients With Keloids: A Systematic Review

BACKGROUND: Keloids have been assessed by numerous methods and severity indices resulting in a lack of standardization across published research. OBJECTIVE: This study aims to evaluate published keloid randomized controlled trials (RCTs) and identify the need for a gold standard of assessment. METHODS AND MATERIALS: PubMed, MEDLINE, and Embase were searched for human RCTs on keloid treatment during a 10-year period. Eligible studies were English language RCTs reporting disease severity outcome measures after keloid treatments. RESULTS: A total of 40 disease outcome measures were used in 41 included RCTs. Twenty-four (59%) of the included studies used more than one disease severity scale. The most frequently used outcome measures were the Vancouver Scar Scale (34%) (n = 14), followed by serial photography (24%) (n = 10). These were followed by adverse events and complications (20%) (n = 8), Visual Analogue Scale (12%) (n = 5), keloid dimensions (12%) (n = 5), and Patient and Observer Scar Assessment Scale (10%) (n = 4). Only one study reported quality of life outcomes. CONCLUSION: There is wide variation in keloid outcome measures in the published literature. A standardized method of assessment should be implemented to reduce the disparities between studies and to better be able to compare the numerous treatment modalities

The Detroit Keloid Scale: A Validated Tool for Rating Keloids

Background: Comparing keloid treatment modalities and assessing response to treatments may be predicted by a better classification system. Objectives: To develop and validate the Detroit Keloid Scale (DKS), a standardized method of keloid assessment. Methods: Forty-seven physicians were polled to develop the DKS. The scale was validated in 52 patients against the Vancouver Scar Scale (VSS), Patient and Observer Scar Assessment Scale (POSAS), and Dermatology Life Quality Index (DLQI). Results: The inter-rater reliability was substantial for observer DKS and only moderate for VSS and observer POSAS (intraclass correlation coefficient were 0.80, 0.60, and 0.47, respectively). Pearson\u27s correlation indicated moderate association between observer DKS with observer POSAS (ρ = 0.56, p \u3c 0.001) and substantial relationship between observer DKS and VSS (ρ = 0.63, p \u3c 0.001). Pearson\u27s correlation indicated moderate association between patient portion of DKS and patient portion of POSAS and patient portion of the DKS and DLQI (0.61 and 0.60, respectively, p \u3c 0.05). DKS total score consistently showed significant substantial relationship with POSAS total score (ρ = 0.65, p \u3c 0.001). Conclusions: The DKS offers a validated keloid-specific outcome measure for comparing keloid treatments