Association of Neighborhood Socioeconomic Disadvantage with Proliferative Diabetic Retinopathy.

OBJECTIVE OR PURPOSE: To evaluate the association between neighborhood socioeconomic deprivation, distance from ophthalmology clinics, and diagnosis of proliferative diabetic retinopathy (PDR). DESIGN: Retrospective cohort study. SUBJECTS, PARTICIPANTS, AND/OR CONTROLS: Adult patients (≥18 years) with diabetes mellitus at Johns Hopkins Hospital and University of Wisconsin-Madison. METHODS, INTERVENTION, OR TESTING: Patient addresses were geocoded and the block group was linked to the 2021 national Area Deprivation Index (ADI). ADI was divided into quartiles, with higher quartiles indicating greater socioeconomic disadvantage. The distance between patient's residence and ophthalmology clinics was calculated. Multivariable logistic regression models were used to analyze the association between ADI quartile, distance from clinic, and PDR, adjusted for demographics and insurance status. The interaction between ADI and distance was tested. MAIN OUTCOME MEASURES: Diagnosis of PDR. RESULTS: 73,618 patients were included. A significant interaction was observed between ADI quartile and distance from ophthalmology clinics (P < .001). Among patients residing within 8 miles of clinics, those in higher ADI quartiles had increased odds of PDR compared to those in ADI Q1 (Q2: OR 1.36, 95% CI 1.12-1.65; Q3: OR 1.79, 95% CI 1.46-2.19; Q4: OR 2.60, 95% CI 2.09-3.25; P<.001 for trend). Conversely, for patients living more than 8 miles from clinics, the odds of PDR were similar across ADI quartiles (Q1: OR 0.85, 95% CI 0.73-0.98; Q2: OR 1.02, 95% CI 0.87-1.12; Q3: OR 1.08, 95% CI 0.90-1.30). However, patients in all ADI quartiles more than 8 miles had greater odds of PDR compared to those in the same ADI quartile within 8 miles (OR 3.15, 95% CI 2.61-3.80, OR 1.97, 95% CI 1.71-2.27, OR 1.79, 95% CI 1.51-2.12, and OR 1.31, 95% CI 1.07-1.61 in ADI Q1 to Q4 respectively). CONCLUSIONS: Patients living in neighborhoods with greater socioeconomic disadvantage and further from ophthalmology clinics have greater odds of PDR. These findings suggest the potential utility of targeted interventions in socioeconomically deprived and distant areas to reduce PDR-related blindness.

Racial and Ethnic Disparities in Receipt of Retinal Imaging Among Patients With Diabetes.

This cohort study examines racial and ethnic differences in varieties of advanced retinal imaging received among patients with diabetes at a single tertiary care institution.

Improving the Identification of Diabetic Retinopathy and Related Conditions in the Electronic Health Record Using Natural Language Processing Methods.

Purpose: To compare the performance of 3 phenotyping methods in identifying diabetic retinopathy (DR) and related clinical conditions. Design: Three phenotyping methods were used to identify clinical conditions including unspecified DR, nonproliferative DR (NPDR) (mild, moderate, severe), consolidated NPDR (unspecified DR or any NPDR), proliferative DR, diabetic macular edema (DME), vitreous hemorrhage, retinal detachment (RD) (tractional RD or combined tractional and rhegmatogenous RD), and neovascular glaucoma (NVG). The first method used only International Classification of Diseases, 10th Revision (ICD-10) diagnosis codes (ICD-10 Lookup System). The next 2 methods used a Bidirectional Encoder Representations from Transformers with a dense Multilayer Perceptron output layer natural language processing (NLP) framework. The NLP framework was applied either to free-text of provider notes (Text-Only NLP System) or both free-text and ICD-10 diagnosis codes (Text-and-International Classification of Diseases [ICD] NLP System). Subjects: Adults ≥18 years with diabetes mellitus seen at the Wilmer Eye Institute. Methods: We compared the performance of the 3 phenotyping methods in identifying the DR related conditions with gold standard chart review. We also compared the estimated disease prevalence using each method. Main Outcome Measures: Performance of each method was reported as the macro F1 score. The agreement between the methods was calculated using the kappa statistic. Prevalence estimates were also calculated for each method. Results: A total of 91 097 patients and 692 486 office visits were included in the study. Compared with the gold standard, the Text-and-ICD NLP System had the highest F1 score for most clinical conditions (range 0.39-0.64). The agreement between the ICD-10 Lookup System and Text-Only NLP System varied (kappa of 0.21-0.81). The prevalence of DR and related conditions ranged from 1.1% for NVG to 17.9% for DME (using the Text-and-ICD NLP System). Conclusions: The prevalence of DR and related conditions varied significantly depending on the methodology of identifying cases. The best performing phenotyping method was the Text-and-ICD NLP System that used information in both diagnosis codes as well as free-text notes. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Neighborhood-Level Social Determinants of Health and Presenting Characteristics for Rhegmatogenous Retinal Detachments.

Importance: Functional outcomes after repair of rhegmatogenous retinal detachments (RRDs) are highly dependent on baseline visual acuity and foveal status. Adverse social determinants of health (SDOH) can present barriers to timely presentation for repair and limit vision outcomes. Objective: To evaluate the association between neighborhood-level SDOH with baseline severity (visual acuity and fovea status) of RRD. Design, Setting, and Participants: This was a retrospective cohort study that included adult patients 18 years and older who underwent primary repair of uncomplicated RRD at the Wilmer Eye Institute from January 2008 to December 2018. Study data were analyzed from December 2023 to April 2024. Exposures: The census block group of patient home addresses were matched to multiple neighborhood-level SDOH including the Area Deprivation Index (ADI), per capita income, percentage of renters, percentage of rent burden, percentage of people using a food assistance program, percentage of uninsured individuals, mode of transportation to work, distance to the nearest transit stop, total road density, National Walkability Index, Index of Medical Underservice score, and aggregate cost of medical care. Main Outcomes and Measures: Odds of presenting with vision worse than 20/40 or fovea-involving RRD using multivariable logistic regression adjusting for age, sex, race and ethnicity, and insurance. Results: A total of 700 patients (mean [SD] age, 57.9 [12.4] years; 432 male [61.7%]) were included. Every decile increase in ADI, indicating more socioeconomic disadvantage, was associated with an increased odds of presenting with worse visual acuity and fovea-involving RRD (odds ratio [OR], 1.14; 95% CI, 1.04-1.24; P = .004 and OR, 1.13; 95% CI, 1.04-1.22; P = .005, respectively). Each $1000 increase in per capita income was associated with lower odds of presenting with worse vision (OR, 0.99; 95% CI, 0.98-0.99; P = .001). Every 1% increase in percentage of workers who drove to work was associated with an increased odds of presenting with worse vision and fovea-involving RRD (OR, 1.02; 95% CI, 1.01-1.03; P = .005 and OR, 1.01; 95% CI, 1.00-1.03; P = .04, respectively). Conclusions and Relevance: Results of this cohort study suggest that patients with a residence in neighborhoods with more socioeconomic deprivation or a higher percentage of workers who drove to work were more likely to present with more severe RRD even after accounting for multiple individual-level characteristics. These findings support consideration of public policy changes to address the barriers faced by patients residing in certain neighborhoods who seek prompt surgical intervention for RRD to reduce health disparities in RRD outcomes.

Severity influences categorical likelihood communications: A case study with Southeast Asian weather forecasters.

Risk assessments are common in multiple domains, from finance to medicine. They require evaluating an event's potential severity and likelihood. We investigate the possible dependence of likelihood and severity within the domain of impact-based weather forecasting (IBF), following predictions derived from considering asymmetric loss functions. In a collaboration between UK psychologists and partners from four meteorological organisations in Southeast Asia, we conducted two studies (N = 363) eliciting weather warnings from forecasters. Forecasters provided warnings denoting higher likelihoods for high severity impacts than low severity impacts, despite these impacts being described as having the same explicit numerical likelihood of occurrence. This 'Severity effect' is pervasive, and we find it can have a continued influence even for an updated forecast. It is additionally observed when translating warnings made on a risk matrix to numerical probabilities.

Place, Race, and Lapses in Diabetic Retinopathy Care.

This cohort study investigates the association of neighborhood-level social determinants of health with lapses in diabetic retinopathy care by race and ethnicity.

Similar Risk of Kidney Failure among Patients with Blinding Diseases Who Receive Ranibizumab, Aflibercept, and Bevacizumab: An Observational Health Data Sciences and Informatics Network Study.

PURPOSE: To characterize the incidence of kidney failure associated with intravitreal anti-VEGF exposure; and compare the risk of kidney failure in patients treated with ranibizumab, aflibercept, or bevacizumab. DESIGN: Retrospective cohort study across 12 databases in the Observational Health Data Sciences and Informatics (OHDSI) network. SUBJECTS: Subjects aged ≥ 18 years with ≥ 3 monthly intravitreal anti-VEGF medications for a blinding disease (diabetic retinopathy, diabetic macular edema, exudative age-related macular degeneration, or retinal vein occlusion). METHODS: The standardized incidence proportions and rates of kidney failure while on treatment with anti-VEGF were calculated. For each comparison (e.g., aflibercept versus ranibizumab), patients from each group were matched 1:1 using propensity scores. Cox proportional hazards models were used to estimate the risk of kidney failure while on treatment. A random effects meta-analysis was performed to combine each database's hazard ratio (HR) estimate into a single network-wide estimate. MAIN OUTCOME MEASURES: Incidence of kidney failure while on anti-VEGF treatment, and time from cohort entry to kidney failure. RESULTS: Of the 6.1 million patients with blinding diseases, 37 189 who received ranibizumab, 39 447 aflibercept, and 163 611 bevacizumab were included; the total treatment exposure time was 161 724 person-years. The average standardized incidence proportion of kidney failure was 678 per 100 000 persons (range, 0-2389), and incidence rate 742 per 100 000 person-years (range, 0-2661). The meta-analysis HR of kidney failure comparing aflibercept with ranibizumab was 1.01 (95% confidence interval [CI], 0.70-1.47; P = 0.45), ranibizumab with bevacizumab 0.95 (95% CI, 0.68-1.32; P = 0.62), and aflibercept with bevacizumab 0.95 (95% CI, 0.65-1.39; P = 0.60). CONCLUSIONS: There was no substantially different relative risk of kidney failure between those who received ranibizumab, bevacizumab, or aflibercept. Practicing ophthalmologists and nephrologists should be aware of the risk of kidney failure among patients receiving intravitreal anti-VEGF medications and that there is little empirical evidence to preferentially choose among the specific intravitreal anti-VEGF agents. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Social Risk Groups in Patients With Diabetes With Differing Eye Care Utilization and Vision Outcomes.

Purpose: To evaluate whether latent class analysis on social determinants of health (SDoH) data can identify social risk groups that differ by adverse SDoH and vision outcomes in patients with diabetes. Methods: This was a prospective cohort study of adults ≥18 years with diabetes who completed a SDoH survey. Latent class analysis was used to cluster patients into social risk groups. The association of social risk group and severity of diabetic retinopathy, history of lapses in diabetic retinopathy care, and visual acuity was evaluated. Results: A total of 1006 participants were included. The three social risk groups differed by sociodemographic characteristics. The average age was 65, 60, and 54 in Groups 1, 2, and 3 respectively. Most (51%) patients in group 1 were non-Hispanic White, 66% in group 2 were non-Hispanic Black, and 80% in group 3 were Hispanic. Group 1 had the lowest burden of adverse SDoH per person (average 3.6), group 2 had 8.2, and group 3 had 10.5. In general, group 1 lacked diabetic retinopathy knowledge, group 2 had financial insecurity and difficulties with transportation, and group 3 had financial insecurity and did not have health insurance. Social risk group was associated with a history of lapses in diabetic retinopathy care, and presenting with worse vision. Conclusions and Translational Relevance: We identified distinct social risk groups among patients seeking care for diabetic retinopathy that differed by social needs, eye care utilization, and vision. Identifying these groups and their specific needs can help guide interventions to effectively address adverse SDoH and improve eye care utilization and vision outcomes among patients with diabetes.

Progress towards health equity in Vietnam: evidence from nationwide official health statistics, 2010-2020.

INTRODUCTION: One of the ultimate goals of strengthening the health system is to achieve health equity. Vietnam is considered one of the 'fast-track countries' to achieve the health-related Millennium Development Goals, but research on its equity strategies remains inadequate. METHODS: Using Vietnamese official health statistics, we investigated inequity in four dimensions including health resources, service delivery, service utilisation and residents' health status from the perspectives of income levels, poverty rates and subnational regions. The Slope Index of Inequality, concentration curve/Concentration Index, absolute difference and Theil Index were used. RESULTS: Four indicators showed 'pro-poor' inequality in health resources, including the per capita health budget, per capita health personnel, per capita health personnel at the community level and per capita hospital beds at the community level, while provincial hospital beds showed 'pro-rich' inequality. Two health service delivery indicators (delivery of antenatal care ≥3 times and proportion of community health service centres with medical doctors) show 'pro-rich' inequality, although two health status indicators, mortality and malnutrition rates for children under five, showed 'pro-poor' inequality. The Northern Midlands and Mountain Areas, and the Central Highlands were disadvantaged regarding service delivery and health status. Intraregional differences were the main factors contributing to the inequalities in delivery of antenatal care ≥3 times, provincial hospital beds and percentage of community health centres with medical doctors, with the Red River Delta and the South East region experiencing the greatest inequalities. CONCLUSION: The overall level of health equity in Vietnam has increased over the past decade, although inequality in health service delivery has hindered progress towards health equity based on income, poverty and subnational regions. Targeted policies need to be introduced to reduce inequities relating to the health workforce and service delivery capacity.

Benzodiazepines for pediatric epilepsies and their risks in a cohort within the French health care data.

OBJECTIVE: The management of antiseizure treatment in patients with epilepsy relies on the benefit-risk ratio. Data on antiseizure medication (ASM) use in children are limited. We described antiseizure medication use in children with epilepsy (CwE) in France, with a focus on the chronic use of benzodiazepines and related implications. METHODS: We conducted a 5-year cohort study from January 2012, using data from the French national health care data system (Système National des Données de Santé). We included CwE identified through International Classification of Diseases, 10th Revision codes and medications from January 2012 to December 2015 and followed them until December 2016. We described ASMs and assessed whether the risk of initiating a polytherapy after a bitherapy depends on whether benzodiazepine was included in the bitherapy. RESULTS: We identified 62 885 CwE. Valproate was the most reimbursed ASM (40%), followed by lamotrigine (17.6%), levetiracetam (9.3%), clobazam (6.1%), and carbamazepine (5.8%). Prescriptions were initiated at the hospital in 74.5% of CwE. We observed a decrease in the number of CwE with at least one benzodiazepine reimbursement from 15.3% in 2013 to 10.1% in 2016 (p < .0001). The prevalence of CwE with levetiracetam reimbursements increased, whereas that of CwE with valproate decreased. A switch from a bitherapy to a polytherapy was more likely when the bitherapy included a benzodiazepine (subdistribution hazard ratio [sHR] = 1.20 [1.03-1.39]). SIGNIFICANCE: The prevalence of CwE with at least one benzodiazepine reimbursement decreased during the study period. Benzodiazepines were associated with an increased use of subsequent ASM polytherapy.

Secondary Mediastinal Bleeding Caused by Parathyroid Adenocarcinoma: A Case Report.

Introduction: The clinical picture of parathyroid tumors is mainly related to hypercalcemia such as kidney stones and bone and muscle pain. However, spontaneous cervical hemorrhage due to parathyroidoma bleeding is rare with clinical manifestations of the painful swelling and bruising of the neck accompanied by dysphagia and dyspnea. Case presentation: We report a case of a 71-year-old female patient who presented with acute cervical swelling and extensive bleeding spreading from the neck to the abdomen and 2 flanks. Investigation of patients revealed increased parathyroid hormone levels and hypercalcemia. The neck ultrasound showed the thyroid nodules in 2 lobes, and goiter plongeant on the right. Computed tomography scan images showed a hematoma spreading from the right side of the neck to the mediastinum. Result: The patient required emergency surgery due to dyspnea and hemodynamic instability. The preoperative diagnosis was cervical bleeding with the likely cause being thyroid nodule rupture. However, during the surgery, the bleeding source was determined to be the right parathyroid tumor located deeply below the superior mediastinum. The patient's histopathological result of the tumor is parathyroid adenocarcinoma. Conclusion: From our experience, the hemorrhage from parathyroid tumor should be considered as a cause of acute neck bleeding when no history of trauma or surgery is identified. Post-surgery histopathological analyses of the tumor are very important to detect parathyroid adenocarcinoma.

Trastuzumab deruxtecan in metastatic breast cancer with variable HER2 expression: the phase 2 DAISY trial.

The mechanisms of action of and resistance to trastuzumab deruxtecan (T-DXd), an anti-HER2-drug conjugate for breast cancer treatment, remain unclear. The phase 2 DAISY trial evaluated the efficacy of T-DXd in patients with HER2-overexpressing (n = 72, cohort 1), HER2-low (n = 74, cohort 2) and HER2 non-expressing (n = 40, cohort 3) metastatic breast cancer. In the full analysis set population (n = 177), the confirmed objective response rate (primary endpoint) was 70.6% (95% confidence interval (CI) 58.3-81) in cohort 1, 37.5% (95% CI 26.4-49.7) in cohort 2 and 29.7% (95% CI 15.9-47) in cohort 3. The primary endpoint was met in cohorts 1 and 2. Secondary endpoints included safety. No new safety signals were observed. During treatment, HER2-expressing tumors (n = 4) presented strong T-DXd staining. Conversely, HER2 immunohistochemistry 0 samples (n = 3) presented no or very few T-DXd staining (Pearson correlation coefficient r = 0.75, P = 0.053). Among patients with HER2 immunohistochemistry 0 metastatic breast cancer, 5 of 14 (35.7%, 95% CI 12.8-64.9) with ERBB2 expression below the median presented a confirmed objective response as compared to 3 of 10 (30%, 95% CI 6.7-65.2) with ERBB2 expression above the median. Although HER2 expression is a determinant of T-DXd efficacy, our study suggests that additional mechanisms may also be involved. (ClinicalTrials.gov identifier NCT04132960 .).

The Impact of Social Determinants of Health on Eye Care Utilization in a National Sample of People with Diabetes.

PURPOSE: To evaluate the association of social determinants of health (SDoH) with eye care utilization among people with diabetes mellitus using the 2013-2017 National Health Interview Survey (NHIS). DESIGN: Retrospective cross-sectional study. PARTICIPANTS: Participants ≥ 18 years of age with self-reported diabetes. METHODS: The SDoH in the following domains were used: (1) economic stability; (2) neighborhood, physical environment, and social cohesion; (3) community and social context; (4) food environment; (5) education; and (6) health care system. An aggregate SDoH score was calculated and divided into quartiles, with Q4 representing those with the highest adverse SDoH burden. Survey-weighted multivariable logistic regression models evaluated the association of SDoH quartile with eye care utilization in the preceding 12 months. A linear trend test was conducted. Domain-specific mean SDoH scores were calculated, and the performance of domain-specific models was compared using area under the curve (AUC). MAIN OUTCOME MEASURE: Eye care utilization in the preceding 12 months. RESULTS: Of 20 807 adults with diabetes, 43% had not used eye care. Greater adverse SDoH burden was associated with decrements in odds of eye care utilization (P < 0.001 for trend). Participants in the highest quartile of adverse SDoH burden (Q4) had a 58% lower odds (odds ratio [OR], 0.42; 95% confidence interval [CI], 0.37-0.47) of eye care utilization than those in Q1. The domain-specific model using economic stability had the highest performing AUC (0.63; 95% CI, 0.62-0.64). CONCLUSIONS: Among a national sample of people with diabetes, adverse SDoH were associated with decreased eye care utilization. Evaluating and intervening upon the effects of adverse SDoH may be a means by which to improve eye care utilization and prevent vision loss. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Health Disparities in Lapses in Diabetic Retinopathy Care.

Objective: To develop a novel methodology to identify lapses in diabetic retinopathy care in electronic health records (EHRs) and evaluate health disparities by race and ethnicity. Design: Retrospective cohort study. Subjects: Adult patients with diabetes mellitus who were evaluated at the Wilmer Eye Institute from January 1, 2013 to April 2, 2022. Methods: The methodology to identify lapses in care first identified diabetic retinopathy screening or treatment visits and then compared the providers' recommended follow-up timeframe with the patient's actual time to next encounter. The association of race and ethnicity with odds of lapses in care was evaluated using a mixed-effects logistic regression model controlling for age, sex, insurance, severity of diabetic retinopathy, presence of other retinal disorders, and glaucoma. Main Outcome Measures: Lapses in diabetic retinopathy care. Results: The methodology to identify diabetic retinopathy-related visits had a 95.0% (95% confidence interval, 93.0-96.6) sensitivity and 98.8% (98.1-99.3) specificity as compared with a gold standard grader. The methodology resulted in a 97.3% (96.2-98.4) sensitivity and 98.1% (97.3-98.9) specificity for detecting a follow-up recommendation, with an average error of -0.05 (-0.31 to 0.21) weeks in extracting the precise timeframe. A total of 39 561 patients with 91 104 office visits were included in the analysis. The average age was 61.4 years. More than 3 (77.6%) in 4 patients had a lapse in care. In multivariable analysis, non-Hispanic Black patients had 1.24 (1.19-1.30) odds and Hispanic patients had 1.26 (1.13-1.40) odds of ever having a lapse in care compared with non-Hispanic White patients (P < 0.001, respectively). Conclusions: We have developed a reliable methodology for identifying lapses in diabetic retinopathy care that is tailored to a provider's recommended follow-up. Using this approach, we find that 3 in 4 patients experience a lapse in diabetic retinopathy care and that these rates are higher among non-Hispanic Black and Hispanic patients. Deploying this methodology in the EHR is one potential means by which to identify and mitigate lapses in critical ophthalmic care in patients with diabetes. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Effect of Training on Physicians' Palliative Care-Related Knowledge and Attitudes in Vietnam.

CONTEXT: Palliative care remains largely inaccessible in low- and middle-income countries (LMICs), and efforts to increase access are impeded by lack of training of proven effectiveness for physicians. OBJECTIVES: To measure the effectiveness of palliative care training for Vietnamese physicians. METHODS: The palliative care-related knowledge, attitudes, and self-assessment of Vietnamese physicians were studied prior to a basic course in palliative care (baseline), just after the physicians completed the course (post), and 6-18 months later (follow-up). RESULTS: The self-assessment scores and knowledge scores increased significantly from baseline to post and decreased significantly from post to follow-up, but the follow-up scores remained significantly higher than baseline. There were significant interactions between changes over time of the knowledge scores and baseline age, degree, years of graduation, training, type of work, and whether participants had ever prescribed morphine for pain. Medically appropriate attitudes increased significantly from baseline to post and did not decrease significantly from post to follow-up. CONCLUSION: Our basic palliative care course in Vietnam resulted in significant and enduring improvements among physicians in palliative care-related knowledge, attitudes, and self-assessed competence. To respond to the enormous unmet need for palliative care in LMICs, primary care providers and physician-specialists in many fields, among others, should receive palliative care training of proven effectiveness, receive ongoing mentoring or refresher training, and be given the responsibility and opportunity to practice what they learn.

The clinical features and genomic epidemiology of carbapenem-resistant Acinetobacter baumannii infections at a tertiary hospital in Vietnam.

OBJECTIVES: To characterise the clinical features of Acinetobacter baumannii infections and investigate the phylogenetic structure and transmission dynamics of A. baumannii in Vietnam. METHODS: Between 2019 and 2020, a surveillance of A. baumannii (AB) infections was conducted at a tertiary hospital in Ho Chi Minh City, Vietnam. Risk factors for in-hospital mortality were analysed using logistic regressions. Whole-genome sequence data were used to characterise genomic species, sequence types (STs), antimicrobial resistance genes, surface antigens, and phylogenetic relatedness of AB isolates. RESULTS: Eighty-four patients with AB infections were enrolled in the study, 96% of whom were hospital-acquired. Half of the AB isolates were identified from ICU-admitted patients, while the remaining isolates were from non-ICU patients. The overall in-hospital mortality was 56%, with associated risk factors including advanced age, ICU stay, exposure to mechanical ventilation/central venous catheterization, pneumonia as source of AB infection, prior use of linezolid/aminoglycosides, and AB treatment with colistin-based therapy. Nearly 91% of isolates were carbapenem-resistant; 92% were multidrug-resistant; and 6% were colistin-resistant. ST2, ST571, and ST16 were the three dominant carbapenem-resistant A. baumannii (CRAB) genotypes, exhibiting distinct AMR gene profiles. Phylogenetic analysis of CRAB ST2 isolates together with previously published ST2 collection provided evidence of intra- and inter-hospital transmission of this clone. CONCLUSIONS: Our study highlights a high prevalence of carbapenem resistance and multidrug resistance in A. baumannii and elucidates the spread of CRAB within and between hospitals. Strengthening infection control measures and routine genomic surveillance are crucial to reducing the spread of CRAB and detecting novel pan-drug-resistant variants in a timely fashion.

Impact of Childhood Onset Psoriasis on Addictive Behaviours, Socioeconomic and Educational Data in Adulthood.

Paediatric psoriasis has been associated with school absenteeism, limitation of physical activities, psychiatric disorders and, in the longer term, with sexual dysfunction and addictions. This raises the hypothesis that childhood onset psoriasis may affect patients' educational development, and further social and professional outcomes. This study evaluated the relationship between childhood onset psoriasis and patients' educational and socioeconomic characteristics, and the development of addictions in adulthood. This cross-sectional ancillary study captured patients' characteristics at baseline in the French PSOBIOTEQ registry. Data in adulthood included: educational (baccalaureate) and socioeconomic (working activity) groups, smoking status (self-reporting of being a current smoker vs past smoker or non-smoker), alcohol consumption (defined as at least 1 glass of alcoholic beverage per day), and living conditions (alone/family/social institutions; child at home). A total of 1,960 patients were included, of whom 26.2% had childhood onset psoriasis. In multivariate analyses, childhood onset psoriasis was associated with smoker status (p = 0.02). No association was observed with educational level, working activity, living conditions, or alcohol consumption. This study provides reassuring data overall with regard to the impact of childhood onset psoriasis on major social outcomes. Evidence for some association with addictive behaviours paves the way for larger prospective studies assessing in depth the social and educational impact of this disease.

Synergistic anti-tumor efficacy of mutant isocitrate dehydrogenase 1 inhibitor SYC-435 with standard therapy in patient-derived xenograft mouse models of glioma.

Clinical outcomes in patients with WHO grade II/III astrocytoma, oligodendroglioma or secondary glioblastoma remain poor. Isocitrate dehydrogenase 1 (IDH1) is mutated in > 70% of these tumors, making it an attractive therapeutic target. To determine the efficacy of our newly developed mutant IDH1 inhibitor, SYC-435 (1-hydroxypyridin-2-one), we treated orthotopic glioma xenograft model (IC-BT142AOA) carrying R132H mutation and our newly established orthotopic patient-derived xenograft (PDX) model of recurrent anaplastic oligoastrocytoma (IC-V0914AOA) bearing R132C mutation. In addition to suppressing IDH1 mutant cell proliferation in vitro, SYC-435 (15 mg/kg, daily x 28 days) synergistically prolonged animal survival times with standard therapies (Temozolomide + fractionated radiation) mediated by reduction of H3K4/H3K9 methylation and expression of mitochondrial DNA (mtDNA)-encoded molecules. Furthermore, RNA-seq of the remnant tumors identified genes (MYO1F, CTC1 and BCL9) and pathways (base excision repair, TCA cycle II, sirtuin signaling, protein kinase A, eukaryotic initiation factor 2 and α-adrenergic signaling) as mediators of therapy resistance. Our data demonstrated the efficacy SYC-435 in targeting IDH1 mutant gliomas when combined with standard therapy and identified a novel set of genes that should be prioritized for future studies to overcome SYC-435 resistance.

Ultra-Deep Sequencing of Plasma-Circulating DNA for the Detection of Tumor- Derived Mutations in Patients with Nonmetastatic Colorectal Cancer.

Identification of tumor-derived mutation (TDM) in liquid biopsies (LB), especially in early-stage patients, faces several challenges, including low variant-allele frequencies, interference by white blood cell (WBC)-derived mutations (WDM), benign somatic mutations and tumor heterogeneity. Here, we addressed the above-mentioned challenges in a cohort of 50 nonmetastatic colorectal cancer patients, via a workflow involving parallel sequencing of paired WBC- and tumor-gDNA. After excluding potential false positive mutations, we detected at least one TDM in LB of 56% (28/50) of patients, with the majority showing low-patient coverage, except for one TDM mapped to KMT2D that recurred in 30% (15/30) of patients.

Nonsyndromic craniosynostosis in Vietnam: initial surgical outcomes of subspecialty mentorship.

OBJECTIVE: There is a global deficit of pediatric neurosurgical care, and the epidemiology and overall surgical care for craniosynostosis is not well characterized at the global level. This study serves to highlight the details and early surgical results of a neurosurgical educational partnership and subsequent local scale-up in craniosynostosis correction. METHODS: A prospective case series was performed with inclusion of all patients undergoing correction of craniosynostosis by extensive cranial vault remodeling at Children's Hospital 2, Ho Chi Minh City, Vietnam, between January 1, 2015, and December 31, 2019. RESULTS: A total of 76 patients were included in the study. The group was predominantly male, with a male-to-female ratio of 3.3:1. Sagittal synostosis was the most common diagnosis (50%, 38/76), followed by unilateral coronal (11.8%, 9/76), bicoronal (11.8%, 9/76), and metopic (7.9%, 6/76). The most common corrective technique was anterior cranial vault remodeling (30/76, 39.4%) followed by frontoorbital advancement (34.2%, 26/76). The overall mean operative time was 205.8 ± 38.6 minutes, and the estimated blood loss was 176 ± 89.4 mL. Eleven procedures were complicated by intraoperative durotomy (14.5%, 11/76) without any damage of dural venous sinuses or brain tissue. Postoperatively, 4 procedures were complicated by wound infection (5.3%, 4/76), all of which required operative wound debridement. There were no neurological complications or postoperative deaths. One patient required repeat reconstruction due to delayed intracranial hypertension. There was no loss to follow-up. All patients were followed at outpatient clinic, and the mean follow-up period was 32.3 ± 18.8 months postoperatively. CONCLUSIONS: Surgical care for pediatric craniosynostosis can be taught and sustained in the setting of collegial educational partnerships with early capability for high surgical volume and safe outcomes. In the setting of the significant deficit in worldwide pediatric neurosurgical care, this study provides an example of the feasibility of such relationships in addressing this unmet need.