Multimorbidity at time of death among persons with type 2 diabetes: a population-based study in Ontario, Canada.

OBJECTIVE: Individuals with Type 2 Diabetes are likely to experience multimorbidity and accumulate multiple chronic conditions over their life. We aimed to identify causes of death and chronic conditions at the time of death in a population-based cohort, and to analyze variations in the presence of diabetes at the time of death overall and across income and immigrant status. RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study of 2,199,801 adult deaths from 1992 to 2017 in Ontario, Canada. We calculated the proportion of decedents with chronic conditions at time of death and causes of death. The risk of diabetes at the time of death was modeled across sociodemographic variables with a log binomial regression adjusting for sex, age, immigrant status, area-level income. comorbiditiesand time. RESULTS: The leading causes of death in the cohort were cardiovascular and cancer. Decedents with diabetes had a higher prevalence of most chronic conditions than decedents without diabetes, including hypertension, osteo and other arthritis, chronic coronary syndrome, mood disorder, and congestive heart failure. The risk of diabetes at the time of death was 19% higher in immigrants (95%CI 1.18-1.20) and 15% higher in refugees (95%CI 1.12-1.18) compared to long-term residents, and 19% higher in the lowest income quintile (95%CI 1.18-1.20) relative to the highest income quintile, after adjusting for other covariates. CONCLUSIONS: Individuals with diabetes have a greater multimorbidity burden at the time of death, underscoring the importance of multiple chronic disease management among those living with diabetes and further considerations of the social determinants of health.

Spinning thermal radiation from twisted two different anisotropic materials.

Thermal radiation has applications in numerous fields, such as radiation cooling, thermal imaging, and thermal camouflage. Micro/nanostructures such as chiral metamaterials with polarization-dependent or symmetry-breaking properties can selectively emit circularly (spin) polarized polarization waves. In this paper, we propose and demonstrate the spinning thermal radiation from two twisted different anisotropic materials. Taking industrial polymer and biaxial hyperbolic material α-MoO3 as an example, it is found that broadband spinning thermal radiation can be obtained from 13 µm to 18 µm. The spin thermal radiation of the proposed twisted structure originates from the combined effect of polarization conversion of circularly polarized wave and selective absorption of linearly polarized wave by the top and bottom layers of anisotropic materials, respectively. Besides, the narrowband spinning thermal radiation with 0.9 circular dichroism is achieved at wavelength of 12.39 µm and 18.93 µm for finite thickness α-MoO3 due to the epsilon-near-zero mode, and the magnetic field distribution can confirm the phenomenon. This work achieves broadband and narrowband spin thermal radiation and significantly enhances circular dichroism, which may have applications in biological sensing and thermal detection.

Pneumocystis pneumonia in patients with primary nephrotic syndrome.

OBJECTIVE: The aim of this study was to analyze the clinical features, risk factors, and outcomes of patients with primary nephrotic syndrome (PNS) who developed Pneumocystis pneumonia (PCP). MATERIALS AND METHODS: We systematically reviewed medical records from 18 PNS patients with PCP admitted to our hospital from April 2007 to April 2019. A total of 180 cases were randomly selected as controls from PNS inpatients without infection. RESULTS: In PCP patients, the mean age at presentation was 48.5 years, mean duration of prednisone treatment was 3.7 months, and mean prednisone dose on admission was 31.3 mg/d. Eight patients (44.4%) had coexisting infections, most often was Cytomegalovirus (4 patients); 11 patients (61.1%) had ICU admission, and 9 patients (50%) had mechanical ventilation. PCP patients had more prednisone, more immunosuppressive therapy, lower CD4+ cell counts and hemoglobin, and higher serum creatinine than those without infections (p < 0.05). All patients survived after treatment. CONCLUSION: PCP was not unusual in PNS patients, and the most important risk factors were prednisone usage, other immunosuppressive therapy, and a lower CD4+ cell count; however, these patients had a good outcome after sufficient treatment.

A nomogram to predict hyperkalemia in patients with hemodialysis: a retrospective cohort study.

BACKGROUND: Hyperkalemia increases the risk of mortality and cardiovascular-related hospitalizations in patients with hemodialysis. Predictors of hyperkalemia are yet to be identified. We aimed at developing a nomogram able to predict hyperkalemia in patients with hemodialysis. METHODS: We retrospectively screened patients with end-stage renal disease (ESRD) who had regularly received hemodialysis between Jan 1, 2017, and Aug 31, 2021, at Lishui municipal central hospital in China. The outcome for the nomogram was hyperkalemia, defined as serum potassium [K+] ≥ 5.5 mmol/L. Data were collected from hemodialysis management system. Least Absolute Shrinkage Selection Operator (LASSO) analysis selected predictors preliminarily. A prediction model was constructed by multivariate logistic regression and presented as a nomogram. The performance of nomogram was measured by the receiver operating characteristic (ROC) curve, calibration diagram, and decision curve analysis (DCA). This model was validated internally by calculating the performance on a validation cohort. RESULTS: A total of 401 patients were enrolled in this study. 159 (39.65%) patients were hyperkalemia. All participants were divided into development (n = 256) and validation (n = 145) cohorts randomly. Predictors in this nomogram were the number of hemodialysis session, blood urea nitrogen (BUN), serum sodium, serum calcium, serum phosphorus, and diabetes. The ROC curve of the training set was 0.82 (95%CI 0.77, 0.88). Similar ROC curve was achieved at validation set 0.81 (0.74, 0.88). The calibration curve demonstrated that the prediction outcome was correlated with the observed outcome. CONCLUSION: This nomogram helps clinicians in predicting the risk of PEW and managing serum potassium in the patients with hemodialysis.

Depression and Diabetes Mellitus Multimorbidity Is Associated With Loss of Independence and Dementia Poststroke.

BACKGROUND AND PURPOSE: Many patients with ischemic stroke present with multiple comorbidities that threaten survival and recovery. This study sought to determine the risks of adverse long-term stroke outcomes associated with multimorbid diabetes mellitus and depression. METHODS: Retrospective analysis of prospectively collected data on consecutive patients without premorbid dementia admitted from the community for a first-ever acute ischemic stroke to comprehensive stroke centers across Ontario, Canada (2003-2013). Premorbid histories of diabetes mellitus and depression were ascertained within 5 years before stroke admission. Adjusted hazard ratios (aHR [95% CI]) of admission to long-term care, incident dementia, readmission for stroke or transient ischemic attack and all-cause mortality, over time among those discharged back into the community poststroke. RESULTS: Among 23 579 stroke admissions, n=20 201 were discharged back into the community. Diabetes mellitus and depression were associated with synergistic hazards of admission to long-term care (X2=5.4; P=0.02) over a median follow-up of 5.6 years. This interaction was observed among women specifically; depression multimorbidity showed particularly high hazards of admission to long-term care (aHRDepression=1.57 [1.24-1.98]) and incident dementia (aHRDepression=1.85 [1.40-2.44]) among women with diabetes mellitus. In the whole cohort, diabetes mellitus and depression were associated individually with long-term care admission (aHRDiabetes=1.20 [1.12-1.29]; aHRDepression=1.19 [1.04-1.37]), incident dementia (aHRDiabetes=1.14 [1.06-1.23]; aHRDepression=1.27 [1.08-1.49]), stroke/transient ischemic attack readmission (aHRDiabetes=1.18 [1.10-1.26]; aHRDepression=1.24 [1.07-1.42]), and all-cause mortality (aHRDiabetes=1.29 [1.23-1.36]; aHRDepression=1.16 [1.05-1.29]). CONCLUSIONS: The risks of dementia and needing long-term care in the years after surviving a stroke were particularly elevated among women when premorbid diabetes mellitus and depression occurred together. Long-term stroke recovery strategies might target high-risk patients with mood and metabolic multimorbidity.

Identification of CD28 and PTEN as novel prognostic markers for cervical cancer.

Cervical cancer (CC) is the most common malignant tumor with poor clinical outcome among women. Identification of novel biomarkers could be beneficial for the clinical diagnosis and treatment of CC. This study aimed to identify prognostic biomarkers for the prediction of prognostic status of CC patients, and explore the effect of the corresponding methylated genes in the occurrence and development of CC. The methylation microarray data of CC was extracted from The Cancer Genome Atlas (TCGA) dataset. The methylation genes associated with the prognostic status were identified based on the information of the relapse-free survival (RFS) of the CC patients. The prognostic gene pairs were further identified. Then, the prognostic signature was identified by the forward search algorithm based on the C-index method. The results were validated by independent dataset. Finally, the functional analysis was performed on the methylation genes. A total of 276 methylation genes and 2508 gene pairs associated with the prognostic status of the CC were identified. A signature composed of eight methylation gene pairs was obtained to predict the prognostic status of cervical patients. A series of genes that played an important role in the occurrence and development of CC were obtained by the functional enrichment analysis. To summary, a prognostic signature consisting of eight methylation gene pairs was obtained. Of note, the CD28 and PTEN gene pair were found to play important roles in the occurrence and development of CC.

Overexpression of MALAT1 contributes to cervical cancer progression by acting as a sponge of miR-429.

Cervical cancer remains a malignant type of tumor and is the fourth leading cause of cancer-related death among females. MALAT1 has been identified as a tumor oncogene in various cancers. Our present study aimed to explore the biological role of MALAT1 in cervical cancer. We observed that MALAT1 was significantly upregulated in human cervical cancer cell lines compared with the ectocervical epithelial cells. MALAT1 was repressed by transfection with LV-shMALAT1, whereas increased by LV-MALAT1 in HeLa and Caski cells. Silencing of MALAT1 obviously reduced cervical cell viability, induced cell apoptosis, and repressed cell invasion capacity. Conversely, overexpression of MALAT1 exhibited an opposite phenomenon. Furthermore, miR-429 was predicted as a direct target of MALAT1, and it was dramatically decreased in cervical cancer cells. It has been shown that miR-429 plays a crucial role in cervical cancer progression. In our current study, the targeting correlation between MALAT1 and miR-429 was confirmed by luciferase reporter assays and RIP experiments. Finally, in vivo animal models were established, and we indicated that MALAT1 inhibited cervical cancer progression via targeting miR-429. These findings revealed that MALAT1 can sponge miR-429 and regulate cervical cancer pathogenesis in vivo and in vitro. In conclusion, we indicated that the MALAT1/miR-429 axis was involved in cervical cancer development.

LINC00657 expedites neuropathic pain development by modulating miR-136/ZEB1 axis in a rat model.

Long non-coding RNAs (lncRNAs) are involved in the progression of several diseases. The interactions among lncRNAs, microRNA (miRNAs) or their targeting genes are reported to play crucial roles in the development of diseases. LINC00657 is observed to be upregulated in several cancers. However, the biological role of LINC00657 in neuropathic pain progress is unclear. Hence, in our study, we aimed to investigate the function of LINC00657 in neuropathic pain development. A chronic constriction injury (CCI) rat model was established, and we found that LINC00657 was greatly increased in CCI rats associated with a decrease of miR-136. Inhibition of LINC00657 suppressed neuropathic pain via alleviating mechanical and thermal hyperalgesia. In addition, miR-136 overexpression can also inhibit the neuropathic pain development. MiR-136 was predicted to serve as a miRNA target of LINC00657, and dual-luciferase reporter assay confirmed the correlation between LINC00657 and miR-136. Moreover, we observed that the decrease of LINC00657 was able to inhibit the neuroinflammation of CCI rats by targeting expression of cyclooxygenase-2, tumor necrosis factor-α and interleukin-1ß while miR-136 inhibitors reversed this phenomenon. Next, by using bioinformatics analysis, ZEB1 was predicted as a direct target of miR-136, and miR-136 could negatively modulate ZEB1 expression. Besides these, ZEB1 was remarkably increased in the CCI rats. Knockdown of ZEB1 can inhibit neuropathic pain development, while miR-136 inhibitors can reverse it. In conclusion, it was implied that LINC00657 can induce the neuropathic pain development via regulating miR-136/ZEB1 axis.

Long-term mortality in mothers of infants with neonatal abstinence syndrome: A population-based parallel-cohort study in England and Ontario, Canada.

BACKGROUND: Opioid addiction is a major public health threat to healthy life expectancy; however, little is known of long-term mortality for mothers with opioid use in pregnancy. Pregnancy and delivery care are opportunities to improve access to addiction and supportive services. Treating neonatal abstinence syndrome (NAS) as a marker of opioid use during pregnancy, this study reports long-term maternal mortality among mothers with a birth affected by NAS in relation to that of mothers without a NAS-affected birth in 2 high-prevalence jurisdictions, England and Ontario, Canada. METHODS AND FINDINGS: We conducted a population-based study using linked administrative health data to develop parallel cohorts of mother-infant dyads in England and Ontario between 2002 and 2012. The study population comprised 13,577 and 4,966 mothers of infants with NAS and 4,205,675 and 929,985 control mothers in England and Ontario, respectively. Death records captured all-cause maternal mortality after delivery through March 31, 2016, and cause-specific maternal mortality to December 31, 2014. The primary exposure was a live birth of an infant with NAS, and the main outcome was all deaths among mothers following their date of delivery. We modelled the association between NAS and all-cause maternal mortality using Cox regression, and the cumulative incidence of cause-specific mortality within a competing risks framework. All-cause mortality rates, 10-year cumulative incidence risk of death, and crude and age-adjusted hazard ratios were calculated. Estimated crude 10-year mortality based on Kaplan-Meier curves in mothers of infants with NAS was 5.1% (95% CI 4.7%-5.6%) in England and 4.6% (95% CI 3.8%-5.5%) in Ontario versus 0.4% (95% CI 0.41%-0.42%) in England and 0.4% (95% CI 0.38%-0.41%) in Ontario for controls (p < 0.001 for all comparisons). Survival curves showed no clear inflection point or period of heightened risk. The crude hazard ratio for all-cause mortality was 12.1 (95% 11.1-13.2; p < 0.001) in England and 11.4 (9.7-13.4; p < 0.001) in Ontario; age adjustment did not reduce the hazard ratios. The cumulative incidence of death was higher among NAS mothers than controls for almost all causes of death. The majority of deaths were by avoidable causes, defined as those that are preventable, amenable to care, or both. Limitations included lack of direct measures of maternal opioid use, other substance misuse, and treatments or supports received. CONCLUSIONS: In this study, we found that approximately 1 in 20 mothers of infants with NAS died within 10 years of delivery in both England and Canada-a mortality risk 11-12 times higher than for control mothers. Risk of death was not limited to the early postpartum period targeted by most public health programs. Policy responses to the current opioid epidemic require effective strategies for long-term support to improve the health and welfare of opioid-using mothers and their children.

Absolute cross sections for chemoradiation therapy: Damages to cisplatin-DNA complexes induced by 10 eV electrons.

In chemoradiation therapy, the synergy between the radiation and the chemotherapeutic agent (CA) can result in a super-additive treatment. A priori, this increased effectiveness could be estimated from model calculations, if absolute cross sections (ACSs) involved in cellular damage are substantially higher, when the CA binds to DNA. We measure ACSs for damages induced by 10 eV electrons, when DNA binds to the CA cisplatin as in chemotherapy. At this energy, DNA is damaged essentially by the decay of core-excited transient anions into bond-breaking channels. Films of cisplatin-DNA complexes of ratio 5:1 with thicknesses 10, 15, and 20 nm were irradiated in vacuum during 5-30 s. Conformation changes were quantified by electrophoresis and yields extrapolated from exposure-response curves. Base damages (BDs) were revealed and quantified by enzymatic treatment. The ACSs were generated from these yields by two mathematical models. For 3197 base-pair plasmid DNA, ACS for single strand breaks, double strand breaks (DSBs), crosslinks, non-DSB cluster damages, and total BDs is 71 ± 2, 9.3 ± 0.4, 10.1 ± 0.3, 8.2 ± 0.3, and 115 ± 2 ×10-15 cm2, respectively. These ACSs are higher than those of nonmodified DNA by factors of 1.6 ± 0.1, 2.2 ± 0.1, 1.3 ± 0.1, 1.3 ± 0.3, and 2.1 ± 0.4, respectively. Since LEEs are produced in large quantities by radiolysis and strongly interact with biomolecules, we expect such enhancements to produce substantial additional damages in the DNA of the nucleus of cancer cells during concomitant chemoradiation therapy. The increase damage appears sufficiently large to justify more elaborate simulations, which could provide a quantitative evaluation of molecular sensitization by Pt-CAs.

Sex Differences in Outcomes after Stroke in Patients with Diabetes in Ontario, Canada.

BACKGROUND: Outcomes after stroke in those with diabetes are not well characterized, especially by sex and age. We sought to calculate the sex- and age-specific risk of cardiovascular outcomes after ischemic stroke among those with diabetes. METHODS: Using population-based demographic and administrative health-care databases in Ontario, Canada, all patients with diabetes hospitalized with index ischemic stroke between April 1, 2002, and March 31, 2012, were followed for death, stroke, and myocardial infarction (MI). The Kaplan-Meier survival analysis and Fine-Gray competing risk models estimated hazards of outcomes by sex and age, unadjusted and adjusted for demographics and vascular risk factors. RESULTS: Among 25,495 diabetic patients with index ischemic stroke, the incidence of death was higher in women than in men (14.08 per 100 person-years [95% confidence interval [CI], 13.73-14.44] versus 11.89 [11.60-12.19]) but was lower after adjustment for age and other risk factors (adjusted hazard ratio [HR], .95 [.92-.99]). Recurrent stroke incidence was similar by sex, but men were more likely to be readmitted for MI (1.99 per 100 person-years [1.89-2.10] versus 1.58 [1.49-1.68] among females). In multivariable models, females had a lower risk of readmission for any event (HR, .96 [95% CI, .93-.99]). CONCLUSIONS: In this large, population-based, retrospective study among diabetic patients with index stroke, women had a higher unadjusted death rate but lower unadjusted incidence of MI. In adjusted models, females had a lower death rate compared with males, although the increased risk of MI among males persisted. These findings confirm and quantify sex differences in outcomes after stroke in patients with diabetes.

Trends in the Association Between Diabetes and Cardiovascular Events, 1994-2019.

This study uses administrative health care data from Ontario, Canada, to assess whether changes in diabetes management practices have affected trends in the association between diabetes vs prior cardiovascular disease and risk of cardiovascular events from 1994 to 2019 among adults aged 20 to 84 years.

A single amino acid substitution in the R3 domain of GLABRA1 leads to inhibition of trichome formation in Arabidopsis without affecting its interaction with GLABRA3.

GLABRA1 (GL1) is an R2R3 MYB transcription factor that regulates trichome formation in Arabidopsis by interacting with the bHLH transcription factor GLABRA3 (GL3) or ENHANCER OF GL3 (EGL3). The conserved [D/E]L×2 [R/K]×3L×6L×3R amino acid signature in the R3 domain of MYB proteins has been shown to be required for the interaction of MYBs with R/B-like bHLH transcription factors. By using genetic and molecular analyses, we show that the glabrous phenotype in the nph4-1 mutant is caused by a single nucleotide mutation in the GL1 gene, generating a Ser to Phe substitution (S92F) in the conserved [D/E]L×2[R/K]×3L×6L×3R amino acid signature of GL1. Activation of the integrated GL2p:GUS reporter gene in protoplasts by cotransfection of GL1 and GL3 or EGL3 was abolished by this GL1-S92F substitution. However, GL1-S92F interacted successfully with GL3 or EGL3 in protoplast transfection assays. Unlike VPGL1GL3, the fusion protein VPGL1-S92FGL3 failed to activate the integrated GL2p:GUS reporter gene in transfected protoplasts. These results suggested that the S92 in the conserved [D/E]L×2 [R/K]×3L×6L×3R amino acid signature of GL1 is not essential for the interaction of GL1 and GL3, but may play a role in the binding of GL1 to the promoters of its target genes.

Epidemiology and Treatment Patterns of Patients with Vitiligo: A Real-World Analysis.

INTRODUCTION: Vitiligo, a chronic autoimmune skin depigmentation disease with an unpredictable course, has been associated with several comorbid autoimmune and psychological conditions. Our current understanding of vitiligo burden and management in the real world is limited. This real-world analysis presents data on vitiligo epidemiology, comorbidities, and treatment of patients in Israel. METHODS: This retrospective study analyzed data from the Maccabi Health Services database. Prevalent patients with vitiligo in 2021 were matched to patients in the general population on the basis of age group, gender, and socioeconomic status. Patient demographics, vitiligo incidence and prevalence, comorbidities, and treatment patterns are reported. Data are presented as percentages, mean, median, P values, and standard mean differences (SMD). RESULTS: In this analysis, 11,412 patients with vitiligo were matched to patients from the general population. Incidence and prevalence rates increased over time from 2005 to 2021. Compared to the general population, patients with vitiligo were more likely to have an immune-mediated comorbidity (29.7% vs 18.4% [P < 0.001; SMD 0.27]) or psychological comorbidity (18.7% vs 15.9% [P < 0.001; SMD 0.07]). Comorbidities included atopic dermatitis (patients with vitiligo vs general population 12.5% vs 8.4%), psoriasis (5.8% vs 3.6%), Hashimoto's thyroiditis (2.9% vs 1.1%), alopecia areata (2.2% vs 0.9%), depression (10.8% vs 9.5%), and sleep disorder/insomnia (5.9% vs 4.4%). Only 74.8% of all patients with vitiligo had ever received treatment, with topical corticosteroids (51.5%) and calcineurin inhibitors (36.5%) most commonly prescribed. At the end of 2021, 83.7% of patients were untreated. CONCLUSION: Patients with vitiligo are more likely to have various immune-related and psychological comorbidities, highlighting the significant impact of the condition on well-being. Nearly a quarter of patients had never received treatment, with many receiving only topical treatments, and medication persistence was low. This highlights the lack of adequate treatment in this population and the need for more effective management options.

Less Is More: Selective-Atom-Removal-Derived Defective MnOx Catalyst for Efficient Propane Oxidation.

Defect manipulation in metal oxide is of great importance in boosting catalytic performance for propane oxidation. Herein, a selective atom removal strategy was developed to construct a defective manganese oxide catalyst, which involved the partial etching of a Mg dopant in MnOx. The resulting MgMnOx-H catalysts exhibited superior low-temperature catalytic activity (T50 = 185 °C, T90 = 226 °C) with a propane conversion rate of 0.29 µmol·gcat.-1·h-1 for the propane oxidation reaction, which is 4.8 times that of pristine MnOx. Meanwhile, a robust hydrothermal stability was guaranteed at 250 °C for 30 h of reaction time. The comprehensive experimental characterizations revealed that the catalytic performance improvement was closely related to the defective structures including the abundant (metal and oxygen) vacancies, distorted crystals, valence imbalance, etc., which prominently weakened the Mn-O bond and stimulated the mobility of surface lattice oxygen, leading to the elevation in the intrinsic oxidation activity. This work exemplifies the significance of defect engineering for the promotion of the oxidation ability of metal oxide, which will be valuable for the further development of efficient non-noble metal catalysts for propane oxidation.

Cost-effectiveness of tirofiban for acute ischemic stroke without large or medium-sized vessel occlusion: A Markov modelling analysis from the Chinese and United States perspectives.

BACKGROUND: The RESCUE BT2 trial recently showcased the efficacy of tirofiban in treating acute ischemic stroke (AIS) without large or medium-sized vessel occlusion. To further assess the value of tirofiban from the perspectives of Chinese and US healthcare system, a study was conducted to evaluate its cost-effectiveness. METHODS: A hybrid model, integrating a short-term decision tree with a long-term Markov model, was developed to assess cost-effectiveness between tirofiban and aspirin for stroke patients without large or medium-sized vessel occlusion. Efficacy data for tirofiban was sourced from the RESCUE BT2 trial, while cost information was derived from published papers. Outcomes measured included respective cost, effectiveness, and incremental cost-effectiveness ratio (ICER). We conducted a one-way sensitivity analysis to assess the robustness of the results. Additionally, we performed probabilistic sensitivity analysis (PSA) through 10,000 Monte Carlo simulations to evaluate the uncertainties associated with the results. RESULTS: The study revealed that tirofiban treatment in AIS patients without large or medium-sized vessel occlusion led to a considerable reduction of 2141 Chinese Yuan (CNY) in total cost, along with a lifetime gain of 0.14 quality-adjusted life years (QALYs). In the US settings, tirofiban also exhibited a lower cost ($197,055 versus $201,984) and higher effectiveness (4.15 QALYs versus 4.06 QALYs) compared to aspirin. One-way sensitivity analysis revealed that post-stroke care costs and stroke utility had the greatest impact on ICER fluctuation in both Chinese and US settings. However, these variations did not exceed the willingness-to-pay threshold. PSA demonstrated tirofiban's superior acceptability over aspirin in over 95% of potential scenarios. CONCLUSION: Tirofiban treatment for AIS without large or medium-sized vessel occlusion appeared dominant compared to aspirin in both China and the US.

Real-World Clinical, Psychosocial, and Economic Burden of Atopic Dermatitis: Results From the ESSENTIAL AD Multicountry Study.

INTRODUCTION: Limited real-world evidence exists about the burden of atopic dermatitis (AD) in patients receiving systemic or non-systemic therapies in clinical practices. ESSENTIAL AD was an observational study that aimed to fill this information gap. METHODS: ESSENTIAL AD enrolled (September 2021-June 2022) adult patients with physician-confirmed AD that was routinely managed with systemic and non-systemic treatment in a real-world setting from 15 countries in Eastern Europe, the Middle East, and Africa. Primary outcome variables were Eczema Area and Severity Index (EASI), SCORing Atopic Dermatitis (SCORAD), and Dermatology Life Quality Index (DLQI) assessed during one office visit. RESULTS: A total of 799 enrolled patients fulfilled selection criteria and were included in the study. Patients mean (standard deviation [SD]) age was 36.3 (14.4) years, 457 (57.2%) were female, and the majority of patients were white (647 [81.0%]). Mean (SD) time since AD diagnosis was 17.6 (15.2) years (median 16.5; interquartile range [IQR] 3.3-26.8). The mean (SD) EASI, SCORAD, and DLQI total scores were 11.3 (11.3 [median 8.1; IQR 3.6-15.8]), 37.8 (17.9 [median 35.5; IQR 24.2-49.0]), and 10.6 (7.2 [median 10.0; IQR 5.0-15.0]), respectively. Patients receiving systemic treatment had significantly higher disease burden (mean [SD] EASI 13.3 [13.0]; median [IQR] 9.6 [3.9-17.9]) versus non-systemic treatment (mean [SD] 9.3 [8.7]; median [IQR] 6.8 [3.0-13.2]; P < 0.0001). Results were similar for SCORAD (39.9 [19.6] vs 35.6 [15.7]; median [IQR] 38.6 [24.7-53.1] vs 32.6 [23.9-44.6]; P = 0.0017), and DLQI total scores (11.4 [7.4] vs 9.9 [6.9]; median [IQR] 11.0 [5.0-16.0] vs 9.0 [5.0-14.0]; P = 0.0033, respectively). CONCLUSION: Patients with AD continue to have substantial disease burden despite treatment with systemic therapy, suggesting that a need for effective disease management remains, including effective therapies that improve psychological outcomes and reduce economic burden of AD, in Eastern Europe, the Middle East, and Africa.

Patients with atopic dermatitis often suffer from debilitating symptoms that impact their everyday lives. Although several treatment options are available, many patients continue to experience symptoms of disease. The ESSENTIAL AD study assessed burden of atopic dermatitis in patients receiving systemic and/or non-systemic therapies in real-life clinical practices across 15 countries in Eastern Europe, the Middle East, and Africa. The results of the study demonstrated that adult patients with atopic dermatitis continue to have substantial disease burden regardless of treatment with systemic therapy or non-systemic therapy. The findings suggest that optimal management of atopic dermatitis needs to be reassessed in Eastern Europe, the Middle East, and Africa, especially as new, more effective treatment options become available to patients.

Atrial fibrillation in ischemic stroke: predicting response to thrombolysis and clinical outcomes.

BACKGROUND AND PURPOSE: Atrial fibrillation (AF) increases the risk of stroke and is associated with poor stroke outcomes. Limited tools are available to evaluate clinical outcomes and response to thrombolysis in stroke patients with AF. METHODS: We applied the iScore (http://www.sorcan.ca/iscore), a validated risk score, to consecutive patients with an acute ischemic stroke admitted to stroke centers in the Registry of the Canadian Stroke Network. The main outcome considered was a favorable outcome (defined as a modified Rankin scale 0-2) at discharge after thrombolysis. Secondary outcomes included intracerebral hemorrhage, death at 30 days, and at 1 year stratified by terciles of the iScore. RESULTS: Among 12 686 patients with an acute ischemic stroke, 2185 (17.2%) had AF. Overall, AF patients had higher risk of death at 30 days (22.3% versus 10.2%; P<0.0001), 1 year (37.1% versus 19.5%; P<0.0001) and death or disability at discharge (69.7% versus 54.7%; P<0.0001) compared with non-AF patients. After adjustment, thrombolysis was associated with a favorable outcome for patients without AF (relative risk, 1.18; 95% CI, 1.10-1.27), but no benefit was observed for patients with AF (relative risk, 0.91; 95% CI, 0.71-1.17). There was a modestly increased risk of intracranial hemorrhage (any type) (16.5% versus 11.6%; relative risk, 1.42; 95% CI, 1.05-1.91) after thrombolysis among AF compared with non-AF patients. In the logistic regression analysis, there was an interaction between tPA and iScore for a favorable outcome (P-value interaction <0.001). The interaction also was significant (P<0.0012) among patients without AF, but did not reach significance (P=0.17) in patients with AF. CONCLUSIONS: Stroke patients with AF have higher mortality, greater risk of intracerebral hemorrhage, and a similar response trend to thrombolysis compared with non-AF patients.

Risk factors, quality of care and prognosis in South Asian, East Asian and White patients with stroke.

BACKGROUND: Stroke has emerged as a significant and escalating health problem for Asian populations. We compared risk factors, quality of care and risk of death or recurrent stroke in South Asian, East Asian and White patients with acute ischemic and hemorrhagic stroke. METHODS: Retrospective analysis was performed on consecutive patients with ischemic stroke or intracerebral hemorrhage admitted to 12 stroke centers in Ontario, Canada (July 2003-March 2008) and included in the Registry of the Canadian Stroke Network database. The database was linked to population-based administrative databases to determine one-year risk of death or recurrent stroke. RESULTS: The study included 253 South Asian, 513 East Asian and 8231 White patients. East Asian patients were more likely to present with intracerebral hemorrhage (30%) compared to South Asian (17%) or White patients (15%) (p<0.001). Time from stroke to hospital arrival was similarly poor with delays >2 hours for more than two thirds of patients in all ethnic groups. Processes of stroke care, including thrombolysis, diagnostic imaging, antithrombotic medications, and rehabilitation services were similar among ethnic groups. Risk of death or recurrent stroke at one year after ischemic stroke was similar for patients who were White (27.6%), East Asian (24.7%, aHR 0.97, 95% CI 0.78-1.21 vs. White), or South Asian (21.9%, aHR 0.91, 95% CI 0.67-1.24 vs. White). Although risk of death or recurrent stroke at one year after intracerebral hemorrhage was higher in East Asian (35.5%) and White patients (47.9%) compared to South Asian patients (30.2%) (p=0.002), these differences disappeared after adjustment for age, sex, stroke severity and comorbid conditions (aHR 0.89 [0.67-1.19] for East Asian vs White and 0.99 [0.54-1.81] for South Asian vs. White). CONCLUSION: After stratification by stroke type, stroke care and outcomes are similar across ethnic groups in Ontario. Enhanced health promotion is needed to reduce delays to hospital for all ethnic groups.

How does hypoxia inducible factor-1α participate in enhancing the glycolysis activity in cervical cancer?

The objective of this study is to explore the role of hypoxia inducible factor-1 (HIF-1) in glycolysis activity and its relationship with malignant biologic behaviors of cervical cancer. Immunohistochemistry was performed to study the protein expression and distribution of HIF-1α and glucose transport protein 1 (GLUT1) in cervical tissue of 158 cases, including 28 with normal cervical epithelium, 32 with cervical intraepithelial neoplasia, and 98 with invasive cervical cancer. Cobalt(II) chloride was used to induce hypoxia in Hela and Siha cells; the biologic behaviors of cells cultured in normal or hypoxic environments were monitored by colorimetric, Transwell, flow cytometry, and enzyme-linked immunosorbent assay; immunocytochemistry, Western blot, and reverse transcription-polymerase chain reaction were used to observe gene and protein expression of HIF-1α, GLUT1, and hexokinase II in cell lines during normoxia and hypoxia. The expression of HIF-1α and GLUT1 gradually increased from normal cervical tissue to cervical intraepithelial neoplasia, then to cervical cancer. There were significant differences among these groups (P < .05). HIF-1α was strongly associated with pathologic differentiation, clinic stage, magnitude of lesions, and patient age, whereas GLUT1 was associated with lymphatic metastasis (P < .05). HIF-1α was strongly associated with expression of GLUT1 (P < .05). In hypoxia, proliferation, invasion, resistance to apoptosis, and glycolysis of both Hela and Siha were enhanced compared with cells in normoxia (P < .05). Both gene and protein expressions of GLUT1 and hexokinase II were strengthened, whereas only the protein expression of HIF-1α was stronger in hypoxia than that in normoxia (P < .05). The results of Hela in normoxia and in hypoxia were similar to those of Siha (P > .05). HIF-1α plays a key role in cervical cancer both in vivo and in vitro. The role of HIF-1α can be implemented mainly by up-regulating its downstream gene, such as GLUT1, and the main mechanism may enhance glycolytic ability. Strong up-regulation and the role of HIF-1α suggest that HIF-1α could be an important factor in the onset and progression of cervical cancer and could be an attractive therapeutic molecular target for that type of cancer.