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Differential mortality of infectious disease in Italian polities: COVID-19, past plague epidemics, and currently endemic respiratory disease

Infect Genet Evol. 2021 Sep 11:105081. doi: 10.1016/j.meegid.2021.105081. Online ahead of print.

ABSTRACT

Coronavirus disease 2019 (COVID-19) has harshly impacted Italy since its arrival in February 2020. In particular, provinces in Italy’s Central and Northern macroregions have dealt with disproportionately greater case prevalence and mortality rates than those in the South. In this paper, we compare the morbidity and mortality dynamics of 16th and 17th century Plague outbreaks with those of the ongoing COVID-19 pandemic across Italian regions. We also include data on infectious respiratory diseases which are presently endemic to Italy in order to analyze the regional differences between epidemic and endemic disease. A Growth Curve Analysis allowed for the estimation of time-related intercepts and slopes across the 16th and 17th centuries. Those statistical parameters were later incorporated as criterion variables in multiple General Linear Models. These statistical examinations determined that the Northern macroregion had a higher intercept than the Southern macroregion. This indicated that provinces located in Northern Italy had historically experienced higher plague mortalities than Southern polities. The analyses also revealed that this geographical differential in morbidity and mortality persists to this day, as the Northern macroregion has experienced a substantially higher COVID-19 mortality than the Southern macroregion. These results are consistent with previously published analyses. The only other stable and significant predictor of epidemic disease mortality was foreign urban potential, a measure of the degree of interconnectedness between 16th and 17th century Italian cities. Foreign urban potential was negatively associated with plague slope and positively associated with plague intercept, COVID-19 mortality, GDP per capita, and immigration per capita. Its substantial contribution in predicting both past and present outcomes provides a temporal continuity not seen in any other measure tested here. Overall, this study provides compelling evidence that temporally stable geographical factors, impacting both historical and current foreign pathogen spread above and beyond other hypothesized predictors, underlie the disproportionate impact COVID-19 has had throughout Central and Northern Italian provinces.

PMID:34520873 | DOI:10.1016/j.meegid.2021.105081

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Association of RAD51 with Homologous Recombination Deficiency (HRD) and clinical outcomes in untreated triple-negative breast cancer (TNBC): analysis of the GeparSixto randomized clinical trial

Ann Oncol. 2021 Sep 11:S0923-7534(21)04478-1. doi: 10.1016/j.annonc.2021.09.003. Online ahead of print.

ABSTRACT

BACKGROUND: Current genetic and genomic tests measuring homologous recombination deficiency (HRD) show limited predictive value. This study compares the performance of an immunohistology-based RAD51 test with genetic/genomic tests to identify patients with HRD primary triple-negative breast cancer (TNBC) and evaluates its accuracy to select patients sensitive to platinum-based neoadjuvant chemotherapy (NACT).

PATIENTS AND METHODS: This is a retrospective, blinded, biomarker analysis from the GeparSixto randomized clinical trial. TNBC patients received neoadjuvant paclitaxel plus Myocet-nonpegylated liposomal doxorubicin (PM) or PM plus carboplatin (PMCb), both arms including bevacizumab. Formalin-fixed paraffin-embedded (FFPE) tumor samples were laid on tissue microarrays. RAD51, BRCA1 and γH2AX were quantified using an immunofluorescence assay. The predictive value of RAD51 was assessed by regression models. Concordance analyses were performed between RAD51 score and tumor BRCA (tBRCA) status or genomic HRD score (myChoiceHRD). Associations with pathological complete response (pCR) and survival were studied. Functional HRD was pre-defined as a RAD51 score ≤10% (RAD51-low).

RESULTS: Functional HRD by RAD51-low was evidenced in 81/133 tumors (61%). RAD51 identified 93% tBRCA-mutated tumors and 45% non-tBRCA mutant cases as functional HRD. The concordance between RAD51 and genomic HRD was 87% (95%CI 79-93%). In patients with RAD51-high tumors, pCR was similar between treatment arms (PMCb 31% vs PM 39%, odds ratio (OR) 0.71, 0.23-2.24, p=0.56). Patients with RAD51-low tumors benefited from PMCb (pCR 66% vs 33%, OR 3.96, 1.56-10.05, p=0.004; interaction test p=0.02). This benefit maintained statistical significance in the multivariate analysis. Carboplatin addition showed similar disease-free survival in RAD51-high (hazard ratio (HR) 0.40, log-rank p=0.11) and RAD51-low (0.45, p=0.11) groups.

CONCLUSIONS: The RAD51 test identifies tumors with functional HRD and is highly concordant with tBRCA mutation and genomic HRD. RAD51 independently predicts clinical benefit from adding Cb to NACT in TNBC. Our results support further development to incorporate RAD51 testing in clinical decision-making.

PMID:34520831 | DOI:10.1016/j.annonc.2021.09.003

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Missing data was handled inconsistently in UK prediction models: a review of method used

J Clin Epidemiol. 2021 Sep 11:S0895-4356(21)00288-2. doi: 10.1016/j.jclinepi.2021.09.008. Online ahead of print.

ABSTRACT

OBJECTIVE: No clear guidance exists on handling missing data at each stage of developing, validating and implementing a clinical prediction model (CPM). We aimed to review the approaches to handling missing data that underly the CPMs currently recommended for use in UK healthcare.

STUDY DESIGN AND SETTING: A descriptive cross-sectional meta-epidemiological study aiming to identify CPMs recommended by the National Institute for Health and Care Excellence (NICE), which summarized how missing data is handled across their pipelines.

RESULTS: 23 CPMs were included through ‘sampling strategy’. Six missing data strategies were identified: complete case analysis (CCA), multiple imputation, imputation of mean values, k-nearest neighbours imputation, using an additional category for missingness, considering missing values as risk-factor-absent. 52% of the development articles and 48% of the validation articles did not report how missing data were handled. CCA was the most common approach used for development (40%) and validation (44%). At implementation, 57% of the CPMs required complete data entry, whilst 43% allowed missing values. 3 CPMs had consistent paths in their pipelines.

CONCLUSION: A broad variety of methods for handling missing data underly the CPMs currently recommended for use in UK healthcare. Missing data handling strategies were generally inconsistent. Better quality assurance of CPMs needs greater clarity and consistency in handling of missing data.

PMID:34520847 | DOI:10.1016/j.jclinepi.2021.09.008

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Global burden of lung cancer attributable to ambient fine particulate matter pollution in 204 countries and territories, 1990-2019

Environ Res. 2021 Sep 11:112023. doi: 10.1016/j.envres.2021.112023. Online ahead of print.

ABSTRACT

INTRODUCTION: Understanding the latest global spatio-temporal pattern of lung cancer burden attributable to ambient fine particulate matter pollution (PM2.5) is crucial to prioritize global lung cancer prevention, as well as environment improvement.

METHODS: Data on lung cancer attributable to ambient PM2.5 were downloaded from the Global Burden of Disease Study (GBD) 2019. The numbers and age-standardized rates on lung cancer mortality (ASMR) and disability-adjusted life years (ASDR) were estimated by age, sex, region, and country. We used estimated annual percentage change (EAPC) to quantify the temporal trends of ASMR and ASDR from 1990 to 2019.

RESULTS: In 2019, the number of global lung cancer deaths and DALYs attributable to ambient PM2.5 was approximately 0.31 million and 7.02 million respectively, among which more deaths and DALYs occurred in males. At GBD region level, the heaviest burden occurred in East Asia, accounting for over 50% worldwide, with China ranked first worldwide. The number of ambient PM2.5 attributable lung cancer deaths and DALYs has over doubled from 1990 to 2019, but high sociodemographic index (SDI) region had a rapid decrease, with EAPC -2.21 in ASMR (95% CI: -2.32, -2.09). The age-specific mortality rate or DALY rate has increased in all age groups in low to middle SDI regions from 1990 to 2019. The ASMR or ASDR showed an inverted V-shaped association with SDI. The EAPC in ASMR or ASDR was highly negatively correlated with ASMR or ASDR in 1990 and SDI in 2019, with coefficients around 0.70.

CONCLUSIONS: The number of ambient PM2.5-related lung cancer deaths and DALYs has largely increased because of the increase of exposure to PM2.5, population growth, and aging. Local governments should do economic activities under the consideration of public health, especially in high-burden areas.

PMID:34520750 | DOI:10.1016/j.envres.2021.112023

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Endothelin-1 Induced Global Ischemia in adult Zebrafish: A Model With Novel Entity of Stroke Research

J Chem Neuroanat. 2021 Sep 11:102025. doi: 10.1016/j.jchemneu.2021.102025. Online ahead of print.

ABSTRACT

BACKGROUND: Stroke is a leading cause of death in the general population, and it occurs three times more frequently in diabetic patients, necessitating extensive research into new therapeutics. The reproducibility, similarity, and technical limitations of current animal models are limited.

METHODS: We developed a stroke induction model using pink zebra-Danio-rerio. Diabetes was induced in zebrafish by giving them D-glucose (111mM) for 14 days, and those with blood glucose levels higher than 100mg/dl were included in the study. In Zebrafish, an experimental stroke was induced by a single oral administration of Endothelin-1 (ET-1, 3l/gm). Swimming, behavioural patterns, and cognitive performance were all recorded and analysed using UMA Tracker. The brains were removed for histopathological analysis.

RESULTS: In both the normal and diabetic groups, ET-1 administration resulted in a statistically significant change in swimming pattern and movements. Furthermore, changes in swimming pattern and recovery time were statistically significant in the diabetic ET-1 treatment group. In the neurocognitive assessment paradigm, the behavioural study of ET-1 treated groups revealed a disturbed cognitive profile and locomotor coordination, with an increase in the number of errors and a decrease in total distance travelled. Histopathological analysis of ET-1 treated groups revealed cortical lesions, shrunken neuronal cells, and thrombocytes in spheroid form with disturbed normal architecture of brain tissue when compared to normal control groups in tectum opticum and telencephalon. In terms of stability, reproducibility, and genetic similarity to human stroke, the current experimental model outperforms other available rodent stroke models.

CONCLUSION: The ET-1 induced experimental zebrafish stroke model opens up new avenues for diabetes-related stroke research due to its novelty, reproducibility, and ability to overcome technical errors found in other recent models.

PMID:34520802 | DOI:10.1016/j.jchemneu.2021.102025

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Does longer storage of blastocysts with equal grades in a cryopreserved state affect the perinatal outcomes?

Cryobiology. 2021 Sep 11:S0011-2240(21)00149-8. doi: 10.1016/j.cryobiol.2021.09.003. Online ahead of print.

ABSTRACT

AIM: Although mammalian embryos could be preserved in liquid nitrogen for thousands of years in theoretical models, the viability of cryopreserved blastocyst with varying grades remains to be speculated. In this study, we aimed to determine whether the longer storage time of blastocysts with equal grades could negatively affect the perinatal outcomes.

MATERIALS AND METHODS: Single vitrified-warmed blastocyst was divided into four grades (AA, AB/BA, BB, BC/CB) according to the blastocyst score when freezing, and each grade of blastocyst was categorized into four storage duration categories: 28 days-1 year, 1-3 years, 3-5 years, and ≥5 years. Then the perinatal outcomes with different storage time were analyzed.

RESULTS: Our results revealed that for blastocysts with the same grade, the length of storage time had no statistical effect on blastocyst survival rate, clinical pregnancy/implantation rate, live birth rate, and abortion rate. In addition, more advanced developmental blastocyst could obtain better pregnancy outcomes regardless of the cryopreservation length. Similar neonatal outcomes were obtained over time.

CONCLUSIONS: Cryopreservation time could not negatively affect the perinatal outcomes of blastocysts with equal grades. Efficient blastocyst cryopreservation technology by vitrification can help older women obtain high-quality embryos at a young age.

PMID:34520741 | DOI:10.1016/j.cryobiol.2021.09.003

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A meta-analysis of comparisons of various surgical treatments for moyamoya diseases

Brain Behav. 2021 Sep 14:e2356. doi: 10.1002/brb3.2356. Online ahead of print.

ABSTRACT

PURPOSE: Ischemia is one of the most familiar complications in the different procedures for moyamoya disease (MMD), but the optimal surgical approaches for MMD remain unknown. We aimed to evaluate the efficiency of various surgical treatments.

METHODS: A literature search word was performed through four databases such as Cochrane Library, Web of Science, PubMed, and EMBASE for the literature published until May 2021. The I2 statistic was used to assess heterogeneity. A random/fixed-effects model was used to pool.

RESULTS: There are a total of 18 studies including three surgical treatments such as including indirect, direct, and combined bypass in this study. The result revealed that indirect bypass was related to a higher incidence of recurrence stroke compared to the direct and combined bypass treatment (p = .001). Furthermore, the cases undergoing direct bypass were associated with a better angiographic change than the indirect bypass (OR = 3.254, p = .013).

CONCLUSION: This meta-analysis demonstrated a positive effect of using the direct and combined bypass to treat MMD compared to indirect bypass due to their lower rates of recurrence stroke.

PMID:34520635 | DOI:10.1002/brb3.2356

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A Comparison of Community-Acquired and Hospital-Acquired Hypernatraemia in Patients who are Acutely Admitted to Hospital

Ir Med J. 2021 Aug 19;114(7):407.

ABSTRACT

Background Hypernatraemia is associated with a short-term mortality of 20-60%. Age-related physiological changes predispose patients to hypernatraemia. This study reviewed acutely admitted patients comparing those with community-acquired (CAH) and hospital-acquired hypernatraemia (HAH). Methods A retrospective study of 102 consecutive acute medical in-patients with serum [Na]>145 mmol/L was conducted. Baseline characteristics, clinical presentation, laboratory values, monitoring, management and outcomes were compared between CAH and HAH groups. Results Patients were exclusively older (>69 years). Forty patients (39.2%) had CAH and sixty-two (61.8%) had HAH. Those with CAH were more likely to be NH residents, have dementia and reduced mobility. Most HAH patients had mild hypernatraemia initially (75.8%, n=47), and higher rates of acute kidney injury (27% (n=11) vs 8% (n=3)/p=0.02) were observed. Monitoring was inadequate and no patient had a free water deficit documented. Medication review and intravenous fluid prescribing was similar between groups. The median length of stay of discharged HAH patients was longer (22.5 vs 8 days/p=0.005). Mortality rates were similar (47% (n=29) vs 37% (n=15)/p=0.416). Time from admission to death was higher in HAH patients (16 vs 8 days/p=0.008). Conclusions Both CAH and HAH present similarly, however, older patients with cognitive/physical impairments are at an increased risk. Early identification of high-risk patients and adherence to best practice guidelines is required.

PMID:34520642

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Rates of skincare product and cosmetic procedure use in patients with acne vulgaris and the effective factors: A multicenter study with 1,755 patients

J Cosmet Dermatol. 2021 Sep 14. doi: 10.1111/jocd.14439. Online ahead of print.

ABSTRACT

BACKGROUND: Skincare products and cosmetic procedures are used as an adjunct or complementary to conventional drug therapy for acne vulgaris (AV).

OBJECTIVE: To evaluate the use of skincare products and the frequency of cosmetic procedures in AV treatment.

METHODS: A total of 1,755 patients with AV completed the survey prepared by the researchers and the Cardiff Acne Disability Index (CADI) questionnaire. The clinical findings and the Food and Drug Administration (FDA) severity scores were recorded by the dermatologists.

RESULTS: For AV, 66.7% of the patients stated that they used skincare products and 26.7% had undergone cosmetic procedures. The use of skincare products was statistically significantly higher in women (female: 74.5%, male: 57.7%, p < 0.0001); older people (users: 22 ± 7.6years, non-users: 21.2 ± 5.7 years, p < 0.0001); patients with a higher CADI score (users: 7 ± 3.7, non-users: 6.9 ± 4.3, p = 0.010); FDA severity score 2 and 3 (FDA-1: 58.1%; FDA-2: 72.4%, FDA-3: 73%, FDA-4: 67%, p < 0.0001); long-term disease (users: 57 ± 43 months; non-users: 47.7 ± 42.3 months, p < 0.0001); facial involvement (present: 70.2%, absent: 51.4%, p = 0.017); high income levels (users: 73.5%; non-users: 26.5%, p = 0.001); and graduate or post-graduate degrees (undergraduate≤%62.8, graduate≥%76.8, p < 0.0001). The rate of cosmetic procedures was higher in those with higher CADI scores (users: 7.8 ± 3.8; non-users: 7.1 ± 3.96, p < 0.0001); older patients (users: 22.7 ± 10.7 years; non-users: 21.3 ± 5 years, p < 0.0001); high school (25.6%); and graduate (28.9%) education (p = 0.043), those with lower disease severity (FDA-1: 31.1%; FDA-2: 28.5%, FDA-3: 27.1%, FDA-4: 20.4%, p = 0.022); smokers (smokers: 32.5%; non-smokers: 25.5%, p = 0.020), and those with AV in the family (present: 29.8%; absent: 24.2%, p = 0.009). The patients most frequently used cleansers (85.2%) as cosmetic products, and most commonly underwent skincare treatment (71%) as an interventional procedure. They mostly learned about such products and methods from the Internet, and 33.3% of the participants had undergone procedures performed by non-physicians.

CONCLUSION: The patients generally choose skincare products as a result of their Internet search and sometimes have these procedures performed by non-physicians. Dermatologists should be aware of this situation and inform their patients about appropriate products and procedures.

PMID:34520610 | DOI:10.1111/jocd.14439

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Application of neurally adjusted ventilatory assist in ventilator weaning of infants ventilator weaning

Brain Behav. 2021 Sep 14:e2350. doi: 10.1002/brb3.2350. Online ahead of print.

ABSTRACT

BACKGROUND: To analyze the application of neurally adjusted ventilatory assist in ventilator weaning of infants.

METHODS: A total of 25 infants (15 boys and 10 girls) who were mechanically ventilated by PICU in Hubei Maternal and Child Health Hospital were selected as the study subjects. After the improvement of the basic disease, regular spontaneous breathing, and the withdrawal of the ventilator, all the children obtained the electrical activity of the diaphragm (EAdi) signal. Then, each child was given CPAP and NAVA mode mechanical ventilation 1 h before the withdrawal of the ventilator. Each detection index was recorded 30 min after each mode of ventilation.

RESULTS: Two of the 25 children were tracheotomized because of respiratory muscle weakness and could not be converted to NAVA mode without the EAdi signal. Hemodynamic indexes were not statistically different between the two groups of CPAP and NAVA. PaCO2 is not significantly different in the two modes, and both were at normal levels. The PIP in NAVA mode is lower than that in CPAP mode (p < .05), and its EAdi signal was correspondingly low. There were significant differences in the peak pressure (Ppeak), mean pressure (Pmean), and compliance and mean arterial pressure (p < .01) between the CPAP and NAVA model ventilation in 23 patients.

CONCLUSION: NAVA can significantly improve the coordination of patients. The therapeutic effect of NAVA was better, which was beneficial to the prognosis of patients and had positive application value in the withdrawal of ventilators in patients.

PMID:34520632 | DOI:10.1002/brb3.2350