Tag: statistics

Stroke Vasc Neurol. 2021 Jun 8:svn-2020-000852. doi: 10.1136/svn-2020-000852. Online ahead of print.

ABSTRACT

BACKGROUND: For patients with stroke with large-vessel occlusion (LVO), study of factors predicting response to intravenous thrombolysis (IVT) would allow identifying subgroups with high expected gain, and those for whom it could be considered as futile, and even detrimental. From patients included in the Mechanical Thrombectomy After Intravenous Alteplase vs Alteplase Alone After Stroke trial, we investigated clinical-imaging factors associated with optimal response to IVT.

METHODS: We included patients receiving IVT alone. Excellent outcome was defined by a 3-month modified Rankin Scale (mRS) score ≤1. Clinical-imaging predictors were assessed on multivariate analysis after multiple imputations. The predictive performance of the model was assessed with the C-statistic.

RESULTS: Among 247 patients with LVO treated with IVT alone, 77 (31%) showed 3-month mRS ≤1. Predictors of 3-month mRS ≤1 were no medical history of hypertension (OR 2.43; 95% CI 1.74 to 3.38; p=0.007); no current smoking (OR 2.76; 95% CI 1.79 to 4.26; p=0.02); onset-to-IVT time (OR 0.47 per hour increase; 95% CI 0.23 to 0.78; p=0.003); diffusion-weighted imaging (DWI) volume (OR 0.78 per 10 mL increase; 95% CI 0.68 to 0.89; p=0.0004); presence of susceptibility vessel sign (SVS) (OR 7.89; 95% CI 1.65 to 37.78; p=0.01) and SVS length (OR 0.87 per mm increase; 95% CI 0.80 to 0.94; p=0.001). The prediction models showed a C-statistic=0.79 (95% CI 0.79 to 0.80).

CONCLUSIONS: In patients with stroke with anterior-circulation LVO treated with IVT alone, predictors of excellent outcome at 3 months were no medical history of hypertension or current smoking, reduced onset-to-IVT time, small DWI volume, presence of SVS and short SVS length. These predictive factors could help practitioners in decision-making for IVT implementation in reperfusion strategies, all the more for the drip and ship paradigm.

TRIAL REGISTRATION NUMBER: NCT01062698.

PMID:34103393 | DOI:10.1136/svn-2020-000852

Hosp Pediatr. 2021 Jun 8:hpeds.2020-005298. doi: 10.1542/hpeds.2020-005298. Online ahead of print.

ABSTRACT

OBJECTIVES: Patients with autoimmune encephalitis (AE) often present with symptoms that are broadly characterized as psychiatric or behavioral, yet little attention is given to the precise symptomatology observed. We sought to more fully define the psychiatric symptoms observed in patients with anti-N-methyl-D-aspartate receptor (NMDAR), anti-glutamic-acid-decarboxylase 65 (GAD65), and anti-voltage-gated-potassium-channel complex (VGKC) antibody-mediated AE using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition nomenclature.

METHODS: We present a case series (n = 25) using a retrospective chart review of 225 patients evaluated for AE in a tertiary care academic medical center between 2014 and 2018. The included patients were ≤18 years old with anti-NMDAR AE (n = 13), anti-GAD65 AE (n = 7), or anti-VGKC AE (n = 5). The frequency of neuropsychiatric symptoms present at the onset of illness and time to diagnosis were compared across groups.

RESULTS: Psychiatric symptoms were seen in 92% of patients in our cohort. Depressive features (72%), personality change (64%), psychosis (48%), and catatonia (32%) were the most common psychiatric symptoms exhibited. On average, patients experienced impairment in ≥4 of 7 symptom domains. No patients had isolated psychiatric symptoms. The average times to diagnosis were 1.7, 15.5, and 12.4 months for anti-NMDAR AE, anti-GAD65 AE, and anti-VGKC AE, respectively (P < .001).

CONCLUSIONS: The psychiatric phenotype of AE in children is highly heterogenous. Involving psychiatry consultation services can be helpful in differentiating features of psychosis and catatonia, which may otherwise be misidentified. Patients presenting with psychiatric symptoms along with impairments in other domains should prompt a workup for AE, including testing for all known antineuronal antibodies.

PMID:34103402 | DOI:10.1542/hpeds.2020-005298

BMJ Glob Health. 2021 Jun;6(6):e004885. doi: 10.1136/bmjgh-2020-004885.

ABSTRACT

INTRODUCTION: COVID-19 has shown an exceptionally high spread rate across and within countries worldwide. Understanding the dynamics of such an infectious disease transmission is critical for devising strategies to control its spread. In particular, Rwanda was one of the African countries that started COVID-19 preparedness early in January 2020, and a total lockdown was imposed when the country had only 18 COVID-19 confirmed cases known. Using intensive contact tracing, several infections were identified, with the majority of them being returning travellers and their close contacts. We used the contact tracing data in Rwanda for understanding the geographic patterns of COVID-19 to inform targeted interventions.

METHODS: We estimated the attack rates and identified risk factors associated to COVID-19 spread. We used Bayesian disease mapping models to assess the spatial pattern of COVID-19 and to identify areas characterised by unusually high or low relative risk. In addition, we used multiple variable conditional logistic regression to assess the impact of the risk factors.

RESULTS: The results showed that COVID-19 cases in Rwanda are localised mainly in the central regions and in the southwest of Rwanda and that some clusters occurred in the northeast of Rwanda. Relationship to the index case, being male and coworkers are the important risk factors for COVID-19 transmission in Rwanda.

CONCLUSION: The analysis of contact tracing data using spatial modelling allowed us to identify high-risk areas at subnational level in Rwanda. Estimating risk factors for infection with SARS-CoV-2 is vital in identifying the clusters in low spread of SARS-CoV-2 subnational level. It is imperative to understand the interactions between the index case and contacts to identify superspreaders, risk factors and high-risk places. The findings recommend that self-isolation at home in Rwanda should be reviewed to limit secondary cases from the same households and spatiotemporal analysis should be introduced in routine monitoring of COVID-19 in Rwanda for policy making decision on real time.

PMID:34103325 | DOI:10.1136/bmjgh-2020-004885

Science. 2021 Jun 8:eabe4832. doi: 10.1126/science.abe4832. Online ahead of print.

ABSTRACT

The COVID-19 pandemic has revealed the pronounced vulnerability of the elderly and chronically-ill to SARS-CoV-2-induced morbidity and mortality. Cellular senescence contributes to inflammation, multiple chronic diseases, and age-related dysfunction, but effects on responses to viral infection are unclear. Here, we demonstrate that senescent cells (SnC) become hyper-inflammatory in response to pathogen-associated molecular patterns (PAMPs), including SARS-CoV-2 Spike protein-1, increasing expression of viral entry proteins and reducing anti-viral gene expression in non-SnCs through a paracrine mechanism. Old mice acutely infected with pathogens that included a SARS-CoV-2-related mouse β-coronavirus experienced increased senescence and inflammation with nearly 100% mortality. Targeting SnCs using senolytic drugs before or after pathogen exposure significantly reduced mortality, cellular senescence, and inflammatory markers and increased anti-viral antibodies. Thus, reducing the SnC burden in diseased or aged individuals should enhance resilience and reduce mortality following viral infection, including SARS-CoV-2.

PMID:34103349 | DOI:10.1126/science.abe4832

J Immunother Cancer. 2021 Jun;9(6):e002718. doi: 10.1136/jitc-2021-002718.

ABSTRACT

BACKGROUND: Previous studies have suggested that inflammatory markers (neutrophil-to-lymphocyte ratio (NLR), lactate dehydrogenase (LDH) and fibrinogen) are prognostic biomarkers in patients with a variety of solid cancers, including those treated with immune checkpoint inhibitors (ICIs). We aimed to develop a model that predicts response and survival in patients with relapsed and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) treated with immunotherapy.

METHODS: Analysis of 100 consecutive patients with unresectable R/M HNSCC who were treated with ICI. Baseline and on-treatment (day 28) NLR, fibrinogen and LDH were calculated and correlated with response, progression-free survival (PFS) and overall survival (OS) using univariate and multivariate analyses. The optimal cut-off values were derived using maximally selected log-rank statistics.

RESULTS: Low baseline NLR and fibrinogen levels were associated with response. There was a statistically significant correlation between on-treatment NLR and fibrinogen and best overall response. On-treatment high NLR and raised fibrinogen were significantly associated with poorer outcome. In multivariate analysis, on-treatment NLR (≥4) and on-treatment fibrinogen (≥4 ng/mL) showed a significant negative correlation with OS and PFS. Using these cut-off points, we generated an on-treatment score for OS and PFS (0-2 points). The derived scoring system shows appropriate discrimination and suitability for OS (HR 2.4, 95% CI 1.7 to 3.4, p<0.0001, Harrell’s C 0.67) and PFS (HR 1.8, 95% CI 1.4 to 2.3, p<0.0001, Harrell’s C 0.68). In the absence of an external validation cohort, results of fivefold cross-validation of the score and evaluation of median OS and PFS on the Kaplan-Meier survival distribution between trained and test data exhibited appropriate accuracy and concordance of the model.

CONCLUSIONS: NLR and fibrinogen levels are simple, inexpensive and readily available biomarkers that could be incorporated into an on-treatment scoring system and used to help predict survival and response to ICI in patients with R/M HNSCC.

PMID:34103355 | DOI:10.1136/jitc-2021-002718

BMJ Open. 2021 Jun 8;11(6):e044353. doi: 10.1136/bmjopen-2020-044353.

ABSTRACT

PURPOSE: The depth and breadth of clinical data within electronic health record (EHR) systems paired with innovative machine learning methods can be leveraged to identify novel risk factors for complex diseases. However, analysing the EHR is challenging due to complexity and quality of the data. Therefore, we developed large electronic population-based cohorts with comprehensive harmonised and processed EHR data.

PARTICIPANTS: All individuals 30 years of age or older who resided in Olmsted County, Minnesota on 1 January 2006 were identified for the discovery cohort. Algorithms to define a variety of patient characteristics were developed and validated, thus building a comprehensive risk profile for each patient. Patients are followed for incident diseases and ageing-related outcomes. Using the same methods, an independent validation cohort was assembled by identifying all individuals 30 years of age or older who resided in the largely rural 26-county area of southern Minnesota and western Wisconsin on 1 January 2013.

FINDINGS TO DATE: For the discovery cohort, 76 255 individuals (median age 49; 53% women) were identified from which a total of 9 644 221 laboratory results; 9 513 840 diagnosis codes; 10 924 291 procedure codes; 1 277 231 outpatient drug prescriptions; 966 136 heart rate measurements and 1 159 836 blood pressure (BP) measurements were retrieved during the baseline time period. The most prevalent conditions in this cohort were hyperlipidaemia, hypertension and arthritis. For the validation cohort, 333 460 individuals (median age 54; 52% women) were identified and to date, a total of 19 926 750 diagnosis codes, 10 527 444 heart rate measurements and 7 356 344 BP measurements were retrieved during baseline.

FUTURE PLANS: Using advanced machine learning approaches, these electronic cohorts will be used to identify novel sex-specific risk factors for complex diseases. These approaches will allow us to address several challenges with the use of EHR.

PMID:34103314 | DOI:10.1136/bmjopen-2020-044353

BMJ Open. 2021 Jun 8;11(6):e045667. doi: 10.1136/bmjopen-2020-045667.

ABSTRACT

INTRODUCTION: As many as 74% of veterans with alcohol use disorders (AUDS) report symptoms of insomnia. Insomnia represents a barrier to alcohol treatment because insomnia symptoms (1) may lead to relapse among those who use alcohol to help them sleep and may negatively impact (2) executive functions and (3) emotion regulation skills. Cognitive-behavioural therapy for insomnia (CBT-I) is an efficacious first-line treatment for insomnia; however, no research has examined the impact of CBT-I on individuals’ response to alcohol treatment. In the Sleep and Alcohol for Veterans (Project SAVE) randomised controlled trial, we hypothesise that CBT-I will enhance the efficacy of alcohol treatment among Veterans with insomnia by enhancing their abilities to attend to treatment, regulate emotions and initiate sleep without alcohol.

METHODS AND ANALYSIS: Eighty Veterans enrolled in alcohol treatment at the Veterans Administration (VA) hospital will be randomly assigned to receive either CBT-I or single-session sleep hygiene (SH) education. Individuals will be eligible to participate if they meet Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for moderate to severe AUD and Insomnia Disorder of at least 1-month duration. Participants will complete assessments at baseline, post-treatment and 6-week follow-up. Preliminary process outcomes include retention/recruitment rates and treatment satisfaction (feasibility and acceptability, respectively). Primary outcomes are insomnia severity, percentage of heavy-drinking days and alcohol-related problems. We will assess a variety of secondary clinical and mechanistic outcomes (eg, post-traumatic stress disorder (PTSD) symptoms, attention and working memory).

ETHICS AND DISSEMINATION: Ethics approval was obtained in October 2018. Data collection began in July 2019 and is planned for completion by July 2021. Trial results will be disseminated at local and national conferences, in peer-reviewed publications and through media outlets, as available. Results will also be shared with interested participants and clinical collaborators at the end of the trial.

TRIAL REGISTRATION NUMBER: clinicaltrials.gov identifier NCT03806491 (pre-results).

PMID:34103317 | DOI:10.1136/bmjopen-2020-045667

Zhonghua Wai Ke Za Zhi. 2021 Jun 1;59(6):513-519. doi: 10.3760/cma.j.cn112139-20200820-00656.

ABSTRACT

Objective: To evaluate the safety and effectiveness of a new Chinese-made surgical biopatch for atrial septum under the establishment of atrial septal defect animal model in miniature pigs. Methods: From June 2018 to April 2019, 26 pigs were divided into experimental group (15 pigs) and the control group (11 pigs). Animal models of atrial septal defect were established by traditional surgical methods. The to-be-evaluated and listed surgical biological patches (with a diameter of 10 mm) were implanted in the experimental group and the control group to repair the atrial septal defect. Cardiac ultrasound and blood examination of all animals were performed before and at 7, 30, 90, 180 days after operation, the results were analyzed with repetitive measurement and analysis of variance. At 90 days and 180 days after the operation, tissue samples were taken from animals after euthanasia. Pathological examination of heart and major organs were conducted. The independent sample t test and rank sum test were used to compare the data between the two groups, and the nonparametric was used to compare the patch calcification score between the two groups. Results: In total of 26 animals, 14 animals in the experimental group(6 at 90 days, 8 at 180 days) and 9 animals in the control group(4 at 90 days, 5 at 180 days) reached the end of the experiment. The other 3 animals (1 in the experimental group and 2 in the control group) died of arrhythmia, whole heart failure and right heart failure, the results of pathological examination showed that the causes of death were unrelated to the experimental materials. Cardiac ultrasound showed no patch leakage in all animals. There was no statistically significant difference in cardiac ultrasound and blood examination between the two groups at different time points after operation (all P>0.05). The pathological results showed that all the implants were intact and had good biocompatibility. There was no significant difference in the mean endothelialization rate between the experimental group and the control group at 90 and 180 days after operation ((80.8±29.1)% vs. (82.5±23.6)%, t=0.095, P=0.927; (78.8±36.4)% vs. (82.0±19.2)%, t=0.182, P=0.859) on 90 and 180 days, there was no significant difference in the patch calcification score between the two groups (1.00(1.25) vs. 2.00(0.75), Z=6.500, P=0.214; 0(0.75) vs. 1.00(2.00), Z=12.000, P=0.139). Conclusion: The new Chinese-made surgical biopatch for atrial septum has comparable safety and efficacy to that of the marketable patch in miniature pig atrial septal defect animal model.

PMID:34102737 | DOI:10.3760/cma.j.cn112139-20200820-00656

Zhonghua Wai Ke Za Zhi. 2021 Jun 1;59(6):525-529. doi: 10.3760/cma.j.cn112139-20201102-00778.

ABSTRACT

Objective: To examine the outcome of endovascular treatment in patients of isolated abdominal aortic dissection. Methods: From February 2012 to June 2020, 61 patients (44 males, 17 females) with an age of (60.2±11.4) years (range: 43 to 87 years) of isolated abdominal aortic dissection who underwent the endovascular treatment, including bifurcated and straight aortic stent graft, in the Department of Vascular Surgery, the Second Xiangya Hospital, Central South University were enrolled. There were 47 patients treated with bifurcated aortic stent grafts and 14 patients with straight aortic stent grafts. Patient demographic, preoperative, intraoperative, perioperative data were collected. Clinical follow-up data, including mortality, relative complications and aortic remodeling, were obtained. Kaplan-Meier method and Log-rank test was used to calculate and compare the rates of survival and freedom from all adverse events. Results: The operative time was (142.4±47.9) minutes (range:70 to 310 minutes) and (95.7±23.7) minutes (range: 70 to 150 minutes) in bifurcated stent group and straight stent group, respectively. The perioperative mortality was 0. One patient had partial occlusion of the left renal artery, and 3 patients had type Ⅰa endoleak post-operation. The follow-up period was (37.1±22.1) months (range: 3 to 91 months). Three patents suffered from type B aortic dissection; one of them progressed into type A aortic dissection and died, another one was treated with secondary endovascular operation, and the remaining one was treated conservatively. One patient had type A aortic dissection and was treated conservatively for 57 months without any discomfort. Stent grafts in iliac artery occlusion happened in 2 patients treated with a bifurcated graft, one of them was treated with a secondary operation because of severe symptom. Aortic remodeling was well with the treatment of bifurcated and straight grafts. There was no difference in the cumulative survival (P=0.584) and freedom from all adverse events (P=0.309) between the two different endovascular treatment strategies. Conclusion: Endovascular aortic repair is an effective and safe treatment strategy for isolated abdominal aortic dissection with reliable mid-term result and excellent aortic remodeling.

PMID:34102739 | DOI:10.3760/cma.j.cn112139-20201102-00778

Zhonghua Wai Ke Za Zhi. 2021 Jun 1;59(6):484-490. doi: 10.3760/cma.j.cn112139-20201224-00883.

ABSTRACT

Objective: To analyze the pathogen distribution and drug resistance in acute,delayed and chronic periprosthetic joint infection (PJI). Methods: The clinical data of 316 patients with periprosthetic infection after primary hip and knee arthroplasty admitted to the Department of Arthroplasty,the First Affiliated Hospital,Xinjiang Medical University from August 2010 to August 2020 were retrospectively analyzed.There were 146 males and 170 females,aged (62.3±14.2) years (range:22 to 89 years).One hundred and sixty one patients underwent total hip arthroplasty and 155 patients underwent total knee arthroplasty.According to the time of postoperative infection,the patients were divided into acute PJI group (65 cases),delayed PJI group (83 cases) and chronic PJI group (168 cases).The results of pathogen species,composition ratio and drug susceptibility tests were collected,and the independent sample t test,Chi-square test or Fisher’s exact probability test were used for comparison. Results: Gram-positive bacteria were the main pathogens of PJI (49.7%,157/316),and the positive rates of culture in patients with acute PJI,delayed PJI and chronic PJI were 33.8% (22/65),55.4% (46/83) and 53.0% (89/168),and the difference was statistically significant(χ²=8.343,P=0.015).The common bacteria were coagulase-negative Staphylococcus (54.8%,86/157) and Staphylococcus aureus (30.6%,48/157),The drug-sensitivity to linezolid,vancomycin and tigacycline was 100%.The gram-negative bacteria were mainly Escherichia coli and Enterobacter cloacae,and the drug resistance rate to carbapenems was low,ranging from 0 to 9.09%.The drug resistance rates of acute PJI patients to rifampicin,ciprofloxacin and erythromycin were significantly higher than those of late onset and chronic PJI patients,the difference was statistically significant(rifampicin:χ²=14.332,P=0.001;ciprofloxacin:χ²=12.086,P=0.002;erythromycin:χ²=9.096,P=0.010);The drug resistance rate of acute PJI patients to levofloxacin,clindamycin and tetracycline was higher than that of chronic PJI patients,and the difference was statistically significant(levofloxacin:χ²=10.500,P=0.002; clindamycin: χ²=7.103,P=0.007; tetracycline: χ²=6.909,P =0.012).The resistance rate of ampicillin/sulbactam in acute PJI (60.0%) was significantly higher than that in chronic PJI (16.7%),and the difference was statistically significant(χ²= 5.853,P=0.040). Conclusion: Gram-positive bacteria are the main pathogens of PJI,and the resistance rate of pathogens of acute PJI is higher than that of late onset and chronic PJI.

PMID:34102732 | DOI:10.3760/cma.j.cn112139-20201224-00883