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  • 3651.
    Zelic, Renata
    et al.
    Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Giunchi, Francesca
    Pathology Department, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
    Fridfeldt, Jonna
    Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Carlsson, Jessica
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Urology.
    Davidsson, Sabina
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Urology.
    Lianas, Luca
    Data-Intensive Computing Division, Center for Advanced Studies, Research and Development in Sardinia (CRS4), Pula, Italy.
    Mascia, Cecilia
    Data-Intensive Computing Division, Center for Advanced Studies, Research and Development in Sardinia (CRS4), Pula, Italy.
    Zugna, Daniela
    Cancer Epidemiology Unit, Department of Medical Sciences, University of Turin, and CPO-Piemonte, Turin, Italy.
    Molinaro, Luca
    Division of Pathology, A.O. Città della Salute e della Scienza Hospital, Turin, Italy.
    Vincent, Per Henrik
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Urology, Karolinska University Hospital, Stockholm, Sweden.
    Zanetti, Gianluigi
    Data-Intensive Computing Division, Center for Advanced Studies, Research and Development in Sardinia (CRS4), Pula, Italy.
    Andrén, Ove
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Urology.
    Richiardi, Lorenzo
    Cancer Epidemiology Unit, Department of Medical Sciences, University of Turin, and CPO-Piemonte, Turin, Italy.
    Akre, Olof
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Urology, Karolinska University Hospital, Stockholm, Sweden.
    Fiorentino, Michelangelo
    Pathology Service, Maggiore Hospital, University of Bologna, Bologna, Italy.
    Pettersson, Andreas
    Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Prognostic Utility of the Gleason Grading System Revisions and Histopathological Factors Beyond Gleason Grade.2022Ingår i: Clinical Epidemiology, ISSN 1179-1349, E-ISSN 1179-1349, Vol. 14, s. 59-70Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The International Society of Urological Pathology (ISUP) revised the Gleason system in 2005 and 2014. The impact of these changes on prostate cancer (PCa) prognostication remains unclear.

    Objective: To evaluate if the ISUP 2014 Gleason score (GS) predicts PCa death better than the pre-2005 GS, and if additional histopathological information can further improve PCa death prediction.

    Patients and Methods: We conducted a case-control study nested among men in the National Prostate Cancer Register of Sweden diagnosed with non-metastatic PCa 1998-2015. We included 369 men who died from PCa (cases) and 369 men who did not (controls). Two uro-pathologists centrally re-reviewed biopsy ISUP 2014 Gleason grading, poorly formed glands, cribriform pattern, comedonecrosis, perineural invasion, intraductal, ductal and mucinous carcinoma, percentage Gleason 4, inflammation, high-grade prostatic intraepithelial neoplasia (HGPIN) and post-atrophic hyperplasia. Pre-2005 GS was back-transformed using i) information on cribriform pattern and/or poorly formed glands and ii) the diagnostic GS from the registry. Models were developed using Firth logistic regression and compared in terms of discrimination (AUC).

    Results: The ISUP 2014 GS (AUC = 0.808) performed better than the pre-2005 GS when back-transformed using only cribriform pattern (AUC = 0.785) or both cribriform and poorly formed glands (AUC = 0.792), but not when back-transformed using only poorly formed glands (AUC = 0.800). Similarly, the ISUP 2014 GS performed better than the diagnostic GS (AUC = 0.808 vs 0.781). Comedonecrosis (AUC = 0.811), HGPIN (AUC = 0.810) and number of cores with ≥50% cancer (AUC = 0.810) predicted PCa death independently of the ISUP 2014 GS.

    Conclusion: The Gleason Grading revisions have improved PCa death prediction, likely due to classifying cribriform patterns, rather than poorly formed glands, as Gleason 4. Comedonecrosis, HGPIN and number of cores with ≥50% cancer further improve PCa death discrimination slightly.

  • 3652.
    Zelic, Renata
    et al.
    Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Giunchi, Francesca
    Department of Pathology, S-Orsola-Malpighi Hospital, Bologna, Italy.
    Lianas, Luca
    Data-Intensive Computing Division, Center for Advanced Studies, Research and Development in Sardinia (CRS4), Pula, Italy.
    Mascia, Cecilia
    Data-Intensive Computing Division, Center for Advanced Studies, Research and Development in Sardinia (CRS4), Pula, Italy.
    Zanetti, Gianluigi
    Data-Intensive Computing Division, Center for Advanced Studies, Research and Development in Sardinia (CRS4), Pula, Italy.
    Andrén, Ove
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Urology.
    Fridfeldt, Jonna
    Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Carlsson, Jessica
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Urology.
    Davidsson, Sabina
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Urology.
    Molinaro, Luca
    Division of Pathology, A.O. Città Della Salute e Della Scienza Hospital, Turin, Italy.
    Vincent, Per Henrik
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Urology, Karolinska University Hospital, Stockholm, Sweden.
    Richiardi, Lorenzo
    Cancer Epidemiology Unit, Department of Medical Sciences, University of Turin, and CPO-Piemonte, Turin, Italy.
    Akre, Olof
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. 7 Department of Urology, Karolinska University Hospital, Stockholm, Sweden.
    Fiorentino, Michelangelo
    Department of Pathology, Maggiore Hospital, University of Bologna, Bologna, Italy.
    Pettersson, Andreas
    Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Interchangeability of light and virtual microscopy for histopathological evaluation of prostate cancer2021Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 11, nr 1, artikel-id 3257Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Virtual microscopy (VM) holds promise to reduce subjectivity as well as intra- and inter-observer variability for the histopathological evaluation of prostate cancer. We evaluated (i) the repeatability (intra-observer agreement) and reproducibility (inter-observer agreement) of the 2014 Gleason grading system and other selected features using standard light microscopy (LM) and an internally developed VM system, and (ii) the interchangeability of LM and VM. Two uro-pathologists reviewed 413 cores from 60 Swedish men diagnosed with non-metastatic prostate cancer 1998-2014. Reviewer 1 performed two reviews using both LM and VM. Reviewer 2 performed one review using both methods. The intra- and inter-observer agreement within and between LM and VM were assessed using Cohen's kappa and Bland and Altman's limits of agreement. We found good repeatability and reproducibility for both LM and VM, as well as interchangeability between LM and VM, for primary and secondary Gleason pattern, Gleason Grade Groups, poorly formed glands, cribriform pattern and comedonecrosis but not for the percentage of Gleason pattern 4. Our findings confirm the non-inferiority of VM compared to LM. The repeatability and reproducibility of percentage of Gleason pattern 4 was poor regardless of method used warranting further investigation and improvement before it is used in clinical practice.

  • 3653.
    Zelic, Renata
    et al.
    Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Zugna, Daniela
    Cancer Epidemiology Unit, Department of Medical Sciences, University of Turin, Turin, Italy ; Centro di Riferimento per l ’ Epidemiologia e la Prevenzione Oncologica (CPO) in Piemonte, Turin, Italy .
    Bottai, Matteo
    Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden .
    Andrén, Ove
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Urology.
    Fridfeldt, Jonna
    Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden .
    Carlsson, Jessica
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Urology.
    Davidsson, Sabina
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Urology.
    Fiano, Valentina
    Cancer Epidemiology Unit, Department of Medical Sciences, University of Turin, Turin, Italy; Centro di Riferimento per l ’ Epidemiologia e la Prevenzione Oncologica (CPO) in Piemonte, Turin, Italy .
    Fiorentino, Michelangelo
    Pathology Service, Addarii Institute of Oncology, Sant’ Orsola-Malpighi Hospital, Bologna, Italy.
    Giunchi, Francesca
    Pathology Service, Addarii Institute of Oncology, Sant’ Orsola-Malpighi Hospital, Bologna, Italy.
    Grasso, Chiara
    Cancer Epidemiology Unit, Department of Medical Sciences, University of Turin, Turin, Italy; Centro di Riferimento per l ’ Epidemiologia e la Prevenzione Oncologica (CPO) in Piemonte, Turin, Italy .
    Lianas, Luca
    Data-Intensive Com puting Division, Center for Advanced Studies, Research and Development in Sardinia, Pula, Italy.
    Mascia, Cecilia
    Data-Intensive Com puting Division, Center for Advanced Studies, Research and Development in Sardinia, Pula, Italy.
    Molinaro, Luca
    Division of Pathology, Azienda Os pedaliero-Universitaria Città della Salute e della Scienza Hospital, Turin, Italy .
    Zanetti, Gianluigi
    Data-Intensive Com puting Division, Center for Advanced Studies, Research and Development in Sardinia, Pula, Italy.
    Richiardi, Lorenzo
    Cancer Epidemiology Unit, Department of Medical Sciences, University of Turin, Turin, Italy; Centro di Riferimento per l ’ Epidemiologia e la Prevenzione Oncologica (CPO) in Piemonte, Turin, Italy .
    Pettersson, Andreas
    Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Akre, Olof
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Urology, Karolinska University Hospital, Stockholm, Sweden.
    Estimation of Relative and Absolute Risks in a Competing-Risks Setting Using a Nested Case-Control Study Design: Example From the ProMort Study2019Ingår i: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 188, nr 6, s. 1165-1173Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In this paper, we describe the Prognostic Factors for Mortality in Prostate Cancer (ProMort) study and use it to demonstrate how the weighted likelihood method can be used in nested case-control studies to estimate both relative and absolute risks in the competing-risks setting. ProMort is a case-control study nested within the National Prostate Cancer Register (NPCR) of Sweden, comprising 1,710 men diagnosed with low- or intermediate-risk prostate cancer between 1998 and 2011 who died from prostate cancer (cases) and 1,710 matched controls. Cause-specific hazard ratios and cumulative incidence functions (CIFs) for prostate cancer death were estimated in ProMort using weighted flexible parametric models and compared with the corresponding estimates from the NPCR cohort. We further drew 1,500 random nested case-control subsamples of the NPCR cohort and quantified the bias in the hazard ratio and CIF estimates. Finally, we compared the ProMort estimates with those obtained by augmenting competing-risks cases and by augmenting both competing-risks cases and controls. The hazard ratios for prostate cancer death estimated in ProMort were comparable to those in the NPCR. The hazard ratios for dying from other causes were biased, which introduced bias in the CIFs estimated in the competing-risks setting. When augmenting both competing-risks cases and controls, the bias was reduced.

  • 3654. Zerdes, Ioannis
    et al.
    Matikas, Alexios
    Lövrot, John
    Sifakis, Emmanouil G.
    Richard, Francois
    Sotiriou, Christos
    Rassidakis, George Z.
    Bergh, Jonas C. S.
    Valachis, Antonis
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län.
    Foukakis, Theodoros
    PD-1 protein and gene expression in early breast cancer: Prognostic implications2020Ingår i: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 38, nr 15 Suppl.Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: We have previously shown the prognostic value of PD-L1 protein and gene expression in early breast cancer (BC), however, the prognostic role of PD-1 expression remains unclear.

    Methods: The prognostic value of PD-1 in early BC was investigated using three different approaches: i) evaluation of PD-1 at the protein (IHC, immunohistochemistry in tissue microarrays) and mRNA levels in a retrospective patient cohort of 586 patients treated for early BC in Stockholm, Sweden between 1997-2005, ii) systematic review and trial-level meta-analysis of studies published in Medline, Embase, Cochrane Library and Web of Science Core Collection libraries on the prognostic value of PD-1 IHC expression, and iii) pooled analysis of transcriptomic data from 39 publicly available datasets for the prognostic capacity of PD-1 gene expression. Univariate and multivariable Cox regression models were used.

    Results: In the retrospective study cohort, PD-1 protein was significantly associated with biologically high-risk characteristics. PD-1 protein, but not gene expression, was correlated with improved overall survival (OS) (adjusted HR = 0.73, 95% CI 0.55 – 0.96, p = 0.023 and adjusted HR = 0.88, 95% CI 0.68 – 1.13, p = 0.307, respectively). In the trial-level meta-analysis, 4736 entries were initially identified and 15 studies, including our original cohort, fulfilled the predefined eligibility criteria. PD-1 IHC expression was not prognostic in unselected patients. However, a significant correlation to improved disease-free survival was seen within the triple-negative subtype (pooled multivariate HR = 0.57, 95% CI 0.29 – 0.90, p = 0.02). In the pooled gene expression analysis, PD-1 gene expression was associated with improved OS in the entire population (adjusted HR = 0.89, 95% CI 0.80 – 0.99, p = 0.025) and in basal-like (adjusted HR = 0.77, 95% CI 0.63 – 0.95, p = 0.014) tumors.

    Conclusions: PD-1 expression at the RNA and protein levels represent promising prognostic factors, especially in the triple-negative and basal-like subtypes. Standardization and further validation are needed prior to clinical implementation.

  • 3655. Zerdes, Ioannis
    et al.
    Zhu, Yajing
    Tzoras, Evangelos
    Matikas, Alexios
    Bergh, Jonas C. S.
    Valachis, Antonis
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län.
    Foukakis, Theodoros
    Tumor-infiltrating lymphocytes (TILs) dynamics in breast cancer patients receiving neoadjuvant therapy: A systematic review and meta-analysis2022Ingår i: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 40, nr 16, artikel-id e12620Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Increased baseline tumor-infiltrating lymphocytes (TILs) are associated with improved pathological complete response rates and better prognosis in HER2+ and triple negative breast cancer (TNBC) patients receiving neoadjuvant therapy (NAT). However, the role of TILs dynamics/change (DTILs) at the neoadjuvant setting remains unclear, thus a meta-analysis of the published studies was carried out.

    Methods: Medline, Embase, Cochrane Library and Web of Science Core Collection were searched for studies reporting on TILs expression in paired invasive breast cancer patient tissue samples before and after NAT. Data were extracted by two investigators (Y.Z., E.T.) and discordances were resolved by a third (I.Z.). Outcomes included pooled TILs rates pre- & post-treatment (also per subtype), pooled rates of DTILs and direction of change after NAT as well as correlation of DTILs with survival outcomes. Heterogeneity was assessed using the I2 statistic.

    Results: Of 1569 identified entries, 22 studies fulfilled the criteria and provided adequate data for the outcomes of interest. Overall, a significantly decreased level of TILs was observed after NAT in paired samples (pooled OR = 1.60, 95% CI: 1.12-2.30, p = 0.01; TILs as categorical variable). Regarding pooled rates of DTILs, a change was observed after NAT, irrespective of BC subtype. Among the different subtypes, the effect of NAT on TILs was most prominent in HER2+ disease with a direction towards decreased TILs to be more common (pooled DTILs rates: 14.4% increased vs 46.2%, decreased). In TNBC, bi-directional TIL kinetics were noted (pooled DTILs rates: 41.6% increased vs 37.1% decreased). An increase in DTILs in TNBC was associated with better disease-free/relapse-free survival in univariate analysis (HR = 0.59, 95% CI: 0.37–0.95, p = 0.03). Substantial between-study heterogeneity was observed in most analyses.

    Conclusions: The first to our knowledge meta-analysis on TILs dynamics during NAT in BC informs about differences in matched pre- and post-treatment patient samples and the prognostic implications of DTILs in TNBC. The potential clinical utility of the longitudinal assessment of immune response during neoadjuvant therapy warrants further investigation in prospective trials.

  • 3656.
    Zhai, Yinghong
    et al.
    Clinical Research Center, School of Medicine, Shanghai Ninth People's Hospital Affiliated to Shanghai JiaoTong University, Shanghai 00011, China.
    Hu, Fangyuan
    Department of Medical Service, Naval Hospital of Eastern theater, Zhejiang, Zhoushan 316000, China; Department of Health Statistics, Second Military Medical University, Shanghai 200433, China.
    Shi, Wentao
    Clinical Research Center, School of Medicine, Shanghai Ninth People's Hospital Affiliated to Shanghai JiaoTong University, Shanghai 00011, China; Department of Health Statistics, Second Military Medical University, Shanghai 200433, China.
    Ye, Xiaofei
    Department of Health Statistics, Second Military Medical University, Shanghai 200433, China.
    Xu, Jingfang
    Department of Health Statistics, Second Military Medical University, Shanghai 200433, China.
    Guo, Xiaojing
    Department of Health Statistics, Second Military Medical University, Shanghai 200433, China.
    Cao, Yang
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Clinical Epidemiology and Biostatistics.
    He, Jia
    Department of Health Statistics, Second Military Medical University, Shanghai 200433, China.
    Xu, Feng
    Clinical Research Center, School of Medicine, Shanghai Ninth People's Hospital Affiliated to Shanghai JiaoTong University, Shanghai 00011, China.
    Pharmacovigilance analysis of cardiac risks associated with Bruton tyrosine kinase inhibitors2023Ingår i: Expert Opinion on Drug Safety, ISSN 1474-0338, E-ISSN 1744-764X, Vol. 22, nr 9, s. 857-869Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Bruton tyrosine kinase inhibitors (BTKIs) can be associated with several cardiac risks.

    RESEARCH DESIGN AND METHODS: This study was conducted based on records from a large spontaneous reporting database, the Food and Drug Administration Adverse Event Reporting System, for cardiac events reported for several BTKI agents. Reporting odds ratio and information components based on statistical shrinkage transformation were utilized to measure disproportionality.

    RESULTS: The final number of records for BTKI-related cardiac events was 10 320. Death or life-threatening events occurred in 17.63% of all associated cardiac records. Significant reporting was captured between BTKI (total/specific) and cardiac events, with the strongest association for ibrutinib. A total of 47 positive signals were evacuated for ibrutinib, with atrial fibrillation being the most commonly reported one. Concomitantly, cardiac failure congestive, cardiac disorder, arrhythmia, pericardial effusion, and atrial flutter, were also noticed for relatively stronger signal and disproportionality. Atrial fibrillation was over-reported in the 3 groups (ibrutinib, acalabrutinib, zanubrutinib), and acalabrutinib had statistically significant lower reporting compared with ibrutinib.

    CONCLUSIONS: Receiving ibrutinib, acalabrutinib or zanubrutinib might increase the chance of cardiac complications, with ibrutinib posing the highest risk. The type of cardiotoxicity involved in ibrutinib was highly variable.

  • 3657.
    Zhai, Yinghong
    et al.
    School of Medicine, Tongji University, Shanghai, China; Department of Health Statistics, Second Military Medical University, Shanghai, China.
    Ye, Xiaofei
    Department of Health Statistics, Second Military Medical University, Shanghai, China.
    Hu, Fangyuan
    Department of Health Statistics, Second Military Medical University, Shanghai, China.
    Xu, Jinfang
    Department of Health Statistics, Second Military Medical University, Shanghai, China.
    Guo, Xiaojing
    Department of Health Statistics, Second Military Medical University, Shanghai, China.
    Cao, Yang
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län.
    Lin, Zhen
    Department of Health Statistics, Second Military Medical University, Shanghai, China.
    Zhou, Xiang
    School of Medicine, Tongji University, Shanghai, China; Department of Health Statistics, Second Military Medical University, Shanghai, China.
    Guo, Zhijian
    Department of Health Statistics, Second Military Medical University, Shanghai, China.
    He, Jia
    School of Medicine, Tongji University, Shanghai, China; Department of Health Statistics, Second Military Medical University, Shanghai, China.
    Cardiovascular Toxicity of Carfilzomib: The Real-World Evidence Based on the Adverse Event Reporting System Database of the FDA, the United States2021Ingår i: Frontiers in Cardiovascular Medicine, E-ISSN 2297-055X, Vol. 8, artikel-id 735466Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Carfilzomib, an effective proteasome inhibitor agent for the therapy of relapsed and refractory multiple myeloma, has been related to a significant number of cardiovascular events. However, patterns of cardiovascular complications associated with this agent remain poorly characterized in real-world settings.

    Objective: To gain further insight into the frequency, spectrum, clinical features, timing, and outcomes of carfilzomib-related cardiovascular toxicities.

    Methods: This disproportionality (case/non-case) study was conducted leveraging records from FAERS database from 2014 to 2019. Cardiovascular events were defined and broadly categorized eight entities using narrow version of the Standardized MedDRA Queries (SMQs). Reporting odds ratios (ROR) and information component (IC) were calculated to measure disproportionality. Additionally, statistical shrinkage was applied to reduce false-positive signals.

    Results: The final number of records involved was 28,479,963, with 3,370 records submitted for carfilzomib related cardiovascular events. Significant disproportionality association between carfilzomib administration and cardiovascular events was captured (IC025/ROR025 = 0.85/1.95) when exploring in the entire database. Upon further analysis, all eight broad categories of cardiovascular toxicities were disproportionately associated with carfilzomib with varying frequencies, time-to-onset, and severities. Cardiomyopathy-related complications (N = 1,301, 38.61%), embolic and thrombotic events (N = 821, 24.36%), and cardiac failure (N = 765, 22.70%) largely comprised the reported problems. Notably, the strongest signal was detected for cardiac failure (IC025/ROR025 = 1.33/2.59), followed by pulmonary hypertension (IC025/ROR025 = 1.19/2.34). Median onset time of cardiovascular events was 41days (Q1-Q3: 9-114 days), with the shortest median time being 16 days (Q1-Q3: 4-85 days) for ischemic heart disease, with the longest time being 68 days (Q1-Q3: 21-139 days) for embolic and thrombotic events. Torsade de pointes/QT prolongation was identified as a new complication (IC025/ROR025 = 0.33/1.29) and was particularly noteworthy for highest death proportion (44.11%).

    Conclusions: Treatment with carfilzomib can lead to severe and versatile cardiovascular events. Early and intensive monitoring is important, particularly in the first 3 months after carfilzomib initiation. Maximizing the benefit while reducing potential cardiovascular harms of carfilzomib should become a priority.

  • 3658.
    Zhai, Yinghong
    et al.
    School of Medicine, Tongji University, Shanghai, China; Department of Health Statistics, Second Military Medical University, Shanghai, China.
    Ye, Xiaofei
    Department of Health Statistics, Second Military Medical University, Shanghai, China.
    Hu, Fangyuan
    Department of Health Statistics, Second Military Medical University, Shanghai, China; Department of Medical Service, Naval Hospital of Eastern Theater, Zhoushan, China.
    Xu, Jinfang
    Department of Health Statistics, Second Military Medical University, Shanghai, China.
    Guo, Xiaojing
    Department of Health Statistics, Second Military Medical University, Shanghai, China.
    Lin, Zhen
    Department of Health Statistics, Second Military Medical University, Shanghai, China.
    Zhou, Xiang
    School of Medicine, Tongji University, Shanghai, China; Department of Health Statistics, Second Military Medical University, Shanghai, China.
    Guo, Zhijian
    Department of Health Statistics, Second Military Medical University, Shanghai, China.
    Cao, Yang
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län.
    He, Jia
    School of Medicine, Tongji University, Shanghai, China; Department of Health Statistics, Second Military Medical University, Shanghai, China.
    Updated Insights on Cardiac and Vascular Risks of Proton Pump Inhibitors: A Real-World Pharmacovigilance Study2022Ingår i: Frontiers in Cardiovascular Medicine, E-ISSN 2297-055X, Vol. 9, artikel-id 767987Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Proton pump inhibitors (PPIs) are among the most widely prescribed medications in clinical practice. However, there are also concerns about the potential risks of long-term PPI use. The present study aimed to examine the safety of PPIs and summarize their potential cardiac and vascular risks in a real-world setting.

    Methods: This pharmacovigilance study extracted records between January 2015 and December 2019 from the FDA Adverse Event Reporting System (FAERS) database. The association of seven PPI medications with cardiac and vascular events (CVEs) were evaluated. Two established pharmacovigilance methods, reporting odds ratio (ROR) and information components (IC) based statistical shrinkage, were used to measure disproportionality.

    Results: In total 62,140 CVE records associated with PPI use were investigated. Women showed a higher proportion (54.37%) of PPI-associated CVEs. The median time from PPI initiation to CVE onset was 97 [interquartile range (IQR): 8-491] days, with the shortest median time of 42 days (IQR: 2-277 days) for esomeprazole, and the longest time of 389 days (IQR: 0-525 days) for dexlansoprazole. Although PPIs were not associated with elevated CVE risks compared those of the whole database (IC025/ROR025 = -0.39/0.74), various signals emerged. Despite some similarities exist between the PPIs, their cardiac and vascular safety profiles varied significantly. Pantoprazole showed the broadest spectrum of signals, from thrombotic thrombocytopenic purpura (IC025/ROR025 = 0.01/1.08) to renal haemangioma (IC025/ROR025 = 3.14/9.58). Esomeprazole showed the second-broadest spectrum of toxicities, ranging from duodenal ulcer hemorrhage (IC025/ROR025 = 0.07/1.28) to hypertensive nephropathy (IC025/ROR025 = 4.09/18.72). Vascular signals were more dominant than cardiac signals, suggesting that vascular function was more heavily affected. Hypertensive nephropathy, renal haemangioma, renal artery stenosis, and renal infarct had strong signals across most PPI regimens and merited further attention.

    Conclusions: PPIs may inflict various CVEs, particularly those involving the vascular system, on the users. Given the wide range of onset times and different toxicity profiles for various PPI medications, they should be prescribed with caution.

  • 3659.
    Zhai, Yinghong
    et al.
    Tongji University School of Medicine, Shanghai, China.
    Ye, Xiaofei
    Department of Health Statistics, Second Military Medical University, Shanghai, China.
    Hu, Fangyuan
    Department of Health Statistics, Second Military Medical University, Shanghai, China; Department of Medical Service, Naval Hospital of Eastern Theater Zhoushan, Zhejiang, China.
    Xu, Jinfang
    Department of Health Statistics, Second Military Medical University, Shanghai, China.
    Guo, Xiaojing
    Department of Health Statistics, Second Military Medical University, Shanghai, China.
    Zhou, Xiang
    Tongji University School of Medicine, Shanghai, China.
    Zheng, Yi
    Department of Health Statistics, Second Military Medical University, Shanghai, China.
    Zhao, Xinxin
    Tongji University School of Medicine, Shanghai, China.
    Xu, Xiao
    Tongji University School of Medicine, Shanghai, China.
    Cao, Yang
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Unit of Integrative Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    He, Jia
    Tongji University School of Medicine, Shanghai, China; Department of Health Statistics, Second Military Medical University, Shanghai, China.
    Metabolic and Nutritional Disorders Following the Administration of Immune Checkpoint Inhibitors: A Pharmacovigilance Study2021Ingår i: Frontiers in Endocrinology, E-ISSN 1664-2392, Vol. 12, artikel-id 809063Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Although several metabolic and nutritional disorders (MNDs) have been reported in the recipients of immune checkpoint inhibitors (ICIs), these events have not been fully captured and comprehensively characterized in real-world population.

    Objectives: To provide complete metabolic and nutritional toxicity profiles after ICIs (single and combined) initiation through an integrated big database.

    Methods: Reporting odds ratios (ROR) and information component (IC) based on statistical shrinkage transformation were utilized to perform disproportionality analysis using the US Food and Drug Administration Adverse Events Reporting System. Both ROR and IC were used to calculate disproportionality when compared with the whole database, but only ROR was used when comparison was made for different ICI strategies. Only when both the lower limits of 95% confidence intervals (CIs) for ROR (ROR025) and IC (IC025) exceeded specified threshold values (1 and 0, respectively) was regarded as a signal.

    Results: A total of 29,294,335 records were involved and 8,662 records were for MNDs in patients exposed to ICIs. Statistically significant association was detected between ICIs use and total MNDs (IC025/ROR025 = 1.06/2.19). For monotherapy, three ICI monotherapies (anti-PD-1, anti-PDL-1, and anti-CTLA-4) were all disproportionately associated with MNDs. Statistically significant differences in reporting frequencies also emerged when comparing anti-PD-1 with anti-PD-L1/anti-CTLA-4 monotherapy, with RORs of 1.11 (95%CI 1.01-1.21), and 1.35 (95%CI 1.23-1.48), respectively. Notably, combination therapy was associated with a higher reporting frequency of theses toxicities compared to monotherapy with a ROR of 1.56 (95%CI 1.48-1.64). Additionally, disproportionality analysis at High-level Group Term level highlighted eight broad entities of MNDs. Further disproportionality analysis at Preferred Term level indicated a wide range and varied strength of signals. For ICI monotherapy, nivolumab and pembrolizumab showed the broadest spectrum of MNDs. For combination therapy, a variety of signals were detected for nivolumab + ipilimumab therapy even comparable to two PD-1 monotherapies.

    Conclusion: Metabolic and nutritional complications could be provoked by ICI monotherapy (especially anti-PD-1) and further reinforced by combination therapy. Clinicians and patients should be informed about these potential risks that might be encountered in real-world practice. Aforehand education and regular monitoring of related biochemical parameters (calcium, sodium, potassium, protein) are recommended to ensure better cancer survivorship.

  • 3660.
    Zhang, Jiming
    et al.
    School of Public Health, Key Laboratory of Public Health Safety of Ministry of Education, Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, Shanghai, China.
    Guo, Jianqiu
    School of Public Health, Key Laboratory of Public Health Safety of Ministry of Education, Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, Shanghai, China.
    Wu, Chunhua
    School of Public Health, Key Laboratory of Public Health Safety of Ministry of Education, Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, Shanghai, China.
    Qi, Xiaojuan
    School of Public Health, Key Laboratory of Public Health Safety of Ministry of Education, Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, Shanghai, China.
    Jiang, Shuai
    School of Public Health, Key Laboratory of Public Health Safety of Ministry of Education, Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, Shanghai, China.
    Lu, Dasheng
    Shanghai Center for Disease Control and Prevention, Shanghai, China.
    Feng, Chao
    ai Center for Disease Control and Prevention, Shanghai, China.
    Liang, Weijiu
    Changning Center for Disease Control and Prevention, Shanghai, China.
    Chang, Xiuli
    School of Public Health, Key Laboratory of Public Health Safety of Ministry of Education, Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, Shanghai, China.
    Zhang, Yubin
    School of Public Health, Key Laboratory of Public Health Safety of Ministry of Education, Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, Shanghai, China.
    Cao, Yang
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län.
    Wang, Guoquan
    Shanghai Center for Disease Control and Prevention, Shanghai, China.
    Zhou, Zhijun
    School of Public Health, Key Laboratory of Public Health Safety of Ministry of Education, Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, Shanghai, China.
    Exposure to carbamate and neurodevelopment in children: Evidence from the SMBCS cohort in China2019Ingår i: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 177, artikel-id 108590Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Carbamate pesticides exposure have been linked with adverse health effects during developmental period. Based on 377 mother-child pairs from Sheyang Mini Birth Cohort Study, the present study aimed to assess carbofuranphenol exposure of three-year-old children and explore the associations between prenatal or postnatal carbofuranphenol exposures and neurodevelopmental indicators.

    METHODS: Urinary carbofuranphenol concentrations were measured by gas chromatography-tandem mass spectrometry. Neural developmental quotient (DQ) of children was evaluated using Gesell Developmental Schedules. Generalized linear models were used to examine the associations between carbofuranphenol concentrations and neurodevelopment.

    RESULTS: Geometric mean, geometric standard deviation, median, inter quartile range of postnatal urinary carbofuranphenol concentrations were 0.653 μg/L, 9.345 μg/L, 0.413 μg/L, 0.150-1.675 μg/L, respectively. Postnatal carbofuranphenol level showed negatively significant trend in language DQ [beta (β) = -0.121; 95% confidence interval (95% CI): 0.212, -0.031; p value (p) = 0.008] and total average DQ (β = -0.059, 95% CI: 0.115, -0.003; p = 0.035). Prenatal carbofuranphenol level showed negative correlations with children's adaptive DQ (β = -0.755; 95% CI: 1.257, -0.254; p = 0.003), social DQ (β = -0.341; 95% CI: 0.656, -0.027; p = 0.032) and total average DQ (β = -0.349; 95% CI: 0.693, -0.005; p = 0.047).

    CONCLUSION: The results of the present study supposed children in agricultural region of China are widely exposed to carbamate pesticides, and both prenatal and postnatal exposure to carbamate pesticides may lead to neurodevelopmental effect.

  • 3661.
    Zhang, Jiming
    et al.
    School of Public Health, Key Laboratory of Public Health Safety of Ministry of Education, Key Lab of Health Technology Assessment, National Health Commission of the People's Republic of China, Fudan University, Shanghai, China.
    Guo, Jianqiu
    School of Public Health, Key Laboratory of Public Health Safety of Ministry of Education, Key Lab of Health Technology Assessment, National Health Commission of the People's Republic of China, Fudan University, Shanghai, China.
    Wu, Chunhua
    School of Public Health, Key Laboratory of Public Health Safety of Ministry of Education, Key Lab of Health Technology Assessment, National Health Commission of the People's Republic of China, Fudan University, Shanghai, China.
    Qi, Xiaojuan
    School of Public Health, Key Laboratory of Public Health Safety of Ministry of Education, Key Lab of Health Technology, Assessment, National Health Commission of the People's Republic of China, Fudan University, Shanghai, China; Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China.
    Jiang, Shuai
    School of Public Health, Key Laboratory of Public Health Safety of Ministry of Education, Key Lab of Health Technology Assessment, National Health Commission of the People's Republic of China, Fudan University, Shanghai, China.
    Lv, Shenliang
    School of Public Health, Key Laboratory of Public Health Safety of Ministry of Education, Key Lab of Health Technology Assessment, National Health Commission of the People's Republic of China, Fudan University, Shanghai, China.
    Lu, Dasheng
    Shanghai Center for Disease Control and Prevention, Shanghai, China.
    Liang, Weijiu
    Changning Center for Disease Control and Prevention, Shanghai, China.
    Chang, Xiuli
    School of Public Health, Key Laboratory of Public Health Safety of Ministry of Education, Key Lab of Health Technology Assessment, National Health Commission of the People's Republic of China, Fudan University, Shanghai, China.
    Zhang, Yubin
    School of Public Health, Key Laboratory of Public Health Safety of Ministry of Education, Key Lab of Health Technology Assessment, National Health Commission of the People's Republic of China, Fudan University, Shanghai, China.
    Cao, Yang
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län.
    Zhou, Zhijun
    School of Public Health, Key Laboratory of Public Health Safety of Ministry of Education, Key Lab of Health Technology Assessment, National Health Commission of the People's Republic of China, Fudan University, Shanghai, China.
    Carbamate pesticides exposure and delayed physical development at the age of seven: Evidence from the SMBCS study2022Ingår i: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 160, artikel-id 107076Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Carbamate pesticides are widely used in agriculture and cause widespread human exposure. The health effect of carbamates on physical development remains unclear. The current study aimed to explore the carbamate's health effect on physical development.

    METHODS: Prenatal, 3-year-old, 7-year-old urinary carbofuranphenol concentration was measured by gas chromatography tandem mass spectrometry and adjusted by creatinine. Anthropometric indices were measured by standard method and z-score standardized. Generalized linear models (GLM) were using to assess associations between exposure measurements and anthropometric indices. The generalized estimate equation (GEE) was applied to analyze the association between multiperiod exposure and anthropometric indices, and time-interaction terms were used to exam health effect consistency of exposure in each period. Gender-stratified analysis were conducted according to results of gender-interaction terms to identify gender-specific effects.

    RESULTS: The gender-interaction term of prenatal exposure with height z-score was significant (β = -0.057; 95% CI: -0.113, -0.001; p = 0.045). The 3-year-old carbofuranphenol level showed negative associations with weight z-score (β = -0.019; 95% CI: -0.038, -0.000; p = 0.040), height z-score (β = -0.015; 95% CI: -0.028, -0.001; p = 0.026), chest circumference (β = -0.086; 95% CI: -0.171, -0.001; p = 0.046), and waist circumference (β = -0.128; 95% CI: -0.230, -0.026; p = 0.014). No statistically significant trend was found for prenatal and 7-year-old carbofuranphenol levels. In GEEs, carbofuranphenol level was negatively associated with weight z-score (β = -0.103; 95% CI: -0.195, -0.011; p = 0.027), height z-score (β = -0.087; 95% CI: -0.152, -0.022; p = 0.008), and chest circumference (β = -0.472; 95% CI: -0.918, -0.026; p = 0.037). Boy's height z-score was inversely associated with carbamate exposure (β = -0.140; 95% CI: -0.227, -0.053; p = 0.001).

    CONCLUSIONS: Prenatal and postnatal carbamate exposure may affect physical developmental process.

  • 3662.
    Zhang, Jiming
    et al.
    School of Public Health/Key Laboratory of Public Health Safety of Ministry of Education/Key Lab of Health Technology Assessment, National Health Commission of the People's Republic of China, Fudan University, Shanghai, China.
    Guo, Jianqiu
    School of Public Health/Key Laboratory of Public Health Safety of Ministry of Education/Key Lab of Health Technology Assessment, National Health Commission of the People's Republic of China, Fudan University, Shanghai, China.
    Wu, Chunhua
    School of Public Health/Key Laboratory of Public Health Safety of Ministry of Education/Key Lab of Health Technology Assessment, National Health Commission of the People's Republic of China, Fudan University, Shanghai, China.
    Qi, Xiaojuan
    School of Public Health/Key Laboratory of Public Health Safety of Ministry of Education/Key Lab of Health Technology Assessment, National Health Commission of the People's Republic of China, Fudan University, Shanghai, China; Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China.
    Jiang, Shuai
    School of Public Health/Key Laboratory of Public Health Safety of Ministry of Education/Key Lab of Health Technology Assessment, National Health Commission of the People's Republic of China, Fudan University, Shanghai, China.
    Zhou, Tong
    School of Public Health/Key Laboratory of Public Health Safety of Ministry of Education/Key Lab of Health Technology Assessment, National Health Commission of the People's Republic of China, Fudan University, Shanghai, China.
    Xiao, Hongxi
    School of Public Health/Key Laboratory of Public Health Safety of Ministry of Education/Key Lab of Health Technology Assessment, National Health Commission of the People's Republic of China, Fudan University, Shanghai, China.
    Li, Wenting
    School of Public Health/Key Laboratory of Public Health Safety of Ministry of Education/Key Lab of Health Technology Assessment, National Health Commission of the People's Republic of China, Fudan University, Shanghai, China.
    Lu, Dasheng
    Shanghai Center for Disease Control and Prevention, Shanghai, China.
    Feng, Chao
    Shanghai Center for Disease Control and Prevention, Shanghai, China.
    Liang, Weijiu
    Changning District Center for Disease Control and Prevention, Shanghai, China.
    Chang, Xiuli
    School of Public Health/Key Laboratory of Public Health Safety of Ministry of Education/Key Lab of Health Technology Assessment, National Health Commission of the People's Republic of China, Fudan University, Shanghai, China.
    Zhang, Yubin
    School of Public Health/Key Laboratory of Public Health Safety of Ministry of Education/Key Lab of Health Technology Assessment, National Health Commission of the People's Republic of China, Fudan University, Shanghai, China.
    Cao, Yang
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län.
    Wang, Guoquan
    Shanghai Center for Disease Control and Prevention, Shanghai, China.
    Zhou, Zhijun
    School of Public Health/Key Laboratory of Public Health Safety of Ministry of Education/Key Lab of Health Technology Assessment, National Health Commission of the People's Republic of China, Fudan University, Shanghai, China.
    Early-life carbamate exposure and intelligence quotient of seven-year-old children2020Ingår i: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 145, artikel-id 106105Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Early-life carbamate exposure during developmental period has been linked with adverse health effects and attracted attention.

    Methods: Three hundred and three children at age of seven were included in the current study. Urinary carbofuranphenol concentrations were measured using gas chromatography-tandem mass spectrometry. Verbal, performance and full-scale intelligence quotients (IQ(V), IQ(P), and IQ(FS)) were assessed using Wechsler Intelligence Scale for Children-Chinese Revised. Generalized linear models were used to explore the associations between carbofuranphenol levels and IQs. Generalized estimating equations were used to explore long-term health effect and sensitive time window.

    Results: Carbofuranphenol was detected in 96.6% of the seven-year-old urinary samples, the geometric mean, median, and inter quartile range of the carbofuranphenol concentrations were 0.67 mu g/L, 0.30 mu g/L, and 0.09-3.72 mu g/L, respectively, which were similar with the level of three-year-old children from the SMBCS cohort. Seven-year-old carbofuranphenol level was negatively associated with IQP [beta = -0.044; 95% confidence interval (CI): -0.087, -0.001; p = 0.045]. Three-year-old carbofuranphenol level was negatively associated with IQP (beta =-0.100; 95% CI: -0.186, -0.014; p= 0.022) and IQFS (beta =-0.087; 95% CI: -0.173, -0.001; p = 0.047). Carbamate exposure of maternal and children at both three and seven years old had negative associations with IQP (beta = -0.089; 95% CI: -0.171, -0.007; p = 0.034), and IQFS (beta = -0.064; 95% CI: -0.127, -0.000; p = 0.049) of children at age of seven.

    Conclusion: Results of the present study verify that children in an agricultural region of China were widely exposed to carbamate pesticides. Carbamate exposure in utero and at three and seven years may adversely impact children's neurodevelopment.

  • 3663.
    Zhang, Jiming
    et al.
    School of Public Health/MOE Key Laboratory of Public Health Safety/NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai, China.
    Li, Zeyu
    School of Public Health/MOE Key Laboratory of Public Health Safety/NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai, China.
    Dai, Yiming
    School of Public Health/MOE Key Laboratory of Public Health Safety/NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai, China.
    Guo, Jianqiu
    School of Public Health/MOE Key Laboratory of Public Health Safety/NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai, China.
    Qi, Xiaojuan
    School of Public Health/MOE Key Laboratory of Public Health Safety/NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai, China; Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China.
    Liu, Ping
    School of Public Health/MOE Key Laboratory of Public Health Safety/NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai, China.
    Lv, Shenliang
    School of Public Health/MOE Key Laboratory of Public Health Safety/NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai, China.
    Lu, Dasheng
    Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China.
    Liang, Weijiu
    Shanghai Changning Center for Disease Control and Prevention, Shanghai, China.
    Chang, Xiuli
    School of Public Health/MOE Key Laboratory of Public Health Safety/NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai, China.
    Cao, Yang
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län.
    Wu, Chunhua
    School of Public Health/MOE Key Laboratory of Public Health Safety/NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai, China.
    Zhou, Zhijun
    School of Public Health/MOE Key Laboratory of Public Health Safety/NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai, China.
    Urinary para-nitrophenol levels of pregnant women and cognitive and motor function of their children aged 2 years: Evidence from the SMBCS (China)2022Ingår i: Ecotoxicology and Environmental Safety, ISSN 0147-6513, E-ISSN 1090-2414, Vol. 244, artikel-id 114051Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Urinary para-nitrophenol (PNP), an exposure biomarker of ethyl parathion (EP) and methyl parathion (MP) pesticides, was still pervasively detected in the general population even after global restriction for years. And the concern whether there is an association of PNP level with child development of the nervous system is increasing. The current study aimed to evaluate the maternal urinary PNP concentrations during late pregnancy and the associations of PNP levels with cognitive and motor function of their children at the age of 2 years.

    METHODS: 323 mother-child pairs from the Sheyang Mini Birth Cohort Study were included in the current study. Gas chromatography-tandem mass spectrometry was used to measure concentrations of PNP, the specific metabolite of EP and MP, in maternal urine samples during pregnancy. Developmental quotients (DQs) scores measured with Gesell Developmental Scales were employed to evaluate cognitive and motor function of children aged 2 years. Generalized linear models were performed to analyze the associations of PNP concentrations in pregnant women's urine samples with cognitive and motor function of their children.

    RESULTS: Maternal PNP was detected in all urine samples with a median of 4.11 μg/L and a range from 0.57 μg/L to 109.13 μg/L, respectively. Maternal urinary PNP concentrations showed a negative trend with DQ of motor area [regression coefficient (β) = - 1.35; 95 % confidence interval (95 %CI): - 2.37, - 0.33; P < 0.01], and the children whose mothers were in the fourth quartile exposure group performed significantly worse compared to the reference group (β = - 1.11; 95 %CI: - 1.80, - 0.42; P < 0.01). As for average DQ score, children with their mothers' urinary PNP concentrations in the third quartile group had higher scores than those in the first quartile group (β = 0.39; 95 %CI: 0.03, 0.75; P = 0.04). In sex-stratified analyses, a negative trend between maternal urinary PNP concentrations and DQ scores in motor area of children was only observed in boys (β = - 1.62; 95 %CI: - 2.80, - 0.43; P < 0.01). Boys in the third quartile group had higher DQ average scores than those in the lowest quartile as reference (β = 0.53; 95 %CI: 0.02, 1.04; P = 0.04).

    CONCLUSIONS: The mothers from SMBCS may be widely exposed to EP and/or MP, which were associated with the cognitive and motor function of their children aged 2 years in a sex-specific manner. Our results might provide epidemiology evidence on the potential effects of prenatal exposure to EP and/or MP on children's cognitive and motor function.

  • 3664.
    Zhang, Jiming
    et al.
    School of Public Health / MOE Key Laboratory of Public Health Safety / NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai, China.
    Wang, Zheng
    School of Public Health / MOE Key Laboratory of Public Health Safety / NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai, China.
    Dai, Yiming
    School of Public Health / MOE Key Laboratory of Public Health Safety / NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai, China.
    Zhang, Lei
    School of Public Health / MOE Key Laboratory of Public Health Safety / NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai, China.
    Guo, Jianqiu
    School of Public Health / MOE Key Laboratory of Public Health Safety / NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai, China.
    Lv, Shenliang
    School of Public Health / MOE Key Laboratory of Public Health Safety / NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai, China.
    Qi, Xiaojuan
    School of Public Health / MOE Key Laboratory of Public Health Safety / NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai, China.
    Lu, Dasheng
    Shanghai Center for Disease Control and Prevention, Shanghai, China.
    Liang, Weijiu
    Changning Center for Disease Control and Prevention, No.39 Yunwushan Road, Shanghai, China.
    Cao, Yang
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Unit of Integrative Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Wu, Chunhua
    School of Public Health / MOE Key Laboratory of Public Health Safety / NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai, China.
    Chang, Xiuli
    School of Public Health / MOE Key Laboratory of Public Health Safety / NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai, China.
    Zhou, Zhijun
    School of Public Health / MOE Key Laboratory of Public Health Safety / NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai, China.
    Multiple mediation effects on association between prenatal triclosan exposure and birth outcomes2022Ingår i: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 215, nr Part 1, artikel-id 114226Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Triclosan is a broad-spectrum antimicrobial, and was thought to affect intrauterine development, but the mechanism remains unclear.

    OBJECTIVE: To explore the association between prenatal triclosan exposure and birth outcomes.

    METHODS: Based on 726 mother-child pairs from the Sheyang Mini Birth Cohort Study (SMBCS), we used the available (published) data of triclosan in maternal urines, the hormones including thyroid-related hormones, gonadal hormones in cord blood, and adipokines, trimethylamine-N-oxide (TMAO) and its precursors in cord blood to explore possible health effects of triclosan on birth outcomes through assessing different hormones and parameters, using Bayesian mediation analysis.

    RESULTS: Maternal triclosan exposure was associated with ponderal index (β = 0.317) and head circumference (β = -0.172) in generalized linear models. In Bayesian mediation analysis of PI model, estradiol (β = 0.806) and trimethylamine (TMA, β = 0.164) showed positive mediation effects, while total thyroxine (TT4, β = -0.302), leptin (β = -2.023) and TMAO (β = -0.110) showed negative mediation effects. As for model of head circumference, positive mediation effects were observed in free thyroxine (FT4, β = 0.493), TMA (β = 0.178), and TMAO (β = 0.683), negative mediation effects were observed in TT4 (β = -0.231), testosterone (β = -0.331), estradiol (β = -1.153), leptin (β = -2.361), choline (β = -0.169), betaine (β = -0.104), acetyl-L-carnitine (β = -0.773).

    CONCLUSION: The results indicated triclosan can affect intrauterine growth by interfering thyroid-related hormones, gonadal hormones, adipokines, TMAO and its precursors.

  • 3665.
    Zhang, Lei
    et al.
    School of Public Health, MOE Key Laboratory of Public Health Safety, NHC Key Lab of Health Technology Assessment Fudan University, Shanghai, China.
    Zhang, Jiming
    School of Public Health, MOE Key Laboratory of Public Health Safety, NHC Key Lab of Health Technology Assessment Fudan University, Shanghai, China.
    Dai, Yiming
    School of Public Health, MOE Key Laboratory of Public Health Safety, NHC Key Lab of Health Technology Assessment Fudan University, Shanghai, China.
    Guo, Jianqiu
    School of Public Health, MOE Key Laboratory of Public Health Safety, NHC Key Lab of Health Technology Assessment Fudan University, Shanghai, China.
    Lv, Shenliang
    School of Public Health, MOE Key Laboratory of Public Health Safety, NHC Key Lab of Health Technology Assessment Fudan University, Shanghai, China.
    Wang, Zheng
    School of Public Health, MOE Key Laboratory of Public Health Safety, NHC Key Lab of Health Technology Assessment Fudan University, Shanghai, China.
    Xu, Sinan
    School of Public Health, MOE Key Laboratory of Public Health Safety, NHC Key Lab of Health Technology Assessment Fudan University, Shanghai, China.
    Lu, Dasheng
    Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China.
    Qi, Xiaojuan
    Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China.
    Feng, Chao
    Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China.
    Liang, Weijiu
    Changning District Center for Disease Control and Prevention, Shanghai, China.
    Xu, Hao
    Changning District Center for Disease Control and Prevention, Shanghai, China.
    Cao, Yang
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län.
    Wang, Guoquan
    Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China.
    Zhou, Zhijun
    School of Public Health, MOE Key Laboratory of Public Health Safety, NHC Key Lab of Health Technology Assessment Fudan University, Shanghai, China.
    Wu, Chunhua
    School of Public Health, MOE Key Laboratory of Public Health Safety, NHC Key Lab of Health Technology Assessment Fudan University, Shanghai, China.
    Prenatal exposure to parabens in association with cord serum adipokine levels and offspring size at birth2022Ingår i: Chemosphere, ISSN 0045-6535, E-ISSN 1879-1298, Vol. 301, artikel-id 134725Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Paraben exposure is linked to the release of adipokine such as leptin and adiponectin, and both paraben and adipokine may affect fetal growth. The present study aimed to explore the associations among maternal paraben exposure, adipokine level and offspring size.

    METHODS: 942 mother-newborn pairs from the Sheyang Mini Birth Cohort Study (SMBCS) were enrolled. Data of birth weight, length, head circumference and ponderal index (PI) were obtained from medical records. Maternal urinary parabens were determined by gas chromatography tandem mass spectrometry. Cord serum leptin and adiponectin were measured using ELISA assay. Generalized linear regression was applied to explore the associations among parabens, adipokines and offspring size.

    RESULTS: The median levels of leptin and adiponectin were 13.13 μg/L and 161.82 μg/mL. Benzylparaben level was positively associated with leptin (regression coefficient (β) = 0.06, 95% confidence interval (CI): 0.03-0.09; p < 0.01). Leptin level was positively associated with neonatal weight (β = 84.11, 95% CI: 63.22-105.01; p < 0.01), length (β = 0.25, 95% CI: 0.14-0.37; p < 0.01), head circumference (β = 0.15, 95% CI: 0.07-0.22; p < 0.01) and PI (β = 0.23, 95% CI: 0.08-0.39; p < 0.01). Adiponectin was positively associated with neonatal weight (β = 75.94, 95% CI: 29.65-122.23; p < 0.01) and PI (β = 0.43, 95% CI: 0.09-0.77; p = 0.01). Urinary propylparaben concentration (β = -0.10, 95% CI: 0.17 to -0.02; p = 0.01) was negatively associated with head circumference. Sex-stratified analyses indicated the negative association of propylparaben and head circumference was only remained in male neonates.

    CONCLUSIONS: Prenatal paraben exposure might affect cord serum leptin levels. Both paraben and adipokine levels may affect fetal growth, and sex-specific differences may exist.

  • 3666.
    Zhang, Xing
    et al.
    Department of Basketball and Volleyball, Chengdu Sport University, Chengdu, China.
    Li, Hansen
    Key Lab of Physical Fitness Evaluation and Motor Function Monitoring of General Administration of Sports of China, College of Physical Education, Institute of Sports Science, Southwest University, Chongqing, China.
    Bi, Shilin
    National Institute of Education, Nanyang Technological University, Singapore, Singapore.
    Luo, Yong
    Department of Basketball and Volleyball, Chengdu Sport University, Chengdu, China.
    Cao, Yang
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Unit of Integrative Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Zhang, Guodong
    Key Lab of Physical Fitness Evaluation and Motor Function Monitoring of General Administration of Sports of China, College of Physical Education, Institute of Sports Science, Southwest University, Chongqing, China.
    Auto-Regulation Method vs. Fixed-Loading Method in Maximum Strength Training for Athletes: A Systematic Review and Meta-Analysis2021Ingår i: Frontiers in Physiology, E-ISSN 1664-042X, Vol. 12, artikel-id 651112Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    The auto-regulation method is a rising training strategy to improve strength and motor performance, and the Autoregulatory Progressive Resistance Exercise (APRE), Rating of Perceived Exertion program (RPE), and Velocity-Based Training (VBT) are the three common auto-regulation programs. However, whether the auto-regulation method is more effective than the traditional strength training (the fixed-loading method) in maximum strength training is still unclear. The present study searched the Pubmed, SPORTDiscus, Web of Science, Embase, EBSCO, Cochrane, CNKI, and CQVIP databases, and included eight related studies published between 2010 and 2020, with a total of 166 subjects including division 1 college players and athletes with at least 1-year training history, and interventions ranging from 5 to 10 weeks. A meta-analysis was performed to check the difference between the two training methods, and analyzed the differences in the existing auto-regulation programs' effectiveness. The overall results showed that the auto-regulation method was more effective than the fixed-loading method in maximum strength training (effect size = 0.64; P < 0.001; I2 = 0%). In specific, the pooled results in subgroup analysis indicated that the auto-regulation method may effectively improve the strength performance in squat (effect size = 4.64; P < 0.05; I2 = 54%) and bench press (effect size = 3.21; P < 0.05; I2 = 62%). Greater benefits of the auto-regulation method on strength improvement could be achieved in an 8-week or even shorter training (effect size = 0.87; P < 0.001; I2 = 0%) compared with those of 8–10 weeks (effect size = 0.32; P < 0.001; I2 = 0%). The APRE is the most effective training program among the three auto-regulation programs (effect size = 0.78; P < 0.001; I2 = 0%). In conclusion, the auto-regulation method could be more effective than the fixed-loading method in maximum strength training. The APRE is a convenient and effective training program that may be considered a practical training program to replace traditional training in athletes.

  • 3667.
    Zhang, Xueli
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Centre for Systems Biology, Soochow University, Suzhou, China.
    Sun, Xiao-Feng
    Department of Oncology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Cao, Yang
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
    Ye, Benchen
    Centre for Systems Biology, Soochow University, Suzhou, China.
    Peng, Qiliang
    Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
    Liu, Xingyun
    Centre for Systems Biology, Soochow University, Suzhou, China.
    Shen, Bairong
    Centre for Systems Biology, Soochow University, Suzhou, China.
    Zhang, Hong
    Örebro universitet, Institutionen för medicinska vetenskaper.
    CBD: a biomarker database for colorectal cancer2018Ingår i: Database: The Journal of Biological Databases and Curation, E-ISSN 1758-0463, artikel-id bay046Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Colorectal cancer (CRC) biomarker database (CBD) was established based on 870 identified CRC biomarkers and their relevant information from 1115 original articles in PubMed published from 1986 to 2017. In this version of the CBD, CRC biomarker data were collected, sorted, displayed and analysed. The CBD with the credible contents as a powerful and time-saving tool provide more comprehensive and accurate information for further CRC biomarker research. The CBD was constructed under MySQL server. HTML, PHP and JavaScript languages have been used to implement the web interface. The Apache was selected as HTTP server. All of these web operations were implemented under the Windows system. The CBD could provide to users the multiple individual biomarker information and categorized into the biological category, source and application of biomarkers; the experiment methods, results, authors and publication resources; the research region, the average age of cohort, gender, race, the number of tumours, tumour location and stage. We only collect data from the articles with clear and credible results to prove the biomarkers are useful in the diagnosis, treatment or prognosis of CRC. The CBD can also provide a professional platform to researchers who are interested in CRC research to communicate, exchange their research ideas and further design high-quality research in CRC. They can submit their new findings to our database via the submission page and communicate with us in the CBD.

  • 3668.
    Zhu, Egui
    et al.
    Faculty of Education, Hubei University, Wuhan, China.
    Cao, Yang
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län.
    What Does the Chinese Public Care About with Regard to Primary Care Physicians: Trustworthiness or Competence?2019Ingår i: Medicina (Kaunas), ISSN 1010-660X, E-ISSN 1648-9144, Vol. 55, nr 8, artikel-id E455Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and Objective: China has launched a series of reforms to enhance primary care. The aims of these reforms are to strengthen the functionality of primary care to encourage patients to use primary care. Patients’ trust in physicians is important in clinical medicine; however, little is known about how Chinese patients’ preferences relate to their trust in primary care physicians. This study’s objectives are to measure the Chinese public’s trust in primary care physicians and to characterize reasons of their preferences for health care.

    Materials and Methods: This quantitative study comprises a face-to-face survey with a convenience sample (n = 273) of people visiting community health centers or stations (CHCSs) in Wuhan, China. We measured the patients’ preferences for the different level of hospitals and their trust in physicians, as well as the reasons of the patients’ preferences, using a Chinese version of the Wake Forest Physician Trust Scale and other variables (such as demographics, health status, and hospital preference).

    Results: Approximately two thirds (68.6%) of the participants had experienced a mild or chronic disease in the year before the survey, but only 26.4% preferred to visit CHCSs in such cases. The negative factors related to this lack of preference are the physicians’ competence (odds ratio [OR] = 0.250), the medical equipment (OR = 0.301), and the popularity of hospitals (OR = 0.172). The positive factors were ease of access (OR = 2.218) and affordability (OR = 1.900). The participants expressed a moderate trust in physicians in CHCSs (score of 3.02 out of 5). There is no association between the patients’ trust and their hospital preference (r = 0.019, p = 0.859). Of the participants, 92 suggested that the physicians in CHCSs should improve in terms of their competence (n = 53), attitude (n = 35), and/or medical ethics (n = 16).

    Conclusions: This study’s results suggest that patients consider improving physicians’ competence to be more important and urgent than improving those physicians’ trustworthiness in terms of reconstructing Chinese primary care. Improving the physicians’ competence would not only reduce the barriers that patients experience regarding CHCSs, but would also increase their trust in the physicians.

  • 3669.
    Zhu, Jianwei
    et al.
    Department of Orthopedic Surgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, P. R. China.
    Chen, Ruoqing
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Davidsson, Sabina
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Urology.
    Carlsson, Jessica
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Urology.
    Messing-Eriksson, Anna
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Urology.
    Fridfeldt, Jonna
    Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Andrén, Ove
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Urology.
    Andersson, Sven-Olof
    Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Valdimarsdóttir, Unnur
    Department of Orthopedic Surgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, P. R. China; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, SA, USA.
    Fang, Fang
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Fall, Katja
    Örebro universitet, Institutionen för medicinska vetenskaper. Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Sweden; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Psychological and physiological impacts of a fast-track diagnostic workup for men with suspected prostate cancer: Preliminary report from a randomized clinical trial2020Ingår i: Cancer communications (London, England), ISSN 2523-3548, Vol. 40, nr 5, s. 239-242Artikel i tidskrift (Refereegranskat)
  • 3670.
    Zhu, Yajing
    et al.
    Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
    Tzoras, Evangelos
    Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
    Matikas, Alexios
    Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden; Breast Center, Theme Cancer, Karolinska University Hospital, Stockholm, Sweden.
    Bergh, Jonas
    Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden; Breast Center, Theme Cancer, Karolinska University Hospital, Stockholm, Sweden.
    Valachis, Antonis
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Oncology.
    Zerdes, Ioannis
    Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden; Breast Center, Theme Cancer, Karolinska University Hospital, Stockholm, Sweden.
    Foukakis, Theodoros
    Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden; Breast Center, Theme Cancer, Karolinska University Hospital, Stockholm, Sweden.
    Expression patterns and prognostic implications of tumor-infiltrating lymphocytes dynamics in early breast cancer patients receiving neoadjuvant therapy: A systematic review and meta-analysis2022Ingår i: Frontiers in Oncology, E-ISSN 2234-943X, Vol. 12, artikel-id 999843Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    PURPOSE: High levels of tumor-infiltrating lymphocytes (TILs) are associated with better outcomes in early breast cancer and higher pathological response rates to neoadjuvant chemotherapy especially in the triple-negative (TNBC) and HER2+ subtypes. However, the dynamic changes in TILs levels after neoadjuvant treatment (NAT) are less studied. This systematic review and meta-analysis aimed to investigate the patterns and role of TILs dynamics change in early breast cancer patients receiving NAT.

    METHODS: Medline, Embase, Web of Science Core Collection and PubMed Central databases were searched for eligible studies. Data were extracted independently by two researchers and discordances were resolved by a third. Pooled TILs rates pre- & post-treatment (overall and per subtype), pooled rates of ΔTILs and direction of change after NAT as well as correlation of ΔTILs with survival outcomes were generated in the outcome analysis.

    RESULTS: Of 2116 identified entries, 34 studies fulfilled the criteria and provided adequate data for the outcomes of interest. A decreased level of TILs was observed after NAT in paired samples across all subtypes. The effect of NAT on TILs was most prominent in TNBC subtype with a substantial change, either increase or decrease, in 79.3% (95% CI 61.7-92.6%) of the patients as well as in HER2+ disease (14.4% increased vs 46.2% decreased). An increase in ΔTILs in TNBC was associated with better disease-free/relapse-free survival in pooled analysis (univariate HR = 0.59, 95% CI: 0.37-0.95, p = 0.03).

    CONCLUSION: This meta-analysis illustrates the TILs dynamics during NAT for breast cancer and indicates prognostic implications of ΔTILs in TNBC. The potential clinical utility of the longitudinal assessment of TILs during neoadjuvant therapy warrants further validation.

  • 3671.
    Zhu, Zheng
    et al.
    Institute of Neurology, Huashan Hospital, Fudan University, Shanghai, China; National Clinical Research Center for Aging Diseases, Shanghai, China.
    Yang, Yang
    Guanghan Personal Hlth Res Inst, Shanghai, Peoples R China..
    Xiao, Zhenxu
    Guanghan Personal Health Research Institute, Shanghai, China.
    Zhao, Qianhua
    Institute of Neurology, Huashan Hospital, Fudan University, Shanghai, China; National Clinical Research Center for Aging Diseases, Shanghai, China.
    Wu, Wanqing
    Institute of Neurology, Huashan Hospital, Fudan University, Shanghai, China; National Clinical Research Center for Aging Diseases, Shanghai, China.
    Liang, Xiaoniu
    Institute of Neurology, Huashan Hospital, Fudan University, Shanghai, China; National Clinical Research Center for Aging Diseases, Shanghai, China.
    Luo, Jianfeng
    Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China.
    Cao, Yang
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län.
    Shao, Minhua
    Guanghan Personal Health Research Institute, Shanghai, China.
    Guo, Qihao
    Institute of Neurology, Huashan Hospital, Fudan University, Shanghai, China; National Clinical Research Center for Aging Diseases, Shanghai, China.
    Ding, Ding
    Institute of Neurology, Huashan Hospital, Fudan University, Shanghai, China; National Clinical Research Center for Aging Diseases, Shanghai, China.
    TOMM40 and APOE variants synergistically increase the risk of Alzheimer's disease in a Chinese population2021Ingår i: Aging Clinical and Experimental Research, ISSN 1594-0667, E-ISSN 1720-8319, Vol. 33, nr 6, s. 1667-1675Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The apolipoprotein E (APOE) epsilon 4 allele is a strong risk factor for Alzheimer's disease (AD) in Caucasian and African American populations. It suggests that other genetic factors may modulate AD pathogenesis in Chinese populations, among which the frequency of this allele is reduced but the AD prevalence is maintained. The translocase of outer mitochondrial membrane 40 (TOMM40), which is located adjacent to APOE,may play an APOE-dependent role in modulating AD pathogenesis.

    Aims: This work aimed to investigate whether TOMM40 polymorphisms modulate AD risk independently of, or in conjunction with APOE polymorphisms in Chinese populations.

    Methods: We conducted a case-control study including 834 patients with AD recruited from the Memory Clinic and 643 cognitively normal participants recruited from the community. The Taqman SNP method was used for APOE genotyping, while TOMM40 polymorphism genotyping was conducted via a polymerase chain reaction-ligase detection reaction.

    Results: TheTOMM40 rs10119 and rs71352238 alleles were associated with AD independently of the patient APO status. The rs10119 AA genotype and rs71352238 CC genotype were risk genotypes of AD. Individuals carrying a TOMM40 rs10119 GG/APOE epsilon 4+ (OR, 3.73; 95% CI 1.49-9.37;P = 0.005), TOMM40 rs10119 AG/APOE epsilon 4+ (OR, 4.16; 95% CI 3.30-5.24;P < 0.001), or TOMM40 rs10119 AA/APOE epsilon 4+ (OR, 14.78; 95% CI 8.56-25.54;P < 0.001) genotype exhibited a significantly higher AD risk. Those carrying a TOMM40 rs71352238 TT/APOE epsilon 4+ (OR, 3.82; 95% CI 2.32-6.29;P < 0.001), TOMM40 rs71352238 CT/APOE epsilon 4+ (OR, 4.40; 95% CI 3.46-5.56;P < 0.001), or TOMM40 rs71352238 CC/APOE epsilon 4+ (OR, 14.02; 95% CI 7.81-25.17;P < 0.001) genotype also exhibited a significantly increased AD risk.

    Discussion and conclusions: This study provides invaluable insights into the mechanisms underlying the prevalence of AD in Chinese populations, and supports that simultaneous TOMM40 and APOE genotyping in the clinical setting may identify individuals at high risk of developing AD.

  • 3672.
    Zhulina, Yaroslava
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Region Örebro län. Department of Internal Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Udumyan, Ruzan
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Henriksson, Ida
    Department of Internal Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden .
    Tysk, Curt
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Region Örebro län. Department of Internal Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Montgomery, Scott
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Region Örebro län.
    Halfvarson, Jonas
    Örebro universitet, Institutionen för läkarutbildning. Region Örebro län. Department of Internal Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Temporal trends in non-stricturing and non-penetrating behaviour at diagnosis of Crohn's disease in Örebro, Sweden: a population-based retrospective study2014Ingår i: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 8, nr 12, s. 1653-1660Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and aim: The incidence of Crohn's disease (CD) is continuing to rise in several countries and in others it appears to have already levelled off after a period of increase. We updated our previous population-based study, by re-extraction of all information on patients diagnosed with CD between 1963 and 2010. Our aim was to assess temporal trends in incidence, prevalence and disease phenotype at diagnosis.

    Methods: Patients of all ages with a potential diagnosis of CD were identified retrospectively by evaluation of medical notes of all current and previous patients at the colitis clinic, Örebro University Hospital amended by computerised search in the inpatient, outpatient, primary care and histopathological records. Diagnosis was confirmed by subsequent evaluation of medical notes. Disease phenotype was defined according to the Montreal classification.

    Results: The incidence increased over time, especially among Crohn's disease, A1 and A3. SaTScan model revealed a statistically significant high incidence during 1991-2010 (p=0.0001). The median age at diagnosis increased from 28 (3-79) years to 37 (5-87) years (p=0.0002). The point prevalence increased from 21/10(5) (14-32) in 1965 to 267/10(5) (244-291) in 2010. Non-stricturing and non-penetrating disease at diagnosis increased from 12.5% in 1963-1965 to 82.3% in 2006-2010 (p<0.0001).

    Conclusion: The incidence of CD increased over time, although it seemed to be plateauing during the most recent decades. A striking increase in non-stricturing, non-penetrating disease at diagnosis was observed, suggesting earlier diagnosis or phenotypic change. The observed point prevalence in 2010 is among the highest reported.

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  • 3673.
    Zhulina, Yaroslava
    et al.
    Region Örebro län. Örebro universitet, Institutionen för medicinska vetenskaper. Department of Gastroenterology.
    Udumyan, Ruzan
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län.
    Tysk, Curt
    Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Halfvarson, Jonas
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Gastroenterology.
    Mortality in patients with Crohn's disease in Örebro, Sweden 1963-20102022Ingår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 57, nr 2, s. 153-164Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Some studies have suggested a reduced life expectancy in patients with Crohn's disease (CD) compared with the general population. The evidence, however, is inconsistent.

    AIMS: Prompted by such studies, we studied survival of CD patients in Örebro county, Sweden.

    METHODS: From the medical records, we identified all patients diagnosed with CD during 1963-2010 with follow-up to the end of 2011. We estimated: overall survival, net and crude probabilities of dying from CD, relative survival ratio (RSR), and excess mortality rate ratios (EMRR) at 10-year follow-up.

    RESULTS: The study included 492 patients (226 males, 266 females). Median age at diagnosis was 32 years (3-87). Net and crude probabilities of dying from CD increased with increasing age and were higher for women. Net survival of patients aged ≥60 at diagnosis was worse for patients diagnosed during 1963-1985 (54%) than for patients diagnosed during 1986-1999 (88%) or 2000-2010 (93%). Overall, CD patients' survival was comparable to that in the general population [RSR = 0.98; 95% CI: (0.95-1.00)]. However, significantly lower than expected survival was suggested for female patients aged ≥60 diagnosed during the 1963-1985 [RSR = 0.47 (0.07-0.95)]. The adjusted model suggested that, compared with diagnostic period 1963-1985, disease-related excess mortality declined during 2000-2010 [EMRR = 0.36 (0.07-1.96)]; and age ≥60 at diagnosis [EMRR = 7.99 (1.64-39.00), reference: age 40-59], female sex [EMRR = 4.16 (0.62-27.85)], colonic localization [EMRR = 4.20 (0.81-21.88), reference: ileal localization], and stricturing/penetrating disease [EMRR = 2.56 (0.52-12.58), reference: inflammatory disease behaviour] were associated with poorer survival.

    CONCLUSION: CD-related excess mortality may vary with diagnostic period, age, sex and disease phenotype.Key summaryThere is inconsistent evidence on life expectancy of patients with Crohn's diseaseCrohn's disease-specific survival improved over time.Earlier diagnosis period, older age at diagnosis, female sex, colonic disease and complicated disease behaviour seems to be associated with excess Crohn's disease-related mortality.

  • 3674.
    Ziegler, Ingrid
    et al.
    Department of Infectious Diseases, Örebro University Hospital , Örebro, Sweden.
    Cajander, Sara
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
    Rasmussen, Gunlög
    Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden; School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Ennefors, Theresa
    Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Mölling, Paula
    Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Strålin, Kristoffer
    School of Health and Medical Sciences, Örebro University, Örebro, Sweden; Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
    High nuc DNA load in whole blood is associated with sepsis, mortality and immune dysregulation in Staphylococcus aureus bacteraemia2019Ingår i: Infectious Diseases, ISSN 2374-4235, E-ISSN 2374-4243, Vol. 51, nr 3, s. 216-226Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Staphylococcus aureus bacteraemia is a disease with varying presentation, ranging from uncomplicated to life-threatening infections. In S. aureus bacteraemia, a high load of bacterial DNA in blood has been linked to mortality. We hypothesized that a high DNA load would also be linked to the presence of sepsis, and to high C-reactive protein (CRP) and lymphopaenia, indicating inflammation and immunosuppression.

    METHODS: Twenty-seven patients with culture-proven S. aureus bacteraemia, 13 (48%) with sepsis and six (22%) non-survivors, were enrolled in a prospective study. Blood samples were collected on days 0, 1-2, 3-4, 6-8, 13-15 and 26-30, and subjected to droplet digital PCR targeting the nuc gene to determine the nuc DNA load.

    RESULTS: nuc DNA was detected on days 0-2 in 22 patients (81%), and on days 6-8 in three patients (all non-survivors). The nuc DNA load on days 1-2 was significantly elevated in patients with sepsis (median 2.69 versus 1.32 log10 copies/mL; p = .014) and in non-survivors (median 2.5 versus 1.0 log10 copies/mL; p = .033). Patients with a high nuc DNA load (>3.0 log10 copies/mL) on days 1-2 had significantly elevated CRP levels at all timepoints, and significantly decreased lymphocyte counts on days 0, 1-2, 13-15 and 26-30.

    CONCLUSIONS: Our results indicate that a high initial load of S. aureus DNA in blood is associated with sepsis, mortality and persistent immune dysregulation in S. aureus bacteraemia patients. Further studies are needed to define the role of bacterial DNA load monitoring in the management of S. aureus bacteraemia.

  • 3675.
    Ziegler, Ingrid
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
    Cajander, Sara
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Infectious Diseases.
    Rasmussen, Gunlög
    Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden; School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Ennefors, Theresa
    Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Mölling, Paula
    Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Strålin, Kristoffer
    School of Health and Medical Sciences, Örebro University, Örebro, Sweden; Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
    nuc DNA in Whole blood in Relation to Immune dysregulation, Sepsis, and Mortality in Staphylococcus aureus BacteremiaManuskript (preprint) (Övrigt vetenskapligt)
  • 3676.
    Ziegler, Ingrid
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Dept Infect Dis, Örebro Univ Hosp, Örebro, Sweden.
    Josefson, Per
    Dept Infect Dis, Örebro Univ Hosp, Örebro, Sweden.
    Olcen, Per
    Dept Lab Med, Örebro Univ Hosp, Örebro, Sweden.
    Mölling, Paula
    Region Örebro län. Dept of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Strålin, Kristoffer
    Dept Infect Dis, Örebro Univ Hosp, Örebro, Sweden; Dept Infect Dis, Karolinska Univ Hosp, Stockholm, Sweden.
    Quantitative data from the SeptiFast real-time PCR is associated with disease severity in patients with sepsis2014Ingår i: BMC Infectious Diseases, E-ISSN 1471-2334, Vol. 14, nr 1, artikel-id 155Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The commercial test, SeptiFast, is designed to detect DNA from bacterial and fungal pathogens in whole blood. The method has been found to be specific with a high rule-in value for the early detection of septic patients. The software automatically provides information about the identified pathogen, without quantification of the pathogen. However, it is possible to manually derive Crossing point (Cp) values, i.e. the PCR cycle at which DNA is significantly amplified. The aim of this study was to find out whether Cp values correlate to disease severity.

    Methods: We used a study cohort of patients with positive results from SeptiFast tests for bacteria from a recent study which included patients with suspected sepsis in the Emergency department. Cp values were compared with disease severity, classified as severe sepsis/septic shock or non-severe sepsis, according to the criteria of the American College of Chest Physicians/Society of Critical Care Medicine.

    Results: Ninety-four patients were included. The prevalence of severe sepsis/septic shock in the study was 29%. SeptiFast positive tests from patients with severe sepsis/septic shock had significantly lower Cp values compared with those from patients with non-severe sepsis, median 16.9 (range: 7.3 - 24.3) versus 20.9 (range: 8.5 - 25.0), p < 0.001. Positive predictive values from the SeptiFast test for identifying severe sepsis/septic shock were 34% at Cp cut-off <25.0, 35% at Cp cut-off <22.5, 50% at Cp cut-off <20.0, and 73% at Cp cut-off <17.5. Patients with a positive Septifast test with a Cp value <17.5 had significantly more severe sepsis/septic shock (73% versus 15%, p < 0.001), were more often admitted to the Intensive Care Unit (23% versus 4%, p = 0.016), had positive blood culture (BC) more frequently (100% versus 32%, p < 0.001) and had longer hospital stays (median 19.5 [range: 4 - 78] days versus 5 [range: 0 - 75] days, p < 0.001) compared with those with a Cp value >17.5.

    Conclusions: Our results suggest that introducing quantitative data to the SeptiFast test could be of value in assessing sepsis severity. Moreover, such data might also be useful in predicting a positive BC result.

  • 3677.
    Zingone, Fabiana
    et al.
    Dept Med & Surg, Univ Salerno, Salerno, Italy.
    Swift, Gillian L.
    Dept Gastroenterol, Univ Hosp Llandough, Cardiff, UK.
    Card, Timothy R.
    Div Epidemiol & Publ Hlth, City Hosp Nottingham, Univ Nottingham, Nottingham, England.
    Sanders, David S.
    Dept Gastroenterol, Royal Hallamshire Hosp, Sheffield, England; Univ Sheffield, Sheffield, England.
    Ludvigsson, Jonas F.
    Region Örebro län. Dept Pediat, Örebro University Hospital, Örebro, Sweden; Dept Med Epidemiol & Biostat, Karolinska Inst, Stockholm, Sweden.
    Bai, Julio C.
    Dept Med, C Bonorino Udaondo Gastroenterol Hosp, Univ Salvador, Buenos Aires DF, Argentina.
    Psychological morbidity of celiac disease: A review of the literature2015Ingår i: United European Gastroenterology journal, ISSN 2050-6406, E-ISSN 2050-6414, Vol. 3, nr 2, s. 136-145Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Background: Celiac disease has been linked to decreased quality of life and certain mood disorders. The effect of the gluten free diet on these psychological aspects of the disease is still unclear. Objectives: The objective of this article is to review the literature on psychological morbidity of celiac disease. Methods: We performed a PubMed search for the time period from 1900 until June 1, 2014, to identify papers on psychological aspects of celiac disease looking specifically at quality of life, anxiety, depression and fatigue. Results: Anxiety, depression and fatigue are common complaints in patients with untreated celiac disease and contribute to lower quality of life. While aspects of these conditions may improve within a few months after starting a gluten-free diet, some patients continue to suffer from significant psychological morbidity. Psychological symptoms may affect the quality of life and the dietary adherence. Conclusion: Health care professionals need to be aware of the ongoing psychological burden of celiac disease in order to support patients with this disease.

  • 3678.
    Zugna, Daniela
    et al.
    Unita Epidemiol Tumori, Dipartimento Sci Med, Univ Turin, Turin, Italy.
    Ludvigsson, Jonas F.
    Region Örebro län. Dept Med Epidemiol & Biostat, Karolinska Inst, Stockholm, Sweden.; Dept Pediat, Örebro Univ Hosp, Örebro, Sweden.
    Improving Our Knowledge on the Risk of Congenital Malformations in Families With Celiac Disease Reply2015Ingår i: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, Vol. 13, nr 3, s. 616-616Artikel i tidskrift (Refereegranskat)
  • 3679.
    Zugna, Daniela
    et al.
    Canc Epidemiol Unit, Centrr Rieferimento Epidemiol & Prevenz Oncol Piemon, Turin, Italy; Univ Turin, Turin, Italy.
    Richiardi, Lorenzo
    Canc Epidemiol Unit, Centrr Rieferimento Epidemiol & Prevenz Oncol Piemon, Turin, Italy; Univ Turin, Turin, Italy.
    Stephansson, Olof
    Clin Epidemiol Unit, Dept Med, Karolinska Inst, Stockholm, Sweden.
    Cnattingius, Sven
    Clin Epidemiol Unit, Dept Med, Karolinska Inst, Stockholm, Sweden.
    Ludvigsson, Jonas F.
    Region Örebro län. Clin Epidemiol Unit, Dept Med, Karolinska Inst, Stockholm, Sweden; Dept Pediat, Örebro University Hospital, Örebro, Sweden; Coll Med, Dept Med & Immunol, Div Gastroenterol & Hepatol, Mayo Clin, Rochester MN, USA.
    Mortality Rate in Children Born to Mothers and Fathers With Celiac Disease: A Nationwide Cohort Study2013Ingår i: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 177, nr 12, s. 1348-1355Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Celiac disease (CD) is associated with increased mortality rate and adverse pregnancy outcome, but little is known about offspring mortality rate. In this nationwide retrospective cohort study, we identified persons whose biopsy-verified CD was diagnosed in Sweden in 19692008. We compared mortality rates in children born to mothers with and without CD (n 16,121 vs. n 61,782) and children born to fathers with and without CD (n 9,289 vs. n 32,984). Median age of offspring at end of follow-up was 28.7 (range, 16.739.7) years. We also examined mortality rates in children born to mothers with undiagnosed CD (later CD diagnosis; n 12,919) and diagnosed CD (n 3,202) to determine if intrauterine exposures associated with CD could affect offspring mortality rate. We estimated hazard ratios for death by using Cox regression. Death rates were independent of maternal CD (60 deaths per 100,000 person-years in children of mothers with CD, vs. 54 in controls) and paternal CD (53 deaths per 100,000 person-years in children of fathers with CD, vs. 53 in controls). Corresponding adjusted hazard ratios were 1.09 (95 confidence interval: 0.95, 1.26) for maternal CD and 1.02 (95 confidence interval: 0.85, 1.23) for paternal CD. Death rates were similar in children born to mothers with undiagnosed CD and in children whose mothers had diagnosed CD during pregnancy. Parental CD does not seem to influence mortality rate in offspring, which suggests that neither genetic influences of CD nor intrauterine conditions have adverse effects on offspring mortality rate.

  • 3680.
    Zugna, Daniela
    et al.
    Canc Epidemiol Unit, ll Centro di Riferimento per l'Epidemiologia e la Prevenzione Oncologica (CPO) Piemonte, Turin, Italy; Univ Turin, Turin, Italy; Dept Med, Clin Epidemiol Unit, Karolinska Inst, Stockholm, Sweden.
    Richiardi, Lorenzo
    Canc Epidemiol Unit, ll Centro di Riferimento per l'Epidemiologia e la Prevenzione Oncologica (CPO) Piemonte, Turin, Italy; Univ Turin, Turin, Italy.
    Stephansson, Olof
    Dept Med, Clin Epidemiol Unit, Karolinska Inst, Stockholm, Sweden; Div Obstet & Gynecol, Dept Womens & Childrens Hlth, Karolinska Inst, Stockholm, Sweden.
    Pasternak, Bjorn
    Dept Epidemiol Res, Statens Serum Inst, Copenhagen, Denmark.
    Ekbom, Anders
    Dept Med, Clin Epidemiol Unit, Karolinska Inst, Stockholm, Sweden.
    Cnattingius, Sven
    Dept Med, Clin Epidemiol Unit, Karolinska Institutet, Stockholm, Sweden.
    Ludvigsson, Jonas F.
    Region Örebro län. Dept Med Epidemiol & Biostat, Karolinska Inst, Stockholm, Sweden; Dept Pediat, Örebro Univ Hosp, Örebro, Sweden.
    Risk of Congenital Malformations Among Offspring of Mothers and Fathers With Celiac Disease: A Nationwide Cohort Study2014Ingår i: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, Vol. 12, nr 7, s. 1108-+Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND & AIMS: Many patients with celiac disease experience malabsorption, weight loss, and anemia; undiagnosed celiac disease during pregnancy has been linked with adverse outcomes. Studies of celiac disease and congenital malformations in offspring have been underpowered. We investigated the risk of congenital malformations among the offspring of parents with celiac disease. METHODS: We performed a nationwide cohort study of data from linked health care registers in Sweden from 1973 through 2009. We collected histopathology data from 28 pathology departments in Sweden to identify individuals with celiac disease (based on the presence of villous atrophy). We estimated the risks of malformations in the offspring of mothers and fathers with and without celiac disease. Logistic regression was used to estimate adjusted prevalence odds ratios (aPORs) with 95% confidence intervals (CIs). RESULTS: Among 11,382 offspring of mothers with celiac disease, there were 672 cases (5.9%) of malformation compared with 2098 cases (5.1%) among 40,922 offspring of mothers without celiac disease. Similarly, 352 (5.9%) of 6002 offspring of fathers with celiac disease and 1009 (5.1%) of 19,600 offspring of fathers without celiac disease had a malformation. In adjusted analyses, the offspring of mothers or fathers with celiac disease had a slightly increased risk of having children with malformations (for those with mothers with celiac disease: aPOR, 1.15; 95% CI, 1.05-1.26; for those with fathers with celiac disease: aPOR, 1.14; 95% CI, 1.00-1.29). However, these excess risks decreased or vanished entirely when we restricted our data to births since 2000 (for those with mothers with celiac disease: aPOR, 1.11; and 95% CI, 0.79-1.56; for those with fathers with celiac disease: aPOR, 1.01; 95% CI, 0.81-1.26). CONCLUSIONS: In a nationwide study, we found an increased risk for malformation among the offspring of mothers or fathers with celiac disease. However, the excess risk is small; the upper limits of the CIs for malformation indicate a 29% maximum relative increase.

  • 3681.
    Zwemer, Catherine H.
    et al.
    Center for Trauma and Critical Care, Department of Surgery, The George Washington University, Washington DC, USA.
    Mohseni, Shahin
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Division of Trauma & Emergency Surgery, Department of Surgery.
    Forssten, Maximilian Peter
    Örebro universitet, Institutionen för medicinska vetenskaper. Division of Trauma & Emergency Surgery, Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Malyavko, Alisa
    Center for Trauma and Critical Care, Department of Surgery, The George Washington University, Washington DC, USA.
    Zebley, James A.
    Center for Trauma and Critical Care, Department of Surgery, The George Washington University, Washington DC, USA.
    Qaddumi, Waleed N.
    Center for Trauma and Critical Care, Department of Surgery, The George Washington University, Washington DC, USA.
    Cornejo, Miglia
    Department of Psychiatry, Division of Child/Adolescent and Family Psychiatry, The George Washington University, Washington DC, USA.
    Sarani, Babak
    Center for Trauma and Critical Care, Department of Surgery, The George Washington University, Washington, DC, USA.
    Kartiko, Susan
    Center for Trauma and Critical Care, Department of Surgery, The George Washington University, Washington DC, USA.
    The relationship of ADHD and trauma mortality: An NTDB analysis2023Ingår i: Trauma, ISSN 1460-4086, E-ISSN 1477-0350Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Nearly 7% of the adult US population has symptomatic Attention Deficit Hyperactivity Disorder (ADHD), which is associated with an increased risk for traumatic injury. There is limited data on the outcome of hospitalized trauma patients with ADHD. This study aimed to use a large nationwide database to investigate the relationship between a diagnosis of ADHD and clinical outcomes in hospitalized patients after major trauma.

    Methods: All patients 18 years or older in the National Trauma Database were retrospectively reviewed. Propensity score analysis was used to match patients with and without the diagnosis of ADHD at a 1:1 ratio based on age, sex, race, highest AIS in each region, comorbidities, and the presence of advanced directives limiting care. Outcomes of patients with ADHD admitted to the trauma service between the years 2015 and 2017 were compared to those without ADHD. The primary outcome of interest was in-hospital mortality, while the secondary outcomes included complications and hospital length of stay.

    Results: There were 9399 patients included in the study with a diagnosis of ADHD. These patients were overall more likely to be younger, male, and Caucasian, compared to their matched counterparts without ADHD. ADHD was associated with a significantly lower in-hospital mortality than patients without ADHD. There was no difference in the ICU admission rate, ICU LOS, ventilator use, or complication rates between patients with and without ADHD.

    Conclusion: A diagnosis of ADHD has a complex association with clinical outcomes after trauma. The current large national analysis found that patients with a diagnosis of ADHD had significantly lower overall in-hospital mortality.

  • 3682.
    Zwemer, Catherine
    et al.
    Department of Surgery, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.
    Kartiko, Susan
    Department of Surgery, The George Washington University Hospital, Washington, District of Columbia, USA.
    Forssten, Maximilian Peter
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Zebley, James A.
    Department of Surgery, The George Washington University Hospital, Washington, District of Columbia, USA.
    Hughes, Joy Dowden
    Division of Trauma, Critical Care and Acute Care Surgery, Department of Surgery, Sheikh Shakhbout Medical City, Abu Dhabi, UAE.
    Sarani, Babak
    Center for Trauma and Critical Care, The George Washington University Hospital, Washington, District of Columbia, USA.
    Mohseni, Shahin
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Division of Trauma and Emergency Surgery, Department of Surgery, Sheikh Shakhbout Medical City, Abu Dhabi, UAE.
    Firearms-related injury and sex: a comparative National Trauma Database (NTDB) Study2023Ingår i: Trauma surgery & acute care open, E-ISSN 2397-5776, Vol. 8, nr 1, artikel-id e001181Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Existing study findings on firearms-related injury patterns are largely skewed towards males, who comprise the majority of this injury population. Given the paucity of existing data for females with these injuries, we aimed to elucidate the demographics, injury patterns, and outcomes of firearms-related injury in females compared with males in the USA.

    MATERIALS AND METHODS: A 7-year (2013-2019) retrospective review of the National Trauma Database was conducted to identify all adult patients who suffered firearms-related injuries. Patients who were males were matched (1:1, caliper 0.2) to patients who were females by demographics, comorbidities, injury patterns and severity, and payment method, to compare differences in mortality and several other post-injury outcomes.

    RESULTS: There were 196 696 patients admitted after firearms-related injury during the study period. Of these patients, 23 379 (11.9%) were females, 23 378 of whom were successfully matched to a male counterpart. After matching, females had a lower rate of in-hospital mortality (18.6% vs. 20.0%, p<0.001), deep vein thrombosis (1.2% vs. 1.5%, p=0.014), and had a lower incidence of drug or alcohol withdrawal syndrome (0.2% vs. 0.5%, p<0.001) compared with males.

    CONCLUSION: Female victims of firearms-related injuries experience lower rates of mortality and complications compared with males. Further studies are needed to elucidate the cause of these differences.

    LEVEL OF EVIDENCE: Level III.

  • 3683.
    Zylberberg, Haley M.
    et al.
    Division of Digestive and Liver Diseases, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, United States; The Celiac Disease Center, Columbia University, New York NY, United States.
    Ludvigsson, Jonas F.
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Division of Digestive and Liver Diseases, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, United States; Department of Medical Epidemiology and Biostatistics, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
    Green, Peter H. R.
    Division of Digestive and Liver Diseases, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, United States; The Celiac Disease Center, Columbia University, New York NY, United States.
    Lebwohl, Benjamin
    Division of Digestive and Liver Diseases, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, United States; Department of Medical Epidemiology and Biostatistics, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, United States; The Celiac Disease Center, Columbia University, New York NY, United States.
    Psychotropic medication use among patients with celiac disease2018Ingår i: BMC Psychiatry, E-ISSN 1471-244X, Vol. 18, artikel-id 76Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Celiac disease is a multi-system disorder with manifestations that may result in psychiatric disorders. We assessed the prevalence of medication use to treat psychiatric disorders in celiac disease patients.

    Methods: We conducted a cross-sectional study of patients undergoing esophagogastroduodenoscopy over 9-years at a celiac disease referral center. We compared the prevalence of psychotropic medication use among celiac disease patients (n = 1293) to a control group (n = 1401) with abdominal pain or reflux.

    Results: Among all patients the mean age was 48.4 years, most were female (69.5%), and 22.7% used any psychotropic medication. There was no difference between overall psychotropic medication use among celiac disease patients and controls (23.9% vs 21.8%, OR 1.16; 95% CI 0.96-1.39, p = 0.12). However, those with celiac disease were more likely to use antidepressants on univariate (16.4% vs 13.4%, p = 0.03) and multivariate analysis (OR 1.28; 95% CI 1.03-1.59; p = 0.03). Use of psychotropic medications was not associated with disease duration or mode of presentation of celiac disease.

    Conclusions: Celiac disease patients use psychotropic medications at similar rates as those with other gastrointestinal diseases, though subgroup analysis suggests they may use more antidepressants. Future studies should investigate whether celiac disease is associated with mood disorders that are not treated with medications.

  • 3684.
    Zügner, Roland
    et al.
    Department of Orthopedics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University, SE-413 45, Göteborg, Sweden; Forskningsenhet Ortopedi, Göteborgsvägen 31, SE-431 80, Mölndal, Sweden.
    Jarl, Gustav
    Region Örebro län. Örebro universitet, Institutionen för hälsovetenskaper. Department of Prosthetics and Orthotics, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; University Health Care Research Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Sundberg, Leif
    Gothenburg Diabetes Association, Gothenburg, Sweden.
    Tang, Ulla Hellstrand
    Department of Orthopedics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University, SE-413 45, Göteborg, Sweden; Department of Prosthetics and Orthotics, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Experiences of using a digital tool, the D-foot, in the screening of risk factors for diabetic foot ulcers2022Ingår i: Journal of Foot and Ankle Research, ISSN 1757-1146, Vol. 15, nr 1, artikel-id 90Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Individuals living with diabetes run an increased risk of developing diabetic foot ulcers (DFUs), leading to high costs to society and reduced quality of life for the individual. Regular screening is important to avoid complications.

    AIM: To evaluate patients' and clinicians' experiences of using a digital tool, the D-Foot, in the screening of risk factors for developing DFUs. The secondary aims were to investigate whether patients had had their feet examined by a nurse or doctor during the past year, had been referred to podiatry and whether patients had received information about self-care.

    METHODS: A prospective study was carried out, comprising 90 patients with diabetes visiting a Department of Prosthetics and Orthotics (DPO). Two Certified Prosthetists and Orthotists (CPOs) were included, and they assessed foot status and the risk of developing DFUs with the D-Foot software, prior to prescribing footwear. The quality of services at the DPO was assessed by the patients using the Orthotics and Prosthetics Users' Survey (OPUS). The CPOs answered the System Usability Scale (SUS) before and after the study to assess the usability of the D-Foot.

    RESULTS: No patient had risk grade 1. One (1%) patient had risk grade 2, 78 (87%) patients had risk grade 3 and 11 (12%) patients had risk grade 4. Patients reported high levels of satisfaction on eight of ten OPUS items and the two items with lower scores were not related to the use of the D-Foot. The two CPOs reported levels above the mean regarding usability both before (77.5 and 90) and after (70 and 97.5) using the D-Foot.

    CONCLUSIONS: Patients expressed a high level of satisfaction with the services when their feet were examined with the D-Foot prior to the provision of footwear. The CPOs found that the D-Foot system was usable. Several comments were made by patients and CPOs and will support the future development and testing of the D-Foot. There is a need to increase referrals for preventive podiatry and improve information on self-care for patients at risk of DFUs.

    TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT04054804.

  • 3685.
    Ástvaldsdóttir, Álfheidur
    et al.
    Department of Dental Medicine, Karolinska institutet, Stockholm, Sweden.
    Boström, Anne-Marie
    Division of nursing, Department of Neurobiology, Care Sciences and Society, Karolinska institutet, Huddinge, Sweden; Theme Aging, Karolinska University Hospital, Huddinge, Sweden; Department of nursing, Western Norway University of Applied Sciences, Haugesund, Norway.
    Davidson, Thomas
    Division of health Care Analysis, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden; Health Technology Assessment-Odontology (HTA-O), Faculty of Odontology, Malmö University, Malmö, Sweden.
    Gabre, Pia
    Department of Preventive Dentistry, Public Dental Health, Uppsala County Council, Uppsala, Sweden; Department of Cariology, Institute of Odontology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Gahnberg, Lars
    Department of Preventive Dentistry, Public Dental Service, Region Västra Götaland, Sweden; Department of Behavioral and Community Dentistry, Institute of Odontology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Englund, Gunilla Sandborgh
    Department of Dental Medicine, Karolinska institutet, Stockholm, Sweden; Academic Center of Geriatric Dentistry, Karolinska institutet, Stockholm, Sweden.
    Skott, Pia
    Academic Center of Geriatric Dentistry, Karolinska institutet, Stockholm, Sweden.
    Ståhlnacke, Katri
    Region Örebro län. Örebro universitet, Institutionen för medicinska vetenskaper.
    Tranaeus, Sofia
    Department of Dental Medicine, Karolinska institutet, Stockholm, Sweden; Health Technology Assessment-Odontology (HTA-O), Faculty of Odontology, Malmö University, Malmö, Sweden.
    Wilhelmsson, Hanna
    University Library, Malmö University, Malmö, Sweden.
    Wårdh, Inger
    Department of Dental Medicine, Karolinska institutet, Stockholm, Sweden; Academic Center of Geriatric Dentistry, Karolinska institutet, Stockholm, Sweden.
    Östlund, Pernilla
    Health Technology Assessment-Odontology (HTA-O), Faculty of Odontology, Malmö University, Malmö, Sweden.
    Nilsson, Mikael
    Health Technology Assessment-Odontology (HTA-O), Faculty of Odontology, Malmö University, Malmö, Sweden.
    Oral health and dental care of older persons: A systematic map of systematic reviews2018Ingår i: Gerodontology, ISSN 0734-0664, E-ISSN 1741-2358, Vol. 35, nr 4, s. 290-304Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Objectives: To examine the current knowledge on oral health status and dental care of older persons through a systematic mapping of systematic reviews of low or moderate risk of bias.

    Background: Geriatric dentistry covers all aspects of oral health and oral care of older persons. Oral health is part of general health and contributes to a person's physical, psychological and social wellbeing.

    Methods: A literature search was performed in three different databases (PubMed, The Cochrane Library and Cinahl) within 12 domains: Dental caries, periodontitis, Orofacial pain and temporomandibular joint (TMJ) pain, mucosal lesions, oral motor function, dry mouth, halitosis, interaction between oral status and other medical conditions, ability to interrelate and communicate, quality of life, ethics and organisation of dental care for older persons. Systematic reviews were identified and scrutinised, highlighting scientific knowledge and knowledge gaps.

    Results: We included 32 systematic reviews of which 14 were judged to be of low/moderate risk of bias. Most of the domains lack systematic reviews with low or moderate risk of bias. In two of the domains evidence was identified; in institutionalised people aged 65 or older, effective oral hygiene can prevent pneumonia. Furthermore, there is an evidence of a relationship between malnutrition (protein energy-related malnutrition, PEM) and poor appetite and edentulousness.

    Conclusions: There is an urgent need for further research and evidence-based knowledge within most domains in geriatric dentistry and in other fields related to oral health and dental care for older persons striving for multi-disciplinary research programmes.

  • 3686.
    Ågren, Per-Henrik
    et al.
    Stockholm Fotkirurgklinik, Sofiahemmet, Stockholm, Sweden.
    Mukka, Sebastian
    Department of Surgical and Perioperative Sciences (Orthopaedics-Sundsvall), Umeå University, Umeå, Sweden.
    Tullberg, Tycho
    Stockholm Spine Center, Stockholm, Sweden.
    Wretenberg, Per
    Region Örebro län. Department of Molecular Medicine and Surgery (Orthopaedics), Karolinska Institute, Stockholm, Sweden.
    Sayed-Noor, Arkan S
    Department of Surgical and Perioperative Sciences (Orthopaedics-Sundsvall), Umeå University, Umeå, Sweden.
    Factors affecting long-term treatment results of displaced intraarticular calcaneal fractures: a post hoc analysis of a prospective, randomized, controlled multicenter trial2014Ingår i: Journal of Orthopaedic Trauma, ISSN 0890-5339, E-ISSN 1531-2291, Vol. 28, nr 10, s. 564-568Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: To study the factors affecting long-term treatment results of displaced intraarticular calcaneal fractures (DIACFs).

    DESIGN: A post hoc analysis.

    SETTINGS: Tertiary care teaching hospitals.

    PATIENTS: Eight to twelve years of results from a randomized controlled multicenter trial of operative versus nonoperative treatment (n = 56) were divided into 2 groups: the superior 50% results (n = 28) and the inferior 50% results (n = 28), regardless of the treatment given. The determinant of this division was a visual analog score for pain and function.

    INTERVENTIONS: The operative treatment consists of open reduction and internal fixation, whereas the nonoperative treatment consists of nonweight bearing and early range of motion exercise.

    MAIN OUTCOME MEASUREMENTS: A visual analog score for pain and function, the short-form 36 (SF-36) general health outcome questionnaire, the American Orthopaedic Foot & Ankle Society (AOFAS) hindfoot scale, and Olerud-Molander score. We compared age, sex, fracture type (Sanders classification), treatment given, Böhler angle, residual articular surface step-off at healing, type of occupation, and injury insurance between the 2 groups.

    RESULTS: Patients of the superior group had higher physical SF-36, AOFAS, and Olerud-Molander score than in the inferior group. Operative treatment, better Böhler angle and articular surface restoration, light labor/retirement, and absence of injury insurance were more common in the superior group. Age, sex, pretreatment Böhler angle, and fracture type were comparable in the superior and inferior groups.

    CONCLUSIONS: The decision making for definitive treatment of intraarticular calcaneal fractures is multifactorial with a spectrum of results and trends such as patient demographic features that should be considered in choosing the best treatment option.

    LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

  • 3687.
    Åkerblom, Hanna
    et al.
    Department of Ophthalmology, Region Västmanland, Västerås, Sweden.
    Franzén, Stefan
    National Diabetes Register, Center of Registers, Gothenburg, Sweden; Health Metrics Unit, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Zhou, Caddie
    National Diabetes Register, Center of Registers, Gothenburg, Sweden.
    Morén, Åsa
    Department of Ophthalmology, Region Västmanland, Västerås, Sweden.
    Ottosson, Johan
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Surgery.
    Sundbom, Magnus
    Department of Surgical Sciences, Upper Gastrointestinal Surgery, Uppsala University, Uppsala, Sweden.
    Eliasson, Björn
    Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden.
    Svensson, Ann-Marie
    National Diabetes Register, Center of Registers, Gothenburg, Sweden; Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden.
    Granstam, Elisabet
    Department of Ophthalmology, Region Västmanland, Västerås, Sweden; Center for Clinical Research, Region Västmanland/Uppsala University, Västerås, Sweden.
    Association of Gastric Bypass Surgery With Risk of Developing Diabetic Retinopathy Among Patients With Obesity and Type 2 Diabetes in Sweden: An Observational Study2021Ingår i: JAMA ophthalmology, ISSN 2168-6165, E-ISSN 2168-6173, Vol. 39, nr 2, s. 200-205Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Importance: Knowledge of the incidence and progression of diabetic retinopathy (DR) after gastric bypass surgery (GBP) in patients with obesity and diabetes could guide the management of these patients.

    Objective: To investigate the incidence of diabetic ocular complications in patients with type 2 diabetes after GBP compared with the incidence of diabetic ocular complications in a matched cohort of patients with obesity and diabetes who have not undergone GBP.

    Design, Setting, and Participants: Data from 2 nationwide registers in Sweden, the Scandinavian Obesity Surgery Registry and the National Diabetes Register, were used for this cohort study. A total of 5321 patients with diabetes from the Scandinavian Obesity Surgery Registry who had undergone GBP from January 1, 2007, to December 31, 2013, were matched with 5321 patients with diabetes from the National Diabetes Register who had not undergone GBP, based on sex, age, body mass index (BMI), and calendar time (2007-2013). Follow-up data were obtained until December 31, 2015. Statistical analysis was performed from October 5, 2018, to September 30, 2019.

    Exposure: Gastric bypass surgery.

    Main Outcomes and Measures: Incidence of new DR and other diabetic ocular complications.

    Results: The study population consisted of 5321 patients who had undergone GBP (3223 women [60.6%]; mean [SD] age, 49.0 [9.5] years) and 5321 matched controls (3395 women [63.8%]; mean [SD] age, 47.1 [11.5] years). Mean (SD) follow-up was 4.5 (1.6) years. The mean (SD) BMI and hemoglobin A1c concentration at baseline were 42.0 (5.7) and 7.6% (1.5%), respectively, in the GBP group and 40.9 (7.3) and 7.5% (1.5%), respectively, in the control group. The mean (SD) duration of diabetes was 6.8 (6.3) years in the GBP group and 6.4 (6.4) years in the control group. The risk for new DR was reduced in the patients who underwent GBP (hazard ratio, 0.62 [95% CI, 0.49-0.78]; P < .001). The dominant risk factors for development of DR at baseline were diabetes duration, hemoglobin A1c concentration, use of insulin, glomerular filtration rate, and BMI.

    Conclusions and Relevance: This nationwide matched cohort study suggests that there is a reduced risk of developing new DR associated with GBP, and no evidence of an increased risk of developing DR that threatened sight or required treatment.

  • 3688.
    Åkerlund, Anna
    et al.
    Division of Clinical Microbiology, County Hospital Ryhov, Jönköping, Sweden; Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Division of Clinical Microbiology, Linköping University Hospital, Linköping, Sweden.
    Jonasson, Emma
    Department of Clinical Microbiology, Central Hospital, Växjö, Sweden; EUCAST Development Laboratory, Växjö, Sweden.
    Matuschek, Erika
    EUCAST Development Laboratory, Växjö, Sweden.
    Serrander, Lena
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Division of Clinical Microbiology, Linköping University Hospital, Linköping, Sweden.
    Sundqvist, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Laboratory Medicine, Clinical Microbiology.
    Kahlmeter, Gunnar
    Department of Clinical Microbiology, Central Hospital, Växjö, Sweden; EUCAST Development Laboratory, Växjö, Sweden.
    EUCAST rapid antimicrobial susceptibility testing (RAST) in blood cultures: validation in 55 European laboratories2020Ingår i: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 75, nr 11, s. 3230-3238Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: When bloodstream infections are caused by resistant bacteria, rapid antimicrobial susceptibility testing (RAST) is important for adjustment of therapy. The EUCAST RAST method, directly from positive blood cultures, was validated in a multi-laboratory study in Europe.

    METHODS: RAST was performed in 40 laboratories in northern Europe (NE) and 15 in southern Europe (SE) from clinical blood cultures positive for Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus or Streptococcus pneumoniae. Categorical results at 4, 6 and 8 h of incubation were compared with results for EUCAST standard 16-20 h disc diffusion. The method, preliminary breakpoints and the performance of the laboratories were evaluated.

    RESULTS: The total number of isolates was 833/318 in NE/SE. The number of zone diameters that could be read (88%, 96% and 99%) and interpreted (70%, 81% and 85%) increased with incubation time (4, 6 and 8 h). The categorical agreement was acceptable, with total error rates in NE/SE of 2.4%/4.9% at 4 h, 1.1%/3.5% at 6 h and 1.1%/3.3% at 8 h. False susceptibility at 4, 6 and 8 h of incubation was below 0.3% and 1.1% in NE and SE, respectively, and the corresponding percentages for false resistance were below 1.9% and 2.8%. After fine-tuning breakpoints, more zones could be interpreted (73%, 89% and 93%), with only marginally affected error rates.

    CONCLUSIONS: The EUCAST RAST method can be implemented in routine laboratories without major investments. It provides reliable antimicrobial susceptibility testing results for relevant bloodstream infection pathogens after 4-6 h of incubation.

  • 3689.
    Åkerlund, Anna
    et al.
    Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden; Division of Clinical Microbiology, Linköping University Hospital, Linköping, Sweden.
    Serrander, Lena
    Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden; Division of Clinical Microbiology, Linköping University Hospital, Linköping, Sweden.
    Sundqvist, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Laboratory Medicine, Clinical Microbiology.
    Short incubation of disc diffusion for Streptococcus pneumoniae and Haemophilus influenzae to reduce time to susceptibility report2023Ingår i: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 78, nr 10, s. 2563-2571Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Rapidly instituted antimicrobial therapy is important in severe infections, and reduced time to the antimicrobial susceptibility testing (AST) report is thus of importance. Disc diffusion (DD) is a cheap, rapidly adaptable, flexible and comprehensive method for phenotypic AST. Previous studies have shown that early reading of inhibition zones for non-fastidious species is possible.

    Objectives: To evaluate zone reading after short incubation of DD in Haemophilus influenzae (n = 73) and Streptococcus pneumoniae (n = 112).

    Methods: The readability was evaluated and susceptibility interpretation (SIR) was performed, using the EUCAST 18 & PLUSMN; 2 h incubation breakpoint table (version 12.0), after 6 and 8 h of incubation. Categorical agreement (CA) and error rates were calculated using standard DD and broth microdilution as reference.

    Results: The proportion of readable zones in H. influenzae was 19% (6 h) and 89% (8 h). The CA was 98% after 8 h. The corresponding readability in S. pneumoniae was 63%/98% and CA was 95%/97% after 6 and 8 h, respectively. Early reading of the screening discs (benzylpenicillin 1 unit in H. influenzae and oxacillin 1 & mu;g in S. pneumoniae) correctly identified 18/22 of the H. influenzae isolates and all the readable S. pneumoniae isolates with reduced & beta;-lactam susceptibility. For non-& beta;-lactam agents, very major errors were most common for quinolones in S. pneumoniae. Introduction of areas of technical uncertainty (ATUs) reduced the error rate to & LE;1.1%.

    Conclusions: We conclude that shortened incubation is feasible for H. influenzae and S. pneumoniae. To reduce the risk of false categorization a buffer zone (i.e. ATU) near the breakpoints must be used.

  • 3690. Åkerlund, Anna
    et al.
    Sundqvist, Martin
    Region Örebro län. Klinisk mikrobiologi, Laboratoriemedicinska Länskliniken, Örebro, Sweden.
    Hanberger, Håkan
    Åhrén, Christina
    Serrander, Lena
    Giske, Christian G.
    Svarstiderna kan kortas vid mikrobiologisk diagnostik av sepsis [Response times can be shortened in microbiological diagnosis of sepsis]: Bättre öppettider på laboratorier och aktiv rådgivning ger snabbare terapi [Better opening hours in laboratories and active advice enables faster therapy]2015Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 112, artikel-id C73SArtikel i tidskrift (Refereegranskat)
    Abstract [sv]

    Early and adequate antimicrobial therapy is lifesaving in patients with bloodstream infections (BSI). Continuous incubation and 24h availability of microbial pathogen identification in clinical microbiology laboratories shortens the time to report. To describe the current status in Swedish clinical microbiology laboratories, a web-based survey was performed. The survey showed major differences in availability both regarding laboratory opening hours and ability to incubate blood culture bottles outside working hours. It also showed differences in what was conveyed verbally to the clinician and in time to report of the bacterial species. Based on this survey, we debate how Swedish healthcare can improve the care of patients with BSI by offering a more rapid diagnostic process. This could be achieved through longer opening hours of the laboratory, better transport systems and blood culture cabinets positioned closer to the patient.

  • 3691.
    Åkerlund, John
    et al.
    Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Region Västra Götaland, Department of Urology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Sundqvist, Pernilla
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Urology.
    Ljungberg, Börje
    Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden.
    Lundstam, Sven
    Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Region Västra Götaland, Department of Urology, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Peeker, Ralph
    Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Region Västra Götaland, Department of Urology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Månsson, Marianne
    Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Grenabo Bergdahl, Anna
    Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Region Västra Götaland, Department of Urology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Predictors for complication in renal cancer surgery: a national register study2023Ingår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 58, nr 1, s. 38-45Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Nationwide register data provide unique opportunities for real-world assessment of complications from different surgical methods. This study aimed to assess incidence of, and predictors for, post-operative complications and to evaluate 90-day mortality  following different surgical procedures and thermal ablation for renal cell carcinoma (RCC).

    MATERIAL AND METHODS: All patients undergoing surgical treatment and thermal ablation for RCC in Sweden during 2015-2019 were identified from the National Swedish Kidney Cancer Register. Frequencies and types of post-operative complications were analysed. Logistic regression models were used to identify predictors for 90-day major (Clavien-Dindo grades III-V) complications, including death.

    RESULTS: The overall complication rate was 24% (1295/5505), of which 495 (8.7%) were major complications. Most complications occurred following open surgery, of which bleeding and infection were the most common. Twice as many complications were observed in patients undergoing open surgery compared to minimally invasive surgery (20% vs. 10%, P < 0.001). Statistically significant predictors for major complications irrespective of surgical category and technique were American society of anesthiologists (ASA) score, tumour diameter and serum creatinine. Separating radical and partial nephrectomy, surgical technique remained a significant risk factor for major complications. Most complications occurred within the first 20 days. The overall 90-day readmission rate was 6.2%, and 30- and 90-day mortality rates were 0.47% and 1.5%, respectively.

    CONCLUSIONS: In conclusion, bleeding and infection were the most common major complications after RCC surgery. Twice as many patients undergoing open surgery suffer a major post-operative complication as compared to patients subjected to minimally invasive surgery. General predictors for major complications were ASA score, tumour size, kidney function and surgical technique.

  • 3692.
    Åström, Håkan
    et al.
    Universitetssjukhuset Örebro, Örebro.
    Blomgren, Lena
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Venöst centrum Karlskoga, Karlskoga; Kärl–toraxkliniken, Universitetssjukhuset Örebro, Örebro.
    Behandling av varicer i Sverige: Information om registreringsplikt till vårdgivare behövs2021Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 118, nr 21-22, artikel-id 20218Artikel i tidskrift (Refereegranskat)
  • 3693.
    Åström, Maria
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län.
    Undersökningar av X-bunden trombocytopeni med talassemi (XLTT) och jämförelser med andra former av myelofibros2010Ingår i: Oss hematologer emellan, Vol. 4, nr 22, s. 39-40Artikel i tidskrift (Övrigt vetenskapligt)
  • 3694.
    Åström, Maria
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Division of Hematology, Department of Medicine, Örebro University Hospital, Örebro, Sweden; Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; iRiSC – Inflammatory Response and Infection Susceptibility Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Tajeddinn, Walid
    iRiSC – Inflammatory Response and Infection Susceptibility Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Karlsson, Mats G.
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine.
    Linder, Olle
    Division of Hematology, Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Palmblad, Jan
    Division of Hematology, Department of Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Lindblad, Per
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Urology.
    Cytokine Measurements for Diagnosing and Characterizing Leukemoid Reactions and Immunohistochemical Validation of a Granulocyte Colony-Stimulating Factor and CXCL8-Producing Renal Cell Carcinoma2018Ingår i: Biomarker Insights, E-ISSN 1177-2719, Vol. 13, artikel-id UNSP 1177271918792246Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Various paraneoplastic syndromes are encountered in renal cell carcinomas. This case report illustrates that a paraneoplastic leukemoid reaction may precede the diagnosis of renal cell carcinoma and be explained by cytokine production from the cancer cells.

    CASE PRESENTATIONS: A 64-year-old man was referred for hematology workup due to pronounced leukocytosis. While being evaluated for a possible hematologic malignancy as the cause, he was found to have a metastasized renal cell carcinoma, and hyperleukocytosis was classified as a leukemoid reaction. A multiplex panel for measurement of 25 serum cytokines/chemokines showed highly elevated levels of granulocyte colony-stimulating factor (G-CSF) and CXCL8 (C-X-C-motif chemokine ligand 8, previously known as interleukin [IL]-8). By immunohistochemistry it was shown that the renal carcinoma cells expressed both these cytokines. Two additional, consecutive patients with renal cell carcinoma with paraneoplastic leukocytosis also showed elevated serum levels of CXCL8, but not of G-CSF. Nonparametric statistical evaluation showed significantly higher serum concentrations of CXCL8, IL-6, IL-10, monocyte chemoattractant protein 1 (MCP-1), and tumor necrosis factor, but lower interferon gamma (IFN-gamma) and IL-1 alpha, for the 3 renal cell carcinoma cases compared with healthy blood donors.

    CONCLUSIONS: In suspected paraneoplastic leukocytosis, multiplex serum cytokine analyses may facilitate diagnosis and provide an understanding of the mechanisms for the reaction. In the index patient, combined G-CSF and CXCL8 protein expression by renal carcinoma cells was uniquely documented. A rapidly fatal course was detected in all 3 cases, congruent with the concept that autocrine/paracrine growth signaling in renal carcinoma cells may induce an aggressive tumor phenotype. Immune profiling studies could improve our understanding for possible targets when choosing therapies for patients with metastatic renal cell carcinoma.

  • 3695.
    Åström, Maria
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län.
    Welander, Edvard
    Pourlotfi, Arvid
    Abawi, Akram
    Ahlstrand, Erik
    Region Örebro län. Örebro universitet, Institutionen för medicinska vetenskaper.
    Ivarsson, Mikael
    Örebro universitet, Institutionen för hälsovetenskaper.
    Activated interferon signaling in cultured BMSC from myelofibrosis patients: core finding of a proteomic study2018Konferensbidrag (Refereegranskat)
  • 3696.
    Åstrøm, A. N.
    et al.
    Department of Clinical Dentistry, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.
    Gulcan, F.
    Department of Clinical Dentistry, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.
    Ekbäck, Gunnar
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Region Örebro län.
    Ordell, S.
    Dental Commissioning Unit, Östergötland County Council, Linköping University, Linköping, Sweden.
    Long-term healthy lifestyle patterns and tooth loss studied in a Swedish cohort of middle-aged and older people2015Ingår i: International Journal of Dental Hygiene, ISSN 1601-5029, E-ISSN 1601-5037, Vol. 13, nr 4, s. 292-300Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The promotion of a healthy lifestyle has become an issue of public health importance in the context of ageing populations and increasing prevalence of chronic diseases.

    Objective: (i) To estimate changes in use of fluoridated tooth paste, use of tooth picks, smoking and alcohol consumption and (ii) to examine whether experience with incident or prevalent tooth loss predict healthy lifestyle transitions from age 50 to 70.

    Method: In 1992, 6346 individuals born in 1942 agreed to participate in a prospective cohort study and 3585 completed follow-up questionnaires in 1997, 2002, 2007 and 2012. Statistical analyses were conducted by chi-square statistics, Cochran's Q and logistic regression.

    Results: In total, 15.7% and 74.0% reported incident (tooth loss only in 2012) and prevalent tooth loss (tooth loss in 1992 and 2012). Significant differences occurred between the 1992 and 2012 prevalence of using toothpicks (from 48.3% to 69.1%), smoking (from 26.9% to 10.1%) and alcohol consumption (from 41.5% to 50.5%), 29% and 15.6% increased use of toothpicks and alcohol consumption, whereas 15.5% stopped daily smoking. Increased use of fluoridated tooth paste, smoking cessation and failure to increase use of toothpicks was associated with prevalent tooth loss between age 50 and 70.

    Conclusion: This study revealed positive and negative trends in oral health behaviours over a 20-year period in persons aged 50 at baseline. Mixed support was obtained for the assumption that oral health promoting lifestyle transitions follow experience with tooth loss. Older people with tooth loss experience could benefit from targeted counselling aimed at coping with oral diseases.

  • 3697.
    Åstrøm, Anne N.
    et al.
    Department of Clinical Dentistry, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.
    Lie, Stein A.
    Department of Clinical Dentistry, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.
    Ekbäck, Gunnar
    Örebro universitet, Institutionen för hälsovetenskaper. Region Örebro län.
    Gülcan, Ferda
    Department of Clinical Dentistry, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.
    Ordell, Sven
    Dental Commissioning Unit, Östergötland County Council, Linköping University, Linköping, Sweden.
    Self-reported dry mouth among ageing people: a longitudinal, cross-national study2019Ingår i: European Journal of Oral Sciences, ISSN 0909-8836, E-ISSN 1600-0722, Vol. 127, nr 2, s. 130-138Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Focusing on Swedish and Norwegian cohorts of community-dwelling older adults between age 65 and 70, this study aimed to identify predictors of the prevalence and incident cases of daytime and night-time xerostomia. It was hypothesized that the prevalence increases with increasing age and is higher in women than in men and that the prevalence of persistent xerostomia and the 5-yr-incident cases are higher in people with consistent use of medication and need for health care. Of the Norwegian participants who completed the 2007 survey (age 65 yr), 70% (n = 2,947) participated in 2012. Individuals participating in both 2007 and 2012 constituted the Swedish panel (80%, n = 4,862). The prevalence of xerostomia was higher in women than in men and increased from age 65 to age 70, most markedly in the Swedish cohort. The risk of persistent xerostomia was greatest for participants with consistent use of medication (OR = 1.3) and contact with a physician (OR = 2.3). The risk of incident cases of xerostomia during daytime was greatest for participants with recent and consistent use of medication and recent contact with a physician. Dental professionals should identify patients with xerostomia, emphasize early prevention, and alleviate oral symptoms in collaboration with physicians.

  • 3698.
    Åstrøm, Anne Nordrehaug
    et al.
    Department of Clinical Dentistry, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.
    Ekbäck, Gunnar
    Örebro universitet, Institutionen för hälsovetenskaper. Region Örebro län.
    Ordell, Sven
    Dental Commissioning Unit, Östergötland County Council, Linköping University, Linköping, Sweden.
    Gulcan, Ferda
    Department of Clinical Dentistry, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.
    Changes in oral health-related quality of life (OHRQoL) related to long-term utilization of dental care among older people2018Ingår i: Acta Odontologica Scandinavica, ISSN 0001-6357, E-ISSN 1502-3850, Vol. 76, nr 8, s. 559-566Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To examine whether long-term utilization of dental care, treatment with fillings and crowns and persistent tooth loss between age 50 and 65 years associate with subsequent changes in OHRQoL from age 65 to 70 years.

    METHOD: In 1992, a census of 50-year-olds received invitation to participate in a questionnaire survey. Of 6346 respondents, 3585 completed follow-ups in 1997, 2002, 2007 and 2012. OHRQoL was measured using the Oral Impacts on Daily Performances (OIDP) inventory.

    RESULTS: Around 70.4%, 11.2% and 18.4% confirmed respectively, no change, worsening, and improvement in OIDP scores between age 65 and 70 years. Compared to those being permanent non-routine dental attenders, ORs of improving and worsening of OIDP were respectively, 0.4 and 0.6 if being a permanent routine dental attender. ORs for improving OIDP was 1.6 if reporting persistent specialist attendance and 2.5 if having received crowns and fillings. Participants with permanent tooth loss were most likely to both worsen and improve OIDP.

    CONCLUSION: Long-term routine dental attendance and permanent tooth loss occurred as predictors simultaneously for improvement and worsening of OIDP. Accumulation of advantages and disadvantages throughout the life-course increases and decreases the probability of improvement and worsening in OIDP among older people in Sweden.

  • 3699.
    Öbrink, Emma
    et al.
    Department of Anaesthesia and Intensive Care, Institution for Clinical Science, Karolinska Institutet, Danderyds Hospital, Stockholm, Sweden.
    Jildenstål, Pether
    Region Örebro län. Department of Anaesthesiology and Intensive Care.
    Oddby, Eva
    Department of Anaesthesia and Intensive Care, Institution for Clinical Science, Karolinska Institutet, Danderyds Hospital, Stockholm, Sweden.
    Jakobsson, Jan G.
    Department of Anaesthesia and Intensive Care, Institution for Clinical Science, Karolinska Institutet, Danderyds Hospital, Stockholm, Sweden.
    Post-operative nausea and vomiting: Update on predicting the probability and ways to minimize its occurrence, with focus on ambulatory surgery2015Ingår i: International Journal of Surgery, ISSN 1743-9191, E-ISSN 1743-9159, Vol. 15, s. 100-106Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Postoperative nausea and vomiting "the little big problem" after surgery/anaesthesia is still a common side-effect compromising quality of care, delaying discharge and resumption of activities of daily living. A huge number of studies have been conducted in order to identify risk factors, preventive and therapeutic strategies. The Apfel risk score and a risk based multi-modal PONV prophylaxis is advocated by evidence based guidelines as standards of care but is not always followed. Tailored anaesthesia and pain management avoiding too liberal dosing of anaesthetics and opioid analgesics is also essential in order to reduce risk. Thus multi-modal opioid sparing analgesia and a risk based PONV prophylaxis should be provided in order to minimise the occurrence. There is however still no way to guarantee an individual patient that he or she should not experience any PONV. Further studies are needed trying to identify risk factors and ways to tailor the individual patient prevention/therapy are warranted.

    The present paper provides a review around prediction, factors influencing the occurrence and the management of PONV with a focus on the ambulatory surgical patient.

  • 3700.
    Örtegren, Joakim
    et al.
    Section of Urology, Department of Surgery, Växjö County Hospital, Växjö, Sweden; epartment of Urology, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Holmberg, Jan Tage
    Section of Urology, Department of Surgery, Växjö County Hospital, Växjö, Sweden; Section of Urology, Department of Surgery, Ljungby Hospital, Ljungby, Sweden.
    Lekås, Edvard
    Section of Urology, Department of Surgery, Växjö County Hospital, Växjö, Sweden.
    Mana, Sabah
    Section of Urology, Department of Surgery, Ljungby Hospital, Ljungby, Sweden.
    Mårtensson, Stig
    Section of Urology, Department of Surgery, Växjö County Hospital, Växjö, Sweden; Section of Urology, Department of Surgery, Ljungby Hospital, Ljungby, Sweden.
    Richthoff, Jonas
    Section of Urology, Department of Surgery, Ljungby Hospital, Ljungby, Sweden.
    Sundqvist, Pernilla
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Urology.
    Kjölhede, Henrik
    Department of Urology, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Region Västra Götaland, Department of Urology , Sahlgrenska University Hospital, Gothenburg, Sweden .
    Bratt, Ola
    Department of Urology, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Region Västra Götaland, Department of Urology , Sahlgrenska University Hospital, Gothenburg, Sweden .
    Liedberg, Fredrik
    Department of Translational Medicine, Lund University , Malmö, Sweden; Department of Urology, Skåne University Hospital, Malmö, Sweden.
    A randomised trial comparing two protocols for transrectal prostate repeat biopsy: six lateral posterior plus six anterior cores versus a standard posterior 12-core biopsy2019Ingår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 53, nr 4, s. 217-221Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To test the hypothesis that a combination of 6 posterior and 6 anterior cores detects more cancer than 12 posterior cores at a repeat transrectal prostate biopsy in men who have had one previous benign systematic biopsy.

    Patients and methods: Three hundred and forty men with persistently raised serum PSA were randomly allocated 1:1 to either a standard 12-core biopsy (12 cores from the lateral peripheral zone through a side-fire biopsy canal) or an experimental 12-core biopsy protocol with 6 anterior cores through an end-fire biopsy canal and 6 cores from the lateral peripheral zone through a side-fire biopsy canal. All biopsies were obtained transrectally with ultrasound guidance. The primary endpoint was cancer detection. Secondary endpoints were detection of ISUP Grade Groups/Gleason Grade Group ≥2 cancer, total biopsy cancer length and complications leading to medical intervention.

    Results: Prostate cancer was detected in 42/168 men (25%) in the experimental biopsy group and in 36/172 (21%) in the standard biopsy group (p = 0.44). The corresponding proportions for Gleason score ≥7 were 12% and 7% (p = 0.14). Median total cancer length was 4 (inter quartile range [IQR] = 1.5 - 6) mm in the end-fire group and 3 (IQR = 1.3 - 7) mm in the side-fire group. Ten men in the end-fire group and three in the side-fire group had a medical intervention for biopsy-related complications (p = 0.05).

    Conclusion: The biopsy protocol that included six end-fire anterior cores did not detect more cancer and was associated with more complications.

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