Publications by authors named "E Bonora"

396 Publications

Time series of diabetes attributable mortality from 2008 to 2017.

J Endocrinol Invest 2021 Sep 30. Epub 2021 Sep 30.

Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Hospital Trust of Verona, Università di Verona, Piazzale Stefani, 1, 37126, Verona, Italy.

Purpose: Diabetes is a growing health problem. The aim of this study was to capture time trends in mortality associated with diabetes.

Methods: The mortality database of the Veneto region (Italy) includes both the underlying causes of death, and all the diseases mentioned in the death certificate. The annual percent change (APC) in age-standardized rates from 2008 to 2017 was computed by the Joinpoint Regression Program.

Results: Overall 453,972 deaths (56,074 with mention of diabetes) were observed among subjects aged ≥ 40 years. Mortality rates declined for diabetes as the underlying cause of death and from diabetes-related circulatory diseases. The latter declined especially in females - 4.4 (CI 95% - 5.3/- 3.4), while in males the APC was - 2.8 (CI 95% - 4.0/- 1.6).

Conclusion: We observed a significant reduction in mortality during the period 2008-2017 in diabetes either as underlying cause of death or when all mentions of diabetes in the death certificate were considered.
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http://dx.doi.org/10.1007/s40618-021-01549-wDOI Listing
September 2021

Gastrointestinal Tolerability of Once-Weekly Dulaglutide 3.0 mg and 4.5 mg: A Post Hoc Analysis of the Incidence and Prevalence of Nausea, Vomiting, and Diarrhea in AWARD-11.

Diabetes Ther 2021 Oct 12;12(10):2783-2794. Epub 2021 Sep 12.

Eli Lilly and Company, Indianapolis, IN, 46285, USA.

Background: Gastrointestinal (GI) events are the most frequent treatment-emergent adverse events (TEAEs) reported for glucagon-like peptide-1 receptor agonist therapies. This post hoc analysis of the AWARD-11 phase 3 trial assessed the GI tolerability of dulaglutide at once-weekly doses of 1.5, 3.0, and 4.5 mg.

Methods: The AWARD-11 trial randomized patients to once-weekly dulaglutide 1.5 mg (n = 612), 3.0 mg (n = 616), or 4.5 mg (n = 614) for 52 weeks. Patients started on dulaglutide 0.75 mg for 4 weeks before escalating stepwise every 4 weeks until the final randomized dose was reached. This study analyzes the onsets, incidences, prevalences, and severities of nausea, vomiting, and diarrhea events reported through 52 weeks.

Results: The highest incidences of nausea (≤ 8%), vomiting (≤ 2%), and diarrhea (≤ 4%) were primarily observed soon after the initiation of dulaglutide treatment at 0.75 mg. Incidence then declined throughout the remainder of the study, even with dose escalation to 1.5, 3.0, and 4.5 mg. Most of these GI TEAEs were mild to moderate in severity, with severe nausea, vomiting, or diarrhea events occurring in ≤ 0.6% of patients. Treatment discontinuation due to nausea was low across treatment groups (≤ 1.5%).

Conclusions: The tolerability profiles of dulaglutide 3.0 mg and 4.5 mg were consistent with that of the 1.5-mg dose. Patients experiencing GI events were most likely to do so within 2 weeks of treatment initiation, and few patients experienced a new GI event after escalating to the 3.0-mg or 4.5-mg dose. Severe events were infrequent, and when they did occur, no relationship with dose at time of event was observed. Supplementary file1 (MP4 33880 kb).
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http://dx.doi.org/10.1007/s13300-021-01140-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8479017PMC
October 2021

Glycaemic efficacy of an expanded dose range of dulaglutide according to baseline glycated haemoglobin (HbA1c) subgroup: Post hoc analysis of AWARD-11.

Diabetes Obes Metab 2021 Aug 31. Epub 2021 Aug 31.

Eli Lilly and Company, Indianapolis, Indiana, USA.

The AWARD-11 trial demonstrated the safety and efficacy of dulaglutide 3.0 and 4.5 mg compared to dulaglutide 1.5 mg in patients with type 2 diabetes inadequately controlled with metformin. This post hoc analysis examined the change from baseline in glycated haemoglobin (HbA1c) and proportions of patients achieving HbA1c <7% at weeks 36 and 52 with dulaglutide 1.5 mg, 3.0 mg or 4.5 mg across clinically relevant baseline HbA1c subgroups (<8%; 8.0% to < 9.0%; 9.0% to < 10%; and ≥ 10%). Mean reductions in HbA1c were observed across all baseline HbA1c subgroups at 36 weeks (range of HbA1c change: 1.5 mg: -1.0% to -2.2%; 3.0 mg: -1.2% to -2.5%; and 4.5 mg: -1.2% to -3.2%). More patients randomized to 3.0 mg or 4.5 mg (vs. 1.5 mg) achieved HbA1c <7% at 36 weeks regardless of baseline HbA1c; the difference in proportions was greater at higher baseline HbA1c (P-interaction = 0.096). Similar patterns in glycaemic improvement and proportions achieving HbA1c <7% were observed at 52 weeks. Hypoglycaemia and gastrointestinal adverse events were similar among the HbA1c subgroups. Glycaemic control was improved with dulaglutide dose escalation from 1.5 mg to 3.0 mg or 4.5 mg across baseline HbA1c subgroups (<8%; 8.0% to < 9.0%; 9.0% to < 10%; and ≥ 10%).
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http://dx.doi.org/10.1111/dom.14533DOI Listing
August 2021

Hamartoma Tumor Syndrome: Skin Manifestations and Insights Into Their Molecular Pathogenesis.

Front Med (Lausanne) 2021 27;8:688105. Epub 2021 Jul 27.

Department of Medical and Surgical Sciences, Center for Studies on Hereditary Cancer, University of Bologna, Bologna, Italy.

Germline pathogenic variants cause a spectrum of disorders collectively labeled Hamartoma Tumor Syndrome (PHTS) and featured by hamartomas, developmental anomalies and increased cancer risk. Studies on experimental models provided evidence that is a "haploinsufficient" tumor-suppressor gene, however, mechanisms involved in the pathogenesis of clinical manifestations in PHTS patients remain elusive. Beyond analyzing clinical and molecular features of a series of 20 Italian PHTS patients, we performed molecular investigations to explore the mechanisms involved in the pathogenesis of -associated manifestations, with special focus on mucocutaneous manifestations. Typical mucocutaneous features were present in all patients assessed, confirming that these are the most important clue to the diagnosis. The most frequent were papules located in the trunk or extremities (73.7%), oral mucosa papules (68.4%), acral/palmoplantar keratosis and facial papules (both 57.9%), according with literature data. Molecular analyses on one trichilemmoma suggested that the wild-type allele was retained and expressed, reinforcing the evidence that does not require a second somatic hit to initiate pathogenic processes. Unexpectedly, one patient also displayed a cutaneous phenotype consistent with atypical mole/melanoma syndrome; no variants were detected in known melanoma genes, but Whole Exome Sequencing showed the rare truncating variant c.495G>A in the gene that might have cooperated with -haploinsufficiency to generate such phenotype. Our findings confirm the reproducibility of known PHTS manifestations in real-world practice, highlighting the role of mucocutaneous manifestations in facilitating prompt diagnosis of the syndrome, and provide some insights into the pathogenic process induced by alterations, which may contribute to its understanding.
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http://dx.doi.org/10.3389/fmed.2021.688105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353102PMC
July 2021

The continuity of effect of schizophrenia polygenic risk score and patterns of cannabis use on transdiagnostic symptom dimensions at first-episode psychosis: findings from the EU-GEI study.

Transl Psychiatry 2021 08 10;11(1):423. Epub 2021 Aug 10.

Department of Psychiatry, Early Psychosis Section, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands.

Diagnostic categories do not completely reflect the heterogeneous expression of psychosis. Using data from the EU-GEI study, we evaluated the impact of schizophrenia polygenic risk score (SZ-PRS) and patterns of cannabis use on the transdiagnostic expression of psychosis. We analysed first-episode psychosis patients (FEP) and controls, generating transdiagnostic dimensions of psychotic symptoms and experiences using item response bi-factor modelling. Linear regression was used to test the associations between these dimensions and SZ-PRS, as well as the combined effect of SZ-PRS and cannabis use on the dimensions of positive psychotic symptoms and experiences. We found associations between SZ-PRS and (1) both negative (B = 0.18; 95%CI 0.03-0.33) and positive (B = 0.19; 95%CI 0.03-0.35) symptom dimensions in 617 FEP patients, regardless of their categorical diagnosis; and (2) all the psychotic experience dimensions in 979 controls. We did not observe associations between SZ-PRS and the general and affective dimensions in FEP. Daily and current cannabis use were associated with the positive dimensions in FEP (B = 0.31; 95%CI 0.11-0.52) and in controls (B = 0.26; 95%CI 0.06-0.46), over and above SZ-PRS. We provide evidence that genetic liability to schizophrenia and cannabis use map onto transdiagnostic symptom dimensions, supporting the validity and utility of the dimensional representation of psychosis. In our sample, genetic liability to schizophrenia correlated with more severe psychosis presentation, and cannabis use conferred risk to positive symptomatology beyond the genetic risk. Our findings support the hypothesis that psychotic experiences in the general population have similar genetic substrates as clinical disorders.
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http://dx.doi.org/10.1038/s41398-021-01526-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355107PMC
August 2021
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