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  • 1
    In: Journal of Antimicrobial Chemotherapy, Oxford University Press (OUP), Vol. 75, No. 11 ( 2020-11-01), p. 3344-3348
    Kurzfassung: Integrase strand transfer inhibitors (INSTIs) are increasingly used in patients living with HIV due to their safety, effectiveness and high genetic barrier. However, an association with weight gain has recently been suggested and several cases of diabetes mellitus have been reported with raltegravir and dolutegravir. The long-time metabolic impact of these recent molecules remains unclear. Objectives To assess if an INSTI as a third agent is statistically associated with new-onset diabetes mellitus compared with an NNRTI or a PI. Patients and methods Patients undergoing first-line combined ART (cART) without diabetes at baseline were retrospectively included from the Dat’AIDS French cohort study (ClinicalTrials.gov NCT02898987). Incident diabetes mellitus was defined as a notification of new diabetes in the medical history, a glycated haemoglobin (HbA1c) level superior to 7.5% or the start of a diabetes therapy following the initiation of ART. Results From 2009 to 2017, 19 462 patients were included, among which 265 cases of diabetes mellitus occurred. Multivariate and survival analyses did not highlight an increase in new-onset diabetes in patients undergoing cART with an INSTI as a third agent compared with an NNRTI or a PI. BMI & gt;30 kg/m2, age & gt;37 years old (in survival analysis), black race or Hispanic ethnicity, arterial hypertension and AIDS were associated with a higher proportion of incident diabetes. Conclusions INSTIs were not statistically associated with new-onset diabetes. However, clinicians should remain aware of this possible metabolic comorbidity, particularly in patients with a high BMI and older patients.
    Materialart: Online-Ressource
    ISSN: 0305-7453 , 1460-2091
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2020
    ZDB Id: 1467478-6
    SSG: 15,3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    In: Journal of Antimicrobial Chemotherapy, Oxford University Press (OUP), Vol. 77, No. 1 ( 2021-12-24), p. 196-204
    Kurzfassung: Maintenance ART with dolutegravir-based dual regimens have proved their efficacy among HIV-1-infected subjects in randomized trials. However, real-life data are scarce, with limited populations and follow-up. Objectives We assessed virological failure (VF) and resistance-associated mutations (RAMs) on dolutegravir maintenance regimens in combination with rilpivirine or with lamivudine or emtricitabine (xTC) and analysed the factors associated with VF. Methods Between 2014 and 2018, all HIV-1-infected adults included in the Dat’AIDS cohort and starting dolutegravir/rilpivirine or dolutegravir/xTC as a maintenance dolutegravir-based dual regimen were selected. VF was defined as two consecutive HIV RNA values & gt;50 copies/mL or a single value & gt;400 copies/mL. We compared cumulative genotypes before initiation of a maintenance dolutegravir-based dual regimen with genotype at VF. Results We analysed 1374 subjects (799 on dolutegravir/rilpivirine and 575 on dolutegravir/xTC) with a median follow-up of 20 months (IQR = 11–31) and 19 months (IQR = 11–31), respectively. VF occurred in 3.8% (n = 30) of dolutegravir/rilpivirine subjects and 2.6% (n = 15) of dolutegravir/xTC subjects. Among subjects receiving dolutegravir/rilpivirine, two genotypes harboured emerging RAMs at VF: E138K on NNRTI (n = 1); and E138K+K101E on NNRTI and N155H on INSTI (n = 1). Among subjects receiving dolutegravir/xTC, no new RAM was detected. The only predictive factor of VF on dolutegravir/rilpivirine was the history of failure on an NNRTI-based regimen (adjusted HR = 2.97, 95% CI = 1.28–6.93). No factor was associated with VF on dolutegravir/xTC. Conclusions In this large real-life cohort, dolutegravir/rilpivirine and dolutegravir/xTC sustained virological suppression and were associated with a low rate of VF and RAM emergence. Careful virological screening is essential before switching to dolutegravir/rilpivirine in virologically suppressed patients with a history of NNRTI therapy.
    Materialart: Online-Ressource
    ISSN: 0305-7453 , 1460-2091
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2021
    ZDB Id: 1467478-6
    SSG: 15,3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
    In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 73, No. 9 ( 2021-11-02), p. e3266-e3274
    Kurzfassung: The arrival of highly effective, well-tolerated, direct-acting antiviral agents (DAA) led to a dramatic decrease in hepatitis C virus (HCV) prevalence. Human immunodeficiency virus (HIV)-HCV–coinfected patients are deemed a priority population for HCV elimination, while a rise in recently acquired HCV infections in men who have sex with men (MSM) has been described. We describe the variations in HIV-HCV epidemiology in the French Dat’AIDS cohort. Methods This was a retrospective analysis of a prospective cohort of persons living with HIV (PLWH) from 2012 to 2018. We determined HCV prevalence, HCV incidence, proportion of viremic patients, treatment uptake, and mortality rate in the full cohort and by HIV risk factors. Results From 2012 to 2018, 50 861 PLWH with a known HCV status were followed up. During the period, HCV prevalence decreased from 15.4% to 13.5%. HCV prevalence among new HIV cases increased from 1.9% to 3.5% in MSM but remained stable in other groups. Recently acquired HCV incidence increased from 0.36/100 person-years to 1.25/100 person-years in MSM. The proportion of viremic patients decreased from 67.0% to 8.9%. MSM became the first group of viremic patients in 2018 (37.9%). Recently acquired hepatitis represented 59.2% of viremic MSM in 2018. DAA treatment uptake increased from 11.4% to 61.5%. More treatments were initiated in MSM in 2018 (41.2%) than in intravenous drug users (35.6%). In MSM, treatment at the acute phase represented 30.0% of treatments in 2018. Conclusions A major shift in HCV epidemiology was observed in PLWH in France from 2012 to 2018, leading to a unique situation in which the major group of HCV transmission in 2018 was MSM. Clinical Trials Registration. NCT02898987.
    Materialart: Online-Ressource
    ISSN: 1058-4838 , 1537-6591
    RVK:
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2021
    ZDB Id: 2002229-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
    In: BJS Open, Oxford University Press (OUP), Vol. 6, No. 1 ( 2022-01-06)
    Kurzfassung: Postoperative acute kidney injury (AKI) is a common complication of major gastrointestinal surgery with an impact on short- and long-term survival. No validated system for risk stratification exists for this patient group. This study aimed to validate externally a prognostic model for AKI after major gastrointestinal surgery in two multicentre cohort studies. Methods The Outcomes After Kidney injury in Surgery (OAKS) prognostic model was developed to predict risk of AKI in the 7 days after surgery using six routine datapoints (age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker). Validation was performed within two independent cohorts: a prospective multicentre, international study (‘IMAGINE’) of patients undergoing elective colorectal surgery (2018); and a retrospective regional cohort study (‘Tayside’) in major abdominal surgery (2011–2015). Multivariable logistic regression was used to predict risk of AKI, with multiple imputation used to account for data missing at random. Prognostic accuracy was assessed for patients at high risk (greater than 20 per cent) of postoperative AKI. Results In the validation cohorts, 12.9 per cent of patients (661 of 5106) in IMAGINE and 14.7 per cent (106 of 719 patients) in Tayside developed 7-day postoperative AKI. Using the OAKS model, 558 patients (9.6 per cent) were classified as high risk. Less than 10 per cent of patients classified as low-risk developed AKI in either cohort (negative predictive value greater than 0.9). Upon external validation, the OAKS model retained an area under the receiver operating characteristic (AUC) curve of range 0.655–0.681 (Tayside 95 per cent c.i. 0.596 to 0.714; IMAGINE 95 per cent c.i. 0.659 to 0.703), sensitivity values range 0.323–0.352 (IMAGINE 95 per cent c.i. 0.281 to 0.368; Tayside 95 per cent c.i. 0.253 to 0.461), and specificity range 0.881–0.890 (Tayside 95 per cent c.i. 0.853 to 0.905; IMAGINE 95 per cent c.i. 0.881 to 0.899). Conclusion The OAKS prognostic model can identify patients who are not at high risk of postoperative AKI after gastrointestinal surgery with high specificity. Presented to Association of Surgeons in Training (ASiT) International Conference 2018 (Edinburgh, UK), European Society of Coloproctology (ESCP) International Conference 2018 (Nice, France), SARS (Society of Academic and Research Surgery) 2020 (Virtual, UK).
    Materialart: Online-Ressource
    ISSN: 2474-9842
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2022
    ZDB Id: 2902033-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
    Online-Ressource
    Online-Ressource
    Springer Science and Business Media LLC ; 2016
    In:  Intensive Care Medicine Experimental Vol. 4, No. S1 ( 2016-9)
    In: Intensive Care Medicine Experimental, Springer Science and Business Media LLC, Vol. 4, No. S1 ( 2016-9)
    Materialart: Online-Ressource
    ISSN: 2197-425X
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2016
    ZDB Id: 2740385-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
    In: BJS Open, Oxford University Press (OUP), Vol. 5, No. 6 ( 2021-11-09)
    Kurzfassung: The intermediate-term impact of acute kidney injury (AKI) in patients after major gastrointestinal and liver surgery has not been well characterized. This study aimed to evaluate the 1-year mortality rate and renal outcomes associated with postoperative AKI in a national prospective cohort. Methods This prospective multicentre, observational cohort with 1-year postoperative follow-up included adults undergoing major gastrointestinal and liver surgery across the UK and Ireland between 23 September and 18 November 2015. AKI was defined according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. The primary outcome was death at 1-year after surgery, and the secondary outcome was Major Adverse Kidney Events (MAKE-365). Cox proportionate and multilevel logistic regression were used to account for case mix. Results Of 5745 patients across 173 centres, 1-year follow-up data was completed for 3504 patients (62.2 per cent, 126 centres), with attrition largely explained by centre non-participation (63.1 per cent). Some 13.6 per cent (475 of 3504) patients developed AKI by 7 days after surgery (stage 1: 9.2 per cent; stage 2/3: 4.3 per cent). At 1 year, 10.8 per cent (378 patients) experienced a MAKE-365 endpoint (303 patients had died, 61 had renal replacement therapy and 78 had renal dysfunction). Patients who experienced AKI by 7 days after surgery had a higher hazard of death at 1 year for KDIGO stage 1 (hazard ratio 1.50 (95 per cent c.i. 1.08 to 2.08), P = 0.016) and KDIGO stage 2/3 (hazard ratio 2.96 (95 per cent c.i. 2.02 to 4.33), P & lt; 0.001). Both KDIGO stage 1 (odds ratio 2.09 (95 per cent c.i. 1.50 to 2.92), P & lt; 0.001) and stage 2/3 (odds ratio 9.26 (95 per cent c.i. 6.31 to 13.59), P & lt; 0.001) AKI were independently associated with MAKE-365. Conclusion AKI events within 7 days after gastrointestinal or liver surgery are associated with significantly worse survival and renal outcomes at 1 year.
    Materialart: Online-Ressource
    ISSN: 2474-9842
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2021
    ZDB Id: 2902033-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 7
    In: The Lancet Digital Health, Elsevier BV, Vol. 4, No. 7 ( 2022-07), p. e520-e531
    Materialart: Online-Ressource
    ISSN: 2589-7500
    Sprache: Englisch
    Verlag: Elsevier BV
    Publikationsdatum: 2022
    ZDB Id: 2972368-1
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 8
    Online-Ressource
    Online-Ressource
    Elsevier BV ; 2011
    In:  Clinical Microbiology and Infection Vol. 17, No. 1 ( 2011-01), p. 102-103
    In: Clinical Microbiology and Infection, Elsevier BV, Vol. 17, No. 1 ( 2011-01), p. 102-103
    Materialart: Online-Ressource
    ISSN: 1198-743X
    Sprache: Englisch
    Verlag: Elsevier BV
    Publikationsdatum: 2011
    ZDB Id: 2020034-1
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 9
    In: British Journal of Surgery, Oxford University Press (OUP), Vol. 108, No. 12 ( 2021-12-01), p. 1448-1464
    Kurzfassung: This study aimed to determine the impact of pulmonary complications on death after surgery both before and during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Methods This was a patient-level, comparative analysis of two, international prospective cohort studies: one before the pandemic (January–October 2019) and the second during the SARS-CoV-2 pandemic (local emergence of COVID-19 up to 19 April 2020). Both included patients undergoing elective resection of an intra-abdominal cancer with curative intent across five surgical oncology disciplines. Patient selection and rates of 30-day postoperative pulmonary complications were compared. The primary outcome was 30-day postoperative mortality. Mediation analysis using a natural-effects model was used to estimate the proportion of deaths during the pandemic attributable to SARS-CoV-2 infection. Results This study included 7402 patients from 50 countries; 3031 (40.9 per cent) underwent surgery before and 4371 (59.1 per cent) during the pandemic. Overall, 4.3 per cent (187 of 4371) developed postoperative SARS-CoV-2 in the pandemic cohort. The pulmonary complication rate was similar (7.1 per cent (216 of 3031) versus 6.3 per cent (274 of 4371); P = 0.158) but the mortality rate was significantly higher (0.7 per cent (20 of 3031) versus 2.0 per cent (87 of 4371); P  & lt; 0.001) among patients who had surgery during the pandemic. The adjusted odds of death were higher during than before the pandemic (odds ratio (OR) 2.72, 95 per cent c.i. 1.58 to 4.67; P  & lt; 0.001). In mediation analysis, 54.8 per cent of excess postoperative deaths during the pandemic were estimated to be attributable to SARS-CoV-2 (OR 1.73, 1.40 to 2.13; P  & lt; 0.001). Conclusion Although providers may have selected patients with a lower risk profile for surgery during the pandemic, this did not mitigate the likelihood of death through SARS-CoV-2 infection. Care providers must act urgently to protect surgical patients from SARS-CoV-2 infection.
    Materialart: Online-Ressource
    ISSN: 0007-1323 , 1365-2168
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2021
    ZDB Id: 2006309-X
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 10
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 113, No. 21 ( 2016-05-24)
    Kurzfassung: We examined whether persistence of epigenetic DNA methylation (DNA-me) alterations at specific loci over two different time points in people with diabetes are associated with metabolic memory, the prolonged beneficial effects of intensive vs. conventional therapy during the Diabetes Control and Complications Trial (DCCT) on the progression of microvascular outcomes in the long-term follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) Study. We compared DNA-me profiles in genomic DNA of whole blood (WB) isolated at EDIC Study baseline from 32 cases (DCCT conventional therapy group subjects showing retinopathy or albuminuria progression by EDIC Study year 10) vs. 31 controls (DCCT intensive therapy group subjects without complication progression by EDIC year 10). DNA-me was also profiled in blood monocytes (Monos) of the same patients obtained during EDIC Study years 16–17. In WB, 153 loci depicted hypomethylation, and 225 depicted hypermethylation, whereas in Monos, 155 hypomethylated loci and 247 hypermethylated loci were found (fold change ≥1.3; P 〈 0.005; cases vs. controls). Twelve annotated differentially methylated loci were common in both WB and Monos, including thioredoxin-interacting protein ( TXNIP ), known to be associated with hyperglycemia and related complications. A set of differentially methylated loci depicted similar trends of associations with prior HbA1c in both WB and Monos. In vitro, high glucose induced similar persistent hypomethylation at TXNIP in cultured THP1 Monos. These results show that DNA-me differences during the DCCT persist at certain loci associated with glycemia for several years during the EDIC Study and support an epigenetic explanation for metabolic memory.
    Materialart: Online-Ressource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: Proceedings of the National Academy of Sciences
    Publikationsdatum: 2016
    ZDB Id: 209104-5
    ZDB Id: 1461794-8
    SSG: 11
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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