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Article ; Online: Clinical Outcomes of Renin-Angiotensin Aldosterone Blockade in Patients with Advanced Chronic Kidney Disease: A Systematic Review and Meta-Analysis.

Vendeville, Nicolas / Lepage, Marc-Antoine / Festa, M Carolina / Mavrakanas, Thomas A

2024

Abstract: Background: The cardiovascular and renal benefits of renin-angiotensin aldosterone system (RAAS) blockade are not well-established in patients with advanced CKD. We conducted a systematic review and meta-analysis to identify potential risks and benefits ...

Abstract	Background: The cardiovascular and renal benefits of renin-angiotensin aldosterone system (RAAS) blockade are not well-established in patients with advanced CKD. We conducted a systematic review and meta-analysis to identify potential risks and benefits from RAAS blockade in patients with CKD stage 4-5. Methods: A Medline search from inception to November 2022 was conducted to identify randomized controlled trials (RCTs) in patients with CKD stage 4-5 (estimated GFR ≤ 30 mL/min/1.73m Results: Nine RCTs (1,150 patients) were included. In RCTs, RAAS blockade was associated with a significant reduction in progression to ESKD: RR 0.84 (95% confidence interval [CI] 0.74 - 0.96; p = 0.01). There was no benefit from RAAS blockade on all-cause mortality or MACE: RR 1.02 (95% CI 0.63 - 1.65; p = 0.93) and RR 0.87 (95% CI 0.49- 1.57; p = 0.65), respectively. Conclusions: RAAS blockade may be considered in selected patients with CKD stage 4-5 to delay progression to ESKD.
Language	English
Publishing date	2024-03-06
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	632813-1
ISSN	1916-7075 ; 0828-282X
ISSN (online)	1916-7075
ISSN	0828-282X
DOI	10.1016/j.cjca.2024.02.027
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Article: Volume Status Assessment by Lung Ultrasound in End-Stage Kidney Disease: A Systematic Review.

Kharat, Aileen / Tallaa, Faissal / Lepage, Marc-Antoine / Trinh, Emilie / Suri, Rita S / Mavrakanas, Thomas A

Canadian journal of kidney health and disease

2023 Volume 10, Page(s) 20543581231217853

Abstract: Purpose of review: Lung ultrasound is a noninvasive bedside technique that can accurately assess pulmonary congestion by evaluating extravascular lung water. This technique is expanding and is easily available. Our primary outcome was to compare the ... ...

Abstract	Purpose of review: Lung ultrasound is a noninvasive bedside technique that can accurately assess pulmonary congestion by evaluating extravascular lung water. This technique is expanding and is easily available. Our primary outcome was to compare the efficacy of volume status assessment by lung ultrasound with clinical evaluation, echocardiography, bioimpedance, or biomarkers. The secondary outcomes were all-cause mortality and cardiovascular events. Sources of information: We conducted a MEDLINE literature search for observational and randomized studies with lung ultrasound in patients on maintenance dialysis. Methods: From a total of 2363 articles, we included 28 studies (25 observational and 3 randomized). The correlation coefficients were pooled for each variable of interest using the generic inverse variance method with a random effects model. Among the clinical parameters, New York Heart Association Functional Classification of Heart Failure status and lung auscultation showed the highest correlation with the number of B-lines on ultrasound, with a pooled Key findings: Lung ultrasound may be considered for the identification of patients with subclinical volume overload. Trials did not show differences in clinically important outcomes. The number of studies was small and many were of suboptimal quality. Limitations: The included studies were heterogeneous and of relatively limited quality.
Language	English
Publishing date	2023-12-25
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2765462-X
ISSN	2054-3581
ISSN	2054-3581
DOI	10.1177/20543581231217853
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Article ; Online: Safety and effectiveness concerns of lopinavir/ritonavir in COVID-19 affected patients: a retrospective series.

Lepage, Marc-Antoine / Rozza, Nicholas / Kremer, Richard / Grunbaum, Ami

Clinical toxicology (Philadelphia, Pa.)

2021 Volume 59, Issue 7, Page(s) 644–647

Abstract: ... 19) despite minimal experience in this markedly different population and an in-vitro derived EC50 ...

Abstract	Context: Originally developed for treatment of human immunodeficiency virus (HIV), the antiviral combination lopinavir/ritonavir (LPV/r) is being repurposed for treating the novel coronavirus disease (COVID-19) despite minimal experience in this markedly different population and an in-vitro derived EC50 against SARS-CoV-2 several hundred-fold greater than for HIV. We present a case series including a case of severe hyponatremia and a 32-fold overdose raising safety and effectiveness concerns in COVID-19 patients. Methods: We measured LPV trough concentrations in 12 patients and reviewed their clinical charts for side effects known to occur in HIV patients. Findings: Compared to established LPV trough concentrations in HIV patients, concentrations in COVID-19 patients were 3-fold greater (19.37 ± 10.12 mcg/mL versus 6.25 mcg/mL). In addition, cholestasis and dyslipidemia toxicity thresholds were exceeded in 12/12 and 11/12 patients respectively. No patients achieved the presumed therapeutic concentration. Side effects included gastrointestinal symptoms (5/12), electrolyte imbalances (4/12), liver enzyme disturbances (5/12) and triglyceride elevations (2/12). Conclusion: No patients reached presumed therapeutic LPV concentrations despite experiencing side effects and exceeding cholestasis and dyslipidemia toxicity thresholds. This raises concerns for the safety and effectiveness of LPV/r. Clinicians should consider closely monitoring for side effects and not necessarily attribute them to COVID-19.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Antiviral Agents/adverse effects ; COVID-19/diagnosis ; COVID-19/drug therapy ; COVID-19/virology ; Drug Combinations ; Drug Monitoring ; Drug Overdose/etiology ; Female ; Host-Pathogen Interactions ; Humans ; Hyponatremia/blood ; Hyponatremia/chemically induced ; Hyponatremia/diagnosis ; Lopinavir/adverse effects ; Male ; Middle Aged ; Patient Safety ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Ritonavir/adverse effects ; SARS-CoV-2/drug effects ; SARS-CoV-2/pathogenicity ; Time Factors ; Treatment Outcome
Chemical Substances	Antiviral Agents ; Drug Combinations ; lopinavir-ritonavir drug combination ; Lopinavir (2494G1JF75) ; Ritonavir (O3J8G9O825)
Language	English
Publishing date	2021-03-01
Publishing country	England
Document type	Journal Article
ZDB-ID	204476-6
ISSN	1556-9519 ; 0009-9309 ; 0731-3810 ; 1556-3650
ISSN (online)	1556-9519
ISSN	0009-9309 ; 0731-3810 ; 1556-3650
DOI	10.1080/15563650.2020.1842882
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Article: Geriatric Syndromes in Older Adults Hospitalized with COVID-19 in Montreal, Canada.

Couture, Sandrine / Lepage, Marc-Antoine / Godard-Sebillotte, Claire / Sourial, Nadia / Talbot-Hamon, Catherine / Kremer, Richard / Grunbaum, Ami

Canadian geriatrics journal : CGJ

2022 Volume 25, Issue 3, Page(s) 269–278

Abstract: Background: Older adults are more vulnerable to severe infection and mortality due to COVID-19. They have atypical presentations of the disease without respiratory symptoms, making early diagnosis clinically challenging. We aimed to compare the baseline ...

Abstract	Background: Older adults are more vulnerable to severe infection and mortality due to COVID-19. They have atypical presentations of the disease without respiratory symptoms, making early diagnosis clinically challenging. We aimed to compare the baseline characteristics, presentation, and disease course of older (≥70 yrs & ≥90 yrs) and younger (<70 yrs) patients hospitalized with COVID-19. Methods: Retrospective review of 429 consecutive patients hospitalized at two tertiary care hospitals in Montreal, Canada, with PCR-confirmed COVID-19. Baseline characteristics, presentation, in-hospital complications, and outcomes were recorded. Desegregation by age was performed to compare older versus younger individuals. Additional subgroup analyses were performed amongst patients ≥70 stratifying by sex, living situation, and those presenting with geriatric syndromes compared to those without. Results: Patients ≥70 (n=260) presented less frequently with respiratory symptoms compared to patients <70 (n=169) (52% vs. 32%). 11% of patients ≥70 and 24% of patients ≥90 presented with a geriatric syndrome as their sole symptom compared to 3% of those <70. Older adults were more likely to develop disease complications (including delirium, acute kidney injury, and hypernatremia) and had higher in-hospital mortality (32% vs. 13%). Subgroup analyses revealed heightened vulnerability to complications in older men, those from long-term care, and those with at least one geriatric syndrome upon presentation. Conclusions: Older adults presenting to hospital with COVID-19 often have no respiratory symptoms and can present with only a geriatric syndrome. New geriatric syndromes in older individuals should trigger evaluation for COVID-19 and consideration for early initiation of multidisciplinary care to prevent complications.
Language	English
Publishing date	2022-09-02
Publishing country	Canada
Document type	Journal Article
ISSN	1925-8348
ISSN	1925-8348
DOI	10.5770/cgj.25.579
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Article ; Online: Safety and Efficacy Concerns of Lopinavir/Ritonavir in COVID-19 Affected Patients: A Retrospective Series

Lepage, Marc-Antoine / Rozza, Nicholas / Kremer, Richard / Grunbaum, Ami

Abstract: Context: Originally developed for the treatment of human immunodeficiency virus (HIV), the antiviral combination lopinavir/ritonavir (LPV/r) is being investigated for use against coronavirus disease (COVID-19). We present a case series raising safety and ...

Abstract	Context: Originally developed for the treatment of human immunodeficiency virus (HIV), the antiviral combination lopinavir/ritonavir (LPV/r) is being investigated for use against coronavirus disease (COVID-19). We present a case series raising safety and efficacy concerns in COVID-19 affected patients. Methods: We measured LPV trough concentrations in 12 patients treated at our center and reviewed their clinical charts for side effects known to occur in HIV patients. Results: Compared to established LPV trough concentrations in HIV treated patients, concentrations in COVID-19 affected patients were 3-fold greater (20.64 +/- 10.14 mcg/mL versus 6.25 mcg/mL). In addition, cholestasis and dyslipidemia toxicity thresholds were exceeded in 12/12 and 11/12 patients respectively. No patients achieved the presumed therapeutic concentration. The side effects noted were mainly gastrointestinal symptoms (5/12, 42%), electrolytes imbalances (4/12, 33%), liver enzyme disturbances (5/12, 42%), and triglyceride elevations (2/12, 17%). Conclusion: None of our patients reached presumed therapeutic LPV concentrations despite experiencing side effects and exceeding cholestasis and dyslipidemia toxicity thresholds. This raises concerns for the safety and efficacy of LPV/r. Clinicians should consider closely monitoring for side effects and not necessarily attribute them to COVID-19 itself.
Keywords	covid19
Publisher	MedRxiv; WHO
Document type	Article ; Online
Note	WHO #Covidence: #20153932
DOI	10.1101/2020.07.23.20153932
Database	COVID19

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Article ; Online: Safety and Efficacy Concerns of Lopinavir/Ritonavir in COVID-19 Affected Patients: A Retrospective Series

Lepage, Marc-Antoine / Rozza, Nicholas / Kremer, Richard / Grunbaum, Ami

medRxiv

Abstract	Context: Originally developed for the treatment of human immunodeficiency virus (HIV), the antiviral combination lopinavir/ritonavir (LPV/r) is being investigated for use against coronavirus disease (COVID-19). We present a case series raising safety and efficacy concerns in COVID-19 affected patients. Methods: We measured LPV trough concentrations in 12 patients treated at our center and reviewed their clinical charts for side effects known to occur in HIV patients. Results: Compared to established LPV trough concentrations in HIV treated patients, concentrations in COVID-19 affected patients were 3-fold greater (20.64 +/- 10.14 mcg/mL versus 6.25 mcg/mL). In addition, cholestasis and dyslipidemia toxicity thresholds were exceeded in 12/12 and 11/12 patients respectively. No patients achieved the presumed therapeutic concentration. The side effects noted were mainly gastrointestinal symptoms (5/12, 42%), electrolytes imbalances (4/12, 33%), liver enzyme disturbances (5/12, 42%), and triglyceride elevations (2/12, 17%). Conclusion: None of our patients reached presumed therapeutic LPV concentrations despite experiencing side effects and exceeding cholestasis and dyslipidemia toxicity thresholds. This raises concerns for the safety and efficacy of LPV/r. Clinicians should consider closely monitoring for side effects and not necessarily attribute them to COVID-19 itself.
Keywords	covid19
Language	English
Publishing date	2020-07-27
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2020.07.23.20153932
Database	COVID19

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Article ; Online: Clinical presentation and in-hospital outcomes of older patients hospitalized with COVID-19 in Montreal, Canada: a retrospective review

Couture, Sandrine / Lepage, Marc-Antoine / Godard-Sebillotte, Claire / Sourial, Nadia / Talbot-Hamon, Catherine / Kremer, Richard / Grunbaum, Ami

medRxiv

Abstract: Background Older adults are more vulnerable to severe infection and mortality due to COVID-19. They often have atypical presentations of the disease without respiratory symptoms, which makes early diagnosis clinically challenging. We aimed to compare the ...

Abstract	Background Older adults are more vulnerable to severe infection and mortality due to COVID-19. They often have atypical presentations of the disease without respiratory symptoms, which makes early diagnosis clinically challenging. We aimed to compare the baseline characteristics, presentation, and disease course of older and younger patients hospitalized with COVID-19. Methods The charts of 429 consecutive patients hospitalized in Montreal, Canada, with PCR-confirmed COVID-19 were retrospectively reviewed. Baseline health, presentation, in-hospital complications, and outcomes were recorded. Desegregation by age was performed to compare older (>= 70) versus younger (<70) individuals. Results Older patients presented with more comorbidities compared to younger patients as captured by the Charlson Comorbidity Index (mean 6 vs 2), including higher rates of cardiovascular, cerebrovascular, chronic obstructive pulmonary, and chronic kidney disease. Older patients were less likely than younger patients to present with cough (27% vs 47%) or dyspnea (33% vs 48%). Fifty-two (52%) had no respiratory symptoms on presentation compared to 32% in the younger group (p<0.001); however, they were more likely to present with geriatric syndromes such as delirium (29% vs 7%), functional decline (14% vs 0.6%), or falls (15% vs 5%). Twelve (12%) of older patients presented with a geriatric syndrome as their sole symptom compared to 3% in the younger group (p=0.002). Older adults were more likely to develop acute kidney injury (35% vs 22%), malnutrition (9% vs 4%), delirium (29% vs 17%) and hypernatremia (32% vs 17%). They had higher in-hospital mortality (33% vs 13%, p<0.001). Discussion Older adults presenting to hospital with COVID-19 commonly have no respiratory symptoms and can present with only a geriatric syndrome. A new geriatric syndrome in an older person should trigger isolation and evaluation for COVID-19. Furthermore, older adults are particularly vulnerable to complications related to dehydration, warranting early initiation of multidisciplinary care.
Keywords	covid19
Language	English
Publishing date	2021-03-01
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2021.02.27.21252596
Database	COVID19

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Article: Breeding expansion of sandhill cranes in Quebec

Casabona I Amat, Clara / Adde, Antoine / Mazerolle, Marc J. / Lepage, Christine / Darveau, Marcel

journal of wildlife management. 2022 Apr., v. 86, no. 3

2022

Abstract: Sandhill cranes (Antigone canadensis) were broadly extirpated from much of their historical range in North America at the beginning of the twentieth century. Various conservation‐related legislation, such as the United States Migratory Bird Treaty Act, ... ...

Abstract	Sandhill cranes (Antigone canadensis) were broadly extirpated from much of their historical range in North America at the beginning of the twentieth century. Various conservation‐related legislation, such as the United States Migratory Bird Treaty Act, have assisted with population recovery. The eastern population of sandhill cranes has been growing rapidly since the 1980s and is thought to have expanded its geographic range to Quebec, Canada. Understanding the colonization and habitat use by the species in previously unoccupied breeding areas is necessary to develop and apply management measures. Using a dynamic occupancy modeling approach, we investigated the recent colonization and extirpation patterns of sandhill cranes in Quebec from 2004–2019. We combined data from 3 data sets (helicopter surveys, breeding bird atlas surveys, and eBird) to increase the spatial coverage and the number of species occurrence records while accounting for imperfect detection probability. Detection probability was highest for the helicopter survey (0.70), whereas the 2 other data sets had relatively low detection levels (0.10–0.26). Based on a simulation study, we found that excluding the eBird data from the analysis produced more biased estimates than excluding the atlas and helicopter survey data sets. Throughout the study, sandhill cranes seemed to have completed their colonization of western Quebec and only recently started to nest in eastern areas. Initial occupancy increased with wetland cover and colonization probability increased weakly with the cover of agricultural areas, suggesting that in our study area sandhill cranes rely essentially on natural wetlands during the breeding season.
Keywords	Antigone canadensis ; geographical distribution ; habitat preferences ; laws and regulations ; migratory birds ; probability ; surveys ; wetlands ; wildlife management ; Quebec
Language	English
Dates of publication	2022-04
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	JOURNAL ARTICLE
ZDB-ID	410712-3
ISSN	0022-541X
ISSN	0022-541X
DOI	10.1002/jwmg.22169
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: A cost-effective sequencing method for genetic studies combining high-depth whole exome and low-depth whole genome.

NPJ genomic medicine

2024 Volume 9, Issue 1, Page(s) 8

Abstract: Whole genome sequencing (WGS) at high-depth (30X) allows the accurate discovery of variants in the coding and non-coding DNA regions and helps elucidate the genetic underpinnings of human health and diseases. Yet, due to the prohibitive cost of high- ... ...

Abstract	Whole genome sequencing (WGS) at high-depth (30X) allows the accurate discovery of variants in the coding and non-coding DNA regions and helps elucidate the genetic underpinnings of human health and diseases. Yet, due to the prohibitive cost of high-depth WGS, most large-scale genetic association studies use genotyping arrays or high-depth whole exome sequencing (WES). Here we propose a cost-effective method which we call "Whole Exome Genome Sequencing" (WEGS), that combines low-depth WGS and high-depth WES with up to 8 samples pooled and sequenced simultaneously (multiplexed). We experimentally assess the performance of WEGS with four different depth of coverage and sample multiplexing configurations. We show that the optimal WEGS configurations are 1.7-2.0 times cheaper than standard WES (no-plexing), 1.8-2.1 times cheaper than high-depth WGS, reach similar recall and precision rates in detecting coding variants as WES, and capture more population-specific variants in the rest of the genome that are difficult to recover when using genotype imputation methods. We apply WEGS to 862 patients with peripheral artery disease and show that it directly assesses more known disease-associated variants than a typical genotyping array and thousands of non-imputable variants per disease-associated locus.
Language	English
Publishing date	2024-02-07
Publishing country	England
Document type	Journal Article
ZDB-ID	2813848-X
ISSN	2056-7944 ; 2056-7944
ISSN (online)	2056-7944
ISSN	2056-7944
DOI	10.1038/s41525-024-00390-3
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Article ; Online: FOLFIRI Plus Durvalumab With or Without Tremelimumab in Second-Line Treatment of Advanced Gastric or Gastroesophageal Junction Adenocarcinoma: The PRODIGE 59-FFCD 1707-DURIGAST Randomized Clinical Trial.

Tougeron, David / Dahan, Laetitia / Evesque, Ludovic / Le Malicot, Karine / El Hajbi, Farid / Aparicio, Thomas / Bouché, Olivier / Bonichon Lamichhane, Nathalie / Chibaudel, Benoist / Angelergues, Antoine / Bodere, Anaïs / Phelip, Jean-Marc / Mabro, May / Kaluzinski, Laure / Petorin, Caroline / Breysacher, Gilles / Rinaldi, Yves / Zaanan, Aziz / Smith, Denis /

Gouttebel, Marie-Claude / Perret, Clément / Etchepare, Nicolas / Emile, Jean-François / Sanfourche, Ivan / Di Fiore, Frédéric / Lepage, Côme / Artru, Pascal / Louvet, Christophe

JAMA oncology

2024

Abstract: Importance: Efficacy of second-line chemotherapy in advanced gastric or gastrooesphageal junction (GEJ) adenocarcinoma remains limited.: Ojectives: To determine the efficacy of 1 or 2 immune checkpoint inhibitors combined with FOLFIRI (leucovorin [ ... ...

Abstract	Importance: Efficacy of second-line chemotherapy in advanced gastric or gastrooesphageal junction (GEJ) adenocarcinoma remains limited. Ojectives: To determine the efficacy of 1 or 2 immune checkpoint inhibitors combined with FOLFIRI (leucovorin [folinic acid], fluorouracil, and irinotecan) in the treatment of advanced gastric/GEJ adenocarcinoma. Design, setting, and participants: The PRODIGE 59-FFCD 1707-DURIGAST trial is a randomized, multicenter, noncomparative, phase 2 trial, conducted from August 27, 2020, and June 4, 2021, at 37 centers in France that included patients with advanced gastric/GEJ adenocarcinoma who had disease progression after platinum-based first-line chemotherapy. Intervention: Patients were randomized to receive FOLFIRI plus durvalumab (anti-programmed cell death 1 [PD-L1]) (FD arm) or FOLFIRI plus durvalumab and tremelimumab (anti-cytotoxic T-lymphocyte associated protein 4 [CTLA-4]) (FDT arm). The efficacy analyses used a clinical cutoff date of January 9, 2023. Main outcome and measures: The primary end point was progression-free survival (PFS) at 4 months according to RECIST 1.1 criteria evaluated by investigators. Results: Overall, between August 27, 2020, and June 4, 2021, 96 patients were randomized (48 in each arm). The median age was 59.7 years, 28 patients (30.4%) were women and 49 (53.3%) had GEJ tumors. Four month PFS was 44.7% (90% CI, 32.3-57.7) and 55.6% (90% CI, 42.3-68.3) in the FD and FDT arms, respectively. The primary end point was not met. Median PFS was 3.8 and 5.4 months, objective response rates were 34.7% and 37.7%, and median overall survival was 13.2 and 9.5 months in the FD and FDT arms, respectively. Disease control beyond 1 year was 14.9% in the FD arm and 24.4% in the FDT arm. Grade 3 to 4 treatment-related adverse events were observed in 22 (47.8%) patients in each arm. A combined positive score (CPS) PD-L1 of 5 or higher was observed in 18 tumors (34.0%) and a tumor proportion score (TPS) PD-L1 of 1% or higher in 13 tumors (24.5%). Median PFS according to CPS PD-L1 was similar (3.6 months for PD-L1 CPS ≥5 vs 5.4 months for PD-L1 CPS <5) by contrast for TPS PD-L1 (6.0 months for PD-L1 TPS ≥1% vs 3.8 months for PD-L1 TPS <1%). Conclusions and relevance: Combination of immune checkpoint inhibitors with FOLFIRI in second-line treatment for advanced gastric/GEJ adenocarcinoma showed an acceptable safety profile but antitumor activity only in a subgroup of patients. Trial registration: ClinicalTrials.gov Identifier: NCT03959293.
Language	English
Publishing date	2024-04-04
Publishing country	United States
Document type	Journal Article
ISSN	2374-2445
ISSN (online)	2374-2445
DOI	10.1001/jamaoncol.2024.0207
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