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1.
Int J Cancer ; 2022 Jan 09.
Article in English | MEDLINE | ID: covidwho-1615974

ABSTRACT

The SARS-Cov2 may have impaired care trajectories, patient overall survival (OS), tumor stage at initial presentation for new colorectal cancer (CRC) cases. This study aimed at assessing those indicators before and after the beginning of the pandemic in France. In this retrospective cohort study, we collected prospectively the clinical data of the 11.4 million of patients referred to the Greater Paris University Hospitals (AP-HP). We identified new CRC cases between 1 January 2018 and 31 December 2020, and compared indicators for 2018-2019 to 2020. pTNM tumor stage was extracted from postoperative pathology reports for localized colon cancer, and metastatic status was extracted from CT-scan baseline text reports. Between 2018 and 2020, 3602 and 1083 new colon and rectal cancers were referred to the AP-HP, respectively. The 1-year OS rates reached 94%, 93% and 76% for new CRC patients undergoing a resection of the primary tumor, in 2018-2019, in 2020 without any Sars-Cov2 infection and in 2020 with a Sars-Cov2 infection, respectively (HR 3.78, 95% CI 2.1-7.1). For patients undergoing other kind of anticancer treatment, the percentages are 64%, 66% and 27% (HR 2.1, 95% CI 1.4-3.3). Tumor stage at initial presentation, emergency level of primary tumor resection, delays between the first multidisciplinary meeting and the first anticancer treatment did not differ over time. The SARS-Cov2 pandemic has been associated with less newly diagnosed CRC patients and worse 1-year OS rates attributable to the infection itself rather than to its impact on hospital care delivery or tumor stage at initial presentation.

2.
J Clin Med ; 10(24)2021 Dec 15.
Article in English | MEDLINE | ID: covidwho-1572535

ABSTRACT

(1) Background: Based on its antiviral activity, anti-inflammatory properties, and functional inhibition effects on the acid sphingomyelinase/ceramide system (FIASMA), we sought to examine the potential usefulness of the H1 antihistamine hydroxyzine in patients hospitalized for COVID-19. (2) Methods: In a multicenter observational study, we included 15,103 adults hospitalized for COVID-19, of which 164 (1.1%) received hydroxyzine within the first 48 h of hospitalization, administered orally at a median daily dose of 25.0 mg (SD = 29.5). We compared mortality rates between patients who received hydroxyzine at hospital admission and those who did not, using a multivariable logistic regression model adjusting for patients' characteristics, medical conditions, and use of other medications. (3) Results: This analysis showed a significant association between hydroxyzine use and reduced mortality (AOR, 0.51; 95%CI, 0.29-0.88, p = 0.016). This association was similar in multiple sensitivity analyses. (4) Conclusions: In this retrospective observational multicenter study, the use of the FIASMA hydroxyzine was associated with reduced mortality in patients hospitalized for COVID-19. Double-blind placebo-controlled randomized clinical trials of hydroxyzine for COVID-19 are needed to confirm these results, as are studies to examine the potential usefulness of this medication for outpatients and as post-exposure prophylaxis for individuals at high risk for severe COVID-19.

4.
Intensive Care Med ; 47(12): 1426-1439, 2021 12.
Article in English | MEDLINE | ID: covidwho-1442081

ABSTRACT

PURPOSE: The Coronavirus disease 2019 (COVID-19) has led to an unparalleled influx of patients. Prognostic scores could help optimizing healthcare delivery, but most of them have not been comprehensively validated. We aim to externally validate existing prognostic scores for COVID-19. METHODS: We used "COVID-19 Evidence Alerts" (McMaster University) to retrieve high-quality prognostic scores predicting death or intensive care unit (ICU) transfer from routinely collected data. We studied their accuracy in a retrospective multicenter cohort of adult patients hospitalized for COVID-19 from January 2020 to April 2021 in the Greater Paris University Hospitals. Areas under the receiver operating characteristic curves (AUC) were computed for the prediction of the original outcome, 30-day in-hospital mortality and the composite of 30-day in-hospital mortality or ICU transfer. RESULTS: We included 14,343 consecutive patients, 2583 (18%) died and 5067 (35%) died or were transferred to the ICU. We examined 274 studies and found 32 scores meeting the inclusion criteria: 19 had a significantly lower AUC in our cohort than in previously published validation studies for the original outcome; 25 performed better to predict in-hospital mortality than the composite of in-hospital mortality or ICU transfer; 7 had an AUC > 0.75 to predict in-hospital mortality; 2 had an AUC > 0.70 to predict the composite outcome. CONCLUSION: Seven prognostic scores were fairly accurate to predict death in hospitalized COVID-19 patients. The 4C Mortality Score and the ABCS stand out because they performed as well in our cohort and their initial validation cohort, during the first epidemic wave and subsequent waves, and in younger and older patients.


Subject(s)
COVID-19 , Adult , Cohort Studies , Hospitals, University , Humans , Paris , Prognosis , Retrospective Studies , SARS-CoV-2
5.
Cancers (Basel) ; 13(19)2021 Sep 23.
Article in English | MEDLINE | ID: covidwho-1438522

ABSTRACT

BACKGROUND: COVID-19 may be more frequent and more severe in cancer patients than in other individuals. Our aims were to assess the rate of COVID-19 in hospitalized cancer patients, to describe their demographic characteristics, clinical features and care trajectories, and to assess the mortality rate. METHODS: This multicenter cohort study was based on the Electronic Health Records of the Assistance Publique-Hôpitaux de Paris (AP-HP). Cancer patients with a diagnosis of COVID-19 between 3 March and 19 May 2020 were included. Main outcome was all-cause mortality within 30 days of COVID-19 diagnosis. RESULTS: A total of 29,141 cancer patients were identified and 7791 (27%) were tested for SARS-CoV-2. Of these, 1359 (17%) were COVID-19-positive and 1148 (84%) were hospitalized; 217 (19%) were admitted to an intensive care unit. The mortality rate was 33% (383 deaths). In multivariate analysis, mortality-related factors were male sex (aHR = 1.39 [95% CI: 1.07-1.81]), advanced age (78-86 y: aHR = 2.83 [95% CI: 1.78-4.51] vs. <66 y; 86-103 y: aHR = 2.61 [95% CI: 1.56-4.35] vs. <66 y), more than two comorbidities (aHR = 2.32 [95% CI: 1.41-3.83]) and C-reactive protein >20 ng/mL (aHR = 2.20 [95% CI: 1.70-2.86]). Primary brains tumors (aHR = 2.19 [95% CI: 1.08-4.44]) and lung cancer (aHR = 1.66 [95% CI: 1.02-2.70]) were associated with higher mortality. Risk of dying was lower among patients with metabolic comorbidities (aHR = 0.65 [95% CI: 0.50-0.84]). CONCLUSIONS: In a hospital-based setting, cancer patients with COVID-19 had a high mortality rate. This mortality was mainly driven by age, sex, number of comorbidities and presence of inflammation. This is the first cohort of cancer patients in which metabolic comorbidities were associated with a better outcome.

6.
Yearb Med Inform ; 30(1): 233-238, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1392947

ABSTRACT

OBJECTIVES: To summarize key contributions to current research in the field of Clinical Research Informatics (CRI) and to select best papers published in 2020. METHOD: A bibliographic search using a combination of Medical Subject Headings (MeSH) descriptors and free-text terms on CRI was performed using PubMed, followed by a double-blind review in order to select a list of candidate best papers to be then peer-reviewed by external reviewers. After peer-review ranking, a consensus meeting between two section editors and the editorial team was organized to finally conclude on the selected four best papers. RESULTS: Among the 877 papers published in 2020 and returned by the search, there were four best papers selected. The first best paper describes a method for mining temporal sequences from clinical documents to infer disease trajectories and enhancing high-throughput phenotyping. The authors of the second best paper demonstrate that the generation of synthetic Electronic Health Record (EHR) data through Generative Adversarial Networks (GANs) could be substantially improved by more appropriate training and evaluation criteria. The third best paper offers an efficient advance on methods to detect adverse drug events by computer-assisting expert reviewers with annotated candidate mentions in clinical documents. The large-scale data quality assessment study reported by the fourth best paper has clinical research informatics implications, in terms of the trustworthiness of inferences made from analysing electronic health records. CONCLUSIONS: The most significant research efforts in the CRI field are currently focusing on data science with active research in the development and evaluation of Artificial Intelligence/Machine Learning (AI/ML) algorithms based on ever more intensive use of real-world data and especially EHR real or synthetic data. A major lesson that the coronavirus disease 2019 (COVID-19) pandemic has already taught the scientific CRI community is that timely international high-quality data-sharing and collaborative data analysis is absolutely vital to inform policy decisions.


Subject(s)
Biomedical Research , Medical Informatics , Computer Security , Data Mining , Electronic Health Records , Humans , Machine Learning , Pharmacovigilance , Phenotype
7.
J Clin Endocrinol Metab ; 106(9): e3364-e3368, 2021 08 18.
Article in English | MEDLINE | ID: covidwho-1362074

ABSTRACT

CONTEXT: Diabetes is reported as a risk factor for severe coronavirus disease 2019 (COVID-19), but whether this risk is similar in all categories of age remains unclear. OBJECTIVE: To investigate the risk of severe COVID-19 outcomes in hospitalized patients with and without diabetes according to age categories. DESIGN SETTING AND PARTICIPANTS: We conducted a retrospective observational cohort study of 6314 consecutive patients hospitalized for COVID-19 between February and 30 June 2020 in the Paris metropolitan area, France; follow-up was recorded until 30 September 2020. MAIN OUTCOME MEASURE(S): The main outcome was a composite outcome of mortality and orotracheal intubation in subjects with diabetes compared with subjects without diabetes, after adjustment for confounding variables and according to age categories. RESULTS: Diabetes was recorded in 39% of subjects. Main outcome was higher in patients with diabetes, independently of confounding variables (hazard ratio [HR] 1.13 [1.03-1.24]) and increased with age in individuals without diabetes, from 23% for those <50 to 35% for those >80 years but reached a plateau after 70 years in those with diabetes. In direct comparison between patients with and without diabetes, diabetes-associated risk was inversely proportional to age, highest in <50 years and similar after 70 years. Similarly, mortality was higher in patients with diabetes (26%) than in those without diabetes (22%, P < 0.001), but adjusted HR for diabetes was significant only in patients younger than age 50 years (HR 1.81 [1.14-2.87]). CONCLUSIONS: Diabetes should be considered as an independent risk factor for the severity of COVID-19 in young adults more so than in older adults, especially for individuals younger than 70 years.


Subject(s)
COVID-19/epidemiology , Diabetes Mellitus/physiopathology , Hospital Mortality/trends , Hospitalization/statistics & numerical data , SARS-CoV-2/isolation & purification , Severity of Illness Index , Aged , Aged, 80 and over , COVID-19/virology , Female , France/epidemiology , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Factors
8.
J Clin Endocrinol Metab ; 106(9): e3364-e3368, 2021 08 18.
Article in English | MEDLINE | ID: covidwho-1249569

ABSTRACT

CONTEXT: Diabetes is reported as a risk factor for severe coronavirus disease 2019 (COVID-19), but whether this risk is similar in all categories of age remains unclear. OBJECTIVE: To investigate the risk of severe COVID-19 outcomes in hospitalized patients with and without diabetes according to age categories. DESIGN SETTING AND PARTICIPANTS: We conducted a retrospective observational cohort study of 6314 consecutive patients hospitalized for COVID-19 between February and 30 June 2020 in the Paris metropolitan area, France; follow-up was recorded until 30 September 2020. MAIN OUTCOME MEASURE(S): The main outcome was a composite outcome of mortality and orotracheal intubation in subjects with diabetes compared with subjects without diabetes, after adjustment for confounding variables and according to age categories. RESULTS: Diabetes was recorded in 39% of subjects. Main outcome was higher in patients with diabetes, independently of confounding variables (hazard ratio [HR] 1.13 [1.03-1.24]) and increased with age in individuals without diabetes, from 23% for those <50 to 35% for those >80 years but reached a plateau after 70 years in those with diabetes. In direct comparison between patients with and without diabetes, diabetes-associated risk was inversely proportional to age, highest in <50 years and similar after 70 years. Similarly, mortality was higher in patients with diabetes (26%) than in those without diabetes (22%, P < 0.001), but adjusted HR for diabetes was significant only in patients younger than age 50 years (HR 1.81 [1.14-2.87]). CONCLUSIONS: Diabetes should be considered as an independent risk factor for the severity of COVID-19 in young adults more so than in older adults, especially for individuals younger than 70 years.


Subject(s)
COVID-19/epidemiology , Diabetes Mellitus/physiopathology , Hospital Mortality/trends , Hospitalization/statistics & numerical data , SARS-CoV-2/isolation & purification , Severity of Illness Index , Aged , Aged, 80 and over , COVID-19/virology , Female , France/epidemiology , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Factors
9.
Br J Clin Pharmacol ; 87(10): 3766-3775, 2021 10.
Article in English | MEDLINE | ID: covidwho-1127455

ABSTRACT

AIMS: To examine the association between dexamethasone use and mortality among patients hospitalized for COVID-19. METHODS: We examined the association between dexamethasone use and mortality at AP-HP Greater Paris University hospitals. Study baseline was defined as the date of hospital admission. The primary endpoint was time to death. We compared this endpoint between patients who received dexamethasone and those who did not in time-to-event analyses adjusted for patient characteristics (such as age, sex and comorbidity) and clinical and biological markers of clinical severity of COVID-19, and stratified by the need for respiratory support, i.e. mechanical ventilation or oxygen. The primary analysis was a multivariable Cox regression model. RESULTS: Of 12 217 adult patients hospitalized with a positive COVID-19 reverse transcriptase-polymerase chain reaction test, 171 (1.4%) received dexamethasone orally or by intravenous perfusion during the visit. Among patients who required respiratory support, the end-point occurred in 10/63 (15.9%) patients who received dexamethasone and 298/1129 (26.4%) patients who did not. In this group, there was a significant association between dexamethasone use and reduced mortality in the primary analysis (hazard ratio, 0.46; 95% confidence interval 0.22-0.96, P = .039). Among patients who did not require respiratory support, there was no significant association between dexamethasone use and the endpoint. CONCLUSIONS: In this multicentre observational study, dexamethasone use administered either orally or by intravenous injection at a cumulative dose between 60 mg and 150 mg was associated with reduced mortality among patients with COVID-19 requiring respiratory support.


Subject(s)
COVID-19 , Coronavirus Infections , Adult , COVID-19/drug therapy , Dexamethasone , Hospitalization , Humans , Retrospective Studies , SARS-CoV-2
10.
Eur J Cancer ; 150: 260-267, 2021 06.
Article in English | MEDLINE | ID: covidwho-1101196

ABSTRACT

INTRODUCTION: The dissemination of SARS-Cov2 may have delayed the diagnosis of new cancers. This study aimed at assessing the number of new cancers during and after the lockdown. METHODS: We prospectively collected the clinical data of the 11.4 million patients referred to the Assistance Publique Hôpitaux de Paris Teaching Hospital. We identified new cancer cases between 1st January 2018 and 31st September 2020 and compared indicators for 2018 and 2019 to 2020 with a focus on the French lockdown (17th March to 11th May 2020) across cancer types and patient age classes. RESULTS: Between January and September, 28,348, 27,272 and 23,734 new cancer cases were identified in 2018, 2019 and 2020, respectively. The monthly median number of new cases reached 3168 (interquartile range, IQR, 3027; 3282), 3054 (IQR 2945; 3127) and 2723 (IQR 2085; 2,863) in 2018, 2019 and 2020, respectively. From March 1st to May 31st, new cancer decreased by 30% in 2020 compared to the 2018-19 average; then by 9% from 1st June to 31st September. This evolution was consistent across all tumour types: -30% and -9% for colon, -27% and -6% for lung, -29% and -14% for breast, -33% and -12% for prostate cancers, respectively. For patients aged <70 years, the decrease of colorectal and breast new cancers in April between 2018 and 2019 average and 2020 reached 41% and 39%, respectively. CONCLUSION: The SARS-Cov2 pandemic led to a substantial decrease in new cancer cases. Delays in cancer diagnoses may affect clinical outcomes in the coming years.


Subject(s)
COVID-19 , Neoplasms/epidemiology , Aged , Female , France/epidemiology , Health Policy , Humans , Male , Middle Aged , Neoplasms/diagnosis , Quarantine , SARS-CoV-2
11.
PLoS One ; 16(2): e0247122, 2021.
Article in English | MEDLINE | ID: covidwho-1090547

ABSTRACT

BACKGROUND: Haloperidol, a widely used antipsychotic, has been suggested as potentially useful for patients with COVID-19 on the grounds of its in-vitro antiviral effects against SARS-CoV-2, possibly through sigma-1 receptor antagonist effect. METHODS: We examined the associations of haloperidol use with intubation or death and time to discharge home among adult patients hospitalized for COVID-19 at Assistance Publique-Hôpitaux de Paris (AP-HP) Greater Paris University hospitals. Study baseline was defined as the date of hospital admission. The primary endpoint was a composite of intubation or death and the secondary endpoint was discharge home among survivors in time-to-event analyses. In the primary analyses, we compared these two outcomes between patients receiving and not receiving haloperidol using univariate Cox regression models in matched analytic samples based on patient characteristics and other psychotropic medications. Sensitivity analyses included propensity score analyses with inverse probability weighting and multivariable Cox regression models. RESULTS: Of 15,121 adult inpatients with a positive COVID-19 PT-PCR test, 39 patients (0.03%) received haloperidol within the first 48 hours of admission. Over a mean follow-up of 13.8 days (SD = 17.9), 2,024 patients (13.4%) had a primary end-point event and 10,179 patients (77.6%) were discharged home at the time of study end on May 1st. The primary endpoint occurred in 9 patients (23.1%) who received haloperidol and 2,015 patients (13.4%) who did not. The secondary endpoint of discharge home occurred in 16 patients (61.5%) who received haloperidol and 9,907 patients (85.8%) who did not. There were no significant associations between haloperidol use and the primary (HR, 0.80; 95% CI, 0.39 to 1.62, p = 0.531) and secondary (HR, 1.30; 95% CI, 0.74 to 2.28, p = 0.355) endpoints. Results were similar in multiple sensitivity analyses. CONCLUSION: Findings from this multicenter observational study suggest that haloperidol use prescribed at a mean dose of 4.5 mg per day (SD = 5.2) for a mean duration of 8.4 days (SD = 7.2) may not be associated with risk of intubation or death, or with time to discharge home, among adult patients hospitalized for COVID-19.


Subject(s)
Antipsychotic Agents/administration & dosage , Antiviral Agents/administration & dosage , COVID-19/mortality , COVID-19/therapy , Haloperidol/administration & dosage , Hospitalization , SARS-CoV-2 , Adolescent , Adult , Aged , Disease-Free Survival , Female , Humans , Male , Middle Aged , Receptors, sigma/antagonists & inhibitors , Survival Rate
12.
Clin Drug Investig ; 41(3): 221-233, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1070973

ABSTRACT

INTRODUCTION: Chlorpromazine has been suggested as being potentially useful in patients with coronavirus disease 2019 (COVID-19) on the grounds of its potential antiviral and anti-inflammatory effects. OBJECTIVE: The aim of this study was to examine the association between chlorpromazine use and mortality among adult patients hospitalized for COVID-19. METHODS: We conducted an observational, multicenter, retrospective study at Assistance Publique-Hôpitaux de Paris (AP-HP) Greater Paris University hospitals. Study baseline was defined as the date of first prescription of chlorpromazine during hospitalization for COVID-19. The primary endpoint was death. Among patients who had not been hospitalized in intensive care units (ICUs), we compared this endpoint between those who received chlorpromazine and those who did not, in time-to-event analyses adjusted for patient characteristics, clinical markers of disease severity, and other psychotropic medications. The primary analysis used a Cox regression model with inverse probability weighting. Multiple sensitivity analyses were performed. RESULTS: Of the 14,340 adult inpatients hospitalized outside ICUs for COVID-19, 55 patients (0.4%) received chlorpromazine. Over a mean follow-up of 14.3 days (standard deviation [SD] 18.2), death occurred in 13 patients (23.6%) who received chlorpromazine and 1289 patients (9.0%) who did not. In the primary analysis, there was no significant association between chlorpromazine use and mortality (hazard ratio [HR] 2.01, 95% confidence interval [CI] 0.75-5.40; p = 0.163). Sensitivity analyses included a Cox regression in a 1:5 ratio matched analytic sample that showed a similar result (HR 1.67, 95% CI 0.91-3.06; p = 0.100) and a multivariable Cox regression that indicated a significant positive association (HR 3.10, 95% CI 1.31-7.34; p = 0.010). CONCLUSION: Our results suggest that chlorpromazine prescribed at a mean daily dose of 70.8 mg (SD 65.3) was not associated with reduced mortality.


Subject(s)
COVID-19/drug therapy , Chlorpromazine/therapeutic use , SARS-CoV-2 , Adolescent , Adult , Aged , Aged, 80 and over , Female , Hospitalization , Humans , Male , Middle Aged , Proportional Hazards Models , Retrospective Studies , Severity of Illness Index , Young Adult
13.
Mol Psychiatry ; 26(9): 5199-5212, 2021 09.
Article in English | MEDLINE | ID: covidwho-1065840

ABSTRACT

A prior meta-analysis showed that antidepressant use in major depressive disorder was associated with reduced plasma levels of several pro-inflammatory mediators, which have been associated with severe COVID-19. Recent studies also suggest that several antidepressants may inhibit acid sphingomyelinase activity, which may prevent the infection of epithelial cells with SARS-CoV-2, and that the SSRI fluoxetine may exert in-vitro antiviral effects on SARS-CoV-2. We examined the potential usefulness of antidepressant use in patients hospitalized for COVID-19 in an observational multicenter retrospective cohort study conducted at AP-HP Greater Paris University hospitals. Of 7230 adults hospitalized for COVID-19, 345 patients (4.8%) received an antidepressant within 48 h of hospital admission. The primary endpoint was a composite of intubation or death. We compared this endpoint between patients who received antidepressants and those who did not in time-to-event analyses adjusted for patient characteristics, clinical and biological markers of disease severity, and other psychotropic medications. The primary analysis was a multivariable Cox model with inverse probability weighting. This analysis showed a significant association between antidepressant use and reduced risk of intubation or death (HR, 0.56; 95% CI, 0.43-0.73, p < 0.001). This association remained significant in multiple sensitivity analyses. Exploratory analyses suggest that this association was also significant for SSRI and non-SSRI antidepressants, and for fluoxetine, paroxetine, escitalopram, venlafaxine, and mirtazapine (all p < 0.05). These results suggest that antidepressant use could be associated with lower risk of death or intubation in patients hospitalized for COVID-19. Double-blind controlled randomized clinical trials of antidepressant medications for COVID-19 are needed.


Subject(s)
COVID-19 , Depressive Disorder, Major , Antidepressive Agents/therapeutic use , Depressive Disorder, Major/drug therapy , Humans , Intubation, Intratracheal , Multicenter Studies as Topic , Observational Studies as Topic , Retrospective Studies , SARS-CoV-2
16.
NPJ Digit Med ; 3: 109, 2020.
Article in English | MEDLINE | ID: covidwho-728999

ABSTRACT

We leveraged the largely untapped resource of electronic health record data to address critical clinical and epidemiological questions about Coronavirus Disease 2019 (COVID-19). To do this, we formed an international consortium (4CE) of 96 hospitals across five countries (www.covidclinical.net). Contributors utilized the Informatics for Integrating Biology and the Bedside (i2b2) or Observational Medical Outcomes Partnership (OMOP) platforms to map to a common data model. The group focused on temporal changes in key laboratory test values. Harmonized data were analyzed locally and converted to a shared aggregate form for rapid analysis and visualization of regional differences and global commonalities. Data covered 27,584 COVID-19 cases with 187,802 laboratory tests. Case counts and laboratory trajectories were concordant with existing literature. Laboratory tests at the time of diagnosis showed hospital-level differences equivalent to country-level variation across the consortium partners. Despite the limitations of decentralized data generation, we established a framework to capture the trajectory of COVID-19 disease in patients and their response to interventions.

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