AP-HP Health Data Space (AHDS) to the Test of the Covid-19 Pandemic.

Sharing observational and interventional health data within a common data space enables university hospitals to leverage such data for biomedical discovery and moving towards a learning health system. OBJECTIVE: To describe the AP-HP Health Data Space (AHDS) and the IT services supporting piloting, research, innovation and patient care. METHODS: Built on three pillars - governance and ethics, technology and valorization - the AHDS and its major component, the Clinical Data Warehouse (CDW) have been developed since 2015. RESULTS: The AP-HP CDW has been made available at scale to AP-HP both healthcare professionals and public or private partners in January 2017. Supported by an institutional secured and high-performance cloud and an ecosystem of tools, mostly open source, the AHDS integrates a large amount of massive healthcare data collected during care and research activities. As of December 2021, the AHDS operates the electronic data capture for almost +840 clinical trials sponsored by AP-HP, the CDW is enabling the processing of health data from more than 11 million patients and generated +200 secondary data marts from IRB authorized research projects. During the Covid-19 pandemic, AHDS has had to evolve quickly to support administrative professionals and caregivers heavily involved in the reorganization of both patient care and biomedical research. CONCLUSION: The AP-HP Data Space is a key facilitator for data-driven evidence generation and making the health system more efficient and personalized.

Hydroxyzine Use and Mortality in Patients Hospitalized for COVID-19: A Multicenter Observational Study.

(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.

Dexamethasone use and mortality in hospitalized patients with coronavirus disease 2019: A multicentre retrospective observational study.

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.

Observational study of haloperidol in hospitalized patients with COVID-19.

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.

Association of Antihypertensive Agents with the Risk of In-Hospital Death in Patients with Covid-19.

PURPOSE: The role of angiotensin receptor blockers (ARB), angiotensin-converting enzyme inhibitors (ACEi), or other antihypertensive agents in the case of Covid-19 remains controversial. We aimed to investigate the association between antihypertensive agent exposure and in-hospital mortality in patients with Covid-19. METHODS: We performed a retrospective multicenter cohort study on patients hospitalized between February 1 and May 15, 2020. All patients had been followed up for at least 30 days. RESULTS: Of the 8078 hospitalized patients for Covid-19, 3686 (45.6%) had hypertension and were included in the study. In this population, the median age was 75.4 (IQR, 21.5) years and 57.1% were male. Overall in-hospital 30-day mortality was 23.1%. The main antihypertensive pharmacological classes used were calcium channel blockers (CCB) (n=1624, 44.1%), beta-blockers (n=1389, 37.7%), ARB (n=1154, 31.3%), and ACEi (n=998, 27.1%). The risk of mortality was lower in CCB (aOR, 0.83 [0.70-0.99]) and beta-blockers (aOR, 0.80 [0.67-0.95]) users and non-significant in ARB (aOR, 0.88 [0.72-1.06]) and ACEi (aOR, 0.83 [0.68-1.02]) users, compared to non-users. These results remain consistent for patients receiving CCB, beta-blocker, or ARB as monotherapies. CONCLUSION: This large multicenter retrospective of Covid-19 patients with hypertension found a reduced mortality among CCB and beta-blockers users, suggesting a putative protective effect. Our findings did not show any association between the use of renin-angiotensin-aldosterone system inhibitors and the risk of in-hospital death. Although they need to be confirmed in further studies, these results support the continuation of antihypertensive agents in patients with Covid-19, in line with the current guidelines.

Observational Study of Chlorpromazine in Hospitalized Patients with COVID-19.

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.

Association between antidepressant use and reduced risk of intubation or death in hospitalized patients with COVID-19: results from an observational study.

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.

Natural Language Processing for Rapid Response to Emergent Diseases: Case Study of Calcium Channel Blockers and Hypertension in the COVID-19 Pandemic.

BACKGROUND: A novel disease poses special challenges for informatics solutions. Biomedical informatics relies for the most part on structured data, which require a preexisting data or knowledge model; however, novel diseases do not have preexisting knowledge models. In an emergent epidemic, language processing can enable rapid conversion of unstructured text to a novel knowledge model. However, although this idea has often been suggested, no opportunity has arisen to actually test it in real time. The current coronavirus disease (COVID-19) pandemic presents such an opportunity. OBJECTIVE: The aim of this study was to evaluate the added value of information from clinical text in response to emergent diseases using natural language processing (NLP). METHODS: We explored the effects of long-term treatment by calcium channel blockers on the outcomes of COVID-19 infection in patients with high blood pressure during in-patient hospital stays using two sources of information: data available strictly from structured electronic health records (EHRs) and data available through structured EHRs and text mining. RESULTS: In this multicenter study involving 39 hospitals, text mining increased the statistical power sufficiently to change a negative result for an adjusted hazard ratio to a positive one. Compared to the baseline structured data, the number of patients available for inclusion in the study increased by 2.95 times, the amount of available information on medications increased by 7.2 times, and the amount of additional phenotypic information increased by 11.9 times. CONCLUSIONS: In our study, use of calcium channel blockers was associated with decreased in-hospital mortality in patients with COVID-19 infection. This finding was obtained by quickly adapting an NLP pipeline to the domain of the novel disease; the adapted pipeline still performed sufficiently to extract useful information. When that information was used to supplement existing structured data, the sample size could be increased sufficiently to see treatment effects that were not previously statistically detectable.