Does Time and Size Matter in Retrograde Intrarenal Surgery? Results Analysis Using a Low-Pressure Technique.

PURPOSE: Kidney stone disease affects 5% of the population and is associated with non-negligible morbidity. Retrograde intrarenal surgery and percutaneous nephrolithotomy are the treatments of choice. We analyzed the results from our patients who underwent retrograde intrarenal surgery at controlled pressure. MATERIALS AND METHODS: We conducted an observational, descriptive, retrospective study of 403 patients who underwent retrograde intrarenal surgery at the Hospital Clínico Universitario Lozano Blesa (Zaragoza, Spain) between January 2013 and December 2019. RESULTS: The mean surgical time was 111.1 minutes, with a mean stone volume of 3.5 cm3 (maximum volume, 38.3 cm3). A total of 70 patients (17.3%) developed postoperative Clavien-Dindo complications-64 minor (91.4%) and 6 major (8.6%). In addition, 28 patients (6.9%) presented with an early complication (<3 months), with urinary tract infection and pyelonephritis being the most common. The stone-free rate was 69.0%, with a retreatment rate of 4.7%. CONCLUSIONS: Sex was statistically significantly related to the onset of minor Clavien postoperative complications (p = 0.001). Similarly, corticosteroid use was associated with the onset of major Clavien complications (p = 0.030). Neither surgical time nor stone volume was found to be statistically significantly related to the onset of Clavien postoperative complications or early complications.

Association between Functional Inhibitors of Acid Sphingomyelinase and Reduced Risk of Intubation or Death in Individuals Hospitalized for Severe COVID-19: results from an observational multicenter study

Several medications commonly used for a number of medical conditions share a property of functional inhibition of acid sphingomyelinase (ASM), or FIASMA. Preclinical and clinical evidence suggest that the (ASM)/ceramide system may be central to SARS-CoV-2 infection. We examined the potential usefulness of FIASMA use among patients hospitalized for severe COVID-19 in an observational multicenter retrospective study conducted at Greater Paris University hospitals. Of 2,846 adult patients hospitalized for severe COVID-19, 277 (9.7%) were taking a FIASMA medication at the time of their hospital admission. The primary endpoint was a composite of intubation and/or death. We compared this endpoint between patients taking vs. not taking a FIASMA medication in time-to-event analyses adjusted for sociodemographic characteristics and medical comorbidities. The primary analysis was a Cox regression model with inverse probability weighting (IPW). Over a mean follow-up of 9.2 days (SD=12.5), the primary endpoint occurred in 104 patients (37.5%) who were taking a FIASMA medication, and 1,060 patients (41.4%) who were not. Taking a FIASMA medication was associated with reduced likelihood of intubation or death in both crude (HR=0.71; 95%CI=0.58-0.87; p<0.001) and the primary IPW (HR=0.58; 95%CI=0.46-0.72; p<0.001) analyses. This association remained significant in multiple sensitivity analyses and was not specific to one FIASMA class or medication. These results show the potential importance of the ASM/ceramide system as a treatment target in COVID-19. Double-blind controlled randomized clinical trials of these medications for COVID-19 are needed.

Association between benzodiazepine receptor agonist use and increased mortality among patients hospitalized for COVID-19: results from an observational study

ObjectiveTo examine the association between benzodiazepine receptor agonist (BZRA) use and mortality in patients hospitalized for COVID-19. MethodsWe conducted an observational multicenter retrospective cohort study at AP-HP Greater Paris University hospitals. The sample involved 14,381 adult patients hospitalized for COVID-19. 686 (4.8%) inpatients received a BZRA within at the time of hospital admission at a mean daily diazepam-equivalent dose of 19.7 mg (SD=25.4). The study baseline was the date of hospital admission and the primary endpoint was death. We compared this endpoint between patients who received BZRAs and those who did not in time-to-event analyses adjusted for patient characteristics (such as age, sex, obesity and comorbidity) and other medications. The primary analysis was a Cox regression model with inverse probability weighting (IPW). ResultsOver a mean follow-up of 14.5 days (SD=18.1), the primary endpoint occurred in 186 patients (27.1%) who received a BZRA and in 1,134 patients (8.3%) who did not. There was a significant association between BZRA use and increased mortality both in the crude analysis (HR=3.20; 95% CI=2.74-3.74; p<0.01) and in the primary IPW analysis (HR=1.61; 95% CI=1.31-1.98, p<0.01), with a significant dose-dependent relationship (HR=1.55; 95% CI=1.08-2.22; p=0.02). This association remained significant in multiple sensitivity analyses. ConclusionsBZRA use was associated with increased mortality among patients hospitalized for COVID-19 with a dose-dependent relationship, suggesting a potential benefit of decreasing dose or tapering off these medications when possible in these patients.

Optimizing SARS-CoV-2 vaccination strategies in France: Results from a stochastic agent-based model

The COVID-19 pandemic is a major global societal, economic and health threat. The availability of COVID-19 vaccines has raised hopes for a decline in the pandemic. We built upon a stochastic agent-based microsimulation model of the COVID-19 epidemic in France. We examined the potential impact of different vaccination strategies, defined according to the age, medical conditions, and expected vaccination acceptance of the target non-immunized adult population, on disease cumulative incidence, mortality, and number of hospital admissions. Specifically, we examined whether these vaccination strategies would allow to lift all non-pharmacological interventions (NPIs), based on a sufficiently low cumulative mortality and number of hospital admissions. While vaccinating the full adult non-immunized population, if performed immediately, would be highly effective in reducing incidence, mortality and hospital-bed occupancy, and would allow discontinuing all NPIs, this strategy would require a large number of vaccine doses. Vaccinating only adults at higher risk for severe SARS-CoV-2 infection, i.e. those aged over 65 years or with medical conditions, would be insufficient to lift NPIs. Immediately vaccinating only adults aged over 45 years, or only adults aged over 55 years with mandatory vaccination of those aged over 65 years, would enable lifting all NPIs with a substantially lower number of vaccine doses, particularly with the latter vaccination strategy. Benefits of these strategies would be markedly reduced if the vaccination was delayed, was less effective than expected on virus transmission or in preventing COVID-19 among older adults, or was not widely accepted.

Association between Hydroxyzine Use and Reduced Mortality in Patients Hospitalized for Coronavirus Disease 2019: Results from a multicenter observational study

ObjectiveTo examine the association between hydroxyzine use and mortality in patients hospitalized for COVID-19, based on its anti-inflammatory and antiviral properties. DesignMulticenter observational retrospective cohort study. SettingGreater Paris University hospitals, France. Participants7,345 adults hospitalized for COVID-19 between 24 January and 1 April 2020, including 138 patients (1.9%) who received hydroxyzine during the visit at a mean dose of 49.8 mg (SD=51.5) for an average of 22.4 days (SD=25.9). Data sourceAssistance Publique-Hopitaux de Paris Health Data Warehouse. Main outcome measuresThe study endpoint was death. We compared this endpoint between patients who received hydroxyzine and those who did not in time-to-event analyses adjusting for patient characteristics (such as age, sex, and comorbidities), clinical and biological markers of diseases severity, and use of other medications. The primary analysis was a multivariable Cox model with inverse probability weighting. Sensitivity analyses included a multivariable Cox model and a univariate Cox regression model in a matched analytic sample in a 1:1 ratio. ResultsOver a mean follow-up of 20.3 days (SD=27.5), 994 patients (13.5%) had a primary end-point event. The primary multivariable analysis with inverse probability weighting showed a significant association between hydroxyzine use and reduced mortality (HR, 0.42; 95% CI, 0.25 to 0.71; p=0.001) with a significant dose-effect relationship (HR, 0.10; 95% CI, 0.02 to 0.45; p=0.003). This association was similar in sensitivity analyses. In secondary analyses conducted among subsamples of patients, we found a significant association between hydroxyzine use and a faster decrease in biological inflammatory markers associated with COVID-19-related mortality, including neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-C-reactive protein ratio (LCRP), and circulating interleukin 6 levels (IL-6) (all p<0.016), with a significant dose-effect relationship for NLR and LCRP (both p<0.037). ConclusionsIn this retrospective observational study, hydroxyzine use was associated with reduced mortality in patients hospitalized for COVID-19. This association may be partially mediated by specific anti-inflammatory properties of H1 antihistamines. Double-blind controlled randomized clinical trials of hydroxyzine for COVID-19 are needed to confirm these results.

Observational Study of Haloperidol in Hospitalized Patients with Covid-19

BackgroundHaloperidol, a widely used antipsychotic, has been suggested as potential effective treatment for Covid-19 on the grounds of its in-vitro antiviral effects against SARS-CoV-2. MethodsWe examined the association between haloperidol use and respiratory failure at AP-HP Greater Paris University hospitals. Data were obtained regarding all adult patients hospitalized with Covid-19 since the beginning of the epidemic. 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. We compared outcomes between patients who were exposed to haloperidol and those who were not, using a multivariable Cox regression model with inverse probability weighting according to the propensity score. ResultsOf the 13,279 hospitalized adult patients with positive Covid-19 RT-PCR test, 667 patients (5.0%) were excluded because of missing data. Of the remaining 12,612 patients, 104 (0.8%) were exposed to haloperidol. Over a mean follow-up of 20.8 days, the primary endpoint of respiratory failure respectively occurred in 27 patients (26.0%) exposed to haloperidol and 1,700 patients (13.6%) who were not. Among survivors, the secondary endpoint of discharge home occurred in 26 patients (32.1%) who received haloperidol and 6,110 patients (55.3%) who did not. In the main analysis, there were no significant associations between haloperidol use and the primary (HR, 1.09; 95% CI, 0.60 to 1.97, p=0.772) and secondary (HR, 0.88; 95% CI, 0.50 to 1.53, p=0.643) endpoints. Results were similar in multiple sensitivity analyses. ConclusionIn this observational study involving patients with Covid-19 who had been admitted to the hospital, haloperidol use was not associated with risk of intubation or death, or with time to hospital discharge home. These results suggest that haloperidol is unlikely to have a clinical efficacy for Covid-19.

Observational Study of Chlorpromazine in Hospitalized Patients with Covid-19

On the grounds of its anti-inflammatory and potential antiviral effects, chlorpromazine has been suggested to be effective treatment for Covid-19. We examined the association between chlorpromazine use and respiratory failure among all hospitalized adults with Covid-19 at the 39 Greater Paris University hospitals since the beginning of the epidemic. Study baseline was defined as the date of hospital admission. The primary endpoint was a composite of intubation or death in a time-to-event analysis adjusting for numerous potential confounders. We used a multivariable Cox model with inverse probability weighting according to the propensity score. Of the 12,217 adult inpatients with a positive Covid-19 RT-PCR test included in the analyses, 57 (0.47%) received chlorpromazine. Over a mean follow-up of 20.8 days, the primary endpoint occurred in 29 patients (50.9%) exposed to chlorpromazine and 1,899 patients (15.6%) who were not. In the main analysis, there was a positive significant association between chlorpromazine use and the outcome (HR, 1.67; 95% CI, 1.09 to 2.56, p=0.019), while a Cox regression in a matched analytic sample yielded non-significant association (1.38; 95% CI, 0.91 to 2.09, p=0.123). These findings suggest that chlorpromazine is unlikely to have a clinical efficacy for Covid-19.

Lockdown exit strategies and risk of a second epidemic peak: a stochastic agent-based model of SARS-CoV-2 epidemic in France

Most European countries have responded to the COVID-19 threat by nationwide implementation of barrier measures and lockdown. However, assuming that population immunity will build up through the epidemic, it is likely to rebound once these measures are relaxed, possibly leading to a second or multiple repeated lockdowns. In this report, we present results of epidemiological modelling that has helped inform policy making in France. We used a stochastic agent-based microsimulation model of the COVID-19 epidemic in France, and examined the potential impact of post-quarantine measures, including social distancing, mask-wearing, and shielding of the population the most vulnerable to severe COVID-19 infection, on the diseases cumulative incidence and mortality, and on ICU-bed occupancy. The model calibrated well and variation of model parameter values had little impact on outcome estimates. While quarantine is effective in containing the viral spread, it would be unlikely to prevent a rebound of the epidemic once lifted, regardless of its duration. Both social distancing and mask-wearing, although effective in slowing the epidemic and in reducing mortality, would also be ineffective in ultimately preventing the overwhelming of ICUs and a second lockdown. However, these measures coupled with shielding of vulnerable people would be associated with better outcomes, including lower cumulative incidence, mortality, and maintaining an adequate number of ICU beds to prevent a second lockdown. Benefits would nonetheless be markedly reduced if these measures were not applied by most people or not maintained for a sufficiently long period, as herd immunity progressively establishes in the less vulnerable population.

Facing the COVID-19 epidemic in NYC: a stochastic agent-based model of various intervention strategies

Global spread of coronavirus disease 2019 (COVID-19) has created an unprecedented infectious disease crisis worldwide. Despite uncertainties about COVID-19, model-based forecasting of competing mitigation measures on its course is urgently needed to inform mitigation policy. We used a stochastic agent-based microsimulation model of the COVID-19 epidemic in New York City and evaluated the potential impact of quarantine duration (from 4 to 16 weeks), quarantine lifting type (1-step lifting for all individuals versus a 2-step lifting according to age), post-quarantine screening, and use of a hypothetical effective treatment against COVID-19 on the diseases cumulative incidence and mortality, and on ICU-bed occupancy. The source code of the model has been deposited in a public source code repository (GitHub(R)). The model calibrated well and variation of model parameter values had little impact on outcome estimates. While quarantine is efficient to contain the viral spread, it is unlikely to prevent a rebound of the epidemic once lifted. We projected that lifting quarantine in a single step for the full population would be unlikely to substantially lower the cumulative mortality, regardless of quarantine duration. By contrast, a two-step quarantine lifting according to age was associated with a substantially lower cumulative mortality and incidence, up to 71% and 23%, respectively, as well as lower ICU-bed occupancy. Although post-quarantine screening was associated with diminished epidemic rebound, this strategy may not prevent ICUs from being overcrowded. It may even become deleterious after a 2-step quarantine lifting according to age if the herd immunity effect does not had sufficient time to become established in the younger population when the quarantine is lifted for the older population. An effective treatment against COVID-19 would considerably reduce the consequences of the epidemic, even more so if ICU capacity is not exceeded.

[Study of accessibility costs and satisfaction comparing a MAS unit incorporated in a Hospital versus a theoretical model in a peripheral centre]. / Estudio del coste de la accesibilidad y de la satisfacción comparando una unidad de CMA integrada en un hospital frente a un modelo teórico en un centro periférico.

INTRODUCTION: Geographical barriers are a determining factor in the accessibility of Hospital health care, and structural changes to improve geographic accessibility must be introduced. The purpose of this study is to compare accessibility costs and the level of satisfaction obtained in an adapted Specialist Centre with a peripheral MAS (Major Ambulatory Surgery) Unit, with an already existing one incorporated into the Virgen de la Luz Hospital (Cuenca, Spain) to obtain quality health care in the sub-population nearest the peripheral Centre. MATERIAL AND METHODS: A study was made on a comparison of the costs attributable to accessibility of 133 patients operated on due to hernia disorders in 2008 in the Cuenca Hospital of Castille-La Mancha Health Service (SESCAM), and who lived in its health area. These were compared using a simulation study for an ambulatory surgical Centre, functionally operational, but with no Major Ambulatory Surgery activity nearest to this patient population. The opinions of the patients and the increased cost-effectiveness for each alternative proposal were studied. RESULTS: The accessibility cost, taking into account the theoretical use of the Ambulatory Centre would be 208,028.09 € and the real costs of the Hospital were 209,088.94 €, with a minimum difference between the two of 1,060.85 €, assuming similar clinical results. CONCLUSIONS: Although there are no significant differences in accessibility costs by using an ambulatory surgery Centre compared to the Hospital, a special assessment of the use of the former is important, expressed in the satisfaction of the patients.