Background and objectives Several studies have suggested that activation of the complement system is a contributing pathogenic mechanism in IgA nephropathy (IgAN). C4d staining is an inexpensive and easy-toperform method for the analysis of renal biopsies. This study aimed to assess the clinical and prognostic implications of C4d staining in IgAN.Design, setting, participants, & measurements This retrospective cohort study included 283 patients with IgAN in 11 hospitals in Spain who underwent a renal biopsy between 1979 and 2010. The primary predictor was mesangial C4d staining. Secondary predictors included demographic, clinical, and laboratory characteristics, and Oxford pathologic classification criteria. The primary end point was the cumulative percentage of patients who developed ESRD, defined as onset of chronic dialysis or renal transplantation. C4d was analyzed by immunohistochemical staining using a polyclonal antibody. Kaplan-Meier and Cox proportional hazards analyses were performed to evaluate the effect of C4d staining on renal survival.Results There were 109 patients (38.5%) and 174 patients (61.5%) who were classified as C4d positive and C4d negative, respectively. Renal survival at 20 years was 28% in C4d-positive patients versus 85% in C4d-negative patients (P,0.001). Independent risk factors associated with ESRD were as follows: proteinuria (hazard ratio [HR] per every 1 g/d increase. 1.16; 95% confidence interval [95% CI], 1.03 to 1.31; P=0.01), eGFR (HR per every 1 ml/min per 1.73 m 2 increase, 0.96; 95% CI, 0.94 to 0.97; P,0.001), T2 Oxford classification (tubular atrophy/ interstitial fibrosis, .50%; HR, 4.42; 95% CI, 1.40 to 13.88; P=0.01), and C4d-positive staining (HR, 2.45; 95% CI, 1.30 to 4.64; P=0.01).Conclusions C4d-positive staining is an independent risk factor for the development of ESRD in IgAN. This finding is consistent with the possibility that complement activation is involved in the pathogenesis of this disease.

Objective: To examine the association between hydroxyzine use and mortality in patients hospitalized for COVID-19, based on its anti-inflammatory and antiviral properties. Design: Multicenter observational retrospective cohort study. Setting: Greater Paris University hospitals, France. Participants: 7,345 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 source: Assistance Publique-Hopitaux de Paris Health Data Warehouse. Main outcome measures: The 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 disease 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 1:1 ratio matched analytic sample. Results: Over 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). Conclusions: In 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.

Objective: To examine the association between dexamethasone use and mortality among hospitalized patients for COVID-19. Design: Multicenter observational retrospective cohort study. Setting: Greater Paris University hospitals, France. Participants: 12,217 adults hospitalized with COVID-19 between 24 January and 20 May 2020, including 171 patients (1.4%) who received dexamethasone orally or by intravenous perfusion during the visit. Data source: Assistance Publique-Hôpitaux de Paris Health Data Warehouse. Main outcome measures: 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 adjusting for sex, age, obesity, current smoking status, any medical condition associated with increased COVID-19-related mortality, and clinical and biological severity of COVID-19 at admission, while stratifying by the need of respiratory support (i.e., oxygen or intubation). The primary analysis was a multivariable Cox model and the secondary analysis used a univariate Cox regression in a matched analytic sample. Results: Among patients who required respiratory support, the end-point event of death occurred in 10 patients (15.9%) who received dexamethasone and 298 patients (26.4%) who did not. In this group of patients, there was a significant association between dexamethasone use and reduced mortality in both the crude, unadjusted analysis (hazard ratio (HR), 0.40; 95% CI, 0.18 to 0.87, p=0.021) and the adjusted multivariable analysis (HR, 0.46; 95% CI, 0.22 to 0.96, p=0.039). In the sensitivity analysis, the univariate Cox regression model in the matched analytic sample yielded a same tendency, albeit non-significant (HR, 0.31; 95% CI, 0.08 to 1.14, p=0.077). Among patients without respiratory support, the end-point event of death occurred in 14 patients (13.0%) who received dexamethasone and 1,086 patients (10.0%) who did not. In this group of patients, there was no significant association between dexamethasone use and the endpoint. When examining the association between the cumulative dose of dexamethasone received during the visit and the endpoint, we found that the administration of a cumulative dose between 60 mg to 150 mg among patients who required respiratory support was significantly associated with a lower risk of death in the crude, unadjusted analysis (HR, 0.28; SE, 0.58, p=0.028), the adjusted multivariable analysis (HR, 0.24; SE, 0.65, p=0.030), and in the univariate Cox regression model in the matched analytic sample (HR, 0.32; SE, 0.58, p=0.048), whereas no significant association was observed with a different dose. Among patients without respiratory support, there was no significant association between the cumulative dose of dexamethasone and the endpoint in the crude and in the adjusted multivariable analyses. Conclusions: In this observational study involving patients with Covid-19 who had been admitted to the hospital, dexamethasone use administered either orally or by intravenous injection at a cumulative dose between 60 mg and 150 mg was associated with decreased mortality among those requiring respiratory support.

Factor analysis is used to evaluate relationships among inorganic ions to provide a qualitative determination of the kind of ion sources Spanish wet deposition. This procedure identifies four factors: sea, soil, aerosol, and industrial. The factor that reproduces a larger fraction of the variance is the soil or soil/aerosol and the factor reproducing a lower fraction of the variance is the industrial. The conditional probability function (CPF) [Ashbaugh e! al., 1985] is used to identify possible sources for each ion, in geographical terms. The Mediterranean region is the most important source of inorganic ions and the British Isles the single source, although intermediate, of acid rain. 1. binations of ions, which can then be used to assess sources [Sievering, 1987; Zeng and Hopke, 1989]. Crawley and Sievering [1986] used factor analysis to establish relationships among ion concentrations in the MAP3S/RAINE USA precipitation network. This technique has also been used by Post et al. [1991] and Bridgman [1992] to establish qualitative relationships among ion concentrations in wet deposition in SE Australia, by Ayers and Manton [1991] for the same use at BAPMON regional stations in Australia, and by Kessler et al. [1992] to assess the sources of different wet deposition components in Texas (United States).In this paper, factor analysis is used to establish qualitative relationship among inorganic ion concentrations in Spanish wet deposition and to establish emission sources that contribute to wet deposition composition.Factor analysis may show the nature of the source but not find its location. To achieve that, it is necessary to introduce meteorological information. This has been made, for example, by Raynor and Hayes [1982] or Singh et al. [1987]. It has been shown [Miller et al., 1978; Asman et al., 1981] that air mass trajectories at the synoptic scale account for major variations

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Premature mortality rates showed higher premature mortality in the most deprived districts.

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