Comprehensive dissection of prevalence rates, sex differences, and blood level-dependencies of clozapine-associated adverse drug reactions

Clozapine is often underused due to concerns about adverse drug reactions (ADRs) but studies into their prevalences are inconclusive. We therefore comprehensively examined prevalences of clozapineassociated ADRs in individuals with schizophrenia and demographic and clinical factors associated with their occurrence. Data from a multi-center study (n=698 participants) were collected. The mean number of ADRs during clozapine treatment was 4.8, with 2.4% of participants reporting no ADRs. The most common ADRs were hypersalivation (74.6%), weight gain (69.3%), and increased sleep necessity (65.9%), all of which were more common in younger participants. Participants with lower BMI prior to treatment were more likely to experience significant weight gain (>10%). Constipation occurred more frequently with higher clozapine blood levels and doses. There were no differences in ADR prevalence rates between participants receiving clozapine monotherapy and polytherapy. These findings emphasize the high prevalence of clozapine-associated ADRs and highlight several demographic and clinical factors contributing to their occurrence. By understanding these factors, clinicians can better anticipate and manage clozapine-associated ADRs, leading to improved treatment outcomes and patient well-being

High Risk of Secondary Infections Following Thrombotic Complications in Patients With COVID-19

Background. This study’s primary aim was to evaluate the impact of thrombotic complications on the development of secondary infections. The secondary aim was to compare the etiology of secondary infections in patients with and without thrombotic complications. Methods. This was a cohort study (NCT04318366) of coronavirus disease 2019 (COVID-19) patients hospitalized at IRCCS San Raffaele Hospital between February 25 and June 30, 2020. Incidence rates (IRs) were calculated by univariable Poisson regression as the number of cases per 1000 person-days of follow-up (PDFU) with 95% confidence intervals. The cumulative incidence functions of secondary infections according to thrombotic complications were compared with Gray’s method accounting for competing risk of death. A multivariable Fine-Gray model was applied to assess factors associated with risk of secondary infections. Results. Overall, 109/904 patients had 176 secondary infections (IR, 10.0; 95% CI, 8.8–11.5; per 1000-PDFU). The IRs of secondary infections among patients with or without thrombotic complications were 15.0 (95% CI, 10.7–21.0) and 9.3 (95% CI, 7.9–11.0) per 1000-PDFU, respectively (P = .017). At multivariable analysis, thrombotic complications were associated with the development of secondary infections (subdistribution hazard ratio, 1.788; 95% CI, 1.018–3.140; P = .043). The etiology of secondary infections was similar in patients with and without thrombotic complications. Conclusions. In patients with COVID-19, thrombotic complications were associated with a high risk of secondary infections

Entropy contribution to the nickel(III)/nickel(II) redox change in six-coordinating systems. Investigation of the role of the negative charge of the ligand in the stabilization of high oxidation states of the metal center

Entropy changes ΔS°rc assocd. with the 2 half-reactions (i) [NiIIIL2]3+ + e- = [NiIIL2]2+ and (ii) [NiIIIY]0 + e- = [NiIIY] (L = 1,4,7-triazacyclononane H3Y = 1,4,7-triazacyclononane-N,N',N''-triacetic acid) were detd. through the investigation of the temp. dependence of the E1/2(NiIII/NiII) parameter over the 0.1-3.5M concn. range of the background electrolyte (NaCl). The ΔS°rc for half-reaction (i) is pos., and its value decreases with an increasing concn. of the supporting electrolyte, whereas ΔS°rc for half-reaction ii is neg. and its value increases (becoming less neg.) with an increasing concn. of NaCl. The above results were interpreted in terms of variation in the size of the hydration sphere of the electroactive species, which are related to changes of the elec. charge on the complexes. In particular, it was shown that such polyneg. charged ligands as Y3- favor access to unusually high oxidn. states of the metal center due a very favorable entropy term: this reflects a substantial increase of translational entropy, assocd. with the release of H2O mols. from the hydration sphere of the complex during the [NiIIY]/[NiIIIY]0 oxidn. proces

New human remains from the Late Epigravettian necropolis of Arene Candide (Liguria, northwestern Italy): Direct radiocarbon evidence and inferences on the funerary use of the cave during the Younger Dryas

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