The introduction of antipsychotics in the 1950s revolutionised the treatment of schizophrenia, but it soon became apparent that a substantial number of patients demonstrated a suboptimal response to these antipsychotics. Clozapine proved to be beneficial in patients whose symptoms were treatment resistant, but it too had limitations, with as many as 40-70% of those treated with clozapine demonstrating inadequate response to this drug as well. The availability of other 'atypical' antipsychotics offers options, but clozapine appears to remain the most effective option in treatment-resistant schizophrenia. This, of course, raises the question of what to do when clozapine is only partially effective. To address the issue of treatment in patients who have demonstrated a suboptimal response to clozapine, efforts have focused on a variety of augmentation strategies, including numerous medications and electroconvulsive therapy. The current body of evidence consists largely of data from smaller open trials and case series/reports, although data from a limited number of controlled studies are now available. Not surprisingly, the evidence drawn from the former is more supportive of augmentation strategies, although the controlled trials are not without positive findings. The available information is certainly not so overwhelming as to endorse any single augmentation approach. Indeed, it argues for more controlled data and cautions us regarding the cost-benefit ratio in adopting this strategy. Over and above the added adverse effects of another treatment, there is evidence to indicate that actual clinical worsening can occur. Without compelling evidence, clinicians must resort to guiding principles. The potential benefits of augmentation cannot be ruled out, but it should be approached with caution and in a systematic fashion. Factors compromising clozapine response should first be ruled out, and any augmentation trials should be guided by existing evidence and a treatment plan that incorporates a clear understanding of target symptoms. A means of evaluating outcome effectively needs to be in place, and the trial should be circumscribed to prevent needless polypharmacy. A priori, an endpoint needs to be established and the trial discontinued unless results firmly support added benefits.

Background Coronavirus-associated acute respiratory distress syndrome (CARDS) has limited effective therapy to date. NLRP3 inflammasome activation induced by SARS-CoV-2 in COVID-19 contributes to cytokine storm. Methods This randomised, multinational study enrolled hospitalised patients (18–80 years) with COVID-19-associated pneumonia and impaired respiratory function. Eligible patients were randomised (1:1) via Interactive Response Technology to DFV890 + standard-of-care (SoC) or SoC alone for 14 days. Primary endpoint was APACHE II score at Day 14 or on day-of-discharge (whichever-came-first) with worst-case imputation for death. Other key assessments included clinical status, CRP levels, SARS-CoV-2 detection, other inflammatory markers, in-hospital outcomes, and safety. Findings Between May 27, 2020 and December 24, 2020, 143 patients (31 clinical sites, 12 countries) were randomly assigned to DFV890 + SoC ( n = 71) or SoC alone ( n = 72). Primary endpoint to establish clinical efficacy of DFV890 vs. SoC, based on combined APACHE II score, was not met; LSM (SE), 8·7 (1.06) vs. 8·6 (1.05); p = 0.467. More patients treated with DFV890 vs. SoC showed ≥ 1-level improvement in clinical status (84.3% vs. 73.6% at Day 14), earlier clearance of SARS-CoV-2 (76.4% vs. 57.4% at Day 7), and mechanical ventilation-free survival (85.7% vs. 80.6% through Day 28), and there were fewer fatal events in DFV890 group (8.6% vs. 11.1% through Day 28). DFV890 was well tolerated with no unexpected safety signals. Interpretation DFV890 did not meet statistical significance for superiority vs. SoC in primary endpoint of combined APACHE II score at Day 14. However, early SARS-CoV-2 clearance, improved clinical status and in-hospital outcomes, and fewer fatal events occurred with DFV890 vs. SoC, and it may be considered as a protective therapy for CARDS. Trial registration ClinicalTrials.gov, NCT04382053. Supplementary Information The online version contains supplementary material available at 10.1007/s15010-022-01904-w.

In a pneumatic tire, the contained air carries the load of the vehicle and also augments performance for other functional requirements, such as, rolling resistance, ride and handling, durability, and so on. The inner liner of the tire is responsible to ensure air retention by virtue of its high air impermeability. The present study focused on developing inner‐liner compounds of improved air impermeability by utilizing platelet filler (layered silicate). The obtained organoclay was subjected to a pre‐treatment process called exfoliation to increase the d spacing between the clay layers that further improved the morphological aspect of the compound. The inner‐liner compound has been modified by partial replacement of carbon black with organically modified bentonite clay in 1:1 and 2.5:1 ratio. Air impermeability of rubber compounds was tested in a gas permeability tester. Field emission scanning electron microscope, transmission electron microscope, atomic force microscope, and x‐ray diffraction were utilized to understand the distribution and dispersion of clay in the rubber compounds. Fatigue crack growth analysis was carried out to measure the fatigue life of the materials. The modified compounds exhibited air impermeability improvement from 7% to 30% vs the reference carbon‐black filled compound with improved mechanical properties and filler dispersion.

Cardiac arrhythmias are common in patients of COVID -19 and frequently complicate the clinical course of critically ill patients. Life threatening arrhythmia including ventricular fibrillation less common but are reported to be more common in patients with elevated cardiac troponins. The mechanisms of arrhythmia in COVID 19 are multifactorial and arise from either direct cardiac involvement, from consequences systemic affection or drug interactions. The successful management requires correct identification of the cause. We report a case of VF storm in a patient with COVID 19 who responded to steroid therapy. Controlling the fulminant inflammation may reduce the burden of arrhythmia in appropriate cases.

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