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Patients with cancer are at high risk of severe coronavirus disease 2019 (COVID-19), with high morbidity and mortality. Furthermore, impaired humoral response renders severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines less effective and treatment options are scarce. Randomized trials using convalescent plasma are missing for high-risk patients. Here, we performed a randomized, open-label, multicenter trial ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001632-10/DE ) in hospitalized patients with severe COVID-19 (n = 134) within four risk groups ((1) cancer (n = 56); (2) immunosuppression (n = 16); (3) laboratory-based risk factors (n = 36); and (4) advanced age (n = 26)) randomized to standard of care (control arm) or standard of care plus convalescent/vaccinated anti-SARS-CoV-2 plasma (plasma arm). No serious adverse events were observed related to the plasma treatment. Clinical improvement as the primary outcome was assessed using a seven-point ordinal scale. Secondary outcomes were time to discharge and overall survival. For the four groups combined, those receiving plasma did not improve clinically compared with those in the control arm (hazard ratio (HR) = 1.29; P = 0.205). However, patients with cancer experienced a shortened median time to improvement (HR = 2.50; P = 0.003) and superior survival with plasma treatment versus the control arm (HR = 0.28; P = 0.042). Neutralizing antibody activity increased in the plasma cohort but not in the control cohort of patients with cancer (P = 0.001). Taken together, convalescent/vaccinated plasma may improve COVID-19 outcomes in patients with cancer who are unable to intrinsically generate an adequate immune response., (© 2022. The Author(s).)

Objective: An increasing number of children and youth in Canada are taking medical cannabis for complex medical conditions. While they deserve safe and consistent access to pharmacotherapy throughout the day, administrative policies on cannabis use in schools are inconsistent. A scoping review identified policies and publications associated with medical cannabis in Canadian schools. Methods: Five databases (Scopus, PubMed, CINAHL, EMBASE, and Web of Science) were searched to identify scientific literature. Legislation in each province and territory and Ministry of Education webpages were reviewed for pertinent laws and policies regarding cannabis use in schools. Results: The scientific search resulted in 1289 articles. The five included articles pertain to implications for school nurses in the United States, which are not relevant to the Canadian context. A search of Ministry of Education websites identified only one policy with information regarding medical cannabis in schools (from Ontario). Federal legislation (the Cannabis Act ) does not specifically address medical cannabis in schools, and there is a lack of consistency in terminology and clarity within provincial and territorial laws. All provinces and territories prohibit smoking and vaping of cannabis on school property and some provinces prohibit any method of cannabis consumption. Conclusions: In Canada, there is a lack of guidance for medical cannabis administration, storage, and disposal in schools, with some policies explicitly prohibiting this type of treatment. This shifts the burden to families to individually create plans school by school. A federally harmonized approach to supporting children who take cannabis for medical purposes ought to be explored.

There is a high need for novel treatment options in relapsed and refractory diffuse large B-cell lymphoma. Single agent mammalian target of rapamycin (mTOR) inhibitor treatment has shown promising efficacy in this entity. Here, we report on the results of the mTOR-inhibitor temsirolimus combined to standard rituximab-DHAP salvage regimen in a prospective, multicenter, phase II, open-label study. The STORM regimen consisted of rituximab 375 mg/m 2 (day 2) and DHAP (dexamethasone 40 mg day 3-6, cisplatinum 100 mg/m 2 day 3, cytarabine 2 × 2  g/m 2 day 4) with temsirolimus added on day 1 and 8 of a 21-day cycle, with 2 to 4 cycles planned. In part I, dose levels of 25, 50, 75, and 100 mg for temsirolimus were predefined. Based on the observed toxicity profile, a temsirolimus dose of 25 mg was defined as recommended dose for the part II extension cohort of the trial. The intention-to-treat cohort comprised 53 patients. Median age was 63 years and median number of prior regimen was 1. All but 1 patient had prior rituximab exposure. Temsirolimus dose was 50 mg on day 1 and 8 in 6 patients from the part I of the trial and 25 mg in the remaining 47 patients. In general, treatment was well tolerated with leucopenia and thrombocytopenia as most frequent severe adverse events. The overall response rate after the last cycle of temsirolimus R-DHAP was 66% with 24% complete responses. The ability to mobilize stem cells was not impaired by the treatment regimen. Twenty-eight patients received consolidation treatment with high-dose therapy (HDT) and stem cell transplantation. Median duration of response was not reached. The total 2-year progression-free survival (PFS) and overall survival (OS) were 53% and 59%. Patients who were consolidated with HDT achieved a 2-year PFS and a 2-year OS of 77.8% and 82.1%, respectively. We conclude that temsirolimus can be safely added to rituximab and DHAP with promising activity., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.)

Background: Because cannabis use in children can have negative consequences, the recent legalization of recreational cannabis for adults in Canada creates an urgent need for youth education., Method: A multidisciplinary clinical rotation was developed wherein nursing and pharmacy students collaborated with youth (grades 7 through 10) to construct an educational program about cannabis. Four schools participated, representing a variety of socioeconomic demographics. Feedback was solicited from students and stakeholders. The purpose of this project was to create REACH (Real Education About Cannabis and Health), a toolkit and curriculum resource that includes lesson plans for teachers covering the science of cannabis, social science implications, peer pressure, decision making and harm reduction, videos featuring youth testimonials, and supplemental resources., Results: Preliminary feedback suggests the materials are engaging and informative., Conclusion: A collaboration of health science students with youth in schools resulted in an authentic and relatable educational program about cannabis. Future studies will evaluate REACH's effectiveness in seventh- and ninth-grade students. [J Nurs Educ. 2020;59(8):465-469.]., (Copyright 2020, SLACK Incorporated.)

The manufacturing of pharmaceuticals also produces wastes, mainly wastewaters (WWs). These WWs must be responsibly managed. Sometimes, the organic contents of these WWs are not easily removable in standard WW treatment, hence technical options must be investigated to pretreat such WWs in order to remove or destroy the recalcitrant compounds, mostly the active pharmaceutical ingredients themselves. This contribution from a pharmaceuticals company describes WW assessment and management principles, the search for pretreatment options and several case studies on WW (pre)treatment at some pharma production sites of the Roche Group.

In low risk MDS, increased apoptosis of erythroid progenitors mediated via CD95 (Fas) activation has been described to result in peripheral cytopenia. Blockade of the CD95 system can improve erythropoiesis in MDS. Asunercept (APG101) is a fusion protein consisting of the extracellular domain of human CD95 and the Fc domain of human IgG1 blocking the interaction between CD95 and its ligand. Here we report on results from a phase I study in 20 transfusion-dependent low and intermediate risk MDS patients treated with intravenous asunercept (EudraCT 2012-003027-37). Primary objectives were safety and tolerability as well as pharmacodynamic effects. Secondary objectives were hematologic improvement, incidence and time to leukemic progression as well as overall survival. Frequency and severity of adverse events were in range of what could be expected in a patient cohort comprising of elderly MDS patients. Two patients experienced a serious adverse event with a suspected relationship to asunercept. The incidence of disease progression was low. In the 20 patients a decrease of the transfusion need from a mean of 10,8 (±5,1) pRBCs during the 12 weeks treatment phase to a mean of 10,0 (±4,2) pRBCs at the end of the study was observed. In conclusion, asunercept was well tolerated and showed efficacy in transfusion-dependent low and intermediate risk MDS patients. Further clinical investigation is warranted, particularly in combination with erythropoiesis stimulating agents (ESAs)., (Copyright © 2018. Published by Elsevier Ltd.)

Q fever is a zoonotic disease caused by the bacterium Coxiella burnetii. Clinical presentation in humans varies from asymptomatic to flu-like illness and severe sequelae may be seen. Ruminants are often sub-clinically infected or show reproductive disorders such as abortions. In Egypt, only limited data on the epidemiology of Q fever in animals are available. Using a stratified two stage random sampling approach, we evaluated the prevalence of Coxiella burnetii specific antibodies among ruminants and camels in 299 herds. A total of 2,699 blood samples was investigated using enzyme-linked-immunosorbent assay (ELISA). Coxiella burnetii specific antibodies were detected in 40.7% of camels (215/528), 19.3% of cattle (162/840), 11.2% of buffaloes (34/304), 8.9% of sheep (64/716) and 6.8% of goats (21/311), respectively. Odds of seropositivity were significantly higher for cattle (aOR: 3.17; 95% CI: 1.96-5.13) and camels (aOR: 9.75; 95% CI: 6.02-15.78). Significant differences in seropositivity were also found between domains (Western Desert, Eastern Desert and Nile Valley and Delta) and 25 governorates (p < 0.001), respectively. Animal rearing in the Eastern Desert domain was found to be a significant risk factor (aOR: 2.16; 95% CI: 1.62-2.88). Most seropositive animals were older than four years. No correlation between positive titers and husbandry practices or animal origin were found (p > 0.05). Only 8.7% of the interviewed people living on the farms consumed raw camel milk and none reported prior knowledge on Q fever. Findings from this nationwide study show that exposure to Coxiella burnetii is common in ruminants and camels. Disease awareness among physicians, veterinarians and animal owners has to be raised. Future epidemiological investigations have to elucidate the impact of Q fever on human health and on the economy of Egypt.

In the multicentre prospective randomized HD2002 trial, rituximab maintenance therapy (375 mg/m(2) every 3 months for 2 years) versus observation was evaluated for CD20(+) B-cell lymphoma. Out of 321 patients [161 randomized to the treatment group (TG), 160 to the observation group (OG)], 295 data sets were evaluable for statistical analysis. Estimated 5-year relapse-free survival (RFS) was 81% in the TG and 70% in the OG (logrank test, P = 0·047). In the diffuse large B-cell lymphoma (DLBCL) subgroup (n = 152), 5-year RFS was excellent, at 87% in the TG and 84% in the OG (logrank test, P = 0·35). Of note, only in male patients of the DLBCL subgroup was RFS significantly superior in the TG in comparison to the OG (5-year RFS: 88% vs. 74%; logrank test, P = 0·05). Cox regression analysis showed a significant interaction between treatment and gender regarding overall survival (OS) (P = 0·006) and RFS (P = 0·02), with a lower hazard in females than males in the OG [OS: hazard ratio (HR) (female:male) = 0·11; 95% confidence interval (CI) = 0·00-1·03; RFS: HR (female:male) = 0·27; 95% CI = 0·05-0·97], and no significant differences between males and females in the TG. We conclude that Rituximab maintenance therapy improves survival in male patients with DLBCL., (© 2015 John Wiley & Sons Ltd.)

An increasing number of pharmaceutical active substances are produced through biotechnological processes. For sustained and safe growth of the host organisms as well as optimal expression, purification, and formulation of the product, biotechnological manufacturing processes need optimal and robust environmental conditions, which are attained through the use of buffers, chelators, and antibiotics, beside nutrients. These ancillary substances are drained with the wastewater to a wastewater treatment plant (WWTP) and are released after treatment with the effluent to receiving waters. The potential risks of such substances to WWTPs and surface waters were investigated. Three common buffers (morpholinoethane sulfonic acid [MES], morpholinopropanesulfonic acid [MOPS], 1,4-piperazine (diethanesulfonic acid) [PIPES]), one chelator (ethylenediaminetetraacetic acid [EDTA]), and one antibiotic (gentamycin) were searched in the literature for environmental data or tested for biodegradability and inhibition of activated sludge as well as acute toxicity to algae, daphnids, and fish. Amounts of the ancillary substances used in the European biotechnological production plants of F. Hoffmann-La Roche Ltd in Basle (Switzerland) and Penzberg (Germany), and actual wastewater fluxes through the respective WWTP, as well as realistic dilution factors for the local receiving water, were documented. Based on this information, site-specific predicted environmental concentrations (PECs) for the WWTPs and surface waters in Basle and Penzberg were extrapolated. These PECs were compared with predicted no effect concentrations (PNECs) for the WWTP and surface waters, derived from sludge inhibition and ecotoxicity results, respectively. For all five ancillary substances investigated, all PEC/PNEC risk characterization ratios are <1, indicating no significant risk to the WWTPs or the receiving waters at both sites., (Copyright © 2011 SETAC.)