Resilience in adolescence during the COVID-19 crisis in Canada.

BACKGROUND: The COVID-19 pandemic constitutes a social crisis that will have long-term health consequences for much of the global population, especially for adolescents. Adolescents are triply affected as they: 1) are experiencing its immediate, direct effects, 2) will carry forward health habits they develop now into adulthood, and 3) as future parents, will shape the early life health of the next generation. It is therefore imperative to assess how the pandemic is influencing adolescent wellbeing, identify sources of resilience, and outline strategies for attenuating its negative impacts. METHODS: We report the results of longitudinal analyses of qualitative data from 28 focus group discussions (FGDs) with 39 Canadian adolescents and of cross-sectional analyses of survey data from 482 Canadian adolescents gathered between September 2020 and August 2021. FGD participants and survey respondents reported on their: socio-demographic characteristics; mental health and wellbeing before and during the pandemic; pre- and during-pandemic health behaviours; experiences living through a crisis; current perceptions of their school, work, social, media, and governmental environments; and ideas about pandemic coping and mutual aid. We plotted themes emerging from FGDs along a pandemic timeline, noting socio-demographic variations. Following assessment for internal reliability and dimension reduction, quantitative health/wellbeing indicators were analyzed as functions of composite socio-demographic, health-behavioural, and health-environmental indicators. RESULTS: Our mixed methods analyses indicate that adolescents faced considerable mental and physical health challenges due to the pandemic, and were generally in poorer health than expected in non-crisis times. Nevertheless, some participants showed significantly better outcomes than others, specifically those who: got more exercise; slept better; were food secure; had clearer routines; spent more time in nature, deep in-person social relationships, and leisure; and spent less time on social media. CONCLUSIONS: Support for youth during times of crisis is essential to future population health because adolescence is a period in the life course which shapes the health behaviours, socio-economic capacities, and neurophysiology of these future parents/carers and leaders. Efforts to promote resilience in adolescents should leverage the factors identified above: helping them find structure and senses of purpose through strong social connections, well-supported work and leisure environments, and opportunities to engage with nature.

Clinical Trial of the Pan-Caspase Inhibitor, IDN-6556, in Human Liver Preservation Injury.

Cold ischemia/warm reperfusion (CI/WR) injury remains a problem in liver transplantation. The aim of the current study was to assess the utility of the pan-caspase inhibitor IDN-6556 on CI/WR injury during human liver transplantation. This report is a post hoc analysis of a Phase II, multi-center, randomized, placebo-controlled, double-blinded, parallel group study. Subjects were assigned to four treatment groups: Group 1 (Organ storage/flush: Placebo-Recipient: Placebo); Group 2 (Organ storage/flush: 15 microg/mL-Recipient: Placebo); Group 3 (Organ storage/flush: 5 microg/mL-Recipient: 0.5 mg/kg); and Group 4 (Organ storage/flush: 15 microg/mL-Recipient: 0.5 mg/kg). Liver cell apoptosis was assessed by serum concentrations of the apoptosis-associated CK18Asp396 ('M30') neo-epitope, TUNEL assay and caspase 3/7 immunohistochemistry. Liver injury was assessed by serum AST/ALT determinations. Serum markers of liver cell apoptosis were reduced in all groups receiving drug as compared to placebo. However, TUNEL, caspase 3/7 positive cells and serum AST/ALT levels were only consistently reduced in Group 2 (drug exposed to organ only). This reduction in serum transaminases was significant and observed across the study. In conclusion, IDN-6556 when administered in cold storage and flush solutions during liver transplantation offers local therapeutic protection against CI/WR-mediated apoptosis and injury. However, larger studies are required to confirm these observations.

Supporting pharmaceutical studies for FDA submissions: diversifying the drug monitoring laboratory.

Well-founded pharmacokinetic information is one of the cornerstones of a New Drug Application (NDA) to the Food and Drug Administration (FDA) required to introduce a new drug or a generic equivalent (ANDA) to the marketplace. The service that laboratories engaged in therapeutic drug monitoring provide to support clinical activities is also needed by the pharmaceutical industry during the evaluation and introduction of drugs to the marketplace. In considering this alternative service activity, one must be aware of and compliant with rules established by the FDA for performance of such studies. As specified in CFR 21, Parts 58, 211, and 320, good clinical and laboratory practice indicates that the laboratory should employ a Lab Study Director, who is responsible for the validation of all procedures implemented to support a study protocol, ensures that the laboratory carries out the study following these defined procedures, and personally reviews the results of all testing. The laboratory must validate each procedure by demonstrating and documenting that the procedure does what it is designed to do while meeting the analytical performance specifications required by the study. Laboratory records of all activities must be maintained and available for inspection by the FDA on request. The FDA has authority over all activities related to NDA and ANDA submissions and can bring criminal charges if results of a study are changed because a laboratory deviates from standard procedure. Competent drug monitoring laboratories are fully capable of participating in clinical trials testing activities. Laboratory staff should be fully versed in the FDA rules governing these activities, validate all procedures, and establish systems to verify the procedures are carried out as specified.

Single- and multiple-dose-response relationships of beta-carotene in cystic fibrosis.

Concentrations of carotenoids are low in patients with cystic fibrosis (CF) and are associated with essential fatty acid deficiency and increased markers of inflammation. We conducted single- and multiple-dose studies of beta-carotene supplementation in patients with CF. Dose-proportional increases in beta-carotene concentrations were found, although clearance was independent of dose. Large doses of beta-carotene were necessary to achieve normal plasma levels.

Clinical pharmacology of cytarabine in patients with acute myeloid leukemia: a cancer and leukemia group B study.

The pharmacokinetics of cytarabine (ara-C) were determined in 265 patients with acute myeloid leukemia (AML) receiving ara-C (200 mg/m2 per day for 7 days as a continuous infusion) and daunorubicin during induction therapy. The mean (standard deviation) ara-C concentration at steady-state (Css) and systemic clearance (Cl) were 0.30 (0.13) microM and 134 (71) l/h per m2 respectively. Males had a significantly faster ara-C Cl (139 vs 131 l/h per m2, P = 0.025) than females. Significant correlations were noted between ara-C Cl and the pretreatment, peripheral white blood cell count (P = 0.005) and pretreatment blast count (P = 0.020). No significant differences in ara-C Css or Cl were noted in patients achieving complete remission compared with those failing therapy (P = 0.315, P = 0.344, respectively). No significant correlations were observed between ara-C pharmacokinetic parameters and several indices of patient toxicity. Our findings indicate that variability in ara-C disposition in plasma at this dosage level does not correlate with remission status or toxicity in patients with AML receiving initial induction therapy with ara-C and daunorubicin.

Treatment effects of alprazolam and imipramine: physiological versus subjective changes in patients with generalized anxiety disorder.

The correspondence between changes in physiological activity and somatic symptom reports was assessed in generalized anxiety disorder patients treated with alprazolam or imipramine. After 6 weeks, the two medications produced comparable reductions in self-reported somatic symptoms. However, patients taking alprazolam showed decreases in systolic blood pressure, epinephrine, and norepinephrine, and patients taking imipramine showed increases in heart rate, blood pressure, electromyographic activity, and norepinephrine. Thus, though the physiological changes associated with alprazolam treatment were consistent with changes in symptom reports, treatment with imipramine produced a desynchrony: patients reported significant decreases in cardiovascular symptoms and muscle tension in spite of the fact that heart rate, blood pressure, and electromyographic activity increased. Possible explanations for this counterintuitive phenomenon are discussed.

Removal of an endogenous antigen from an antibody to increase its effective affinity constant, as illustrated by triiodothyronine assay.

Antisera to triiodothyronine were shown to contain large quantities of the hormone, well in excess of normal circulating concentrations. Extracting the triiodothyronine from the antiserum with alkaline ethanol yielded an antibody of increased affinity. Use of this antibody in a radioimmunoassay resulted in a fourfold increase in sensitivity as compared with the unextracted material.

A system of interpretation of infrared spectra of calculi for routine use in the clinical laboratory.

We have devised systematic schemes for objectives qualitative analysis of the IR spectra of calculi. These schemes are presented as flow charts based on questions each requiring a yes or no answer before going on to the next step. The specific question asked in each step concerns the similarity of a limited region of the spectrum to reference spectra. For renal calculi, 5 regions are evaluated and a maximum of 10 decisions is necessary to complete the analysis. Biliary calculi are treated similarily, with 5 spectral regions evaluated and a maximum of 8 yes-no decisions required. The method requires less technician time and is much less susceptible to differences in subjective judgment than the wet chemical procedure. Three percent of stones contain unusual components and are quickly recognized as such and identified using a library of reference spectra.

Sample stability: a suggested definition and method of determination.

We propose defining the stability of any chemical constituent of stored samples in terms that are quantitatively related to the precision of the measurement by which it is determined. We suggest that a constituent may be considered stable, for a stated period and under exactly defined conditions, when the average change in its measured value is less than a chosen number, K, of standard deviations of the data obtained by the measuring method over the concentration range in question. Based on this definition a technique utilizing a graphical truncated normal sequential test is presented as the appropriate experimental and statistical design for measuring stability. The statistical basis for the proposal is presented.