Pre-Antiretroviral Therapy Serum Selenium Concentrations Predict WHO Stages 3, 4 or Death but not Virologic Failure Post-Antiretroviral Therapy

A case-cohort study, within a multi-country trial of antiretroviral therapy (ART) efficacy (Prospective Evaluation of Antiretrovirals in Resource Limited Settings (PEARLS)), was conducted to determine if pre-ART serum selenium deficiency is independently associated with human immunodeficiency virus (HIV) disease progression after ART initiation. Cases were HIV-1 infected adults with either clinical failure (incident World Health Organization (WHO) stage 3, 4 or death by 96 weeks) or virologic failure by 24 months. Risk factors for serum selenium deficiency (<85 μg/L) pre-ART and its association with outcomes were examined. Median serum selenium concentration was 82.04 μg/L (Interquartile range (IQR): 57.28–99.89) and serum selenium deficiency was 53%, varying widely by country from 0% to 100%. In multivariable models, risk factors for serum selenium deficiency were country, previous tuberculosis, anemia, and elevated C-reactive protein. Serum selenium deficiency was not associated with either clinical failure or virologic failure in multivariable models. However, relative to people in the third quartile (74.86–95.10 μg/L) of serum selenium, we observed increased hazards (adjusted hazards ratio (HR): 3.50; 95% confidence intervals (CI): 1.30–9.42) of clinical failure but not virologic failure for people in the highest quartile. If future studies confirm this relationship of high serum selenium with increased clinical failure, a cautious approach to selenium supplementation might be needed, especially in HIV-infected populations with sufficient or unknown levels of selenium.     

Time to Administration of Antibiotics among Inpatients with Severe Sepsis or Septic Shock

Background

Current evidence suggests that administration of appropriate antibiotic therapy within 1 h after the onset of hypotension significantly improves mortality rates among patients with severe sepsis and septic shock.

Objectives:

To determine the interval from recognition of severe sepsis or septic shock in inpatients to initial administration of antibiotic and to assess institutional compliance with the Surviving Sepsis Campaign’s recommendation for early antibiotic therapy.

Methods:

A 6-month retrospective chart analysis was conducted to determine the interval from documented onset of hypotension to initial administration of antibiotic for patients with severe sepsis or septic shock. Patients who were admitted to a general medicine ward, a surgery ward, or the intensive care unit (ICU) of a 475-bed university-affiliated hospital and who met the criteria for severe sepsis or septic shock were eligible for inclusion. Patients who received antibiotics before meeting the criteria for severe sepsis or septic shock were excluded.

Results:

Charts for 100 patients with severe sepsis or septic shock were reviewed. The mean age was 69.0 years (standard deviation 18.7 years), and 56% were men. The median interval from onset of severe sepsis or septic shock to administration of antibiotic was 4.00 h (interquartile range [IQR] 1.80–6.45 h). The median interval from the time a physician ordered an antibiotic to administration of the drug was 1.28 h (IQR 0.57–3.05 h). The interval between ordering and administration differed significantly for patients on the wards (5.67 h), those with onset in the ICU (4.00 h), and those with onset in the emergency department (3.28 h) (p = 0.039). The overall survival rate was 56%.

Conclusion:

At the study hospital, the interval from onset of severe sepsis or septic shock to initial administration of antibiotic to inpatients exceeded the 1-h period recommended by the Surviving Sepsis Campaign. These results will be used as a baseline for future quality assurance and improvement initiatives aimed at minimizing the time to antibiotic administration for this group of patients, who are at high risk of death.     

Cancer risk of immunosuppressants in manufacturing

During the chemical and pharmaceutical production of active pharmaceutical substances which are intended for immunosuppressive therapy, the employees may be exposed to these substances via inhalation. Immunosuppressants are linked to development of certain types of cancers e.g., lymphoma or skin cancer in transplant patients. The development of these cancers in patients is linked to the level of immunosuppression needed for transplantation in order to avoid organ rejection. Below these levels, with the immune system functioning uninhibited, cancer is unlikely to develop.     

Implications of Marijuana Legalization for Adolescent Substance Use

ABSTRACT. Marijuana that is legally available for adults has multiple implications for adolescent substance use. One potential effect that legalization may have is an increase in adolescent use to due increased availability, greater social acceptance, and possibly lower prices. Legalization may also facilitate the introduction of new formulations of marijuana (edible, vaporized) and with potentially higher potencies. It is unknown what adolescent consumption patterns will be if marijuana is widely available and marketed in different forms, or what effects different patterns of adolescent use will have on cognition, the development of marijuana use disorders, school performance, and the development of psychotic illnesses. Also unclear is whether adolescent users will be experiencing higher levels of tetrahydrocannabinol (THC) compared with previous generations of users due to higher potencies. Although previous studies of the effects of adolescent marijuana use provide some guidance for current policy and public health recommendations, many new studies will be needed that answer questions in the context of use within a legal adult environment. Claims that marijuana has medicinal benefits create additional challenges for adolescent prevention efforts, as they contrast with messages of its harmfulness. Prevention and treatment approaches will need to address perceptions of the safety of marijuana, claims of its medicinal use, and consider family-wide effects as older siblings and parents may increasingly openly consume and advocate for marijuana use. Guidance for primary care physicians will be needed regarded screening and counseling. Widespread legalization and acceptance of marijuana implies that as law enforcement approaches for marijuana control decline, public health, medical, and scientific efforts to understand and reduce negative consequences of adolescent marijuana use need to be substantially increased to levels commensurate with those efforts for tobacco and alcohol.     

Aversive Learning in Adolescents: Modulation by Amygdala–Prefrontal and Amygdala–Hippocampal Connectivity and Neuroticism

Neuroticism involves a tendency for enhanced emotional and cognitive processing of negative affective stimuli and a propensity to worry and be anxious. It is known that this trait modulates fear learning and the activation of brain regions involved in it such as the amygdala, hippocampus, and prefrontal cortex and their connectivity. Thirty-nine (21 female) 14-year-old healthy adolescents participated in functional magnetic resonance imaging (fMRI) of aversive pavlovian differential delay conditioning. An unpleasant sound served as unconditioned stimulus (US) and pictures of neutral male faces as conditioned stimuli (CS+ followed by the US in 50% of the cases; CS− never followed by the US). During acquisition (CS+/− differentiation), higher levels of neuroticism were associated with a stronger interaction between the right amygdala and the right hippocampus as well as the right amygdala and prefrontal cortical regions, specifically ventromedial prefrontal cortex, dorsolateral prefrontal cortex, and anterior cingulate cortex. The association of stronger conditionability of fear and connectivity of brain regions related to consolidation of fear associations and neuroticism points to underlying mechanisms of the enhanced propensity for anxiety disorders in highly neurotic participants. This is especially important in adolescence, a vulnerable time for the onset of mental disorders such as anxiety disorders.