Mid-upper arm circumference predicts death in adult patients admitted to a TB ward in the Philippines: A prospective cohort study.

BACKGROUND: The Philippines is ranked 3rd globally for tuberculosis incidence (554/100,000 population). The tuberculosis ward at San Lazaro Hospital, Manila receives 1,800-2,000 admissions of acutely unwell patients per year with high mortality. Objectives of this prospective cohort study were to quantify the association of under-nutrition (primary) and diabetes (secondary) with inpatient mortality occurring between 3-28 days of hospital admission in patients with suspected or previously diagnosed TB. METHODS AND RESULTS: We enrolled 360 adults (≥18 years); 348 were eligible for the primary analysis (alive on day 3). Clinical, laboratory, anthropometric and enhanced tuberculosis diagnostic data were collected at admission with telephone tracing for mortality up to 6 months post-discharge. In the primary analysis population (mean age 45 years, SD = 15.0 years, 70% male), 58 (16.7%) deaths occurred between day 3-28 of admission; 70 (20.1%) between day 3 and discharge and documented total post-day 3 mortality including follow-up was 96 (27.6%). In those in whom it could be assessed, body mass index (BMI) ranged from 11.2-30.6 kg/m2 and 141/303 (46.5%) had moderate/severe undernutrition (BMI<17 kg/m2). A sex-specific cut-off for mid-upper arm circumference predictive of BMI<17 kg/m2 was associated with inpatient Day 3-28 mortality in males (AOR = 5.04, 95% CI: 1.50-16.86; p = 0.009; p = 0.032 for interaction by sex). The inability to stand for weight/height for BMI assessment was also associated with mortality (AOR = 5.59; 95% CI 2.25-13.89; p<0.001) as was severe compared to normal/mild anaemia (AOR = 9.67; 95% CI 2.48-37.76; p<0.001). No TB specific variables were associated with Day 3-28 mortality, nor was diabetes (HbA1c ≥6.5% or diabetes treatment). Similar effects were observed when the same multivariable model was applied to confirmed TB patients only and to the outcome of all post-day 3 in-patient mortality. CONCLUSION: This research supports the use of mid-upper arm circumference for triaging acutely unwell patients and the design and testing of nutrition-based interventions to improve patient outcomes.

Cannabinoid modulation of cortical adrenergic receptors and transporters.

We previously reported that administration of the synthetic cannabinoid agonist WIN 55,212-2 causes an increase in norepinephrine (NE) efflux in the frontal cortex (FC). The present study examined the expression levels of alpha2- and beta1-adrenergic receptors (ARs) as well as the norepinephrine transporter (NET) in the FC of rats following exposure to WIN 55,212-2. Rats received systemic injection of WIN 55,212-2 (3 mg/kg) acutely or for 7 days. Another group of rats received repeated WIN 55,212-2 treatment followed by a period of abstinence. Control rats received vehicle injections. Rats were euthanized 30 min after the last WIN 55,212-2 injection, the FC was microdissected, and protein extracts were probed for alpha2-AR, beta1-AR, and NET. Results showed that beta1-AR expression was significantly decreased following repeated WIN 55,212-2 treatment but significantly increased following a period of abstinence. alpha2-AR expression showed no significant change in all groups examined. NET expression was significantly decreased following acute WIN 55,212-2 treatment, with no changes following chronic administration or a period of abstinence. Alterations in NET may arise from modulation of cannabinoid receptors (CB1) that are localized to noradrenergic axon terminals as we demonstrate colocalization of CB1 receptor and NET in the same cortical axonal processes. The present findings support significant alterations in adrenergic receptor and NET expression in the FC after WIN 55,212 exposure that may underlie the reported changes in attention, cognition, and anxiety commonly observed after cannabinoid exposure.