Short- and medium-term prognosis of HIV-infected patients receiving intensive care: a Brazilian multicentre prospective cohort study.

OBJECTIVES: The characteristics of critically ill HIV-positive patients and the causes of their admission to intensive care units (ICUs) are only known through retrospective and unicentric studies. This study aims to fill this knowledge gap. METHODS: This is a prospective, multicentre cohort study of short- and medium-term prognostic factors. The setting consisted of ICUs of three tertiary referral hospitals from the three largest metropolitan areas in Brazil in the period January 2014 to November 2015. In all, 161 HIV patients over 18 years old were included. RESULTS: The clinical data of the outcomes (ICU mortality, hospital mortality and 90-day survival) were extracted from medical records using the REDCap®ï¸ web-based form and analysed with the MedCalc®ï¸ application. Median age was 41.7 [interquartile range (IQR): 34-50] years, the Simplified Acute Physiologic Score 3 (SAPS 3) was 64 (IQR: 56-74), and the Sequential Organ Failure Assessment Score (SOFA) was 6 (IQR: 4-9) points. The main causes of admission were sepsis (54.5%) and acute respiratory failure (13.7%). ICU and hospital mortality rates were 32.3% and 40.4%, respectively. In a multivariate analysis, time until ICU admission ≥ 3 days (P = 0.0013), performance status (Eastern Cooperative Oncology Group score, P = 0.0344), coma (Glasgow Coma Scale ≤ 8 points, P = 0.0213) and sepsis (P = 0.0003) were associated with increased hospital mortality. Coma (P = 0.0002) and sepsis (P = 0.0008) were independently associated with 90-day survival. CONCLUSIONS: Delayed ICU admission and the severity of critical illness determine the short- and medium-term mortality rates of HIV-infected patients admitted to the ICU, rather than factors associated with HIV infection. These results suggest that prognostic factors of HIV-infected patients in the ICU are similar to those of non-HIV-infected populations.

Thyroid hormone upregulates MDM2 in rat type I fibre: Implications for skeletal muscle mass regulation.

AIM: Based upon a microarray assay, we have identified that triiodothyronine (T3) upregulates MDM2 gene expression in the rat skeletal muscle. As MDM2 protein is an E3 ligase, we hypothesized that this enzyme could play a role in T3 effects on skeletal muscle mass control. METHODS: To test our hypothesis, male rats (2 months old) were randomly assigned into the following groups: intact controls, treated with 20 physiological doses of T3 for 0.5, 1 and 7 days, or with 5, 20 and 50 physiological doses of T3 for 7 days. For in vitro experiments, myotubes and C2C12 cells were treated with T3 for 3 days. RESULTS: After validation of the microarray finding throughout RT-PCR and confirmation that T3 induces increases in MDM2 protein expression in a dose-dependent manner, we observed that MDM2 was upregulated by T3 exclusively in fibre type I. Moreover, detailed histological evaluation showed that MDM2 overexpression distributes punctiformily along the cross section of the fibre and also inside nuclei. MDM2 colocalizes with PAX7 in control muscle and T3 downregulates this myogenic factor. Pharmacological inhibition of MDM2 in cultured myotubes caused a severe decrease in their diameter (~35%, P < .001 vs Control), enhancing the effect of T3 (from ~12% to ~35%, P < .001) alone upon myotube diameter and mRNA levels of atrogenes. Finally, we observed that FOXO3 (MDM2 target) is kept outside the nucleus under T3 stimulation. CONCLUSION: Our results indicate that MDM2 might be involved in the pro-trophic effects of T3 in skeletal muscle.

Comparison of two databases to detect potential drug-drug interactions between prescriptions of HIV/AIDS patients in critical care.

WHAT IS KNOWN AND OBJECTIVE: Adverse drug events (ADE), common and underestimated in ICU patients, have direct consequences on length of stay, mortality and hospital costs. Critically ill patients with HIV/AIDS are at a high risk of ADE because of their need for multiple drug therapies. ADE can be prevented, especially by the identification of potentially harmful drug-drug interactions (DDIs). Electronic databases are useful tools for the investigation of DDIs to avoid potential ADEs, thereby increasing patient safety. The purpose of this study was to compare the classification and severity rating of potential adverse drug interactions seen in the prescriptions for patients with HIV/AIDS in two databases, one with free access (Drugs.com(™)) and another requiring payment for access (Micromedex(®)). METHODS: A cross-sectional retrospective study of the prescriptions issued for 40 ICU HIV/AIDS patients on mechanical ventilation, admitted for more than 48 h, in a referral hospital for infectious diseases in Rio de Janeiro, Brazil, was undertaken. One prescription was reviewed each week for each patient from the second day after admission. A list of all drug-drug interactions was generated for each patient using the two drug-drug interactions databases. The weighted kappa index was estimated to assess the agreement between the classifications of DDIs identified by both databases and qualitative assessment made of any discordant classification of recorded drug-drug interactions. RESULTS AND DISCUSSION: Of the 106 prescriptions analysed, Micromedex(®) and Drugs.com identified 347 and 615 potential DDIs, respectively. A predominance of moderate interactions and pharmacokinetic interactions was observed. The agreement between the databases regarding the severity rating was only 68.3%. The weighted kappa of 0.44 is considered moderate. Better agreement (82.4%) was observed in the classification of mechanism of interaction, with a weighted kappa of 0.61. WHAT IS NEW AND CONCLUSION: DDIs are common between the prescriptions of patients with HIV/AIDS admitted to the ICU. Although both databases were able to identify the clinically relevant DDIs, we observed a significant discrepancy in the classification of the severity of DDIs in the two bases. The free access database could serve as an alternative to the identification of DDIs in resource-limited settings; however, there is a need for better evidence-based assessments for your use on clinical management of more serious DDIs.