2 Minute Medicine Rewind October 2, 2017

Effect of Individualized vs Standard Blood Pressure Management Strategies on Postoperative Organ Dysfunction Among High-Risk Patients Undergoing Major Surgery

There is currently a lack of consensus on how to best prevent intraoperative hypotension. Whether blood pressure (BP) management should be an individualized strategy, where the target threshold is adjusted to premorbid values is also unclear. In this randomized controlled trial, 298 patients with increased postoperative risk were randomized to a standard or individualized BP treatment strategy during surgery in order to study the effects on the primary outcome, defined as a composite of systemic inflammatory response syndrome (SIRS) and dysfunction of at least one organ system. Patients receiving standard care were given ephedrine intravenous treatment when their systolic BP was below 80 mmHg or 40% lower than the patient’s preoperative reference blood pressure. Patients receiving individualized treatment had their BP targeted to remain within 10% of their reference BP using a continuous infusion of norepinephrine. Results showed that within the first 7 days after surgery, patients in the individualized treatment strategy had a significantly lower risk for primary outcome events (risk difference -14%, 95% CI -25% to -2%; RR 0.73, 95% CI 0.56 to 0.94, p=0.02).  The results of this study suggest that using an individualized SBP management strategy can lower the incidence of postoperative organ dysfunction. It is important to note, however, that the study used a limited patient population, as patients were age 50 years or older, evaluated to have high postoperative risk for kidney injury, and predominantly underwent abdominal surgery. Furthermore, more than 80% of patients in this study had chronic hypertension. As such, it is important to recognize that the results of this study may not be generalizable to other patient populations without further study.

Changes in the prevalence of human papillomavirus following a national bivalent human papillomavirus vaccination

Human papilloma virus (HPV) infection by HPV types 16,18, 31, 33, and 45 can lead to cervical cancer. Vaccination programs have been introduced to prevent HPV infection. The large-scale effects of vaccination in women, however, have not been well studied. In this 7-year cross-sectional study in Scotland, the investigators collected 8584 cervical screen samples for HPV genotyping and linked the results to vaccination records in order to report on the effectiveness of a bivalent HPV vaccine. In Scotland, school-based HPV vaccination began in 2008 and targeted girls who were 12-13 years old. By collecting cervical cytology samples from 2009-2015 from 20-21 year old women who were born from 1988-1995, investigators were able to compare results for cohorts that were offered vaccination at age 12-13 and groups that were not. Vaccination records showed that the proportion of vaccinated individuals increased with study year from 1.5% in 2009 to 86% in 2015. Results from genotyping showed a statistically significant decrease in the prevalence of HPV types 16 and 18 from 30.0% (95% CI 26.9% to 31.1%) in the 1988 cohort to 4.8% (95% CI 3.8% to 5.9%) in the 1995 cohort (OR 0.12, 95% CI 0.10 to 0.16, p<0.0001). There was also a statistically significant decrease in the prevalence of HPV types 31, 33, and 45 from 14.2% (95% CI 12.0% to 16.7%) in the 1988 cohort to 2.6% (95% CI 1.9% to3.6%) in the 1995 cohort. Linking vaccination records to genotype results showed that the age of women at vaccination changed the efficacy of the vaccine. Women vaccinated with three doses at age 18 or older had a vaccine efficacy for HPV types 16 and 18 of 28.9% (95% CI 4.5% to 47.8%) in comparison to the 89.1% efficacy observed in women vaccinated at age 12 or 13 (95% CI 85.1% to 92.3%); a similar trend was also observed for HPV types 31, 33, and 45. The number of vaccine doses was also shown to make a difference, as three doses of vaccine led to an increase in vaccine effectiveness for HPV types 16 and 18 in comparison to two or one doses. Overall, results from this study show that vaccination programs for HPV types 16, 18, 31, 33, and 45 can reduce the prevalence of HPV infection in the population. The results also show that protection offered by a bivalent vaccine can endure for at least 7 years, which suggests that cervical cancer screening could start at a later age than 20-21 years. Long-term follow-up, however, is needed to provide more information on the longevity of vaccination effectiveness.

Age of Red Cells for Transfusion and Outcomes in Critically Ill Adults

Red blood cells are currently stored for up to 42 days in blood banks, and the oldest available compatible units are usually the ones issued when a transfusion is needed. Two previous studies have shown no significant difference between using fresher versus older red blood cells (RBCs) however due to limitations in these studies, the question as to whether transfusion of older red cells leads to worse outcomes still persists. In this randomized controlled trial, 4994 intensive care unit (ICU) patients who received red-cell transfusions were randomized to receive either the freshest RBCs (short-term storage) or oldest RBCs available (long-term storage) in order to examine the effect on 90-day all-cause mortality. The mean storage duration of transfused red cells was 11.8 ± 5.3 days for the short-term storage group and 22.4 ± 7.5 days for the long-term storage group. Results showed that there were no significant differences in the all-cause mortality rates for the two groups, as death occurred in 24.8% of the short-term storage group and 24.1% in the long-term storage group (OR 1.04, 95% CI 0.91 to 1.18, p=0.57). Overall results indicate that there is no significant difference in outcomes when ICU patients are given fresher versus older blood

Correlation of Peripheral Immunity With Rapid Amyotrophic Lateral Sclerosis Progression

Patients with amyotrophic lateral sclerosis (ALS) experience progressive motor degeneration with an average survival of 3 to 5 years after diagnosis. While numerous factors potentially contribute to disease, no single cause has been identified for sporadic ALS. As ALS involves neuroinflammation, there is interest in role the immune system plays in ALS pathogenesis. In this longitudinal cohort study, investigators drew blood from 35 healthy controls and 119 participants with ALS and analyzed cellular populations and myeloid surface marker expression in order to study whether specific leukocyte populations or myeloid subpopulations accelerate the rate of ALS progression. Results showed that participants with ALS had a higher mean number of total leukocytes per mL of blood than healthy controls (p<0.001). Participants with ALS also had higher mean numbers of neutrophils (p<0.001), CD16+ monocytes (p=0.002), CD16 monocytes (p=0.01), and natural killer cells (p=0.007).  Blood samples from 51 ALS participants showed that on average, total numbers of leukocytes, neutrophils, and natural killer cells increased over time while the total number of CD4 T cells decreased during the first years of disease progression. A multivariate linear regression was generated to correlate changes in the immune cell population counts with changes in the Revised Amyotrophic Lateral Sclerosis Functioning Rating Scale (ALSFRS-R). This model showed a significant correlation between a decrease in ALSFRS-R score (indicating worse disease progression) and an increase in the total number of leukocytes per year (p<0.001). A decrease in ALSFRS-R score was also correlated with an increase in the number of neutrophils (p<0.001) and a decrease in the number of CD4 T cells (p<0.001). Multivariate regression generated statistically significant correlations between disease progression and certain surface markers for myeloid subpopulations. Overall, results from this study support an immunological contribution in ALS pathogenesis. Specifically, results from the multivariate linear regression suggest that leukocytes, neutrophils, and CD4 T cells may play a pathogenic role in disease progression, although it is unclear whether this role is positive or negative.

Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes

Patients with type 2 diabetes are at an increased risk of death due to cardiovascular disease compared to the general population. Previous studies have shown that some newer glucose-lowering agents are associated with a lower risk of major adverse cardiovascular events (MACE) in patients, while other agents have no beneficial effect on cardiovascular outcome. In this randomized controlled trial, 14,752 patients with type 2 diabetes were randomized to receive placebo or exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, in order to examine the effects on MACE. MACE was defined in this study as a three-component composite of death from cardiovascular disease, nonfatal myocardial infarction, or nonfatal stroke. Researchers found that there was no statistically significant difference in MACE incidence between groups (HR 0.91, 95% CI 0.83 to 1.00). There was, however, a significant difference in efficacy outcome as patients on exenatide had a lower risk of receiving additional glucose-lowering agents than patients in the placebo group (HR 0.67, 95% CI 0.63 to 0.71, p<0.001). In terms of changing glycemic control, patients who received exenatide also had a mean glycated hemoglobin level that was 0.53% lower than the mean for the placebo group (95% CI -0.57% to -.50%, p<0.001). Results overall indicate that exenatide does not alter the risk of MACE in patients with type 2 diabetes, which differs from the results of trials that found a lowering of MACE risk with two other GLP-1 receptor agonists, liraglutide and semaglutide. This difference in results suggests that different GLP-1 receptor agonists may not be bioequivalent. This study on exenatide, however, was limited in that the usual-care regimens for patients were not standardized, and patients in the placebo group had a disproportionate use of diabetes therapies known to reduce cardiovascular risk.

Image: PD

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