2 Minute Medicine Rewind May 18 – May 24, 2015

In this section, we highlight the key high-impact studies, updates, and analyses published in medicine during the past week.

Permissive Underfeeding or Standard Enteral Feeding in Critically Ill Adults

Optimal nutritional support is an essential part of caring for critically ill adults, however the appropriate caloric goal for such patient remains unclear. Some of the literature surrounding nutritional support in the critically ill adult suggest that hypocaloric nutrition (permissive underfeeding) may beneficial. In this randomized control trial, 894 critically ill adults were assigned to either the permissive underfeeding group (60-70 % of estimated caloric requirement; n = 448) or the standard enteral feeding group (90-100 % of the estimate caloric requirement; n = 446) for 14 days. Despite the differences in total caloric intake, each intervention group received the same amount of protein (1.2-1.5 grams per kilogram of body weight per day). The goal of the study was to analyze the effect of permissive underfeeding on 90-day mortality. Secondary outcomes were mortality in the ICU, 28-day mortality, in-hospital mortality, 180-day mortality and serial SOFA scores. There was no significant difference in 90-day mortality between the permissive underfeeding group and the standard-feeding group (RR 0.94; 95% CI 0.76 to 1.16; p = 0.58). Similarly, there were no significant differences between the two groups with respect to mortality in the ICU, 28-day mortality, in-hospital mortality, 180-day mortality, or serial SOFA scores. Strengths of this study include its multicenter design as well as the efforts made to ensure generalizability of results (investigators included critically ill adults admitted with medical, surgical, or trauma-related issues). Some important limitations in this study include the inability to blind researchers to the intervention as well as an inability to obtain target caloric intake in some patients. Overall this study aligns with previous studies suggesting that standard enteral feeding is not associated with a lower mortality rate than that associated with permissive underfeeding in critically ill adults.

Racial Differences in Circulating Natriuretic Peptide Levels: The Atherosclerosis Risk in Communities Study

Natriuretic peptides are important for promoting natriuresis, diuresis, and vasodilation. Several hospital-based studies have looked at racial differences amongst levels of circulating natriuretic peptides in order to ascertain whether or not such differences may account for increased rates of hypertension and cardiac hypertrophy amongst African Americans. Investigators used data from the Atherosclerosis Risk in Communities (ARIC) study to assess whether or not there are any difference in levels of plasma NT-proBNP in African Americans and Caucasians. A total of 9137 ARIC study participants without cardiovascular disease were included in the study. 22% of these participants were self reported as African American. NT-proBNP levels were significantly lower in African Americans (median 43 pg/mL; interquartile range 18 to 88) when compared to Caucasians (median 68 pg/mL; interquartile range 36 to 124; p < 0.0001). This study adds to the growing body of research suggesting that low levels of plasma NTproBNP in African Americans may contribute to increased risk of hypertension and cardiac hypertrophy in this population.

Primary Chemotherapy Versus Primary Surgery for Newly Diagnosed Advanced Ovarian Cancer (CHORUS): An Open-Label, Randomised, Controlled, Non-Inferiority Trial

Last year, more than 21, 000 American women received a diagnosis of ovarian cancer. At present, the standard of care for women with a suspected advanced stage ovarian cancer involves surgical debulking of the tumor followed by aggressive chemotherapy. In this randomized controlled trial, 550 women in the United Kingdom or New Zealand with suspected advanced stage (stage 3 or 4) ovarian cancer were assigned to receive either primary surgery [initial surgery then 6 cycles of chemotherapy] (n = 251) or primary chemotherapy [three cycles of chemotherapy then surgery followed by 3 more cycles of chemotherapy] (n = 253). Participants were assigned to groups between March 1, 2004 and August 30, 2010; by May 31, 2014, death had occurred in 451 participants (231 in the primary surgery group and 220 in the primary chemotherapy group). Median overall survival was 22.6 months with primary surgery and 24.1 months with primary chemotherapy. The hazard ratio for death was 0.87 in favor of primary chemotherapy (95 % CI 0.72 to 1.05). Despite the fact that survival with primary chemotherapy was found to be non-inferior to primary surgery in this study, it is important to continue to consider the adverse effects of chemotherapy, including fatal toxic effects, like neutropenic sepsis.    

Trial of Short-Course Antimicrobial Therapy for Intraabdominal Infection

Complicated intraabdominal infections remain a significant cause of morbidity and mortality in the United States. Guidelines outlining the choice of antimicrobial agents as well as the duration of antimicrobial treatment for patients with intraabdominal infections evolve frequently. Traditionally, physicians have treated patients with intraabdominal infections with the appropriate antibiotics until all evidence of SIRS have resolved (7-14 days), however, recent studies have suggested that a shorter course (3-5 days) of antibiotics may be as effective in reducing morbidity and mortality. In this randomized controlled trial, 518 patients with complicated intraabdominal infection and adequate source control were assigned to either a control group (n = 260), where participants received antibiotics until 2 days after the resolution of SIRS with no more than 10 days of therapy, or an experimental group (n=257), where patients received antibiotics for 3-5 days. Investigators found no significant difference in measured primary outcome, which was a composite of surgical-site infection, recurrent intraabdominal infection, or death within 30 days after the index source-control procedure (absolute difference, -0.5 percentage point, 95% CI, =7.0 to 8.0; p = 0.92). A significant limitation in this study lies in it originally being designed/powered for a much larger group of participants (1010); funding for the trial to reach target enrollment was not possible once the interim analysis was done and showed no significant difference between the control and experimental groups.       

Long –Term Effects of Lithium on Renal, Thyroid, and Parathyroid Function: A Retrospective Analysis of Laboratory Data

Lithium is a widely used and effective treatment for mood disorders. Its strengths include its ability to protect from the extremes of mood (depression and mania), while reducing risk of suicide. Major limitations to lithium use lie within its adverse effects, which include a decline in renal and thyroid function, as well as hypercalcemia. In this retrospective analysis of laboratory data from Oxford University Hospitals National health Service Trust, investigators looked at the incidence of renal, thyroid, and parathyroid dysfunction in patients over the age of 18 who had > 2 creatinine, thyrotropin, calcium, glycated hemoglobin, or lithium measurements between October 1, 1982 and March 31, 2014. Primary outcomes in this study were the incidence of renal, thyroid, and parathyroid dysfunction in patients on lithium compared to controls (not on lithium). Lithium use was associated with an increased risk of chronic kidney disease (HR 1.93, 95% CI 1.76 – 2.12; p < 0.0001), hypothyroidism (HR 2.31, 95% CI 2.05 – 2.60; p < 0.0001), and raised total serum calcium (HR 1.43, 95% CI 1.21 – 1.69; p < 0.0001). These findings are consistent with previous findings which suggest that patients on lithium need close monitoring.

Image: PD

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