2 Minute Medicine Rewind February 10, 2019

Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial

1. Study findings suggest that early administration of intravenous dexamethasone during acute respiratory distress syndrome may decrease duration of mechanical ventilation and mortality rates.

Evidence Level: 1 (Excellent)

Acute respiratory distress syndrome (ARDS), characterized by acute hypoxemic respiratory failure and bilateral pulmonary infiltrates, is associated with significant mortality rates and currently have no proven pharmacological therapies. Although a previous meta-analysis provided evidence for the potential application of corticosteroids as a treatment option, there has been insufficient evidence to suggest a mortality benefit. In this multicenter, randomized controlled trial, 277 patients with established moderate-to-severe ARDS in a network of 17 intensive care units (ICUs) in Spain were enrolled and assigned to either serve as controls or receive intravenous (IV) dexamethasone during their hospital stay. The primary outcome measure was the number of ventilator-free days at 28 days (defined as days alive and free from mechanical ventilation from day of randomization to day 28), and the secondary outcome measure was all-cause mortality 60 days after randomization. The treatment group, which received 20mg of IV dexamethasone once daily from day 1 to day 5 and 10mg IV dexamethasone once daily day 6 to day 10, was observed to have significantly greater ventilator-free days versus controls (between-group difference 4.8 days [95% CI 2.57 to 7.03]; p<0.0001). All-cause mortality at 60 days was also significantly lower in the treatment group compared to control, with 21% in the former and 36% in the latter (between group difference -15.3% [95% CI -25.9 to -4.9]; p<0.005). This is the first randomized trial testing the efficacy of dexamethasone in patients with ARDS, and suggests that early therapy with dexamethasone could potentially modify the host immune response leading to greater ventilator free days and pose a mortality benefit. With further investigation, dexamethasone may present itself as one of the first pharmacologic therapies for the treatment of ARDS.

 Associations of Processed Meat, Unprocessed Red Meat, Poultry, or Fish Intake With Incident Cardiovascular Disease and All-Cause Mortality

1. Findings from this cohort study suggest that diets including processed meat, unprocessed, or poultry have significant associations with incidence of cardiovascular disease while fish do not

2. Processed meats and unprocessed red meats have significant association with all-cause mortality while poultry and fish did not

Evidence Rating: 2 (Good)

The concept of lifestyle modifications as first line therapy for prevention for cardiovascular disease (CVD) has long been an established norm in medicine. While positive associations have been established between processed meats, CVD, and mortality, the association between unprocessed red meat, poultry, or fish intake with these outcomes remains uncertain.. In this cohort study consisting of data from 6 prospective cohort study of US adults, investigators sought to address this knowledge gap and examine the relationship between poultry, unprocessed red meat, and fish consumption with all-cause mortality and CVD incidence. The intake data of 29,682 participants were collected between 1985 to 2002 with follow up until August 31, 2016. Regular consumption of processed red meat (adjusted HR, 1.07 [95% CI, 1.04-1.11]), unprocessed red meat (adjusted HR 1.03, [95% CI, 1.01-1.06]), or poultry (adjusted HR, 1.04 [95% CI, 1.01-1.06]) were significantly associated with incident CVD while fish intake was not (adjusted HR, 1.00 [95% CI, 0.98-1.02]). Similarly, intake of processed meat (adjusted HR, 1.03 [95% CI, 1.02-1.05]) or unprocessed red meat (adjusted HR 1.03 [95% CI, 1.01-1.05]) was associated with significantly increased all-cause mortality while poultry and fish consumption was not. Although the observed effect sizes were small, the potential impacts on public health can be large as these findings continue to support the notion that minute lifestyle modifications can surmount to significant impacts on individual health outcomes.

A Comparison of Psoriasis Severity in Pediatric Patients Treated With Methotrexate vs Biologic Agents

1. Treatment with biologics in pediatric patients with moderate to severe psoriasis was significantly associated with greater reduction in psoriasis severity than methotrexate, though methotrexate remains an effective treatment for the condition.

Evidence Rating: 2 (Good)

Psoriasis is a highly debilitating chronic inflammatory skin disorder that affects up to 1.37% of children, with its highly visible nature contributing to significantly impaired quality of life and necessitating therapy. While most cases of psoriasis are responsive to topical therapy, 20% of children have more severe forms of the disease that require systemic therapy. Methotrexate is currently the most commonly prescribed and least expensive disease modifying anti-rheumatic drug. While multiple biologic agents have been approved as alternative treatment options, no investigations have prospectively compared their efficacy against methotrexate, aside from a previous study that found adalimumab to be a potentially superior option. In this retrospective cohort study, clinical data from 234 pediatric patients with moderate to severe psoriasis who had received at least 3 months of biologic or methotrexate treatment were analyzed. Primary outcome measures were the Psoriasis Area and Severity Index (PASI) and Physician Global Assessment (PGA) as operational measures of psoriasis severity and responsiveness to treatment. A PASI75 score indicates 75% or greater improvement and PGA0/1 represents a clear or minimal assessment. Drug survival rates were additionally analyzed. At 6 months follow up, 75% or greater improvement in PASI was achieved in 71.4% of patients receiving biologic agent treatment versus 40% in the methotrexate group. Likewise, achievement of PASI75 or PGA0/1, and decreased mean PASI and PGA scores were more strongly associated with biologic agent usage than methotrexate. Finally, after 1, 3, and 5 years of use, overall drug survival rates for methotrexate were 77.5%, 50.3%, and 35.9% versus 83.4%, 64.3%, and 57.1% for biologic agents, demonstrating a significantly higher survival rate for biologics than methotrexate (HR, 2.23; 95% CI, 1.21-4.10; p = .01). Prior research has found biologics to be additionally associated with fewer treatment related toxic effects and requiring less monitoring during administration. As such, while methotrexate remains a cost-effective strategy in the treatment of moderate to severe psoriasis, study findings suggest that biologic treatment may be a more effective and safe treatment option when compared to methotrexate, with the caveat of being more expensive.

Effect of Hydrocortisone vs Pasireotide on Pancreatic Surgery Complications in Patients With High Risk of Pancreatic Fistula

1. Hydrocortisone is not noninferior to pasireotide in the reduction of postoperative complications in patients undergoing distal pancreatectomy.

Evidence Rating: 1 (Excellent)

Partial pancreatectomies carry high risk profile for complications, with pancreatic fistulas being one of the major sources of serious postoperative complications. Despite various alterations to surgical methodology and pharmacologic therapies being suggested, the risk of a clinically significant pancreatic fistula being developed postoperatively remains as high as up to one-third of patients receiving the treatment. Perioperative hydrocortisone and pasireotide, a somatostatin analog, have been suggested by previous research to be two pharmacologic agents that are effective in preventing perioperative fistula, though no investigations have formally compared the efficacy of the two.  In this noninferiority, parallel-group, individually randomized clinical trial conducted at an academic center between May 2016 to December 2018, 281 patients undergoing partial pancreactectomy were randomly assigned to receive either perioperative pasireotide or hydrocortisone as treatment. Rates of pancreatic fistula development and the Comprehensive Complication Index (CCI) score, a measure taking into account all cumulative complications from an operation, were used as study outcome measures. The hydrocortisone group mean (SD) CCI score was 30.11(20.47) compared to the pasireotide group’s mean of 23.94 (17.06), not meeting the predetermined noninferiority limit of 9 CCI points. Fistulas were detected in 54% of patients in the pasireotide group and 62% in the hydrocortisone group (odds radio, 1.39. 95% CI, 0.68-2.82; p = .37). Further subgroup analysis of patients undergoing distal pancreatectomy revealed a significantly lower CCI score and significantly lower rates of pancreatic fistula formation in the pasireotide group versus the hydrocortisone group. Study results did not reinforce previous findings that put forth hydrocortisone as a potentially noninferior, more cost-effective alternative to pasireotide for postoperative care in patients receiving pancreatectomy.

Adolescent obesity and midlife cancer risk: a population-based cohort study of 2·3 million adolescents in Israel

1. Adolescent obesity was significantly associated with cancer incidence in young and mid adulthood, and could be an important intervention target for early cancer prevention

Evidence Rating: 2 (Good)

Despite obesity being an established causal factor for at least 12 types of cancer, the relationship between youth obesity and cancers have been poorly characterized due to the vast majority of prior literature being focused on middle aged or older patients or spanning a wide age range. In this nationwide, population-based cohort study, the height and weight of 2.3million Israeli adolescents under 17 years old were measured between 1967-2010 and tracked for up to 25 years. In 29,542,735 person-years of follow up in men, cancer incidence increased gradually across BMI percentiles, with the adjusted HR being 1.26 (95% CI, 1.18-1.35) among men with adolescent obesity. The association between adolescent obesity and incidence of cancer in men was evident even before the age of 30. In women with adolescent obesity, when excluding cervical and breast cancers, which were primarily driven by an inverse relationship, the adjusted HR was 1.27 (95% CI,1.13-1.44). Strong associations were found between adolescent BMI with colon, esophageal, hepatocellular, pancreatic, and kidney cancers in men, and colon, esophageal, liver and biliary, and ovarian cancers in women. Study findings strongly support that adolescent obesity is a major risk factor for cancer incidence in young and mid adulthood for both males and females, further emphasizing the importance of early lifestyle modification in obese youth, especially in light of increasing rates of severe adolescent obesity worldwide.

Image: PD

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