2 Minute Medicine Rewind October 26 – November 2, 2014

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

Clinical Illness and Outcomes in Patients with Ebola in Sierra Leone

With more than 10,100 reported cases, the current Ebola virus disease (EVD) outbreak is the largest and most widespread outbreak in history. Given a 45 to 90% fatality rate and no currently approved treatment, a greater understanding of the virus is urgent. Starting with the first patient diagnosed on May 25, 2014, this study reviewed records from the first 106 cases of EVD in Sierra Leone. The overall study fatality rate of 74% while that of patients under 21 years of age was 57% and that above 45 years of age was 94%. At presentation, 89% of patients had fever, 80% had a headache, 66% had weakness, 60% had dizziness, 51% had diarrhea, and 40% had abdominal pain. Of those, fever, weakness, dizziness, and diarrhea were associated with a fatal outcome. This was also the case for increasing levels of blood urea nitrogen, and creatinine, suggesting a role for dehydration and worsening renal function. Most patients who died from EVD were also acidotic and had elevated AST levels. Finally, patients who presented with fewer than 100,000 EBOV copies/mL had a case fatality rate of 33%, whereas those with a viral load of greater than 10 million EBOV copies/mL had a significantly higher case fatality rate of 94% (P=0.003). Based on these findings, a scoring system, such as the modified Acute Physiology and Chronic Health Evaluation (APACHE), could be developed as a prognostic indicator.

Milk intake and risk of mortality and fractures in women and men: cohort studies

Milk contains calcium, phosphorus, and vitamin D, all of which are of important for bone health. Its consumption has thus long been encouraged to reduce the likelihood of osteoporotic fractures. However, in animal studies, chronic exposure to D-galactose has been shown to cause oxidative stress damage, chronic inflammation, neurodegeneration, decreased immune response, and gene transcriptional changes, all of which contributed to a shortened life span in the studied animals. In this study, 61,433 women and 45,339 men from two large Swedish cohorts were administered food frequency questionnaires, and associations between milk consumption and time to mortality or fracture were analyzed. Similarly to animal models, there was a positive association between milk intake and both urine 8-iso-PGF2α and serum interleukin 6, oxidative stress and inflammatory biomarkers, respectively. Three or more glasses of milk a day compared with less than one glass a day was associated with a hazard ratio of total mortality of 1.93 (95% CI: 1.80 to 2.06) in women. The women’s cardiovascular mortality was similar to that of total mortality while cancer mortality was slightly lower (HR: 1.44; 95% CI: 1.23 to 1.69). Similarly, the risk of fracture in women increased with milk consumption (HR: 1.16; 95% CI: 1.08 to 1.25). Men saw no increase or decrease in mortality (HR: 1.01; 95% CI: 0.99 to 1.03) or fracture rate (HR: 1.03; 95% CI: 0.99 to 1.07). This study therefore demonstrates a positive relationship between milk consumption, fracture rate and mortality.

Dementia Risk After Traumatic Brain Injury vs Nonbrain Trauma

Sixty percent of all hospitalizations for traumatic brain injury (TBI) occur in adults 55 years of age and older, with the highest rates among those 75 years and older. The relationship between TBI and dementia, which has important public health implications, is not, however, well characterized. In this retrospective cohort study, 164 661 patients 55 years or older with no baseline dementia and a TBI or non-TBI trauma (NTT) were followed. Of these patients, 8.4% of TBI patient developed dementia compared with 5.9% of NTT patients (HR: 1.46; 95% CI: 1.41-1.52; P < .001). Stratified adjusted analyses demonstrated that with increasing age, the brain became more susceptible to dementia with TBIs of decreasing severity. Specifically, mild TBI was more strongly associated with the development of dementia in adults 65 to 74 years of age (HR: 1.25; 95% CI: 1.04-1.51; P = 0.02) than in those 55 to 64 years of age (HR: 1.11; 95% CI: 0.80-1.53; P = 0.55). Contrarily, moderate to severe TBI was associated with increased risk of dementia across both the age 55 to 64 (HR: 1.72; 95% CI: 1.40-2.10; P < 0.001) and the 65 to 74 (HR: 1.46; 95% CI: 1.30-1.64; P < 0.001) age groups. The results of this study therefore suggests TBI prevention in older adults as important in preventing dementia.

One-Unit versus Two-Unit Cord-Blood Transplantation for Hematologic Cancers

Umbilical-cord blood is often used as the source of hematopoietic stem cells for transplantation and has the advantages of a relative absence of donor attrition and a reduced risk of graft-versus-host disease (GVHD) compared with stem-cell grafts from adult donors. However, because of the finite number of hematopoietic progenitor cells that can be collected from the placenta, its application is restricted primarily to children. Recent research has therefore been aiming to determine whether two partially HLA-matched cord-blood units were better than one. In this multicenter Phase 3 randomized controlled trial, 224 patients with hematologic cancer less than 21 years old were randomly assigned to double-unit or single-unit cord-blood transplantation after undergoing a myeloablative conditioning regimen. There was no significant difference in 1-year survival rate between the double (65%; 95% CI: 56 to 74) and single cord-blood units (73%; 95% CI: 63 to 80) (P=0.17). Disease-free survival was also not significantly different, with rates of 64% (95% CI: 54 to 72) and 70% (95% CI: 60 to 77) for the double-unit and single-unit recipients, respectively (P = 0.11). The only difference between the two groups was a significantly lower incidence of grade III and IV acute and extensive chronic GVHD in the single cord-blood unit group (9%; 95% CI: 4 to 14) compared to the double cord-blood unit group (15%; 95% CI: 8 to 22) (P = 0.05). Adding a second cord-blood unit group added no additional benefits and instead brought further complications; thus, two partially HLA-matched cord-blood units cannot be recommended for treatment of hematologic cancer based on this study.

Cost-effectiveness of Dalteparin vs Unfractionated Heparin for the Prevention of Venous Thromboembolism in Critically Ill Patients

The Prophylaxis for Thromboembolism in Critical Care Trial (PROTECT) recently compared the effectiveness of low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) for thromboprophylaxis and found no difference in deep-vein thrombosis between the groups but a reduced rate of pulmonary embolus and heparin-induced thrombocytopenia in patients who received LMWH. Because of historically lower costs, however, UFH is more often used in American hospitals. Investigating whether the added benefits warrants the extra initial cost is therefore warranted. In this prospective economic evaluation of the PROTECT study, costs, effects, and incremental cost-effectiveness of LMWH vs UFH were measured in 2344 patients. There was no significant difference in hospital median and mean costs per patient between the LMWH group ($39,508 and $63 290, respectively) and the UFH group ($40 805 and $61 800, respectively) (P = 0.41 and P = 0.53). Furthermore, using LMWH was more effective and less costly in 78% of observed scenarios, driven by lower rates of pulmonary embolus and heparin-induced thrombocytopenia and corresponding lower overall use of resources. Thus, this study favors the use of LMWH for thromboprophylaxis in critically ill patients.

Image: PD

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