2 Minute Medicine Rewind August 14, 2017

Associations Between Midlife Vascular Risk Factors and 25-Year Incident Dementia in the Atherosclerosis Risk in Communities (ARIC) Cohort

Vascular risk factors have been implicated in the development of dementia. In this retrospective cohort study, 15,477 individuals in midlife were followed up from 1987-1989 through 2011-2013 to explore associations between midlife vascular risk factors and late life risk of cognitive decline. Midlife vascular risk exposures included obesity, smoking, diabetes, prehypertension, hypertension, hypercholesterolemia and APOE ε4 genotype. The primary outcome was a diagnosis of dementia after 25 years of follow-up as determined by a battery of neurocognitive tests, interviews, and adjudicated reviews. Researchers found that, among the 15,744 participants, 1516 cases of dementia were diagnosed. Participants with the following midlife vascular risk factors were found to be at a higher risk of experiencing cognitive decline: smoking (HR 1.41, 95% CI 1.23 to 1.61), diabetes (HR 1.77, 95% CI 1.53 to 2.04), prehypertension (HR 1.31, 95% CI 1.14 to 1.51) and hypertension (HR 1.39, 95% CI 1.22 to 1.59). Other risk factors associated with the onset of dementia included Black race (HR 1.36, 95% CI 1.21 to 1.54), older age (HR 8.06, 95% CI 6.69 to 9.72 for participants 60-66 years), lower educational attainment (HR 1.61, 95% CI 1.28 to 2.03), and APOE ε4 genotype (HR 1.98, 95%CI 1.78 to 2.21). This study therefore shows that modifiable midlife risk factors including smoking, diabetes, hypertension, and prehypertension are associated and likely contribute to the development of vascular dementia.

Effect of Levosimendan on Low Cardiac Output Syndrome in Patients With Low Ejection Fraction Undergoing Coronary Artery Bypass Grafting With Cardiopulmonary Bypass

Coronary artery bypass grafting (CABG) poses significant mortality risk in patients with existing left ventricular dysfunction with ejection fractions <40%. Often, these patients face low cardiac output syndrome, which increases the rate of complications such as myocardial infarction, renal failure, and pulmonary impairment. The use of levosimendan, a calcium channel sensitizer has been posited to reduce the risk of low cardiac output syndrome following CABG. In this randomized controlled trial, 336 patients with reduced left ventricular ejection fraction undergoing CABG with cardiopulmonary bypass alone or combined with valve surgery were assigned in a 1:1 fashion to either levosimendan or placebo to assess a composite of 3 elements that reflect low cardiac output syndrome. These included catecholamine infusion persisting beyond 48 hours after infusion of levosimendan, need for left ventricular assist device in the post-operative period, or the need for renal replacement therapy during the intensive care unit stay. Secondary endpoints included in-hospital mortality, number of days with mechanical assist device, and number of days with renal replacement therapy among others. Baseline characteristics were similar across the levosimendan and placebo groups. Researchers found that the primary endpoint occurred in 87 levosimendan patients (52%) and 101 placebo patients (61%) (p=0.15). The three primary endpoints were not affected by levosimendan administration, and no significant difference was found in any of the secondary endpoints. This study’s limitations include the small levosimendan dose with no initial bolus that could have contributed to the minimal effect of levosimendan, and also with the timing of the drug being potentially close to myocardial injury, reducing the protective effect of the drug. Ultimately, this study suggests levosimendan does not help reduce the risk of low cardiac output failure in patients with left ventricular dysfunction that are undergoing CABG with cardiopulmonary bypass.

Analysis of Plasma Epstein–Barr Virus DNA to Screen for Nasopharyngeal Cancer

Circulating Epstein-Barr Virus (EBV) DNA is a biomarker for nasopharyngeal carcinoma. In this prospective cohort study conducted in Hong Kong, EBV DNA in plasma specimens were analyzed from 20,174 men ages 40-62 years to investigate whether EBV DNA in plasma samples could be used in screening for early nasopharyngeal carcinoma in asymptomatic patients. Blood plasma screening by real-time polymerase-chain-reaction (RT-PCR) for EBV was performed at enrollment, re-evaluated at 4 weeks, and deemed positive on the basis of 2 EBV samples. Screen-positive patients were referred for nasopharynx evaluation by endoscopy and MRI, and biopsies were taken for diagnosis of nasopharyngeal carcinoma. Researchers found that EBV DNA was detectable in plasma samples obtained from 5.5% (n=1112) of participants, with 1.5% (n=309) having persistently positive results on the repeated sample. Among these 309 men, 300 underwent endoscopic examination, of which 11% (n=34) were found to have nasopharyngeal carcinoma. Compared to a non-screened historical cohort, stage I or II nasopharyngeal cancer was detected in a higher proportion of patients (71% vs. 20%, p < 0.0001). Progression-free survival was also higher in the current study population than in the comparison cohort (97% vs. 70%, HR 0.10, 95% CI 0.05 to 0.18, p<0.001). The number needed to treat (NNT) was 593, at a cost of $28,600. Sensitivity and specificity of EBV DNA screening were 97.1% and 98.6%, respectively. Overall, in asymptomatic participants with persistently elevated serum EBV were diagnosed with nasopharyngeal carcinoma at higher rates than expected, and were diagnosed at an earlier stage. This has important implications for the screening and management of nasopharyngeal carcinoma

Effect of Cerebral Embolic Protection Devices on CNS Infarction in Surgical Aortic Valve Replacement

There are an increasing number of surgical aortic valve replacements (SAVR) and transcatheter aortic valve replacements (TAVR) procedures being performed each year due to aortic stenosis. The prevalence of aortic stenosis increases with age. Despite procedural improvements, central nervous system (CNS) infarctions remain a serious complication with significant negative impacts on survival, quality of life, and health care costs. Intraoperative cerebral embolic protection devices were developed to reduce the incidence of CNS infarction post-SAVR. In this randomized clinical trial of 383 patients aged 60 or older undergoing SAVR, patients were randomized in a near 1:1:1 manner to either intra-aortic filtration device with a heparin-coated mesh filter, suction-based extraction, or control where a standard aortic perfusion cannula was used to determine the efficacy and adverse effects of cerebral embolic protection devices in reducing ischemic CNS injury during SAVR. The primary outcome was freedom from clinical or radiographic CNS infarction at 7 days post-procedure, supplemented with serial neurological assessments using the National Institutes of Health (NIH) Stroke Scale score. Researchers found that rates of freedom from CNS infarction were not significantly different between the suction-based extraction group and control group (32.0% vs. 33.3%, between-group difference -1.3%, 95% CI -13.8% to 11.2%), or between the intra-aortic filtration group and the control group (25.6% vs. 32.4%, between-group difference -6.9%, 95% CI -17.9% to 4.2%). The 30-day composite endpoint was also not significantly different between groups. However, delirium rates declined in the cerebral embolic protection group compared to control. At postoperative day 7, 6.3% of patients in the suction-based extraction group experienced delirium versus 15.3% of patients in the control group (between-group difference -9.1%, 95% CI -17.1% to -1.0%). Similarly, 8.1% of patients in the intra-aortic filtration group experienced delirium versus 15.6% of patients in the control group (between-group difference -7.4%, 95% CI -15.5% to 0.6%). Limitations of this study included imaging performed at post-operative day 7, which is beyond the optimal timeframe used to assess and treat CNS infarction Nonetheless, this study shows notable findings that cerebral embolic protection devices do not reduce CNS infarction incidence 7 days post-operation, but reduce rates of delirium.

Expansion of Treatment for Hepatitis C Virus Infection by Task Shifting to Community-Based Nonspecialist Providers

The development of direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection has raised the possibility of rapid treatment expansion and widespread cure, although many patients face barriers to acquiring treatment. Currently, only 43% of patients are aware of HCV diagnosis, and only 16% are being treated. This is a problem that could be addressed by non-specialist providers. In this non-randomized clinical trial, 600 patients were assigned to receive treatment of ledipasvir-sofosbuvir from a nurse practitioner (NP), primary care provider, or specialist with the primary outcome of sustained virologic response (SVR). Researchers found that 86% of patients responded to treatment and achieved SVR (95% CI 83.0% to 88.7%), where similar results were observed for non-specialist and specialist cohorts. Patient loss to follow-up was a major cause of non-SVR across provider groups. Additionally, no major safety concerns were observed during the trial. In total, 98 participants had adverse events, of which 98% were grade 1 or grade 2. Study limitations included the lack of surveillance for hepatocellular carcinoma or reinfection, both of which are serious long-term outcomes. Nonetheless, this study has important implications in at the management of patients at urban federally-qualified health centers, as it demonstrates that HCV treatment provided by non-specialist providers may be as safe and effective as that provided by specialists. With this larger population of providers, more patients may be able to receive HCV treatment and address current gaps in care.

Image: PD

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