2 Minute Medicine Rewind July 16, 2018

Effect of a Home-Based Wearable Continuous ECG Monitoring Patch on Detection of Undiagnosed Atrial Fibrillation: The mSToPS Randomized Clinical Trial

The detection of atrial fibrillation (AF) is imperative in preventing associated adverse health outcomes, including stroke. This study aimed to determine the effect of a self-applied wearable electrocardiogram (ECG) patch in detecting AF and the clinical consequences associated with such a detection strategy. This randomized clinical trial and prospective matched observational cohort study randomized 1364 individuals to an active home-based monitoring ECG patch to start immediately or delayed by 4 months after enrollment. For the observational study, 2 matched controls were selected for each actively monitored individual (mean age 73.7 years, median CHA2DS2-VASc score 3.0). The primary end point was the incidence of a new diagnosis of AF at 4 months among those randomized to immediate monitoring versus delayed monitoring. Researchers found that new AF was identified by 4 months in 3.9% of the immediate group versus 0.9% in the delayed group, with an absolute difference of 3.0% (95% CI 1.8% to 4.1%). In addition, active monitoring was associated with increased initiation of anticoagulants (5.7 vs. 3.7 per 100 person-years, difference 2.0 (95% CI 1.9 to 2.2)), outpatient cardiology visits (difference 7.5, 95% CI 7.2 to 7.9), and primary care visits (difference 0.9, 95% CI 0.4 to 1.5). There was no significant difference in AF-related emergency department visits and hospitalizations with a difference of 0.1.This study therefore shows that among individuals at high risk for AF, immediate monitoring with a home-based wearable ECG sensor patch, compared with delayed monitoring, resulted in a higher rate of AF diagnosis after 4 months.

Effect of Acupuncture vs Sham Acupuncture or Waitlist Control on Joint Pain Related to Aromatase Inhibitors Among Women With Early-Stage Breast Cancer A Randomized Clinical Trial

Many postmenopausal women with early-stage breast cancer are administered aromatase inhibitors as part of their cancer care. However, for some patients, joint pain can be a debilitating side effect of this therapy, leading to discontinuation of this medication. Small studies have suggested that acupuncture may decrease aromatase inhibitor-related joint symptoms. In this randomized controlled trial, 110 patients were randomized to receive true acupuncture, while 59 were randomized to receive sham acupuncture, and 57 were randomized to a waitlist control group, to determine the effect of acupuncture in reducing aromatase inhibitor-related joint pain. True acupuncture and sham acupuncture protocols consisted of 12 acupuncture sessions over 6 weeks (2 sessions per week), followed by 1 session per week for 6 weeks. The waitlist control group did not receive any intervention. All participants were offered 10 acupuncture sessions to be used between weeks 24 and 52. The primary end point was the 6-week Brief Pain Inventory Worst Pain (BPI-WP) score. Researchers found that from baseline to 6 weeks, the mean observed BPI-WP score decreased by 2.05 points in the true acupuncture group, by 1.07 points in the sham acupuncture group, and by 0.99 points in the waitlist control group. The difference in BPI-WP between true acupuncture versus sham acupuncture was statistically significant at 0.92 points (95% Cl 0.20 to 1.65, p=0.01) as was the difference between true acupuncture versus the waitlist control at 0.96 points (95% Cl 0.24 to 1.67, p=0.01). As expected, the patients in the true acupuncture group experienced more grade 1 bruising compared with patients in the sham acupuncture group (47% vs 25%, p=0.01). This study therefore shows that in postmenopausal patients with early stage breast cancer that experience aromatase inhibitor-related arthralgias, true acupuncture may result in significant reduction in joint pain at 6 weeks, although the clinical significance of these findings requires further study.

Effect of Alteplase vs Aspirin on Functional Outcome for Patients With Acute Ischemic Stroke and Minor Nondisabling Neurologic Deficits: The PRISMS Randomized Clinical Trial

The use of intravenous alteplase forms the standard of care in patients with ischemic stroke who present with disabling symptoms. It is unclear, however, whether its use is medically useful or necessary in patients who present with minor neurologic deficits. Many of these patients go on to have sustained neurologic deficits and/or functional disability 90 days after stroke. In this randomized controlled trial, 313 patients were randomized to receive intravenous alteplase (0.9 mg/kg) with oral placebo (n=156) or oral aspirin (325 mg) with intravenous placebo (n=157) to evaluate the efficacy and safety of alteplase in patients with acute ischemic stroke and minor, non-disabling neurologic deficits. The primary outcome studied was the difference in favorable functional outcome, defined as a modified Rankin Scale score of 0 or 1 at 90 days via the Cochran-Mantel-Haenszel test stratified by pretreatment NIHSS (National Institutes of Health Stroke Scale) score, age, and time from onset to treatment. Researchers found that at 90 days of follow-up, 122 patients (78.2%) in the alteplase group and 128 patients (81.5%) in the aspirin group achieved a favorable outcome. This corresponded to a non-significant difference of -1.1% (95% Cl -9.4% to 7.3%). In addition, 5 alteplase-treated patients (3.2%) versus 0 aspirin-treated patients experienced symptomatic intracranial hemorrhage, with a difference of 3.3% (95% Cl 0.8% to 7.4). The trial was terminated early. This study therefore shows that use of intravenous alteplase in patients with minor, nondisabling acute ischemic stroke does not increase the likelihood of favorable functional outcomes at 90 days, and may lead to significant harm.

Evaluation of a mosaic HIV-1 vaccine in a multicentre, randomised, double-blind, placebo-controlled, phase 1/2a clinical trial (APPROACH) and in rhesus monkeys (NHP 13-19)

The rate of HIV diagnosis worldwide remains high, with 1.8 million new cases of HIV-1 infection diagnosed in 2016. This multi-centre, randomized, double blind, placebo-controlled phase 1/2 trial aimed to evaluate the optimal vaccine regimen of a mosaic adenovirus serotype 26 based HIV-1 vaccine in candidates in parallel studies in humans and rhesus monkeys. Human participants included healthy, HIV-1 uninfected individuals considered at low risk for infection. Participants in the intervention group were given Ad26.Mos.HIV expressing mosaic HIV-1 envelope (Env)/Gag/Pol antigens at weeks 0 and 12 and given boosters at weeks 24 and 48 with the same strain or modified vaccinia Ankara with or without high dose (250 μg) or low dose (50 μg) aluminum adjuvanted clade C Env gp140 protein. Participants in the control group received 0.9% saline. Primary endpoints were safety and tolerability of the vaccine regimens and Env-specific binding antibody responses at week 28. Researchers found that the mosaic Ad26/Ad26 plus high-dose gp140 boost vaccine was the most immunogenic in humans; it elicited Env-specific binding antibody responses (100%) and antibody-dependent cellular phagocytosis responses (80%) at week 52, and T-cell responses at week 50 (83%). The Ad26/Ad26 plus gp140 boost induced similar magnitude, durability, and phenotype of immune responses in rhesus monkeys as compared with humans and afforded 67% protection against acquisition of simian-human immunodeficiency virus (SHIV-SF162P3) infection. This study therefore showed that the mosaic Ad26/Ad26 plus gp140 HIV-1 vaccine induced comparable and robust immune responses in humans and rhesus monkeys.

Prevention of M. tuberculosis Infection with H4:IC31 Vaccine or BCG Revaccination

Mycobacterium tuberculosis (TB) infection remains a leading cause of mortality among global infectious diseases. It has been shown that primary bacilli Calmette-Guerin (BCG) vaccinations may offer partial protection against infection. Another vaccine candidate, H4:IC31, has also been shown to have protection against TB in preclinical models. In this phase 2 trial, 990 adolescents in a high risk setting who had undergo neonatal BCG vaccination were randomly assigned to receive the H4:IC31 vaccine, BCG revaccination, or placebo to evaluate the BCG and H4:IC31 vaccines in the prevention of TB infection. All participants had negative results on testing for M. tuberculosis infection on the QuantiFERON-TB Gold In-tube assay (QFT) and for the human immunodeficiency virus at baseline. The primary outcomes were safety and acquisition of M. tuberculosis infection, as defined by initial conversion on QFT that was performed every 6 months during a 2-year period. Researchers found that QFT conversion occurred in 14.3% of participants in the H4:IC31 group, 13.1% of participants in the BCG group, and 15.8% of participants in the placebo group. The rate of sustained conversion was 8.1% in the H4:IC31 group and 6.7% in the BCG group, as compared with 11.6% in the placebo group. Neither the H4:IC31 vaccine (p=0.63) nor the BCG vaccine (p=0.29) prevented initial QFT conversion, with efficacy point estimates of 9.4% and 20.1%, respectively. However, the BCG vaccine reduced the rate of sustained QFT conversion, with an efficacy of 45.4% (p=0.03); the efficacy of the H4:IC31 vaccine was 30.5% (p=0.16). There were no clinically significant between-group differences in the rates of serious adverse events, although mild-to-moderate injection-site reactions were more common with BCG revaccination. This study therefore shows that the vaccination of adolescents with either the BCG or H4:IC31 vaccine reduces the rate of sustained QFT conversion in a high-transmission setting, although neither the H4:IC31 vaccine nor BCG revaccination prevented initial QFT conversion.

Image: PD

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