Primecuts-This Week in the Journals

January 8, 2018


By: Justin Feit, MD

We were welcomed to 2018 with the coldest New Year’s in New York City in over 50 years with a cool 10°F recorded in Times Square [1]. The onslaught of frigid weather continued as the northeastern United Status battled the ‘Bomb Cyclone’ this week [2]. We turn our minds to warmer thoughts as we take a look at this week’s medical news.

Safety of Magnetic Resonance Imaging in Patients with Cardiac Devices

Patients who have pacemakers or implantable cardioverter-defibrillators (ICDs) are often precluded from undergoing magnetic resonance imaging (MRI) [3] due to concerns of myocardial thermal injury and changes in the pacing properties of these implantable devices [4]. There have been a number of small studies looking at various implantable devices that have been deemed “MRI-conditional” by the Food and Drug Administration [4], but the majority of implantable devices currently in use have not been studied. These older devices, also known as “legacy devices”, are thus contraindicated for many MRI studies [4]. Investigators from the University of Pennsylvania and Johns Hopkins University sought to address this concern in their recently published study in the NEJM [5].

This study was a prospective, non-randomized, single-center study that looked at a total of 1509 patients with legacy devices who had a clinical indication to undergo magnetic resonance imaging. The primary outcome of the study was the number of adverse events or changes in device parameters. Fifty eight percent of participants (880) had pacemakers and 42% (629) had ICDs.

For all 1509 patients, device interrogation was performed prior to and immediately after the MRI. A total of 9 MRI examinations (0.4% of examinations, 95% CI 0.2 to 0.7) in eights patients (0.5%, 95% CI 0.2 to 0.9) experienced transient power-on resets during the examinations. Of these 9 MRI examinations, 1 examination resulted in mild physical symptoms, which was described as a pulling sensation in their chest. There were short-term changes in device parameters in about 4% of MRI examinations, none of which were large enough to result in device reprogramming or lead revision.

One of the limitations in this study was that although there were many different legacy devices studied, the amount of each individual device was small compared to the overall number included in the study. Nevertheless, the findings of this study suggest that many legacy devices that are in fact MRI-safe, which may result in more patients undergoing MRIs who previously were precluded from such examinations due to their pacemaker or ICD.

Effects of Calcium or Vitamin D on Fractures in Older Adults

The prevalence of osteoporosis in the United States is predicted to rise to nearly 20 million people by the year 2020. Osteoporosis is predicted to account for a cumulative health care cost of $25.3 billion by 2025 [6]. Current practice guidelines recommend calcium and vitamin D supplementation in the older population to prevent the burdensome complications resulting from osteoporosis [7]. While there have been many studies looking at associations between calcium and/or vitamin D supplementation with osteoporotic fracture risk, there has not been a consistent conclusion reached among these studies regarding this association [8]. Investigators from the Department of Orthopedic Surgery from two different Chinese hospitals sought to reconcile the different conclusions among studies that looked at various combinations of calcium and vitamin D supplementation with respect to fracture incidence [7].

This study was a meta-analysis of randomized controlled trials published in other systematic reviews/meta-analyses from 2006 to 2016. A total of 33 randomized controlled trials that included over 50,000 community-dwelling participants were analyzed. The primary outcome was hip fractures and the secondary outcomes were non-vertebral fractures, vertebral fractures and total fractures.

There was no statistically significant association between calcium supplementation (RR 1.53, 95% CI 0.97 to 2.42), vitamin D supplementation (RR 1.21, 95% CI 0.99 to 1.47) and calcium plus vitamin D supplementation (RR 1.09, 95% CI 0.85 to 1.39) and number of hip fractures in the included participants. There was also no statistically significant association between calcium supplementation, vitamin D supplementation, and combined calcium plus vitamin D supplementation and the various secondary outcomes as well.

Because this analysis primarily identified trials from previously published meta-analyses and systematic reviews, it may have missed some trials that fit the inclusion criteria here. Nonetheless, the findings of this meta-analysis do not support routine calcium and/or vitamin D supplementation in community-dwelling older adults.

Rifampin Use in Staphylococcus Aureus Bacteremia

Staphylococcus aureus bacteremia is a common and deadly infection seen around the world [9]. Despite the frequency with which S. aureus bacteremia is encountered in hospital settings, there is minimal trial data regarding optimal antibiotic therapy. Rifampin, an antibiotic that inhibits bacterial DNA-dependent RNA synthesis [10], has been thought to improve outcomes in S. aureus bacteremia, but evidence supporting this has been weak overall [11]. Researchers, as part of the ARREST trial, sought to investigate the role of rifampin in addition to standard antibiotic therapy in a multicenter, randomized, double blind, placebo-controlled trial [11] for patients with Staphylococcus aureus bacteremia.

Over 750 participants among 29 UK hospitals were randomly assigned to receive standard antibiotic therapy (left up to the discretion of the attending physician) in addition to either rifampin (N=370) or placebo (N=388) for two weeks. The primary outcome of the study was time to bacteriologically confirmed treatment failure (signs/symptoms of infection for more than 14 days), disease recurrence, or all-cause death from the time of randomization to 12 weeks.

After 12 weeks, the primary outcome occurred in 17% of patients treated with rifampin versus 18% of patients treated with placebo (absolute risk difference of -1.4%, 95% CI -7.0 to 4.3, hazard ratio of 0.96, 95% CI 0.68 to 1.35). In the analysis of secondary outcomes, fewer patients treated with rifampin (1%) as compared to patients treated with placebo (4%) had signs and/or symptoms of disease recurrence (p 0.01). However, there were more antibiotics-modifying adverse events in the rifampin group (89 events) as compared to the placebo group (52 events). This study ultimately concluded that, among patients with S aureus bacteremia, rifampin in addition to individually-determined standard antibiotic therapy did not have a significant effect on mortality or duration of bacteremia.

One of the limitations of this trial was the heterogeneity of participants from the different centers (ranging from 1 to 164 per center) and the resultant different antibiotics used as part of standard therapy in addition to either placebo or rifampin. Further studies that standardize the backbone antibiotic therapy may lead to different results in both the efficacy and safety outcomes.

Effectiveness of Blood Pressure Control Mechanisms

Hypertension is the leading preventable risk factor that contributes to premature death worldwide [12]. While there are many medications and life-style modifications that have been shown to reduce morbidity from hypertension [13], less than 15% of adults with hypertension have their blood pressures well-controlled [14]. Investigators from Tulane University sought to examine the effectiveness of different blood pressure control strategies in their recent systematic review and meta-analysis published in Annals of Internal Medicine.

Over 100 articles including over 55,000 hypertensive patients were included in this review article. Eight different implementation strategies of antihypertensive regimens were examined, including home blood pressure monitoring, team-based care with medication titration by physicians, and team-based care with titration of medications by non-physicians. Interventions that were associated with improved blood pressure control included health coaches (systolic BP reduced by 4.3 mm Hg, 95% CI 2.6 to 5.9), home blood pressure monitoring (systolic BP reduced by 2.2 mm Hg, 95% CI 1.0 to 3.5), team-based care with physician-led medication titration (systolic BP reduced by 5.7 mm Hg, 95% CI 3.5 to 7.9), and team-based care with non-physician-led medication titration (systolic BP reduced by 6.6 mm Hg, 95% CI 4.2 to 9.0). This review concluded that achieving controlled hypertension in the community is most effective with multilevel, multicomponent implementation strategies—including physicians, nurses, medical assistants, and community health workers.

One of the limitations of this study is the ability to implement these multicomponent strategies to be implemented in resource-poor areas, which is often where there are higher rates of uncontrolled hypertension [12]. Devoting more money to implementing these proven effective strategies in particularly high-risk communities, could reduce overall less morbidity and mortality from hypertension.

Minicuts

The DAWN trial showed the endovascular thrombectomy with medical care, as compared to medical therapy alone, improved disability outcomes at 90 days, among patients who were last known well within 6-24 hours of presentation and had symptomatic deficits out of proportion to infarct volume [15]. The data helps extend the time frame for performing thrombectomy in a select group of patients.

The National Institute on Drug Abuse sponsored a cost-effectiveness study of publicly-funded treatment of opioid use disorders in California. Modeling immediate methadone access to those with opioid use disorders compared to the standard of care with medically managed withdrawal resulted in significant cost savings that would amount to nearly $4 billion for the state of California while also giving participants accumulate more quality-adjusted life-years [16].

A more expensive but more efficacious new adjuvanted herpes zoster subunit vaccine was found to be more cost effective over the long run compared to the traditional live-attenuated vaccine that is commonly used for our elderly population [17].

For those suffering from diffuse cutaneous systemic sclerosis, the SCOT investigators found that myeloablative autologous hematopoietic stem-cell transplantation resulted in longer event-free and overall survival compared to traditional monthly cyclophosphamide infusions [18].

Justin Feet, MD is a 1st year internal medicine at NYU Langone Health

Peer Reviewed by Ian Henderson, MD Associate Editor, Clinical Correlations

Picture Courtesy of Wikimedia Commons

References:

  1. The Associated Press. Crystal Ball Drops in Frigid Times Square to Mark 2018. New York Times. January 1, 2018.
  2. The New York Times. ‘Bomb Cyclone’: Rare Snow in South as North Braces for Bitter Cold. New York Times. January 3, 2018.
  3. American College of Radiology. Appropriateness criteria. 2016 (https://acserarch.acr.org/list).
  4. Beinart R, Nazarian S. Effects of external electrical and magnetic fields on pacemakers and defibrillators: from engineering principles to clinical practice. Circulation 2013;128:2799-809.
  5. Nazarian S, Hansford R, Rahsepar AA, et al. Safety of Magnetic Resonance Imaging in Patients with Cardiac Devices. New England Journal of Medicine 2017;377:2555-2564.
  6. Burge R, Dawson-Hughes B, Solomon DH, et al. Incidence and economic burden of osteoporosis‐related fractures in the United States, 2005–2025. Journal of bone and mineral research3 (2007): 465-475.
  7. Zhao JG, Zeng XT, Wang J, et al. Association Between Calcium or Vitamin D Supplementation and Fracture Incidence in Community-Dwelling Older Adults. JAMA 2017;318(24):2466-2482.
  8. Bolland MJ, Grey A. A case study of discordant overlapping meta-analyses: vitamin D supplements and fracture. PLoS One. 2014 Dec 31;9(12):e115934.
  9. Naber CK. Staphylococcus aureus bacteremia: epidemiology, pathophysiology, and management strategies. Clinical Infectious DiseasesSupplement 4(2009):S231-S237.
  10. Wehrli W. Rifampin: mechanisms of action and resistance. Reviews of infectious diseasesSupplement_3 (1983): S407-S411.
  11. Thwaites GE, Scarborough M, Szubert A, et al. Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicenter, randomized, double-blind, placebo-controlled trial. The Lancet December 14, 2017;http://dx.doi.org/10.1016/S0140-6736(17)32456-X.
  12. Mills KT, Bundy JD, Kelly TN, et al. Global disparities of hypertension prevalence and control. Circulation6 (2016): 441-450.
  13. Gay HC, Rao SG, Vaccarino V, et al. Effects of Different Dietary Interventions on Blood Pressure. Hypertension(2016): HYPERTENSIONAHA-115.
  14. Mills KT, Obst KM, Shen W, et al. Comparative Effectiveness of Implementation Strategies for Blood Pressure Control in Hypertensive Patients: A Systematic Review and Meta-analysis. Annals of Internal Medicine 2017; doi:10.7326/M17-1805.
  15. Nogueira RG, Jadhav AP, Haussen A, et al. Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct. New England Journal of Medicine1 (2017).
  16. Krebs E, Enns B, Evans E, et al. Cost-Effectiveness of Publicly Funded Treatment of Opioid Use Disorder in California. Annals of internal medicine(2017).
  17. Le P, Rothberg MB. Cost-effectiveness of the Adjuvanted Herpes Zoster Subunit Vaccine in Older Adults. JAMA Internal Medicine.Published online January 02, 2018. doi:10.1001/jamainternmed.2017.7431
  18. Sullivan KM, Goldmuntz EA, Keyes-Elstein L, et al. Myeloablative Autologous Stem-Cell Transplantation for Severe Scleroderma. New England Journal of Medicine1 (2017).