By Stephanie Charles, MD
Peer Reviewed
This week marked an important point in our national health care debate. The American Health Care Act put forth by the Republican party failed to pass by Congress, allowing for the continuation of the Affordable Care Act, at least for now. Read below to learn of the important work published by the medical community this week.
Trial of Pregabalin for Acute and Chronic Sciatica
Pregabalin (Lyrica, Pfizer) is an antiepileptic medication that has been shown to reduce symptoms of neuropathic pain in patients with post-herpetic neuralgia and peripheral neuropathy. This double-blind, placebo-controlled, randomized trial sought to investigate the role of pregabalin in the treatment of acute sciatica [1]. 108 patients with sciatica were randomized to receive pregabalin while 101 patients received placebo. Inclusion criteria included sciatic pain for a minimum of one week and a maximum of one-year, moderate-severe intensity leg pain, and 18 years of age. Exclusion criteria included serious spinal pathology, pregnancy, breastfeeding, planned spinal surgery, the concomitant use of antiepileptic, antidepressant, or sedative medications, or a history of severe depression with suicidal ideation. Patients in the treatment group received a starting dose of pregabalin 150 mg with gradual increases to a maximum of 600 mg daily; the study period lasted for a total of 8 weeks. The primary outcome was leg-pain intensity assessed at week 8 and week 52. Secondary outcomes included extent of disability, back pain, and quality of life. The mean difference between the two groups in leg-pain intensity score was not significant at week 8 (3.7 in treatment group, 3.1 in placebo group, P =0.19), nor at week 52 (3.4 in the pregabalin group, 3.0 in the placebo group, P= 0.46). There was no effect of pregabalin, as compared with placebo, observed in the secondary outcomes of disability at week 8, back pain intensity at week 8, and quality of life scale at week 8 and week 52. The number of reported serious adverse events was small and similar in both groups; however, the number of reported overall adverse events was significantly higher in the treatment group (227 in the treatment group versus 68 in the control group, P=0.002), with dizziness being the most common reported symptom. The study concluded that pregabalin did not reduce symptoms of acute sciatic or improve quality of life compared to placebo. This implies that the frequent use of pregabalin in clinical practice for the treatment of sciatica is functionally ineffective, and that alternate modalities of treatment should be explored instead.
Uninterrupted Dabigatran versus Warfarin for Ablation in Atrial Fibrillation
Catheter ablation is a commonly employed treatment for atrial fibrillation. Anticoagulation in patients undergoing ablation is important to reduce the risk of periprocedural stroke or transient ischemic attack, however there is little consensus on the management of anticoagulation pre or post-procedure [2]. In this multicenter trial published in the NEJM, patients undergoing catheter ablation for atrial fibrillation were randomized to receive either dabigatran (150 mg twice daily) or warfarin (target INR 2-3). The trial consisted of four consecutive periods: a screening period of 0-2 weeks, a preablation treatment period of 4 to 8 weeks, a postablation treatment period of 8 weeks, and a follow up period of one week. The primary end point was incidence of a major bleeding event from time of ablation to 8 weeks. Secondary end points included incidence of composite stroke, systemic embolism, or TIA, and minor bleeding events during ablation through 8 weeks. 317 patients were randomized to receive dabigatran while 318 received warfarin. The patients received their respective anticoagulant during the preablation period to allow for patients to achieve a therapeutic INR in the warfarin group. The percentage of patients with major bleeding was significantly lower in the dabigatran group compared with warfarin [5 patients (1.6%) vs. 22 patients (6.9%), P<0.001]. There were no events of stroke, systemic embolism, or TIA in the dabigatran group and only one event in the warfarin group from ablation until 8 weeks later. This study concluded that anticoagulation with uninterrupted dabigatran was associated with fewer bleeding events than uninterrupted warfarin in patients undergoing ablation for atrial fibrillation, and may be the preferred method of anticoagulation.
Prevention of Hereditary Angioedema Attacks with a Subcutaneous C1 Inhibitor
Hereditary angioedema is a potentially fatal condition caused by deficiency or dysfunction of the C1 inhibitor protein. The disorder is characterized by episodes of swelling without urticaria or pruritus. Regular intravenous C1 inhibitor replacement is effective at reducing the frequency and severity of attacks. However, regular venous administration can be technically difficult and inconvenient. The objective of this study was to evaluate the efficacy and safety of a self-administered subcutaneous CSL830 in patients with type I or type II hereditary angioedema. The trial was an international, multicenter, randomized, double-blind, placebo-controlled phase 3 trial [3]. Patients were randomized to one of four treatment groups in a cross-over design for 16-week periods: 40IU or 60IU of CSL830 per kilogram body weight twice weekly followed by placebo, or vice versa. The primary outcome was number of attacks of angioedema, and secondary outcomes included percentage of patients who had a response and number of times that rescue medication was used. 90 patients were enrolled in the study, with 45 patients randomized to each treatment arm. Both 40IU and 60IU of CSL830, as compared to placebo, reduced the rate of attacks of hereditary angioedema (mean difference with 40IU, -2.42 attacks per month; mean difference with 60IU, -3.51 attacks per month, P<0.001 for both comparisons). The use of rescue medications was reduced from 5.55 uses per month in the placebo group to 1.13 in the 40IU group, and from 3.89 uses in the placebo group to 0.32 uses in the 60IU group. Adverse events were not significantly different between the treatment and placebo groups. Thus, in patients with hereditary angioedema, the use of a prophylactic self-administered twice-weekly C1 inhibitor reduced the frequency of attacks, and may become standard of care for this rare but potentially fatal condition.
The Definitive Management of Primary Hyperparathyroidism. Who Needs an Operation?
New guidelines for the definitive management of primary hyperparathyroidism were published in JAMA surgery earlier this year, and the guidelines were reviewed this week in JAMA [4]. A multidisciplinary panel reviewed the relevant medical literature between 1985 and 2015 on PubMed and determined the guidelines based on their findings and expert consensus [5]. The guidelines recommend initial evaluation of a patient with suspected primary hyperparathyroidism with 25-hydroxyvitamin D measurement, 24-hour urine calcium measurement, dual-energy x-ray absorption, and supplementation for vitamin D deficiency. The panel recommends that symptomatic patients, as well as asymptomatic patients with osteoporosis, a 24-hour urine calcium level greater than 400mg/dl, a serum calcium level grater than 1mg/dl above the normal range, age younger than 50 years, or decreased renal function be considered for surgery. The panel expanded the number of surgical candidates by including patients with neurocognitive and neuropsychiatric symptoms attributed to elevated parathyroid hormone and some patients with cardiovascular disease. The panel emphasized that primary hyperparathyroidism is a biochemical diagnosis, and does not require imaging for diagnosis. The guidelines recommend preoperative thyroid ultrasonography to detect thyroid neoplasms and/or nodules as a large proportion of patients with primary hyperparathyroidism have concurrent functional thyroid disease at the time of surgery. The guidelines conclude that both minimally invasive parathyroidectomy and bilateral exploration are appropriate and effective options to achieve high cure rates. Postoperatively, patients should be observed for hematoma, evaluated for hypocalcemia, and monitored to assess for cure and hypocalcemia requiring calcium supplementation.
Minicuts
In this week’s edition of the New England Journal of Medicine, two powerful articles on physician burnout and the stigma of mental health disorders among physicians were published. Kathryn explores how one medical school was impacted by the suicide of a fourth-year student, and how the school is changing its culture of medicine [6]. Breaking the Stigma is an autobiographical piece about one physician’s struggle with depression, and addresses the stigma physicians often face when battling their own mental health challenges [7].
The Lancet published an article on the optimal duration of trastuzamab for early HER2-posiive breast cancer, concluding that one year of treatment significantly improves long-term disease-free survival compared with observation, while two years of treatment had no additional benefit. [8]
Dr. Stephanie Charles is a 1st year resident at NYU Langone Medical Center.
Peer reviewed by Dr. Amar Parikh, Contributing Editor, Clinical Correlations and 3rd-year resident at NYU Langone Medical Center.
Image courtesy of www.forbes.com
References
- Mathieson S. Trial of Pregabalin for Acute and Chronic Sciatica. NEJM. 2017; 376 (12): 1111-1120 http://www.nejm.org/doi/full/10.1056/NEJMoa1614292
- Calkins H, Williams S, et al. Uninterrupted Dabigatran versus Warfarin for Ablation in Trial Fibrillation. NEJM.org. 2017: 1-10 http://www.nejm.org/doi/full/10.1056/nejmoa1701005%20-%20t=article
- Longhurst H. Prevention of Hereditary Angioedema Attacks With a Subcutaneous C1 Inhibitor. NEJM. 2017; 376 (12): 1131-1140 http://www.nejm.org/doi/full/10.1056/NEJMoa1613627?query=featured_home
- Wilhelm SM, Wang TS, Ruan DT, et al. The American Association of Endocrine Surgeons Guidelines for Definitive Management of Primary Hyperparathyroidism. JAMA Surg. 2016; 151(10): 959-968. http://jamanetwork.com/journals/jama/article-abstract/2612601
- Campbell MJ. The Definitive Management of Primary Hyperparathyroidism. Who Needs an Operation? JAMA. 2017; 317 (11): 1167-1168
- Muller, D. Kathryn. NEJM. 2017; 376 (12): 1101-1103 http://www.nejm.org/doi/full/10.1056/NEJMoa1614292?query=featured_home
- Hill, AB. Breaking the Stigma- A Physician’s Perspectibe on Self-Care and Recovery. NEJM. 2017; 376 (12): 1103-1105 http://www.nejm.org/doi/full/10.1056/NEJMp1615974
- Specht, JM, Davidson NE. Optimal Duration of Trastuzumab for early HER2-positive Breast Cancer. The Lancet. 2017; 389 (10075): 1167-1168 http://thelancet.com/journals/lancet/article/PIIS0140-6736(17)30322-7/abstract