By Jessica Taff, MD
Peer Reviewed
While the world’s political attention turned to conflict in Ukraine this week, the New York Times turned national attention to several physicians with big political ambitions [1]. Currently, 17 physicians sit in the House or Representatives and 3 in the Senate, numbers that are expected to grow in the near future. While keen medical knowledge may not always translate to savvy political skill, the two fields do have a common theme of perpetual change and controversy. In both, new data continually emerges to raise questions to commonly held thoughts and practices. In this week’s Primecuts, we review some new research that begs the question: is watchful waiting really best, or should we pursue more aggressive approaches to disease and comorbidity prevention and treatment?
To start, The New England Journal of Medicine revisited the hot topic of prostate cancer treatment by publishing a randomized cohort study of nearly 700 men with early prostate cancer undergoing either watchful waiting or radical prostatectomy [2]. During the 23-year study-period, disease-specific mortality was reduced in the surgery group (18%) compared to the observation group (29%). When stratified by gleason score, low-risk patients undergoing surgery showed a significant reduction in rate of death from all-causes, but not specifically from prostate cancer. Men in the intermediate-risk group undergoing surgery did show a significant absolute reduction in overall mortality (15.5 percentage points), death from prostate cancer (24.2 percentage points) and metastasis (19.9 percentage points). Surgical treatment did not reduce any of the named end-points in men with high-risk prostate cancer.
When stratified by age, the risk reduction of surgery was most significant for those younger than 65 years (relative risk [RR] 0.45) and with intermediate-risk prostate cancer (RR 0.38). In patients older than 65, radical prostatectomy was associated with a reduced risk of metastasis and need for palliative therapy, but not mortality. This new evidence of benefit from surgery complicates the already confusing patient-physician discussions that take place prior to screening, and may even bolster an argument for aggressive diagnosis and treatment [3]. However, it should be noted that fewer patients undergoing watchful waiting experienced urinary leakage (11% vs. 41% in the surgical group), perhaps still suggesting improved quality of life with a less invasive treatment strategy.
Turning to women’s health, a case-control analysis published in the British Medical Journal measured the effectiveness of the quadrivalent human papillomavirus (HPV) vaccine against cervical abnormalities at time of first cervical screening in women vaccinated between ages 12 and 26 [4]. Nearly 12,000 women found to have cervical abnormalities were matched to almost 100,000 controls with normal cytology. Three doses of the HPV vaccine were found to have an effectiveness of 46% against high-grade cytology (odds ratio [OR] 0.54, 95% CI 0.43-0.67) and 34% against other abnormalities (OR 0.66, CI 0.62-0.70). The study estimates that approximately 22 women require vaccination to prevent one cervical abnormality, an impressive statistic that reinforces the importance of vaccination in young women.
Now focusing on thromboembolic disease, The Journal of Cardiology released an ahead-of print article online investigating the survival effects of inferior vena cava (IVC) filter placement in patients with venous thromboembolism (VTE) and significant bleeding risk [5]. Often, the patients who warrant IVC filters have comorbidities that make anticoagulation too risky. This prospective cohort study examined 40,142 patients with VTE from a worldwide registry of symptomatic patients. Of these patients, 371 were identified as having significant bleeding risk and underwent IVC filter placement, with some also receiving anticoagulants. They were matched with 344 control patients who only received anticoagulation despite elevated bleeding risks. At 30 days, the all-cause mortality did not differ between the groups. However, death from pulmonary embolism (PE) did favor the filter group (risk adjusted mortality rate of 1.7 vs 4.9%, p=0.03), although recurrent VTE was tenfold higher in the IVC filter group (6.1 vs 0.6% p>0.001). This data suggests that although we often rush to place IVC filters to prevent “the second deadly PE” in an at-risk patient, this thinking may be inaccurate. It instead suggests that IVC filters may in fact put patients at increased risk of recurrent VTE and confer benefit via a mechanism distinct from anticoagulation [6].
Another, albeit less life threatening, concern for patients with deep vein thrombosis (DVT) is the development of post-thrombotic syndrome (PTS). This complication occurs in 25-50% of patients after DVT and may cause limb swelling, skin discoloration and/or ulcerations that are disruptive to a patient’s quality of life. To date, there are few preventive measures available for PTS, with elastic compression stockings (ECS) thought to be the best intervention to decrease risk. The Lancet published a multicenter randomized placebo-controlled trial of active vs. placebo ECS to assess their efficacy in preventing PTS [7]. Nearly 800 patients with a first DVT were randomized and assessed at 6 months for PTS using the Ginsberg Criteria of leg pain and swelling of over 1 month. The cumulative incidence of PTS was 14.2% in the active ECS vs 12.7% in the placebo ECS (Hazard ratio 1.13 95% CI 0.73-1.76, p=0.58), although this was statistically not significant. Despite this lack of convincing data, an accompanying editorial notes that compliance (defined as wearing the ECS for 3 or more days per week) reported in the trial over a two-year observation period was only 55.6% [8]. They argue that improved compliance could potentially alter results and clinical recommendations should be individualized, given that so few options exist for prevention and treatment of PTS.
Other noteworthy articles in the literature:
The European Journal of Endocrinology released new guidelines on the treatment of hyponatremia, which accounts for 15-20% of inpatient admissions and is associated with significant mortality, morbidity, and length of hospital stay [9]. These guidelines are a result of collaboration between three European Societies (the European Society of Intensive Care Medicine, the European Society of Endocrinology and the European Renal Association) and offer graded evidence as well as algorithms for diagnosis and management of hyponatremia in everyday practice.
Circulation joined the guideline game and published new recommendations on medical, surgical, and postoperative management of patients with valvular heart disease (VHD) as a collaborative effort by the American Heart Association and the American College of Cardiology [10]. Most notably, these guidelines offer a new system of stages A-D to classify and treat patients based on VHD risk and symptom severity.
The Lancet Infectious Disease released a prospective cohort study of antibiotic prescription strategies for acute sore throat in the primary care setting [11]. The study looked at just under 12,000 patients and found that 1.4% developed complications, the most common being otitis media and sinusitis (62%). Although immediate antibiotic prescription was associated with fewer complications, delayed prescription of antibiotics for non-resolving symptoms provided similar benefits for the patient.
Dr. Jessica Taff is a 3rd year resident at NYU Langone Medical Center
Peer reviewed by Matthew Vorsanger, Associate Editor, Clinical Correlations
Image courtesy of Wikimedia Commons
References:
1. Peters JW. Is there a doctor in the House? Yes, 17. And 3 in the Senate. The New York Times. March 7, 2013. http://www.nytimes.com/2014/03/08/us/politics/doctors-confident-in-their-healing-powers-rush-for-congress.html?_r=0
2. Bill-Axelson A, Holmberg L, Germo H, et al. Radical Prosatectomy or Watchful Waiting in Early Prostate Cancer. N Engl J Med 2014; 370:932-942 DOI: 10.1056/NEJMoa1311593. http://www.nejm.org/doi/full/10.1056/NEJMoa1311593
3. Chou R, Croswell JM, Dana T, et al. Screening for Prostate Cancer: A Review of the Evidence for the U.S. Preventive Services Task Force. Annals of Internal Medicine. 2011 Dec;155(11):762-771. http://annals.org/article.aspx?articleid=1033197&resultClick=3
4. Crowe E, Pandeya N, Brotherton JML, et al. Effectiveness of quadrivalent human papillomavirus vaccine for the prevention of cervical abnormalities: a case-control study nested within a population based screening programme in Australia. BMJ 2014;348:g1458. doi: http://dx.doi.org/10.1136/bmj.g1458. http://www.bmj.com/content/348/bmj.g1458
5. Muriel A, Jiménez D, Aujesky D, et al. Survival Effects of Inferior Vena Cava Filter in Patients with Acute Symptomatic Venous Thromboembolism and a Significant Bleeding Risk, Journal of the American College of Cardiology (2014). doi:10.1016/j.jacc.2014.01.058. http://www.sciencedirect.com/science/article/pii/S0735109714011711
6. Morris T, Do IVC Filters Prevent Death from Pulmonary Embolism?, Journal of the American College of Cardiology (2014). doi: 10.1016/j.jacc.2014.01.057. http://www.sciencedirect.com/science/article/pii/S0735109714011681
7. Kahn SR, Shapiro S, Wells PS, et al, for the SOX trial investigators. Compression stockings to prevent post-thrombotic syndrome: a randomised placebo-controlled trial. Lancet 2013; published online Dec 6. http://dx.doi.org/10.1016/S0140-6736(13)61902-9. http://www.sciencedirect.com/science/article/pii/S0140673613619029
8. Cate-Hoek A. Elastic compression stockings – is there any benefit? Lancet. March 2013. 383:851-853. http://dx.doi.org/10.1016/ http://www.sciencedirect.com/science/article/pii/S0140673613623478
9. G Spasovski, R Vanholder, B Allolio, et al. Clinical practice guidelines on diagnosis and treatment of hyponatraemia. Eur J Endocrinol 170 G1-G47, doi: 10.1530/EJE-13-1020 http://eje-online.org/content/170/3/G1.full.pdf+html
10. Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC Guidelines for the Management of Patients with Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. March 3 2014, doi:10.1161/CIR.0000000000000031 http://circ.ahajournals.org/content/early/2014/02/27/CIR.0000000000000031.full.pdf+html
11. Little P, Staurt B, Hobbs FDR, et al. Antibiotic prescription strategies for acute sore throat: a prospective observational cohort study. Lancet Infect Dis 2014;14: 213–19. http://dx.doi.org/10.1016/S1473-3099(13)70294-9