Primecuts-This Week in the Journals

August 6, 2013

By: Matthew Weiss, MD

Though Don Draper publicly explained to us “Why I’m Quitting Tobacco” as far back as 1965, we’re still collectively dealing with the repercussions of those smokers, Don included, who didn’t follow his sage advice. Lung cancer today, 85% of which is attributable to cigarette use, makes up more than a quarter of all cancer deaths and claims roughly 160,000 American lives yearly – more than the toll from colorectal, breast and prostate cancers combined [1]. Nearly 90 percent of patients with lung cancer ultimately die from it, but perhaps often because it is diagnosed “too late.”

For decades now doctors have been struggling to succeed in guiding their patients to quit – or better yet, to not start – smoking. All too frequently that message seems to fall on deaf ears, and instead the main medical objective becomes not one of primary prevention but one of treatment of frank disease. In the 1970s the American Cancer Society recommended chest X-rays as a screening modality to diagnose “early” lung cancer, but that recommendation was ultimately withdrawn in 1980 after it was concluded to have insufficient evidence for improved mortality [2]. This week the tide is again turning for lung cancer screening as the United States Preventive Services Task Force (USPSTF) has tentatively formalized a new recommendation to screen “high risk” patient populations with low-dose computed tomography (LDCT) scans [3,4].

The basis for this recommendation comes from a new report published this week in the Annals of Internal Medicine [5]. With the goal of updating the USPSTF, which last addressed the screening issue in 2004 and does not currently endorse chest X-ray or CT screening, this group of researchers sifted through over 8,000 abstracts and 67 full-text articles which addressed the issue [6]. Ultimately they focused on four trials in particular which they deemed to best assess the effectiveness of LDCT [7-11]. Of those four studies, two in particular showed reduced lung cancer related mortality with LDCT use, while two other studies, which the group deemed of “fair or poor quality” and less applicable to American populations, did not. The current group focused most closely on the National Lung Screening Trial (NLST) from 2011, which compared three annual LDCTs versus conventional chest x-rays in 50,000 patients aged 55-74 with smoking histories of greater than 30 pack-years. The current group emphasized the findings of the NLST, namely that after 6.5 years of follow-up, lung cancer mortality was reduced by 20% (95% CI, 6.8% to 26.7%) in the LDCT group with a number needed to screen (NNS) to prevent one lung cancer death of 320. Additionally, all-cause mortality was reduced by 6.7% with NNS of 219 [11]. Of note, these numbers compare favorably with other, now standard–of-care, screening practices – NNS via mammography to prevent once breast cancer death being 1339 for women 50-59 after up to 20 years of follow-up; as well as the NNS via flexible sigmoidoscopy of 817 for colon cancer related death [12-14].

The results of this review and the USPSTF’s new recommendation have major implications for patients and the healthcare system as a whole, however there are some significant gaps. None of the newest analysis specifically addressed gender, racial or ethnic groups, nor did it address the issue of radiation exposure via repeated CT scans. A USPSTF recommendation carries with it major financial implications, including payment coverage by most insurances (including Medicare), but again the studies to date did little to address the screening issues of overdiagnosis and false-positive related anxiety. While a “free” screening LDCT may comfort many patients with a strong smoking history, will the risk of a false-positive or frequent radiation exposure push them to a cigarette to ease their anxiety?

Last week offered an interesting case from the NYU intensive care unit of a 70 year-old woman presenting with hypotension in the setting of three weeks of watery diarrhea with an unrevealing initial workup. A concomitant report from the New York City Department of Health and Mental Health suggested NYC medical providers be on the alert for exactly such cases in the setting of a nationwide outbreak of cyclosporiasis, a protozoal disease notably not routinely tested for on laboratory ova and parasites (O+P) tests [15]. Currently 400 cases have been reported (41 confirmed) within the 16 states and 22 patients hospitalized. As of this week the CDC and FDA have issued a traceback investigation report confirming at least two Iowa and Nebraska cases as secondary to pre-packaged salad dressing contaminants. The source appears to be a food services company by the name of Taylor Farms de Mexico which supplies restaurants including Red Lobster and Olive Garden. Unlimited salad bar? No thanks. Of educational note, this report should refresh the practitioner’s memory of cyclospora, a fecal-orally transmitted human intracellular protozoal parasite capable of causing a typically self-limited diarrheal illness sometimes associated with generalized symptoms. Diagnostic screening requires a modified acid fast stain, not always included as part of the standard O+P. Typical treatment course involves a seven-day course of oral trimethoprim-sulfamethoxazole.

A new meta-analysis from the British Medical Journal reassesses the current 2009 European Society of Cardiology (ESC) class I recommendation regarding perioperative initiation of beta-blockade in those at risk for cardiac events undergoing high- or intermediate- risk surgery or vascular surgery [16]. Prior pro-beta-blocker data and recommendations stem largely from the DECREASE family of studies first published in 1999 and now much discredited secondary to the lead author’s well publicized violations of academic integrity [17,18]. The latest meta-analysis includes 10,000 patients in nine randomized controlled trials (DECREASE excluded) of initiation of beta-blockers before non-cardiac surgery. Findings show that initiation of a course of beta-blockers before surgery caused a 27% risk increase in 30-day all-cause mortality (p=0.04). Subgroup analysis found that while beta-blockade reduced non-fatal myocardial infarction (RR 0.73, p=0.001), risk of stroke and hypotension were increased (RR 1.73, p=0.05 and RR 1.51, p<0.00001, respectively). This data has major implications within the U.S. and especially in Europe where perioperative beta-blockers are still routinely recommended per the ESC 2009 guidelines.

Lastly, the British Medical Journal reports new data from a meta-analysis which combined six studies with roughly 900,000 type-2 diabetic patients who experienced severe hypoglycemia in non-acute hospital setting to assess the associated risk of cardiovascular disease [19]. All studies reviewed showed a strong positive association between hypoglycemia and cardiovascular disease (RR 1.60 to 3.45). Traditionally the association between hypoglycemia and worsened cardiovascular outcomes has been attributed to comorbid illness. However, further analysis to eliminate confounding from unmeasured comorbid severe illnesses (renal and liver disease, etc.) suggests that these illnesses may not explain the observed association between severe hypoglycemia and cardiovascular disease. Suggested physiologic explanations include catecholamine response, increased platelet activation, leukocyte mobilization and subsequent coagulation with resulting adverse effects on the myocardium and vascular system as a result of hypoglycemia. This meta-analysis suggests the story may be more straightforward with a possible direct correlation between hypoglycemia and adverse cardiovascular events. This data adds to the already known risks of intense glucose control established in the ACCORD trial where strict glycemic control goals led to a 22% increase in total mortality [20] and suggests more moderate goals for glycemic control in patients with type-2 diabetes.

Also interesting in the journals recently…

1. Iglehart J. The Residency Mismatch. N Engl J Med. July, 25 2013. 369;4. http://www.nejm.org/doi/full/10.1056/NEJMp1306445.  A new Perspective piece from the New England Journal points to the growing disparity between the number of students receiving medical education within the United States and the number of Graduate Medical Education positions available for residency training suggesting that “it may soon be impossible for all graduates of U.S. medical and osteopathic colleges to secure GME slots.”

2. Agnieszka P. Knowledge about heart failure in primary care: Need for strengthening of continuing medical education. Cardiology Journal. Vol 20, No 4, 2013. http://czasopisma.viamedica.pl/cj/article/view/CJ.2013.0093 .  Also with regard to medical education, a new study from Poland suggests that general practitioner age is inversely proportional to appropriate outpatient management of heart failure. Older physicians were more likely to point to electrocardiogram and chest films as exclusion criteria for systolic heart failure and were less likely to prescribe angiotensin receptor blockers and beta blockers, instead preferring spironolactone and digitalis while younger physicians opted for newer beta blockers such as carvedilol (p<0.05).

3. Sabayan B. Association of visit-to-visit variability in blood pressure with cognitive function in old age: prospective cohort study. BMJ 2013; 347. http://www.bmj.com/content/347/bmj.f4600 . New data from a prospective study of 5,000 patients of mean age 75 who were at risk for cardiovascular disease suggests that high variability in blood pressure, independent of mean blood pressure (as measured from visit-to-visit) was associated with impaired cognitive function. The magnitude of the association was similar to the observed differences between groups of apolipoprotein E genotype positive patients where it has been shown that people who carry this risk factor for dementia have a four-times higher risk of developing late onset Alzheimer’s disease. Further study is warranted to determine if reduced variability in BP might decrease the risk of cognitive impairment in old age.

Matthew Weiss, MD is a second year resident at NYU Langone Medical Center

Peer Reviewed by Matthew Vorsanger, MD, Associate Editor, Clinical Correlations

References

1. American Cancer Society. Cancer Facts & Figure 2013. Atlanta, GA: American Cancer Soc; 2013. http://www.cancer.org/research/cancerfactsstatistics/allcancerfactsfigures/index .

2. Eddy D. ACS report on the cancer-related health checkup. CA Cancer J Clin. 1980; 30: 193-240. http://www.ncbi.nlm.nih.gov/pubmed/6774802?dopt=Abstract .

3. Tavernise S. Task Force Urges Scans for Smokers at High Risk. The New York Times. July, 29 2013. http://www.nytimes.com/2013/07/30/health/task-force-recommends-screening-for-heavy-smokers.html.

4. Panel Backs Lung Cancer Screening for Some Smokers. The Associated Press via NPR. July, 29 2013. http://www.npr.org/templates/story/story.php?storyId=206764757 .

5. Humphrey L. Screening for Lung Cancer with Low-Dose Computed Tomography: A Systematic Review to Update the U.S. Preventive Services Task Force Recommendation. Ann Intern Med. July, 30 2013. http://annals.org/article.aspx?articleid=1721248 .

6. U.S. Preventive Services Task Force. Lung cancer screening: recommendation statement. Ann Intern Med. 2004; 140:738-9. http://annals.org/article.aspx?articleid=717423 .

7. Infante M. A randomized study of lung cancer screening with spiral computed tomography: three-year results from the DANTE trial. Am J Respir Crit Care Med. 2009;180:445-53. http://www.atsjournals.org/doi/abs/10.1164/rccm.200901-0076OC .

8. Infante M. Lung cancer screening with spiral CT: baseline results of the randomized DANTE trial. Lung Cancer. 2008;59:355-63. http://www.lungcancerjournal.info/article/S0169-5002(07)00511-9/abstract .

9. Saghir Z. CT screening for lung cancer brings forward early disease. The randomized Danish Lung Cancer Screening Trial: status after five annual screening rounds with low-dose CT. Thorax. 2012;67:296-301. http://thorax.bmj.com/content/67/4/296.abstract .

10. Pastorino U. Annual or biennial CT screening versus observation in heavy smokers: 5-year results of the MILD trial. Eur J Cancer Prev. 2012;21:308-15. http://journals.lww.com/eurjcancerprev/Abstract/2012/05000/Annual_or_biennial_CT_screening_versus_observation .15.aspx.

11. Aberle DR. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011; 365:395-409. http://www.nejm.org/doi/full/10.1056/NEJMoa1102873 .

12. Humphrey L. Breast cancer screening: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2002;137:347-60. http://annals.org/article.aspx?articleid=715608 .

13. Nelson H. Screening for Breast Cancer: Systematic Evidence Review Update for the U.S. Preventive Services Task Force. Rockville, MD: Agency for Healthcare Research and Quality; 2009. Report 10-05142-EF-1. http://annals.org/article.aspx?articleid=745247 .

14. Schoen R. Colorectal-cancer incidence and mortality with screening flexible sigmoidoscopy. N Engl J Med. 2012;336:2345-57. http://www.nejm.org/doi/full/10.1056/NEJMoa1114635 .

15. NYC DOHMH. Nationwide Outbreak of Cyclosporiasis. http://cdc.gov/parasites/cyclosporiasis/outbreaks/investigation-2013.html .

16. Bouri S. Meta-analysis of secure randomized controlled trials of B-blockade to prevent perioperative death in non-cardiac surgery. Heart. Published Online First: July 31, 2013. http://heart.bmj.com/content/early/2013/07/30/heartjnl-2013-304262.abstract .

17. Poldermans D. The Effect of Bisoprolol on Perioperative Mortality and Myocardial Infarction in High-Risk Patients Undergoing Vascular Surgery. N Engl J Med 1999; 341:1789-1794. http://www.nejm.org/doi/full/10.1056/NEJM199912093412402 .

18. Erasmus MC fires Poldermans; ESC reviews his work. http://www.theheart.org/article/1315171.do .

19. Atsushi G. Severe hypoglycemia and cardiovascular disease: systematic review and meta-analysis with bias analysis. BMJ 2013, July 30. http://bmj.com/content/347/bmj.f4533 .

20. Gerstein HC. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008;358:2545-59. http://www.nejm.org/doi/full/10.1056/NEJMoa0802743 .

 

 

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