Primecuts – This Week In The Journals

December 15, 2014

By Joseph Plaksin

Peer Reviewed

This week, the Senate Intelligence Committee declassified a 500-page report that outlined and described uses of torture by the CIA to interrogate suspected terrorists after the attacks of 9/11 [1]. While CIA Director John Brennan tried to defend his agency’s actions, Senator Dianne Feinstein, who chaired the committee that released the report, described the CIA’s interrogation program “a stain on our values and our history.”

Amidst these new revelations, protests in response to the grand jury decisions in the deaths of Michael Brown and Eric Garner continued this week. On Wednesday, medical students from 70 schools across the country, including NYU, joined these protests and staged die-ins in their respective medical centers under the social media campaign #WhiteCoats4BlackLives [2].

Racial and Ethnic Disparities among Enrollees in Medicare Advantage Plans [3]

A special article in NEJM this week underscores recent events and the national conversation about race and racial disparities in America. Black men and women have a 4-5 year shorter life expectancy than whites; a significant portion of this difference in mortality is accounted for by increased rates of poorly controlled cardiovascular disease and diabetes. Since 1997, Medicare has tracked the quality of care in HMO’s across the country using the Healthcare Effectiveness Data and Information set (HEDIS). This dataset includes information about testing for LDL and hemoglobin A1c as well as control of blood pressure, LDL, and hemoglobin A1c in patients with hypertension, cardiovascular disease, and diabetes, respectively. Previously, it was shown that disparities in LDL and hemoglobin A1c testing were reduced from 1997 to 2003, but that disparities in control of these risk factors remained.

This study collected data on blood pressure, LDL, and hemoglobin A1c in Medicare enrollees between ages 65-85 in 2006 and 2011. Control of these risk factors, after adjusting for age and sex, was significantly less for blacks than whites across the country in 2006. By 2011 these differences had disappeared in the Western region of the country and for patients enrolled in Kaiser Permanente health plans, but persisted in the Northeast, Midwest, and South. The differences in these areas could largely be accounted for by enrollment of blacks in lower-quality health plans than whites. This study suggests that while current healthcare disparities persist in the healthcare system across the country, effective and systematic efforts to reduce these can be successful.

Association of the 2011 ACGME Resident Duty Hour Reforms with Mortality and Readmissions among Hospitalized Medicare patients [4]

This week’s JAMA is their Medical Education issue, and one interesting article looks at the effects of the 2011 ACGME duty hour reforms for residents, which limited interns to working 16 consecutive hours and residents to working 24 consecutive hours. While these reforms were implemented due to concerns about resident fatigue and medical errors, critics have said that they negatively affect resident education and result in more frequent handoffs, which also is a source of medical errors.

This study collected data from Medicare patients admitted to short-term, acute care, non-federal hospitals across the country in the 2 years before the duty hour reforms were put in place as well as 1 year afterward. In total, this resulted in data on over 6 million hospital admissions. For each admission, the primary outcomes were 30-day all-location mortality and 30-day all-cause readmission. There was no change in the mortality or readmission rates after implementation of the 2011 ACGME duty hour reforms. There were also no differences between teaching hospitals and non-teaching hospitals. Possible reasons for this non-significant finding include the relatively minor changes to duty hours (compared to the reforms in 2003), unknown adherence to the new duty hours, and improved faculty supervision of residents that could be increasing quality of care and offsetting any negative effects of the shorter work hours.

Diabetes in Midlife and Cognitive Change Over 20 Years [5]

Returning to patient-focused research, an article in the Annals of Internal Medicine examined the association between diabetes in middle age and later cognitive decline. Diabetes has been shown to be a risk factor for dementia, but diabetes and hyperglycemia have not been firmly linked to long-term cognitive decline. Since patients with cognitive decline often progress to dementia, it is important to identify risk factors for cognitive decline and intervene on them whenever possible. This study collected data from 13,351 adults in the Atherosclerosis Risk in Communities (ARIC) prospective cohort study, 1779 of which had diabetes. Baseline data from this cohort was collected in 1987-1989 and then patients returned for follow-up visits approximately every 3 years until 2011-2013. Neuropsychological testing was performed at the second, fourth, and fifth visits (1990-1992, 1996-1998, and 2011-2013 respectively).

Patients with diabetes were older, less educated, had lower cognitive scores and more cardiovascular risk factors, and a much higher mortality rate (46% vs. 22%) than their non-diabetic counterparts. Overall patients with diabetes had a 19% greater cognitive decline compared to patients without diabetes. Among patients with diabetes, cognitive decline was directly related to hemoglobin A1c levels, with poorly controlled diabetics having significantly greater cognitive decline than those with well-controlled blood sugar. Having diabetes for a longer period of time was also significantly associated with greater cognitive decline. This is the first prospective long-term, large-scale study that has shown a link between diabetes and later cognitive decline, suggesting that efforts to prevent or control diabetes earlier in life could also protect against cognitive decline later in life.

Beta-Lactam Monotherapy vs. Beta-Lactam-Macrolide Combination Treatment in Moderately Severe Community-Acquired Pneumonia [6]

Finally, a randomized controlled trial (RCT) in JAMA Internal Medicine compared treatment options for community acquired pneumonia (CAP). Standard treatment in North America for CAP is to use a beta-lactam to cover Streptococcus pneumoniae and a macrolide or fluoroquinolone to cover atypical pathogens such as Legionella or Mycoplasma pneumoniae. However, macrolides are associated with adverse cardiovascular events and there is real concern that unnecessary use could promote resistance of S. pneumoniae to multiple antibiotic classes. Results from previous meta-analyses have been mixed. A meta-analysis of observational studies found a significant survival benefit in patients who received combination therapy, but a meta-analysis of RCT’s found no benefit [7].

This study recruited 580 adult patients who were admitted for suspected CAP. Patients were randomized to receive monotherapy with a beta-lactam (either cefuroxime or amoxicillin and clavulanic acid) or combination therapy with a beta-lactam and a macrolide (clarithromycin). The primary outcome was the number of patients who did not reach clinical stability (defined using validated criteria consisting mostly of abnormal vital signs) within 7 days of admission. On day 7, 41.2% of patients receiving monotherapy and 33.6% of patients receiving combination therapy had not reached clinical stability. While this difference was not statistically significant, it was above the pre-defined boundary for non-inferiority. Subgroup analysis showed that this non-inferiority was driven by a delay in reaching clinical stability in patients with either severe CAP (Pneumonia-severity-index category IV) or with proven atypical pathogens. The monotherapy group also had a significantly higher rate of 30-day readmission but there were no differences between the groups on a number of other secondary outcomes including length of stay, introduction of new antibiotics, transfer to intensive care, recurrence of pneumonia, complicated pleural effusions requiring chest tube placement, or 30- and 90-day mortality. Overall, these results led the authors to conclude that patients benefit from combination therapy, although larger studies are needed and mechanism of the dual therapy benefit continues to fuel debate.

In other news…

A European RCT published in The Lancet found that PSA testing for asymptomatic men aged 50-74 had a 21% relative risk reduction in prostate cancer after 13 years [8]. Despite this apparent risk reduction, the study did not quantify the rates of over-diagnosis and the harms from unnecessary treatments.

A retrospective cohort study in the JACC examined the effects of antithrombotic therapy for patients with both atrial fibrillation and chronic kidney disease (CKD) [9]. They found that warfarin was associated with lower mortality in CKD patients with CHADS2DS2-VASC score greater than 2 regardless of whether patients were on renal replacement therapy.

Another retrospective cohort study in JAMA characterized the pattern of use of hypofractionated whole breast irradiation (WBI) and conventional WBI after lumpectomy in women diagnosed with breast cancer [10]. Hypofractionated WBI (3-5 weeks of treatment) was previously found to be equivalent to conventional WBI (5-7 weeks of treatment) in patients younger than 50 with early stage (T1 or T2N0) breast cancer and no prior chemotherapy [11], but only 34.5% of patients who met these criteria received hypofractionated WBI in 2013.This concerning finding suggests that common practice using WBI may lag behind evidence-based medicine.

A prospective cohort study in the Journal of the American Society of Nephrology found that improved glycemic control in patients with Type 1 Diabetes and proteinuria delays decrease in glomerular filtration rate and the onset of end-stage renal disease [12].

Joseph Plaksin, a 3rd year medical student at NYU School of Medicine

Peer reviewed by Jessica Taff, MD,  Associate Editor, Clinical Correlations

Image courtesy of Wikimedia Commons


1. Mazetti M. “Panel Faults C.I.A. Over Brutality and Deceit in Terrorism Interrogations.” NY Times Online. December 9, 2014.

2. Workneh L. “#WhiteCoats4BlackLives: Health Care Workers Stage Nationwide Protests Against Police Brutality.” Huffington Post. December 10, 2014.

3. Ayanian JZ, Landon BE, Newhouse JP, Zaslavsky AM. Racial and ethnic disparities among enrollees in Medicare Advantage plans. NEJM. 2014;371;2288-2297.

4. Patel MS, Volpp KG, Small DS, Hill AS, Even-Shoshan O, Rosenbaum L, Ross RN, Bellini L, Zhu, Silber JH. Association of the 2011 ACGME resident duty hour reforms with mortality and readmissions among hospitalized Medicare patients. JAMA. 2014;312(22);2364-2373.

5. Rawlings AM, SHarrett R, Schneider ALC, Coresh J, Albert M, Couper D, Griswold M, Gottesman RF, Wagenknecht LE, Windham BG, Selvin E. Diabetes in midlife and cognitive change over 20 years. Annals of Internal Medicine. 2014;161;785-793.

6. Garin N, Genne D, Carballo S, Chuard C, Eich G, Hugli O, Lamy O, Nendaz M, Petignat PA, Perneger T, Rutschmann O, Seravalli L, Harbarth S, Perrier A. ?-lactam monotherapy vs ?-lactam-macrolide combination treatment in moderately severe community-acquired pneumonia: A randomized noninferiority trial. JAMA Internal Medicine. 2014;174(12);1894-1901.

7. Lee JS, Fine MJ. The debate on antibiotic therapy for patients hospitalized for pneumonia: Where should we go from here? JAMA Internal Medicine. 2014;174(12);1901-1903.

8. Schroder FH, Hugosson J, Roobol MJ, Tammela TLJ, Zappa M, Nelen V, Kwiatkowski M, Lujan M, Maattanen L, Lilja H, Denis LJ, Recker F, Paez A, Bangma CH, Carlsson S, Puliti D, Villers A, Rebillard X, Hakama M, Stenman UH, Kujala P, Taari K, Aus G, Huber A, van der Kwast TH, van Schaik RHN, de Koning HJ, Moss SM, Auvinen A. Screening and prostate cancer mortality: Results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up. The Lancet. 2014;384;2027-2035.

9. Bonde AN, Lip GYH, Kamper AL, Hansen PR, Lamberts M, Hommel K, Hansen ML, Gislason GH, Torp-Pedersen C, Olesen JB. Net clinical benefit of antithrombotic therapy in patients with atrial fibrillation and chronic kidney disease: A nationwide observational cohort study. JACC. 2014;64(23)2472-2482.

10. Bekelman JE, Sylwestrzak G, Barron J, Liu J Epstein AJ, Freedman G, Malin J, Emanual EJ. Uptake and costs of hypofractionated vs. conventional whole breast irradiation after breast conserving surgery in the United States, 2008-20143. JAMA. 2014; E1-E9.

11. Smith BD, Bentzen SM, Correa CR, Hahn CA, Hardenbergh PH, Ibbott GS, McCormick B, McQueen JR, Pierce LJ, Powell SN, Recht A, Taghian AG, Vicini FA, White JR, Haffty BG. Fractionation for whole breast irradiation: an American Society for Radiation Oncology (ASTRO) evidence-based guideline. Int J Radiat Oncol Biol Phys. 2011;81(1)59-68.

12. Skupien J, Warram JH, Smiles A, Galecki A, Stanton RC, Krolewski AS. Improved glycemic control and risk of ESRD in patients with type 1 diabetes and proteinuria. J Am Soc Nephrol. 2014;25;2916-1925.