Primecuts – This Week In The Journals

October 6, 2014

By Asher Schranz, MD

Peer Reviewed

For the past week, thousands of protesters have flooded Hong Kong streets to demand democracy. The umbrella, initially used by protesters as a shield from pepper spray, has become a central symbol. In the US and abroad, Ebola remained at the top of headlines. A Liberian man visiting Dallas was diagnosed with the disease only after being sent home from an ER several days earlier, potentially exposing up to 100 people. Abroad, Ebola cases continue to balloon, as more US troops were sent to West Africa for aid. Meanwhile, Bobby Jindal, governor of Louisiana, called on the federal government to block flights from stricken countries, a move that many experts have said will likely make little difference in combating spread. Lastly, local film buffs learned that the Museum of Modern Art’s longtime film curator, Mary Lea Bandy, passed away. Not only did Ms. Bandy direct one of the great hubs of New York cinema, she was also a champion for preserving and archiving historic and rare prints.

In medical news this week…

Reassessing Early Goal Directed Therapy for Septic Shock

Since Emanuel “Manny” Rivers’ landmark trial in 2001, the concept of Early Goal Directed Therapy (EGDT) has reigned supreme in the management of septic shock [1]. Yet, recently, investigators have been reevaluating its utility. This week sees the release of the second major study this year to question EGDT. In the ARISE trial, 1600 patients with septic shock in Australia, New Zealand, Hong Kong and Europe were randomized 1:1 to receive either EGDT or usual care (physician-guided, non-protocolized treatment without ScvO2 monitoring) during the first 6 hours of their care [2]. The primary outcome was survival at 90 days. Unsurprisingly, more patients in the EGDT group received vasopressors, RBC transfusions and dobutamine, and EGDT patients got slightly more IV fluids (approximately 250ml). EGDT patients had a MAP that was 1.2mmHg higher at the end of the intervention period, a finding that was statistically significant but unlikely to be of clinical relevance. Most importantly, there was no difference in death from any cause at 90 days (18.6% in EGDT vs. 18.8%, p=0.9).

This study confirms what was seen in the ProCESS trial, which took place in multiple US centers, earlier this year: a protocol-based approach to septic shock is unlikely to have a long-term effect on mortality [3]. This suggests that we likely can cut back our use of certain therapies, such as blood transfusions, inotropes and vasopressors, as well as ScvO2 monitoring, in the early treatment of septic shock.

Acupuncture for Knee Pain

The ever-controversial question of the medical benefit of acupuncture was opened again this week in JAMA. To date, it appears that acupuncture has shown to have a modest effect in improving joint pain [4, 5]. Hinman et al. examined the benefit of acupuncture for patients with chronic knee pain due to osteoarthritis [6]. Roughly 70 patients per group aged 50 or older with chronic knee pain were randomized to either control, acupuncture, laser acupuncture or sham laser acupuncture and underwent 12 weeks of treatment. Symptom questionnaires were monitored up to one year. Small improvements in overall pain score were seen at 12 weeks for patients receiving needle [-1.1 point change on pain scale (out of 10), 95% CI -1.8,-0.4] or laser acupuncture (-0.8 point change, CI -1.5,-0.1). Patients receiving needle acupuncture had a small improvement in physical function at 12 weeks as well. However, no effect was seen at one year in any group, and the sham laser acupuncture group had no benefit at any point. The authors ultimately conclude that acupuncture is not of benefit for older patients with moderate to severe chronic knee pain.

This trial is notable for its unique design. Patient attitudes about acupuncture may bias participant selection; such studies are likely to enroll patients with baseline positive attitudes towards acupuncture. To overcome this, the investigators implemented a “Zelen-design” trial, in which the offer of acupuncture was only mentioned following randomization to those assigned to that intervention group. Patients in the control group never knew acupuncture was a part of the study. Unaware they were part of a comparative treatment study, they did not know their data would be used in this way. Zelen trials offer the ability to overcome certain biases, but, without careful consent procedures, they may be highly unethical.

Can CT Differentiate Between Malignant and Benign Pleural Effusions?

Published in Chest online this week is a unique study that creates and validates a scoring system to differentiate malignant from benign pleural effusions using CT scan [7]. 343 patients with pleural effusions who underwent thoracentesis and chest CT with contrast and had an eventual diagnosis were identified. 34% of these patients had malignant effusions, of which 94% were metastatic. Lung cancer was the most common pleural malignancy, but accounted for only 36.5%. Radiologic findings from these patients were evaluated for association with malignancy. All statistically significant radiologic variables were then assessed by multivariate analysis to derive seven weighted parameters: “any pleural lesion equal to or greater than 1 cm (5 points), liver metastases (3 points), abdominal mass (3 points), lung mass or lung nodule equal to or greater than 1 cm (3 points), absence of pleural loculations (2 points), no pericardial effusion (2 points), and non-enlarged cardiac silhouette (2 points).” This 20-point scale was validated in a separate cohort of 80 patients. A score greater than or equal to 7 had a sensitivity of 88%, specificity 94%, likelihood ratio (LR) positive 13.8 and LR negative 0.13 for malignancy. A score<5 argues against malignancy.

The study is introduced by noting that pleural fluid cytology is only 60% sensitive. After thoracentesis however, we may want more information before proceeding to an invasive pleural biopsy. This study suggests that more can be gleaned from data that may already be available in a CT scan to separate malignant from benign pleural effusions. The scoring system, while not a diagnostic tool, is a suggestive one to help guide differential diagnosis.

Hospital Administration Costs are Highest in the US – Surprised?

In Health Affairs, public health experts from five countries coauthored a comparative analysis of hospital administrative costs among eight nations [8]. The countries analyzed include a wide variety of payment systems, from single public payer (Canada, UK) to primarily private, “loosely regulated” multipayer (US) and some comprising a spectrum in between (France, Germany, Netherlands). The researchers used Medicare cost data to differentiate administrative from clinical costs in the US. They attempted to replicate that process with data from the other countries and map it alongside the US data. The authors supply the caveat that comparing health systems is inherently limited: in different countries, delivery of healthcare is not just paid for differently, it may also be structured differently.

Hospital administration costs were highest in the US, accounting for 25.3% of hospital costs in 2010, which equates to 1.43% of the gross domestic product (GDP) – a number that has been steadily rising since at least 2000. The Netherlands was in second place with administration accounting for 19.8% of hospital costs; Scotland was lowest with 11.6%. Why the disparities? The authors offer two suggestions. First, complexity of medical billing. In the US and Netherlands, an array of different payers demand diverse “documentation requirements and billing procedures.” Secondly, they relate it to the procurement of capital funds. Hospitals in many countries studied can rely on direct government grants for growth and modernization. In contrast, hospitals in the US require administrative effort to identify profit sources to enable growth.

The authors note that current initiatives in the US to control cost and optimize quality, such as accountable care organizations and pay-for-performance models, may create new documentation requirements and bureaucratic structures that may deepen administrative costs. Instead, they offer the suggestion of a single-payer system for the US to mitigate administrative expenses.

Also in the news this week …

Significant disparities exist among young and middle-aged patients with aggressive cancers [9]. A study of nearly a half-million 18-64 year old patients with one of the ten deadliest cancers found that those with Medicaid or without insurance were significantly more likely to present with distant disease compared to those with other insurances (29.1% vs 16.9% respectively, p<0.001). Furthermore, they are less likely receive aggressive treatment with surgery or radiation and had higher cancer-related mortality (HR 1.44-1.47, p<0.001).

Cephalosporin-resistant gonorrhea looms as a major public health threat. Currently, ceftriaxone is the only recommended treatment; yet some patients may require an alternative regimen. Clinical Infectious Diseases presents a multicenter study that was conducted across the US, which demonstrated 100% efficacy of combination gentamicin/azithromycin for treatment and 99.5% efficacy for gemifloxacin/azithromycin, suggesting that these two regimens may be reasonable alternatives to ceftriaxone therapy [10].

In the NEJM, a randomized, double-blinded trial of 2,485 patients with COPD and prior exacerbations examined the effect of withdrawing an inhaled glucocorticoid (fluticasone, in this case) [11]. After one year of follow-up, there was no difference in the time to next COPD exacerbation between the studied groups. Patients who had a glucocorticoid withdrawn had decreases in FEV1, although there were no differences in symptoms.

Dr. Asher Schranz is a 2nd year resident at NYU Langone Medical Center.

Peer Reviewed by Cilian J. White, M.D., Internal Medicine Resident, NYU Langone Medical Center

Image courtesy of Wikimedia Commons


1. Rivers E, Nguyen B, Havstad S, et al. Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock. New England Journal of Medicine. 2001; 345(19):1368–1377.

2. The ARISE Investigators and the ANZICS Clinical Trials Group. Goal-Directed Resuscitation for Patients with Early Septic Shock. The New England Journal of Medicine. 2014. Epub ahead of print.

3. Yealy DM, Kellum JA, et al. ProCESS Investigators. A Randomized Trial of Protocol-Based Care for Early Septic Shock. The New England Journal of Medicine. 2014;370(18):1683–1693.

4. Manheimer E, Cheng K, Linde K, et al. Acupuncture for peripheral joint osteoarthritis. Cochrane database of systematic reviews (Online). 2010;1: CD001977.

5. Vickers AJ, Cronin AM, Maschino AC, et al. Acupuncture for chronic pain: individual patient data meta-analysis. Archives of Internal Medicine. 2012;172(19):1444–1453.

6. Hinman RS, McCrory P, Pirotta M, et al. Acupuncture for chronic knee pain: A randomized clinical trial. JAMA. 2014;312(13):1313–1322.

7. Porcel JM, Pardina M, Bielsa S, et al. Derivation and validation of a CT scoring system for discriminating malignant from benign pleural effusions. Chest. 2014. Epub ahead of print.

8. Himmelstein DU, Jun M, Busse R, et al. A Comparison Of Hospital Administrative Costs In Eight Nations: US Costs Exceed All Others By Far. Health Affairs. 2014;33(9):1586–1594.

9. Walker GV, Grant SR, Guadagnolo BA, et al. Disparities in Stage at Diagnosis, Treatment, and Survival in Nonelderly Adult Patients With Cancer According to Insurance Status. Journal of Clinical Oncology. 2014;32(28):3118–3125.

10. Kirkcaldy RD, Weinstock HS, Moore PC, et al. The Efficacy and Safety of Gentamicin Plus Azithromycin and Gemifloxacin Plus Azithromycin as Treatment of Uncomplicated Gonorrhea. Clinical Infectious Diseases. 2014;59(8):1083–1091.

11. Magnussen H, Disse B, Rodriguez-Roisin R, et al. Withdrawal of Inhaled Glucocorticoids and Exacerbations of COPD. New England Journal of Medicine. 2014; 371(14):1285–1294.