Primecuts – This Week In The Journals

July 13, 2015

greeceBy David Valentine, MD

Peer Reviewed

In a busy week, here’s some world news highlights: After a month of dramatic drops in the Chinese markets, finances have begun to stabilize, but at the cost of many families’ savings; Greece offered the EU a new plan for a return to fiscal sustainability; the Syrian refugee crisis continued to worsen, with many fleeing into neighboring countries; and Scott Walker added his name to the list of GOP presidential candidates.

Liraglutide for a bit less weight

With obese adults now outnumbering the overweight in America, healthy weight management has never been more important. Therefore, results from a multi-center randomized, controlled trial published in the NEJM [1] this week are particularly important, suggesting that liraglutide–a glucagon-like peptide-1 analogue–may be a powerful agent in helping overweight and obese patients to lose weight, prevent diabetes, and improve cardiovascular health.

Over two years, 3,731 non-diabetic, obese patients were enrolled across 191 institutions, and randomly split in a 2:1 ratio to receive either liraglutide or placebo in a Novo Nordisk FlexPen device. Both groups received lifestyle modification counseling. Primary endpoints included weight change from baseline, the proportion of patients who lost 5% of their baseline body weight and the proportion of patients who lost 10% of their baseline body weight. At 56 weeks more patients taking liraglutide had lost weight (92% vs 65% for placebo), and those taking liraglutide lost significantly more than those on placebo (8.4+7.3kg vs 2.8+6.5kg, respectively). Secondary endpoints including fasting glucose, insulin resistance, beta cell function, blood pressure, and scores on quality of life questionnaires were all better in the liraglutide group. However liraglutide was associated with significant gastrointestinal distress (nausea, vomiting) and a greater propensity for gallstones and pancreatitis. It is also worth noting that the study was funded by Novo Nordisk. However overall the authors suggest that liraglutide could be a powerful new tool for clinically meaningful weight loss and a strategy to delay the onset of diabetes.

Mass Spectrometry for the Masses

Nature this week published a method by which spectrometers can be miniaturized to the size of a cell phone camera module [2], opening up new possibilities for on-site diagnosis and lab tests. Traditional spectrometry relies on the separation of light bands by gratings followed by measurement of the intensity of each of the individual light rays. While current machines are expensive and relatively large, this technique is invaluable in the diagnosis of metabolic disorders, toxicology screens, protein measurements, pharmaceutical activity, cancer detection and more.

Colloidal quantum dots (CQDs) are relatively inexpensive nanocrystals that can be made of various nontoxic, environmentally friendly materials. Based on the size, shape and material of these nanocrystals, they absorb different wavelengths of light. By using a collection of light detectors behind an array of 195 unique CQDs with a spectral range of 390-690nm, researchers have managed to duplicate the measured emission spectra of a standard, contemporary spectrometer, in a much smaller and more efficient unit. Future research will work to improve the spectral resolution and range of the CQD spectrometer by increasing the number of nanocrystals in the detection array, improving the algorithms that compute the detected light bands, and the creation of more air-stable quantum dots. So, who knows, perhaps the iPhone 10 or next pocket medical device will include a diagnostic lab-on-a-chip, which would have profound implications for field physicians, researchers, and third-world outreach.

A working H. pylori vaccine in the works?

The Lancet reports that a stage 3 trial from researchers in Jiangsu, China shows promise for a lasting H. pylori vaccine. H. pylori, which infects over half of the world depending on age, region and even socioecononmic status, remains a significant public health burden, causing gastritis, duodenal and gastric ulcers, and gastric adenocarcinoma [3,4]. Prevention of initial infection must come very early in life, particularly in developing countries, in order to meaningfully reduce the burden of this disease.

This study included 4403 children who underwent urea breath testing and ELISA to ensure they were not infected with H. pylori before the study’s initiation. They were split into two groups. The vaccine group received a three-dose regimen in which 15mg of fusion proteins (urease B subunit and heat-labile enterotoxin B subunit) were dissolved in water with mannitol and EDTA-Na2 before ingestion, and the placebo group received only mannitol and EDTA-Na2 dissolved in water without the protein fusion. Follow up was performed at months 4, 8, 12, 24 and 36, with breath samples taken at each point. For positive samples, ELISA was done to confirm a new H. pylori infection. The primary endpoint was number of new H. pylori infections in the first year after vaccination. Secondary endpoints included geometric mean titer (GMT) and serum IgG and salivary IgA against the urease B subunit. Over the first year, the vaccine had a 71.8% efficacy, with 50 of the placebo group showing a new occurrence of H. pylori versus only 14 in the vaccine group. The NNT was 61.7, slightly higher than an average flu vaccine. The second and third years, however, revealed a dramatic decline in efficacy–only around 55%. Drops in antibody titers over this time suggests that boosters may be required. The authors suggest that future studies should focus on diversifying vaccine subjects, as the current sample was relatively homogenous. Overall, such results are promising and could shift our approach to H. pylori from one of management to one of prevention.

Sunnier prospects for patients with erythropoietic protoporphyria

The New England Journal published a phase 3, multicenter, randomized trial from both Europe and the United States that suggests afamelanotide can provide symptomatic relief for patients suffering from erythropoietic protoporphyria [5]. In this condition, an inborn error of metabolism, low ferrochelatase levels, allows phototoxic protoporphyrin to build up in the skin and react with sunlight to form reactive oxygen species, leading to severe neuropathic pain for hours to days after only a minute of sun exposure. Currently, there is no treatment for this condition, and pain management is usually ineffective. However, melanin is photoprotective through neutralization of reactive oxygen species and free radicals in the skin. This study investigated the efficacy of afamelanotide, an analogue of alpha-melanocyte-stimulating hormone, for symptomatic management of erythropoietic protoporphyria.

The study was done in two parts, the first in Europe and the second in the USA. The 168 patients were split into an experimental group receiving periodic implant formulations of 16mg afamelanotide, and the placebo group receiving the same implants but without the afamelanotide. With the primary endpoint being duration of direct sun exposure without pain, the patients on afamelanotide could remain in the sun significantly longer than those on placebo (in the American arm, the time was 70 hours for the treatment group and 40 for placebo, while the European arm, which used a far more stringent pain metric, showed 6 and 0.8 hours, respectively). Despite differences in methodology between the European and American arms, they both supported the efficacy of afamelanotide, which dampened both severity and duration of phototoxic reactions. However neither showed a consequent increase in quality of life. A major limiting factor of this study is that some afamelanotide treated patients reported hyperpigmentation, and thus the study may have been partially unblinded. As a whole, though, this study offers at least a bit of hope for reduced pain in patients for whom there are few other options.

Other News in the Journals

The NEJM comments on India’s continuously shifting, paradoxical healthcare system [6], and the Annals of Internal Medicine provides thoughts on the integration of mental health and substance abuse treatment into primary care [7].

Dr. David Valentine, Internal Medicine, NYU Langone Medical Center

Peer reviewed by Matthew Dallos, MD, Chief Resident, NYU Langone Medical Center

Image courtesy of Wikimedia Commons


  1. Pi-Sunyer X et al. A randomized, controlled trial of 3.0mg of Liraglutide in weight management. NEJM. 2015;373(1):11-22.  
  2. Bao J & Bawendi MG. A colloidal quantum dot spectrometer. Nature. 2015;523:67-70.
  3. Zeng M et al. Efficacy, safety, and immunogenicity of an oral recombinant Helicobacter pylori vaccine in children in China: a randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet. 2015; Advanced Online Publication.
  4. Ford AC & Axon AT. Epidemiology of Helicobacter pylori infection and Public Health Implications. Helicobacter. 2010;Supp 1:1-6.
  5. Langendonk JG et al. Afamelanotide for Erythropoietic Protoporphyria. NEJM. 2015;371(1):48-59.  
  6. Reddy KS. India’s Aspirations for Universal Health Coverage. NEJM. 2015;373:1-5
  7. Crowley RA et al. The Integration of Care for Mental Health, Substance Abuse, and Other Behavioral Health Conditions into Primary Care: An American College of Physicians Position Paper. Ann of Int Med. 2015; Online First  
  8. Yang LY & Colditz GA. Prevalence of Overweight and Obesity in the United States, 2007-2012. JAMA Intern Med. 2015; Published online June 22, 2015.