Primecuts – This Week in the Journals

March 29, 2019

PrimeCuts 6 min read

By Jessica Lichter, MD

Peer Reviewed

With medicine advancing at such a rapid pace, it is crucial for physicians to keep up with the medical literature.  This can quickly become an overwhelming endeavor given the sheer quantity and breadth of literature released on a daily basis. Primecuts helps you stay current by taking a shallow dive into recently released articles that should be on your radar. Our goal is for you to slow down and take a few small sips from the medical literature firehose.

β blockers to prevent decompensation of cirrhosis in patients with clinically significant portal hypertension (PREDESCI): a randomised, double-blind, placebo-controlled, multicentre trial

Over time, liver cirrhosis progresses from a stage of compensation to that of decompensation, defined by the occurrence of ascites, variceal bleeding or hepatic encephalopathy. Portal hypertension is the main factor responsible for this transition, heralding significant clinical deterioration.

In PREDESCI1, a randomized, double-blind, placebo-controlled trial, Villaneuva and colleagues questioned whether this transition could be forestalled with beta blockers. Specifically, they investigated whether giving non-selective beta blockers to patients with compensated cirrhosis who had already developed clinically significant portal hypertension (CSPH) could prevent progression to decompensated cirrhosis or death, which they defined as the primary outcome. To that end, investigators assessed patients across eight hospitals in Spain for eligibility from 2010 to 2013, and included those with compensated cirrhosis and CSPH (defined by a hepatic venous pressure gradient ≥ 10 mm Hg) without high-risk varices. Of the 631 patients evaluated, 201 were randomly assigned into study arms, with 101 to placebo and 100 to treatment (67 propranolol and 33 carvedilol). Over the course of five years, decompensation or death occurred in 16% of patients in the beta blocker groups vs. 27% of the placebo group (HR 0.51, 95% CI 0.26-0.97, p = 0.04). The difference in outcome was largely due to a decreased risk of developing ascites with beta blockers (HR = 0.44, 95% CI 0.20–0.97, p = 0.03).

In conclusion, this study demonstrates that in patients with compensated cirrhosis and CSPH, long-term treatment with non-selective beta blockers approximately halves the risk of decompensation or death. Importantly, these results suggest that patients with compensated cirrhosis should be screened for CSPH, and started on a non-selective beta blocker if it is present.

Acute Illness Associated With Cannabis Use, by Route of Exposure: An Observational Study 

As more states move to decriminalize and legalize marijuana, its availability and use will likely only grow, in large part because of the popular perception that it is relatively harmless. To the dismay of more ardent marijuana supporters, however, recent research reveals that the drug can have significant medical consequences, which vary depending on the route of administration.

In a retrospective study, Monte and colleagues2 reviewed the records of patients presenting to the UCHealth University of Colorado Hospital ED from 2012 to 2016 in an effort to describe the adult ED visits related to cannabis exposure. Specifically, they sought to compare those visits stemming from inhaled vs. edible cannabis consumption. Overall, patients exposed to inhaled cannabis were more likely to present with cannabinoid hyperemesis syndrome (18.0% vs. 8.4%), while those with edible exposures were more likely to present with intoxication (48% vs. 28%), acute psychiatric symptoms such as acute anxiety or psychosis (18.0% vs. 10.9%), or cardiovascular symptoms (8.0 vs. 3.1%).  Interestingly, edible cannabis accounted for only 0.32% of total cannabis sales in Colorado from 2014-2016, but was responsible for 10.7% of cannabis-attributable ED visits during this period. One rationale for these observations lie in the difference in pharmacokinetics between the two forms of cannabis; compared to the inhaled form, edible cannabis kicks in later, lasts longer and has more variable bioavailability3, which could cause people to consume more than they intend to initially, resulting in more severe symptoms later on.

As a whole, this article demonstrates that edible cannabis led to a disproportionate number of ED visits, with arguably more intense symptoms compared to its inhaled counterpart. More broadly speaking, this article illustrates that the specific ways in which people consume marijuana have health implications, and highlights the need for more consistency, transparency and standardization in how the drug is sold to the public.

Effect of Additional Oral Semaglutide vs Sitagliptin on Glycated Hemoglobin in Adults With Type 2 Diabetes Uncontrolled With Metformin Alone or With Sulfonylurea: The PIONEER 3 Randomized Clinical Trial

Although metformin is first-line therapy in type two diabetes, many patients will require additional agents to achieve glycemic control. Two classes of drugs commonly used as second-line, adjuvant therapy are glucagon-like peptide 1 receptor agonists (GLP-1RAs) and dipeptidyl peptidase 4 (DPP-4) inhibitors. Currently, DPP-4 inhibitors such as sitagliptin are available in pill form and widely prescribed, whereas GLP-1RAs such as semaglutide are only administered in via subcutaneous injection.

In PIONEER 3, a randomized, double-blind trial, researchers compared the efficacy of an oral formulation of semaglutide with that of sitagliptin when added to metformin with or without a sulfonylurea in patients with uncontrolled type 2 diabetes4. From 2016 to 2018, the authors screened 2463 patients at 206 sites in 14 countries for eligibility, and randomized 1864. Patients were randomized to receive once daily oral semaglutide (3mg, 7mg or 14mg) or sitagliptin 100mg once daily for 78 weeks. The primary endpoint was change in glycated hemoglobin (HbA1c) from baseline to week 26 and the critical secondary endpoint was change in body weight over the same period. Oral semaglutide at 7mg and 14mg, compared to sitagliptin significantly reduced HbA1c (differences, –0.3%, 95% CI –0.4% to –0.1% and –0.5%, 95% CI –0.6% to –0.4%, respectively; p < 0.001 for both) and body weight (differences, -1.6 kg, 95% CI –2.0 to –1.1 kg and –2.5 kg, 95% CI –3.0 to –2.0 kg, respectively; p < 0.01 for both) from baseline to week 26. At week 78, HbA1c reductions from baseline remained significantly greater with oral semaglutide 14mg, and body weight reductions were greater with all doses of semaglutide compared with sitagliptin.

In conclusion, this study demonstrated that oral semaglutide 7mg and 14mg are superior to sitagliptin in reducing HbA1c and body weight in patients already on metformin with or without a sulfonylurea. These findings are particularly relevant for diabetic patients who are also overweight or obese.

State gun laws, gun ownership, and mass shootings in the US: cross sectional time series

Over the years, mass shootings in the United States have evolved into horrific, recurring, widely-publicized tragedies. For all of the attention mass shootings garner, however, little research has been conducted into understanding the state-level factors that could influence their occurrence.

In a new paper published in BMJ, Reeping and colleagues5 investigated whether gun laws or gun ownership were related to mass shootings, defined as events in which four or more people were killed by a firearm. To assess the relative stringency of gun laws in a state, they used the 1998-2015 editions of a reference guide made for gun owners, which rates the gun laws of all 50 states on a restrictiveness-permissiveness scale (with 0 being completely restrictive and 100 being completely permissive). They estimated annual gun ownership from the percentage of suicides committed with a firearm in each state. They then calculated the annual rates of mass shootings in each state using data from the FBI’s Uniform Crime Reporting System. In fully adjusted regression models, the authors showed that mass shootings were associated with both more permissive gun laws and higher levels of gun ownership. Indeed, they found that a 10-unit increase in state gun law permissiveness was linked to an 11.5% higher rate of mass shootings (95% CI 4.2-19.3%, p = 0.002), and a 10% higher state firearm ownership rate was associated with a 36.1% increase in these incidents (95% CI 20.1-54.2%, p < 0.001).

Mini-Cuts: 

  1. Celiac disease is an autoimmune disorder thought to arise when an unknown environmental trigger causes genetically susceptible individuals to become intolerant to gluten. In a prospective cohort study of patients at risk for developing celiac disease, researchers have identified enterovirus as a potential culprit in the development of this inflammatory disorder6.
  2. Aspirin is one of the world’s oldest medications, with a wide variety of uses. Now, researchers have discovered that medicine’s jack of all trades may have yet another skill—preventing hepatocellular carcinoma in patients with chronic hepatitis B7.
  3. For many patients with major depression, medications and psychotherapy are often insufficient for controlling their symptoms. Non-surgical brain stimulation is emerging as an alternative or add-on therapy for such patients8.

Dr. Jessica Lichter, is a 1st year resident at NYU Langone Health

Peer reviewed by Dana Zalkin, MD, chief resident, internal medicine, NYU Langone Health

Image courtesy of Wikimedia Commons

References: 

  1. Villanueva C, Albillos A, Genescà J, Garcia-Pagan JC, Calleja JL, Aracil C, Bañares R, Morillas RM, Poca M, Peñas B, Augustin S, Abraldes JG, Alvarado E, Torres F, Bosch J. β blockers to prevent decompensation of cirrhosis in patients with clinically significant portal hypertension (PREDESCI): a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2019 Mar 22. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31875-0/fulltext
  2. Andrew A. Monte, Shelby K. Shelton, Eleanor Mills, Jessica Saben, Andrew Hopkinson, Brandon Sonn, Michael Devivo, Tae Chang, Jacob Fox, Cody Brevik, Kayla Williamson, Diana Abbott. Acute Illness Associated With Cannabis Use, by Route of Exposure: An Observational Study. Annals of Internal Medicine, 2019; DOI: 10.7326/M18-2809  https://annals.org/aim/fullarticle/2729208/acute-illness-associated-cannabis-use-route-exposure-observational-study
  3. Grotenhermen F. Pharmacokinetics and pharmacodynamics of cannabinoids.Clin Pharmacokinet. 2003;42:327-60.
  4. Rosenstock J, Allison D, Birkenfeld AL, et al. Effect of Additional Oral Semaglutide vs Sitagliptin on Glycated Hemoglobin in Adults With Type 2 Diabetes Uncontrolled With Metformin Alone or With Sulfonylurea: The PIONEER 3 Randomized Clinical Trial. Published online March 23, 2019. doi:10.1001/jama.2019.2942  https://jamanetwork.com/journals/jama/fullarticle/2729339
  5. Reeping PM, Cerdá M, Kalesan B, Wiebe DJ, Galea S, Branas CC. State gun laws, gun ownership, and mass shootings in the US: cross sectional time series. BMJ. 2019 Mar 6;364:l542. https://www.bmj.com/content/364/bmj.l542
  6. Kahrs CR, Chuda K, Tapia G, Stene LC, Mårild K, Rasmussen T, Rønningen KS, Lundin KEA, Kramna L, Cinek O, Størdal K. Enterovirus as trigger of coeliac disease: nested case-control study within prospective birth cohort. BMJ. 2019 Feb 13;364:l231.
  7. Lee TY, Hsu YC, Tseng HC, Yu SH, Lin JT, Wu MS, Wu CY. Association of Daily Aspirin Therapy With Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B. JAMA Intern Med. 2019 Mar 18. https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2728447
  8. Mutz J, Vipulananthan V, Carter B, Hurlemann R, Fu CHY, Young AH. Comparative efficacy and acceptability of non-surgical brain stimulation for the acute treatment of major depressive episodes in adults: systematic review and network meta-analysis. BMJ. 2019 Mar 27;364:l1079.