Preventing Overweight Using Novel Dietary Strategies Study (POUNDS LOST)

Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) study was a clinical trial designed to test the effects of four heart-healthy diets varying in fat, protein, and carbohydrate composition on the weight loss and its long term maintenance. Participants were assigned to one of four diets and asked to record their food intake in a diary or an online tool that showed how intake compared with goals. The diets were low or high in total fat (20 or 40 percent of calories) with average or high protein (15 or 25 percent of calories). Carbohydrate content ranged from 35 to 65 percent of calories. The diets all used the same calorie reduction goals and were heart-healthy—low in saturated fat and cholesterol while high in dietary fiber. Study participants were 811 free-living overweight or obese adults ages 30-70 from Boston, MA and Baton Rouge, LA. All participants were offered group and individual counseling sessions over two years.

Weight loss after six months and two years was similar among participants assigned to the four diets. On average, participants lost 13 pounds at six months and maintained a 9 pound loss at two years. Participants also reduced their waistlines by 1 to 3 inches by the end of the study. Craving, fullness, hunger, and diet satisfaction were all similar across the four diets. All diets improved risk factors for cardiovascular disease at both six months and two years in ways consistent with previous studies. Improved risk factors include reduced levels of triglycerides, LDL (bad) cholesterol, lowered blood pressure, and increased HDL (good) cholesterol. The results indicate that heart-healthy, reduced-calorie diets, regardless of which macronutrients they emphasize, can help overweight and obese adults achieve and maintain weight loss.

Selected References:

Sacks FM, Bray GA, Carey VJ, et al. Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates. N Engl J Med 2009;360:859-73.


Metformin during pregnancy safer than insulin : Study

Study: Having a Parent With Type 1 Diabetes May Raise ADHD Risk

In a recent study, researchers from Sweden, China, and New York City looked to see if a family history of type 1 diabetes was tied to a higher risk of ADHD in children.

People with type 1 diabetes were tracked using the Swedish National Hospital Discharge Register and Swedish Outpatient Register in Sweden and were then linked to the Swedish Multi-Generation Register to identify their children.

ADHD and type 1 diabetes

Cox regression analysis was then used to calculate the hazard ratio of ADHD in children of patients with type 1 diabetes compared with rates of ADHD in children who don’t have parents with type 1 diabetes.

The researchers gathered data from 15,615 individuals born after one of their parents was diagnosed with type 1 diabetes and then controlled for various factors.

Is ADHD More Likely if a Parent Has Type 1 Diabetes?

They found that children from type 1 parents had a much higher risk for developing ADHD (hazard ratio of 1.29).

The higher risk belonged to children born to a mother with type 1 diabetes versus father with type 1 diabetes but the difference was deemed “not statistically significant” by the researchers.

The study authors conclude in their study abstract that “In this retrospective cohort study, we found that a parental history of [type 1 diabetes] was associated with a 29% increased risk of being diagnosed with ADHD.”

They add that “the underlying mechanisms need to be explored in future studies”.

Uninterrupted apixaban therapy vs. warfarin during AF ablation: A question of safety and efficacy

Catheter ablation is increasingly being performed for patients with paroxysmal and persistent atrial fibrillation (AF). Atrial fibrillation ablation carries a significant risk of thromboembolism and bleeding due to thrombus formation in the left atrium and intraprocedural conversion from AF to sinus rhythm. Multiple strategies are commonly employed peri-AF ablation to reduce the risk of thromboembolic complications, including the use of transesophageal echocardiography, intracardiac echocardiography, irrigated ablation catheters, and intraprocedural anticoagulation. [1]

Historically, patients treated with vitamin k antagonists (VKA) would typically discontinue this medication and be bridged with low-molecular-weight heparin prior to ablation. However, recent recommendations state that patients undergoing an AF ablation can safely undergo the procedure without discontinuation. [1]

Direct oral anticoagulants (DOACs), have emerged as an increasingly common therapy for thromboembolism prevention in AF. However, strategies for its use in the setting of AF ablation have been varied and may be associated with an increased incidence of thromboembolism. [2]

A recent multicenter study published in The American Journal of Cardiology evaluated the safety and efficacy of uninterrupted apixaban versus warfarin anticoagulation in the periprocedural AF ablation setting. [3] There were no thromboembolic events in the apixaban group or the VKA group. There were no significant differences observed in major bleeding endpoints, minor bleeding, pericardial effusion or groin hematoma. Interestingly, the heparin requirement was the same for both warfarin and apixaban; however, while the periprocedural activated clotting time (ACT) in warfarin group was significant, minimum ACT throughout AF ablation was lower. This might suggest that periprocedural apixaban anticoagulation leads to a more consistent ACT in this setting.

Similar comparisons have been made with other DOACs, although study protocols may differ slightly and there is no direct comparison to assess the role, safety and efficacy of each DOAC. There has been conflicting data, with Steinberg et al, [2] and Sardar et al, [4] demonstrating an increase in neurologic complications with dabigatran compared to VKA. This is contrary to the meta-analysis conducted by Honhloser et al, [5] and Providencia et al, [6] who demonstrated no significant differences in the composite of neurologic and bleeding complications between the dabigatran and uninterrupted VKA groups.

There is even less data for Rivaroxaban, although results of prospective observational [7] and randomised [8] trials with uninterrupted rivaroxaban suggest that this therapy appears to be as safe and efficacious in preventing bleeding and thromboembolic events in patients undergoing AF ablation as uninterrupted warfarin therapy.

More recent data from the RE-CIRCUIT (no increase in thromboembolic endpoints; major bleeding reduction with uninterrupted dabigatran) and AEIOU (no differences in thromboembolic or bleeding endpoints with apixaban-either uninterrupted or interrupted by a single dose- or warfarin) trials are also reassuring, and reinforce that in the near future catheter ablation could possibly move towards uninterrupted DOAC anticoagulation to prevent the difficulties with variable INRs.

However, one must emphasize the need for more information to guide the periprocedural use of both DOACs and VKAs in the real-world setting.

This cardionote was prepared by Dr Amelia Carro-Hevia (Spain) and published simultaneously on Cardio Debate and CardioMaster websites, as part of an ongoing collaboration between the two educational platforms. For more information on Cardiomaster please visit


  1. Calkins H, Hindricks G, Cappato R, Kim YH, Saad EB, Aguinaga L, Akar JG et al. 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: Executive summary. J Arrhythm. 2017;33(5):369-409.
  2. Steinberg BA, Hasselblad V, Atwater BD, Bahnson TD, Washam JB, Alexander JH, et al. Dabigatran for periprocedural anticoagulation following radiofrequency ablation for atrial fibrillation: a meta-analysis of observational studies. J Interv Card Electrophysiol. 2013;37 (3):213–21.
  3. Shah RR, Pillai A, Schafer P, Meggo D, McElderry T, et al. Safety and Efficacy of Uninterrupted Apixaban Therapy Versus Warfarin During Atrial Fibrillation Ablation. Am J Cardiol. 2017;120(3):404-407.
  4. Sardar P, Nairooz R, Chatterjee S, Wetterslev J, Ghosh J, Aronow WS. Meta- analysis of risk of stroke or transient ischemic attack with dabigatran for atrial fibrillation ablation. Am J Cardiol. 2014;113(7):1173-7.
  5. Hohnloser SH, Camm AJ. Safety and efficacy of dabigatran etexilate during catheter ablation of atrial fibrillation: a meta-analysis of the literature. Europace. 2013;15(10):1407-11.
  6. Providencia R, Albenque JP, Combes S, Bouzeman A, Casteigt B, Combes N, et al. Safety and efficacy of dabigatran versus warfarin in patients undergoing catheter ablation of atrial fibrillation: a systematic review and meta-analysis. Heart. 2014;100(4):324-35.
  7. Lakkireddy D, Reddy YM, Di Biase L, Vallakati A, Mansour MC, Santangeli P, et al. Feasibility and safety of uninterrupted rivaroxaban for periprocedural anticoagulation in patients undergoing radiofrequency ablation for atrial fibrillation: results from a multicenter prospective registry. J Am Coll Cardiol.2014;63(10):982-8.
  8. Cappato R, Marchlinski FE, Hohnloser SH, Naccarelli GV, Xiang J, Wilber D et al; VENTURE-AF Investigators. Uninterrupted rivaroxaban vs. uninterrupted vitamin K antagonists for catheter ablation in non-valvular atrial fibrillation. Eur Heart J. 2015;36(28):1805-11.
  9. Calkins H, Willems S, Gerstenfeld EP, Verma A, Schilling R, Hohnloser SH, Okumura K, Serota H, Nordaby M, Guiver K, Biss B, Brouwer MA, Grimaldi M; RE-CIRCUIT Investigators. Uninterrupted Dabigatran versus Warfarin for Ablation in Atrial Fibrillation. N Engl J Med. 2017;376(17):1627-1636.
  10. 10.- Reynolds MR, Allison JS, Natale A, et al. A prospective randomized trial of apixaban dosing during atrial fibrillation of ablation: the AEIOU (Apixaban Evaluation of Interrupted or Uninterrupted Anticoagulation for Ablation of Atrial Fibrillation) Trial. Heart Rhythm Society (HRS) Scientific Sessions 2017; May 11, 2017; Chicago, IL. Abstract C-LBCT01-05

Younger women and women with STEMI ‘less likely’ to be prescribed evidence-based medicines

Results from a study funded by the British Heart Foundation and published in Journal of the American Heart Association have hit the headlines claiming that women who suffer heart attacks are not being offered the same treatment as men. [1]

The report from the SWEDEHEART study analysed data from 48,118 patients, 35.4% of whom were women, and all who were diagnosed with acute myocardial infarction. The primary endpoint of this analysis was all-cause mortality, however researchers also looked at the likelihood of patients receiving the recommended evidence-based pharmacological drugs.

This study revealed that, on the surface women had a better adjusted prognosis than men after an acute MI. However, scratch beneath the surface and a different picture emerges.

Younger women (aged under 60 years) and women with ST-elevation Myocardial Infarction (STEMI) had a worse prognosis, and were less likely to be prescribed evidence-based treatment than their male counterparts. Furthermore, this discrepancy in gender did not decrease over two decades. [1]

Women in the study were more likely to have previously been diagnosed with hypertension or type II diabetes, and were also more likely to develop prehospital cardiogenic shock or in-hospital heart failure.

Sub-group analyses showed that the estimated risk for developing prehospital cardiogenic shock was higher for women compared to men (OR 1.67, 95% Cl 1.30 to 2.16, P<0.001), and the risk in women with STEMI was also higher compared to the risk in men (OR 1.31, 95%Cl 1.16 to 1.48). [1]

Other findings show that women with STEMI were less likely to undergo coronary angiography than men, and after adjustment of traditional CV risk factors women were less likely to receive evidence-based treatments including beta-blockers, ACE inhibitors, statins and P2Y12 inhibitors.

The reasons for this are unclear and certainly warrant further investigation. It is common for women to present at a later stage in the disease than men for a variety of reasons. For example, as Professor Angela Maas, Professor Women’s Cardiac Health, Cardiology Department, Radboud University Medical Center, Nijmegen, The Netherlands told Cardio Debate: “We often think hypertension is asymptomatic, but it can actually give a lot of symptoms, especially in women who are middle aged,” adding that: “It is easy to discriminate between stress-related elevated blood pressure and severe developmental hypertension. Just ask questions about pregnancy [e.g., the presence of gestational diabetes] or the family history.” [2]

However the study authors suggest the presence of ‘systemic undertreatment’ in women. [1] Professor Juan Tamargo, Professor of Pharmacology, Universidad Complutense, Madrid, Spain has previously addressed this issue with Cardio Debate, saying: “We need to clarify to people that there is a problem and that there are some ways to improve it.” [3]

“There is the feeling that male physicians usually consider that women need less strict treatments; we don’t give the same advice to women as we do to men. There are lots of things (regarding gender differences and gender treatment bias) that should be included in position papers and clinical guidelines [to avoid undertreatment in women].” [3]

Patients should be prescribed evidence-based medicines regardless of their gender, and this should be a given. Hopefully this study will steer the conversation in the right direction, and encourage the medical community to address this serious issue.


  1. Redfors B, Angeras O, Ramunddal T, et al. Trends in gender differences in cardiac care and outcome after acute myocardial infarction in Western Sweden: A report from the Swedish Web System for Enhancement of Evidence-Baed Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART). J Am Heart Assoc DOI: 10.1161/JAHA.115.001995

Australian Study: Parents Should Stop Supplying Alcohol

Teens getting alcohol from adults had greatest risk for adverse outcomes

Action Points

  • Note that this survey-based study found that kids who get alcohol from their parents are at higher risk for alcohol use disorders than those who have no ready “source” of alcohol.
  • Those who received alcohol from both their parents and others were at even higher risk.

Parents often provide alcohol to their teenage children in an effort to teach responsible drinking, but a recent Australian study found that the practice may backfire more often than not.

Teenagers who received alcohol only from their parents had higher odds of subsequent binge consumption (OR 2.58, 95% CI 1.96–3.41, P<0.0001), alcohol-related harm (OR 2.53, 1.99–3.24, P<0.0001), and symptoms of alcohol use disorder (OR 2.51, 1.46–4.29, P=0.0008) compared with teenagers who had no alcohol supply, found Richard Mattick, PhD, of the University of New South Wales and colleagues, writing online in The Lancet Public Health.

“Our study is the first to analyze parental supply of alcohol and its effects in detail in the long term, and finds that it is, in fact, associated with risks when compared to teenagers not given alcohol,” stated Mattick. “This reinforces the fact that alcohol consumption leads to harm, no matter how it is supplied. We advise that parents should avoid supplying alcohol to their teenagers if they wish to reduce their risk of alcohol-related harms.”

Writing in an accompanying editorial, Stuart Kinner and Rohan Borschmann, both of Murdoch Children’s Research Institute in Australia, emphasized that “the findings strongly suggest that parental supply of alcohol to adolescents does not protect against future alcohol-related harm, and might in fact increase risk.”

For the study, Mattick and colleagues recruited 1,927 teenagers and their parents from secondary schools in Perth, Sydney, and Hobart (Australia) between 2010 and 2011. The teenagers and their parents completed separate questionnaires each year from 2010 to 2016 regarding how the teen accessed alcohol (from parents, other non-parental sources, or both); binge drinking levels (defined as drinking more than four drinks on a single occasion in the past year); experience with alcohol-related harm; and alcohol abuse symptoms.

At the end of the study, 81% (632/784) of teenagers who received alcohol through their parents and others reported binge drinking, compared with 62% (224/361) of those who accessed alcohol via other people only and 25% (33/132) who were given alcohol by their parents only.

Teenagers who received alcohol from both their parents and other sources were at the greatest risk of leading adverse outcomes, as follows:

  • 632 of 784 (81%) adolescents reported they had binged
  • 671 (86%) experienced alcohol-related harm
  • 102 (13%) reported alcohol abuse symptoms
  • 145 (18%) had at least three dependence symptoms
  • 284 (36%) reported at least two alcohol use disorder symptoms

The most frequently reported alcohol use disorder symptoms in adolescents who received alcohol from their parents were tolerance (34%); drinking larger amounts or for longer than intended (31%); and spending time getting, consuming, or recovering from alcohol (17%).

Parents were more likely to supply alcohol as teens became older, increasing from 15% at the study’s “wave 1” (mean age of 12.9) to 57% at wave 6 (age 17.8). The most common context for parental supply at wave 6 was “with family on a special occasion,” and parents usually provided a maximum of two drinks, the researchers noted.

In terms of future alcohol prevention priorities, Mattick and colleagues called for a focus on parents, not just school-based education and legislation enforcement: “Parents, policymakers, and clinicians need to be made aware that parental provision of alcohol is associated with risk, not with protection, to reduce the extent of parental supply in high-income countries, and in low- and middle-income countries that are increasingly embracing the consumption of alcohol.”

Kinner and Borschmann agreed, but added that “before drawing firm conclusions, it will be important to replicate this finding in larger samples that permit more granular characterization of both exposures and outcomes, and in samples with at least proportionate representation of socioeconomically disadvantaged families.”

Mattick and colleagues listed several study limitations, including that there was an under-representation of teenagers from low socioeconomic backgrounds and the use of a conservative binge drinking measure. Additionally, the results may not apply to other countries where there is lower alcohol consumption than Australia, and the research does not account for the amount of alcohol supplied by the parents.

COMPASS Trial: Aspiration as good as stent retrievers for large vessel clot removal in stroke

DEFUSE 3 trial-Brain-scan guided emergency stroke treatment beneficial, says NEJM Study

Study Looks at Link Between Asthma and Type 1 Diabetes


Finnish researchers acknowledged that the associations between asthma and type 1 diabetes are still unclear so they conducted a study to look more into the link between these two immune-mediated conditions.

In their study abstract they state that they conducted a nationwide case-cohort study with Finnish children and used a novel statistical approach.

The children in the study were born between January 1st 1981 and December 31st 2008. There were 81,473 diagnosed with asthma and 9,541 diagnosed with type 1 diabetes up to age 16 by the end of 2009. This data was located in the Central Drug Register that the Social Insurance Institution of Finland keeps.

Regarding the new statistical approach, researchers used “a multistate modelling approach to estimate transition rates between healthy and disease states since birth. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to represent the change in the transition rate between the disease states.”They adjusted for sex and birth decade.

What are the Ties Between Type 1 and Asthma?

The researchers found that a previous asthma diagnosis raised the risk of developing type 1 diabetes by a whopping 41%.

Conversely, a previous diagnosis of type 1 diabetes lowered the risk of developing asthma by 18%.

Based on these findings the researchers conclude that there is an implication here that the relationship between type 1 diabetes and asthma is “more complex than previously thought, and its direction depends on the sequential appearance of the diseases.”

Do you have asthma and type 1 diabetes and if so, which diagnosis came first?

Safety, Tolerability of Dasiglucagon Examined for Severe Hypoglycemia


Treatment of severe hypoglycemia outside of the hospital setting is limited to glucagon formulations requiring reconstitution before use, which may lead to erroneous or delayed glucagon administration. We compared the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics and safety and tolerability of different doses of dasiglucagon, a novel soluble glucagon analog, with approved pediatric and full doses of GlucaGen in insulin-induced hypoglycemia in patients with type 1 diabetes.


In this single-center, randomized, double-blind trial, 58 patients with type 1 diabetes received single subcutaneous injections of 0.1, 0.3, 0.6, or 1.0 mg dasiglucagon or 0.5 or 1.0 mg GlucaGen in a state of hypoglycemia (blood glucose target 55 mg/dL) induced by an intravenous insulin infusion.


Dasiglucagon demonstrated a dose-dependent and rapid increase in plasma concentrations, reaching a maximum at ∼35 min with a half-life of ∼0.5 h. Dasiglucagon rapidly increased plasma glucose (PG) by ≥20 mg/dL (9–14 min) to PG ≥70 mg/dL (within 6–10 min), similar to GlucaGen, but with a longer-lasting and greater effect on PG. All patients on both treatments reached these end points within 30 min (predefined success criteria). Both treatments were well tolerated. Nausea was the most frequent adverse event, occurring at a similar rate (44–56%).


Dasiglucagon was well tolerated and showed an early PD response similar to that of GlucaGen at corresponding doses, suggesting comparable clinical effects of the two glucagon formulations. Dasiglucagon has the potential to become an effective and reliable rescue treatment for severe hypoglycemia in a ready-to-use pen.