Dr. Bray Links

Thursday, November 15, 2018

Novel Agent Lowers Lp(a), Meets All End Points in Phase 2

A novel antisense agent is relatively safe and highly effective in lowering levels of lipoprotein(a) in patients with both elevated Lp(a) and established cardiovascular disease (CVD), new research suggests.

In a dose-finding phase 2b trial that examined five regimens in more than 200 patients with CVD and Lp(a) levels of 60 mg/dL or higher. Treatment with the subcutaneous injectable drug known as AKCEA-APO(a)-LRX (Akcea Therapeutics/Ionis Pharmaceuticals) was associated with a dose-dependent effect on these levels from baseline to week 25 to 27, meeting the primary end point.

In addition, for the patients receiving the highest active dose evaluated, 20 mg/week, there was a mean 80% reduction in Lp(a) from baseline.

Lead author Sotirios Tsimikas, MD, vice president of Global Cardiovascular Development at Ionis Pharmaceuticals and professor of medicine at the University of California, San Diego, noted that this is especially dramatic compared with currently available treatments, including proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors.

"Looking at current therapies, PCSK-9 inhibitors lower Lp[a] by about 15% to 25% and niacin can lower it by 20% to 30%. So this is two to three times more potent than what's currently available to lower Lp(a)," Tsimikas told theheart.org | Medscape Cardiology.

Results also showed that 98% of the participants "got to goal," defined as Lp(a) less than 50 mg/dL. "This means almost everybody who got on the drug got to a level that we think has very low risk," Tsimikas said.

In addition, the 20 mg/week dose met all secondary outcomes, including mean change from baseline in low-density-lipoprotein cholesterol (LDL-C), ApoB, and oxidized phospholipids on apoB particles (OxPL-apoB and OxPl-apo[a]).

https://www.medscape.com/viewarticle/904891

Low-Carbohydrate Diets May Increase Energy Expenditure

 Lowering dietary carbohydrate intake could help in maintaining weight loss, new research suggests. However, some experts say the trial methodology makes drawing conclusions difficult.

Findings from a randomized trial comparing the metabolic effects of diets of varying carbohydrate-to-fat ratio were presented November 14 here at Obesity Week 2018 by David S. Ludwig, MD, and Cara B. Ebbeling, MD, both of the New Balance Foundation Obesity Prevention Center, Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts. The findings were simultaneously published in BMJ.

The study found that lowering dietary carbohydrate increased energy expenditure during weight loss maintenance, especially among those with high insulin secretion. However, the investigators' use of doubly labeled water to measure energy expenditure was called into question during the Obesity Week symposium by Kevin Hall, PhD, a senior investigator at the National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland.

The bottom line, symposium chair and Obesity Society president Caroline M. Apovian, MD, told Medscape Medical News, is, "We need to do more studies to show that this is actually the case. There's controversy...This may mean that we haven't yet figured out how to find out what each individual person needs to eat for better health."

https://www.medscape.com/viewarticle/904956

Wednesday, November 14, 2018

Effect of Amla fruit (Emblica officinalis Gaertn.) on blood glucose and lipid profile of normal subjects and type 2 diabetic patients

Overall, the results of the present study suggest that Amla fruit (E. officinalis, Gaertn.) has both anti-hyperglycemic and lipid-lowering properties and might be used as an ideal plant food supplement in developing successful alternative therapies in the prevention and treatment of diabetes, dyslipidemia, obesity and cancers in general population. 

https://www.tandfonline.com/doi/full/10.3109/09637486.2011.560565?scroll=top&needAccess=true

Efficacy and safety of Amla (Phyllanthus emblica L.) in non-erosive reflux disease: a double-blind, randomized, placebo-controlled clinical trial. - PubMed - NCBI

BACKGROUND:

Gastroesophageal reflux disease (GERD) is one of the most common gastrointestinal complaints. GERD, caused by the reflux of stomach contents into the esophagus, leads to troublesome symptoms such as heartburn and regurgitation. It is classified into two types: erosive esophagitis, characterized by visible esophageal mucosa erosion in endoscopy, and non-erosive reflux disease (NERD). GERD is a chronic and recurrent disease that impairs the quality of life and imposes socioeconomic and therapeutic burdens to both patients and society.
OBJECTIVE:

Due to the failure of the conventional treatments for GERD and to the traditional use of Amla (Phyllanthus emblica L.), in addition to beneficial effects shown in recent studies, we evaluated the safety and efficacy of Amla tablet for improvement of symptoms of patients with NERD.
DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS:

We designed a double-arm, randomized, double-blind, placebo-controlled clinical trial. Sixty-eight patients who had classic symptoms of GERD (heartburn, regurgitation and epigastralgia) for at least three months before the start of the trial were randomized in two parallel groups. Patients in the Amla group received two 500 mg Amla tablets twice a day, after meals, for 4 weeks. In the control group, patients received placebo tablets similar to the Amla prescription.
MAIN OUTCOME MEASURES:

The patients were visited at baseline, and at the end of the 2nd and 4th weeks of intervention; their symptoms were measured on a frequency and severity scale for the symptoms of NERD, according to the quality of life in reflux-associated disease questionnaire.
RESULTS:

Frequencies of heartburn and regurgitation in both groups of the study were significantly reduced after intervention (P < 0.001). Repeated measures logistic regression analysis showed that, in the Amla group, there was a more significant reduction in regurgitation frequency, heartburn frequency, regurgitation severity and heartburn severity during the study period, compared with the placebo group (P < 0.001).
CONCLUSION:

This randomized double-blind, placebo-controlled clinical trial demonstrated that Amla could reduce frequencies of heartburn and regurgitation and improve heartburn and regurgitation severity in patients with NERD.

https://www.ncbi.nlm.nih.gov/pubmed/2952623

AHA.18: Nonstatin therapies, CAC testing claim larger role in cholesterol guidelines

New cholesterol guidelines from the American Heart Association (AHA) and the American College of Cardiology (ACC) recommend adding ezetimibe and/or PCSK9 inhibitors to statin therapy for select high-risk patients, and also propose using coronary artery calcium scoring as "a tiebreaker" to guide statin decisions for those at intermediate risk of atherosclerotic cardiovascular disease (ASCVD).

"How we treat and how we prevent (CVD) can vary from patient to patient," said ACC vice president Richard Kovacs, MD. "This guideline gives clinicians the tools that we need to have those conversations with patients about the most appropriate treatment for high cholesterol."

The 121-page guideline, which was presented Nov. 10 at the AHA's Scientific Sessions in Chicago, was also published online in Circulation and the Journal of the American College of Cardiology.

https://www.cardiovascularbusiness.com/topics/lipids-metabolic/nonstatin-therapies-cac-screening-headline-new-cholesterol-guidelines

AHA.18: VITAL, REDUCE-IT deliver mixed results for fish oil products

VITAL and REDUCE-IT—both highly anticipated trials revolving around the cardiovascular benefits of fish oil products—delivered mixed results at this year's AHA Scientific Sessions in Chicago, with one trial observing few heart benefits from omega-3s while the other saw a 25 percent reduction in major cardiovascular events with a purified eicosapentaenoic acid (EPA) product.


https://www.cardiovascularbusiness.com/topics/lipids-metabolic/vital-reduce-it-deliver-mixed-results

AHA.18: US government updates physical activity guidelines for first time since 2008

As for adults, experts still recommend anywhere between 150 and 300 minutes of moderately intense aerobic activity, like power walking or dancing, each week in addition to two days of strength training. As a whole, recommendations for seniors also stayed the same.

The new guidelines expanded on recommendations for preschoolers aged 3 through 5, who Giroir and colleagues said should be active throughout the day to enhance growth and development. They recommend at least three hours of activity a day, ideally in a variety of settings.

A breadth of new evidence

According to Giroir, new data allowed the guideline committee to take into account a series of unique health considerations. We're now more aware of the extensive health benefits that come with physical activity, as well as the risks associated with being sedentary.

Sedentary behavior, in particular, was a major talking point for this year's guidelines. The first key recommendation for adults is to "move more and sit less"—a tip based in evidence that increased sedentary behavior leads to more heart disease, high blood pressure and all-cause death. Giroir also underlined the fact that evidence now suggests exercise has immediate health benefits, including reducing anxiety and blood pressure, improving sleep quality and increasing insulin sensitivity.

The new guidelines also account for unique patient populations, like pregnant women and those with chronic health conditions or disabilities. Those groups are advised to aim for 150 minutes of physical activity a week and should consult with their specialists before beginning any kind of training program.


https://www.cardiovascularbusiness.com/topics/practice-management/government-updates-physical-activity-guidelines

Patient engagement falls short as ‘blockbuster drug’ physicians are seeking

Medical organizations across the country are trending toward patient-centered care, incorporating meaningful patient activation and engagement (PAE) into their clinical routines. But, despite a push for more personalized medicine, the majority of physicians and assistants still fail to fully understand what PAE means, and much less how to incorporate it into practice.

It's widely accepted that patients and families who are actively engaged in their care see more favorable health outcomes, first author Manish K. Mishra, of the Geisel School of Medicine at Dartmouth, and colleagues wrote in BMJ Open. Techniques like goal-setting, motivational interviewing and shared decision-making are all regarded as successful approaches to PAE.

"If patient engagement is the new 'blockbuster drug,' why are we not seeing spectacular effects?" Mishra et al. wrote. "Studies have shown that activated patients have improved health outcomes, and patient engagement has become an integral component of value-based payment and delivery models, including accountable care organizations (ACOs). Yet the extent to which clinicians and managers at ACOs understand and reliably execute patient engagement in clinical encounters remains unknown."

https://www.cardiovascularbusiness.com/topics/practice-management/patient-engagement-falls-short-physicians

Even ‘intermittent’ exposure to Western lifestyle leads to BP increases

A study of two neighboring communities living in the remote Venezuelan rainforest is poking holes in the idea that blood pressure inevitably increases with age.  

Residents of one community, the Yanomami, demonstrated a flat BP throughout the life course, as indicated by age-BP intercepts and slopes derived from blood pressure measurements in 72 participants aged 1 to 60. On the other hand, Yekwana participants showed average annual increases of 0.25 mm Hg for systolic BP and 0.18 for diastolic BP, based on measurements from 83 participants. Overall, the average blood pressures for the Yanomami and Yekwana, respectively, were 95.4/62.9 mm Hg and 104/66.1 mm Hg.

Both communities are inaccessible by land, but the Yekwana village is near a small airstrip, which has allowed for missionaries to visit as well as intermittent exposure to "aspects of Western lifestyle" like salt, medicine and processed foods. The Yanomami, however, "are among the least acculturated peoples in the world" and have the lowest known BP measurements of any adults, Noel T. Mueller, PhD, MPH, and colleagues wrote in JAMA Cardiology.

https://www.cardiovascularbusiness.com/topics/hypertension/even-intermittent-exposure-western-lifestyle-leads-bp-increases

Tuesday, November 13, 2018

Pricey Precision Medicine Often Financially Toxic For Cancer Patients | Kaiser Health News

Insurers say costs aren't their only concern. Evidence is lacking that the precision medicine approach will work consistently, they argue.

America's Health Insurance Plans, an industry group, said genetic sequencing remains unproven.

Cathryn Donaldson, the group's spokeswoman, described recent scientific advances as "remarkable and noteworthy." But she said insurers "need a more definitive answer" about whether the tests help the average patient live longer.

The South Dakota State Employee Health Plan — which runs Kilmer's insurance plan — said it bases its coverage decisions on science and reviews "published, randomized data about the safety and efficacy of the requested drugs."

Although genetic testing has become the standard of care for melanoma and a common type of lung cancer, no one knows if genomic sequencing will extend the lives of people with other types of cancer, said Dr. Carolyn Presley, an assistant professor at the Ohio State University Comprehensive Cancer Center.

https://khn.org/news/pricey-precision-medicine-often-financially-toxic-for-cancer-patients/

Brain Inflammation Seen for First Time in Fibromyalgia

Researchers have reported for the first time that they have found inflammation in the brains of patients with fibromyalgia.

Daniel S. Albrecht, PhD, a postdoctoral fellow with the Department of Radiology at Massachusetts General Hospital, and Harvard Medical School, Boston, and colleagues, joined with a research team led by Anton Forsberg, PhD, of the Department of Clinical Neuroscience at the Karolinska Institute in Stockholm, Sweden, to broaden generalizability and boost statistical power of the study.

The researchers write that although there has been mounting evidence that brain inflammation plays some role in fibromyalgia, this research is the first to show direct evidence of brain glial activation in the poorly understood and difficult-to-treat chronic condition.

The findings were published online September 14 in Brain, Behavior, and Immunity.

https://www.medscape.com/viewarticle/904827

Wednesday, November 7, 2018

Multiple metal exposures and metabolic syndrome: A cross-sectional analysis of the National Health and Nutrition Examination Survey 2011-2014

Epidemiologic studies suggest toxic metals are linked with diabetes and cardiovascular disease, while experimental studies indicate nutritionally essential metals are involved in the metabolism of macronutrients and defense against oxidative stress.
OBJECTIVES:

We sought to evaluate how essential and toxic metals are cross-sectionally related to metabolic syndrome, a clustering of cardiometabolic conditions.
METHODS:

Using data from the 2011-2014 National Health and Nutrition Examination Survey (n = 1088), we characterized metal concentrations as measured in spot urine (arsenic, cadmium, and inorganic/elemental mercury), whole blood (manganese, lead, methylmercury, and selenium), and serum (copper and zinc) samples. Principal component analysis was performed to derive patterns of exposures. Metabolic syndrome was defined according to the 2009 Joint Scientific Statement as the presence of ≥ 3 of the following conditions: high blood pressure, high triglycerides, low HDL cholesterol, high fasting glucose, and abdominal obesity.
RESULTS:

After adjustment for potential confounders, prevalence ratios for metabolic syndrome comparing the highest to the lowest quartiles were 1.41 (95% CI: 1.18-1.67) for the arsenic-inorganic/elemental mercury pattern, 0.95 (0.78-1.16) for the methylmercury-manganese pattern, 0.73 (0.57-0.94) for the cadmium-lead pattern, 0.91 (0.76-1.10) for the copper pattern, and 1.36 (1.13-1.63) for the selenium-zinc pattern. The positive associations observed for the arsenic-inorganic/elemental mercury pattern were due to an elevated prevalence of high blood pressure, low HDL cholesterol, and high triglycerides among those with greater exposures. Associations for the selenium-zinc pattern were driven by a positive relationship with high triglycerides. Greater lead-cadmium co-exposures were related to a lower prevalence of dyslipidemia and abdominal obesity.
CONCLUSIONS:

These cross-sectional findings suggest both toxic and essential metal exposures may contribute to cardiometabolic health, but need to be confirmed with prospective data.

https://www.ncbi.nlm.nih.gov/pubmed/30388496

Quercetin, but Not Epicatechin, Decreases Plasma Concentrations of Methylglyoxal in Adults

Methylglyoxal (MGO) is the most potent precursor of advanced glycation end products (AGEs). MGO and AGEs have been associated with diabetes, its complications, and other age-related diseases. Experimental studies have shown that the flavonoids quercetin and epicatechin are able to scavenge MGO and lower AGE formation.
Objective:

Data on the effects of these flavonoids on MGO and AGE concentrations in humans are not yet available. We therefore investigated the effect of quercetin and epicatechin on the concentrations of MGO and AGEs in a post hoc analysis.
Methods:

Thirty-seven apparently healthy, nonsmoking adults with a systolic blood pressure between 125 and 160 mm Hg at screening were included in a randomized, double-blind, placebo-controlled crossover trial. Participants ingested (-)-epicatechin (100 mg/d), quercetin 3-glucoside (160 mg/d), or placebo capsules for periods of 4 wk separated by 4-wk washout periods. Fasting blood samples were collected at the start and end of each intervention period. Liquid chromatography-tandem mass spectrometry was used to determine plasma concentrations of the dicarbonyl compounds MGO, glyoxal (GO), and 3-deoxyglucosone (3-DG) and free and protein-bound AGEs. Gene expression of glyoxalase 1 (GLO1), the enzyme involved in the degradation of MGO, was determined by either microarray or quantitative reverse transcriptase-polymerase chain reaction.
Results:

The treatment effect (Δtreatment - Δplacebo) of quercetin on MGO was -40.2 nmol/L (95% CI: -73.6, -6.8 nmol/L; P = 0.019), a decrease of 11% from baseline values, whereas GO, 3-DG, and free and protein-bound AGEs did not change significantly. Epicatechin did not affect the concentrations of dicarbonyls and free and protein-bound AGEs. We did not find a significant change in expression of GLO1.
Conclusions:

In apparently healthy (pre)hypertensive men and women, quercetin but not epicatechin decreased plasma MGO concentrations. Quercetin may potentially form a new treatment strategy for diseases in which MGO plays a pivotal role. This study was registered at clinicaltrials.gov as NCT01691404.

https://www.ncbi.nlm.nih.gov/pubmed/30398646

Human drugs flowing into the animal kingdom - Times Union

Modern medicines are moving through sewage treatment systems and into aquatic insects and the animals that eat them, according to an environmental study in Australia that involved a Hudson Valley researcher.

Tests of six Australian streams near the city of Melbourne found animals there contained high doses of painkillers, antidepressants and other drugs that had gotten into the water after passing through municipal sewer systems that are unequipped to remove them.

https://m.timesunion.com/7dayarchive/article/Human-drugs-flowing-into-the-animal-kingdom-13367091.php#photo-16458812

Sunday, November 4, 2018

Cancer Fears Over Cell Phones, Again, but FDA Disagrees

Scientists from the National Toxicology Program (NTP), part of the National Institute of Environmental Health Sciences within the National Institutes of Health, issued a report on November 1 in which they said that their study clearly showed that male rats exposed to high levels of RFR developed heart schwannomas, a form of cancer that is very rare in humans.

They also said that there was some evidence to suggest that exposed male rats were at increased risk of developing tumors in the brain and adrenal glands.

John Bucher, PhD, senior scientist at the NTP, said in a release: "We believe that the link between radio frequency radiation and tumors in male rats is real, and the external experts agreed."

https://www.medscape.com/viewarticle/904317

Wednesday, October 31, 2018

Common Household Chemicals Tied to Language Delays in Kids

Early prenatal exposure to phthalates — the synthetic chemicals commonly found in household items and personal care products — has been tied to language delays in children, new research shows.

In the first study of its kind, the collaboration between investigators from the Icahn School of Medicine at Mount Sinai, New York City, and Karlstad University, Sweden, showed that the risk for language delay was as much as 30% greater in children whose mothers were exposed to twice the levels of dibutyl phthalate and butyl benzyl phthalate, two chemicals commonly found in such everyday items as cosmetics, plastic toys, and food.

"The bottom line here is that the phthalates that a mother is exposed to in early pregnancy can affect the development of the brain in her children, particularly in this area of language development," principal investigator Shanna Swan, PhD, professor of environmental and public health at the Icahn School of Medicine at Mount Sinai, told Medscape Medical News.

"Unfortunately, these results point to different phthalates than we've found to be bad actors in the past. We've previously observed negative associations with di-ethylhexyl phthalate, which is more commonly found in food. Now we have more phthalates to worry about," said Swan.

The study was published online October 29 in JAMA Pediatrics.


https://www.medscape.com/viewarticle/904083

Common Household Chemicals Tied to Language Delays in Kids

Saturday, October 27, 2018

Plant-Based Diet to Lower Type 2 Diabetes Risk: Is It All or Nothing?

A Plant-Based Dietary Index

We embedded these analyses in the Rotterdam study, a large population-based cohort in the Netherlands, where almost 15,000 people were followed over time. We measured their diets at baseline.

For each participant, we scored how much they consumed of plant-based foods—such as vegetables, nuts, and legumes—and of animal-based foods, such as meat, dairy, eggs, and fish. We computed an overall score, with higher scores reflecting more plant-based and less animal-based foods.

When we analyzed this plant-based diet score in relation to incident diabetes and insulin resistance—controlling for body mass index, physical activity, smoking, and several other factors—we consistently found that higher scores on the plant-based dietary index were related to lower diabetes risk and lower levels of insulin resistance in the general population.

Overall, these findings strengthen current dietary recommendations that support the adoption of a more plant-based diet for lowering the risk of developing type 2 diabetes.

https://www.medscape.com/viewarticle/903699

Thursday, October 18, 2018

Vitamin C cocktail for sepsis: randomized trials to test efficacy - PulmCCM

Since Marik et al announced exceptional survival rates among patients with septic shock given a cocktail of vitamin C, thiamine, and hydrocortisone, physicians taking care of septic patients have expressed both enthusiasm and skepticism about the cocktail's reported lifesaving effects.

Soon, more rigorous testing from randomized, double-blind placebo-controlled trials should provide harder data about the sepsis cocktail's efficacy.

Jonathan Sevransky, MD of Emory University announced plans for a clinical trial enrolling between 500 and 2,000 patients at multiple centers over about 18 months, completing by the end of 2019. Patients with septic shock would get either the cocktail, or placebo. Mortality will be tested, as well as days free of vasopressors or a ventilator. The study will be funded by a private foundation.

Michael Donnino, MD of Harvard's Beth Israel plans to enroll 200 patients at multiple centers, also testing the cocktail vs. placebo in patients with septic shock. Organ failure, mortality, and other outcomes will be compared. Major funding will come from the Open Philanthropy Project. The study should be completed in the autumn of 2019.


https://pulmccm.org/infectious-disease-sepsis-review/vitamin-c-cocktail-for-sepsis-randomized-trials-to-test-efficacy/

Saturday, October 13, 2018

High-Quality Diet Linked to Better Outcomes in Bipolar Disorder

A high-quality diet was one that included an abundance of fruits and vegetables, whereas poorer-quality diets included more saturated fat, refined carbohydrates, and alcohol.

https://www.medscape.com/viewarticle/903342