Women who consumed a higher proportion of their daily calories later in the evening were more likely to be at greater risk for cardiovascular disease than women who did not, according to preliminary research to be presented at the American Heart Association’s Scientific Sessions 2019 — November 16-18 in Philadelphia. The Association’s Scientific Sessions is an annual, premier global exchange of the latest advances in cardiovascular science for researchers and clinicians.
Researchers assessed the cardiovascular health of 112 women (average age 33, 44% Hispanic) using the American Heart Association’s Life’s Simple 7® measures at the beginning of the study and one year later. Life’s Simple 7 represents the risk factors that people can improve through lifestyle changes to help achieve ideal cardiovascular health and include not smoking, being physically active, eating healthy foods and controlling body weight, along with measuring cholesterol, blood pressure and blood sugar levels. A heart health score based on meeting the Life’s Simple 7 was computed.
Study participants kept electronic food diaries by computer or cell phone to report what, how much and when they ate for one week at the beginning of the study and for one week 12 months later. Data from the food diary completed by each woman was used to determine the relationship between heart health and the timing of when they ate.
Researchers found:
While most study participants consumed some food after 6 p.m., those who consumed a higher proportion of their daily calories after this time had poorer heart health.
With every 1% increase in calories consumed after 6 p.m., heart health declined.
Specifically, women who consumed more of their calories after 6 p.m. were more likely to have higher blood pressure, higher body mass index and poorer long-term control of blood sugar.
Similar findings occurred with every 1% increase in calories consumed after 8 p.m.
The impact on blood pressure was more pronounced in Hispanic women who consumed most of their calories in the evening and persisted even after adjusting for age and socioeconomic status.
“So far, lifestyle approaches to prevent heart disease have focused on what we eat and how much we eat,” said lead study author Nour Makarem, Ph.D., an associate research scientist at Columbia University’s Vagelos College of Physicians and Surgeons in New York. “These preliminary results indicate that intentional eating that is mindful of the timing and proportion of calories in evening meals may represent a simple, modifiable behavior that can help lower heart disease risk.”
The results should be confirmed in a larger sample and in other populations, said Makarem who is a member of the American Heart Association’s Council on Epidemiology and Prevention Early Career Committee.
Kristin Newby, M.D., chair of the oversight advisory committee for the Go Red for Women Strategically Focused Research Network, said this type of research is important to help women of all ages better understand and manage their health risks.
“I think it’s an important study, it’s foundational more than definitive at this point, but I think it provides some really interesting insights into an aspect of nutrition and how it relates to cardiovascular risk factors that we really haven’t thought about before,” said Newby, professor of medicine and cardiology at Duke University in Durham, North Carolina. “It is never too early to start thinking about your heart health whether you’re 20 or 30 or 40 or moving into the 60s and 70s. If you’re healthy now or if you have heart disease, you can always do more. That goes along with being heart smart and heart healthy.”
It might soon be possible to completely treat HIV. Researchers at the American Gene Technologies (AGT), a pharmaceutical company in the US, have claimed that they have developed a permanent cure for HIV.
HIV is one of the biggest public health concerns around the world today. It has claimed more than 32 million lives since the 1980s. This virus damages the immune system, so the person is not able to fight any infection. Currently, HIV is treated with antiretroviral therapy that controls the growth of the virus but does not completely eliminate it from the body.
However, AGT scientists used a different approach to treat the disease. Instead of targetting the virus, they focussed on the immune system and genetically strengthened it in such a way that it could fight the HIV virus on its own.
The drug is currently known as AGT103T. American Gene Technologies has already given an IND (Investigational Drugs and Devices) application to the US Food and Drug Administration (FDA) to let them test the drug on human volunteers in a phase 1 trial.
The research
AGT103T is actually a virus-based single-dose gene therapy. To develop it, the research team at AGT collected blood samples from HIV positive people and then separated a specific type of cells — T helper cells — from it. T helper (or CD4+) cells are specifically targetted by the HIV virus. A small fraction of all the T helper cells evolve to fight HIV in an infected person. These cells are highly susceptible to HIV and so are unable to eliminate the virus.
To solve these problems, the AGT team used a virus and transferred a special fragment of DNA into the isolated T helper cells. The DNA fragment made the cells resistant to HIV damage. Millions of copies of these resistant cells were then created in the lab. The whole process took 11 days. Now in the next phase, the team is going to test the safety of the therapy and then reinject the cells into an HIV positive patient.
Not the first gene therapy
It is not the first time that scientists have thought of using gene therapy for HIV treatment. Preventing the entry of HIV into the cell, cutting out infected DNA from healthy cells, removing HIV virus from infected cells and producing HIV resistant cells – have all been tried already. However, what makes this research stand out is that it is focussing on increasing the capacity of the immune system to fight against the virus.
In a press release by American Gene Technologies, C. David Pauza, Chief Science Officer at AGT, explained why this therapy is better than its predecessors. “By providing high doses of virus-specific helper T cells, which are protected from HIV damage by a safe genetic modification, AGT’s goal is to rebuild the capacity for normal, unhindered immune responses against HIV that may control the infection and protect against future virus exposures.”
An ablative procedure intended to promote regrowth of duodenal mucosa was safe and had disease-modifying metabolic effects in a randomized study including patients with type 2 diabetes, according to investigators.
A single duodenal mucosal resurfacing (DMR) procedure improved glycemic, hepatic, and body weight measures at 24 weeks in the multicenter study, investigators will report at the annual meeting of the American Association for the Study of Liver Diseases.
The novel and minimally invasive endoscopic procedure treats the duodenum, which is increasingly recognized as a key metabolic signaling center, according to the study authors, including senior author Arun Sanyal, MD, professor in the gastroenterology division of the department of internal medicine at Virginia Commonwealth University School of Medicine in Richmond.
“Duodenal mucosal hyperplasia is a potential therapeutic target for insulin-resistance–related metabolic diseases,” Dr. Sanyal and coauthors said in a late-breaking abstract for the study published in the AASLD meeting proceedings.
In a previous international open-label, prospective, multicenter study, published in July in the journal Gut, DMR was feasible and safe, producing durable glycemic improvement in patients with type 2 diabetes with suboptimal control on oral glucose-lowering mediation, according to investigators.
The present study, conducted at nine sites in the European Union and two in Brazil, is the first sham-controlled, double-blind, and prospective study of the modality in patients with suboptimally controlled type 2 diabetes, according to Dr. Sanyal and coauthors.
A total of 39 patients in the study underwent DMR, while 36 underwent a sham procedure, according to the published abstract. The mean HbA1c for those patients was 8.3, BMI was 31.1 kg/m2, and most (77%) were male.
Median change in HbA1c from baseline to 24 weeks, one of two primary endpoints in the study, was –0.6% for DMR, and –0.3% for the sham procedure (P less than 0.05), according to the study abstract.
Likewise, the primary efficacy endpoint of change in a nonalcoholic steatohepatitis (NASH) biomarker favored the DMR arm. The median change in liver magnetic resonance imaging-proton density fat fraction (MRI-PDFF) from baseline to 12 weeks was –5.4% for DMR and –2.4% for the sham procedure (P less than 0.05), according to the reported data.
Hypoglycemia rates were similar in the DMR and sham arms, and over 24 weeks of study, there were no unanticipated adverse effects attributable to the device, and no serious adverse events, Dr. Sanyal and colleagues reported.
Dr. Sanyal reported disclosures related to Fractyl Laboratories, Sanyal Bio, Exhalenz, Akarna, Genfit, Durect, Indalo, Tiziana, Novartis, Merck, Galectin, Janssen, Merck, and more.
Doctors who transplanted a complete penis and scrota onto the body of a soldier wounded by an improvised explosive device in Afghanistan reported Wednesday that the man has regained near-normal erections and the ability to achieve orgasm more than one year after the surgery was completed.
The landmark 14-hour operation was done at Johns Hopkins Hospital in Baltimore, Maryland, on March 26, 2018, by nine plastic surgeons and two urological surgeons.
The transplant included part of the abdominal wall, but not the testicles. Previously, only four successful penis-only transplants have been reported.
“His recovery has exceeded expectations,” Dr. Richard Redett III, a professor of plastic and reconstructive surgery at Johns Hopkins, told Reuters Health in an email.
He and his colleagues report in a letter to the New England Journal of Medicine, online November 6, that the soldier, who lost both legs above the knee as a result of the IED, “has normal sensation to the shaft and tip of the transplanted penis and can localize touch sensation.”
“The patient urinates while standing, without straining, frequency, or urgency, with the urine discharged in a strong stream,” the Redett team writes in its report. “The patient has returned to school full-time and continues to live independently using leg prostheses. He reports an improved self-image and ‘feeling whole’ again and states that he is very satisfied with the transplant and the implications it carries for his future.”
The team had been preparing for such surgery on the man since 2013, Redett said. “Our patient was initially referred for an evaluation using conventional reconstructive techniques. Because he had concomitant extremity injuries (flap donor sites) and his defect was so large and included the lower abdominal wall, penis and scrotum, and some medial thigh tissue, conventional reconstructive options were very limited. At the same time, we had started exploring penile transplantation.”
The man was on a wait-list for 15 months.
In addition to matching blood and tissue types, the procedure, known as vascularized composite allograft (VCA) surgery, “also requires matching other features such as skin tone, size and age of the graft,” Redett noted. “When people sign up as an organ donor they are not authorizing a VCA donation. The family makes the decision about VCA donation after death, which adds another step to the approval process.”
The process included infusions of bone marrow from the donor to the soldier beginning two weeks after the surgery to tamp down the immune system’s response to the donated tissue.
The marrow transplant was designed to allow the patient to only need a single small dose of the drug tacrolimus each day to suppress immune rejection of the transplant.
A quick injection that blocks the stellate ganglion relieves symptoms of posttraumatic stress disorder (PTSD) and may represent a new and urgently needed treatment option.
Results of a randomized, sham-controlled trial in active-duty military members showed that stellate ganglion block (SGB) relieved distress, anxiety, and depression in this cohort.
Interestingly, those with the most severe PTSD achieved the greatest benefit.
Kristine Rae Olmsted, MSPH
“SGB can represent a new treatment option for PTSD but should be used as much as possible in concert with psychotherapy,” principal investigator Kristine L. Rae Olmsted, MSPH, a research epidemiologist at Research Triangle Institute, Durham, North Carolina, told Medscape Medical News.
Research suggests that extreme trauma may stimulate the sympathetic nervous system. The stellate ganglion, a collection of nerves located at the base of the neck, is part of that nervous system and is “sort of a weigh station for the fight or flight” reaction, said Rae Olmsted.
The SGB procedure involves injecting a short-acting local anesthetic in and around the stellate ganglion to temporarily block its function. The procedure is “very quick,” taking only about 5 minutes, said Rae Olmsted.
It’s unclear how SGB works with respect to PTSD, but some experts believe it “reboots” the sympathetic nervous system to its pretrauma state, perhaps by providing feedback to the amygdala, which is closely aligned with emotional processing.
The procedure isn’t new; it has been used to treat pain conditions since the 1940s. Several case studies showed promising results in patients with PTSD, although in one clinical trial, the results were negative.
The new study included 113 active-duty military personnel (100 men and 13 women; mean age, 37.3 years) at three sites. Participants were required to have been diagnosed with PTSD and to have been stable through the use of psychotropic medication for a period of at least 3 months. Patients were excluded from the study if they had a history of moderate or severe traumatic brain injury.
Patients were randomly assigned to receive two right-sided SGB treatments or sham procedures 2 weeks apart. None of the participants had a patient-physician relationship with the clinician who administered the treatment.
Those in the active-SGB group were injected with 7 to 10 mL of ropivacaine 0.5% around and into the ganglion at the level of the C6 anterior tubercle. The sham-treatment group received 1 to 2 mL of preservative-free normal saline injected into deep musculature anterolateral to the anterior tubercle of C6.
Participants were blinded with respect to which procedure they received; drapes were used to limit their field of vision. Although clinicians could not be blinded, their interactions with participants were scripted.
Of the total, 108 individuals (95.6%) remained in the study through the 8-week follow-up.
The study’s primary outcome was change in overall total symptom severity scores on the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). Scores on that scale range from 0 to 80 points, with higher scores indicating greater PTSD symptom severity. A 10-point change in the CAPS score was considered clinically meaningful.
The analysis showed that at 8 weeks, the SGB group benefited more than the sham-treatment participants. The mean symptom change after adjustment for study site and baseline CAPS-5 score was –12.6 points for SGB group compared with –6.1 points for the sham-treatment group, which represented a significant difference.
The treatment appeared to work better for those with more severe PTSD symptoms. For each 1-point increase in initial CAPS-5 score, there was an estimated additional 0.2-point reduction at 8 weeks.
Unclear Mechanism
The reasons for this are unclear, but other studies have reported similar findings, said Rae Olmsted. She speculated that patients with more severe symptoms may have “more opportunity to get better.”
Secondary outcomes included scores for a number of symptoms highly correlated with PTSD, including depression, distress, anxiety, pain, physical functioning, and mental functioning. For all these outcomes, those receiving SGB had significantly improved scores on relevant scales compared with those receiving the sham procedure.
Six adverse events were reported, including coughing as well as pain and redness at the injection site. None of these were serious.
The new results contrast with those of the first pilot, randomized clinical trial of SGB for combat-associated PTSD. That study did not find a significant difference between the SGB group and the saline-injection control group.
The authors note the following differences between that study and the current one: the previous was smaller; it included a single site; it used only one SGB instead of two; it utilized less ropivacaine; and exclusion criteria were less rigorous.
The potential for participants to recognize signs of Horner syndrome is a limitation of the study. Horner syndrome, a possible side effect of the SGB procedure, is characterized by “a droopy eye, constricted pupil, and red eye on right-hand side,” said Rae Olmsted.
“This was a concern, but one we couldn’t control for. We had our clinicians and clinical staff tell everybody, regardless of treatment group, that it was potential outcome,” she said.
The fact that the study population was highly specified might limit clinical generalizability, say the authors. Also, the overall severity level of PTSD symptoms in the sample was low to moderate, which might limit generalizability with respect to patients routinely seen in outpatient practice.
“However, we view inclusion of active-duty service members with subthreshold signs as a strength, given emerging evidence suggesting PTSD symptoms may be best seen as a continuum,” the authors write.
The investigators are planning a large-scale, multisite cohort study that will follow PTSD patients for a year after they receive SGB. The researchers will assess factors such as symptom trajectory, the degree to which patients improve over time, and how long they remain better.
Questions Remain
Commenting on the findings for Medscape Medical News, Gary H. Wynn, MD, Col, MC, Uniformed Services University of the Health Sciences, and senior scientist, Center for the Study of Traumatic Stress, Bethesda Maryland, said the study was “well done.”
These findings suggest that “SGB should be in the tool box for PTSD, but we’re just not sure how best to use the tool yet,” said Wynn.
“We have to figure out if we should we use it early in the process of treatment or later on in the process of treatment, in combination with psychotherapies or in combination with other medicines. Do you start off with this and wait until patients get some symptom relief and then initiate medicines?” he said.
Although questions still need to be answered about the treatment, Wynn said, “It’s very clear from this study that there is some validity to its use.”
He’s concerned that people will interpret these positive results to mean that SGB is “curative,” when “the truth is, this is a modest result.”
He also pointed out that the procedure must be performed by an anesthesiologist who is very familiar with SGB. “So there are some limitations to the construct of this that suggest we’re not going to roll this out to all 400,000 Veterans Affairs beneficiaries who have a diagnosis of PTSD.”
Also commenting, retired military psychiatrist Elspeth Cameron Ritchie, MD, chief of psychiatry at Medstar Washington Hospital Center, Washington, DC, who has expertise in PTSD among combat veterans, said she’s “really excited” by the findings.
This is the first study to show that the procedure works on a wide scale, said Ritchie, and that’s “incredibly significant.”
However, she pointed out that the treatment isn’t effective for everyone. “One of the challenges is to determine who it works for,” she said.
Ritchie agreed that study participants who developed Horner syndrome likely suspected that they had been given the active treatment. But she noted the difficulty of conducting a sham study that involves injecting an agent into the participants.
“No study is perfect, and the fact that they got as many people as they did into this one and that they showed a significant difference on the standardized measure is very exciting.”
Ritchie said she and her colleagues “would love” to see this type of study carried out in a Veterans Administration setting in which there is a “very large population of potential subjects” with chronic conditions.
Rae Olmsted reports having a cooperative agreement for the funding of this study with the US Army during the conduct of the study. Wynn and Ritchie report no relevant financial relationships.
JAMA Psychiatry. Published online November 6, 2019. Abstract
Women who consumed a higher proportion of their daily calories later in the evening were more likely to be at greater risk for cardiovascular disease than women who did not, according to preliminary research to be presented at the American Heart Association’s Scientific Sessions 2019 — November 16-18 in Philadelphia. The Association’s Scientific Sessions is an annual, premier global exchange of the latest advances in cardiovascular science for researchers and clinicians.
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