Medical Drink Falls Short in Early Alzheimer's Trial

Medical Drink Falls Short in Early Alzheimer's Trial

A nutrient-packed drink may have some limited benefit in people with prodromal Alzheimer’s disease (AD), but experts urge caution in drawing any firm conclusions.

Over 2 years, the daily nutritional drink (vs inactive control drink) had no significant impact on performance on the neuropsychological test battery (NTB), the primary endpoint, or on conversion to dementia in patients with prodromal AD. However, some evidence suggested less worsening in Clinical Dementia Rating-Sum of Boxes (CDR-SB) score and a slowing of hippocampal atrophy.

The study was published online October 30 in Lancet Neurology.

Mixed Results

LipiDiDiet is a research consortium funded by the European Union that studies the impact of nutrition in AD. The nutritional drink tested in the study is available in the United Kingdom as Souvenaid (Nutricia). 

Fortasyn Connect, the active component of Souvenaid, was developed on the basis of the premise that a specific combination of nutrients enhances synaptic functions.  It contains docosahexaenoic acid and eicosapentaenoic acid; uridine monophosphate; choline; vitamins B12, B6, C, and E, and folic acid; phospholipids; and selenium.

 The LipiDiDiet trial, conducted at 11 centers in Finland, Germany, the Netherlands, and Sweden, enrolled 311 patients aged 55 to 85 years who met criteria for prodromal AD; 153 were randomly allocated to the active intervention (125 mL once-daily drink containing Fortasyn Connect) and 158 to an inactive isocaloric control drink.

There was no statistically significant difference between groups in the primary endpoint,  mean change in a composite score of cognitive performance based on the NTB (–0.028 in the intervention group and –0.108 in the control group; estimated mean treatment difference, 0.098; 95% confidence interval [CI],  –0.041 to 0.237; P = .166).   The researchers note that the decline in NTB in the control group was less than the prestudy estimate of –0.4 over 24 months, rendering this analysis statistically underpowered.

Two secondary endpoints showed a difference in favor of the nutritional drink. The CDR-SB score worsened less in the active group over the study period, with an effect size of 0.33 (P = .005). 

“The worsening in CDR-SB was 45% less in the active group than in the control group, based on the estimated change from baseline over 24 months,” the researchers report.  Supplementation with the nutritional drink also slowed hippocampal atrophy rate, with an effect size of 0.22 (P = .005).

During the 24-month study period, 62 (41%) patients in the active group and 59 (37%) in the control group were diagnosed with dementia.  Sixty-six (21%) patients dropped out of the study. Serious adverse events occurred in 34 (22%) patients in the active group and 30 (19%) in the control group, none of which were considered related to the study intervention.

“Further study of nutritional approaches with larger sample sizes, longer duration, or a primary endpoint more sensitive in this pre-dementia population, is needed,” the authors conclude in their article.

In a press release, Hilkka Soininen, PhD, from the University of Eastern Finland in Kuopio, who led the trial, said these results are “extremely valuable as they bring us closer to understanding the impact of nutritional interventions on prodromal Alzheimer’s, which we are now better at diagnosing but unable to treat due to a lack of approved pharmaceutical options. The LipiDiDiet study illustrates that this nutritional intervention can help to conserve brain tissue and also memory and patients’ ability to perform everyday tasks — possibly the most troubling aspects of the disease.”

No Proof of Efficacy

In a comment published with the study, Hussein Yassine, MD, from Keck School of Medicine University of California, Los Angeles, urges caution in interpreting the findings.

This trial, together with past trials, “does not provide sufficient evidence for the use of Fortasyn Connect in mild or prodromal Alzheimer’s disease. The suggestion of benefit in two of the secondary outcomes is encouraging, but needs to be confirmed in further research,” he writes. 

Maria C. Carrillo, PhD, Alzheimer’s Association chief science officer, also urged caution in interpreting the study results.

“This study failed to meet its primary endpoint. This product has not been proven efficacious,” she told Medscape Medical News.

Dr Carrillo also noted that the finding of reduction in functional decline and brain atrophy relative to the control group should be viewed only as “scientific points of interest. The results reported in the article may provide information and direction for future studies that will give us more definitive information about efficacy in these populations.”

The Alzheimer’s Association recently launched the Protect through a Lifestyle Intervention to Reduce Risk (US POINTER) study, a 2-year clinical trial to test whether lifestyle interventions focused on combining healthy nutrition, physical activity, social and intellectual challenge, and increased medical monitoring of vascular and metabolic conditions can protect cognitive function in older adults at increased risk for cognitive decline. 

“US POINTER is the first study to examine this combined multi-dimensional intervention in a large-scale U.S.-based population,” Dr Carrillo said.

The LipiDiDiet trial was funded by the European Commission 7th Framework Programme. Several authors have indicated financial relationships with pharmaceutical companies. All are listed with the original article. Dr Yassine has received grants from the Alzheimer’s Association. Dr Carrillo has disclosed no relevant financial relationships.

Lancet Neurol. Published online October 30, 2017. Abstract, Comment

For more Medscape Neurology news, join us on Facebook and Twitter

Source link

'Hybrid' Procedure on Par With CABG, PCI in Pilot Study

'Hybrid' Procedure on Par With CABG, PCI in Pilot Study

DENVER, CO — A randomized comparison of a hybrid coronary revascularization strategy with standard PCI and CABG in patients with multivessel CAD showed few differences between approaches in outcomes at either 30 days or 12 months^[1].

The rate of residual ischemia by SPECT imaging at 12 months, the trial’s primary end point, ranged nonsignificantly from 6% to 8% for the trial’s three strategies, standard CABG vs PCI with contemporary drug-eluting stents (DES) vs a staged combination of minimally invasive direct coronary artery bypass (MIDCAB) surgery followed several days later by PCI with the same kinds of DES.

Nor was there a significant difference at 12 months for the secondary end point of major adverse cardiovascular and cerebrovascular events (MACCE), a composite of death, MI, stroke, or clinically driven target-vessel revascularization (TVR).

The Hybrid Revascularization Versus Standards (HREVS) trial, with only 155 patients, was described here at TCT 2017 as de facto pilot study to prepare for the kind of larger, longer-term randomized trials needed to truly test the hybrid approach in such patients.

MIDCAB consisted of off-pump surgical bypass of the left anterior descending artery (LAD) by a left internal mammary artery (LIMA) through a “keyhole” thoracotomy in the HREVS trial, which was presented here today by Dr Roman Tarasov (State Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo, Russia).

In the current study, Tarasov told theheart.org | Medscape Cardiology, patients who underwent the hybrid procedure or PCI received dual antiplatelet therapy (DAPT) for 12 months.

Almost 10% of patients assigned to the hybrid actually underwent standard CABG, the crossover decision made intraoperatively, he said. And hospitalization time was significantly shorter with PCI alone.

“I think this study, for me, confounds the questions regarding multivessel revascularization, and in fact, yet again proves that we’ve reached a point of clinical equipoise for PCI,” Dr Jonathan M Hill (King’s College Hospital, London, UK) at a media briefing on the study. In a low- to intermediate-risk cohort, he said, “it again shows that the performance with the latest-generation stents is as good as surgery.”

HREVS “can be interpreted several ways,” according to Dr Mark A De Belder (James Cook University Hospital, Middlesbrough, UK), speaking as a panelist following Tarasov’s formal presentation of the trial. One could say none of the three approaches was better or worse than another; or one could say, “why bother, just do some stenting,” he said.

“But I think there are individual cases where you’ve got incredibly complex LAD disease, which is very difficult to stent, where these results would be encouraging that the hybrid approach is good.”

Patients in HREVS had multivessel CAD with LAD involvement, with either a >70% stenosis, a 50% to 69% stenosis plus pressure-wire fractional flow reserve (FFR) indicating functional impairment, or SPECT evidence of regional ischemia. Also, all patients had to be appropriate for all three procedures.

There were no significant differences in baseline features among the three groups. More than half in each group had a history of MI, mean LVEF ranged from 53% to 56%, and almost half of patients had at least triple-vessel disease.

Excluded were patients with any coronary revascularization history, left main stenoses, or CTO or needing cardiac surgery other than CABG.

With 50 randomized to CABG only, 52 to MIDCAB plus PCI, and 53 to PCI only, the rates of residual ischemia by SPECT at 12 months, the primary end point, were 6.7%, 6.4%, and 7.9% (P=0.46), respectively. MACCE-free survival at that point was 88%, 86.6%, and 86.8%, respectively.      

Outcomes of Three Revascularization Strategies Compared

End points	CABG, n=50	MIDCAB/PCI, n=52	PCI, n=53	P
30 d
MACCE (%)	8	5.8	3.8	0.37
Hospital days	13.8	13.5	4.5	<0.001
12 Mo
MACCE (%)	12	13.4	13.2	0.83
Target vessel or graft failure (%)	12	11.5	11.3	0.98

HREVS is “the first pilot study that actually has hybrid revascularization, multivessel PCI, and CABG all in the same study,” and it shows that all three are safe, said Dr Roxana Mehran (Mount Sinai School of Medicine, New York, NY) at the media briefing.

Even before the advent of DES, she said, surgeons said the best bypass results were with LIMA to the LAD. “So the best of two worlds would be a LIMA to the LAD, and drug-eluting stents that do extremely well in the non-LAD distribution.”

The idea of hybrid procedures has been around a long time, but minimally invasive coronary revascularization didn’t catch on as much as many anticipated, so the hybrid approach didn’t either.

In an interview, Dr Cindy L Grines (Hofstra Northwell School of Medicine, Hempstead, NY) explained that MIDCAB is a beating-heart cardiac surgery that takes lots of expertise to do well. The procedure is also time-consuming, and studies over the past decade suggest that its grafts, overall, aren’t as long-lasting as arterial grafts at standard CABG.

“So that incentivized a lot of physicians to abandon the beating-heart surgery because it was more difficult for them,” she said. “As physicians we want to first do no harm, second we want to do what’s easy for us, and we want to be reimbursed for our time. So if it takes you longer, and they’re not reimbursing you any more, why would you do it?” she said.

“There still isn’t a great buy-in to this in the United States,” agreed Dr David J Cohen (Saint Luke’s Mid America Heart Institute, Kansas City, MO) in an interview.

That’s largely “because of logistic challenges coordinating the two procedures between two different specialties,” he said. “And when there are lots of questions around the logistics, and there’s no proven benefit, it gets hard to mount a strong campaign to support the technique.”

Tarasov and his coauthors on the study declared they have no relevant financial relationships. Mehran discloses within the past 12 months she has had a financial interest/arrangement or affiliation with Abiomed, Abbott Vascular, CardioKinetix, Spectranetics, AstraZeneca, Bayer, Eli Lilly, Novartis, OrbusNeich, Medtronic, Bristol-Myers Squibb, Claret Medical, Janssen, Osprey Medical, the Medicines Company, Boston Scientific, Shanghai Braccosine, Elixer, and Medscape. Hill discloses within the past 12 months he has had a financial interest/arrangement or affiliation with Abbott Vascular, Abiomed, Boston Scientific, St Jude Medical, and Medtronic. De Belder has no relevant financial relationships. Grines discloses within the past 12 months she has had a financial interest/arrangement or affiliation with Abbott Vascular and Volcano Corp. Cohen discloses within the past 12 months he has had a financial interest/arrangement or affiliation with Abbott Vascular, AstraZeneca, Boston Scientific, Edwards Lifesciences, Medtronic, Merck/Schering Plough, Corvia Medical, and Svelte Medical.

Follow Steve Stiles on Twitter: @SteveStiles2. For more from theheart.org | Medscape Cardiology, follow us on Twitter and Facebook.

Source link

Climate Change in the Air at APHA 2017

Climate Change in the Air at APHA 2017

ATLANTA — The effect of climate change on health outcomes and healthcare systems will dominate sessions at the upcoming American Public Health Association (APHA) 2017 Annual Meeting.

Dr Georges Benjamin

The theme of the conference — Creating the Healthiest Nation: Climate Changes Health — is underscored by the string of recent hurricanes affecting the United States and other places around the world, said APHA Executive Director Georges Benjamin, MD.

“The impact of global warming on infectious disease will be relevant,” he said, especially for “physicians practicing in areas where the weather is warming up and they’re not necessarily used to seeing these vector-borne diseases in abundance, such as West Nile, Zika, and dengue.”

A presentation looking at emergency preparedness from a climate perspective will be especially topical, and not just for obvious reasons, Dr Benjamin told Medscape Medical News.

“When a hurricane hits, everyone is focused on the impact on a hospital system,” he explained, “but at the end of the day, the big impact is on practicing clinicians and their offices.”

An example of this is the damage done to the primary care network in Houston, where major flooding followed Hurricane Harvey in August. “Rebuilding that is going to be difficult,” he said.

When a hurricane hits, everyone’s focused on the impact on a hospital system, but at the end of the day, the big impact is on practicing clinicians and their offices.

Plenaries will also focus on climate change, from a primer explaining the phenomenon to a session on how hospitals and health systems are reducing their individual carbon footprints, Dr Benjamin said.

Dr Padmini Murthy

The plan is to look at the impact climate change will have on “global health — whether related to policies, communities, or health outcomes,” Padmini Murthy, MD, from New York Medical College in Valhalla, who is the APHA program planner for international health

Dr Murthy added that she is looking forward to spending time with meeting attendees who hail from dozens of countries and approach public health problems in unique ways.

“It reiterates the fact that people are working in different ways to promote health, some of which are successful and can be replicated,” she told Medscape Medical News.

Other public health topics — ranging from opioid addiction to gun violence, healthcare equity, tobacco, and vaccines — will be addressed in presentations, roundtables, poster sessions, and panel discussions.

And a global public health film festival will be airing documentaries and short clips that highlight topics such as the environmental impact of coal mining, sex trafficking, cyber bullying, and the harms of pornography.

APHA Live, a new feature this year, will allow viewers from around the world to attend some sessions virtually, and to earn continuing education credit while doing so.

Dr Isis Mikhail

“APHA is taking advantage of technology to provide the option of virtual meeting attendance live and on demand,” said Isis Mikhail, MD, DrPH, from the National Institute on Aging, who is the APHA program planner for aging and public health.

“This is a great advantage, particularly for public health professionals who are unable to attend the meeting,” Dr Mikhail told Medscape Medical News.

Meanwhile, those who travel to Atlanta can take advantage of Learning Institutes, half- or full-day courses that offer an interactive educational experience. Topics covered will include leadership in complex public health systems, population health and the future of healthcare, and public health law.

And attendees wanting to take a mental or physical break can visit the Wellness Center, which will offer activities such as yoga, games, meditation, stretching, and massages.

The APHA engages in a “public policy process” in each city in which it holds its annual meeting. Despite attempts to become a smoke-free city, Atlanta has fallen short of this goal, Dr Benjamin reported, so the APHA has drafted a letter to local officials, urging them to complete the transition.

Dr Benjamin, Dr Murthy, and Dr Mikhail have disclosed no relevant financial relationships.

Follow Medscape on Twitter @Medscape and Maureen Salamon @maureensalamon

Source link

Unique Drug Combo Promising for Severe, Intractable Pain

Unique Drug Combo Promising for Severe, Intractable Pain

SAN DIEGO — Low doses of the hormone oxytocin along with the anesthetic ketamine may provide a unique and effective therapeutic approach to some patients with severe, intractable pain

This therapeutic approach is “incredibly unique” and is safe and effective in some patients with intractable pain. “If you put these two together, you could replace any short-acting opiate,” Caron Pedersen, FNP-C, DC, BSN, BS-PT, a nurse practitioner, chiropractor, and physical therapist specializing in patients with spinal pain, told Medscape Medical News.

Dr Caron Pedersen

Dr Pedersen has been working with pain management expert, Forest Tennant, MD, DPH, Veract Intractable Pain Clinic, West Covina, California, to find better ways to treat patients with very severe pain.

Such patients, said Dr Pedersen, “are pretty much opioid-dependent and have been for long time, and are not getting relief.”

Dr Pedersen presented some of her research here at the Academy of Integrative Pain Management (AIPM) 28th Annual Meeting.

Alternative to Opioids?

A variety of antiseizure, antidepressant, and anti-inflammatory agents, as well as muscle relaxants and adrenergic blocking agents, provide mild to moderate pain relief. But these approaches are not always a substitute for opioids in patients with severe pain.

Both oxytocin and ketamine provide analgesia by mechanisms other than stimulating opioid receptors.

Produced in the hypothalamus, oxytocin is a potent natural pain reliever. The hormone is released in pregnant women during labor and also in other painful conditions or stressful events.

It has been reported to relieve pain in patients with headache, chronic back pain, and fibromyalgia, and there is “a mountain of research” on oxytocin’s complex production, release, and receptor system, said Dr Pedersen.

Dr Tennant explained that some of the hormone is released into the peripheral circulation via the posterior pituitary and some into the central nervous system, including the spinal fluid.

Oxytocin receptors are found at multiple sites in the brain and throughout the spinal cord, said Dr Tennant. In addition to activating its own receptors and decreasing pain signals, oxytocin binds to opioid receptors and stimulates endogenous opioid release in the brain.

In addition to relieving pain, oxytocin lowers serum cortisol and can produce a calming effect and improve mood.

“It has the effect of making people happy, making them feel a little less anxious,” said Dr Pedersen. “It changes the central nervous system; it makes the hypothalamus pump out chemicals that are telling the body it’s okay, calm down.”

Oxytocin can block “anticipatory pain,” added Dr Pedersen. Patients with intractable pain are constantly waiting for “the next burse of pain” so are “in constant stress,” she said.

However, when they take oxytocin, “they may actually get a lot of relief based on the fact that they are no longer having that anticipation.”

Pain Free, No Side Effects

The investigators are working to determine optimal doses and routes of administration for oxytocin. They have experimented with combining oxytocin with low-dose naltrexone, benzodiazepines, neuropathic agents, opioids, and now ketamine, an N-methyl-D-aspartic acid receptor antagonist.

There has been a resurgence of interest in ketamine as a possible therapy for chronic pain conditions, including neuropathic pain, complex regional pain syndrome, fibromyalgia, postherpetic neuralgia, migraines, and spinal cord injury. 

At relatively high doses, ketamine has significant psychomimetic and euphoric properties that have led to abuse. Oral ketamine, sometimes called Special K, has become a popular nightclub drug.

Dr Tennant and Dr Pedersen have been experimenting with low-dose ketamine added to oxytocin in patients with the most severe intractable pain.

The study they presented at the AIPM meeting included five such patients (mean age, about 40 years) who had used oxycodone, morphine, hydrocodone, or hydromorphone for over a year.

Patients had not taken their short-acting opiate for several hours when they received 0.5 mL (2 mg — half of a syringe, or 20 units) of liquid oxytocin sublingually. Within 10 minutes, all five patients reported varying degrees of pain relief.

About 15 minutes after receiving the oxytocin, patients then received 0.25 to 0.50 mL (12.5 to 25 mg) of liquid ketamine, also sublingually.

The ketamine enhanced the pain relief. With the combination, two patients became completely pain free. These patients would “positively not” have been pain free with opioids, said Dr Pedersen.

The pain relief lasted about 4 hours with no side effects.

The Worst of the Worst

Dr Pedersen said the study patients were “the very worst” of pain patients. In her clinic, many patients suffer intractable pain — pain that never completely goes away with surgery or with drugs. “Some have had, say, seven or eight back surgeries and they have so much inflammation in their spine.”

Some are battling an autoimmune disease, such as lupus. Others have arachnoiditis, an incurable inflammatory condition of the arachnoid mater, the middle layer of the meninges.

Because oxytocin is a hormone, its pain-relieving ability varies from patient to patient and its effectiveness is related, among other things, to blood levels, pain severity, and sex. 

In her experience, Dr Pedersen has found that men tend to have a better response to the combination of oxytocin and ketamine than women.

But women also respond “fabulously,” she said. She described one 38-year-old female patient in her practice with a disc herniation who had been taking opioids, which were not helping her much. “She stopped taking them when she started using this combination therapy.”

Other patients have been able to cut back on opioids “significantly enough that if they had to stop taking them, they would be okay,” said Dr Pedersen.

The combination therapy may also address the issue of addiction, said Dr Pedersen. Some of her patients had become addicted to opioids, but after using the oxytocin-ketamine regimen, they’re not craving or abusing opioids.

The liquid form taken sublingually provides “the best delivery system” and is much more effective than pills, said Dr Pedersen.

Although liquid oxytocin typically has a shelf life of only about 10 days, Dr Pedersen has found pharmacies that put the hormone in a suspension that lasts for 3 months.

Intriguing Results

Commenting on the research for Medscape Medical News, Charles E. Argoff, MD, professor of neurology, and director, Comprehensive Pain Center, Albany Medical College, New York, said it “provides intriguing results.”

However, he said, a single-center open-label study of only five patients “is insufficient to draw any conclusions.”

While the use of oxytocin as an analgesic is supported by basic science, “this study does not add significantly to the human studies already completed, given its size and design,” said Dr Argoff.

Adding ketamine “dampens enthusiasm” for this therapeutic approach because of concerns about dependency and side effects, said Dr Argoff.

Adverse effects of ketamine can include nausea, headaches, fatigue, and dysphoria.

The authors have disclosed no relevant financial relationships.

Academy of Integrative Pain Management (AIPM) 28th Annual Meeting. Abstract 24. Presented October 21, 2017. 

For more Medscape Neurology news, join us on Facebook and Twitter

Source link

Key Elements in the 'Palliative Care Syringe' Identified

Key Elements in the 'Palliative Care Syringe' Identified

SAN DIEGO, California ― Palliative care that is integrated early into the oncology care regimen improves quality of life (QOL), mood, and the delivery of end-of-life care for patients with advanced cancer. However, it has been unclear which specific elements of palliative care practice are associated with these beneficial outcomes.

Now come the results of the first known study to address this subject. The study was presented here at the Palliative Care in Oncology Symposium (PCOS) 2017.

The investigators report that the consistent hallmarks of palliative care are addressing coping skills, which may improve QOL and depression, and managing symptoms, which is tailored to unique patient needs.

“People commonly ask, ‘What is it in the palliative care syringe? What is it that we actually do?” said lead author Michael Hoerger, PhD, an assistant professor of psychology, psychiatry, and oncology at Tulane University School of Medicine and the Tulane Cancer Center, New Orleans, Louisiana.

To answer those questions, Dr Hoerger and his colleagues conducted a study that aimed to determine the key elements of early palliative care across the illness trajectory.

The cohort included 171 patients with incurable lung or noncolorectal gastrointestinal cancer. The patients were randomly assigned to receive early palliative care integrated with standard oncology care. Patients completed measures of quality of life (Functional Assessment of Cancer Therapy–General [FACT-G]) and mood (the Hospital Anxiety and Depression Scale [HADS] and the Patient Health Questionnaire–9 [PHQ-9]) at baseline and at 24 weeks.

In addition, palliative care clinicians completed electronic post-visit surveys that documented the content of each visit. The authors assessed when the visit covered key content areas (rapport, symptom management, coping), and they examined variations in visit content over time.

A total of 2921 visits took place. The typical patient experienced at least 17 visits, and most patients had more than three visits.

The average time per visit was about half an hour. Of the total cohort, 83% were outpatients, and 10% were inpatients (10%). Seven percent of the patients participated in in-depth telephone visits (7%).

Oncologists attended 23% of the visits and attended at least one visit for 84% of the patients.

“Over time, palliative care visits were consistently focused on symptom management and helping patients cope with life-threatening disease,” said Dr Hoerger.

Rapport was another important element and was particularly helpful at the beginning of the palliative care regimen. Dr Hoerger pointed out that 100% of clinicians reported that they focused their time on establishing rapport during the initial visit. As rapport was established, it became less important over time.

Understanding of illness was also an important element. Although the importance of understanding illness was steady over time, less attention was paid to it than with coping with illness.

“Then the more ‘difficult’ topics, such as treatment decisions, advance care planning, and discharge disposition, got less focus than other topics but received more attention during the patient’s final three visits,” he said.

Most visits were focused on coping (64.2%) and symptom management (74.5%). At 24 weeks, patients for whom a higher percentage of visits were focused on coping experienced an improvement in QOL (FACT-G QOL: B = .19, P = .02), and depression (PHQ-9 Depression: B = -.22; P = .004; HADS Depression: B = -.26, P = .002; PHQ-9: P = .005).

Interestingly, symptom management was associated with worsening in QOL, depression, and anxiety during this period (FACT-G QOL: B = .-19, P = .02; PHQ Depression: B = .20, P = .01; HADS Anxiety: B = .17, P = .02). “We would hope that focusing on symptom management would lead to some discernable improvements in outcomes, but this is more consistent with clinicians attending more to symptoms among patients experiencing declines,” Dr Hoerger explained.

In cases in which a higher percentage of visits focused on treatment decisions, there was a reduction in the odds of patients receiving new chemotherapy (OR =.56, P = .02), undergoing hospitalization (OR = .62, P = .001), or being admitted to the emergency department ( P = .04) in the 60 days prior to death.

Advance care planning was associated with increased odds of receiving hospice care (OR, 1.85, P = .02) and of death at home (OR, 1.35, P = .04). “This association was also consistent with the hypothesis that clinicians may promote comfort at death through advance care planning,” Dr Hoerger noted.

The Individual Patient

In a discussion of the study, Keith M. Swetz, MD, an associate professor of medicine at the University of Alabama and section chief of palliative care, Birmingham VA Medical Center, noted that this study sought to gain a clear understanding of what palliative care is and how it works.

The authors identified what they saw as key elements that are essential to good palliative care, he noted.

“But what makes a successful palliative care intervention may or may not include those interventions,” Dr Swetz said. “It really comes down to the patient, and while we are looking for some consistency, we are dealing with individual patients with individual needs.

“We want to make sure that we address their needs and give them the opportunity to have those needs met,” he added.

Dr Swetz also pointed out that it is necessiary to identify goals of care. “What may be needed for one patient may not be helpful for another, and not effective,” he said. “We really need a clear understanding of what their goals are in order to design patient-centered care.”

A Louisiana clinical and translational science visiting scholar grant was funded by the National Institute of Nursing Research and the National Institute of General Medical Sciences. Dr Hoerger and Dr Swetz have disclosed no relevant financial relationships.

Palliative Care in Oncology Symposium (PCOS) 2017. Abstract 154, presented October 27, 2017.

For more news, join us on Facebook and Twitter

Source link

Metabolic Rate Equations Overestimate Caloric Needs for Blacks

Metabolic Rate Equations Overestimate Caloric Needs for Blacks

WASHINGTON, DC — Commonly used resting metabolic rate equations overestimate an individual’s caloric needs, particularly for African Americans, new research shows.

The findings were presented October 30, 2017 here at Obesity Week 2017 by James Reneau, BS, a third-year medical student at the Medical College of Wisconsin, Milwaukee.

Mr Reneau and colleagues compared resting metabolic rate measured by the gold standard — indirect calorimetry, which is impractical in the clinic — with those estimated by three commonly used clinical formulas that incorporate height, weight, gender, and age, but not race.

These equations — all decades old — are widely used in clinical settings such as by dieticians and in weight-loss clinics for estimating resting metabolic rate, and from that, daily caloric needs and the necessary daily deficit in order to lose weight are calculated.

But, he noted, “It was our observation that many patients will fail to lose weight despite strictly adhering to dietary restrictions based on these equations.”

Among 79 white and 36 African American subjects, the Mifflin (Am J Clin Nutr. 2009;51:241-247), Harris-Benedict (Proc Natl Acad Sci. 1918;4:370–373), and Cunningham (Am J Clin Nutr. 1980;33:2372-2374) all overestimated caloric needs overall, but to a much greater degree among African Americans, amounting to the equivalent extra calories of about a can of sugared soda every day or a pound of fat every 12 to 15 days. “It was quite a big difference,” Mr Reneau commented during his presentation.

The study also suggested that the addition of variables such as respiratory quotient, lean body mass, total fat mass, race, and hip circumference could improve the accuracy of future equations for estimating resting metabolic rate.

Asked to comment, obesity expert Steven B Heymsfield, MD, professor of medicine at the Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, said “This study shows that African Americans have lower metabolic rates than whites for the same weight, height, and age.…I think it’s very important to know that because then we’re overestimating how many calories blacks should be eating.”

Moreover, Dr Heymsfield added, “There’s been a lot of research over the years looking at these kinds of prediction equations in whites,” but much less in blacks. “We need more research in black populations, with very carefully measured metabolic rates.”

In the meantime, he said, clinicians could advise black patients to consume 10% fewer calories than they would normally recommend based on the current equations, taking into account the usual amount of physical activity per day.

Large Overestimation of Calorie Needs in Black Subjects

Mr Reneau and colleagues measured resting metabolic rate in the 115 healthy fasted subjects using indirect calorimetry and used dual-energy X-ray absorptiometry to assess lean body mass, total fat mass, and estimated visceral adipose tissue.

The 36 black and 79 white subjects differed significantly by percent female (53% of blacks were women vs 75% of whites, respectively), age (35 vs 50 years), and waist circumference (101 vs 113 cm) (P < .05 for all), but there was no significant difference between the races in body mass index (33 vs 36 kg/m²).

The white group also had significantly higher total fat mass, percent fat mass, and respiratory quotient (P < .05 for all).

Measured resting metabolic rates by indirect calorimetry were 1663 kcal/day for whites and 1554 kcal/day for African Americans. For the white subjects, the three equations overpredicted those values by 40 to 120 kcal/day (5%-10%), with only the Harris-Benedict reaching statistical significance (P < .0001).

However, the equations overestimated resting metabolic rates among the black group to a much greater extent, by 12% to 18%, ranging from 190 kcal/day for the Mifflin to 282 kcal/day for the Harris-Benedict, an equation that was published in 1918 and still in use today.

Overall, the difference between the measured and predicted resting metabolic rates were highly statistically significant (P < .0001).

Clinical Variables Could Improve Prediction

In linear regression analysis, negative predictors of resting metabolic rate included age, race, height, and respiratory quotient, while lean and fat mass were positive predictors. There were no significant predictors for resting metabolic rate that differed between white and African American subjects, Mr Reneau noted.

In a second analysis using only significant (P < .05) variables that are routinely measured in clinical practice, age, race, sex, and hip circumference were negative predictors while weight was a positive predictor.

For example, a weight increase of 1 kg equated to a 15.6-kcal increase in resting metabolic rate, while aging 1 year corresponded to a 5.2-kcal decrease. African Americans had a 148-kcal lower metabolic rate than did whites, and females had 118-kcal lower resting metabolic rates than males.

Dr Heymsfield told Medscape Medical News that although previous studies had shown in general that the equations tend to overestimate resting metabolic rate, “the effect in blacks is real. It’s been seen in other studies but not so clearly as in this one.”

As to why, he said the most likely mechanism is differences in body structure, with black individuals tending to have “more muscle and bone and less metabolically active organs for same height, weight and age. We all differ. There are probably evolutionary differences.…I think we have to have equations for predicting energy requirements that are race-specific.”

 Mr Reneau and Dr Heymsfield have no relevant financial relationships. Dr Heymsfield was formerly global director of scientific affairs at Merck.

Obesity Week 2017. October 30, 2017; Washington, DC. Abstract T-OR-2003

For more diabetes and endocrinology news, follow us on Twitter and on Facebook.

 

Source link

EXCEL: PCI, CABG Offer Similar Quality of Life at 3 Years

EXCEL: PCI, CABG Offer Similar Quality of Life at 3 Years

DENVER, CO — Although PCI treatment of left main disease carries a higher risk of repeat revascularizations, quality of life (QoL) is comparable to CABG surgery through 3 years, according to new results from EXCEL^[1].

Not surprisingly, PCI resulted in significantly better health status on all QoL scales at 1 month. But by 12 and 36 months, there were no significant differences between PCI and CABG in QoL measures assessing angina, dyspnea, or general health concerns like pain, mobility, and depression.

“Taken together with the 3-year clinical data from EXCEL, these results suggest that PCI and CABG provide comparable intermediate-term outcomes for appropriately selected patients with left main coronary artery disease,” Dr Suzanne J Baron (St Luke’s Mid America Heart Institute, Lee’s Summit, MO) reported in a late-breaking trial session here at TCT 2017 and in the Journal of the American College of Cardiology.

At last year’s meeting, the question of whether drug-eluting stents should be preferred over CABG in patients with left main disease met with conflicting data from EXCEL and NOBLE.

Perhaps the most provocative finding in the new substudy is the lack of a significant signal for greater anginal relief with CABG, a benefit that emerged at 3 years and remained at 5 years in both the FREEDOM and SYNTAX trials, Baron told theheart.org | Medscape Cardiology.

The 5-year health status assessment for EXCEL has been canceled due to budget constraints, but “my guess is we wouldn’t see that much difference at 5 years, but it’s hard to know, and we may never know,” she added.

Dr Davide Capodanno (University of Catania, Italy) was among several panelists who congratulated the authors for bringing patient-reported outcomes to the main arena, “because there is more and more understanding that these kinds of outcomes are as important as clinical outcomes.”

He said the earlier recovery with PCI is not surprising but agreed “the novelty here is that if you put these results into the perspective of FREEDOM and SYNTAX, you see that these angina differences have been really blunted and nullified in this trial.”

“We remember with the [plain-old-balloon angioplasty] POBA era, the [bare-metal stent] era, the first-generation routine stent era, there was this difference in anginal relief with CABG, and now it’s blunted, disappeared actually. So it’s very beautiful to see this in the natural history of what we do with PCI,” he added.

EXCEL randomized 1905 patients with low or intermediate-risk SYNTAX scores (<32) to a second-generation everolimus-eluting stent (Xience, Abbott Vascular) or CABG with or without pulmonary bypass.

With complete 3-year clinical follow-up now available, outcomes remained relatively unchanged in terms of the primary outcome or its components, although there was a significantly higher rate of repeat revascularizations with PCI vs bypass surgery (12.5% vs 7.5%; P<0.01) and a trend for higher all-cause mortality (8.0% vs 5.8%; P=0.08).

This trend was highlighted in a press briefing on the study, with Baron remarking that rates of cardiovascular mortality were roughly identical between the PCI and CABG groups and that the benefit for all-cause mortality with CABG might be a statistical blip.

Among the 1788 patients in the QoL substudy, PCI-treated patients had higher scores on several Seattle Angina Questionnaire (SAQ) subscales at 1 month compared with CABG, but there were no significant differences by 12 and 36 months.

Similar to the SAQ findings, 60% of PCI-treated patients vs 44% of CABG-treated patients had dyspnea at 1 month as measured by the Rose Dyspnea Scale (P<0.01), but those differences were no longer significant by 12 months (49% vs 46%; P=0.40) and 36 months (43% vs 42%; P=0.77).

PCI-treated patients also had more rapid improvements on generic health-status measures including the 12-item Short Form Health Survey physical and mental summary components.

Using the more specific Patient Health Questionnaire (PHQ)-8, a truncated version of the PHQ-9, the percentage of patients categorized as having clinically significant depression was significantly lower with PCI than CABG at 1 month (8% vs 19%; P<0.01) and at 12 months (8% vs 12%; P=0.03) but not at 36 months (9% vs 8%; P=0.77).

Panelist and NOBLE principal investigator Dr Evald Christiansen (Aarhus University Hospital, Denmark) said they did not collect QoL outcomes in NOBLE but that the current data will be helpful when presenting left main treatment strategies to patients.

“I think this goes in favor of PCI in left main disease, and also the less depression with PCI is an important finding,” he said.

In subgroup analyses at 3 years, there was a suggestion of an interaction between angina relief and baseline SYNTAX score, but it was in a counterintuitive direction, with CABG appearing to provide greater benefit among patients with a low SYNTAX score and no difference in those with intermediate or high SYNTAX scores (mean treatment effect of PCI vs CABG -3.3, 0.8, and -0.2 points, respectively), Baron said. However, this finding did not achieve the prespecified statistical significance level of P=0.01 (P for interaction=0.03), and all other subgroup analyses including baseline angina frequency were negative, she added.

Cappadano said play of chance of could justify why the low-risk SYNTAX score shows a counterintuitive effect for CABG but that it is important to look further at the subgroup analyses.

Overall, panelist Dr John Spertus (St Luke’s Mid America Heart Institute) said the substudy provides physicians with an ideal opportunity to give patients a choice between an earlier recovery with angioplasty vs very similar outcomes in the long term with angioplasty or bypass.

“So for me, this helps me feel that angioplasty for less complex coronary disease is really probably the preferred option,” he said.

He noted that patient- and clinician-reported outcomes that measure how patients feel or function were recognized earlier this year as medical device development tools (MDDT) by the US Food and Drug administration, which recently designated the 23-item Kansas City Cardiomyopathy Questionnaire as an MDDT for use in patient-reported heart-failure outcomes.

Dr Roxana Mehran (Icahn School of Medicine at Mount Sinai, New York, NY), who chaired the press briefing, observed that guidelines are usually driven by clinical end points, not quality of life. “But hopefully we can change that, because I do think it’s an incredibly important area for our patients to bring the patient into this shared decision-making.”

Finally, Drs Daniel B Mark and Manesh R Patel (Duke Clinical Research Institute, Durham, NC) write in an accompanying editorial^[2] that what patients want to know is the overall treatment experiences and responses “for people like me,” but that trial and meta-analysis data instead provide complex, disaggregated information for a hypothetical average patient.

Compounding the problem is that patients often arrive with preexisting preferences based on unrealistic beliefs about the benefits of revascularization that are not easily corrected.

“However, if we are really serious about moving to a patient-centric model of medicine, we need to meet patients where they are in understanding and answer the existential questions that matter most to them. Although much work on this has already been done, EXCELlence is still a long way off,” Mark and Patel conclude.

EXCEL and the quality-of-life substudy were funded by a research grant from Abbott Vascular. Baron reported consulting income from Edwards Lifesciences and St Jude Medical. Disclosures for the coauthors are listed in the paper. Mark reported institutional grants from Eli Lilly, Gilead, AstraZeneca, Bristol Myers Squibb, Merck, and Oxygen Therapeutics. Patel reported institutional research grants from and serving as an advisory board member for Bayer, Jansen, and AstraZeneca. Capodanno reports receiving payments for consulting or honoraria from AstraZeneca, Bayer, Daiichi Sankyo, Eli Lilly, and the Medicines Company. Spertus founded Health Outcomes Sciences. Mehran previously reported grant support from/research contracts with Daiichi Sankyo/Eli Lilly, Bristol-Myers Squibb, AstraZeneca, the Medicines Company, OrbusNeich, Bayer, and CSL Behring; consultant fees/honoraria from or being on a speaker’s bureau for Janssen Pharmaceuticals, Osprey Medical, Watermark Research Partners, and Medscape; equity in Claret Medical and Elixir Medical; and other financial support from Abbott Vascular.  

Follow Patrice Wendling on Twitter: @pwendl. For more from theheart.org | Medscape Cardiology, follow us on Twitter and Facebook.

Source link