Sniffing Rosemary Can Increase Memory By 75%

Memory problems are becoming increasingly common, and medication seems to be the only way to fix it. Have you ever wondered how you could naturally treat memory problems?


“We wanted to build on our previous research that indicated rosemary aroma improved long-term memory and mental arithmetic. In this study we focused on prospective memory, which involves the ability to remember events that will occur in the future and to remember to complete tasks at particular times this is critical for everyday functioning,” said Dr. Mark Moss, one of the study conductors.

A series of tests were performed including one where the test subjects were placed into a room with a diffuser filled with four drops of Rosemary essential oil. After the amount of time, the subjects were asked to perform certain tasks including one where they were instructed to find certain objects and hand said objects over to instructors at a certain time. The results showed that the subjects placed into the rosemary scented room performed on the prospective memory tasks than the placebo group.

“These findings may have implications for treating individuals with memory impairments. It supports our previous research indicating that the aroma of rosemary essential oil can enhance cognitive functioning in healthy adults, here extending to the ability to remember events and to complete tasks in the future. Remembering when and where to go and for what reasons underpins everything we do, and we all suffer minor failings that can be frustrating and sometimes dangerous. Further research is needed to investigate if this treatment is useful for older adults who have experienced memory decline.”

Rosemary breaks down acetylcholine, a chemical found in the brain. This potentially allows nerve cells to communicate better with one another,

Rosemary has been linked to memory throughout history. Shakespeare said it best in Hamlet,” There’s rosemary that’s for remembrance: pray, love, remember.” It is also said that the Tudor house Of England believed Rosemary to enhance memory.

Shake Off the Sadness and Learn How to Be Happy Again

“Even a happy life cannot be without a measure of darkness, and the word happy would lose its meaning if it were not balanced by sadness. It is far better take things as they come along with patience and equanimity.” ~ Carl Jung

Shake off the Sadness and Learn How to Be Happy Again

We all go through painful experiences. We all have moments when we feel lost, sad, abandoned, betrayed, hurt, abused and unfairly treated. We have moment when we fall down, moments when things fall apart and we no longer seem to feel as happy, as courageous, as balanced and as cheerful as we used to. And even though it can be quite challenging to pick ourselves up, dust ourselves off, and start all over again, it’s very important that we do it. Why? Because if we don’t, we risk allowing a season of sadness, painful challenges and dark experiences to become a lifetime of unhappiness. We risk falling into depression and then living our entire lives from a dark, fearful and very cold place.

“Even if happiness forgets you a little bit, never completely forget about it.” ~ Jacques Prévert

Here are 7 things you can do to shake off the sadness and negativity from your life and learn how to be happy again:

1. Feel the pain but don’t mistake it for who you are

I remember talking to a friend of mine who was in a very dark and unhappy place for many months. She told me how during all that time she didn’t take care about anything or anyone. She stopped exercising, meditating, she stopped going out, stopped seeing her friends and family, she stopped taking care of her physical appearance and something that really shocked me, especially because she always described herself as a clean freak, she stopped cleaning her house. Yes! She didn’t feel like doing anything, and later on she realized that because she stopped taking good care of herself, she stayed in that state for way longer than she was supposed to.

You see, this what happens when you allow yourself to identify with the pain you are feeling and become one with it. You forget how to be happy and you allow your mind to trick you into thinking that your life is over just because something bad happened along the way.  Pain is just a feeling. it’s not who you are. It’s just something that we all feel from time to time, but not something we should identify ourselves with. So feel the pain, allow it to be there and to teach you what it has to teach you, but never identify yourself with it. 

2. Mobilize yourself

Even though it may feel quite challenging at times to do the things that you usually do when you feel happy and full of life – physical exercise, meditation, creative work, socializing with friends, gardening, spending time in nature, playing with your pet or children, etc., you have to do it. You have to push yourself to do the things that you don’t feel like doing so that you can shake off  the sadness, boost your energy, increase your happiness levels and regain your appetite for life. Don’t allow your mind to make you think that you should sink deeper into the pain you are feeling because if you do, the sadness will soon turn into a very thick darkness and you might end up mistaking your sadness with depression!

3. Never ever call yourself “depressed”

Never ever tell yourself or anyone else that you are “depressed. The word “depression” is a very heavy one and has such a negative charge. You don’t want to bring all that negativity upon you, nor do you want to have its heavy weight pressing on your shoulders. It’s normal to feel sad, to feel hurt, to feel pain, but if you start calling yourself “depressed” and if you continue to repeat this nonsense to yourself, soon enough your occasional sadness will become a depression.

4. Come back into the present moment

Bring yourself back into the present moment by constantly focusing on your breath. On an inhale, mentally count to 4 as you breathe in, then exhale to the count of 5. Do this as often as possible and in time you will realize how much power lies in your breath and how much your breath can help you to be happy again. 

5. Get bigger than your sadness

Whenever my mind leads me astray, and whenever I fall down into a “dark hole” feeling sad and drained of energy, and perceiving my negative moods as being way bigger than I am, I remind myself the story of David and Goliath, and I tell myself:

“Just as “little” David defeated the gigantic Goliath, so can you “defeat” your “giants”.  And then I do it. I “defeat them all… with LOVE :)

You are way bigger than any sadness and any problem you might be facing. And whenever you think otherwise, it’s only because you allowed your mind to think all kind of fearful thoughts that made you look very small in comparison with your problems. Don’t believe the nonsense your mind is often asking you to believe. Get bigger than your sadness and you’ll immediately know how to love your pain away and how to bring light to those places where there was once so much sadness and so much darkness.

6. Claim back your personal power

In his book, The Power of Now, Eckhart Tolle talk about how powerful our mind is, and how, if we don’t learn to use it, it will start using us: “The mind is a superb instrument if used rightly. Used wrongly, however, it becomes very destructive. To put it more accurately, it is not so much that you use your mind wrongly—you usually don’t use it at all. It uses you. All the things that truly matter — beauty, love, creativity, joy, inner peace — arise from beyond the mind…”

Don’t allow your mind to drag into the most painful, dark and cold places by believing every fearful and toxic thought you think. Know that you are in control of your own life, not your mind. Take authority over your thought and feelings and learn to differentiate between the thoughts that are real and the ones that are not.

7. Appreciate yourself into life

“Gratitude unlocks the fullness of life. It turns what we have into enough, and more. It turns denial into acceptance, chaos to order, confusion to clarity. It can turn a meal into a feast, a house into a home, a stranger into a friend.” ~ Melody Beattie

In the same way you would want the world to love and appreciate you, learn to love and appreciate yourself. Stop bullying yourself. Let go of the need to constantly repeat to yourself that you should be feeling a lot better by now, and that it’s not normal to feel sad for so long, and just be kind to yourself. Be gentle with yourself. Treat yourself with compassion and instead of complaining about all the things you think you’ve done wrong, appreciate yourself for all the things you did right. Appreciate yourself for your strength, your courage and your resilience. Open your eyes, your heart and your mouth and start appreciating the beauty, the perfection and the splendor of who you.

Appreciate yourself into life.

Look at yourself, your life… all the things you’ve built, crafted and experienced, and everything you’ve been through and learn to express your gratitude and appreciation for all of them. You’ve went through a lot, and you deserve to be appreciated. You deserve to be acknowledged and you deserve to be loved.

Mild Kidney Disease Tied to Adverse Pregnancy Outcomes

Across all stages of kidney disease, the risk for adverse pregnancy outcomes increases, according to a prospective observational study published online March 12 in the Journal of the American Society of Nephrology. Yet the data also indicate that good maternal–fetal outcomes are possible even in the presence of advanced disease.

These findings may be useful for counseling and monitoring affected women during pregnancy, note researchers led by nephrologist Giorgina Piccoli, MD, from San Luigi University Hospital, University of Turin, Italy.
The Torino-Cagliari Observational Study (TOCOS) compared pregnancy outcomes in 504 women with chronic kidney disease (CKD) with those in 836 well-matched low-risk women. The mean age of mothers with CKD in Turin and Cagliari was 31.9 years, and the mean age of the controls in both centers was 29.9 years. The majority of participants were white, and more than half of patients and control participants were nulliparous (56.2% and 58.1%, respectively).

Baseline assessments included hypertension, proteinuria (>1 g/day), systemic disease, and CKD stage at referral. The researchers followed the women, noting adverse outcomes including caesarean section, preterm delivery (<37 weeks), early preterm delivery (<34 weeks), small size for gestational age (SGA), neonatal intensive care unit (NICU) use, new onset of maternal hypertension, new onset or doubling of proteinuria, and CKD stage shift. In addition, they assessed the pregnancies for general combined outcome (preterm delivery, NICU, SGA) and severe combined outcome (early preterm delivery, NICU, SGA).

The risk for adverse outcomes increased in stepwise fashion across all disease stages. For stage 1 vs stages 4 to 5, the general combined outcome was 34.1% vs 90.0%; the severe combined outcome was 21.4% vs 80.0% (P < .001).

In stage 1 CKD, preterm delivery was associated with baseline hypertension, systemic disease, and proteinuria. However, even after adjusting for these classic risks, stage 1 CKD remained associated with adverse pregnancy outcomes even in women without baseline hypertension, proteinuria, or systemic disease (odds ratio, 1.88; 95% confidence interval, 1.27 – 2.79) compared with women in control group.

In terms of specific maternal–fetal outcomes, in women with stage 1 CKD, the rate of caesarean section was 48.4% vs 70.1% for stage 2, 78.4% for stage 3, and 70.0% for stages 4 to 5 (P < .001). Preterm delivery rate was 23.5% for stage 1 vs 50.6% for stage 2, 78.4% for stage 3, and 88.9% for stages 4 to 5 (P < .001). NICU rates by stage were 10.3%, 27.6%, 44.4%, and 70.0% (P < .001). SGA (<10%) by stage was 13.3%, 17.9%, 18.9%, and 50.0% (P = .023). General combined outcome ranged from 34.1% to 90.0% (P < .001), and severe combined outcome from 21.4% 80.0% (P < .001).
New-onset maternal hypertension ranged from 7.9% in stage 1 to 50.0% in stages 4 to 5 (P < .001). New-onset or doubling of proteinuria was 20.5% in stage 1 and 70.0% in stages 4 to 5 (P < .001).

The risk for intrauterine death did not differ between patients and controls.

“Renal function matters, and its effect is likely to be continuous: considering only the cases with a live-born baby, our data confirm a stepwise increase in pregnancy-related risks from stage 1 to stage 4-5,” the authors write. “Interestingly, there is a significant increase in risk from stage 1 to stage 2 CKD, which represents a sort of ‘gray’ area with regard to kidney function.”

The authors also note that the TOCOS data contrast with the data from a 2009 population-based study that found no additional risk with a mild reduction in glomerular filtration rate, thus suggesting that the clinical definition of CKD is more complex than the mere evaluation of glomerular filtration rate.

They recommend that clinicians take special care when treating pregnant women with CKD, even in the absence of known risk factors.

Commenting in an American Society of Nephrology press release, lead author Dr Piccoli said, “The findings indicate that any kidney disease — even the least severe, such as a kidney scar [from] a previous episode of kidney infection, with normal kidney function — has to be regarded as relevant in pregnancy, and all patients should undergo a particularly careful follow-up.” She added that “a good outcome was possible in patients with advanced CKD, who are often discouraged to pursue pregnancy.”

MSSA Bloodstream Infection: Beta-Lactams or Vancomycin?

Beta-lactams are superior to vancomycin for definitive therapy, but not empiric treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infection, according to a large retrospective study.

Jennifer S. McDanel, PhD, from the University of Iowa in Iowa City and the Iowa City Veterans Affairs Health Care System, and colleagues published their findings online April 21 in Clinical Infectious Diseases.

Although prior research has linked vancomycin therapy to poor patient outcomes such as recurrence, treatment failure, and death, the validity of this construct with respect to empiric therapy has remained unclear.

“Vancomycin is often prescribed empirically for patients suspected of having S. aureus bloodstream infections since it has activity against both methicillin-resistant and methicillin susceptible strains,” the authors write.
“However, for a patient infected with [MSSA], organizations such as the Infectious Diseases Society of America…recommend switching therapy to a beta-lactam, such as cefazolin or an antistaphylococcal penicillin (nafcillin or oxacillin) once the isolate is known to be MSSA.”

Accordingly, the researchers analyzed data for MSSA culture-positive patients at 122 Veterans Affairs hospitals who received either a beta-lactam or vancomycin alone as empiric therapy (n = 2659 and 3125, respectively) or definitive treatment (n = 4698 and 935, respectively) during 2003 to 2010.

The researchers defined empiric therapy as treatment started 2 days before through 4 days after collection of the first culture positive for MSSA; definitive therapy started 4 to 14 days after collection of the first culture positive for MSSA.

Empiric use of beta-lactam monotherapy had no effect on 30-day mortality compared with vancomycin (hazard ratio [HR], 1.03; 95% confidence interval [CI], 0.89 – 1.20).

As expected, however, definitive therapy with a beta-lactam rather than vancomycin was associated with a significant 35% decrease in 30-day mortality (HR, 0.65; 95% CI, 0.52 – 0.80), with use of cefazolin or an antistaphylococcal penicillin yielding further benefit (HR, 0.57; 95% CI, 0.46 – 0.71).
Although the researchers made adjustments for variables such as age, dialysis/end-stage renal disease, Acute Physiology and Chronic Health Evaluation (APACHE) III score, and Charlson Comorbidity index, the authors note that the findings may be limited by the elderly nature of the study population, and some of the reported deaths may not have been attributable to MSSA. In addition, the researchers did not stratify the definitive therapy analysis by empiric therapy, and therefore did not account for potential switching-related survival benefits.

AVERT: Very Early Mobilization Harmful in Stroke

A very early and more intensive rehabilitation program was associated with a reduced likelihood of achieving a favorable outcome at 3 months vs usual care in the first large-scale randomized trial of rehabilitation therapy in patients with acute stroke.

The AVERT study results were presented by Professor Julie Bernhardt, PhD, Florey Institute of Neuroscience and Mental Health, Heidelberg, Victoria, Australia, at the inaugural European Stroke Organisation (ESO) Conference 2015. They were also simultaneously published online in The Lancet.

“Our data show that an early, lower-dose out-of-bed activity regimen is preferable to very early, frequent, higher-dose intervention,” Professor Bernhardt concluded.

“This was an unexpected and intriguing result,” she added. “But it tells us something very important. Earlier intensive rehabilitation was significantly worse than usual care. We have to listen to that.”
Professor Julie Bernhardt
She said that preclinical work and previous smaller studies have suggested that more intensive earlier rehabilitation would be beneficial. “But our results suggest we need to do more work to look at what is the right time for the brain to be challenged with this ‘out of bed’ intervention.”

To Medscape Medical News she commented that the study had only just finished and it was too premature to issue strong recommendations.
“It is very early days,” she said. “We will be coming up with clear recommendations for clinical practice, but for now we can say that earlier high-dose rehabilitation is not better than usual care, which in this study was still early but not quite as early or intensive as the more aggressive arm.”

“However, the challenge is not as simple as just recommending usual care, because usual care is complex and this study was also delivered early and varied from center to center, and we had 56 centers in 5 countries. We have to unpack this so we can give clinicians guidance about their practice and this will be the next step.”

She added: “We do know from previous studies that patients in stroke units who receive earlier rehabilitation than patients on general medical wards have better outcomes. So our message is not that patients should stay in bed for days.”

This was an unexpected and intriguing result.Professor Julie Bernhardt

Groundbreaking Trial

Even though the trial had a negative result, it is regarded as groundbreaking and was very well received by stroke physicians at the ESO conference, with Professor Bernhardt given a standing ovation after her presentation.

ESO president Professor Kennedy Lees, MD, University of Glasgow, described the trial as “a huge achievement.”

Keith Muir, MD, also from the University of Glasgow, said: “AVERT is a fantastic trial. It is hugely relevant for how we organize services.”

“Unfortunately they got a negative result but it shows that large rehabilitation trials comparing two different strategies are feasible so we know now that more trials like this can be done in the future,” Valeria Caso, MD, University of Perugia, Italy, and ESO president-elect, commented to Medscape Medical News. “Until now we haven’t had a scientific approach like this for evaluating rehabilitation.”

Dr Caso suggested that the worse outcome with very early more intensive rehabilitation was probably due to the patients still being hemodynamically unstable. “I think it shows that patients should not be moved too early — that passive mobilization is better in the first 24 hours.”

Asked why she thought this was the case, she replied, “Maybe the circulation needs some time to accept the new situation of brain trauma.”

Professor Bernhardt added: “In stroke, we don’t really understand the cascade that happens in the acute phase of stroke. It appears that the higher-dose, very early intervention may be interfering with the recovery process in some way.”

For the study, 2104 patients were randomly assigned to receive very early mobilization or usual care. Median time to randomization was 18 hours after stroke; 45% of patients had a moderate to severe stroke; 26% were older than 80 years; and 24% of patients had received tissue plasminogen activator.

The very early mobilization intervention included three crucial elements: (1) beginning within 24 hours of stroke onset; (2) focusing on sitting, standing, and walking (ie, out-of-bed) activity; and (3) resulting in at least three additional out-of-bed sessions to usual care.

Patients in the very early intensive group began mobilizing at a median of 18.5 hours after stroke compared with 22.4 hours in the usual care group, and they had a median of 6.5 sessions compared with 3 sessions in the usual care group. Patients in the very early intensive group received a median of 31 minutes of therapy per day vs 10 minutes in the usual care group; they received a total of 201 minutes of therapy compared with 700 minutes in the usual care group.

The primary outcome was functional independence, defined as a modified Rankin Scale (mRS) score of 0 to 2 at 3 months. This showed a significantly worse result in the very early intensive group.

Table. AVERT: Primary Endpoint

Endpoint Very Early Intensive Therapy (%) Usual Care (%) Odds Ratio (95% Confidence Interval) PValue
mRS score of 0 – 2 at 3 months 46 50 0.73 (0.59 – 0.90) .004


Eight percent of patients in the very early intensive group died compared with 7% of patients in the usual care group, and nonfatal serious adverse events occurred in 19% and 20% of patients, respectively. These differences were not significant.

Immobility-related complications also did not significantly differ between the two groups.

Subgroup analysis suggested that the higher-intensity earlier rehabilitation may have been more harmful in patients with intracerebral hemorrhage and more severe ischemic strokes. “But this was not statistically significant and we need look at this in more detail,” Professor Bernhardt said.

In the Lancet paper, the authors note, “Components of our intervention are already part of routine clinical care; therefore, understanding which components might affect outcome is a priority.”

They add: “By further exploration of this rich dataset, our trial provides the best opportunity yet to develop evidence-based guidelines for patients with stroke about the timing, frequency, and amount of out-of-bed activity to improve outcome (or prevent harm). Consequently, as outlined in our published statistical analysis plan, our next priority will be to undertake a dose–response analysis to establish the effect of dose of rehabilitation (rather than group) on efficacy and safety outcomes.”

Professor Bernhardt noted that it has been “notoriously difficult” to do rehabilitation trials, with previous studies having an average sample size of just 52 patients. “There are some trials of several hundred patients but we managed to recruit more than 2000.”

The trial did take 8 years to complete, however, which Professor Bernhardt attributed partly to starting the intervention so early.

“We wanted to randomize patients within 24 hours of stroke onset and the vast majority of patients don’t come into hospital in this time,” she said. “This is very problematic on many levels from a public health point of view, and also for conducting this trial. Future trials will probably look at slightly later timeframes and so should be quicker to recruit.”

Tonsillectomy Appears to Protect Against Tonsil Cancer

Having your tonsils out will get you ice cream ― and perhaps protection from tonsil cancer. The finding from a large Danish population-based study seems intuitive, but really had not been shown before.

But lead researcher Carole Fakhry, MD, of Johns Hopkins School of Medicine, Baltimore, Maryland, said she “would not encourage people to get a tonsillectomy” in the hope of reducing their risk for this type of oral cancer, which is rare. However, a “side benefit” of tonsillectomy might be the reduction in risk for these cancers, she told Medscape Medical News.

The study was published online April 20 in Cancer Prevention Research.
The incidence of oropharyngeal carcinoma, which includes cancers arising from the tonsils, oropharynx, pharynx, Waldeyers’ ring, and branchial cleft, is increasing globally, particularly in younger age groups, driven largely by sexually transmitted human papillomavirus (HPV) infection, Dr Fakhry and colleagues note in their article.

For example, about 77% of tonsil cancers in Denmark, which is the data source for the new study, occurring between 2000 and 2010 were related to HPV. At the same time, tonsillectomy for hypertrophic tonsils and recurrent tonsillitis has “lost previously held general acceptance,” they point out about Western countries.

“We are asked this question all of the time by patients: ‘Could I have prevented this [oropharyngeal cancer] by having a tonsillectomy?’ ” Dr Fakhry said.

So she and her colleagues decided to investigate.

Using data from 1977 to 2012 on more than 3.8 million adults in the Danish Cancer Registry, they analyzed the incidence of tonsillectomies and oropharyngeal carcinoma and whether tonsillectomy reduces the future risk for oropharyngeal carcinoma.
Since 1977, the incidence of tonsillectomy has fallen significantly (P < .001), most markedly after 1995, they report. The rate of tonsillectomy has declined by 1.1% annually, on average. During a 35-year period, this corresponds to a 33.8% decrease in the incidence of tonsillectomies.

During the same period, the incidence of oropharyngeal carcinoma increased “dramatically,” the researchers report.

Importantly, tonsillectomy was not associated with the risk for oropharyngeal carcinoma or cancer of other anatomic sites, including the base of tongue. However, tonsillectomy was associated with a 60% reduction in risk for tonsil cancer (rate ratio [RR], 0.40; 95% confidence interval [CI], 0.22 – 0.70).

“Notably,” say the researchers, the risk for diagnosis of tonsil carcinoma before age 60 years was significantly reduced after tonsillectomy (adjusted RR, 0.15; 95% CI, 0.06 – 0.41).

Tonsillectomy within 1 year of diagnosis of tonsil carcinoma was associated with significantly improved overall survival (hazard ratio, 0.53; 95% CI, 0.38 – 0.74).

“Tonsillectomy likely reduces the palatine lymphoid tissue susceptible to carcinogenic factors, and subsequent potential for malignant transformation,” the researchers say.

But again, they do not recommend prophylactic tonsillectomy for the general population. For one thing, tonsil carcinoma is rare, as noted above. If a biomarker of “high predictive value” for the development of oropharyngeal cancer could be identified, people with such a marker might benefit from tonsillectomy, although that would require study, they suggest.

“If early tonsil lesions could be identified through a combination of biomarkers for risk stratification, imaging, and cytologic evaluation, then tonsillectomy in a select well-defined population may reduce the incidence of tonsil carcinoma,” they add.

Limitations of the study include the lack of some “clinically relevant information,” including HPV tumor status, stage, and tobacco use, which introduces the potential for residual confounding, the researchers note.

Also, the limited number of oropharyngeal carcinoma cases overall (n = 52) and of tonsil carcinomas (n = 12) following tonsillectomy could imply that the observed associations were by chance. “Although the estimates of the effect of tonsillectomy may have low precision and relatively wide CIs, the significant point estimates are far from null and highly significant, therefore supporting a true association,” they say.

This study “provides the first insight into the association of tonsillectomy with risk of oropharyngeal cancers,” Anil Chaturvedi, PhD, with the Division of Cancer Epidemiology at the National Institutes of Health, notes in an accompanying editorial.

It shows “an ecologic correlation” between declining incidence of tonsillectomies in Denmark and rising oropharyngeal cancer incidence over time, he points out. Still, the question remains regarding the extent to which a decline in tonsillectomies has contributed to the rise in tonsil cancer incidence in recent years, he adds.

Echoing the authors, Dr Chaturvedi says, “at this time, prophylactic tonsillectomies should not be considered as a secondary prevention strategy for oropharyngeal cancers.”

“Although a common surgical procedure, tonsillectomy is not without minor complications, such as postoperative bleeding, pain, and nausea, as well as major complications, such as hemorrhage and death,” he writes.

WHO Issues Folate Recommendations for Women

Optimal red blood cell (RBC) folate concentrations should exceed 400 ng/mL in women of reproductive age to prevent neural tube defects (NTDs), according to World Health Organization (WHO) guidelines described in an article published in the April 24 issue of the Morbidity and Mortality Weekly Report.

“[NTDs] such as spina bifida, anencephaly, and encephalocele are serious birth defects of the brain and spine that occur during the first month of pregnancy when the neural tube fails to close completely,” write Amy M. Cordero, MPA, from the National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia, and colleagues.
“Randomized controlled trials and observational studies have shown that adequate daily consumption of folic acid before and during early pregnancy considerably reduces the risk for NTDs. The US Public Health Service recommends that women capable of becoming pregnant consume 400 μg of folic acid daily for NTD prevention.”

Although the WHO estimates the global incidence of NTDs at about 300,000 annually, the true count is unknown because many countries do not collect birth defects data.

The WHO issued the new recommendations to help countries lower the risk for NTDs by determining population risk and the need for prevention programs, as well as by implementing and assessing the effectiveness of such programs. Key strategies include folic acid fortification of staple foods and periconceptional supplementation. It would be useful to examine the risk for NTDs while birth defects surveillance systems are being developed or to supplement data from existing systems.

Specific WHO recommendations are as follows:

To prevent the greatest number of NTDs, RBC folate concentrations at the population level should exceed 400 ng/mL (906 nmol/L) in women of reproductive age (strong recommendation, low-quality evidence).

Among women of reproductive age, the RBC folate threshold of >400 ng/mL (906 nmol/L) can be used as a marker of folate insufficiency (strong recommendation, low-quality evidence). The authors warn that this marker is only useful at the population level because all cases of NTDs are not caused by low folate concentrations. Clinicians cannot use this threshold to predict a specific woman’s risk for having a NTD-affected pregnancy.

At the population level, the WHO has not recommended a serum folate threshold to prevent NTDs in women of reproductive age (strong recommendation, low-quality evidence). Before attempting to use such an indicator, countries should first determine the association between both serum and RBC folate concentrations and use the threshold value for RBC folate concentration to determine the corresponding serum threshold.

The most reliable option yielding comparable results for RBC folate concentration across countries is microbiological assay (strong recommendation, moderate-quality evidence).

“[A]lthough the guidelines provide an important tool to assist with NTD prevention interventions, birth defects surveillance continues to be critical for monitoring the prevalence of birth defects because not all NTDs are folate sensitive,” the guidelines authors conclude.

Topical Gel Promising in Migraine

A fast-acting transdermal gel using a proprietary formulation of the nonsteroidal anti-inflammatory drug (NSAID) ketoprofen (Topofen, Achelios Therapeutics) reduced pain severity in patients with severe migraine with and without aura compared with placebo and had few adverse effects.

Results from a phase 2a trial of the gel were presented here at the American Academy of Neurology (AAN) 67th Annual Meeting.
“This research sheds new and highly welcome light on our understanding of how severe headaches are caused by neurogenic inflammation, and how we can rationally interrupt pathologic feed-forward signaling in the trigeminal system,” lead researcher, Wolfgang Liedtke, MD, PhD, associate professor of neurology, anesthesiology and neurobiology, Duke University, Durham, North Carolina, and an advisor and consultant to Achelios Therapeutics, told Medscape Medical News.

“Once confirmed in later stages of clinical trials, it can change our neurological practice significantly, possibly heralding a new era of topical, transdermal treatments for migraine and related headaches, and also for other pain disorders.”

Oral NSAIDS inhibit the cyclooxygenase (COX) enzyme, which is expressed in trigeminal ganglion nociceptor neurons. They also reduce neurogenic inflammation thought to be a key factor in the development of migraine attacks.

But although these drugs relieve pain and decrease inflammation, they’re associated with undesirable gastrointestinal (GI) adverse effects.

It’s believed that the main mechanism of action for the new tropical gel is also inhibition of cyclooxygenase 1 and 2, and a reduction of neuroinflammation.
The randomized, crossover, double-blind, placebo-controlled study included 42 adults aged 18 to 65 years with a history of episodic migraine with and without aura at two US centers. Patients were instructed to apply a pea-sized amount of the gel on the skin over the peripheral trigeminal nerve ends, on both sides of the face (six points in total) — even if they had pain only on one side — during five moderate to severe migraines.

Researchers grouped patients according to baseline headache intensity (moderate = grade 2 and severe = grade 3). They asked patients to follow each migraine for 24 hours after applying the gel. Patients recorded their symptoms in an electronic diary.

Researchers assessed efficacy at baseline (ie, immediately before dosing) and at multiple time points up to 24 hours after administration.

Compared to a reference topical ketoprofen gel, the proprietary product was absorbed quickly. At 2 hours, absorption of the competing product is “minimal to nonexistent” compared to the new drug, which “reaches the target because the formulation allowing the drug to go through the skin is so efficient,” said Dr Liedtke. “It’s so much better than anything we have seen.”

The analysis included a total of 130 treated headache attacks. Twenty-two patients experienced 49 severe headaches, with 22 treated with active gel, and 27 with placebo.

Of the patients with severe migraine, 77% treated with the gel had relief of pain and migraine-associated symptoms; 45% had sustained pain relief from 2 to 24 hours compared with 15% of headaches treated with placebo. By 4 hours, 23% of headaches treated with the gel were pain-free compared with 15% with placebo.

At 24 hours, 50% of headaches treated with the active agent had pain relief and were pain-free vs 25% of placebo-treated headaches.

At this time point, “the gel still has the same efficacy as before; it doesn’t lose its efficacy at 24 hours,” commented Crist J. Frangakis, PhD, president and CEO of Achelios Therapeutics. “There is still drug in the tissue.”

The efficacy of the drug is based on the amount accumulated in the tissue rather than the amount circulating in the blood, explained Dr Frangakis. “That’s why it’s put on in different areas — exactly where the nerves are.”

The idea is that in future the gel will be used “as a prophylactic, applied once a day,” he added.

Patients whose headaches were treated with the gel were at least three times as likely to experience relief of associated symptoms (nausea, photophobia) as those receiving placebo.

According to Dr Liedtke, the more moderate effect for mild migraine attacks could have been due to confounding by the placebo effect.

“The data are more striking in those who reach the definition of severe,” he said. “This is also true for symptomatic relief and for concurrent use of rescue medication.”

An unwanted effect of the gel was irritation at the application site, which was predominantly mild or moderate and resolved quickly, said Dr Frangakis.

Phase 2b and 3 studies are now needed, said Dr Liedtke, as well as additional mechanistic studies, including animal and human cell experiments.

A topical gel for migraine offers an alternative to “swallowing pills” and may be one answer to the growing “worldwide” problem of medication-overuse headaches, said Dr Liedtke.

Medication Overuse Headache

Mia Minen, MD, assistant professor, neurology, and director, Headache Services, NYU Langone, New York, agreed that although “a lot remains to be determined with the topical form,” this new formulation could protect against medication overuse headache.

She pointed out that taking oral NSAIDs more than 15 days a month can cause such headaches.

A possible advantage of a topical NSAID is that patients might be able to combine it with a triptan drug, said Dr Minen. “For moderate to severe headaches, we may tell patients to take a triptan, but there has been data that shows that the combination of triptan and NSAID can have the best benefit.”

She pointed out that triptans are approved by the US Food and Drug Administration for use only 2 days per week.

Another advantage, said Dr Minen, is that a topical agent can be given to patients who because of gastrointestinal adverse effects, such as bleeding, can’t take oral NSAIDs.

Dr Minen said she found the presentation on the new topical agent “really interesting” and said its focus on targeting the trigeminal nerve is “exciting.”

Practice-Changing Study in HIV-Related Lymphoma

Patients with HIV-related lymphoma should now be considered candidates for stem cell transplantation if need be, and the treatment does not need to be limited to certain centers, according experts commenting on the results of a new study.

Autologous hematopoietic stem cell transplantation (AHCT) has been offered to patients with relapsed or treatment-resistant HIV-related lymphoma since the late 1990s, observed lead study author Joseph Alvarnas, MD, of City of Hope Medical Center, in Monrovia, California.

But transplantation has been limited to centers with HIV-specific expertise, Dr Alvarnas explained to reporters at a press conference here at the American Society of Hematology (ASH) 56th Annual Meeting.

Dr Joseph Alvarnas

In addition, most clinical trials of AHCT have excluded patients with HIV, he added.

In an effort to open up these two closed worlds, a clinical trial of AHCT was undertaken in patients with HIV-related lymphoma that had relapsed or was refractory.

Among 40 patients who participated, the overall 1-year survival rate was 86.6%, and the progression-free survival rate was 82.3%, both of which compared well with 151 matched control patients with lymphoma who did not have HIV.

In fact, there was no statistically significant difference between the HIV-related lymphoma patients and the control patients for rates of survival, treatment failure, disease progression, and treatment-related mortality.

Dr Alvarnas summarized that patients with HIV-related lymphoma that is responsive to antiviral treatment “should be considered candidates for autologous HCT if they meet standard transplant criteria.”

The implication was that these patients can be treated in a much wider range of facilities and not just centers with HIV specialization.

Another expert agreed.

I think the data you saw today will change the standard of practice.Dr Brad Kahl

“I think the data you saw today will change the standard of practice,” said Brad Kahl, MD, of the University of Wisconsin Carbone Cancer Center, in Madison. “The impact is large,” he added.

The exclusion of these patients in clinical trials “on the basis of HIV infection alone” is “no longer justified,” added Dr Alvarnas.

And thus another barrier in HIV disease should be dropped, suggested both clinicians.

Prognosis Used to Be Less Than 2 Months

The limited opportunities for patients with HIV-related lymphoma are a legacy of their dismal prognosis before the advent of combination antiviral therapy (cART), suggested Dr Alvarnas.

“When I started in San Francisco at UCSF back in 1985, the median survival for someone [with HIV] diagnosed with one of these lymphomas was less than 2 months,” he told an audience of reporters at a meeting press conference.

Dr Alvarnas explained that the effectiveness of cART for HIV enabled this new study.

He said that the hallmarks of cART ― such as viral suppression, recovery of T-cell immunity, and decreased infections ― allowed oncologists to offer standard antilymphoma therapies to HIV- infected patients.

In the new study, researchers from the National Cancer Institute Bone Marrow Transplant Clinical Trials Network worked in collaboration with the AIDS Malignancy Consortium.

All 40 patients had received fewer than 2 salvage regimens. Prior to transplant, 30 patients (75%) were in complete remission (CR), eight (20%) were in partial remission (PR), and two (5%) had relapsed/progressive disease (RPD).

Patients underwent AHCT using the BEAM regimen (carmustine 300 mg/m2 [day -6], etoposide 100 mg/m2 twice daily [days -5 to -2], cytarabine 100 mg/m2 [days -5 to -2], and melphalan 140 mg/m2 [day -1]).

Patients received AHCT on day 0 and standard supportive care through discharge. Antiviral therapy was withheld during the preparative regimen and until any therapy-related GI toxicity (nausea and vomiting) had resolved.

At 100 days posttransplant, 36 patients (92.3%) had achieved complete response, one (2.6%) had reached partial remission, and two (5.1%) had relapsed.

Within a year after transplant, 17 patients (42.5%) developed a total of 42 unique infections. Nine of 17 patients developed severe infection.
By 1 year posttransplant, five patients had died (three from recurrent/persistent disease, one from cardiac arrest, and one from invasive fungal infection). The cumulative incidence of treatment-related mortality was 5.2%. This was a secondary outcome and was also not statistically significantly different from the outcomes seen in control patients.

Naltrexone/Bupropion Approved as Mysimba for Obesity in EU

The European Commission has granted marketing authorization for naltrexone HCl/bupropion HCl prolonged release (Mysimba, Orexigen Therapeutics) for the treatment of obesity, the company has announced. The marketing authorization applies to all 28 EU member states.

The exact indication is as an adjunct to a reduced-calorie diet and increased physical activity for the management of weight in adult patients (≥18 years) with an initial body mass index (BMI) of ≥ 30 kg/m2 (obese) or ≥ 27 kg/m2 to < 30 kg/m2 (overweight) in the presence of one or more weight-related comorbidities (eg, type 2 diabetes, dyslipidemia, or controlled hypertension).

Treatment with Mysimba should be discontinued after 16 weeks if patients have not lost at least 5% of their initial body weight.

In the United States, naltrexone HCl/bupropion HCl prolonged release was approved for the treatment of obesity in September 2014, where it is marketed as Contrave .

More Treatment Options for Obesity for Doctors in the European Union

This is the second obesity drug to be approved this week in Europe, on the heels of the marketing authorization forliraglutide (Saxenda, Novo Nordisk).

This gives physicians treating obesity in Europe two new therapeutic options.

They have long bemoaned the fact that they have not had access to any of the newer agents for weight loss that have been available in the United States.

Due to safety concerns, the European Medicines Agency rejected two agents that were cleared for use in weight loss in the United States in 2012: lorcaserin (Belviq, Eisai) and phentermine/topiramate (Qsymia, Vivus).

Prior to the approval of Saxenda and Mysimba, only orlistat was available to treat obesity in Europe; it is available without a prescription in a low dose (Alli, GlaxoSmithKline) or by prescription at a higher dose (Xenical, Genentech).