Migraine in Men Not Uncommon but Not Always Diagnosed


It is not uncommon for men to suffer migraines, but they are less likely than women with this condition to consult a doctor, and if they do, they are less likely to be diagnosed with migraine.

Those are some of the conclusions of a study on sex differences in migraine burden presented at the American Headache Society (AHS) 58th Annual Scientific Meeting.

“While migraine is more common in women than in men, it does afflict 6% of American men,” said Richard Lipton, MD, professor and vice chair of neurology, Albert Einstein College of Medicine, and director, Montefiore Headache Center, New York City.

“The myth that migraine is a women’s disease may contribute to the stigma of migraine and certainly denies men access to medical care.”
Dr Richard Lipton
Dr Lipton reminded physicians that migraine is “very common in men” and that men may be reluctant to talk about their headaches.

For this Chronic Migraine Epidemiology and Outcomes (CaMEO) study, participants with migraine completed a baseline survey and a second online survey 3 months later.
Researchers assessed sociodemographic information; headache features; headache-related disability, using the Migraine Disability Assessment Scale (MIDAS); symptom severity, as measured by the Migraine Symptom Severity Score; cutaneous allodynia, using the Allodynia Symptoms Checklist; and treatments.

Of the 16,789 respondents, 25.6% were men. The mean age of respondents was 42.0 years for men and 40.8 years for women.

The men reported fewer headache days per month than women (4.3 vs 5.3; P < .001).

MIDAS scores were generally lower in men (P < .001). Whereas 24.1% of women were in the highest MIDAS category, only 15.7% of men were in this category.

Higher MIDAS scores among women suggest that their migraines have a more severe impact on their daily life in areas such as time lost from work or school and social and leisure activities.

Sex hormones contribute to the increased incidence and severity of migraine in women, Dr Lipton noted.

“The risk of migraine in women increases with sexual maturation,” he said, adding that there may also be sex differences in symptom reporting.

Interestingly, migraine is more common in boys than girls before puberty. The risk “takes off” in women after the onset of the menstrual cycle, said Dr Lipton.

“But our major points are that migraine is common in men even though it is more common in women and that it is severe in men even though it is more severe in women.”

Significantly fewer men than women in the study reported allodynia (32.6% vs 49.7%; P < .001). Allodynia is defined as experiencing typically nonpainful stimuli ― for example, wearing a hat or laying your head on a pillow ― as painful during a migraine.

“Allodynia develops as a response to attack frequency and severity and is one of the pieces of evidence that migraine is worse in women,” commented Dr Lipton.

Men were less likely than women to report seeing a physician to manage their headaches (28.6% vs 31.1%; P < 0.01).

Although men generally seek medical care less often than women for a range of conditions, in the case of headaches, “the myth that migraine is a women’s disease may make men with migraine more reluctant to seek care,” said Dr Lipton.

If men in the study did consult a physician, they were less likely than women to receive a migraine diagnosis (59.2% vs 77.7%; P < .001), suggesting that migraine is underdiagnosed in men, said Dr Lipton.

As for treatment, 24.1% of men and 28.2% of women reported using prescription medications to treat headaches (P < .001). Men and women used prescription preventive treatments in a similar manner.

Benjamin W. Friedman, MD, associate professor of emergency medicine, Albert Einstein College of Medicine, who is a colleague of Dr Lipton’s but was not involved in the current study, commented on the findings for Medscape Medical News.

“It is interesting that there were both patient-related reasons (lower levels of consulting) and physician-related reasons (failure to diagnose) for men obtaining appropriate treatment for migraine less frequently,” Dr Friedman noted.

“Men do seem to experience migraine differently than women. This is reflected elsewhere in the medical literature,” he added. “Epidemiologically, even though men experience migraine less frequently than women, this is still a highly prevalent illness that affects hundreds of millions of men worldwide.”

Continuous L-Dopa Enteric Infusion Relieves RLS Symptoms


Patients with restless legs syndrome (RLS) for whom conventional therapies are contraindicated may benefit from a treatment usually reserved for patients with advanced Parkinson’s disease and augmentation phenomena, a case report suggests.

In a presentation here at the 20th International Conference of Parkinson’s Disease and Movement Disorders, Jesús Pérez-Pérez, MD, of the Movement Disorders Unit at the Hospital de la Santa Creu i Sant Pau, in Barcelona, Spain, described the case of a 70-year-old man who had experienced RLS with augmentation for 3 years. The patient was successfully treated using a 24-hour infusion of carbidopa/levodopa enteral gel (Duopa, AbbVie Inc).

His condition had initially responded well to dopaminergic medication, but after 1 year of therapy with dopaminergic drugs, augmentation began, and RLS was present all day and was worse at night. Augmentation is a phenomenon of worsening symptoms after dopaminergic drug exposure.

The patient had severe, chronic obstructive pulmonary disease and had undergone several hospitalizations in less than a year because of respiratory decompensation. For these reasons, drugs such as benzodiazepines, opioids, gabapentin (multiple brands), and pregabalin (Lyrica, PF Prism CV) were contraindicated. Because of RLS, the patient was unable to use nocturnal continuous positive airway pressure, which led to hypercapnic respiratory failure.

The treating physicians then offered, and the patient accepted, 24-hour constant infusion with carbidopa/levodopa enteral gel delivered by pump directly into the small intestine through a tube with a jejunal extension introduced percutaneously into the stomach. Because of the continuous drug delivery, this system avoids the pulsatile dosing effect that leads to augmentation.

Three months after starting therapy with the enteral gel formulation, the patient’s RLS symptoms were greatly improved, as was his quality of life, Dr Pérez-Pérez reported.

Table. Results of Switching Patient From Oral to Enteral Infusion Medication

Intervention/Period RLS Rating Scale Score RLS Quality-of-Life Questionnaire
Oral/preintervention* 36 (very severe) 22
Enteric gel at 3 months 9 (mild) 74
Enteric gel at 1 year 4 (mild) 100
*Levodopa/carbidopa 150 mg 5x/day plus levodopa/carbidopa retard 200 mg at night.

Symptoms and quality-of-life scores continued to improve during the first year of treatment, as reflected in Clinical Global Impression–Improvement scale scores.
The patient has not experienced any adverse effects or complications from the medication or the implantation procedure and was hospitalized only once during the year.

Olga Klepitskaya, MD, associate professor of neurology at the University of Colorado, in Denver, who has a special interest in the use of deep brain stimulation to treat RLS, commented to Medscape Medical News that although the presentation involved a single case report, it was well done and is important. “They described very well why they did [it] and what they did and what are the implications of that,” she said.

“Just like in Parkinson’s disease, with RLS…pulsatile dopaminergic stimulation is not healthy for our dopamine receptors in the brain, and that’s why it causes all these problems of augmentation,” she said. The mainstream treatment of augmentation is to use longer-acting dopaminergic medications, such as rotigotine transdermal patches (Neupro, UCB Pharma, Inc), longer-acting pramipexole (Miraprex ER, Boehringer Ingelheim Pharmaceuticals, Inc), and ropinirole (Requip XL, GlaxoSmithKline).

The treatments that provide constant dopaminergic stimulation are better physiologically for the brain, “and Duopa is the ultimate long-acting medication,” she said. “It’s administered through the GI system, and I assume it can be used for very, very severe RLS with augmentation that cannot be treated by anything else.”

Calling delivery of the medication through a percutaneous indwelling tube “a little bit extreme,” she said the authors “really justified why they used this…for this particular patient, because he had a lot of comorbidities that can [lead to] a lot of side effects.”

For this patient, the choice of this continuous but somewhat invasive treatment, which led to significant improvement in quality of life, appeared correct, she said.

Dr Klepitskaya said she believes that treatments that provide continuous stimulation ― whether pharmacologic or electrical ― would be best.

“That’s why I have put my hopes in my study, deep brain stimulation for RLS,” she said, “and deep brain stimulation and Duopa now can be not completely interchangeable, but we are considering both as treatments available in the United States in patients with very advanced Parkinson’s disease and trying to find which of those treatments will fit that particular patient profile the best.”

The current case report and other reports on the use of deep brain stimulation suggest that difficult-to-treat RLS may be amendable to these treatments as well.

CRP Levels Elevated in Migraine


Levels of the inflammatory marker C-reactive protein (CRP) are significantly elevated in young adults with migraine, which may not only offer insights into the pathogenesis of the condition but also point to novel therapeutic avenues, researchers say.

Delegates here at the American Headache Society (AHS) 58th Annual Scientific Meeting heard that levels of the protein, as measured on high-sensitivity CRP (hsCRP) assay, were higher by 11% in people with migraine compared with those in unaffected individuals, rising to 17% among women.

Gretchen Tietjen, MD, professor and chair of neurology and director of UTMC Headache Treatment and Research Program, University of Toledo, Ohio, and colleagues say the study findings show “a positive association between migraine diagnosis and elevated hsCRP, with a significant effect size,” particularly in young women.

Conflicting Results

Although there has been a great deal of interest in potential association between markers of inflammation and migraine, the evidence linking increased CRP levels with the condition is limited, and there have been conflicting results from population-based studies. However, it is notable that those studies were conducted in different age groups from that in the current analysis.

The researchers therefore examined data on 9269 adults aged 24 to 32 years taking part in Wave 4 of the Add Health Study, as part of which participants discussed diagnoses of migraine, depression, and anxiety with their healthcare provider. In addition, dried capillary whole blood spots were obtained from the individuals during in-home visits, on which blood hsCRP assay was performed.

The team found that 1049 (11.3%) participants reported migraine.

Linear regression analysis, taking into account sociodemographic factors, body mass index, infections, current pregnancies, subclinical symptoms, anxiety, and depression, indicated that mean hsCRP levels were significantly higher in individuals with migraine than in those without.

Specifically, participants with migraine had an hsCRP level of 5.54 ± 9.04 mg/L vs 4.40 ± 7.47 mg/L in those without migraine (P < .001).

Although women had higher mean hsCRP levels than men, the difference in levels between those with and without migraine was significantly different only in men, at 3.63 ± 6.32 mg/L vs 3.05 ± 5.25 mg/L in men (P = .03) and 6.26 ± 9.78 mg/L vs 5.75 ± 8.97 mg/L in women (P = .08).
Interestingly, when all potential confounding factors were taken into account, migraine was significantly associated with log hsCRP levels across the whole sample, at an r value of 0.11 (P = .04), and in women, at an r value of 0.17 (P = .01), but not in men (r = 0.01; P = .94).

Dr Tietjen believes that the relationship between CRP levels and migraine could be direct. “I think that it is possible that it is a consequence of having migraine, in that, when there’s changes within the brain in the endothelium, that can increase levels of things like [CRP] and inflammation,” she said.

Noting that the relationship was more pronounced in women, she added: “Whether it has something to do with endothelial activation being more easily triggered in women than in men I think is interesting, but I don’t think we can say for sure why we would see it more frequently in women than men.”

Nevertheless, Dr Tietjen said the current findings may point to therapies that target inflammation in general, and CRP levels in particular, potentially being beneficial in migraine.

She highlighted the JUPITER trial, in which the statin rosuvastatin was shown to reduce the incidence of major cardiovascular events in individuals with high CRP levels, although she acknowledged that concerns have been raised about the study’s methodology.

In addition, Catherine Buettner MD, MPH, and colleagues conducted a randomized, double-blind, placebo-controlled trial of simvastatin plus vitamin D, finding that the combination is effective for prevention of headache in adults with episodic migraine.

“Why would it be an effective migraine treatment unless something tied into the migraine pathogenesis had either something to do with cholesterol or inflammation or something that statins actually work on?” Dr Tietjen commented.

“I did think that that was very intriguing, as [CRP] might be something that would guide us as to which patients would be most likely to respond to which therapies,” she added.

Dr Tietjen concluded: “I think it’s an area ripe for more study, but I do believe that it makes sense in what we’re learning both about the importance of the endothelium potentially in migraine and the fact that we are seeing that some therapies that actually have an effect on [CRP] may be effective in migraine in a relatively young, healthy population of people.”

Commenting on these findings, Stephen Silberstein, MD, professor, Department of Neurology, Thomas Jefferson University and Jefferson Health, and director, Jefferson Headache Center, Department of Neurology, Jefferson Hospital for Neuroscience, Philadelphia, Pennsylvania, said the results “look interesting.”

However, he told Medscape Medical News that the wide overlap in the confidence intervals were “of concern” and limited the degree to which the study could be interpreted.

How the Brexit Decision Might Affect Healthcare


The world is reeling from the United Kingdom’s (UK) historic vote on Thursday to leave the European Union (EU). The ramifications will be felt in all aspects of life, from economic, to travel and immigration, to national security, and not the least, to health.

The future of the UK’s National Health Service (NHS) featured prominently in the run-up to yesterday’s referendum, and will figure prominently in the changes brought about by the decision.

 While the “Leave” camp claimed the cash that the UK currently gives to the central leadership of the EU in Brussels, Belgium could now be ploughed back into health services, the “Remain” camp warned that economic turmoil from the British Exit (Brexit) threatened the fragile finances of the NHS.

But the bell has been rung. Now that 51.9% of the UK’s citizens chose to get out of the EU, while 48.1% backed remaining part of the club of 28 nations, what might the impending exit mean for the future of health and social care in the UK?

Timing

Firstly, nothing significant is going to change today or tomorrow.

Soon after the result was declared, Prime Minister David Cameron announced he would stand down in the autumn, by which time another member of the conservative party will be chosen to be the new leader in the UK.

 It will be up to the next prime minister to decide when to pull the lever to leave the EU, known as Article 50 of the Lisbon Treaty, which would give the UK 2 years to negotiate withdrawal terms.

Will There Be More Cash for the NHS?

Supporters of Leave originally claimed that quitting the EU would give the UK an additional £350 million a week to spend on health and other public services.

 However, an analysis this month by the Institute for Fiscal Studies (IFS) disputed this figure, saying that after taking into account money received back from the EU, the UK’s net contribution was £150 million a week.

However, this takes no account of any financial turmoil that could hit government finances.

The IFS analysis predicted that Brexit will add an additional 2 years of austerity to the UK’s economy. Carl Emmerson, IFS deputy director and an author of the report, said: “the overwhelming weight of analysis suggests that the economy would shrink by more than enough to offset the positive effect on the public finances of the reduced financial contribution to the EU budget.”

Will Containing Immigration Cut NHS Costs?

Immigration and its effect on health and other public services was a key topic during the referendum campaign.

 A recent analysis by the Nuffield Trust estimated that in 2014, migration from the EU added £160 million in additional costs for the NHS across the UK.

However, it says this was a relatively small sum when set against the £1.4 billion in additional costs caused by other factors such as treating an ageing population and migrants from outside the EU.

The report also pointed out that immigrants are taxpayers as well as patients and that they could even be making a net contribution to available resources.

Will Health Insurance Cards Still Work in the EU?

British travellers to EU and European Economic Area (EEA) countries can carry a European Health Insurance Card (EHIC) giving them the right to access state-provided healthcare on temporary stays at a reduced cost or, in many cases, for free.

 But once the UK leaves the EU, and if it also left the EEA, British tourists and retirees abroad would have to cover health care costs from their own pockets or from travel insurance in these countries.

However, it is possible that the UK could negotiate specific agreements with EU and EEA countries for EHIC to remain valid.

What About the NHS Staff?

A total of 55,000 out of the 1.2 million staff in the NHS in England are citizens of other EU countries — equivalent to 5% of NHS workers.

That is close to the 4.7% of the UK population who were born in other EU countries.

According to the Nuffield Trust, 10% of physicians and 4% of nurses are from other EU countries.

The NHS’s most senior physician, Sir Bruce Keogh, MD, has called on NHS leaders to send out a message to European staff working in the health service that they are valued and welcome in the wake of the referendum result. Sir Bruce told the Health Service Journal: “It is really important we make them feel welcome.

“If you are a European doctor or nurse you might not feel too welcome at the moment.”

The British Medical Association (BMA) urged politicians not to play games with the UK’s health services. BMA council chief, Mark Porter, MD, said in a statement: “We stand together as one profession with our colleagues from Europe and across the world, with whom we live, work and study and on whom the NHS depends.”

What About Medical Research?

UK medical science has benefited from EU funding for decades.

In the wake of the result, several leading experts issued statements about what it could mean for research.

 Nobel Laureate Sir Paul Nurse, PhD, director of the Francis Crick Institute, said: “This is a poor outcome for British science and so is bad for Britain.

“Science thrives on the permeability of ideas and people, and flourishes in environments that pool intelligence, minimise barriers, and are open to free exchange and collaboration.

“British scientists will have to work hard in the future to counter the isolationism of BREXIT if our science is to continue to thrive.”

 Professor Anne Glover, PhD, vice-principal external affairs and dean for Europe at the University of Aberdeen, said: “I am personally heartbroken and I have great concern for the future of British science, engineering and technology.

“Our success in research and resulting impact relies heavily on our ability to be a full part of European Union science arrangements and it is hard to see how they can be maintained upon a Brexit.”

Could the Exit Affect Access to Medicines?

Leading figures from the life sciences industry recently expressed their fears that Brexit could jeopardise the UK’s central role in the European pharmaceutical industry and call into question the country’s access to innovative medicines.

 Following the result, Mike Thompson, the head of the Association of the British Pharmaceutical Industry (ABPI), said in a news releases that leaving the EU would create “immediate challenges for future investment, research and jobs in our industry in the UK.”

Meanwhile, the BioIndustry Association (BIA) said in a statement that “key questions about the regulation of medicine, access to the single market and talent, intellectual property and the precise nature of the future relationship of the UK are now upon us.”

Before the vote, the ABPI, BIA, and business leaders and organizations for the life-sciences industry, had signed a letter warning that the UK leaving the EU would put access to cutting-edge medicines at risk, according to the ABPI release.

 An early sign of the threat posed to the UK’s position came as the association representing Germany’s pharmaceutical industry, Beraten Analysieren Handeln, called for the European Medicines Agency (EMA), the UK’s equivalent to the US Food and Drug Administration, to be relocated from its central seat in London to Bonn, Germany following the UK’s departure from the EU.

8 Signs You’re Eating Too Much Sugar


Sugar is delicious. Anyone who denies that is lying. But because life is unfair, sugar, especially in copious amounts, is really bad for your health. In fact, once you learn about all the ways sugar impacts your body, it’s difficult to look at it the same way (despite knowing how heavenly it tastes).

So how do you know if you’re eating too much? Here are eight red flags your body is sending you that it’s time to cut back on the sweet stuff.

1. You constantly crave sugary things. The more sugar you eat, the more you’ll crave it. “More cravings then equal consuming more sugar—it becomes a vicious and addictive cycle,” Brooke Alpert, M.S., R.D., author of The Sugar Detox: Lose Weight, Feel Great and Look Years Younger, tells SELF. This isn’t just because your taste buds have adapted and left you needing more and more to get that same taste, but also because of how sugar gives you a high followed by a crash, just like an actual drug. “By eating a high sugar diet, you cause a hormonal response in your body that’s like a wave, it brings you up and then you crash down and it triggers your body to want more sugar.”

2. You feel sluggish throughout the day. What goes up must come down. After sugar causes an initial spike of insulin and that “high” feeling, it causes an inevitable crash. “Energy is most stable when blood sugar is stable, so when you’re consuming too much sugar, the highs and lows of your blood sugar lead to highs and lows of energy,” Alpert says. Eating a lot of sugar also means it’s likely you’re not eating enough protein and fiber, both important nutrients for sustained energy.

3. You’ve been putting on some weight. Excess sugar is excess calories, and since it has no protein or fiber, it doesn’t fill you up (so you just keep eating it). It also triggers the release of insulin, a hormone that plays a big role in weight gain. When we eat sugar, the pancreas releases insulin, which carries sugar to our organs so it can be used for energy. When you load up on sugar, your body’s told to produce more insulin—over time, that excessive output can lead to insulin resistance. Insulin resistance means our bodies can’t respond to normal amounts of insulin properly and therefore can’t use sugar the right way. The initial weight gain from simply eating too many calories from sugar is being compounded by the disruption to your normal insulin response (there’s a link between insulin resistance and obesity). What’s more, when the pancreas works in overdrive for too long you can develop diabetes.

Why does something that tastes so good have to be so bad for us?

4. Your skin won’t stop breaking out. “Some people are sensitive to getting a spike in insulin from sugar intake, which can set off a hormonal cascade that can lead to a breakout like acne or rosacea,” Rebecca Kazin, M.D., of the Washington Institute of Dermatologic Laser Surgery and the Johns Hopkins department of dermatology, tells SELF. A sugar binge can show up on your face in just a few days. If your skin’s unruly, Kazin recommends reassessing your diet, otherwise “you may be treating skin for other issues without getting to the bottom of what’s really going on.”

5. You’re way moodier than usual. The blood sugar crash that happens when you’re coming off a sugar high can cause mood swings and leave you feeling crabby. Not to mention, if your energy is also tanking, that just contributes to a bad attitude.

6. You’ve been getting more cavities. When bacteria chow down on food particles in between the teeth, acid is produced, which causes tooth decay. Our saliva maintains a healthy balance of bacteria on its own, but eating sugar can impact the pH and throw off the natural ecosystem. This gives the bacteria a chance to thrive and multiply, leading to cavities.

7. Your brain tends to get foggy, especially after a meal. This fog is a common symptom oflow blood sugar. When you eat a lot of sugar, your blood sugar levels rapidly rise and fall instead of gradually doing so. “Poor blood sugar control is a major risk for cognitive issues and impairment,” says Alpert.

8. Nothing tastes as sweet as it used to. “Eating too much sugar basically bombards your taste buds,” Alpert says. “This sugar overkill causes your taste bud sugar tolerance to go up, so you need more and more sugar to satisfy that sweet craving.” When your taste buds need lots of sugar to feel like something is sweet enough, it can be tough to lower your base level. However, it you cut back and suffer through it in the beginning, you’ll eventually lower your tolerance again and be content with minimal sugar. You might even start to feel like things are too sweet for you and—gasp!—be happier consuming sugar in moderation.

Treat Chronic Hepatitis C Virus Infection in Decompensated Cirrhosis – Pre- or Post-liver Transplantation?


Abstract

The management of hepatitis C virus (HCV) infection in patients with decompensated cirrhosis has evolved dramatically over the past few years mainly due to the availability of all-oral antiviral regimens. The currently approved all-oral direct-acting antivirals (DAA) containing sofosbuvir, ledipasvir, daclatasvir and ribavirin, in various combinations, have shown to be safe and effective in patients with decompensated cirrhosis with sustained virological response (SVR) rates nearly comparable to those with well-compensated liver disease. Unique issues yet remain such as the challenges with renal insufficiency, tolerability of ribavirin and risk of further hepatic decompensation with a protease inhibitor-based regimen. While most patients who achieve SVR have demonstrated improvement in hepatic synthetic function over the short course of follow, the long-term beneficial effects are unknown. Further, the baseline predictors of improvement in hepatic function have not been well delineated and thus have left us in a quandary as to what we might expect with successful therapy and thus we are at a loss to well educate our patients. The major concern, in potential liver transplant candidates, is of unintended ‘harm’ by achieving SVR but without improvement in hepatic function to an extent where the patients might function well. As HCV therapies are as effective in liver transplant recipients, there is a growing sentiment in some of the transplant quarters that those with decompensated liver disease and awaiting liver transplant be treated for HCV after liver transplant. This strategy would thus eliminate any concern of leaving a patient in ‘no person’s’ land by treating HCV successfully pretransplant but not to the point of functional normalcy, while also would maintain the risk of HCC. Yet a contrarian view would be that not all patients have access to liver transplantation (LT), cannot bear the cost, have comorbidities or contraindications to LT. While the debate continues, it is essential that we develop robust predictors of improvement in liver function so that we can carefully select our patients for therapy in the context of liver transplantation.

Love Is a Much-Debated Thing


As Huey Lewis and The News notably taught us, “The power of love is a curious thing.” Recently Medscape ran an interview with Dr Dean Ornish, a clinical professor of medicine at University of California, San Francisco, and founder of the nonprofit Preventive Medicine Research Institute. Dr Ornish discussed the concept of love as an underused lifestyle recommendation and a source of healing. He then outlined the health implications associated with a lack of real connection to other human beings, and went on to describe some of the measures he was taking to encourage a human connection in medicine. The interview received many impassioned responses, overwhelmingly positive, regarding “the touchy-feely stuff.” Here, we provide a sampling of the feedback. [Editor’s note: Some comments have been edited for clarity or length.]

Healthcare professionals spoke out in favor of love and a more humane philosophy of treatment. One internist was eloquent:

Affection heals, or significantly contributes to overcoming not just heart disease but just about any disease. Allopathic medicine, while extremely successful in certain situations, tends to ignore this essential fact with many chronic diseases. Too many people have never experienced true unconditional love and affection, and this lies at the core of their health problems.

A preventive medicine specialist also saw this approach as the perfect antidote for an overly mechanical view of medicine, saying, “Doctors should work as doctors, not as technicians. The magic touch with a holistic approach yields better outcomes than treating patients as business clients with a quick-fix approach.”

Another healthcare professional looked to the news to support this policy, saying, “After reading about the number of people killed by guns—strongly related to an endemic lack of connection and community—this article was a breath of fresh air. We have a system that is anxious to use and pay for the fanciest machinery, but not for attentive, hands-on approaches to helping people change.”

A cardiologist cited historic precedence for this kind of treatment but also raised a warning flag:

The Catholic Church got it right: confession (via a connection to someone) is good for the soul. We physicians can slow down and spend more time with the patient, and get connected. But that will result in my problem: an enormous pay cut. As difficult as it may seem, pick and choose your ethics carefully, they will likely spread throughout your life.

A primary care physician offered a pithy maxim: “To be a healer you need to connect at a visceral level. All physicians should strive to be healers.”

Nurses, too, came out in favor of keeping an eye on the humanity of patients. One nurse wrote, “I am a palliative care nurse and I see the difference that touch and compassion can make every day.”
One primary care physician, however, did not see the value in all of this tenderness. In particular, he had pointed criticism for the kinds of programs described by Dr Ornish, saying “We are turning humans into plus-size bonobos—I thought the goal was to advance our evolution. I would feel better too if I paid all that for a group hug.”

But a cardiologist fired back, defending the use of empathy in healthcare on grounds both humanitarian and financial:

My patients are more likely to follow recommendations when they feel that I care about their outcomes, which I do. As a profession, we have lost the ability to show them that we care. It’s not rocket science; it should already be part of your life and work (billable) practice.

Another cardiologist questioned the style while supporting the substance of Dr Ornish’s approach, saying, “I applaud the article but object to relegating this essential practice of medicine to ‘touchy-feely stuff.’ Providing the best care is what we should be doing as a matter of course. If you call it ‘touchy-feely stuff,’ you may as well just call it ‘cooties.'”

An internist offered a heartfelt personal account:

I just lost a dear friend who was immensely popular; worked pretty much 24/7. He was only 59 when he died and I feel he’d been depressed all his life. His favorite quote was: “The only thing worse than being alone is wanting to be.” What does that say about the state of medicine today?

A retired pediatrician bemoaned the direction that modern medicine has taken. “Now we are being told not to waste time or touch patients but to spend millions on investigations. It made me quit a few years earlier than I would have wished. I wonder whether our planners and managers ever think about humanity as such.”

The last word goes to a preventive medicine specialist who wryly underscored the pressure of modern practice. “Love and connection? That sounds wonderful. What’s the CPT code for that?”

Most Antidepressants Ineffective for Kids With Depression


With the possible exception of fluoxetine (multiple brands), the vast majority of antidepressants are ineffective, and some may even be unsafe, for use in children and teens with major depressive disorder (MDD), new research shows.

“The only treatment that is evidence-based is fluoxetine,” lead researcher Andrea Cipriani, PhD, associate professor, Department of Psychiatry, University of Oxford, United Kingdom, told Medscape Medical News.

However, Dr Cipriani stressed that this applies to children with moderate to severe depression for whom psychotherapy or other nonpharmacologic interventions have been tried without success or in situations in which such interventions are unavailable.

“And it doesn’t mean that if I have a patient who is responding to escitalopram [Lexapro, Forest Laboratories, Inc], that I should stop escitalopram and put that patient on fluoxetine, because these are average data for an average patient.”

Dr Cipriani also stressed that the use of antidepressants in children is “not cookbook medicine. Everything has to be individualized to the specific patient.”

The findings were published online June 8 in the Lancet

One Drug Better Than Placebo

MDD is one of the most common mental disorders in children and adolescents, the investigators note. However, whether to use pharmacologic agents in this population and which drugs are optimal remains controversial.
To compare and rank antidepressants and placebo for the treatment of MDD in young patients, the researchers conducted a meta-analysis to identify both direct and indirect evidence from relevant trials.

They searched for double-blind, randomized controlled trials involving the use of antidepressants for the acute treatment of MDD in children and adolescents through May 31, 2015. The analysis included 34 trials in which 5260 patients were enrolled; 14 antidepressants were assessed for efficacy and tolerability.

The mean study sample size was 159 participants; the mean age of the patients was 13.6 years; and the median duration of acute treatment was 8 weeks. About two thirds of the trials (65%) were funded by pharmaceutical companies.

In terms of study quality, 29% of the trials were rated as having a high risk for bias, 59% as having a moderate risk, and 12% as having a low risk.

The primary outcome was mean overall change in depressive symptoms and the proportion of patients who discontinued treatment due to any adverse events. To assess change in depressive symptoms, the investigators extracted a score from scales used in the studies. These scales included the Children’s Depression Rating Scale Revised, the Beck Depression Inventory, and the Children’s Depression Inventory.

Secondary outcomes included response rate, all-cause discontinuation, and suicidal behavior and ideation. Response rate was determined on the basis of the proportion of patients who achieved a reduction of 50% or more in depressive symptoms or whose scores on the Clinical Global Impression scale were much improved or very much improved.

Suicidality Risk

The researchers performed a “network” meta-analysis that allowed them to use indirect as well as direct evidence from the relevant trials to calculate comparisons and to rank probabilities for all treatments.

The analysis showed that in terms of efficacy, only fluoxetine was better than placebo (standardized mean difference [SMD], – 0.51; 95% credible interval [CrI], -0.99 to -0.03).

However, the authors point out that “the large credible interval and its upper limit close to the point of no difference raise the question of whether this estimate is robust enough to inform clinical practice.”

Nortriptyline (multiple brands) was significantly less effective than seven other antidepressants and placebo.

In terms of tolerability, fluoxetine was significantly better than duloxetine (Cymbalta, Eli Lilly and Company) (odds ratio [OR], 0.13; 95% CrI, 0.13 – 0.95) and imipramine (multiple brands) (OR, 0.23; 95% CrI, 0.04 – 0.78). Citalopram and paroxetine (multiple brands) were significantly better tolerated than imipramine alone (OR, 0.27 and 0.22, respectively). Imipramine was significantly less well tolerated than placebo, as was venlafaxine (multiple brands) and duloxetine.

For the most part, the results for secondary outcomes “were not materially different from, and lent support to, the findings for primary outcomes,” the authors write.

Although the current study could not comprehensively assess the risk for suicidality for all drugs, there was robust evidence suggesting a significantly increased risk for suicidality for young people given venlafaxine.

The ranking of treatments, based on cumulative probability plots and surface under the cumulative ranking curve, showed that the most effective treatment was fluoxetine (76.6%) and that the least effective was nortriptyline (3.7%). Fluoxetine also came out on top in terms of tolerability (75.7%), with imipramine coming in last (13.1%).

Advantages of Fluoxetine

Fluoxetine has a number of advantages, said Dr Cipriani. Being the first new-generation antidepressant (selective serotonin reuptake inhibitor), it has been “very well studied” and has many years of “real-world use.”

It has a long half-life, requiring a few weeks to metabolize. Because of this, missing a dose may not be a problem.

“With children, there is sometimes a problem with compliance, and if you have a drug with a very short half-life, and you don’t take it regularly, you might have withdrawal symptoms,” said Dr Cipriani.

Fluoxetine is also widely available. “It’s one of the WHO [World Health Organization] essential medicines, so it’s available everywhere, including developing countries and where there’s a refugee crisis,” said Dr Cipriani.

But it is not without disadvantages. For example, switching from fluoxetine to another medication requires a washout period, and fluoxetine can interact with other medications.

“You need to be careful if you are adding other treatments, such as antibiotics,” said Dr Cipriani.

The authors caution about clinical interpretation of the findings, owing to the uncertainty of estimates and potential bias due to selective reporting. As well, unpublished studies were not included in the analysis, and published reports may overestimate the efficacy of treatments.

In 2003, the US Food and Drug Administration (FDA) and other regulatory agencies added a black box warning to the labeling of prescription antidepressants, highlighting the possibility of suicidality in some children with MDD.

According to Dr Cipriani, there is an increased risk for suicidality, but the risk is not the same for all drugs.

Although the data gathered by the FDA are not powered to provide “clear answers,” there is “a trend” of some drugs being worse than others in terms of suicidality risk, said Dr Cipriani. “The one-size-fits-all approach is misleading.” The evidence suggests that sertraline and fluoxetine are not associated with an increased risk for suicidality, she added.

Children Not Small Adults

What is becoming clear from the research, said Dr Cipriani, is that children with MDD significantly differ from adults with depression. In children, the brain is still developing, and the clinical features of depression in children are different from those in adults.

“In adults, mainly in the elderly, depression is a lot about mood, while in young people, it’s a lot about irritability and difficulty with concentration,” said Dr Cipriani. “We tend to call it all depression and assume that the same drugs work for young people.”

A main problem is lack of knowledge about the pathophysiology of the disorder and identifying markers. “We don’t have hard outcomes to test a treatment.”

A question plaguing trials of antidepressants ― among adults as well as children ― is the high placebo response rate. According to Dr Cipriani, 50% to 60% of patients respond to an antidepressant, and about 40% respond to placebo, so the “added value” is about 10% to 15%.

The placebo response has increased over the years ― it was about 20% in the 1980s ― probably because of methodologic differences in trials. One example would be differences regarding the inclusion of less severe patients, who tend to respond more to placebo.

“But in real practice, we don’t use a placebo,” said Dr Cipriani.

Childhood depression is “a huge problem” that is growing, according to Dr Cipriani. About 3% of children younger than 12 years suffer major depression, as do 6% of persons aged 13 to 18 years.

Adverse Events Underreported

In an accompanying editorial, Jon Jureidini, MD, a child psychiatrist at the University of Adelaide and Women’s and Children’s Hospital, in Australia, writes that the evidence for the use of antidepressants in children is even weaker than the current study suggests.

“The data that the authors were working from was what were available in published articles and clinical study reports,” Dr Jureidini told Medscape Medical News. “Unless you have access to individual patient-level data, you can’t be confident that what’s in those tables and spreadsheets that these authors had to work from is actually an accurate representation of what was found.”

From his own research, Dr Jureidini has learned that “adverse events are underreported, and some outcome measures are distorted.”

One problem is that some of the clinical trials are carried out by pharmaceutical companies, which “control the flow of information,” he said.

Anther problem is that doctors are often convinced that these medicines do work, he added.

“They don’t do it deliberately, but they look at things with more of a positive lens, because they want to show that these drugs they regard as positive and valuable are in fact positive and valuable.”

What is particularly bothersome, said Dr Jureidini, is that even though these drugs are not first-line therapy, “the idea seems to be that you give the antidepressants anyway,” he said. “That’s just bad medicine; if they’re not good drugs, then you should avoid giving them.”

The use of an antidepressant in a child should usually be done only in the inpatient setting, said Dr Jureidini.

He himself has not initiated antidepressant therapy in a child more than once or twice in the past 5 years. However, it is not uncommon for him assume care for a child who is already receiving an antidepressant, “and I wouldn’t necessarily stop that.”

In the absence of available psychotherapy, there are other nondrug approaches clinicians can take to treat a child with depressive symptoms.

One is to look for a better explanation for the symptoms than to just call it major depression. “Very often, symptoms are caused by life circumstances, and sometimes those life circumstances can be addressed in a way that resolves the symptoms.”

In situations in which there is no apparent explanation for the symptoms or in which nothing can be done about them directly, Dr Jureidini suggests taking a “watchful waiting” approach, even in cases of moderate and severe depression.

It might be a matter of helping the child make sense of what they are feeling. For example, he or she might still be grieving from the loss of a beloved grandmother.

Dr Jureidini pointed out that depression usually lasts weeks, not months.

Does he think the use of antidepressants in children will disiminish significantly in response to this new study? “I hope so, but probably not.”

He sees two factors standing in the way of getting the message across ― pharmaceutical marketing, and key opinion leaders.

“In any community, particularly in North America, you find senior, often academic child psychiatrists and others who are enthusiastic prescribers of antidepressants and who will influence the prescribing pattern of many other doctors.”

He anticipates that “prominent figures” will “stand up and say either publicly or within their academic communities that this paper is misleading, that antidepressants save lives, and that we should all continue prescribing them.

Pregnant Women May Overestimate Risk of Some Drugs


Pregnant women are often steering clear of drugs that might ease problems like nausea and urinary tract infections even though the treatments may be safe, a U.K. study suggests.

Researchers surveyed 1,120 women about common problems they experienced during pregnancy and whether they thought medications to treat these issues were harmful or beneficial.

Overall, about 76 percent of the women reported taking medication for at least one of eight common conditions during pregnancy including nausea, heartburn, constipation, colds, urinary tract infections, neck or pelvic pain, headaches and sleeping problems.

But for some problems, many women didn’t take medications, even when drugs might not be harmful or forgoing treatment might be dangerous, researchers report in the International Journal of Clinical Pharmacy, online May 30.

“Many women avoid medications as they fear harming the child,” said lead study author Michael Twigg, a pharmacy researcher at the University of East Anglia.

“We don’t want women to avoid medication and suffer unnecessarily from conditions that can be treated relatively easily,” Twigg added by email.

To understand how women think about medication use during pregnancy, Twigg and colleagues analyzed data from an online survey of women in England, Scotland, Wales and Northern Ireland.

Roughly 40 percent of the participants were pregnant when they completed the survey, while the rest had given birth within the previous year.

About 17 percent of the women reported having a chronic medical condition, most often asthma, allergies, depression, anxiety or thyroid issues.

For common pregnancy issues like nausea, sleep problems and constipation, women often avoided medication even though there are certain treatments available that are not considered harmful, the study found.

Even though about 79 percent of women experienced nausea during pregnancy, for example, only around 10 percent of them took medication.

Non-prescription anti-nausea drugs offer an example of how women may needlessly suffer and potentially allow small problems to escalate into bigger ones by avoiding treatment, said Angela Lupattelli, a study coauthor and pharmacy researcher at the University of Oslo in Norway.
“Nausea and vomiting can be very devastating for women, and it is very important that women do not become dehydrated or unhealthy as a result of pregnancy sickness,” Lupattelli added by email.

With sleep, 67 percent of women reported problems but only about 1 percent of them took drugs even though there are some nonprescription options that are not considered harmful during pregnancy.

Roughly 55 percent of women said they suffered from constipation, but only 19 percent of them turned to medication for relief. In this case, too, certain medications are thought to be safe during pregnancy.

Most worrisome, only about 65 percent of women who developed urinary tract infections during pregnancy took medications, a concern because these can escalate into kidney infections that can be life threatening for both mothers and their babies.

“Some untreated conditions such as urinary tract infections mentioned in the article, but also chronic conditions including depression, may cause severe complications, endangering the health of the mother and her unborn child,” said Marleen van Gelder, a pharmacy researcher at Radboud University Medical Center in the Netherlands who wasn’t involved in the study.

One problem, of course, is that drug trials exclude pregnant women for ethical reasons, limiting how much we know about whether many treatments are truly safe during pregnancy, van Gelder added by email.

Safety can also vary by trimester, and the benefits and harms of treatment may depend on the severity of women’s symptoms and other aspects of their pregnancy or medical history, ven Gelder noted.

One limitation of an online study is that the subset of women who choose to participate may not reflect the broader population, the authors note. The study team also lacked participants’ medical records or data on their drug use during pregnancy to assess how the severity of certain conditions might have influenced the women’s opinions about medication.

Women should ask a health professional when they have questions about drugs during pregnancy, Twigg advised.

“The consequences of not discussing appropriate use of medicines during pregnancy . . . can be serious,” Twigg said.

Recurrent C. difficile Infection More Common in IBD


People with inflammatory bowel disease (IBD) are at increased risk of experiencing recurrent Clostridium difficile infection (CDI), according to a new study.

“In addition to finding that IBD patients had higher rates of recurrent C. difficile infection than non-IBD patients, we also found that these recurrent infections often occurred well beyond 6 months,” Dr. Geoffrey C. Nguyen from the University of Toronto, Ontario, Canada, told Reuters Health by email.

“This is in contrast to non-IBD patients who experienced recurrent CDI within the first 6 months. I think this is an indication that IBD patients have ongoing risk factors related to their disease or its treatment,” he said.

CDI is twice as common among hospitalized IBD patients and is associated with more than triple hospital mortality rates compared with non-IBD patients. Recurrent CDI remains a significant challenge for IBD patients, Dr. Nguyen and colleagues note in The American Journal of Gastroenterology, online May 24.

The team investigated the incidence of recurrent CDI among 503 patients with CDI, 110 (22%) of whom were IBD patients.

During more than 13,000 person-months of follow-up, nearly a third of IBD patients (31.8%) experienced recurrent CDI, compared to 23.9% of non-IBD patients (p<0.01).

The incidence of recurrent CDI was 2.04 episodes per 100 person-months for IBD patients, compared with 1.25 episodes per 100 person-months for non-IBD patients (p<0.001).

The mean time to first recurrence of CDI was significantly shorter in the non-IBD group (76 days) than among patients with IBD (157 days).

IBD patients were more likely than non-IBD patients to require colectomy after CDI (6.4% vs. 0.3%, p<0.001). There were no CDI-attributable deaths among IBD patients, but 12.2% of non-IBD patients died because of CDI.
Compared with IBD patients who had only a single episode of CDI, IBD patients with recurrent CDI were significantly more likely to report recent antibiotic therapy, 5-aminosalicylic acid (5-ASA) use, steroid use, and biologic therapy.

Significant independent predictors of recurrent CDI in IBD patients included non-ileal Crohn’s disease and the use of 5-ASA.

Compared with non-IBD patients, IBD patients were 48% less likely to have a recurrence within six months, but 4.88-fold more likely to experience one after six months.

“The predisposing factors for CDI and recurrent CDI are likely different for those with IBD than those without,” Dr. Nguyen said. “We need to further understand these risk factors in order to reduce the burden of CDI in the IBD population.”

“I think physicians need to remain vigilant for recurrent CDI in IBD patients even years after the initial infection,” Dr. Nguyen concluded. “So we need to continue to test for C. difficile during diarrhea-predominant IBD flares.”

Dr. David G. Binion, director of translational IBD research at the University of Pittsburgh School of Medicine, told Reuters Health by email that “Much of the morbidity and mortality related to C. difficile stems from recurrent infection.”

“The paper is very interesting and important and sheds new light on the challenge of C. difficile infection in patients with IBD,” said Dr. Binion, who was not involved in the study.