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.

Dietary Supplement May Prevent Cognitive Decline


A dietary supplement containing ingredients commonly found in health food stores appears to prevent the decline in brain structure and function typically seen in Alzheimer’s disease, the results of an animal study indicate.

In a mouse model of accelerated aging and severe cognitive decline, a combination of vitamins and minerals, as well as nutraceuticals, such as beta carotene, bioflavonoids, cod liver oil, flax seed, garlic, and green tea extract, not only maintained brain cell numbers and mass and cognitive function but also appeared to prevent deterioration of sight and smell.

The study was led by Jennifer Lemon, PhD, research associate in the Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, Ontario, Canada.

She said that she was “shocked, along with everybody else” that a nutraceutical combination “that’s considered by most practitioners in the medical field to be either ineffective or benign can actually have such a profound effect on function.”

Dr Lemon told Medscape Medical News that she is nevertheless “optimistic” that the effects of the supplement will translate into humans. One of the main reasons is that “the supplement works on fundamental mechanisms that are pretty much ubiquitous across any organism that breathes air, essentially.”

These mechanisms, which include oxidative stress, inflammation, and mitochondrial dysfunction, “happen in a multitude of species as they get older” and are not “something that is specifically a human phenomenon that has been attempted to be recreated in a mouse model,” she noted.

The study was published online May 20 in Environmental and Molecular Mutagenesis.

Cognitive Function Restored

Previous research by the team showed that the supplement extended longevity and reduced cognitive and age-related physical deterioration in both normal mice and transgenic growth hormone mice (TGM). TGM are characterized by accelerated aging accompanied by severe cognitive decline, as well long-term oxidative stress, insulin resistance, and other traits.
For the current study, the team mated heterozygous TGM and normal mice to create equal numbers of TGM and normal mice with a similar genetic background. The mice were then randomly assigned at weaning either to receive a liquid form of the supplement every day, with the doses of the ingredients adjusted to correspond to the amounts recommended for humans, or to be left untreated.

The mice then underwent a series of somatosensory tests to determine the severity of age-related losses in motor coordination and overall mobility. Their brains were examined for histologic changes, and the degree of apoptosis and changes in cell counts were assessed. Single-photon emission computed tomography and positron-emission tomography scanning was also performed.

The team found that compared with normal mice, untreated TGM displayed brain cell losses, deterioration of sensory function, and reductions in cerebral metabolic rate and blood perfusion that were equivalent to those seen in patients with Alzheimer’s disease.

Specifically, the mice had greater than a 50% loss at a cellular level, a 36% reduction in brain mass, and at least twofold reductions in brain metabolism and blood flow at 12 months. Furthermore, in the untreated TGM, motor and cognitive functions were severely compromised.

Although the supplement did not have significant effects on brain cell numbers, brain weight, or brain metabolism or perfusion in normal mice, it had striking effects in TGM.

With the supplement, brain mass and brain cell density were maintained at levels seen in young mice. Brain metabolic activity was comparable to that in control mice, with no significant difference between the groups. Moreover, the supplement was associated with a twofold increase in brain perfusion in TGM.

The results also showed that the supplement restored cognitive function in TGM and led to significant improvements in motor coordination. It also appeared to reduce anxiety, allowing TGM to explore “unsafe/novel” environments.

The team found that the supplement appeared to offset deterioration of visual acuity in TGM. It was associated with increases in the thickness of the retinal outer nuclear layer and outer segment of 26% and 29%, respectively, in TGM compared with untreated mice.

TGM that received the supplement also showed improvements in olfactory sensitivity and greater numbers of mitral cells in the olfactory bulb in comparison with untreated mice. Inasmuch as olfactory loss is associated with an increased risk of developing severe neurodegenerative conditions, the researchers say these findings suggest that the supplement may be offsetting neurodegeneration throughout the brain.

Striking a Balance

For Dr Lemon, the findings support the notion that nutraceuticals are more likely to be effective when taken in combination with other supplements rather than when taken alone as a single supplement.

“Our criteria for including things in the supplement were mainly that there was scientific evidence to show that they worked on a particular mechanism. It didn’t have to be that it had a great whole-body effect, because most individual supplements don’t,” she said.

“That is typically because our cells are working in such a complex way that we have many mechanisms that are occurring simultaneously, and when something’s going wrong, it’s usually knocking everything out of balance.”

Dr Lemon explained that when the level of one particular component is increased in the cells, “you tend to also knock everything out of whack.

“There are a lot of studies that show that high doses of single things, like vitamin E, for instance, can create disease or can make disease worse. A lot of that has to do with the fact that the cell works optimally when it’s balanced, and when you put one thing in, particularly something that is used as an antioxidant, you can turn it into a pro-oxidant, exacerbating free radical production within the cells,” she said.

One aspect of the supplement that sets it apart from a novel pharmaceutical agent is that it is not subject to the same degree of intellectual property protection, owing to the fact that it is composed of nutraceuticals that are available in health food stores.

Acknowledging that this “will always be a problem here,” Dr Lemon said that although a company has licensed the formulation from McMaster University to commercialize it, it is likely that, should the supplement be shown to have similar effects in humans, “people would try to make versions of it.”

 There are, however, “some very specific things that we’ve done to try to make that a little bit more difficult,” Dr Lemon added.

Specifically, she noted that mice do not have diurnal rhythms such as those seen in humans. The team has therefore worked on formulating the supplement as two pills, one to be taken in the morning, and the other in the evening, “depending on what functions you’re trying to protect.”

Ebola Survivors Pose Little Risk to Care Providers Six Weeks After Viremia Clearance


Patients who are recovering from Ebola virus infection probably pose little risk to healthcare workers six weeks after viremia has cleared, according to a new study.

Dr. Edward Green, of the Royal Liverpool University Hospital in Liverpool, U.K., and colleagues analyzed data on 112 Ebola virus disease survivors who participated in a survivor-clinic follow-up investigation last year. All had been discharged from the Kerry Town, Sierra Leone, Ebola treatment unit. Median age was 21.5 years, and 50 participants were male.

The researchers collected and tested specimens from several body sites using reverse transcription polymerase chain reaction (RT-PCR). In all, they tested 555 specimens: 105 from mouth, 103 from the axilla, 93 from blood, 92 from conjunctiva, 69 from urine, 54 from forehead, 21 from the vagina, 17 from the rectum, and one from semen.

The median time from treatment discharge to specimen collection was 142 days (interquartile range, 127-159 days). However, 15 participants had 74 swabs taken fewer than 100 days from discharge.

The semen sample from one participant tested positive for Ebola virus at 114 days after discharge, but samples from the same participant taken from other body sites tested negative, as did all other samples for the other participants, the researchers report in The Lancet Infectious Diseases, online May 16.

“Our results indicate that survivors of Ebola virus disease who do not meet the case definition for acute Ebola virus disease pose a very low risk to healthcare providers undertaking routine clinical procedures 42 days after initial infection,” they write.

They conclude, “Personal protective equipment after this time might be limited to standard barrier precautions, unless contact with fluids from sanctuary sites is envisaged.”

PET/CT Cuts Dissections Not Survival in Advanced Head and Neck CA


Survival was similar among patients with squamous-cell carcinoma of the head and neck and advanced nodal disease (stage N2 or N3) whether they underwent PET/CT-guided surveillance or planned neck dissection, a prospective, randomized, controlled study from the U.K. has demonstrated.

And while the quality-of-life scores in the two groups were similar, surveillance spared about 80% of patients from undergoing a neck dissection and cost £1,492 ($2,190 U.S.) less per patient than surgery, Hisham Mehanna, PhD, from the University of Birmingham and colleagues reported online in the New England Journal of Medicine.
The 2-year overall survival rate was 84.9% (95% CI 80.7 -89.1) in the surveillance group and 81.5% (95% CI, 76.9-86.3) in the planned-surgery group, said the investigators.

“Our trial showed that PET/CT-guided surveillance was non-inferior to planned neck dissection and equally effective in both HPV-positive and HPV-negative patient groups. Patients in the surveillance group were not disadvantaged by undergoing delayed neck dissection; the global quality-of-life scores and rates of surgical complications were similar in this group and in the group of patients who underwent earlier planned neck dissection.”

“This study confirms previous retrospective studies showing that PET/CT after chemoradiation is cost effective in reducing the number of unnecessary planned neck dissections, without compromising survival,” Hassan Arshad, MD, from Roswell Park Cancer Institute in Buffalo, NY, said in an interview. Arshad, a head and neck cancer surgeon, was not affiliated with the study.

“The paper still leaves open the question of whether a patient with an N3 neck should have a planned neck dissection,” he told MedPage Today. “Ideally, we hope to have a method to identify those patients who would require a planned neck dissection, before they undergo chemoradiation.”

In the multicenter, nationwide study, 564 patients were recruited from 37 head and neck cancer centers in the U.K. from 2007 through 2012. A total of 282 patients were in the planned-surgery group and the same number were in the surveillance group.

Among these patients, 17% had nodal stage N2a disease; 61% had stage N2b disease; 84% had oropharyngeal cancer; and 75% had tumor specimens positive for the p16 protein, indicating that HPV played a role in causing the cancer.

PET/CT-guided surveillance was performed 12 weeks after the end of chemoradiotherapy in patients with stage N2 or N3 disease. Neck dissection was performed only if PET/CT showed an incomplete or equivocal response. Patients were followed for up to 5 years with a median follow-up of 36 months.
The study showed that while the rates of surgical complications were similar in the two groups, PET/CT-guided surveillance resulted in fewer neck dissections than did planned dissection surgery (54 versus 221).

The hazard ratio for death slightly favored PET/CT-guided surveillance and indicated non-inferiority (95% CI; HR<1.50; P=0.004).

There was no significant difference between the groups in terms of p16 expression, which was highly prognostic for overall survival in both groups. There was a significant difference in overall survival between the planned-surgery and surveillance groups among patients with p16-positive tumors (HR 0.74; 95% CI 0.40-1.37) and those with p16-negative tumors (HR 0.98; 95% CI 0.58 -1.66), the study showed.
The feasibility of PET/CT-guided surveillance in routine clinical practice is confirmed by the high concordance between local radiologic and central laboratory assessments, said Mehanna and colleagues. They added that this trial may have underestimated the benefit of PET/CT-guided surveillance in patients with advanced head and neck cancer, given a recent study suggesting that nodal disease may take longer to involute in patients with HPV-positive disease.

“It is therefore conceivable that patients in our trial who had HPV-positive tumors and equivocal PET/CT findings — especially with enlarged nodes — at the 3-month assessment might have achieved a cure without neck dissection if they had undergone PET/CT at a later time,” wrote the study authors. “Other researchers have reported that nodes with no FDG uptake have very high rates of regional control [93%], especially in HPV-positive disease.”

Mehanna and colleagues recommended that patients with an equivocal FDG uptake continue to undergo neck dissection, especially in the presence of HPV-negative disease. However, they emphasized, patients with HPV-positive cancers and enlarged nodes but no FDG uptake after chemoradiotherapy “may be considered for close follow-up with serial CT or PET/CT. This strategy may spare even more patients from undergoing a neck dissection.”

The investigators warned, however, that physicians should be cautious about extrapolating data from this trial into routine clinical practice since few patients had low-prevalence, N3 (stage IVb) disease.

“Although 5 of the 9 patients with stage N3 disease in the PET/CT surveillance group had complete responses, extrapolation of a PET/CT-guided surveillance policy to this higher-risk group of patients cannot currently be justified because of the small number of such patients in the trial.”

A Safe And Effective Vaccination Alternative?


The mainstream medical industry has pulled the wool over the public’s eyes for years, but their plans are unraveling as natural, safe medicines become more widely known and accepted. 

With the recent controversy over the movie Vaxxed, we are becoming more conscious of the need for truth and transparency. While some clamor to learn more details of reported malfeasance in government agencies, others chant “la-la- la-la” in an effort to drown out any opposing view to the status quo. Is the public even conscious?

Consciousness: The state of being awake, aware of one’s surroundings, and able to think. (Oxford Dictionary)

Google, YouTube, Twitter, Facebook and other social media have exploded with information that is difficult to ignore. Maybe we shouldn’t try to ignore, but wake up to the realization that acts of corruption are clearly invading government, education, medicine, agriculture, finance, and our daily lives to a degree that can no longer be drowned out. But enough of pointing out the obvious problems. We must create a new paradigm of suggesting solutions. And we must be conscious enough to explore possibilities that are different from the thinking that created the issues in the first place, as Albert Einstein has suggested.

There IS a problem with the current vaccine campaign. If there weren’t, why would there be have so much discussion, polarization, name-calling, and character defamation? Why would William Thompson, PhD, a senior scientist at the CDC issue a statement through his attorney (http://morganverkamp.com/statement-of-william-w-thompson-ph-d-regarding-the-2004-article-examining-the-possibility-of-a-relationship-between-mmr-vaccine-and-autism/) saying,

…I regret that my coauthors and I omitted statistically significant information in our 2004 article published in the journal PEDIATRICS. The omitted date suggested that African American males who received the MMR vaccine before age 36 months were at increased risk for autism. Decisions were made regarding findings to report after the data were collected, and I believe that the final study protocol was not followed… There have always been recognized risks for vaccination and I believe it is the responsibility of the CDC to properly covey the risks associated with receipt of those vaccines.” (Thompson, 2014)”

The Behemoths of Business

Pharmaceutical companies have become a global market with exponentially rapid growth and a changing status in the marketplace. The World Health Organization predicts its revenue to reach $100 billion by 2025. (http://www.who.int) They are immune to public litigation regarding vaccines since 1986 as a result of congress creating the National Vaccine Injury Compensation Program. (http://www.hrsa.gov/vaccinecompensation/) This program has paid out over $3 billion in compensation for acknowledged vaccine related injuries and deaths. (http://www.hrsa.gov/vaccinecompensation/data/statisticsreport.pdf) With any degree of consciousness we can predict where this is headed. First mandatory vaccines for children, then childcare workers, then adults, then the elderly. The profit margins have no ceiling. But not everyone is focused on the escalating fiduciary implications.

Parents are rumbling about more immediate concerns. Why so many vaccines at such a young age? What about all these toxic additives and foreign animal proteins? How can they say “safe” when vaccine injuries do happen? What about our skewed relationship to bacteria and ever-mutating viruses? These real concerns are increasing along with the overly bloated schedule of recommended vaccines.

What’s the Solution?

In 1799 Samuel Hahnemann, a medical doctor, chemist, and linguist, discovered that the homeopathic medicine called belladonna was effective as a preventative for scarlet fever. Cristoph Hufeland (1762-1836), described as the greatest German clinician of the late 18thcentury (Habrich 1991) and who founded a respected and still extant medical journal in Göttingen, reported that:

I. The proper use of belladonna has, in most cases, prevented infection, even in those instances where, by the continual intercourse with patients labouring under scarlet fever, the predisposition towards it was greatly increased.

II. Numerous observations have shown that, by the general use of belladonna, epidemics of scarlet fever have actually been arrested.

III. In those few instances where the use of belladonna was insufficient to prevent infection, the disease has been invariably slight.

IV. There are exceptions to the above three points, but their number is extremely small. (The Lancet 1829)

Thus the first application of something called Homeoprophylaxis, frequently called “HP,” was utilized. Surely the physicians of the era were not pleased with this renegade amongst their ranks introducing something outside the accepted norm of the day. This must have bordered on blasphemy to the conventional medical profession.

What Do the Studies Show?

Today, over 200 years later, things are not much different. But now there is more evidence. HP has been effectively used to prevent Leptospirosis in a group of 3.2 million people (Bracho, G, Varela, E, Fernandez, R, et al. “Large-scale application of highly-diluted bacteria for Leptospirosis epidemic control.” Homeopathy. 99 (2010): 156-166.), as well as Meningitis in 85,000 people (Mroninski, Adriano, Mattos. Homeopathic Links, Winter 2001, Vol 14(4)), Influenza (International Journal of High Dilution Research 2011; 10(36):174-176), and for the prevention of childhood illnesses in 3500 children (Golden, Isaac. “Homeoprophylaxis-A Fifteen Year Clinical Study: A Statistical Review of Efficacy and Safety of Long Term Homeoprophylaxis. Gisborne. Vic. 2004). These are not small samples. Effectiveness has been robust and in many cases exceeds the effectiveness of conventional vaccines.

Most notable is the fact that there has never been a reported death or injury as a result of using HP. Additionally, long term tracking has been conducted to assess results 10, 15, and 20 years later. Where are the long term studies with vaccines?

How does it work?

HP is produced from the actual disease, much like the original concept of vaccines. The difference lies in the degree of attenuation, or weakening of the original antigen. With HP the source material is diluted serially until no original molecules remain. This form of attenuation goes far beyond the preparation of conventional vaccines.

The substance is rendered harmless and has become ‘energetic’ as opposed to ‘material.’ This diluted solution is then anointed onto pellets and taken orally where secretory IgA immune response originates in the mucous membrane. The energetic frequency delivers information to the recipient, familiarizing him/her with the disease pattern. When later encountered in nature, the disease is either not contracted at all, or if contracted, addressed effectively with a natural immune response.

What’s the Difference?

In short, HP is clean, green, and side-effect free. It contains no additives, no adjuvents, noantibiotics, no preservatives, no human diploid cells and no animal proteins. Its point of contact is where natural immunity begins – the mucous membrane, and it’s administered one disease at a time, the same way that we bump up against disease in nature.

It does not create super bacteria or wildly mutating viruses that require more and more “boosters” to control. Remember, nine out of ten cells in and on our bodies are not human cells; they are bacteria, viruses, parasites and fungi living symbiotically with us. (GreenMedInfo, 2015) Respecting the fact that we share our environment with these organisms and that eventually “life finds a way,” is it rational to assume that optimal health and robust immunity simply require more and more vaccines?

Can We Expand to Embrace such a Concept?

HP is not yet a mainstream consideration to most conventional scientists. Expanded consciousness may be required to explore something so natural, so logical, and so harmless. It doesn’t garner large profits. It doesn’t require needles or refrigerated vials to administer. It can be administered by parents to their own children.

Is the world ready for such a concept? Can consciousness expand to include an energetic form of disease prevention that works? Many parents have already embraced the use of HP as a viable choice in their quandary about how to protect children. Open-minded healthcare providers are recommending this option and seeking out more information to share with their patients. The world IS changing and homeoprophylaxis may be on the leading edge of safer and more conscious healthcare.

Parents Do Have a Vaccine Alternative


Parents Do Have a Vaccine Alternative

Could a safe, effective and inexpensive alternative to vaccination already exist? 

Lily was my third child. She was born in China, in the city of Jiujang, in Jiangxhi Province.  She was ten months old when we traveled to get her and weighed a mere 10 pounds.

Lily was beautiful. She was more like a newborn than a one year old. She could barely hold up her head and was so accustomed to being heavily swaddled in layers of clothing that she cried when the air touched her skin the first time we carefully unwrapped her. Her tiny features were so delicate. She was as quiet as a mouse. She slept through the night without a peep. She was perfect.

Looking back, I can see that Lily was suffering from “failure to thrive,” or the lack of weight gain and physical growth that many orphans suffer when inadequately nurtured and underfed.  Combine this with a challenged immune system and the trauma of leaving the familiarity of the orphanage, and you have a child who is very vulnerable.

Once home, the pediatrician suggested that Lily needed her vaccines; the Chinese records could not be trusted.  Having never even questioned vaccines before, I agreed, and Lily was given herDPT, hepatitis B, polio, and the MMR.  What I know now is that this amounts to eight separate disease agents at once, not to mention the additives in each injection.  A chemical cocktail.

Shortly after, Lily’s leg swelled to twice the size. She became more and more agitated, crying loudly.  Long woeful shrieks were coming from her and nothing soothed her.  Her temperature was 103 F. and rising. She was clearly in great distress and I ran her back to the pediatrician where she was diagnosed with aseptic meningitis. This is an inflammation of the membrane covering the brain and spinal cord. She was given IV antibiotics and her fever continued to climb to about 105 F.  I tried to accept the fact that she might die and spent the next forty eight hours holding her warm, limp body and praying.

The Merck Manual is one of the world’s most trusted medical references. First published in 1899, The “Merck Manual of Diagnosis and Therapy” is a concise and complete medical reference for doctors, medical students, and healthcare professionals.

From its pages I read: “Disorders and drugs are common causes of meningitis. Disorders that most commonly cause meningitis include disorders that cause inflammation, including the inflammation that occurs when the body’s immune system malfunctions and attacks the body’s own tissues (autoimmune disorders).” [1] Among the culpable drugs listed are vaccines.

Eager for validation, back I went to the pediatrician, armed with my information, certain she would agree with me for unearthing the actual cause of Lily’s illness. I was sadly mistaken.  She informed me with complete confidence and authority that there was no connection whatsoever to the vaccines.  Completely impossible. And furthermore, she delivered a terse lecture on the horrors of children dying from communicable diseases and how she had seen these horrors in the field.  End of conversation.  I was speechless.

In the months and years that followed, I underwent a total reorganization of my belief system. The stark realization hit me that no one was going to look out for my kids as I do. It was up to me. The sheer responsibility felt overwhelming. But at the same time, it felt somehow empowering. I wasn’t going to trust what someone else told me without doing my own research ever again My choices eventually led me back to school where I spent four years earning a degree in homeopathic medicine. It was there that I learned more about how the healthy immune system operates.

Homeoprophylaxis – Another Choice

As a parent and as a healer, I take very seriously my commitment to “do no harm.” I always try to choose the path of least risk.

Every decision we make for our children has consequences. The choice regarding whether or not to vaccinate can be a complex and difficult one for parents. The CDC has told us that “adverse events have been reported after administration of all vaccines.” [2] Thus vaccines do carry “unavoidable risks.” My own path has led me through initially vaccinating my children, experiencing a vaccine injury with Lily, and then investigating an alternative called homeoprophylaxis.

Homeoprophylaxis has been utilized for over 200 years for epidemics as well as endemic contagious disease. The application as an alternative to the recommended immunization schedule has been clinically studied since 1985 by Dr. Isaac Golden, PhD of Australia.  It’s a concept met with skepticism by some conventional medical practitioners due to lack of understanding.  Dr. Golden is a pioneer with his emerging evidence of effectiveness, ease, and safety of the method. His work stands as the keystone to future applications of homeoprophylaxis for infectious childhood diseases. [3]

Homeoprophylaxis is the use of diluted and potentized disease products, called “nosodes,” to elicit an immune response.   While the original intent of vaccines was similarly to provide a weakened dose of the original disease, the most obvious difference today is the purity of homeopathic nosodes compared to conventional vaccines. Homeopathic nosodes contain no additives whatsoever. No antibiotics, no preservatives, no detergents no foreign DNA, or unknown viruses are present. The intent of homeoprophylaxis is to educate the immune system in a way that has been clinically shown to reduce the incidence of both infectious as well as chronic disease.

Dr. Golden’s work found improved long term health outcomes of using homeoprophylaxis for children instead of conventional vaccination. It seems that allowing exposure to the natural disease in energetic form carries this benefit without any of the risks.   Dr. Golden explains, “I would suggest that HP remedies stimulate the energetic immune response and this must lead to a maturing of the response in an analogous way that infection with simple diseases can help to mature the physical immune response.” [4]

I’ve gone on to use homeoprophylaxis with my own children and countless other children whose parents are looking for a safe alternative. I’ve met with Dr Golden and others who have successfully applied homeoprophylaxis for epidemics in Australia, Cuba, S. America, India and other nations. In October 2015 Dr Golden along with others from around the world will be gathering to present their findings at a conference called “Homeoprophylaxis: A Worldwide Choice for Disease Protection.” [5]

It’s empowering to know that there are choices and ways to keep our children safe that are natural and non-toxic.

My greatest hope is that you will research homeoprophylaxis as a valid approach to keeping your children safe. Serious study will reveal its overwhelming usefulness.