Angelina’s mastectomy… and other medical stories of 2013


With a baby cured of HIV and breakthroughs in dementia, it’s been a year where two of the great scourges of our time have been put on the back foot.

Meanwhile a vision of the future of medicine has emerged, with scientists growing miniature organs -including brains – and performing the first steps of human cloning.

BBC health and science reporter James Gallagher reviews the year in medical science.

HIV baby cure

HIV virus

One of the most remarkable stories of the year was a baby girl in the US seemingly being “cured” of HIV.

Her mother had an uncontrolled HIV infection and doctors suspected the baby would be infected too, so they decided to give antiretroviral drugs at birth.

Normally the drugs hold the virus in check, but the very early treatment seems to have prevented HIV taking hold.

The baby is now three, has been off drugs for more than a year and has no sign of infection.

However, as this analysis explains, a cure for HIV is still a distant prospect. Yet there have been other developments – two patients have been taken off their HIV drugs after bone-marrow transplants seemed to clear the virus.

HIV was once thought to be impossible to cure; now there is real optimism in the field.

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Post-menopausal pregnancy

Dr Kazuhiro Kawamura
Dr Kazuhiro Kawamura of the St Marianna University medical school holding the newborn

Going through an early-menopause used to be seen as the end of a woman’s reproductive life.

But this year a baby was born after doctors, in the US and Japan, developed a technique to “reawaken” the ovaries of women who had a very early menopause.

They removed a woman’s ovaries, activated them in the laboratory and re-implanted fragments of ovarian tissue.

Any eggs produced were then taken and used during normal IVF.

Fertility experts described the findings as a “potential game-changer”.

However, things will not change for women going through the menopause at a normal age as poor egg quality will still be a major obstacle.

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Angelina and Andy

Angelina Jolie and Andrew Marr

The cult of celebrity catapulted two diseases into the public eye this year – breast cancer and strokes.

Hollywood actress Angelina Jolie had a double mastectomy after her doctors said she had an 87% chance of developing breast cancer during her lifetime.

She has a mutation in her DNA, called BRCA1, which greatly increases the odds of both breast and ovarian cancer.

In a newspaper article she said: “I feel empowered that I made a strong choice that in no way diminishes my femininity…for any woman reading this, I hope it helps you to know you have options.”

BBC presenter Andrew Marr had a stroke after an intensive rowing machine session and a year of “heavily overworking”.

It put a spotlight on the standard of care for stroke patients and raised the question why do healthy people have strokes?

He says he’s “lucky to be alive” and is back presenting, although the stroke has affected “the whole left hand side of my body”.

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Lab-grown mini organs

Cross-section of miniature human brains termed cerebral organoids

This purple and green image is of a very special human brain which was grown from skin cells entirely in a laboratory.

The pea-sized “cerebral organoid” is similar to the brain of a nine-week-old foetus.

It has distinct brain regions such as the cerebral cortex, the retina, and an early hippocampus, which would be heavily involved in memory in a fully developed adult brain.

Scientists hope the organoids, which are not capable of thought, will transform the understanding of the development of the brain and neurological disorders.

And it’s not just brains. Japanese researchers said they were “gobsmacked” at making tiny functioning livers in the same way.

They think transplanting thousands of these liver buds could help to reverse liver failure.

On a larger scale, researchers have made full-sized kidneys for rats which were able to make urine.

Their vision is to take a donor kidney and strip it of all its old cells to leave a honeycomb-like scaffold, which would then be used to build a new kidney out of a patient’s own cells.

Expect more from the “grow-your-own organs” field in the coming years.

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Dementia on the back foot

Brain
Loss of tissue in a demented brain compared with a healthy one

Understanding the billions of neurons which make up the human brain, one of the most complex structures in the universe, is one of the greatest challenges in medical science.

This year marked a major breakthrough in defeating neurodegenerative diseases such as Alzheimer’s.

A team of UK Medical Research Council scientists used a chemical to stop the death of brain cells, in a living brain, that would have otherwise died due to a neurodegenerative disease.

This is a first and a significant discovery. One prominent scientist said this moment would “be judged by history as a turning point in the search for medicines to control and prevent Alzheimer’s disease”.

Dementia has also become a major global priority in 2013 amid fears it is rapidly becoming the health and social care problem of a generation.

The G8 group of nations have pledge to fund research aimed at curing the disease by 2025.

It is just one aspect of a flood of money entering brain research.

President Obama has dedicated millions of dollars for mapping the connections in the brain and in Europe the billion pound Human Brain Project to simulate the organ using computers is now under way.

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Human cloning

Row of babies

Human cloning was used to produce early embryos which a group of US scientists described as a “significant step” for medicine.

It has been a long struggle to reach this stage, the same technique was used to produce Dolly the sheep way back in 1996.

No-one is considering attempting to let a cloned embryo develop.

Instead the cloned embryos were used as a source of stem cells, which can make new heart muscle, bone, brain tissue or any other type of cell in the body.

However, it is an ethically charged field of research and there have been calls for a ban.

Meanwhile, the first trial of stem cells produced from a patient’s own body has been approved by the Japanese government.

Scientists will use the cells to attempt to treat a form of blindness – age-related macular degeneration.

And a new era of regenerative medicine could be opened up by transforming tissue inside a living animal back to an embryonic state.

It’s an inherently dangerous thing to do; the tissues became cancerous in the experiments, but if it was controlled then it could be used to heal the body.

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A new role for sleep and body clock resets

Brain in a head

Scientists have found a new explanation for why we sleep – for a spot of housework.

As well as being involved in fixing memories and learning, it seems the brain uses sleep to wash away the waste toxins built up during a hard day’s thinking.

They think failing to clear some toxic proteins may play a role in brain disorders such as Alzheimer’s diseases.

Meanwhile, a separate group of researchers think it may be possible to slow the decline in memory and learning as we age by tackling poor sleep.

And there is no doubt about the impact a poor night’s sleep has on the whole body. The activity of hundreds of genes was altered when people’s sleep was cut to less than six hours a day for a week.

Of course you could blame the moon after a “lunar influence” on sleeping patterns was discovered. It showed that the extra light from a full moon makes it harder to sleep.

There may be good news on the horizon for shift workers and jet setters who will be intimately familiar with the pains of having a body clock out of sync with the world around them.

A team at Kyoto University has found the body clock’s “reset button” inside the brain.

They tested a drug which let the body clock rapidly adjust to new timezones, instead of taking days. It brings the prospect of drugs to avoid jet lag much closer.

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Deadly infections new and old

Coronavirus

Two new viruses have attracted global attention and concern this year.

A new bird flu, H7N9, emerged in China infecting more than 130 people and causing 45 deaths.

However, most were confined to the beginning of the year when the virus first emerged. Closing live poultry markets in affected areas has largely cut the spread of the virus.

And Saudi Arabia is at the centre of an outbreak of Middle East respiratory syndrome coronavirus. The animal source of the virus has not yet been confirmed, although camels are a likely culprit.

Meanwhile, polio has returned to war-torn Syria for the first time in 14 years.

And in the UK, an outbreak of measles infected 1,200 people – as a result of a drop in vaccination during the completely unfounded MMR-autism scare a decade earlier. The World Health Organization warned Europe risked failing to meet its pledge to eliminate measles by 2015.

Odds, ends and an impotent James Bond

The mobile app in action: Scanning the back of the eye

There were many interesting one-off stories this year too – some serious, some not…

A modified smartphone is being tested in Kenya to see if it can prevent blindness in some of the poorest parts of the world.

Doctors warned that antibiotics were running out and could lead to an “antibiotic apocalypse”.

Scientists claimed a milestone moment for cancer after finding 21 major mutations behind that accounted for 97% of the most common cancers.

There was a shift in understanding psychiatric disorders when it was shown autism, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder and schizophrenia all shared several genetic risk factors.

A surgical knife which can sniff out tumours was developed to improve cancer surgery.

The iKnife

New teeth have been grown out of the most unlikely of sources, human urine.

A treatment to banish bald spots is a step closer after human hair was grown in the laboratory, however, there are still engineering challenges to get the hairs the same shape, size and as long as before.

Another thing to blame your parents and grandparents for…behaviour can be affected by events in previous generations which have been passed on through a form of genetic memory.

A wheelchair was controlled with a pierced tongue.

The UK’s first hand transplant took place in Leeds while in China a severed hand was kept alive on an ankle.

Brain scans showed babies could decipher speech as early as three months before birth.

Lullabies may help sick children by reducing pain and improving their wellbeing.

And finally… James Bond’s sexual prowess was seriously questioned with doctors describing him as an “impotent drunk”.

James Bond
Doctors say James Bond, played here by actor Daniel Craig, has a drink problem
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MAGNEsium Trial In Children (MAGNETIC): a randomised, placebo-controlled trial and economic evaluation of nebulised magnesium sulphate in acute severe asthma in children.


There are few data on the role of nebulised magnesium sulphate (MgSO4) in the management of acute asthma in children. Those studies that have been published are underpowered, and use different methods, interventions and comparisons. Thus, no firm conclusions can be drawn.
OBJECTIVES: Does the use of nebulised MgSO4, when given as an adjunct to standard therapy in acute severe asthma in children, result in a clinical improvement when compared with standard treatment alone?
DESIGN: Patients were randomised to receive three doses of MgSO4 or placebo, each combined with salbutamol and ipratropium bromide, for 1 hour. The Yung Asthma Severity Score (ASS) was measured at baseline, randomisation, and at 20, 40, 60 (T60), 120, 180 and 240 minutes after randomisation.
SETTING: Emergency departments and children`s assessment units at 30 hospitals in the UK. 
PARTICIPANTS: Children aged 2-15 years with acute severe asthma.
INTERVENTIONS: Patients were randomised to receive nebulised salbutamol 2.5 mg (ages 2-5 years) or 5 mg (ages >/= 6 years) and ipratropium bromide 0.25 mg mixed with either 2.5 ml of isotonic MgSO4 (250 mmol/l, tonicity 289 mOsm; 151 mg per dose) or 2.5 ml of isotonic saline on three occasions at approximately 20-minute intervals. MAIN OUTCOME MEASURES: The primary outcome measure was the ASS after 1 hour of treatment. Secondary measures included `stepping down` of treatment at 1 hour, number and frequency of additional salbutamol administrations, length of stay in hospital, requirement for intravenous bronchodilator treatment, and intubation and/or admission to a paediatric intensive care unit. Data on paediatric quality of life, time off school/nursery, health-care resource usage and time off work were collected 1 month after randomisation.
RESULTS: A total of 508 children were recruited into the study; 252 received MgSO4 and 256 received placebo along with the standard treatment. There were no differences in baseline characteristics. There was a small, but statistically significant difference in ASS at T60 in those children who received nebulised MgSO4 {0.25 [95% confidence interval (CI) 0.02 to 0.48]; p = 0.034} and this difference was sustained for up to 240 minutes [0.20 (95% CI 0.01 to 0.40), p = 0.042]. The clinical significance of this gain is uncertain. Assessing treatment-covariate interactions, there is evidence of a larger effect in those children with more severe asthma exacerbations ( p = 0.034) and those with a shorter duration of symptoms ( p = 0.049). There were no significant differences in the secondary outcomes measured. Adverse events (AEs) were reported in 19% of children in the magnesium group and 20% in the placebo group. There were no clinically significant serious AEs in either group. The results of the base-case economic analyses are accompanied by considerable uncertainty, but suggest that, from an NHS and Personal Social Services perspective, the addition of magnesium to standard treatment may be cost-effective compared with standard treatment only. The results of economic evaluation show that the probability of magnesium being cost-effective is over 60% at cost-effectiveness thresholds of pound1000 per unit decrement in ASS and pound20,000 per quality-adjusted life-year (QALY) gained, respectively; it is noted that for some parameter variations this probability is much lower, reflecting the labile nature of the cost-effectiveness ratio in light of the small differences in benefits and costs shown in the trial and the relation between the main outcome measure (ASS) and preference based measures of quality of life used in cost-utility analysis (European Quality of Life-5 Dimensions; EQ-5D).
CONCLUSIONS: This study supports the use of nebulised isotonic MgSO4 at the dose of 151 mg given three times in the first hour of treatment as an adjuvant to standard treatment when a child presents with an acute episode of severe asthma. No harm is done by adding magnesium to salbutamol and ipratropium bromide, and in some individuals it may be clinically helpful. The response is likely to be more marked in those children with more severe attacks and with a shorter duration of exacerbation. Although the study was not powered to demonstrate this fully, the data certainly support the hypotheses that nebulised magnesium has a greater clinical effect in children who have more severe exacerbation with shorter duration of symptoms.

 

Follow-Up Care Crucial for Pediatric Cancer Survivors.


Today 80 percent of children with cancer survive for five years or longer after their diagnosis, and most young survivors grow up to lead long lives. But many deal with after-effects of cancer for their entire lifetimes. Nearly three-quarters of these childhood cancer survivors will later develop a chronic health problem as a delayed effect of treatment, making long-term health monitoring critical to their well-being.

Pictured: Charles Sklar

Pediatric endocrinologist Charles Sklar directs Memorial Sloan-Kettering’s Long-Term Follow-Up Program, which has screened and managed the health of about 2,000 pediatric cancer survivors since its launch in 1990. Dr. Sklar is an active participant in a national research group known as the Childhood Cancer Survivor Study, which monitors the health of pediatric cancer survivors into adulthood to analyze the late effects of cancer treatment and determine how to better detect and treat them.

In a recent interview, Dr. Sklar discussed the Long-Term Follow-Up Program’s role in raising awareness of these lingering effects and why lifelong vigilance is essential.

Are parents of pediatric survivors typically prepared for dealing with late effects of treatment that can impact their child long-term or for the rest of their lives?

Most families that come to us now have heard of these effects, which is somewhat different than when our program started. Oncologists typically discuss most of these potential late effects at the time of diagnosis.

That being said, when you’re the parent of a child with a life-threatening illness, there’s only a limited amount of information you can take in. And often the survivors themselves are not aware because they may have been very young at the time of diagnosis, so these aren’t things that were necessarily discussed with them directly. That’s something we often need to do when we see them in our clinic.

What are the most common delayed effects of cancer treatment such as chemotherapy or radiation on children?

It’s difficult to generalize because treatments are very different for different diseases, and younger children have different vulnerabilities compared to older children. Endocrine, growth, and reproductive problems are very common. Heart and lung problems certainly do occur, but only in select groups of people, and there are very few people who actually suffer from clinically important heart or lung impairments.

How do you diagnose and treat late effects?

Every patient gets a tailored treatment summary that looks at all the therapies they received – including the types and doses of chemotherapy or radiation – as well as the patient’s gender and age at the time of treatment.

We develop a care plan based both on our own experience as well as published guidelines we were instrumental in developing, and we begin a screening program. Some screenings require a yearly blood test; specialized testing like echocardiograms or pulmonary function testing; or sending patients to experts for tests such as neurocognitive testing.

If the tests continue to be normal, there’s obviously nothing to do but continue the screening. Along the way we educate families and survivors about the need to do many of these tests for the rest of their lives.

If we see abnormalities in our screening tests, we treat them or send the patients to specialists who can treat them or perhaps follow them with more sophisticated testing.

How has research on late effects of cancer treatment changed the way that pediatric cancer patients are now treated after their initial cancer diagnosis?

Many changes in treatment have been informed by these types of studies. It’s important to understand that the full scope of late effects and a complete understanding of their prevalence can take 20 to 30 years to come about, so there’s a lot we don’t know yet.

But now we do know, for example, that radiation to the brain – which used to be a standard treatment for almost all children with leukemia – put these children at risk for learning, growth, and endocrine problems. Today, radiation to the brain is only given to a very tiny fraction of children with leukemia, the most common cancer that we see in children.

Radiation to the chest, particularly for young women with Hodgkin’s disease, has now been associated with a very high risk of breast cancer as well as heart problems for both men and women. So the volume, dose, and even the use of radiation has been reduced among these patients over the last 20-plus years.

Are there any new findings from the Childhood Cancer Survivor Study that you find especially compelling?

One study just coming out looked at the interaction between traditional cardiovascular risk factors like high blood pressure, diabetes, and high cholesterol in patients who had cancer treatments that put them at risk for heart problems, such as radiation to the heart area.

While we knew that these children are at risk for certain kinds of heart problems as they age, now we also know that adding in traditional cardiovascular risk factors increases their cardiovascular risks several fold. Their lifetime risk for heart problems and death from heart disease can be significantly reduced if appropriately managed.

What challenges remain in helping childhood cancer survivors?

We need to educate and train physicians and other health care providers to be experts in survivorship. We now have a fellowship here in pediatric survivorship offering specialized, in-depth training to people who want to have a career in taking care of survivors. It’s just now becoming available as a formal area of medical specialization.

USFDA approves breakthrough drug for hepatitis C.


The nod represents a significant shift in treatment paradigm

The U.S. has approved a breakthrough therapy for treatment of chronic hepatitis C that is expected to offer a more palatable cure to millions of people infected with the liver-destroying viral disease.

Approved by the Food and Drug Administration, the pill, Sovaldi (sofosbuvir) is the first drug that has demonstrated safety and efficacy to treat certain types of HCV infection without the need for co-administration of interferon, an official announcement said on Friday.

“Today’s (Friday’s) approval represents a significant shift in the treatment paradigm for some patients with chronic hepatitis C,” said Edward Cox, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research.

Sovaldi is the second drug approved by the FDA in the past two weeks to treat chronic HCV (hepatitis C virus) infection.

On November 22, the FDA had approved Olysio (simeprevir).

Sovaldi is marketed by Gilead, based in Foster City, California. Olysio is marketed by Raritan, New Jersey-based Janssen Pharmaceuticals.

Clinical trials

The FDA said Sovaldi’s effectiveness was evaluated in six clinical trials consisting of 1,947 participants, who had not previously received treatment for their disease (treatment-naive) or had not responded to previous treatment (treatment-experienced), including participants co-infected with HCV and HIV.

Hepatitis C is a viral disease that causes inflammation of the liver that can lead to diminished liver function or liver failure.

About 3.2 million Americans are infected with hepatitis C, according to the Centers for Disease Control and Prevention, the CNN said.

Symptoms

Symptoms may include fever, fatigue, loss of appetite, vomiting, nausea, abdominal pain, dark urine, clay—coloured bowel movements, joint pain and jaundice, according to the CDC.

The once-a-day pill is the first approved to treat certain types of hepatitis C infection without the need for interferon, an injected drug that can cause severe flu-like symptoms. Hepatitis C, which is often undiagnosed, affects about 3.2 million Americans, killing more than 15,000 each year, mostly from illnesses such as cirrhosis and liver cancer. Most patients will be treated with the $1,000-a-day drug for 12 weeks, resulting in a total list price of $84,000, according to Gilead spokeswoman Cara Miller.

Last year, the CDC recommended that all baby boomers, born from 1945 to 1965, be tested for the virus. Introduction of blood and organ screening in the 1990s has dramatically lowered infection rates for younger generations.

The Gilead drug’s approval was supported by several studies showing that it helped to eradicate the virus in significantly more patients, with fewer side effects, than the current drug regimen.

Sovaldi is the first in a new class of medications known as nucleotide analogue inhibitors, or “nukes,” designed to block a specific protein that the hepatitis C virus needs to copy itself.

Pump provides liver disease relief


pump diagram
The rechargeable pump sits underneath the skin and can be switched off at night

Patients at the Royal Free Hospital in London are testing a device that provides relief from a common side-effect of liver disease.

The pump siphons off excess fluid that can build up in the abdomen after liver failure and diverts it to the bladder so it can be urinated out.

A liver transplant may be the only option for patients with cirrhosis.

Doctors say the pump could buy time and may even allow the liver to recover, avoiding the need for a transplant.

“Start Quote

It can improve quality of life for patients and keep them out of hospital for longer”

Prof Rajiv Jalan

So far eight patients at the Royal Free have had one fitted.

The Alphapump sits beneath the skin of the abdomen and is connected to two small tubes that do the siphoning.

Ascites

When patients have cirrhosis, the liver and kidneys stop working properly and fluid, known as ascites, can accumulate.

Litres of fluid can gather inside the abdominal cavity, making the patient appear pregnant as well as being painful.

Patients may have to make weekly or monthly trips to hospital to have the fluid drained.

Rajiv Jalan, professor of hepatology at University College London’s institute for liver and digestive health at the Royal Free, is the doctor running the trial.

He said: “With cirrhosis, patients can accumulate litres and litres of fluid. They might need to come to hospital fortnightly to have up to 20 litres drained from their tummy.

“The pump can avoid this by draining about 15 millilitres every 15 minutes. It means they’ll pass a little bit more urine but they can turn the pump off at night.

“It can improve quality of life for patients and keep them out of hospital for longer.”

ICU Stay Linked to Long-term Cognitive Impairment.


Long-term Cognitive Impairment After Critical Illness

Study Summary

People who survive life-threatening illness often have long-term, disabling cognitive impairment. However, few studies have addressed this serious complication.

The investigators studied 821 adults with respiratory failure or shock in the medical or surgical intensive care unit. At baseline, 6% had cognitive impairment, and 74% developed delirium during their hospitalization. Using the Repeatable Battery for the Assessment of Neuropsychological Status and the Trail Making Test, Part B, the investigators tested global cognition and executive function at 3 and 12 months after discharge.,

Global cognition scores at 3 months were 1.5 SD below the population means (or similar to scores for patients with moderate traumatic brain injury) in 40% of patients. Scores were 2 SD below the population means (or similar to scores for patients with mild Alzheimer disease) in 26% of patients. Younger patients as well as older patients had these deficits, which were persistent. At 12 months, 34% of all patients had scores similar to those with moderate traumatic brain injury, and 24% had scores similar to those with mild Alzheimer disease.

Longer duration of delirium was an independent predictor of worse global cognition at 3 months (P = .001) and at 12 months (P = .04) and of worse executive function at 3 months (P = .004) and at 12 months (P = .007). In contrast, sedative or analgesic use was not consistently associated with cognitive impairment at 3 and 12 months, after adjustment for delirium.

Viewpoint

This large, multicenter, prospective cohort study with a diverse patient population had several limitations. These included inability to test patients’ cognition before their illness, inability of some patients to complete all cognitive tests, and possible bias related to unmeasured confounders.

Nonetheless, this study showed that cognitive impairment after critical illness is very common and may persist in some patients for at least 1 year. At 12 months after critical illness, 1 of every 4 patients had cognitive impairment similar in severity to that of patients with mild Alzheimer disease, and 1 of 3 had impairment similar to that seen in moderate traumatic brain injury.

 

Cognitive deficits were more likely in patients with a longer duration of delirium. Although the mechanisms underlying this association are still unclear, delirium is associated with inflammation and neuronal apoptosis, which may result in brain atrophy. These findings suggest that interventions to reduce delirium could have the potential to reduce brain injury associated with critical illness.

Source: NEJM

 

 

Today is World Diabetes Day


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Let today be the beginning of the end of your diabetes. Today being the World Diabetes Day, there is no better a day to take a new step for the awareness of the lifestyle disease, Diabetes. Every year, World Diabetes Day is co-ordinated by the International Diabetes Federation (IDF) with a particular theme; between 2009 and 2013 the theme has been ‘education and prevention’.

Opioids Prove Effective for Restless Legs Syndrome.


In a new, placebo-controlled study, prolonged-release opioid treatment with an oxycodone-naloxone combination product produced impressive relief of symptoms in patients with severe restless legs syndrome for whom other therapies had failed.

The study, published online October 18 in Lancet Neurology, was led by Claudia Trenkwalder, MD, Paracelsus-Elena Hospital, Kassel, Germany.

“We found an 8-point reduction in the mean International RLS Study Group rating scale sum score vs placebo,” Dr. Trenkwalder commented to Medscape Medical News. “This is the most effective treatment response ever seen in restless legs syndrome. A reduction of more than 3 points is thought to be clinically significant. While between-study comparisons are always difficult, dopaminergic drugs ― the main agents used ― are associated with reductions of about 4 to 6 points vs placebo. A reduction of 8 points has never been seen before.”

Professor Trenkwalder explained that there has been much interest in using opioids in restless legs syndrome for many years, after a small study conducted in 1993 showed a positive effect in 8 patients. This has been followed by other small case series and anecdotal reports, but there has never been a controlled clinical trial before.

“This trial is long overdue. It has taken us 20 years to get it done, largely because no one wanted to pay for it. But we eventually managed to get funding from MundiPharma and have now definitely proven that this opioid-based combination works and works very well in reducing all symptoms of restless legs syndrome ― sensory, restlessness, pain, and sleep,” she said.

She added that doctors have been using different opioids at different dosages over the years, but this study provides solid evidence in support of one combination product used at a low dosage and given twice a day.

Professor Trenkwalder noted that the inclusion of the opioid antagonist naloxone counters peripheral side effects of the oxycodone in the gastrointestinal system and so minimizes constipation, the major side effect of long-term opioid therapy. She also highlighted the importance of taking the drug combination twice a day ― morning and evening. “Some people just take medication for restless legs syndrome at night, but you then get high levels at night and a trough during the day. It is important to have stable levels of opiates in the brain to get good symptom improvement.”

In an accompanying commentary, Arthur S. Walters, MD, Vanderbilt University School of Medicine, Nashville, Tennessee, says that the data are “especially convincing because the study included patients who were refractory to other treatments. Such patients would normally be much more likely to fail an alternative treatment than patients who have not had previous treatment failure.”

Although he notes that no direct comparisons can be made between drugs, “the treatment difference between groups of 8.15 points is much greater than that for most approved drugs for restless legs syndrome.”

For the study, Professor Trenkwalder and colleagues randomly assigned 306 patients who had had symptoms for at least 6 months and whose International RLS Study Group severity rating scale sum score was at least 15 to study drug or placebo. Study drug was oxycodone 5 mg, naloxone 2.5 mg twice daily, up-titrated according to investigator’s opinion to a maximum of oxycodone 40 mg, naloxone 20 mg twice daily.

The primary outcome was mean change in severity of symptoms according to the International RLS Study Group severity rating scale sum score at the end of the 12-week double-blind phase.

Mean score at baseline was 31.6. This was reduced by 16.5 points in the oxycodone-naloxone group vs 9.4 points in the placebo group ― a difference of 8.15 points.

Primary Outcome: International RLS Study Group Severity Rating Scale Sum Score at 12 Weeks

Oxycodone-Naloxone Placebo Treatment Difference (95% CI) PValue
Mean sum score at 12 weeks 15.1 22.1 8.15 (5.46 – 10.85) <.0001

Intrarenal Resistive Index after Renal Transplantation.


BACKGROUND

The intrarenal resistive index is routinely measured in many renaltransplantation centers for assessment of renal-allograft status, although the value of the resistive index remains unclear.

METHODS

In a single-center, prospective study involving 321 renal-allograft recipients, we measured the resistive index at baseline, at the time of protocol-specified renal-allograft biopsies (3, 12, and 24 months after transplantation), and at the time of biopsies performed because of graft dysfunction. A total of 1124 renal-allograft resistive-index measurements were included in the analysis. All patients were followed for at least 4.5 years after transplantation.

RESULTS

Allograft recipients with a resistive index of at least 0.80 had higher mortality than those with a resistive index of less than 0.80 at 3, 12, and 24 months after transplantation (hazard ratio, 5.20 [95% confidence interval {CI}, 2.14 to 12.64; P<0.001]; 3.46 [95% CI, 1.39 to 8.56; P=0.007]; and 4.12 [95% CI, 1.26 to 13.45; P=0.02], respectively). The need for dialysis did not differ significantly between patients with a resistive index of at least 0.80 and those with a resistive index of less than 0.80 at 3, 12, and 24 months after transplantation (hazard ratio, 1.95 [95% CI, 0.39 to 9.82; P=0.42]; 0.44 [95% CI, 0.05 to 3.72; P=0.45]; and 1.34 [95% CI, 0.20 to 8.82; P=0.76], respectively). At protocol-specified biopsy time points, the resistive index was not associated with renal-allograft histologic features. Older recipient age was the strongest determinant of a higher resistive index (P<0.001). At the time of biopsies performed because of graft dysfunction, antibody-mediated rejection or acute tubular necrosis, as compared with normal biopsy results, was associated with a higher resistive index (0.87±0.12 vs. 0.78±0.14 [P=0.05], and 0.86±0.09 vs. 0.78±0.14 [P=0.007], respectively).

CONCLUSIONS

The resistive index, routinely measured at predefined time points after transplantation, reflects characteristics of the recipient but not those of the graft.

 

Souirce: NEJM

 

 

Adrenal fatigue symptoms and seven ways to support and heal your adrenal glands.


In our modern world, adrenal fatigue is extremely common and estimated by some experts to affect approximately 80 percent of the population to some degree. Adrenal fatigue is caused by all types of stress – physical and emotional – and if left unchecked, it can lead to other illnesses such as type 2 diabetes, thyroid disease and heart attack.

fatigue

The symptoms caused by adrenal fatigue are numerous and varied. The following are some of the more common ones:

  • Anxiety
  • Panic attacks
  • Diarrhea
  • Frequent urination
  • Thyroid issues
  • Salt cravings
  • Sugar cravings
  • Insomnia
  • Waking tired
  • Needing caffeine to ‘get going’ in the morning
  • Feeling stressed
  • Inability to handle stress
  • Overthinking (having a brain that won’t turn off)
  • Dizziness when rising from seated or lying position
  • Fluid retention in feet and ankles
  • Low blood pressure


As you can see, adrenal fatigue can cause many symptoms and eventually lead to many health challenges. However, the good news is that there are plenty of things we can do to support our adrenal glands to help return them to a healthy state.

Reduce or eliminate stimulants

Stimulants such as caffeine, alcohol, nicotine and drugs cause a stress response in the body and, if used chronically, will wear out the adrenal glands. Those who feel that they need their morning coffee should understand that, although it might feel as though caffeine is helping, it is actually stealing their health by exacerbating their adrenal fatigue.

Practice meditation

Meditating daily can help reduce stress levels. Finding even 10 or 15 minutes a day to quiet the mind by meditation has been proven to be of benefit for reducing stress.

Clean up your diet

Eating a highly processed diet creates stress in the body. Many people don’t consider the stress caused to the body by eating processed foods. Processed foods contain chemicals that have no place in the body, such as preservatives, colors, stabilizers and more. These chemicals can have negative effects on the various systems of the body and add additional waste products that need to either be eliminated or stored.

Make good use of adaptogenic herbs

There are a number of adaptogens that are useful for the adrenal glands. These herbs can be taken in the form of teas, tinctures, powders or capsules and include:

  • Rhodalia
  • Ashwaganda
  • Tulsi, or Holy basil
  • Korean Ginseng
  • He Shou Wu
  • Licorice (Note: Licorice can raise blood pressure)

 

Make time to relax

Take time to chill out and make the time to do the things that you love doing and make you happy.

Eat more salt

Adrenal glands love salt. Buy a good quality, unprocessed salt, such as Celtic sea salt or Himalayan salt, and use it liberally.

Try this adrenal cocktail

Try taking this adrenal cocktail either before bed if you suffer from insomnia or upon rising if you have trouble getting going in the morning. It really works!

1/2 cup orange juice (or another form of vitamin C)
1/2 teaspoon cream of tartar
1/2 teaspoon Celtic sea salt
Mix and drink.

Finally, don’t watch horror movies and don’t do things that get your adrenaline pumping. They will simply cause more stress for your already overworked adrenal glands, leaving you feeling tired and wired.