Lifestyle and Neuropathy interview with an expert in the field

Okay, most HIV patients who also have neuropathy, try to change their lifestyle in some way, to try reduce some of the worst effects of the disease. That's normal; it's not obligatory, it's just a normal reaction to try something out if someone advises you that it will help...so how does a bad diet, drinking and recreational drug use affect people's neuropathy? These are just some of the questions in this interview for Aidsmap.com files (see link below) with Dr Hadi Manji, one of only a handful of neurologists in the UK with extensive clinical experience of HIV-related neuropathy.

ATU: How can you tell whether the neuropathy is caused by HIV or by the medicines used to treat it?

Dr Hadi Manji:The presentation of HIV neuropathy is very similar to drug-related neuropathy, but there are some clues to tell whether it is the drugs or not. Sometimes the drug-related neuropathies come on very rapidly, almost explosively.My impression is that drug-related neuropathies may also be more painful. And if there's involvement of the fingers, that, to my mind, would be more drug – than HIV-related.

ATU: How many people have both HIV and drug-related neuropathy together?

HM: In my experience, a lot of people – up to 60% – who develop neuropathy that is attributed to the drugs are still left with neuropathy when they stop the offending drug, despite some improvement. My feeling is that these individuals probably had asymptomatic HIV related neuropathy that was unmasked by the drugs.

ATU:What other factors can make neuropathy worse?

HM:The bottom line is, if you've got nerve -related problems for whatever reason – HIV or antiretrovirals – and you add another factor that damages nerves, you are more likely to cause further damage. For example, when I see patients, I ask about alcohol intake, because alcohol damages nerves, making you more vulnerable to neuropathy.

ATU: How much alcohol is too much?

HM: It would seem reasonable that anyone who drinks more than the recommended 21 units a week for men [14 for women] may be more vulnerable. It's impossible to be categorical about these things because the other factor in alcohol-related neuropathy is vitamin B deficiency due to poor diet.

ATU: Does that also mean that people who use recreational drugs, and have a poor diet, could get neuropathy?

HM:There's no evidence that recreational drugs themselves cause neuropathy. However, the poor nutrition that can accompany drug-taking could certainly be a factor, since it is deficiency of the B vitamins which is important for nerve function.The cause of neuropathy in people who eat badly for any reason is usually thiamine (vitamin B1) deficiency.

ATU:Would you suggest that people whose diet is likely to be poor, for whatever reason, supplement with a vitamin B-complex tablet?

HM: I think that's reasonable, but with a caveat. One of the B-complex vitamins, B6, if taken in excess, causes neuropathy. At one stage in New York, B6 overdose was a common cause of neuropathy, because people were taking too much in their supplements. It's also worth checking B12 levels if you're a vegetarian, or if you have chronic diarrhoea.

ATU:What else do you check for when you see your patients for the first time?

HM: Diabetes is a cause of neuropathy, so I always check my patients' blood sugar. I also check to see if there are any other drugs that could cause neuropathy. For example, isoniazid, which is used to treat TB, can cause neuropathy.

ATU: What about co-infection with hepatitis C?

HM: Although there is a mechanism by which hepatitis C can cause neuropathy, it is very rare. I haven't seen more neuropathy in coinfected patients.

ATU: Are all the d-drugs equally likely to cause neuropathy, and of all the HAART medications, is it only d-drugs that can cause neuropathy?

HM: Of the antiretrovirals, only ddC, ddI and d4T are associated with neuropathy.The others aren't. ddC used to be the worst offender, but use of that drug has reduced significantly. In fact, compared with the early studies, incidence of neuropathy from all of these drugs is reducing for two reasons. First, lower drug doses are being used. Secondly, people aren't quite so immunosuppressed when they start the drugs, so they don't run the risk of this asymptomatic HIV-related neuropathy, as it is less likely to occur in people with higher CD4 counts.

ATU: How do you treat people with neuropathy who have no option but to
remain on d-drugs?

HM: Often, if the person is doing well as far as CD4 count and viral load are concerned, both the patient and HIV doctor are not that keen on stopping the d-drug.You could consider reducing the dose of the offending drug, but then there are concerns about resistance. Otherwise, all we can do then is to control the symptoms by using other drugs to make life a bit more bearable.

ATU: Do you prescribe antidepressants?

HM: I think they have a role to play, so I wouldn't write them off completely. I tend to use one of the tricyclics, amitryptyline.The crucial
thing is to start at the lowest possible dose (10mg), since it causes drowsiness. However,this does work in the patients' favour,particularly if they take it at night, because they can get a decent night's sleep.

ATU: Given the promising pain-reducing qualities of smoked marijuana presented at the recent Retroviruses Conference, would you support its use in the UK?

HM: In terms of other neuropathies, I have had patients who have said that smoking cannabis may be helpful.These results from San Francisco are preliminary, and it's never been trialled in a formal setting. Since there is no definite evidence to its benefit, I currently wouldn't be able to recommend it.

ATU: Before HAART, about one third of people reported HIV-related neuropathy. Why hasn't the incidence of neuropathy decreased in the HAART era?


HM: It's a combination of people living longer, and use of the d-drugs.We may see even more neuropathies appear as people with HIV are living longer.This is because there may well be increased risks for other causes of neuropathy that we currently see in non-HIV peripheral nerve clinics – diabetes, for example. So, when doctors see patients who are ageing with HIV, they will have to consider not just HIV or the drugs they take, but the other causes, too.

http://www.aidsmap.com/files/file1000724.pdf

A NEW QUALITY CONTROL PATHWAY IN THE CELL

Proteins are important building blocks in our cells and each cell contains millions of different protein molecules. They are involved in everything from structural to regulatory aspects in the cell. Proteins are constructed as linear molecules but they only become functional once they are folded into specific three-dimensional structures. Several factors, like mutations, stress and age, can interfere with this folding process and induce protein misfolding. Accumulated misfolded proteins are toxic and to prevent this, cells have developed quality control systems just like any other production chain or manufacturing process

A team of researchers at the Centre for Genomic Regulation in Barcelona has just published a paper inScience describing a new quality control system in our cells. It is specific to the inner nuclear membrane, a specialised part of the endoplasmic reticulum (ER), a network of membranes that spreads throughout the cell and which also forms the nuclear envelope that wraps the chromosomes.

Other quality control systems have been described but exactly how misfolded proteins in the inner nuclear membrane were degraded was not known. Ombretta Foresti, Victoria Rodríguez-Vaello and Pedro Carvalho, from the Organelle Biogenesis and Homeostasis laboratory at the CRG have just described the new system. "We have found that this quality control system has two key functions. It gets rid of misfolded proteins and, surprisingly, it also helps prevent the nucleus accumulating proteins that should not be there," explains Pedro Carvalho, principal investigator of this paper.

The studies have been conducted using a unicellular model organism (Baker's yeast) but they may also apply to human physiology. The newly identified quality control system protects the nucleus by targeting foreign proteins that could enter the nucleus by mistake. This could be particularly significant in non-dividing cells where the inner nuclear membrane is isolated from the rest of the ER for long periods of time

These findings have been made possible thanks to funding from the Howard Hughes Medical Institute (HHMI) and MCCIN at the CRG in Barcelona.

Support for the Feet

Anyone who has neuropathy problems in their feet knows exactly what this post is talking about. You do end up walking differently,either because you can't feel parts of your feet anymore, or they're so painful you invent a sort of 'self-protection' walk for yourself. Quite often it's not until somebody asks, "Why are you walking like that?" or starts making Monty Python, 'Ministry of Funny Walks' jokes, that you realise what you are subconsciously doing. Of course, it's absolutely no joke and it's very important that we take any measures necessary not to fall, or damage things further.
The problem is that by adjusting our walks, we aren't doing our feet any favours and there are plenty of bones, muscles and nerves in the feet to make your life miserable if you damage them. For that reason alone, investing in the right shoes or in-soles, to give as much support as possible, has to be a wise move. Dr. Scholl won't be available in every country but there will probably be an equivalent, or at least an orthopaedic practitioner/retailer who can make shoes to measure. Buying from the Internet is probably not a good idea because of the personal attention needed - everybody's neuropathic needs are different. This is another helpful post by Canadian, Bob Leahy, writing for positivelite.com

Good news (I think) for relieving that hurting feeling from peripheral neuropathy- affected feet
Bob Leahy checks out Dr Scholl’s Foot Mapping Technology and Custom Fit Orthotic Inserts

So regular readers will know my feet are a mess, the product of peripheral neuropathy caused perhaps by the prescribed drugs I take or have taken, perhaps by HIV itself. I’ve recounted here more than once how this side-effect induced pain in the feet has advanced so that it's hard to get it under control. Firstly my healthcare team has withdrawn Truvada from my five-drug combo and secondly they have added Gabapentin to the mix.

For my part, I have invested in New Balance brand shoes which I wear most of the time – they have a lot of cushioning, come in wide fittings, and are probably the most comfortable shoes I’ve ever owned. But they just can’t stave off the affects of neuropathy. In my case, I walk differently when my feet are hurting, which in turn eventually makes your lower-back hurt and turns you in to one miserable SOB.

So I was definitely in the market for alternative solutions.

Dr Scholls “Orthotic Centre” first caught my eye in our local Wal-Mart. I saw one again at Costco last week and decided to give it a try. It’s a fearsome looking shoulder-high kiosk with a platform you stand on, having removed your shoes. There are two handles to hold on to. A computer screen tells you what to do. Lean forward. Raise one leg and lean forward. Raise the other leg and lean forward. The machine meanwhile is mapping the pressure points on the underside of your feet. The result is a customized recommendation for one particular smodel of Dr Scholl’s orthotic inserts, of which there are many.

The technology behind the kiosk as well as what goes in to the three-layered inserts is described here.

The kiosk contains a supply of the inserts in all the various fits that the computer might recommend. My test resulted in a recommendation for the CF340 model which provides extra-good support for the arches. I know mine had suffered badly though having to walk flat-footed because of the neuropathy, in effect taking pressure off my toes. The inserts aren’t cheap – at Costco they are $70, for which you get two pairs, which realistically you probably need. But that $70 price compares with the hundreds of dollars you would pay for custom-fitted inserts elsewhere. It seemed well worth a try. Besides, the Wal-Mart reviews (an authoritative source if ever there was one, LOL) are pretty glowing.

Now to the important question: do they work? The answer is that based on just two days experience I would say yes. They certainly seem to make your feet feel more comfortable when standing or walking, providing support where you need it (arches) and cushioning elsewhere (heel and toes.) It’s true they do occupy space inside your shoes, so the shoes appear tighter, and that may not work well for some people. Also your first outing in them will almost certainly feel a bit strange: it feels as if there is something balled up under your arches which shouldn’t be there – a sock or something. Also returning to more correct walking form tests neglected leg and back muscles, so you might feel sore at first until your body adjusts.

To be fair, I haven’t tested these inserts long enough to fully evaluate them as an antidote to the debilitating impact of peripheral neuropathy. And the benefits I’m feeling now may in fact be at least partly responsible to the changes in my drug regime I referred to earlier. So it’s hard to judge. But let’s say right now I’m most favourably impressed by this product.

I think what it boils down to is that I’m seeing that the pain from peripheral neuropathy benefits from being attacked on several fronts. Prescription drugs might work, over the counter pain killers might work, dropping troublesome drugs from your regime might work, even acupuncture might work. But you also have to take measures which are kind to your feet. My take is that Dr Scholl’s Custom Fit orthotic inserts might do just that. So yes, I’m a believer.

SCIENTISTS DISCOVER A NEW SLEEP NODE IN THE BRAIN

A sleep-promoting circuit located deep in the primitive brainstem has revealed how we fall into deep sleep. Discovered by researchers at Harvard School of Medicine and the University at Buffalo School of Medicine and Biomedical Sciences, this is only the second "sleep node" identified in the mammalian brain whose activity appears to be both necessary and sufficient to produce deep sleep.

Published online in August in Nature Neuroscience, the study demonstrates that fully half of all of the brain's sleep-promoting activity originates from the parafacial zone (PZ) in the brainstem. The brainstem is a primordial part of the brain that regulates basic functions necessary for survival, such as breathing, blood pressure, heart rate and body temperature.

"The close association of a sleep center with other regions that are critical for life highlights the evolutionary importance of sleep in the brain," says Caroline E. Bass, assistant professor of Pharmacology and Toxicology in the UB School of Medicine and Biomedical Sciences and a co-author on the paper.

The researchers found that a specific type of neuron in the PZ that makes the neurotransmitter gamma-aminobutyric acid (GABA) is responsible for deep sleep. They used a set of innovative tools to precisely control these neurons remotely, in essence giving them the ability to turn the neurons on and off at will.

"These new molecular approaches allow unprecedented control over brain function at the cellular level," says Christelle Ancelet, postdoctoral fellow at Harvard School of Medicine. "Before these tools were developed, we often used 'electrical stimulation' to activate a region, but the problem is that doing so stimulates everything the electrode touches and even surrounding areas it didn't. It was a sledgehammer approach, when what we needed was a scalpel."

"To get the precision required for these experiments, we introduced a virus into the PZ that expressed a 'designer' receptor on GABA neurons only but didn't otherwise alter brain function," explains Patrick Fuller, assistant professor at Harvard and senior author on the paper. "When we turned on the GABA neurons in the PZ, the animals quickly fell into a deep sleep without the use of sedatives or sleep aids."

How these neurons interact in the brain with other sleep and wake-promoting brain regions still need to be studied, the researchers say, but eventually these findings may translate into new medications for treating sleep disorders, including insomnia, and the development of better and safer anesthetics.

"We are at a truly transformative point in neuroscience," says Bass, "where the use of designer genes gives us unprecedented ability to control the brain. We can now answer fundamental questions of brain function, which have traditionally been beyond our reach, including the 'why' of sleep, one of the more enduring mysteries in the neurosciences."

The work was funded by the National Institutes of Health.

The Informed Neuropathy Patient

Today's post from neuropathy.org (see link below) is a short but very important piece of advice from the Neuropathy Association. Basically, it suggests ways of becoming an informed patient regarding your neuropathy and arming yourself with information before and after you go to the doctor with your symptoms. Forearmed is forewarned they say and this is especially true when it comes to neuropathy. It's a disease with endless possibilities and an equal number of uncertainties, so the more you're aware of your situation, the less time will be wasted by your doctor or specialist having to try to explain all the complexities simply. Doing your own research will help you see your problem for what it is and make it less of a fearful mystery.
 

Dealing with nerve diseases - 10 Steps to Becoming an Informed Patient  
The Neuropathy Association 2014


Becoming an informed patient means embarking on a path of continuous learning when it comes to matters concerning your health and well-being. It also means meeting the challenge of adopting a healthy lifestyle. While there is no "best way" to become better informed about nerve diseases, there are a number of steps everyone should take as part of the process:

Prepare for visits with your doctor

Learn as much as you can about your medical diagnosis

Keep a copy of your medical records

Understand and commit to your treatment plan

Read the fine print of your health insurance plan and understand your policy 

Listen to your body and respect it

Seek a healthy work-life balance

Deal with stress and keep it at a minimum

Accept neuropathy as a part of you

Have a supportive and compassionate "go-to" buddy 

You have to become an active partner in managing your healthcare and take a positive stance regarding your neuropathy. When living with a chronic illness like neuropathy or other nerve diseases, it is important to develop a healthy doctor-patient relationship and a supportive network of friends and family. Just as important is listening to what your body tells you via your symptoms and address the situation when you recognize it. By acknowledging your symptoms and seeking an early diagnosis and treatment, you are taking a proactive approach to dealing with neuropathy and halting its progression. Ultimately, think of becoming an informed patient as an exercise in building your communications skills: we hope you continuously listen, learn, and share your knowledge with others! 

http://www.neuropathy.org/site/PageServer?pagename=Living_TenSteps

The Language Of Neuropathy

Today's post from blogs.bmj.com (see link below) looks at the language surrounding neuropathy but it doesn't give definitions or explanations; it's more one doctor talking to other medical professionals. For that reason, it may not be immediately accessible for the patient looking for answers. However, it is interesting in how it gives a rare insight into how many doctors think about the condition and it is thoroughly referenced.

The language of peripheral neuropathy
11 Apr, 2012 | by Arun Krishnan, Web Editor

In daily neurological practice, peripheral neuropathy remains one of the most common reasons for neurological referral. The worldwide diabetes epidemic will no doubt ensure that more and more patients are seen with the classic syndrome of length-dependent sensory and motor impairment that inevitably sets in train a range of investigations: nerve conduction studies, blood tests including the usual suspects such as B12, folate, creatinine and possibly an oral glucose tolerance test. In some centres, coeliac serology may be added to that panel, although I suspect that your hit rate will be low 1. Every so often, we are surprised by what we find when we order these tests. I recently had a patient who actually was B12 deficient and who did improve with appropriate treatment. Some of you may have had patients with copper-deficient myeloneuropathy, which again is amenable to therapy 2.

The occurrence of demyelinating changes on NCS is particularly rewarding as it not only alleviates the inevitable boredom of seeing scores of patients with axonal neuropathy, but also provides an interesting intellectual challenge. Some of these patients may have inherited neuropathy and depending on where you live, this may result in little or no further investigation or potentially a mass of ‘neuropathy panels’ looking for one of the zillion genes that we think may underlie charcot-marie-tooth disease. Without a good family history, the greatest beneficiaries of such intense investigation may be the scores of commercial outfits that provide these investigations. Certainly, in my experience the patient does not always benefit beyond testing for the most common genetic abnormalities (PMP 22, MPZ, mitofusin) and further research may be hampered until another family member comes along with a similar complaint.

In terms of acquired demyelination, we all think about chronic inflammatory demyelinating polyneuropathy, a condition that I use as a retort against my friends’ frequent verbal assaults that generally centre on the all pervading therapeutic nihilism that apparently still characterises 21st century neurology. (Neurology can be summed up in two words, they tell me, “Diagnose, adios”: I ask them what the temperature is like on Mars these days). But yes, CIDP is a breath of fresh air: intravenous immunoglobulin, steroids, cyclosporine, methotrexate, mycophenolate, rituximab 3. Wow…. I am not sure if they all work but they certainly sound great in unison.

Over the years there have been many excellent contributions to JNNP in the area of neuropathy research 1-5 and the trend continues in the May issue of the journal. Two prominent neuropathy groups from Chiba and Rochester suggest that we keep in mind a rare but potentially underrecognised form of demyelinating neuropathy and just when you were coming to grips with DADS, MADSAM, MMNCB 3 and other forms of neuropathy soup, here is another – POEMS syndrome 4,5 (polyneuropathy, organomegaly, endocrinpoathy, M-protein and skin changes). As noted in both these papers and the accompanying Editorial 6, the papers provide clinicians with some clues as to how to separate POEMS patients from ‘run-of-the-mill’ CIDP. In particular, they highlight the fact that POEMS patients appear to have more uniform demyelination along the peripheral nerve trunk, while the changes in CIDP patients are relatively polarized either to proximal or distal regions of the peripheral nervous system. In addition, the changes of axonal loss appear to be more prominent in POEMS, with greater muscle atrophy particularly in the lower limbs. The papers also provide potential ways of differentiating these two disorders on the basis of nerve conduction abnormalities. As noted in the Editorial 6, there may be a very direct clinical benefit from being able to differentiate these condition as the prognosis of POEMS is largely dependent on early identification and treatment, and as highlighted in these papers, a ‘neuropathy presentation’ of this systemic disorder is a common enough occurrence.

Research papers

1. Rosenberg et al. Should coeliac disease be considered in the work up of patients with chronic peripheral neuropathy? J Neurol Neurosurg Psychiatry 2005;76:1415-1419 doi:10.1136/jnnp.2004.048413 http://jnnp.bmj.com/content/76/10/1415.full?sid=27d23c4f-2cc3-459e-bcd8-ff52e2c66545

2.Goodman BP et al. Clinical and electrodiagnostic findings in copper deficiency myeloneuropathy. J Neurol Neurosurg Psychiatry 2009;80:524-527 doi:10.1136/jnnp.2008.144683 http://jnnp.bmj.com/content/80/5/524.full?sid=a2769e05-41c5-4a16-a551-986d4067440e

3.Lunn MPT, Willison HJ. Diagnosis and treatment in inflammatory neuropathies. Journal of Neurology, Neurosurgery & Psychiatry. 2009 Mar;80(3):249-58.http://jnnp.bmj.com/content/80/3/249.full?sid=7f5e07bb-96ec-4d0a-9b06-e7cb750886e5

4. Nasu et al. Different neurological and physiological profiles in POEMS syndrome and chronic inflammatory demyelinating polyneuropathy. J Neurol Neurosurg Psychiatry 2012;83:476-479 Published Online First: 15 February 2012 doi:10.1136/jnnp-2011-301706.http://jnnp.bmj.com/content/83/5/476.full

5. Mauermann et al. Uniform demyelination and more severe axonal loss distinguish POEMS syndrome from CIDP. J Neurol Neurosurg Psychiatry 2012;83:480-486 Published Online First: 6 March 2012 doi:10.1136/jnnp-2011-301472. http://jnnp.bmj.com/content/83/5/480.full

6. Arimura K. Early recognition of POEMS syndrome: what is the role of clinical neurophysiology? J Neurol Neurosurg Psychiatry 2012;83:474 doi:10.1136/jnnp-2012-302477http://jnnp.bmj.com/content/83/5/474.full.

http://blogs.bmj.com/jnnp/2012/04/11/the-language-of-peripheral-neuropathy/

The opening of spring

In a span of three hours..........

Whats The Real Cause Of HIV Neuropathy

Today's post from painblogr.org (see link below) is an excellent attempt to interpret data from studies to establish if and why neuropathy is still a major problem for HIV patients who were not exposed to the older, more toxic HIV drugs. The theory was that the older HIV drugs were primarily responsible for the emergence of severe neuropathy in patients living with HIV but since those drugs have been phased out, neuropathy still remains a problem for people on the most modern HIV combinations. This leads to the inevitable conclusion that HIV is the cause of the nerve damage (by attacking the inflammatory nervous system) and not only the toxic drugs of the past. This is something that has seemed obvious for many years to many people living with both HIV and neuropathy but proving it is another matter. Scientists, researchers and doctors can be a stubborn folk and having reached earlier conclusions, react very conservatively to suggestions that they may have been wrong. This article is a praiseworthy attempt to make sense of statistics. If the technical elements are too confusing; just read the text paragraphs - you'll get the idea.

HIV neuropathy: down, but not out 
Peter Kamerman Posted on: February 22, 2016
 



It has been a while since my last post (I’ve been migrating the site from Wordpress to GitHub Pages), and I thought I would get back into the swing of things with a post on a topic close to my heart, HIV-associated sensory neuropathy (HIV-SN). The neuropathy (damaged nerves) affects the long sensory nerves from the hands and feet, producing reduced sensation. Somewhat counter-intuitively, this loss of sensation is often accompanied by chronic pain in the affected areas. The neuropathy is not fatal, but the loss of sensation, and particularly the pain, causes significant psychological, social, and economic problems for the person affected, their family/friends, and places a large burden on the healthcare system.


The mechanisms underlying the development of the neuropathy have not been clearly described, but one of the major risk factors for the neuropathy is exposure to older generation antiretroviral drugs (ddX: stavudine, didanosine, zalcitabine), which are toxic to neurones. Imagine starting a treatment that saves your life, but potentially leaves you with chronic, intractable pain.


Because of their toxicity (not just neuropathy, but a suite of other complications too), these older drugs were phased out of routine use in developed countries some time ago. More recently, there has been a steady shift away from using these drugs first-line in resource-poor countries too. With the global phasing out of neurotoxic ddX drugs, there is hope that the number of new cases of the neuropathy, and ultimately the total burden of the neuropathy, will fall. However, the epidemiological data to support this claim are scant. Head-to-head longitudinal efficacy and toxicological studies of old versus new antiretroviral treatments reported lower rates of the neuropathy in those people being treated with newer drugs, but these studies were poorly designed for detecting neuropathy in the first place. So where does that leave us in answering the question of whether we are witnessing the beginning of the end of HIV neuropathy?

Enter the CHARTER study

One source of data that may shed light on problem is the National Institutes of Health (NIH)-funded CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study. The study is a prospective, multi-centre study in the US reporting on central (brain and spinal cord) and peripheral nervous system complications of HIV infections in cross-sectional (~1600 participants) and longitudinal (~650 participants) cohorts; all participants undergo comprehensive neurological and neurobehavioural assessment. In 2010, Ronald Ellis and colleagues published a fascinating paper describing the prevalence of HIV neuropathy in 1539 HIV-infected individuals enrolled between 2003 and 2007 (Ellis et al., Arch Neurol 67: 552-558, 2010. DOI: 10.1001/archneurol.2010.76). They reported that 57% (881/1539) of participants had HIV neuropathy (defined as the presence of at least 1 abnormal clinical sign of neuropathy - reduced/absent vibration or pin-prick sensation in the feet and toes, or reduced ankle reflexes). But, despite providing the data (see Table 1 below) they did not report whether the prevalence of HIV neuropathy differed between patients depending on their exposure to neurotoxic antiretroviral drugs.

Since the data are available, I saw an opportunity to look at whether the prevalence of HIV neuropathy did indeed differ between HIV-positive patients from the CHARTER study who were on combination antiretroviral therapy (cART), but who had never been exposed (ddX-naive) to neurotoxic ddX drugs, and those who had been exposed (ddX-exposed) at some time-point in their treatment.

The analysis

Prevalence of HIV-SN

The first step in the analysis involved extracting the relevant data from Table 1 of Ellis et al. (2010). Because the extraction only included a small number of data points I performed the extraction manually.

################
# Extract data #
################
# sn_ddX_exposed: Sensory neuropathy (sn), and have been exposed to ddX
# Data extracted: Currently using ddX + used ddX in the past
sn_ddX_exposed <- span=""> 138 + 413 

# sn_free_ddX_exposed: No sensory neuropathy (sn), and have been exposed to ddX 
# Data extracted: Currently using ddX + used ddX in the past 
sn_free_ddX_exposed <- span=""> 72 + 175 

# sn_ddX_naive: Sensory neuropathy (sn), and never been exposed to ddX 
# Data extracted: ddX-naive - cART-naive 
sn_ddX_naive <- span=""> 330 - 71 

# sn_free_ddX_naive: No sensory neuropathy (sn), and never been exposed to ddX 
# Data extracted: ddX-naive - cART-naive 
sn_free_ddX_naive <- span=""> 441 - 163 

Summary of data extracted from Table 1 of Ellis et al. (2010)

Neuropathy	ddX_exposure	N
Yes	Yes	551
Yes	No	259
No	Yes	247
No	No	278

Once I had extracted the data, I used the data to construct datasets of the number of participants with (sn) and without (sn_free) sensory neuropathy in the ddX-naive and ddX-exposed groups.

##################
# ddX-naive data #
##################
ddX_naive <- span=""> c(rep('sn', sn_ddX_naive),
 rep('sn_free', sn_free_ddX_naive)) %>% # generate the data
 sample(., size = length(.),
 replace = FALSE) # shuffle the pack (for no good reason)

####################
# ddX-exposed data #
####################
ddX_exposed <- span=""> c(rep('sn', sn_ddX_exposed),
 rep('sn_free', sn_free_ddX_exposed)) %>% # generate the data
 sample(., size = length(.),
 replace = FALSE) # shuffle the pack (for no good reason)

Summary of neuropathy prevalence in simulated datasets

Group	Neuropathy (n)	No neuropathy (n)	Total (n)	Prevalence (%)
ddX_exposed	551	247	798	69
ddX_naive	259	278	537	48

With only a glance at the table above you can see that the prevalence of neuropathy in patients exposed to ddX at some time-point in their HIV treatment was greater than that in patients never exposed to any of the ddX drugs (69% vs 48%). But, these are point estimates of disease prevalence, based on the group of people who volunteered to take part in the study. It would be nice to get an estimate of the range of values within which the prevalence is estimated to lie by constructing 95% confidence intervals of the prevalence. A handy approach to generating these confidence intervals is bootstrapping; a resampling method that allows the generation of an estimate of a population parameter (e.g., disease prevalence) from sample data by resampling (with replacement) the sample data. It boils down to using the sample cohort as the population. There are several very good R packages that can be used to calculate bootstrap confidence intervals (the ‘boot’ package by Brain Ripley and Angelo Canty springs to mind), but I chose to use perform the bootstrap use base R functions.

# Step 1: Define function 'bootstrp' to generate the 95% confidence interval of the prevalence
# Generate a list ('boot_resample') containing 'B' bootstrap samples of 'data' (default = 999 samples)
bootstrp <- span=""> function(data, B = 999){
 boot_resample <- span=""> list() # Create empty list
 for(i in 1:B){
 boot_resample[[i]] <- span=""> sample(x = data,
 size = length(data),
 replace = TRUE)
 }
 boot_resample
}

# Step 2: Run the function
ddX_exposed_2 <- span=""> bootstrp(ddX_exposed)
ddX_naive_2 <- span=""> bootstrp(ddX_naive)

# The next two steps could have been included in the 'boostrp' function,
# but I decided to seperate them from the function to keep the
# function as simple as possible.

# Step 3: Create a vector of neuropathy prevalence data for each item
# in the output of 'bootstrp'
ddX_exposed_3 <- span=""> sapply(ddX_exposed_2,
 function(y) round(100 * (length(y[y == 'sn']) / length(y))))
ddX_naive_3 <- span=""> sapply(ddX_naive_2,
 function(y) round(100 * (length(y[y == 'sn']) / length(y))))

# Step 4: Get the lower (0.025) and upper (0.975) limits of the
# vector of prevalence data
ddX_exposed_4 <- span=""> quantile(ddX_exposed_3,
 probs = c(0.025, 0.975))
ddX_naive_4 <- span=""> quantile(ddX_naive_3,
 probs = c(0.025, 0.975))

Figure 1. Point prevalence (with 95% bootstrap confidence intervals) of HIV neuropathy in simulated datasets based on neuropathy prevalence reported by Ellis et al. (2010). Data are shown for patients who were/had been on combination antiretroviral therapy (cART), but had never been exposed to the neurotoxic antiretroviral drugs [Never exposed to ddX; Point prevalence (95% CI): 48% (44 to 53%)], and patients who were/had been on cART, and who had been exposed to ddX [Exposed to ddX; Point prevalence (95% CI): 69% (66 to 72%)].

From the plot, you can clearly see that there was a much (~30%) lower prevalence of HIV neuropathy in those patients never exposed to neurotoxic ddX drugs compared to those who had been exposed (if seeing isn’t believing and you like to see a p-value, then see the table below). But, while the neuropathy was less common in patients treated with the newer drugs, almost half of the patient still had evidence of peripheral nerve damage; a substantial burden.

Pearson's Chi-squared test with simulated p-value (based on 999 replicates): ddX_exposure and sn_status

Test statistic	df	P value
58.3	NA	0.001 * * *

Is the neuropathy still painful?

As I mentioned earlier, pain is a common symptom of the neuropathy, and this pain causes significant dysfuction and distress. Consequently, having shown that exposure to newer, less neurotoxic treatments is associated with reduced prevalence of HIV neuropathy compared with older drugs, it stands to reason that when neuropathy is present, the severity of the neuropathy associated with these newer drugs may be less than that induced by the older drugs. Therefore, I also looked at the frequency of painful symptoms in ddX-exposed and ddX-naive patients reported on by Ellis and colleagues (2010) that had at least one clinical sign of peripheral nerve damage (i.e., only patients who had a neuropathy). This new analysis followed exactly the same procedures as those described above, except that I took the data from Table 2 of Ellis et al. (2010) (see below). So, other than showing which data I extracted from Table 2, I have not shown the R scripts for this section (your can find the full .Rmd file on GitHub)

Here are the data I extracted from Table 2 of Ellis et al. (2010).

################
# Extract data #
################
# pain_ddX_exposed: painful sensory neuropathy (pain), and have been exposed to ddX
# Data extracted: Currently using ddX + used ddX in the past
pain_ddX_exposed <- span=""> 38 + 184 

# pain_free_ddX_exposed: Nonpainful sensory neuropathy (pain_free), and have been exposed to ddX 
# Data extracted: Currently using ddX + used ddX in the past 
pain_free_ddX_exposed <- span=""> 100 + 229 

# pain_ddX_naive: Painful sensory neuropathy (pain), and never been exposed to ddX 
# Data extracted: ddX-naive - cART-naive 
pain_ddX_naive <- span=""> 113 - 29 

# pain_free_ddX_naive: Nonpainful sensory neuropathy (pain_free), and never been exposed to ddX 
# Data extracted: ddX-naive - cART-naive 
pain_free_ddX_naive <- span=""> 217 - 42 

Summary of pain data extracted from Table 2 of Ellis et al. (2010)

Pain	ddX_exposure	N
Yes	Yes	222
Yes	No	84
No	Yes	329
No	No	175

Following data extraction, I simulated datasets of the number of participants with (pain) and without (pain_free) painful sensory neuropathy in the ddX-naive and ddX-exposed groups, and then calculated and plotted bootstrap 95% confidence intervals.

Figure 1. Point prevalence (with 95% bootstrap confidence intervals) of painful HIV neuropathy in simulated datasets based on the prevalence of painfulperipheral neuropathy reported by Ellis et al. (2010). Data are shown for patients with a clinically diagnosed neuropathy, and who were/had been on combination antiretroviral therapy (cART), but had never been exposed to the neurotoxic antiretroviral drugs [Never exposed to ddX; Point prevalence (95% CI): 32% (27 to 38%)], and patients who were/had been on cART, and who had been exposed to ddX [Exposed to ddX; Point prevalence (95% CI): 40% (36 to 44%)].

From the plot, you can see that there was a slightly lower prevalence of painful HIV neuropathy in those patients never exposed to neurotoxic ddX drugs compared to those who had been exposed (there is overlap of the lower limit of the ddX-exposed group and the upper limit of the ddX-naive group). Like before, if seeing isn’t believing and you like to see a p-value, then see the table below. So, the newer drugs do appear to reduce the severity of the painful symptoms of the neuropathy compared with older ddX drugs, but like the findings for neuropathy per se, there still was a high burden of pain in those with neuropathy and who had only ever been exposed to newer treatments.

Pearson's Chi-squared test with simulated p-value (based on 999 replicates): ddX_exposure and pain_status

Test statistic	df	P value
4.628	NA	0.033 *

Take-home message

HIV neuropathy is not going to disappear anytime soon.

While the frequency of HIV neuropathy, and the painful symptoms of the neuropathy, was markedly reduced in patients on modern treatment regimens compared to those exposed to older, neurotoxic treatments, the burden of neuropathy (and pain) was still unacceptably high. These data indicate that the burden of this chronic complication of HIV infection may well decrease over time, but healthcare professionals still need to be cognisant that many of their patients, even if never exposed to ddX drugs, are still at risk of neuropathy, and its painful sequela.

---

Analysis script

The analysis script for this blog post can be found under the ellis-2010 subdirectory of the second-look-PAIN GitHub repository.
Citation

Peter Kamerman (2016). HIV neuropathy: down, but not out. Figshare DOI: 10.6084/m9.figshare.2656255
http://painblogr.org/hiv-neuropathy-down-but-not-out

Neuropathy A Massive Problem In The USA

Today's post from prweb.com (see link below) looks at recent conclusions by the Neuropathy Association that neuropathy is a far larger problem than at first thought. Statistics are deceptive things: they can prove one thing or another but you have to look very closely at what they are based on  and whether they're someone's opinion based on extrapolation of one set of figures or another, or actual hard and fast facts. That said, a few million either side of the truth still makes neuropathy a huge problem in the world today and every country or region can probably draw the same conclusions from the US numbers. That makes it all the more astonishing that so many so-called 'experts' claim that the problem is exaggerated or over-rated. 
 

Neuropathy in U.S. Skyrocketing 
New York, NY (PRWEB) May 13, 2013


Increase in Diabetic Neuropathy Escalates Neuropathy Epidemic Impacting Millions According to The Neuropathy Association.

"Neuropathy impacts 1 in 15 Americans--it is a leading cause of adult disability".

According to The Neuropathy Association, there are now 15-18 million Americans with diabetic peripheral neuropathy (DPN) due to the increasing prevalence of diabetes. 60-70% of the 25.8 million adults and children in the U.S. with diabetes have DPN.* The growing DPN statistic significantly raises the overall number of people with neuropathy in the U.S.

“In the past, we estimated that there were 20 million Americans with all forms of peripheral neuropathy,” notes Tina Tockarshewsky, president and CEO of The Neuropathy Association. “However, with DPN numbers alone now at nearly 20 million, it’s time to acknowledge the need for better data quantifying this epidemic. We are all gravely underestimating the millions of people struggling and suffering with neuropathies. It’s time to ‘do the math’ when counting neuropathy’s prevalence, and finally address it as the public health emergency it is.”

May 13-17 is the ninth annual Neuropathy Awareness Week, an event launched by The Neuropathy Association to promote greater attention to and prevention of this growing national epidemic. For 18 years, The Neuropathy Association has been an active national patient advocacy organization working to change perceptions about this progressive, chronic and often extremely painful neurological disease.

Peripheral neuropathy, or “peripheral nerve damage,” impacts well over 20 million Americans (at least 1 in 15), making it one of the most common chronic diseases and a leading cause of adult disability. Neuropathy disrupts the body’s ability to communicate with its muscles, organs, and tissues. Symptoms can include numbness, tingling, weakness, and pain often beginning in the hands and feet. With early diagnosis, it can often be controlled and quality of life restored. If ignored, symptoms can intensify to loss of sensation, weakness, unremitting pain, and/or disability.

Of the over 100 known types of neuropathy, diabetic neuropathy represents over a third of all neuropathies, making diabetes the leading cause. A third of neuropathies are “idiopathic” (unknown cause). Other neuropathies include autoimmune-related, hereditary, cancer or chemotherapy-related, entrapment or trauma-related, and neuropathies related to causes such as toxin-induced, nutritional deficiencies, gastro-intestinal disorders, metabolic diseases, or infectious diseases (including Lyme and HIV/AIDS).

The millions of Americans with peripheral neuropathy include:

15-18 million with diabetic peripheral neuropathy;
79 million with pre-diabetes who are at risk for developing DPN (source: CDC);
230,000-575,000 with HIV-neuropathy, or 20-50% of HIV patients (source: CDC);
420,000 with chemotherapy-induced neuropathy, or 30% of cancer survivors (source: American Cancer Society);
125,000 with Charcot-Marie Tooth hereditary neuropathy (source: CDC).

“Living with neuropathy can cause tremendous frustration for patients. Many feel isolated because relatives, loved ones, and often even caregivers are not familiar with neuropathy or neuropathic pain,” observes Dr. Thomas Brannagan, III, The Neuropathy Association’s medical advisor.

“Living with chronic pain impacts a patient’s day-to-day functionality,” shares Dr. Sudhir Diwan, chair of The Neuropathy Association’s neuropathic pain management medical advisory council. “Patients get caught up in a vicious cycle of co-morbid conditions connected to their underlying neuropathic pain, resulting in physical and psychological problems including impaired concentration, anxiety, depression, a decline in cognitive abilities, and sleep difficulties. Lack of sleep can, in turn, cause irritability and increased pain sensitivity.”

“Neuropathy’s prevalence is escalating at an alarming rate. Awareness must increase to ensure earlier diagnosis. Until we find the disease-modifying treatments and cures that currently don’t exist, our only cure is prevention,” adds Tockarshewsky. “Additionally, ‘doing the math’ to calculate neuropathy’s insidiousness must also factor the economic burden with the human toll. Medical costs and workplace productivity losses are also increasing. Neuropathy and neuropathic pain patients are often high health care system users as they seek relief from persistent suffering. Those debilitated by neuropathy or coping with chronic pain are challenged with working full-time, and may become unemployable or stay under-employed.”

About The Neuropathy Association

Founded in 1995, The Neuropathy Association is the leading national nonprofit organization providing neuropathy patient support, education, advocacy, and the promotion of research into the causes of and cures for peripheral neuropathies through its nationwide network of members, regional chapters, 15 medical Centers of Excellence, and 150 patient support groups.

References:

Center for Disease Control and Prevention’s (CDC) 2011 National Diabetes Fact Sheet
http://www.diabetes.org/diabetes-basics/diabetes-statistics/

http://www.prweb.com/releases/NeuropathySkyrocketing/DiabeticNeuropathyRises/prweb10725805.htm

The Eighth Intelligence The Naturalist

Indeed. A long overdue recongnition, despite the underdeveloped understanding of it thus far. I am not sure why I thought it was brand new, maybe in the last five years, because really this information was explored in the 80's. Well, at least by this Gardner guy - if you ask me, it was probably the most primitive, original and intrinsic intelligence possessed by humans.

Here are some explanatory links courtesy of google:

Newer Views of Learning

The Eighth Intelligence, by Leslie Owen Wilson

The Seven Intelligences, plus a new eighth

Another basic article with pinpoints

Wikipedia

Yeah - lets me know I'm living my purpose when I get to dig up roots, walk through bogs with a bunch of kids, and shudder with awe as I watch the magic of the great blue heron gracing the sky.

But I have to say, I do wish something a little deeper was revealed here. It all sounds so scientific .... more in the arena of the logical intelligence ....all that sorting and classifying; a small expression of what's really happening. I feel like there is an uncanny gift within the Naturalist. Something that comes from an alchemy of intuition and extra-sensory awareness. Something that recongnizes the interdependence of all living things. Someone who knows that while they are in nature, they are not greater than, or less than, but can seamlessly immerse themselves into the symbiotic dance of nature itself. This awakens the deepest, keenest facets of the intellect and psyche, rendering a dynamic sensitivity to every cell, every line, every expansive shape and predator and vein ... details beyond ordinary, details and patterns with meaning, details which tell secrets. The best scientists are the ones who left room for creativity.

In essence, it is the Artist awakened to Nature that defines the Naturalist.

Putting Neuropathy Experiences Into The Cloud

Today's post from the neuropathy association (see link on the image) is the culmination of many people's input into a neuropathy word cloud. In itself, it means little but if you look at the words, you will see many which you can identify with as a person living with neuropathy. They say that putting your feelings into words can help you put what you're going through into perspective. Some people write diaries, some write articles or books but if that seems too much of an effort, creating your own word cloud may well be a useful therapeutic exercise.

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How Real Is The Connection Between Gluten Intolerance And Neuropathy

Today's post from labroots.com (see link below) follows up on recent articles all over the Net concerning links between gluten intolerance and neuropathy. It's a bit of a chicken and egg story - which disease leads to the other and so on and because of the vague correlation of symptoms, is very difficult to prove. There are people with neuropathy who go on to become glucose intolerant and there are people with celiac disease who go on to develop neuropathy but whether one is responsible for the other, is the big question. For many years, people living with neuropathy have been advised to adopt a more gluten free diet and for many people their symptoms have improved as a result but the science behind it is much more complex than a 'suck it and see' dietary change. More information can be found by using the search facility here on the right of the blog page.
 

Are Celiac Disease and Neuropathy Connected?
May 12, 2015 |Posted by: Ilene Schneider

A new study conducted by Dr. Jonas F. Ludvigsson of the Karolinska Institute in Stockholm, Sweden, and published in JAMA Neurology, shows that people with Celiac Disease are 2.5 times more likely to receive a diagnosis of neuropathy later in life. According to the study, which was reported by Honor Whiteman in Medical News Today (http://www.medicalnewstoday.com/articles/293754.php), the connection between Celiac Disease and nerve damage was reported 50 years ago. Furthermore, untreated Celiac Disease can lead to higher risk of nerve-related conditions, including multiple sclerosis.
 
Celiac Disease and neuropathy appear to be linked.

Celiac Disease, which affects about 1 percent of the U.S. population, “is a condition in which the immune system is abnormally sensitive to gluten, a protein found in wheat, rye, and barley," according to the National Institutes of Health website (http://ghr.nlm.nih.gov/condition/celiac-disease, which goes on to say that the disease is an autoimmune disorder in which the immune system malfunctions and attacks the body's own tissues and organs. The villi of the small intestine are damaged when a person consumes gluten. If a person with Celiac Disease does not maintain a “strict, lifelong gluten-free diet,” the resulting immune system inflammation can lead to a variety of complications. While the disease can affect everyone differently, the condition can result in malnutrition, weight loss, diarrhea, vomiting and abdominal bloating in children and fatigue, bone or joint pain, arthritis and other non-digestive system complications in adults.

The NIH website adds that a Celiac diagnosis typically is not made until more than a decade after symptoms begin, and many of the symptoms might make it look as if the person has another disease. Additionally, some people have what is described as “silent celiac disease, in which they have no symptoms of the disorder.” Most often such people “have immune proteins in their blood (antibodies) that are common in celiac disease. They also have inflammatory damage to their small intestine that can be detected with a biopsy.”

In the new study Dr. Ludvigsson and his colleagues attempted to figure out the absolute and relative risk of neuropathy among a nationwide population-based sample of patients with a confirmed diagnosis of Celiac Disease. Participants in the study included 28,232 individuals from Sweden whose Celiac Disease was confirmed using small-intestine biopsies, alongside 139,473 age- and sex-matched people in a control group. Based on the results of later diagnosis, the researchers figured that participants with Celiac Disease were approximately 2.5 times more likely to receive a later diagnosis of neuropathy than those without Celiac Disease. They calculated that the absolute risk of developing neuropathy was about 64 per 100,000 person-years among participants with Celiac Disease, while the absolute risk of neuropathy was estimated at 15 per 100,000 person-years among participants who did not have the disease.

Cautioning that patients with neuropathy should be screened for Celiac Disease, the researchers concluded, "We found an increased risk of neuropathy in patients with Celiac Disease that persists after Celiac Disease diagnosis. Although absolute risks for neuropathy are low, Celiac Disease is a potentially treatable condition with a young age of onset." 

http://labroots.com/trending/id/1134/are-celiac-disease-and-neuropathy-connected/neuroscience

Looking neuropathy in the face

It has been brought to my attention that posting articles that are all doom and gloom, does nothing for the people who's neuropathy symptoms are considerably milder...except perhaps scaremongering! I take the point, so once more a few truths about the disease:

1) You may feel numbness; or tingling; or pain; or a combination of the above, as a result of your neuropathy.

2) The sensations you experience may just be in one toe; or just the soles of your feet; or your hands; or your calves; or your muscles; or further in your body; or again, a combination of the above.

3) What you're feeling might last for years without changing; or just a few weeks or months, before progressing; or may not progress at all. Progression is not inevitable but may well happen.

4) You may get relief from a particular drug that is prescribed for you; or an alternative therapy; or supplement; or you might have to try a whole range of things before finding something that works; or unfortunately doesn't; or again, a combination of the above.

5)...Can you see where this is going?

Neuropathy is a disease with very few hard and fast rules that can be applied to all patients. This is partly because it has up to a hundred different causes; all of which can be influenced by outside elements and other medical problems and that's without taking into account what sort of neuropathy you have. You may come across a great deal of generalisations on the Internet and also from your doctors but that's because it's such a difficult disease to pin down and treat.

One thing is certain, purely on patient numbers alone, it deserves much more research publicity and deserves much more drug development. However, if you ask the average person on the street what neuropathy is, you'll more than likely be met with a blank stare - then try convincing them that what you're feeling is not between your ears!

HIV combined with neuropathy is just that little more complex, again because of the contributing factors that can change the overal picture but the fact is that it's a growing problem amongst the HIV population because we're living longer and quickly learning that neuropathy may be one more cross to bear because of that.

For all those reasons, you need to treat your neuropathy as something personal. Yes, there are shared experiences and lots of information about treatments and drugs but you need to take that information and apply it to your own particular situation. Take nothing for granted and assume nothing either - the numbness in your toes or fingers may be all that you ever have to worry about (especially if you find something to help) but then again, it may only be the beginning and then you can read about other people's strategies for dealing with the various symptoms and side-effects. The point is that neuropathy doesn't play by the rules of recognised illness - there's no guarantee that B will follow A! You may also unfortunately need to persuade your doctor that your case may not be comparable with everyone else. For many family doctors, unless they've got wide experience of the problem, neuropathy is just another paragraph in the textbook.

However, knowledge is most definitely power (HIV veterans will testify to that) and the exchange of information is and always will be, vital in providing support where and when it is needed. If you know your disease, you can deal with it so much better.

In the same vein, this blog welcomes all reactions and especially contributions, not only from HIV patients but also people with neuropathy stemming from other diseases like Diabetes and Cancer.

Drew50: September 2nd, 2011

Neuropathy The Invisible Disease

Today's post from diabetesnewsjournal.com (see link below) is once again aimed at the diabetic community when in fact the subject matter applies to everybody living with neuropathy. It also concentrates on the African-American and Hispanic-American communities living with neuropathy but in this case, it is to correctly highlight the fact that some communities have more problems finding the right information and treatment than others. In fact, the lack of awareness of neuropathy and its impact on society is a universal problem but certain groups are hit harder for whatever reasons that may be. Neuropathy has been invisible to the general population for ever and for some reason, despite the staggering numbers of people who have neuropathy, it remains a disease that most people have never heard of, never mind understand what the symptoms and treatment are. It's high time that this problem was solved and high time that neuropathy received the publicity its suffering deserves.

Survey Reveals Lack of Awareness About Diabetic Nerve Pain
by Carolina Henriques March 14, 2016

Pfizer, a 150-year-old global pharmaceutical company, collaborated with the American Diabetes Association (ADA) to conduct a joint multicultural survey called Community Health Perspectives.

The survey was sponsored and conducted by Pfizer and the ADA — whose mission is to prevent and cure diabetes — from August to October 2015. A total of 1,000 adults who had been diagnosed with diabetes and experienced symptoms of diabetic nerve pain too party in the survey: 823 non-Hispanic whites, 73 African-Americans, 70 Hispanic-Americans, and 34 respondents of other ethnic backgrounds.

Additionally, 452 African-American and 823 Hispanic-American healthy adults were surveyed as controls, adding up to a total sample size of 1,919 participants. A sample of 308 healthcare providers was also surveyed.

The survey found considerable gaps in awareness, diagnosis and management of a serious complication related to diabetes known as painful diabetic peripheral neuropathy, or diabetic nerve pain. The African-American and Hispanic-American communities experienced the most pronounced diabetic nerve pain symptoms, including burning sensations or shooting pain in their hands and feet.

The Community Health Perspectives survey was conducted to support the program Step On Up, which educates people about diabetic nerve pain and encourages them to speak with their healthcare providers.

“I got involved with Step On Up because I saw firsthand how the pain impacted my father, who has type 2 diabetes and diabetic nerve pain. Results from this survey show he’s not alone, especially in the African-American community,” said actor and comedian Cedric the Entertainer in a Pfizer press release. “Nearly half of African-Americans surveyed had not talked to a healthcare provider about their nerve pain in the feet or hands. I want to encourage people experiencing symptoms of diabetic nerve pain to take action and speak with a doctor about their pain.”

Community Health Perspectives results, combining African-American and Hispanic-American samples, found that:

Answers from African-Americans and Hispanic-Americans indicated that more than 50 percent had not been diagnosed with the condition;

More than 50 percent of African-Americans surveyed said the nerve pain in their feet and hands had a significant impact on their daily lives, more than any other diabetes symptom;

Eighty percent of African-Americans and 74 percent of Hispanic-Americans were less likely than non-Hispanic whites (97 percent) to agree that nerve pain is a common complication of diabetes;

Of the African-Americans and Hispanic-Americans surveyed who had talked about their nerve pain symptoms with doctors and were diagnosed with the condition, the majority wished they had done so sooner (80 percent and 85 percent, respectively).

“Diabetes-related complications are common and debilitating, and 7 out of 10 general respondents diagnosed with diabetic nerve pain said that their nerve pain makes them feel like they are not successfully managing their diabetes,” said ADA Senior Vice President for Medical Affairs and Community Affairs Jane Chiang, M.D.

“Community Health Perspectives confirms the need for ongoing education to motivate more people living with diabetes and symptoms of diabetic nerve pain to visit their doctor and seek some pain relief,” Chiang said.

Carolina holds a BSc in Anthropology and a MSc in Urban Studies., and brings her interdisciplinary skills to her writing on a range of different topics in science, research and advocacy news.

http://diabetesnewsjournal.com/2016/03/14/survey-reveals-lack-awareness-diabetic-nerve-pain/

The Scandal Of Lyrica Gabapentin And Cymbalta For Neuropathy Patients

Today's post from ti.ubc.ca (see link below) reinforces the latest evidence that shows that Lyrica, gabapentin and Cymbalta (pregabalin, gabapentin and duloxetine) have very little effect on patients' nerve pain when compared to placebos. It's enough to make you hopping mad (if hopping weren't so painful!) when you realise that very successful pharmaceutical company advertising campaigns have promoted these drugs to the top of doctors' lists when treating neuropathic pain. The patient clearly comes last in the equation and for years now people have been exposed to these drugs and their side-effects without any proven benefits. Time to have a serious discussion with your doctor or specialist, wherein you can ask them how they can justify their prescriptions. The idea that doctors turned to these drugs to prevent a rapid progression towards opioids is just to weak for words.

Benefits and harms of drugs for “neuropathic” pain 
January 19, 2016 Therapeutics  Cochrane reviews

Chronic pain (at times presumed to be “neuropathic” in origin) is a common problem in clinical practice. It is now well recognized that the results of drug treatment are more often disappointing than not.1 Despite this, from 2005-2014 the number of British Columbians prescribed gabapentin increased 1.8 fold, pregabalin 17 fold, and duloxetine 3.6 fold (from 2008). Use of venlafaxine (mostly for depression/anxiety) has remained relatively stable.

Most gabapentin, pregabalin, and duloxetine use in B.C. is for chronic pain, driven partly by concern about problems with long-term opioid therapy. For the same reason, tricyclic antidepressants (amitriptyline, nortriptyline, imipramine, desipramine) are often prescribed for “neuropathic” pain.

In 2009 Therapeutics Letter 75 on gabapentin2 concluded:
Gabapentin reduces neuropathic pain by < 1 point on a 0-10 point scale and benefits about 15% of carefully selected patients (NNT=6-8).
A similar proportion of people suffer harm (NNH=8).
A test of benefit/harm can be made after 1-2 days at a low dose (100-900 mg/day).
Benefit is unlikely to increase with higher doses or longer treatment.

This Letter updates information on gabapentin and critically appraises randomized clinical trials (RCT) assessing the benefits and harms of three other drugs promoted for neuropathic pain: pregabalin, duloxetine, and venlafaxine. It is based primarily on 4 Cochrane reviews.3-6 Like many systematic reviews, these either did not assess risk of bias, or did not fully reflect the implications of the risk of bias in their conclusions. We attempt to demonstrate how appreciation of the biases in RCTs can be incorporated into the conclusions of systematic reviews.

Benefits

Although all pain metrics have limitations7 a 50% or greater reduction from a baseline pain score has been promoted as a more clinically relevant outcome for “neuropathic” pain because it correlates with improvements in comorbidity, function and quality of life.4 Using this outcome across all 4 Cochrane reviews, the mean number of people who must be treated for one to achieve a ≥ 50% reduction in pain (NNT) compared to placebo is about 6. This calculation is based on all doses that were statistically significantly superior to placebo. The evidence is weakest for venlafaxine, but even for gabapentin, pregabalin, and duloxetine, this NNT is likely very optimistic, as we judged the included RCTs to have a high risk of bias.

The greatest potential bias comes from the likelihood that patients and investigators were unblinded by observing drug adverse effects such as somnolence. Loss of blinding has been shown to be associated with a 68% exaggeration of relative benefits for subjective outcomes such as pain.8 In addition almost all RCTs included in the Cochrane reviews were funded by drug manufacturers. A separate Cochrane review demonstrated that industry funded studies lead to “more favourable results and conclusions” than non industry funded studies.9 Accounting for these biases, we suspect the real NNT for benefit from these drugs is at least 10.

An alternative measure of meaningful benefit is the patient’s reported global impression of change (PGIC). PGIC was not reported in any venlafaxine RCT3 and no meaningful difference was found for duloxetine.4 For gabapentin and pregabalin, the estimated NNT for “much or very much improved” PGIC ranges from 6-10.5,6 Like the ≥50% pain score reduction, this is probably overly optimistic.

The evidence of benefit for tricyclic antidepressants for neuropathic pain is weaker and it is not possible to estimate a meaningful NNT.10-13
 
Harms

Withdrawals due to adverse effects compared with placebo were higher with gabapentin, pregabalin, duloxetine and venlafaxine.3-6 Approximately 80% of people receiving these drugs experienced at least one adverse effect. The most common were somnolence, dizziness, and nausea. Anticholinergic effects, such as dry mouth and constipation, were common with duloxetine. The rate of adverse effects reported in Cochrane reviews almost certainly underestimate the real world rates because patients at higher risk (e.g. from impaired kidney function, alcohol use, or with other morbidities) are excluded from RCTs. Furthermore, official product monographs for these drugs report higher rates of adverse effects than do the Cochrane reviews.

The most common adverse effects reported for the tricyclic antidepressants were dry mouth, sedation and constipation.10-13 Likewise official monographs provide a better and higher estimate of the incidence of harms than the systematic reviews. 

To whom do the Cochrane reviews apply?

Patients averaged 50 years of age, had moderate levels of neuropathic pain, and were free of medical conditions other than those being studied (diabetes, fibromyalgia, or post-herpetic neuralgia). RCTs varied with respect to allowed use of other analgesics from acetaminophen only to the use of multiple analgesics including opioids. 

How soon is pain reduced?

In the majority of trials pain reduction compared with placebo was demonstrable within the first week. Very little additional pain reduction occurred after the second week.

Is there evidence that increasing dose improves response?

For gabapentin, pregabalin, duloxetine and venlafaxine, RCTs demonstrated little or no benefit from doses higher than the lowest dose that was superior to placebo.3-6
 
Clinical implications

Evidence from 8 Cochrane reviews should temper expectations regarding the likelihood and magnitude of pain relief from gabapentin, pregabalin, duloxetine, venlafaxine, amitriptyline, nortriptyline, imipramine or desipramine. When initiating a therapeutic trial with one of these drugs in a patient, it is reasonable to start at the lowest recommended dose and assess the patient for benefit and harm at 1 week. If benefit harm ratio is unacceptable, consider stopping the drug. If insufficient but partial pain relief is achieved, increase the dose and reassess within 1 week. If functionally meaningful benefit is still absent, stop the drug and try something else. For patients who achieve clinically meaningful analgesia, use the lowest individualized effective dose to minimize adverse effects. Reassess regularly (e.g. every 2 weeks), as most patients treated with placebo also improve over time.

Conclusions 
 
The evidence base for drug treatment of neuropathic pain is weak, due to the small magnitude of clinically meaningful effects and the high risk of bias in the RCTs.

Probably less than 1 in 10 patients achieve a meaningful reduction in pain.
Most patients experience some adverse side effects like somnolence, dizziness, nausea, dry mouth and constipation.
To identify patients who respond, a therapeutic trial with early assessment is essential. Reassessment of drug utility is needed to detect people with spontaneous remission or placebo response.
Higher doses are unlikely to achieve greater pain reduction, but are more likely to cause harm.

References 
 
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Therapeutics Initiative. Gabapentin for pain. New evidence from hidden data. Therapeutics Letter. 2009; 75:1-2.
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Lunn MPT, Hughes RAC, Wiffen PJ. Duloxetine for treating painful neuropathy, chronic pain or fibromyalgia. Cochrane Database of Systematic Reviews 2014, Issue 1. Art. No.: CD007115. DOI: 10.1002/14651858.CD007115.pub3.
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The draft of this Therapeutics Letter was submitted for review to 60 experts and primary care physicians in order to correct any inaccuracies and to ensure that the information is concise and relevant to clinicians.
The Therapeutics Initiative is funded by the BC Ministry of Health through a grant to the University of BC. The Therapeutics Initiative provides evidence-based advice about drug therapy, and is not responsible for formulating or adjudicating provincial drug policies .

http://www.ti.ubc.ca/2016/01/19/96-benefits-and-harms-of-drugs-for-neuropathic-pain/