Yes, yes, “F-PA John” is a thing, but mad “respek” for the brewmaster he has become. Please help BM John win a dopey contest by going to:

https://theloaferonline.com/the-art-of-craft/

And vote for JRH Tree Streets Ale.

Vote as many times as you can! I don’t want to have to deal with “Sad BM John” if he loses!

Thank you, as always.

yr obt svt,

Dr Steve

I’m just putting this up here so I don’t have to share it on Facebook any more.  I am working in my synthesizer lab and tried, for the first time, to sync up my Drummer From Another Mother (Moogfest 2017), Electribe 2, and Moog Mother 32.  All running through a cheap-ass Behringer mixer with a little digital reverb tossed in for ambience.   All the clocks are running in sync, BUT, the DFAM has 8 steps, while the Electribe has 16×4=64 steps and the Mother has 4×8 = 32 steps.   So the measures line up every once in awhile and that difference makes the rhythms more interesting.  This was also my first “from scratch” Electribe programming.

Anyway, there’s no sound for the first 30 seconds while I’m trying to figure out how to get it started…I’ll do better next time (yes, there will be a next time;  if you listen to the podcast for free, the quid pro quo is I get to post this stupid crap from time to time.)  🙂

Enjoy!

or, more likely, Ignore!

your pal,

Steve

7 JULY 2017 | GENEVA – Data from 77 countries show that antibiotic resistance is making gonorrhoea – a common sexually-transmitted infection – much harder, and sometimes impossible, to treat.

“The bacteria that cause gonorrhoea are particularly smart. Every time we use a new class of antibiotics to treat the infection, the bacteria evolve to resist them,” said Dr Teodora Wi, Medical Officer, Human Reproduction, at WHO.

WHO reports widespread resistance to older and cheaper antibiotics. Some countries – particularly high-income ones, where surveillance is best – are finding cases of the infection that are untreatable by all known antibiotics.

“These cases may just be the tip of the iceberg, since systems to diagnose and report untreatable infections are lacking in lower-income countries where gonorrhoea is actually more common,” adds Dr Wi.

Each year, an estimated 78 million people are infected with gonorrhoea*. Gonorrhoea can infect the genitals, rectum, and throat. Complications of gonorrhoea disproportionally affect women, including pelvic inflammatory disease, ectopic pregnancy and infertility, as well as an increased risk of HIV.

Decreasing condom use, increased urbanization and travel, poor infection detection rates, and inadequate or failed treatment all contribute to this increase.

Monitoring drug resistance

The WHO Global Gonococcal Antimicrobial Surveillance Programme (WHO GASP), monitors trends in drug-resistant gonorrhoea. WHO GASP data from 2009 to 2014 find widespread resistance to ciprofloxacin [97% of countries that reported data in that period found drug-resistant strains], increasing resistance to azithromycin [81%], and the emergence of resistance to the current last-resort treatment: the extended-spectrum cephalosporins (ESCs) oral cefixime or injectable ceftriaxone [66%].

Currently, in most countries, ESCs are the only single antibiotic that remain effective for treating gonorrhoea. But resistance to cefixime – and more rarely to ceftriaxone – has now been reported in more than 50 countries. As a result, WHO issued updated global treatment recommendations in 2016 advising doctors to give 2 antibiotics: ceftriaxone and azithromycin.

Development of new drugs

The R&D pipeline for gonorrhoea is relatively empty, with only 3 new candidate drugs in various stages of clinical development: solithromycin, for which a phase III trial has recently been completed; zoliflodacin, which has completed a phase II trial; and gepotidacin, which has also completed a phase II trial.

The development of new antibiotics is not very attractive for commercial pharmaceutical companies. Treatments are taken only for short periods of time (unlike medicines for chronic diseases) and they become less effective as resistance develops, meaning that the supply of new drugs constantly needs to be replenished.

The Drugs for Neglected Diseases initiative (DNDi) and WHO have launched the Global Antibiotic Research and Development Partnership (GARDP), a not-for-profit research and development organization, hosted by DNDi, to address this issue. GARDP’s mission is to develop new antibiotic treatments and promote appropriate use, so that they remain effective for as long as possible, while ensuring access for all in need. One of GARDP’s key priorities is the development of new antibiotic treatments for gonorrhoea.

“To address the pressing need for new treatments for gonorrhoea, we urgently need to seize the opportunities we have with existing drugs and candidates in the pipeline. In the short term, we aim to accelerate the development and introduction of at least one of these pipeline drugs, and will evaluate the possible development of combination treatments for public health use,” said Dr Manica Balasegaram, GARDP Director. “Any new treatment developed should be accessible to everyone who needs it, while ensuring it’s used appropriately, so that drug resistance is slowed as much as possible.”

Gonorrhoea prevention

Gonorrhoea can be prevented through safer sexual behaviour, in particular consistent and correct condom use. Information, education, and communication can promote and enable safer sex practices, improve people’s ability to recognize the symptoms of gonorrhoea and other sexually transmitted infections, and increase the likelihood they will seek care. Today, lack of public awareness, lack of training of health workers, and stigma around sexually transmitted infections remain barriers to greater and more effective use of these interventions.

There are no affordable, rapid, point-of-care diagnostic tests for gonorrhoea. Many people who are infected with gonorrhoea do not have any symptoms, so they go undiagnosed and untreated. On the other hand, however, when patients do have symptoms, such as discharge from the urethra or the vagina, doctors often assume it is gonorrhoea and prescribe antibiotics – even though people may be suffering from another kind of infection. The overall inappropriate use of antibiotics increases the development of antibiotic resistance in gonorrhoea as well as other bacterial diseases.

“To control gonorrhoea, we need new tools and systems for better prevention, treatment, earlier diagnosis, and more complete tracking and reporting of new infections, antibiotic use, resistance and treatment failures,” said Dr Marc Sprenger, Director of Antimicrobial Resistance at WHO. “Specifically, we need new antibiotics, as well as rapid, accurate, point-of-care diagnostic tests – ideally, ones that can predict which antibiotics will work on that particular infection – and longer term, a vaccine to prevent gonorrhoea.”

Notes to editors

This press release is based on two papers included in a special supplement of PLOS Medicine to be published just before the STI & HIV World Congress (http://www.stihivrio2017.com) taking place in Rio de Janeiro, Brazil, 9–12 July 2017:

Antimicrobial resistance in Neisseria gonorrhoeae: Global surveillance and a call for international collaborative action
Lead author: Dr Teodora Wi, WHO, Department of Reproductive Health and Research

• Multidrug-resistant gonorrhoea: A research and development roadmap to discover new medicines (PDF)
  Lead author: Dr Emilie Alirol, GARDP/DNDi

At the STI & HIV World Congress, WHO will host a session on “Tackling antimicrobial resistance in Neisseria gonorrhoeae: Need for a comprehensive and collaborative approach”.

More about gonorrhoea

• Global Antibiotic Research and Development Partnership (GARDP)
• Global Action Plan on Antimicrobial Resistance

* Each year, an estimated 35.2 million people are infected in the WHO Western Pacific Region, 11.4 million people in the WHO South-East Asian Region, 11.4 million in the WHO African Region, 11.0 million in the WHO Region of the Americas, 4.7 million in the WHO European Region and 4.5 million in the WHO Eastern Mediterranean Region.

For more information, please contact:

Tarik Jašarevi?
Communications Officer, WHO
Telephone: +41 22 791 5099
Mobile: +41 793 676 214
Email: jasarevict@who.int

Kimberly Chriscaden
Communications Officer, WHO
Telephone: +41 22 791 2885
Mobile: +41 79 603 1891
Email: chriscadenk@who.int

Ilan Moss
Senior Communications Manager, DNDi (North America)
Telephone: + 1 646 616 8681
Mobile: +1 646 266 5216
Email: imoss@dndi.org

Jo Kuper
DNDi (Geneva)
Telephone: +41 22 907 7721
Mobile: +41 79 128 5241
Email: jkuper@dndi.org

As many of you know, I suffered from a “demyelinating polyneuropathy” that gradually worsened last year. My symptoms were ataxia (inability to walk a straight line), loss of proprioception (inability to judge where parts of my body existed in space), and horrible paresthesias (pins and needles) in the extremities. My neurologist basically said “oh well, nothing we can do to fix this!” Frustrated, I did some research on my own and found some medications and nutritional supplements that actually have data behind them to support their use in neuropathies. Below is some of the information I found…maybe it’ll help someone you know.

For patients with cancer who are experiencing Chemotherapy Induced Peripheral Neuropathy (CIPN), duloxetine has the best evidence to recommend it (Grade 2B).

There is insufficient evidence to support a strong recommendation for any other treatment. However, in keeping with the recommendations from ASCO, a therapeutic trial of gabapentin/pregabalin or a tricyclic antidepressant (eg, nortriptyline or desipramine) is reasonable given the limited therapeutic options and the demonstrated efficacy of these drugs for other neuropathic pain conditions. Given the single borderline positive trial in patients with CIPN, it is also reasonable to try a compounded topical gel containing baclofen, amitriptyline HCl, and ketamine, understanding that this can only be manufactured by a compounding pharmacy and that ideally confirmatory results from other randomized trials regarding this treatment are needed.

In a situation where evidence based medicine has failed, it it sometimes appropriate to try, as a last resort, methods that have less strong evidence as long as the treatment plan meets the following criteria:
1) the treatment does not replace a possibly efficacious treatment that has good evidence
2) the treatment’s risk/benefit ratio is favorable
3) there is at least some positive evidence

Other dietary supplements that have some positive data (though none of them have class A evidence (double blind, placebo controlled reproducible trials) and are likely to do little or no harm include:

1) Acetyl L-Carnitine  (ALC)
Http://www.sciencedirect.com/science/article/pii/S0959804905004296
[Curr Pain Headache Rep. 2015 Dec;19(12):56.]
However in one study, ALC was found to worsen chemotherapy induced neuropathy at the 24 week mark
[J Clin Oncol. 2013 Jul 10;31(20):2627-33.]
but this remains controversial:
[J Pain Symptom Manage. 2013 Dec;46(6):887-96.]

2) Alpha Lipoic Acid (ALA)
http://onlinelibrary.wiley.com/doi/10.1111/j.1464-5491.2004.01109.x/full
[J Fam Pract. 2015 Aug;64(8):470-5.]

3) Myo-Inositol
http://www.sciencedirect.com/science/article/pii/002604957990060X

4) Gamma E Complex
Http://www.sciencedirect.com/science/article/pii/S0140673683925989
[Pharmacol Rep. 2014 Feb;66(1):44-8.]
[Int J Vitam Nutr Res. 2013;83(2):101-11]

5) Glutamine (specifically for Chemo Induced Peripheral Neuropathy)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3385273/

6) Vitamin K2-7
http://www.jpharmacol.com/article.asp?issn=0976-500X;year=2018;volume=9;issue=4;spage=180;epage=185;aulast=Mehta

On the “alternative medicine” front, there is some early evidence that Corydalis may be effective in neuropathic pain. Though this remedy has been used for hundreds of years, studies are only now being done and are still murine and murid-based only.
[PLoS One. 2016 Sep 13;11(9):e0162875.]

It should be noted that much of the evidence regarding dietary supplements and neuropathic pain is related to diabetic neuropathy (with the exception of glutamine, noted above), which may require different treatment than chemotherapy induced neuropathy.  Solid evidence continues to be lacking, and patients must be given information regarding the scientific method and how nutritional supplements or off-label drugs may or may not be effective.

Methadone can also be considered in patients with neuropathic pain that is refractory to the above. The advantages of using methadone for refractory pain in cancer patients or in those who could not tolerate the side effects of other opioids are well-cited in recent literature. Advantages of methadone over other opioids include but are not limited to: dual elimination without active metabolites allowing safe use with renal and liver failure, delta receptor activity in addition to mu receptor agonism, multiple routes of administration, rapid onset of action, long half-life, low cost and fewer adverse effects. In particular, methadone has salutary effects on hyperalgesia due to neuropathy, due to its antagonistic effect on NMDA receptors.

Disadvantages of methadone include the large variation in interindividual pharmacokinetics, potential for delayed toxicity,resistance of providers to write this medication, emerging state restrictions on its use, and its association with addiction therapy. Patients need to be screened for congential prolonged QT syndrome prior to initiation of therapy, and need to be followed periodically with EKGs to ensure the QTc is less than 450ms. Patients are counseled to avoid drugs and foods (e.g., ketoconazole or grapefruit juice) that can similarly prolong QT or inhibit CYP450. [Am J Hosp Palliat Care. 2011 Mar;28(2):135-40.]

Fortunately, in my case, my symptoms resolved nearly completely (I still have some hand numbness, but all of the other symptoms are gone) with the nutritional supplements alone. Obviously, my experience is anecdotal, but there’s enough decent evidence in the literature to support at least trying these supplements in refractory patients, because the chance of harm from them is so low. As always, DON’T DO ANYTHING WITHOUT A DISCUSSION WITH YOUR MEDICAL PROVIDER.

So there you go, email me if you have questions regarding the information above, and good luck!

yr obt svt,

Dr Steve

(PS: You can check out the supplements above by going to THIS LINK or click one of the images below.)

By Andrew M. Seaman

(Reuters Health) – The measles, mumps and rubella (MMR) vaccine is not linked to development of autism spectrum disorders, even among children considered to be at risk, a large new study finds.

Among nearly 100,000 children, receipt of the MMR vaccine did not increase the risk for autism spectrum disorder (ASD), regardless of whether kids were at higher risk because an older sibling already had the condition, researchers write in JAMA.

“Even for children who are high-risk, the vaccine does not play a role,” said lead author Dr. Anjali Jain of healthcare consulting firm The Lewin Group in Falls Church, Virginia. “We don’t know what does unfortunately, but it’s not the MMR vaccine.”

The results should be reassuring, she said.  Autism spectrum disorder is a range of symptoms that often includes difficulties with communication and social interaction, according to the U.S. National Institute of Mental Health. It’s may also include restricted and repetitive behaviors. The 1998 study that claimed to find a connection between the MMR vaccine and ASD was later debunked. The Lancet, the medical journal that originally published it, withdrew it. Studies continue to vouch for the safety of the vaccine. Still, some people continue to believe that the vaccine is connected to ASD. Parents of children with ASD may also believe there is a genetic component, and so they decline to vaccinate their other children, Jain and colleagues noted in their report in the Journal of the American Medical Association.

For the new study, the researchers used insurance claims data on 95,727 children followed from birth to at least age five between 2001 and 2012. They also had data on the children’s older siblings. Overall, about 2 percent of the children had an older sibling with ASD. Those children were more likely to go on to develop ASD themselves whether they were vaccinated or not, according to the report. The vaccine didn’t increase their risk, the researchers say.

For example, among high-risk five year olds, ASD developed in 23 of 269 who weren’t vaccinated (8.6 percent), compared to 30 of 796 (3.8 percent) who received two doses of the MMR vaccine.

Among kids not at high risk of ASD, 7,735 were unvaccinated at age five and 56 (0.7 percent) were diagnosed with the condition. That compared to 244 of 45,568 children (0.5 percent) who received two MMR doses. Furthermore, children with an older sibling with ASD were significantly less likely to have received the MMR vaccine in the first place. By age five, about 92 percent of the children without ASD in the family had received at least one MMR dose. By comparison, only 86 percent of children with an older sibling with ASD had been vaccinated by that age.  “I think it’s important to show that the degree of undervaccination in the families with children with autism spectrum disorder was significant,” Jain told Reuters Health.

Alongside the lack of association between the vaccine and ASD, the undervaccination rate deserves attention, she said. Roughly a dozen studies have shown that age of ASD onset and its severity do not differ between vaccinated and unvaccinated children, wrote Dr. Bryan King, program director of the Autism Center at Seattle Children’s Hospital, in an editorial accompanying the new study. The new study, King added, now shows that “the risk of ASD recurrence in families does not differ between vaccinated and unvaccinated children.”

SOURCE: http://bit.ly/1JqtTOK JAMA, online April 21, 2015.

Ha ha some genius who lingers WAY longer heard me tell the story of my magic show in the 7th grade, billed as “Esteban the Magnificent,” and what I really did with the silk foulard that was part of my zombie ball trick.

Anyway, an artist who actually illustrated a book with a character “ESTEBAN THE MAGNIFICENT” (coinkydink?) reached out to me to see if she could get the domain name.  Since whoever did this signed up private on WHOIS, I can’t reach you any other way.

Perhaps the artist will pay for the domain, perhaps other special treats are in store for you, or maybe just a hearty handshake.  But if you work something out with her, I’ll send you some exclusive merch that no one else will have.

Email me through the contact tab on this site!

your pal,

Steve

I’ve been asked so many times about this, that I am past-due for posting on this subject. This is one of the articles I reference, when discussing the treatment of “low normal” testosterone:

A randomized, double-blind, placebo-controlled trial of testosterone gel on body composition and health-related quality-of-life in men with hypogonadal to low-normal levels of serum testosterone and symptoms of androgen deficiency over 6 months with 12 months open-label follow-up.

In other words, in SYMPTOMATIC men (those with symptoms consistent with androgen deficiency, i.e., fatigue, erectile dysfunction, loss of libido, weakness) with “LOW NORMAL” testosterone (i.e., in the low range of “normal” (more on this later)), there is improved QUALITY OF LIFE when these patients are TREATED.

So you may ask, “if they’re in the ‘normal’ range, how can they be also ‘abnormal’?”   The answer is in the way “normal” levels are determined.  Basically take 1000 men and draw testosterone levels on them.  Exclude men with diagnosed hypogonadism (low testosterone), of course.  Then average the results and do a mathematical process to determine 2 “standard deviations from the mean.”   This sets your low and high normal levels.  The real process is a bit more complicated, but that’s the gist of it.

Well, what happens when your pool of “normal” candidates, from whom the normal range is derived, contains a SHIT LOAD of people with undiagnosed hypogonadism?  It is estimated that the vast majority of men with low T go undiagnosed (it may be as high as 95%!).   It follows that these undiagnosed men with hypogonadism will drag the average down, thus creating a normal range that also includes people who have symptomatic disease.

So, if you have symptoms of low T, and they’ve ruled out anemia, sleep apnea, depression and low thyroid, a savvy provider who understands the above may opt to treat (at least for awhile to see if it helps) you even if you’re in the “low normal” range.

Remember, testosterone replacement is real medicine, by prescription only, and should be done under the supervision of a licensed medical provider only.  There are downsides to this as well, and make sure your prescriber discusses the risks, benefits, and alternatives to treatment before embarking on any new regimen.

yr obt svt,

Dr Steve

PS: I’ve fallen to #12 on MoogFest.com!  Until March 23, if you’re reading this, please click on this link:

http://moogfest.com/giveaway?referral=HyuCMEDqe&refSource=copy

click SHARE NOW, enter your first name and email and you’ll get a cool Moog Synthesizer newsletter, and you’ll help Lady Diagnosis and me win a piece of equipment for the studio.  I’m pretty sure there are shenanigans going on with some of the entrants, but I would like to win fair and square.

THANKS!