Biologists develop new method for discovering antibiotics

Science Daily: “Biologists at the University of California, San Diego have developed a revolutionary new method for identifying and characterizing antibiotics, an advance that could lead to the discovery of new antibiotics to treat antibiotic resistant bacteria. The researchers made their discovery by developing a way to perform the equivalent of an autopsy on bacterial cells. “This will provide a powerful new tool for identifying compounds that kill bacteria and determining how they work,” said Joseph Pogliano, a professor of biology at UC San Diego who headed the research team.”” – An “autopsy on bacterial cells”, how cool is that. This is a tremendous discovery as we’ve been slowly losing the war on bacteria for more than a decade. The last time I practiced “clinical pharmacy” was about six years ago and antibiotic resistance was a scary issue back then.

Journal reference:
Poochit Nonejuie, Michael Burkart, Kit Pogliano, and Joe Pogliano. Bacterial cytological profiling rapidly identifies the cellular pathways targeted by antibacterial molecules. Proceedings of the National Academy of Sciences, September 2013; DOI: 10.1073/pnas.1311066110

superbug

(Image taken from The Microbiologist, where source is liked to CNN)

SharePractice – a collaborative clinical reference for physicians

Here’s an interesting concept.

SharePractice is an application that uses the idea of crowdsourcing other physicians to rank treatments for various disease states.

“Good doctors make bad decisions because knowledge sources are incomplete and static. Medical reference tools are biased by business interests and take too long to update. Reading research papers is an antiquated process that most busy doctors just don’t have time to read.

It is challenging for doctors to remain aware of new or effective treatments because there are no easy ways for us to communicate, evaluate and share clinical insights. So we call, text, email, use forums and go to conferences. But this data is not collected and it is lost.

Share Practice gives doctors power to collaborate on treatments and rate clinical efficacy.  Our next generation medical reference gives every doctor the ability to ‘publish’ findings, get feedback from the community, review conventional therapies and incorporate new and integrative medicines into the collective knowledge-base.

Share Practice is the most current source of medical information, contributed to and maintained by doctors around the world. Beautifully simple, mobile and freely available, Share Practice is built for doctors; by doctors.”

Check the video below to get a better idea of what SharePractice is.

Impact of alcohol intake on medication adherence [abstract]

Does alcohol consumption impact medication adherence? I don’t know, but it’s a fair question. I would assume that it all depends on when you drink, how much, how often, if there’s any correlation between drinking time and medication consumption, age and social status of the patient, and so on. The variables one would have to look at would be quite extensive in my opinion. We’re talking about human behavior here, which is notoriously difficult to quantify and control.
Continue reading Impact of alcohol intake on medication adherence [abstract]

Tight glycemic control has no proven benefits for children in the cardiac ICU [article]

It looks like we’re still beating this dead horse. I thought we put the tight glycemic control issue to bed a while back. Then again I’ve been out of the game for quite some time, so it’s quite possible that I’ve missed something. Actually, it’s likely I’ve missed something.

Tight glycemic control was all the rage in intensive care units (ICUs) all over the country in the late 90’s early 2000’s. Tight control was supposed to reduce infection, promote healing, improve outcomes, etc. Then we found out that tight control really didn’t do that, but it did cause a lot of adverse effects, namely severe hypoglycemia. Makes sense when you thing about it. Giving patient aggressive insulin infusions to keep blood glucose less than 110 mg per deciliter is bound to lead you down the path to hypoglycemia. Just sayin’.

Every once in a while a new study shows up looking at tight glycemic control in the ICU. The most recent is a study in children. The nuts and bolts of the study? Basically there was no indication that tight blood glucose control showed any benefit in pediatric patients undergoing heart surgery. The results are from the Safe Pediatric Euglycemia in Cardiac Surgery (SPECS) trial, which was conducted at Boston Children’s and at the University of Michigan C.S. Mott Children’s Hospital. The full article appears in the September 7 online edition of the New England Journal of Medicine. It’s free to read, so I would encourage you to get it while you can. The article should be available in the September 27 print edition as well.

SPECS examined tight glycemic control with insulin compared to standard glucose management in 980 children hospitalized in the cardiac intensive care unit (CICU). Results from the research showed that maintaining “normal” blood glucose levels [80 to 100 mg per deciliter] with insulin had no demonstrable impact on the incidence of care-related infections (such as surgical site infections and pneumonia), length of stay in the CICU, organ failure or mortality. And as expected, the glycemic-control group had a higher rate of severe hypoglycemia (<40 mg per deciliter) than did the standard-care group; 3% versus 1%, respectively. The rate of total hypoglycemia (<60 mg per deciliter) followed a similar pattern; 19% for the glycemic-control group versus 9% for the standard-care group.  Not surprising.

Hey, it wasn’t all for nothing. The primary author of the article, Dr. Michael Agus had this to say, “There were two successes for this trial. One was that we were able to show that children and adults are different when it comes to the benefit of glucose control in an CICU. We were also able to demonstrate that we can safely control glucose in a young, vulnerable, sick population.” And there you have it, children are not adults and we can safely treat children under our care. Who knew.

 


New hydrogel research gives new meaning to “sustained released” medication

Medical Xpress: “Researchers from the University of Cambridge have developed injectable, reformable and spreadable hydrogels which can be loaded with proteins or other therapeutics. The hydrogels contain up to 99.7% water by weight, with the remainder primarily made up of cellulose polymers held together with cucurbiturils – barrel-shaped molecules which act as miniature ‘handcuffs’….

 The hydrogels developed by Scherman, Dr Xian Jun Loh and PhD student Eric Appel are capable of delivering sustained release of the proteins they contain for up to six months, compared with the current maximum of three months. The rate of release can be controlled according to the ratio of materials in the hydrogel.” –  I think you’ll see more and more treatment with proteins in the future as we continue to advance “drug therapy”. Given that chronic conditions cause major problems for healthcare in terms of patient adherence, a system that acts as a six month reservoir offers up some serious potential.

The article referred to can be found below. Unfortunately I could only access the abstract, which was almost useless.

Biased pain medication prescribing

KevinMD.com:

“Undertreated pain is worse than addiction.”

On one end is the doctor who is deeply, morally troubled by patients in pain. This doctor is not unaware of the risk of addiction but is willing to risk being taken advantage of by a wily narcotic seeker rather than leave pain untreated. This doctor knows that undertreated pain can tremendously decrease his/her patients’ quality of life. He/she feels that relieving suffering is one of the most important responsibilities of a physician.

“Addiction is worse than undertreated pain.”

On the other end is the doctor who is deeply, morally troubled by the possibility that he/she may contribute to someone’s narcotic addiction. This doctor is not indifferent to pain but is willing to risk undertreating pain rather than inadvertently create an addict. This doctor knows that every single narcotic addict gets their ongoing pill supply, directly or indirectly, from a physician’s prescription pad. He/she feels that preventing the misuse of these dangerous medications is one of the most important responsibilities of a physician.

The article is interesting because it’s basically true. The author describes two camps in the pursuit of pain and the potential for “addiction”: 1) “Undertreated pain is worse than addiction.” or 2) “Addiction is worse than undertreated pain.” I’ve come across both camps during my stint as a pharmacist.

I think there are a couple of things worth mentioning. First, I would speculate that those on the side of addiction-is-worse-than-undertreated-pain have never been in severe pain. Pain can be both mentally and physically devastating; been there. And second, I believe there is a distinct difference between addiction and dependence. People that are in pain, real pain, will seek pain medication. That doesn’t make them an addict. It makes them humans in search of relief from pain. They are basically dependent on pain medication to maintain a certain quality of life. People with diabetes utilize insulin to maintain a certain quality of life. Do we say that they are addicted to insulin? Not likely.

The controversy surrounding pain medications is troubling to me. I fear that people will needlessly suffer as physicians and other healthcare providers become paranoid about potential addiction and regulatory issues, which will ultimately lead to rampant under treatment of pain. All I’m saying is first and foremost treat the patient.

Scientists find new mechanism behind resistance to cancer treatment

Medical Xpress: “A team of scientists led by Fred Hutchinson Cancer Research Center has discovered a key factor that drives this drug resistance [chemotherapy resistance].Nelson and colleagues found that a type of normal, noncancerous cell that lives in cancer’s neighborhood – the fibroblast – when exposed to chemotherapy sustains DNA damage that drives the production of a broad spectrum of growth factors that stimulate cancer growth. Specifically, the researchers found that DNA-damaging cancer treatment coaxes fibroblasts to crank out a protein called WNT16B within the tumor neighborhood, or microenvironment, and that high levels of this protein enable cancer cells to grow, invade surrounding tissue and resist chemotherapy.” – Interesting finding. I suppose that means we’ll be looking at WNT16B inhibitors soon? Probably not soon. A quick Google search revealed that that protein may contribute to several other processes in the human body.

Article from Nature Medicine below.
Continue reading Scientists find new mechanism behind resistance to cancer treatment

Pharmaceuticals from crab shells

This is pretty cool stuff.

Vienna University of Technology: “Fungi with additional foreign genes have been created at the Vienna University of Technology. They can now turn chitin into pharmaceuticals.

Usually, mould fungi are nothing to cheer about – but now they can be used as “chemical factories”. Scientists at the Vienna University of Technology have succeeded in introducing bacterial genes into the fungus Trichoderma, so that the fungus can now produce important chemicals for the pharmaceutical industry. The raw material used by the fungus is abundant – it is chitin, which makes up the shells of crustaceans."

N-Acetylneuraminic acid (sialic acid or Neu5Ac) is a naturally widespread carbohydrate with several biological functions, including blood protein half-life regulation, variety of toxin neutralization, cellular adhesion and glycoprotein lytic protection. Neu5Ac is also the starting reagent of biochemical derivatives for the synthesis of pharmaceuticals, including antivirals. Basically it’s pretty important, but it’s also very expensive, running about $2600 per gram.

Fortunately the team at Vienna UT uses a genetically altered form of the fungus Trichoderma to help create Neu5Ac from Chitin, which is readily and abundantly available, thus making it a much more cost effective pharmaceutical substrate. Ta-da!

Med Adherence – Difference between prescribed and dosing histories [Article]

Annual Review of Pharmacology and Toxicology (2012 Feb 10;52:275-301. Epub 2011 Sep 19) – No big surprise here, but check out the graphs (posted below), especially the second one where you can see the effect poor compliance/adherence has on therapeutic concentration. Crazy.

Abstract

Satisfactory adherence to aptly prescribed medications is essential for good outcomes of patient care and reliable evaluation of competing modes of drug treatment. The measure of satisfactory adherence is a dosing history that includes timely initiation of dosing plus punctual and persistent execution of the dosing regimen throughout the specified duration of treatment. Standardized terminology for initiation, execution, and persistence of drug dosing is essential for clarity of communication and scientific progress. Electronic methods for compiling drug dosing histories are now the recognized standard for quantifying adherence, the parameters of which support model-based, continuous projections of drug actions and concentrations in plasma that are confirmable by intermittent, direct measurements at single time points. The frequency of inadequate adherence is usually underestimated by pre-electronic methods and thus is clinically unrecognized as a frequent cause of failed treatment or underestimated effectiveness. Intermittent lapses in dosing are potential sources of toxicity through hazardous rebound effects or recurrent first-dose effects.

Continue reading Med Adherence – Difference between prescribed and dosing histories [Article]