EMU Essays December 2011

1. We will not discuss the clinical presentation of migraine nor the pathophysiology, although they claim to be pretty close to defining the pathophysiology (some egghead thing with neurotransmitters) and as such some really far out experimental drugs are now in trials and if it really interests you (and you qualify as an egghead) see Curr Treat Options Neuro 13(1)1
2. Treatment –see ibid 13(1)15.The principles are the following-start early- it is easier to abort a migraine early on. Medication overuse can lead to refractory headaches so migrainers have to be careful about overuse. Have them be selective as to which headaches they will treat – allowing minor ones to subside on their own.
3. NSAIDS and Tritpans are proven to work. NSAIDS work on the inflammatory cascade so are very effective here. Often our patients have tried them already before coming to us. Naproxen has a slight advantage in having a longer half life than ibuprofen- the former 12-15 hours the latter 2 hours.
4. Triptans work great, but should be used early. There are few differences between the many drugs in this class and we will go over them below. These by and large are safe drugs but there may be some minor side effects like chest pressure, myalgias, fatigue, flushing, or asthenia, Contraindications include cardiac, cerebral or peripheral vascular disease. They do increase blood pressure. They should not be given in basilar or hemiplegic migraine. Serotonin syndrome is a concern when used with SSRIs and MAO inhibitors, but there is little evidence at this point.
5. Sumatriptan has the advantages of be able to be given intranasally, by injection by pill form and with naproxen in one pill. Naratriptan has no MAO or P450 interactions but can not be given in renal impairment. Frovatriptan has the longest half life of any triptan- 26 hours. Almotriptan has also no MAO interaction. That is about all there is in differences between these meds.
6. Want a great therapy? Try aspirin 1 gram. One study showed good results- about as good as NSAIDS- which makes sense.
7. Butalbital (a barbiturate) was popular in the past for migraines- this med has been banned in most parts of the world because of ease of developing dependence. Opiates are discouraged but are still the most widely prescribed drugs for acute attacks. The theory is that they are vasodilators, pro inflammatory and maybe pro nocicepetive. Caffeine is not discussed although it is included in many medications, I am not sure why- the last thing I want when I have a migraine is to be awake
8. Other options were also not included. The article seems to feel ergotamines are no longer indicated. Steroids are often used- I have seen articles in CMAJ that were very enthusiastic. One article in Headache showed that propofol helped. High flow oxygen is used by many. Droperidol is supposed to be the best therapy, but it is black boxed in the USA and not available in many parts of the world. Haloperidol seems to be effective if you do not have this- see Headache 2006 . An Israeli study used Valproic acid IV with remarkable results, but it was open labeled and took a full 50 minutes to work. They needed 900 -1200 mg. See Acta Neuro Scand 123(4)257
9. Here is Chris’ take on steroids: “Role for steroids is primarily meant to be in reducing recurrence, as backed by meta-analyses like this but only the 1999 study was actually statistically significant. A more recent DB-RCT found no effect.”
10. Now let’s speak about non pharmacologic treatments, from this article (Curr Treat Options “Neuro 13:28) which has headache guru Rich Lipton as one of the authors. Foods are considered a trigger to migraines but the evidence is actually sparse. Those often implicated are MSG, aspartame, nitrates, red wine and caffeine (more than 200 mg a day). Chocolate and tyramine have even less evidence to support their role in causing headaches. Lifestyle causes include stress irregular meals and lack of sleep. Exercise tends to be protective. Menstruation can also be a trigger. Most migraneurs have identified their triggers.
11. Relaxation therapy shows that about 50% of people have a 50% or more reduction in head ache frequency
12. Biofeedback is “the digital capture of physiological processes which are converted back into a medium that is fed back to the patient” I have no idea what that means. Whatever it means it is done by EMG feedback, hand warming feedback and blood pressure feedback where they learn to contract blood flow to the temporal artery. They are enthusiastic about this therapy as it works well against depression and anxiety- results are similar to relaxation therapy.
13. Cognitive behavioral therapy which is done with a therapist or psychologist works as well as the above. They identify what stressors cause the headaches and how to manage these stressors.
14. Pharmacological therapy is better than behavioral therapy over the short term, but once patients learn how to use behavioral therapy- they equalize in efficacy. One study however showed amazing results using combination drug- behavioral therapy.
15. Complementary therapies have been plagued by remarkably poor studies. It escapes me why practitioners are unwilling to do RCTs like other accepted therapies. Acupuncture is probably the best hope, but there is publication bias- only positive studies are published. So we cannot really know.
16. Spinal manipulation: Case studies and small studies are the rule here- so there is no strong science that this works at all. PT/OT has similar evidence problems,
17. Massage does lower anxiety, hear t rate and cortisol levels- but again evidence is lacking. This may depend on who is doing it.
18. Yoga actually has one controlled trial that showed benefit. On the other hand homeopathy has failed in many trials to show benefit Reflexology which is related to reflex zones in the foot showed possible benefit in one study but it was uncontrolled. Seems most CAM is not first line.
19. Natural medicines actually have somewhat stronger evidence but still not RCTs that would give us a clear answer. Butterbur rhizome is somewhat effective in doses of 100- 150 mg a day in divided dosages.
20. Vitamin B2 at 200 mg twice a day and coenzyme Q10 have some benefit as well. Q10 has one RCT. The article states that most therapies are safe although I do not know how we know this with the paucity of data
21. Not mentioned in the article is a therapy we mentioned in the past- greater occipital nerve block ( Curr Pain Headache Reports 2007). Some neurologist I spoke to say it helps. But like all the above – it isn’t clear how these work and if they work and there may be a significant placebo effect.

1. I can”t really understand how this sentinel article was published only in Curr Opin Infect Dis 24:118. For those with this problem it isn’t funny, and it would be helpful to give these patients hope. The disease presentation is pretty typical- painful nodules, abscesses, draining sinuses, draining sinus typically in skin fold regions. Differential diagnosis included infected epidermal cysts (what we called sebaceous cyst), Bartholin’s gland abscess, nodular acne, and cutaneous Crohn’s disease. This is located in the area of apocrine glands. However they are probably not involved. It seems this probably starts with follicular inflammation and keratin plugging. Bacterial infection is secondary and not the cause. And indeed often the cultures are sterile and antibiotics have variable response rates.
2. High BMI and smoking seem to be involved- and these factors make it worse. Pregnancy seems to improve the situation and pre menstruation and oral contraceptives seem to make things worse. Anti androgen therapy seems to work proving a hormonallyassociation as well.
3. What ever the cause, it is icky and so treatment is desired, even though the disease is usually harmless. Antibiotic creams such as clindamycin, fusidic acid and the like have an effect in mild disease. If there a few lesions, the result of injected the lesions with 2- 5mg of triamcinolone is not that painful and does help the pain rather quickly
4. By mouth, tetracyclines are often used but results have been disappointing. Clinda and rifampin by mouth had impressive results- but only in some patients.
5. Females seem to benefit from estrogen therapy, or finastride (helped their BPH too!) or spironolactone. Isotretinoin is ineffective. Dapsone and cotico steroids seem to be effective. TNF blocking agents have worked in a single case report.
6. Surgical options: incision and drainage usually is not successful as nodules do not drain and often there is scarring and recurrence. Wide excision surgery has the best results but the science is lacking. Laser treatment may be less invasive with similar success
7. I must say this article makes this clearer to me but there are still too many question marks as to what works. What doesn’t work though- is now clearer to me. How about you?

Now our bonus essay from Dec 2006… EMU LOOKS AT : Diabetes Type II

What could I possibly tell you that you do not know already? Firstly, not everyone is an internist. Secondly many new drugs have come out
since many of you have trained. The purpose of this essay is not to treat diabetes but rather to understand what patients are taking when
they come to the ED and also to start or correct therapy when these patients are poorly controlled. The source for this article is the ADA
Consensus Statement in Diabetes Care, Aug 06, and the NEJM, 2 Nov 06. The focus is on the medications, not the theory.

1. Fasting glucose is a good guide, but nowadays, Hemoglobin a-1-c is the standard. Remember the number a-c should be and perhaps even  few times during the space of a week can correlate well with A1C. For following glucose, fasting and preprandial are the best measures
2. We still recommend lifestyle adjustments to lower A1C. Surprisingly, according to this guideline, they can lower A1C as well as insulin. In those who have had surgery for weight reduction, for example, many have seen their diabetes disappear completely. Many people see benefit even with a loss of as little as 4 kg. However, these measures often fail within the first year.
3. Step one with medications is Metformin (Glucophage). This drug is cheap, easy to take, decreases hepatic glucose output and lowers fasting glycemia. Rarely causes hypoglycemia or weight gain. Lactic acid in folks with kidney problems is the scary side effect, but it is rare.
4. Step two is sulfonylureas. We are well beyond the days of Diabenase and Tolinase ( in Israel Orsinon) but the second generations are dependable and cheap. They cause hypoglycemia, though, and weight gain which results in perhaps worse cardiovascular mortality. Overdose is treacherous, and of course even in non overdose cases, hypoglycemic events need admission due to the long half life of these drugs. These drugs work by enhancing insulin release In 2011 I rarely use these
5. Step two could also include TZDs. These drugs are insulin sensitizers. These drugs work more modestly in bringing down A1C, somewhere between .5 and 1.4%. They cause fluid retention, pedal edema, and weight gain. They do however, improve lipid profiles. The prototype for this group is rosilitazone, also known as Avandia- (now in 2011: off the market).
6. After step two, consider other drugs, although you must give thought to going straight to insulin. Glinides work like the sulfonylureas, but bind to different sites . They have a much shorter half life. Seems they cause less hypoglycemia. Repalganide is the most effective in the group (Novonorm in Israel), but it is very expensive.
7. Alpha Glucosidase inhibitors reduce digestion of polysacchrides in the small intestine, they reduce A1C about .5-.8 %. They do not cause malabsorption, but they will cause a lot of gas and discomfort, as more carbohydrate is delivered to the colon. Almost 50% of the patients taking this do not continue therapy. The prototype is Prandase.
8. Glucagon like peptide agonists (exenatide) stimulate insulin release, and are a naturally occurring hormone. They lower postprandial spikes , prevent glucagons release, and lower A1C modestly. Vomiting and diarrhea are very common. It is unavaible in the USA. Pramlintide is a Amylin agonist works similar to and has the same side effects as exanatide. I could not find this drug in the Israeli list of medications (MEDIC)
9. Insulin. This is very effective of course, but you need larger doses in type II to overcome insulin resistance. HDL will go up, triglyceride will go down, but there will be weight gain. New non peaking insulins make hypoglycemia unlikely, and inhaled insulin is the newest rage, but whether it can lower A1C to less than 7% remains to be seen. Recall if your patient is taking Lantus ( a long acting non peaking insulin) you need to admit for observation also if they do have hypoglycemia. If is insulin does not work completely, you may increase it or add metformin or a TZD. In sick hospitalized patients, avoid sliding scales- give a small basal rate and add a regular insulin before meals.
10. I never understood why people send patients to the ED with high sugars who have no ketones on urine tests and are not in a hyperosmolar state, and this guideline does not understand why these patients are hospitalized.