Nail in the coffin for intensive glucose control?

NEJM 3/26/09 – The NICE-SUGAR investigators published the latest of several trials that show no benefit to intensive glucose control (see meta-analysis). In fact, this study shows increased mortality from tight gylcemic control in the ICU.

This appears to be a well done study – over 6,000 subjects, multicenter, both medical and surgical patients, 90-day follow up. Withdrawals were slightly higher in the treatment arm (10 vs 7 percent) but intent-to-treat analysis was used. Insulin use was non-blinded.

So should the intensive glucose control protocol be shelved next to blood-letting and COX-2 inhibitors?

Yes, Statins do everything – even lower BP

What could be crazy enough to end a 4 month hibernation of CTE?

Archives Int Med 4/08 – The UCSD Statin study yielded further evidence that statin treatment reduces blood pressure (although not by much) The RCT enrolled over 900 subjects without known CVD or diabetes. The idea was to independently assess the effect on BP. There was no inclusion / exclusion criteria regarding baseline BP. Subjects were randomized to pravastatin, simvastatin, or placebo.

Treatment with a statin resulted in about a 2-2.5 point drop in SBP and DBP. The treatment was stopped at 6 months, and the blood pressures returned to baseline by month 8 – further suggesting that this was a true effect.

Antibiotics no good for acute sinusitis?

JAMA 12/5/07 – House of God Law #13: “The delivery of good medical care is to do as much nothing as possible.” The last time we saw this rule at work was with otitis media.

A study in JAMA by Williamson et al. sought to see just what good comes from the common practice of prescribing antibiotics and nasal steroids for acute bacterial sinusitis. The study included 240 patients seen by family practitioners in the UK. To be included, the patients had to have 2 or more of the classic clinical diagnostic criteria. No radiology or lab studies were used in diagnosis.

Treatment groups were randomized to receive either antibiotics and nasal steroids, a placebo of one plus the other, or a placebo of both. Patients kept symptom diaries to track outcome.

The findings showed that symptom severity scores were similar for all groups on each of the 10 days following initiation of treatment. In short – symptoms improved by day 10, and at the same rate, regardless of whether the patient received antibiotics and/or steroids vs placebo. The hard part is now to convince patients that they dont need either.

Interestingly – the study does mention the Cochrane review on this subject which DID find a treatment effect for both antibiotics and steroids. However, they point out that the studies included in the review used radiographic evidence as diagnostic criteria – which does not commonly happen in the community. (And the utility of which is whole other bag of worms that will have to be covered another day)

Thimerosal and Vaccines

NEJM – The latest issue contains a study and two editorial articles on the link between Thimerosal and neuropsychological dysfuntion such as autism. Short story – there is no connection. However, I think the need to find somewhere to place blame will cause many families to continue believing that there is some sort of cover-up no matter how many studies are produced.

Review: MRSA infection

NEJM 7/26 – Not an original research article, but a worthwhile read. An article by Daum reviews skin and soft tissue MRSA infection in the Clinical Practice section of the current NEJM. An increasingly common issue for which a refresher is always helpful – I thought the paper was so solid it deserved a mention anyway.

Daum, RS. Clinical practice. Skin and soft-tissue infections caused by methicillin-resistant Staphylococcus aureus. N Engl J Med. 2007 Jul 26;357(4):380-90. Review. PMID: 17652653

Food for thought: Chocolate to lower BP?

JAMA 7/4/07 -  Maybe some wizard medicine applies to muggles as well… An article in JAMA by Taubert et al. tests the theory that flavonols found in dark chocolate may lower blood pressure. 

 The study population consisted of 44 otherwise healthy subjects with upper-range prehypertension or stage 1 hypertension. Patients with any other major medical problems including CVD, diabetes, hyperlipidemia, etc were excluded. Study design was an RCT with investigators blinded, but subjects not – because they couldnt disguise the white and the dark chocolate. Patients were also counseled to abstain from any other cocoa products during the study.  Participants were instructed to take one 5.6(white) or 6.3(dark)  gram piece of chocolate per day.

At 6 weeks – no statistical difference between groups.
12 weeks: dark chocolate group BP was down 2.4/1.3 mmHg from baseline.
At 18 weeks the BP difference in the dark chocolate group was – 2.9/1.9 mmHg.
The white chocolate group: no change.    
Looks like we have a winner.

For the basic science portion of the study, researchers measured plasma S-nitrosoglutathione. Basically they postulate that this compound is an intermediary between nitric oxide stores and active NO in the endothelium. They also measured 8-isoprostane, a measure of oxidative stress. Levels of S-nitrosoglutathione were significantly increased only in the dark chocolate group. 8-isoprostane levels were unchanged with intervention in both groups. Investigators concluded that the effect of dark chocolate was more likley from stimulation of endothelial NO production rather than changes in redox equilibrium between thiol and nitrosothiols. Big words aside – it seemed to work… at least in a healthy, homogenous, untreated population with mild HTN – although I dont seem to have alot of those in my practice….

Do SSRIs reduce bone density?

ArchivesIM 6/25 - The current issue contains a pair of articles that make a connection between SSRI use and bone mineral density (BMD). The pair of observational studies by Diem et al. and Haney et al. seperately studied a cohort of men and women respectively. The study involving women showed a greater yearly decrease in BMD when compared to nonusers as well as trazodone and TCA users. The study of men simply showed overall lower mean BMD associated with SSRIs as well with no effect seen from TCAs.  Obviously both studies suffer from the typical observational methodology pitfalls – but definitely merit further investigation. The main question to be answered is whether this effect translates into a greater clinical risk of fracture or other negative outcomes.  Given the large burden of both depression and osteopenia in the elderly, clearly the interaction needs further study.

Changing the asthma treatment paradigm?

NEJM 5/17/07- I can’t help but wonder if this is a “welcome mat for new drug cocktail” study. Papi et al in the BEST study group publish a paper showing that using a steroid inhaler on an as-needed basis might be just as good as twice daily use.

The double-blind, double dummy design seems pretty robust, although makes the data a little complicated. In short – all subjects took a regular inhaler twice daily, plus an as-needed inhaler – the design just varied what was in the inhalers among groups. The most relevant comparison was – twice daily beclamethasone plus rescue albuterol (old skool method) versus twice daily placebo and rescue beclamethasone and albuterol combo.

It looks as if using a PRN steroid was just as good as the old twice daily method. The money graph seems to show that time to first exacerbation was the same in both groups and clearly better than albuterol rescue alone. Frankly the comparisons of PFTs and symptom scores got a little too crazy for me to handle but a cursory look seems to confirm the equivalence in most comparisons.

Any guesses as to what new combo inhaler we might be seeing soon? Check out the laundry list of financial disclosures at the end – Im sure one of those companies is planning to cash in on this one.

Preventing Post-Op A-fib

JAMA 4/11/07 – A rare surgery related article for today by Halonen(s) et al. from JAMA.

For unclear reasons the incidence of A-fib after CABG and valve surgery is pretty high (20-40%). One theory is that it is somehow related to an inflammatory response,  and maybe can be prevented with steroids.

This double blind RCT compared Q8 hr hydrocortisone for 3 days postop to placebo for the incidence of atrial fibrillation. They found the incidence of postoperative AF was significantly lower in the hydrocortisone group (30%) than in the placebo group (48%)  with a NNT of 5.6.  And the incidence of infection was similar in both groups.

Interesting because I remember blogging about an article that showed an increase in A-fib with pulse dose steroids in Annals last year. What gives? Well the prior study didnt involve surgery and it was observational – but I was still suprised at the opposite conclusions…. hopefully it will become more clear when the exact mechanism is better worked out

Statins and Heart Failure

Circulation 2/6 – Treating to New Targets (TNT) was one of many recent statin trials investigating the utility of high-dose treatment with very low LDL-C goals for improving cardiac outcomes. In a recent issue of Circulation Khush et al. published a subgroup analysis of data related to exacerbations of heart failure among trial participants. The study examined the number of hospitalizations for heart failure among the subjects in both the intervention (high dose atorvastatin) and control (usual dose atorvastatin) group.

The investgators found that those with CHD were about 26% less likely to be hospitalized for HF in the intervention arm. Those with CHD and prior CHF were 41% less likely to be hospitalized for an exacerbation. The authors of the study noted that in most cases there was no preceeding ischemic event such as MI or UA prior to the exacerbation. This led them to conclude that the protective effect in heart failure is not simply from the reduction of coronary stenosis alone, but rather an independent effect of statins on heart failure.