Consider The Evidence: Med/Peds Journal Roundup

April 14, 2007

Preventing Post-Op A-fib

Filed under: Cardiology, JAMA — medblog @ 9:50 am

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

February 20, 2007

Statins and Heart Failure

Filed under: Cardiology, statins — medblog @ 3:06 pm

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.

November 20, 2006

Thiazides increase Diabetes, ALLHAT says dont worry

Filed under: archives of internal medicine, diabetes, hypertension — medblog @ 11:08 pm

Archives IM 11/13- ALLHAT data first made news with the conclusion that older, thiazide type diuretics were just as effective at reducing hypertension related disease as newer types of anti-hypertensives. One result of the study that is less well known is that thiazides appeared to increase the risk of incident diabetes. In the last issue of Archives, the ALLHAT investigators addressed this issue more directly.[Article]

The investigators performed post hoc analyses on the subgroups assigned to Ca-channel blockers, ACE-Is, and thiazides. Patients with known diabetes prior to start of therapy were excluded from analysis, as were those without baseline fasting blood glucose(FG) levels.

The data shows that all subjects had an increase in FG, but the thiazide group had a significantly greater increase in fasting glucose levels than the other groups. In addition, subjects in the thiazide group had significantly greater odds of developing diabetes.

Is this a problem? The investigators state that the increase in DM did not result in a greater rate of adverse events compared to the other groups. Are they trying to sweep the issue under the rug? Or are they postulating that the diabetic state induced by thiazides is less malignant than naturally occuring DM? Adverse events data was only 2 years out – not long enough to show effects from new onset DM. The increased risk may have also been partially washed out by the increase in DM among all groups, and the lack of comparison with placebo. I’m not sure I would dismiss the risk as easily as they suggest – but I guess I dont have to worry about grant money…

With both beta-blockers and thiazides being linked to decreased glucose tolerance, the choice of anti-hypertensives is becoming much more complicated.

November 9, 2006

SIDS breakthrough? Mittens for stroke rehab

Filed under: JAMA, SIDS, stroke — medblog @ 11:26 am

JAMA (11/1)- An article in last weeks issue by Paterson, et al. is showing up in many news reports as a major advance in the understanding of sudden infant death syndrome (SIDS). The investigators explored the role of seritonergic(5-HT) neurons in the pathogenesis of the syndrome. Frankly, alot of it was basic science gobledygook to me but I got the idea that 1.) seretonin neurons in the medulla oblongata are involved with autonomic and respiratory function, 2.) postmortem exams of the brains of SIDS victims show significant differences in the number and location of 5-HT neurons, as well as lower relative density of seritonin transport protein. With 35% of the SIDS samples coming from premature babies, and the number of controls that were premature not being reported – I was left wondering if this was all confounded by normal developmental differences?

In a more immediately applicable study, Wolf et al. took about 200 stroke patients with hemiparesis and and had half of them put a restraining mitt on their good hand. Its called constraint-induced movement therapy (CIMT). The idea was to reinforce the connections to the affected limb by restricting use of the other limb. The subjects were 3 to 9 months out from the stroke. The CIMT group were supposed to wear the mitt during 90% of waking hours for 2 weeks. In addition they had daily task practice sessions with the paretic limb. The control group had usual care stroke rehab. In the end, the CIMT group had significantly better motor function that persisted at 1 year after therapy.

October 27, 2006

should we screen smokers with serial spiral CTs?

Filed under: lung cancer, NEJM — medblog @ 2:37 pm

NEJM – This weeks New England has been getting alot of publicity for an article by Henschke and other investigators from the Early Lung Cancer Action Project (ELCAP).

In 1993 the ELCAP investigators began the annual screening of asymptomatic subjects that were at high risk for developing lung cancer. Over 27,000 subjects were screened by spiral CT with a positive result in 405 at baseline screening and 74 more over the 12 years that the study ran. 85% of those had stage I cancer with an estimated 10 year survival of 88%. Detection of lung cancer at an early stage  dramatically improves the survival outcome. The authors compared this data to the value of mammography for breast cancer and found it to similar detection rates.

The accompanying ediorial by Unger points out some of the pearls and pitfalls. The study was cohort control rather than RCT, but it was large and multi-center. There is also the question of how to define the “high-risk” population – apparently the criteria varied by center in the study.

From the numbers in the study, it seems as though the biggest yield is from the baseline scan – Im sure there will be further debate about the best interval for screening, among many other details.  But for now the debate is whether this study is enough to justify screening at all….

 N Engl J Med. 2006 Oct 26;355(17):1763-71

October 13, 2006

DREAMing of diabetes prevention. Part I

Filed under: Uncategorized — medblog @ 8:03 pm

NEJM 10/12 – ACE-Inhibitors are pretty much standard of care in diabetics for prevention of nephropathy. But some evidence suggests that angiotensin blockade may have direct beneficial effects on glucose tolerance. An editorial in the latest New England by Ingelfinger and Solomon explains the evidence that led to a trial of ramipril for the prevention of diabetes mellitus. Take note of their mention of potential confounding by the often overlooked fact that thiazide diuretics and B-blockers may promote diabetes – and the ACEIs were often compared to these drugs.
The study by the DREAM trial investigators involved subjects with impaired fasting glucose or impaired glucose tolerance. Subjects were given ramipril or placebo and followed for three years. Unfortunately, it didnt appear to work too well. The incidence of diabetes was similar in both ACEI treatment and placebo groups. However, treatment group patients did show a significantly better response in an oral glucose tolerance test. The trial seems to show that there may well be an effect of RAS blockade on glucose homeostasis, but not enough for primary prevention of diabetes.

October 4, 2006

The Eyes Have It: New therapy for macular degeneration

Filed under: NEJM, opthamology — medblog @ 7:46 pm

NEJM – The discovery of Vascular Endothelia Growth Factor (VEGF) opened the door for the production of many novel pharmaceuticals. The newest drugs to inhibit this factor are not targeted at malignancy, but rather at the destructive angiogenesis that occurs in wet macular degeneration. Now maker Genentech has to do is figure out the price point that people will pay to save their eyesight.

One RCT by Rosenfeld et al. and another by Brown. et al appear in the NEJM, demonstrating the efficacy of Ranibizumab for age related wet macular degeneration.

The Rosenfeld et al. study compared monthly intravitreal injections of the compound agains sham injections for 2 years. They were able to do this because they tested subjects with occult lesions, or predominantly non-classic lesions – which currently have no approved therapy. They found a significant increase in mean visual acutity in the treatment group, while the placebo group had a decrease.

The Brown et al. study tested the drug against verteporfin and laser therapy – the only other approved therapy for predominantly classic lesions. In this head to head trial, more than 90% of subjects in the Ranibizumab group showed delayed progression of the disease, while only 64% in the usual treatment group did so. Again the mean visual acuity increased in the new treatment, while the usual treatment group experienced a decrease.

The next question to answer is whether older anti-VEGF drugs such as Avastin, originally targeted at cancer, will provide a cheaper alternative to produce the same or better effect.

September 28, 2006

zzzzzz….all about sleep

Filed under: archives of internal medicine, Uncategorized — medblog @ 8:43 pm

So I’m an issue behind, but I had to blog on the sleep-themed Sept 18th issue of Archives of Int Med. (one of my favorite subjects). Just how important is it?

Steptoe et al. found that young adult subjects that slept less than 6 hours per night were almost twice as likely to report their health as being poor – even after adjustment for socioeconomic factors, physical activity, BMI and Beck Depression Inventory scores. However, I cant help be a little cautioned by the fact that both sleep time and health status were based on self-report.

From the basic science side, Irwin et al. found that monocyte production of the proinflammatory cytokines IL-6 and TNF-alpha was significantly higher on the morning after sleep deprivation. (sounds like a bad thing)

Arzt et al warn of a condition that may obscure the diagnosis of obstructive sleep apnea. Their research found that comorbid heart failure resulted in less daytime sleepiness in sufferers of OSA. Unfortumately, the detrimental effects of poor sleep remained present. Because excessive daytime sleepyness is often the presenting symptom leading to the diagnosis of OSA, the researchers caution that physicians may miss the presence of OSA in HF patients.

And in the midst of the obesity epidemic, Kothatsu et al. show that a significant inverse relationship between sleep duration and BMI also exists in a rural population. Other researchers have already shown the same to be true in the urban and suburban populations. But watch out for that giant 70% confidence interval.

September 10, 2006

Din-o-mite: Intensive Lipid Lowering in CHD

Filed under: cardiovascular, CHD, lancet — medblog @ 8:33 pm

Lancet 9/9 – In the latest set of reccomendations from the NCEP ATP, the panel reccomended that patients with CHD or risk equivalent have a goal LDL of 100mg/dL, with an option of less than 70mg/dL in high-risk patients. Several prior studies have shown that further reductions in LDL may decrese mortality, but further study is needed.

In the most recent issue of the Lancet, Deedwania et al. publish results of the TNT study on the outcomes of this new goal of intensive lipid lowering. The design was a double blind RCT involving 10,000 patients with over a median of 5 years. To fit the inclusion criteria, subjects had to be aged 35-75 with history of MI, revascularization, or angina with objective evidence of atherosclerotic disease. Subjects were randomized to recieve either 10mg or 80mg of atorvastatin.

Mean LDL levels were 99mg/dL in the low dose, and 72.6mg/dL in the high dose group. The outcome was a statistically significant decrease in risk for major cardiovascular events in the high dose group. With an absolute risk reduction of 3.5% which is 29% relative. The levels obtained were convenient because they closely reflected the new LDL goals. It seems as if this study does show data to support those reccomendations. The question remains as to whether the results can be generalized to CHD risk equivalents such as diabetes, because the study only included clinically evident coronary disease. (more…)

September 4, 2006

Revenge of the COX-2 inhibitors ?

Filed under: cancer, NEJM — medblog @ 8:30 pm

NEJM 8/31 – Results of the VIGOR trial in 2001 shook the medical world with controversy as concern over cardiovascular side effects pushed several COX-2 drugs off the market. Cox-2’s were not only interesting for their anti-inflammatory effect, but also due to evidence of protection from colorectal adenomas – the precursor to colorectal cancer. But studies by both Pfizer and Merck regarding this effect ground to a halt after safety concerns sufaced.

A pair of articles by M. M. Bertagnolli et al. and N. Arber et al. in the New England present data on the prevention of colorectal polyps and adenomas with Celecoxib. Both studies were RCT’s in which the subjects had previous adenomatous lesions removed.

Bertagnolli’s RCT followed over 1800 patients from 1-3 years and compared high and low dose celecoxib therapy to placebo. They found a signficant 33% and 45% risk reduction for the formation of colorectal ademonas with the two groups respectively. The downside was that the risk of cardiovascular effects was 2.6 and 3.4 times higher in the celecoxib groups.

The Arber et al. study had similar results with a 46% risk reduction in adenomas and a 50% risk reduction in advanced adenomas. Serious cardiovascular events occurred in 2.5 percent of subjects in the celecoxib group and 1.9 percent of those in the placebo group (relative risk, 1.30).

Many questions remain about COX-2 inhibitors. Some recent data suggests that these drugs are just as dangerous as non-selective NSAIDs. Also the relative risk of harm varies from 1.3 in the Arber studies to 4 in the VIGOR trial. Hopefully the full story will become clear with further research…

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