Friday, May 27, 2016

Perspective and common sense in managing type 2 diabetes in older individuals

A recent JAMA paper reviewed this topic. From the abstract:

Four large randomized clinical trials (RCTs), ranging in size from 1791 to 11 440 patients, provide the majority of the evidence used to guide diabetes therapy. Most RCTs of intensive vs standard glycemic control excluded adults older than 80 years, used surrogate end points to evaluate microvascular outcomes and provided limited data on which subgroups are most likely to benefit or be harmed by specific therapies. Available data from randomized clinical trials suggest that intensive glycemic control does not reduce major macrovascular events in older adults for at least 10 years. Furthermore, intensive glycemic control does not lead to improved patient-centered microvascular outcomes for at least 8 years.

The surrogate endpoints for microvascular disease are things like findings of retinopathy or laboratory evidence of renal involvement. This was the basis for a shrill body of opinion following the release of the UKPDS findings that intensive glycemic control in DM 2 was not effective because the improved endpoints were not “outcomes that mattered” (eg blindness or ESRD resulting in the need for chronic dialysis). I've come to consider statements like that as anti-EBM because under first EBM principles it is the patient who decides what outcomes matter, not someone else from afar. As the JAMA paper authors acknowledge, the surrogate nature of the outcomes lasts about 8 years. Longer term follow up of the UKPDS suggested differences in more robust clinical endpoints. In patient-centered decision making a lot depends on the patient's expected longevity.

The paper goes on:

Data from randomized clinical trials consistently suggest that intensive glycemic control immediately increases the risk of severe hypoglycemia 1.5- to 3-fold. Based on these data and observational studies, for the majority of adults older than 65 years, the harms associated with a hemoglobin A1c (HbA1c) target lower than 7.5% or higher than 9% are likely to outweigh the benefits.

So according to these authors the optimal range for many patients in an internist's practice is an A1c level between 7.5 and 9. That bold statement runs counter to a lot of prevailing diabetes dogma. But the harm associated with intensive glycemic control is more than hypoglycemia. For although intensive control does without question confer microvascular benefit, it also seems to result (with a few particular exceptions) in macrovascular harm. See here.

More from the article:

However, the optimal target depends on patient factors, medications used to reach the target, life expectancy, and patient preferences about treatment. If only medications with low treatment burden and hypoglycemia risk (such as metformin) are required, a lower HbA1c target may be appropriate.

Again, it goes beyond hypoglycemia. Metformin is one of only two diabetes drugs found to confer macrovascular benefit and it is likely a pleiotropic effect, having little if anything to do with blood sugar. It would also be reasonable to say that nonpharmacologic modalities (diet, exercise) would confer benefits across the range of A1c.

The article concludes:

High-quality evidence about glycemic treatment in older adults is lacking. Optimal decisions need to be made collaboratively with patients, incorporating the likelihood of benefits and harms and patient preferences about treatment and treatment burden. For the majority of older adults, an HbA1c target between 7.5% and 9% will maximize benefits and minimize harms.

In discussions of diabetes we have, ever since DCCT and the advent of home glucometers and A1c, developed an obsession with glucose lowering. Diabetes, however, is multifaceted and there is much more to consider. Despite a few omissions, all in all this paper is a great discussion of the treatment of type 2 diabetes in accordance with the principles of evidence based medicine.

Tuesday, May 10, 2016

Fluoroquinolone use, aortic aneurysm and aortic dissection

From a recent study:

Importance Fluoroquinolones have been associated with collagen degradation, raising safety concerns related to more serious collagen disorders with use of these antibiotics, including aortic aneurysm and dissection.

Objective To examine the relationship between fluoroquinolone therapy and the risk of developing aortic aneurysm and dissection.

Design, Setting, and Participants We conducted a nested case-control analysis of 1477 case patients and 147 700 matched control cases from Taiwan’s National Health Insurance Research Database (NHIRD) from among 1 million individuals longitudinally observed from January 2000 through December 2011. Cases patients were defined as those hospitalized for aortic aneurysm or dissection. One hundred control patients were matched for each case based on age and sex.

Exposures Current, past, or any prior-year use of fluoroquinolone. Current use was defined as a filled fluoroquinolone prescription within 60 days of the aortic aneurysm or dissection; past use refers to a filled fluoroquinolone prescription between 61 and 365 days prior to the aortic aneurysm; and any prior-year use refers to having a fluoroquinolone prescription filled for 3 or more days any time during the 1-year period before the aortic aneurysm or dissection.

Main Outcomes and Measures Risk of developing aortic aneurysm or dissection.

Results A total of 1477 individuals who experienced aortic aneurysm or dissection were matched to 147 700 controls. After propensity score adjustment, current use of fluoroquinolones was found to be associated with increased risk for aortic aneurysm or dissection (rate ratio [RR], 2.43; 95% CI, 1.83-3.22), as was past use, although this risk was attenuated (RR, 1.48; 95% CI, 1.18-1.86). Sensitivity analysis focusing on aortic aneurysm and dissection requiring surgery also demonstrated an increased risk associated with current fluoroquinolone use, but the increase was not statistically significant (propensity score–adjusted RR, 2.15; 95% CI, 0.97-4.60).

Conclusions and Relevance Use of fluoroquinolones was associated with an increased risk of aortic aneurysm and dissection. While these were rare events, physicians should be aware of this possible drug safety risk associated with fluoroquinolone therapy.

Monday, May 09, 2016

Sunday, May 08, 2016

Diet therapy for eosiniphilic esophagitis

---is reviewed in this paper.

Options include elemental and elimination diets.

Saturday, May 07, 2016

D dimer to rule out aortic dissection


Abstracts from 800 articles were reviewed, yielding 30 potentially relevant studies that were reviewed in full text. Five studies met all eligibility criteria. Data from 4 studies (1,557 participants) that used a D-dimer cutoff of 0.50 μg/mL were pooled to estimate sensitivity, specificity, and positive and negative likelihood ratios. Overall, sensitivity and negative likelihood ratio were 98.0% (95% confidence interval [CI] 96.3% to 99.1%) and 0.05 (95% CI 0.03 to 0.09), respectively. These measurements had little statistical heterogeneity. Specificity (41.9%; 95% CI 39.0% to 44.9%) and positive likelihood ratio (2.11; 95% CI 1.46 to 3.05) showed significant statistical heterogeneity. When applied to a low-risk population as defined by the American Heart Association (prevalence 6%), the posttest probability for acute aortic dissection was 0.3%.


This meta-analysis suggests that a negative D-dimer result may be useful to help rule out acute aortic dissection in low-risk patients.

Friday, May 06, 2016

CVP: not useless if you use it right

From a review:

Critical care physicians frequently try to manipulate the preload of the heart to optimize cardiac function. There is, however, still debate as to what actually indicates the preload of the heart.

Recent findings: Although central venous pressure (CVP) is commonly used to estimate cardiac filling, it is often argued that it is a poor indicator of preload. This is likely true if one does not understand what preload is, principles of measurement with fluid filled systems, the effect of respiratory efforts on the measurement, the physiological determinants of CVP, and finally which point on the tracing to use as the estimate of the preload of the heart. When these are considered, however, the value of the CVP at the base of the ‘c’ wave gives a good indication of cardiac preload and a value which can be followed.

Summary: When properly measured CVP can be a useful guide to the filling status of the right ventricle. CVP is especially useful when followed over time and combined with a measurement of cardiac output. Importantly, preload is only one of the factors determining cardiac output and it must be integrated into a comprehensive approach that takes into account changes in cardiac function and the return of blood to the heart. Finally, the specific value of preload does not indicate volume responsiveness.

Thursday, May 05, 2016

Chagas disease

This free full text review in the American Journal of Medicine focuses on the cardiac manifestations.