POEMs

				Using the search form

To view this article, including Web-exclusive content, in PDF form, click here.

To view only this article's Web-exclusive content (in PDF form), click here.

Intensive control of blood sugar may be harmful in adults with type 2 diabetes

Clinical question Does intensive control of blood sugar (glycated hemoglobin [A1C] level <7.0%) improve outcomes in adults with type 2 diabetes?

Bottom line Intensive control of blood glucose levels in type 2 diabetics (glycated hemoglobin <7.0%) may reduce the incidence of disease-oriented outcomes, but multiple studies have failed to demonstrate any significant reduction in the incidence of adverse patient-oriented outcomes. In this study, intensive control actually increased the incidence of all-cause mortality. Metformin significantly reduces the risk of both major macrovascular events and all-cause mortality and should remain the treatment of choice for lowering blood sugar in type 2 diabetics. There is no evidence that significantly demonstrates improved patient-oriented outcomes for any other diabetic drug classes, including insulin. (Level of evidence = 1b)

Synopsis Previous studies of type 2 diabetes have not reported any significant patient-oriented benefits for intensive control of blood glucose levels, regardless of treatment modality (BMJ. 2003;327[7405]:1-2). The present investigators identified 10,251 adults, aged 40 to 79 years, with type 2 diabetes and a median A1C level of 8.1%. Eligible subjects randomly received (uncertain allocation concealment) either intensive therapy (targeted A1C <6.0%) or standard therapy (A1C from 7.0% to 7.9%). Treatment regimens were individualized by standard diabetic medications at the discretion of patients and their clinicians. Complete follow-up occurred for 99% of subjects for a mean of 3.5 years. The individuals who measured all outcomes remained blind to treatment group assignment. By intention-to-treat analysis, at 1 year A1C levels were significantly lower in the intensive-therapy group compared with the standard therapy group (6.4% vs 7.5%, respectively). Lower A1C levels in the intensive-therapy group were associated with higher medication use from all diabetic drug groups. However, as a result of an increase in all-cause mortality in the intensive-therapy group compared with standard therapy (257 vs 203 deaths, respectively), the study was discontinued. Subjects in the intensive-therapy group also had a significantly increased rate of hypoglycemia, weight gain, and fluid retention. Another study published in the same journal issue (N Engl J Med. 2008;358[24]:2560-2572) also evaluated the benefit of intensive-control (A1C of 6.5% or less) compared to standard therapy (A1C from 7.0% to 7.9%) in 11,140 adults with type 2 diabetes. Although intensive-control significantly reduced the incidence of disease-oriented microvascular events (primarily nephropathy), intensive control did not significantly reduce any patient-oriented major macrovascular events (including death from cardiovascular causes or all-cause mortality). Severe hypoglycemia was again significantly more common in the intensive-control group.

Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358(24):2545-2559.

Tetracyclines are equally effective for the treatment of acne vulgaris

Clinical question What is the most effective way to use tetracyclines for the treatment of acne vulgaris?

Bottom line There is no difference between tetracyclines regarding their efficacy in reducing lesion counts in acne. Although minocycline and doxycycline cost more, they require only once-daily dosing and may be better tolerated. There is no clear advantage to higher doses. (Level of evidence = 1a–)

Synopsis Tetracyclines have anti-inflammatory and antibacterial properties and are recommended for the treatment of moderate to severe acne vulgaris. In this systematic review, the authors identified clinical trials of tetracycline (48), minocycline (29), doxycycline (10), and lymecycline (7) and included a total of 57 studies after excluding for fewer than six patients, duplicate publication, combination therapies, recent antibiotic therapy, specific forms of acne, non-English language, and crossover studies. The authors focused on lesion count (inflammatory and noninflammatory) as the most objective and widely used outcome measure. Only seven studies had more than 100 patients, only 22 were double-blinded and used only intention-to-treat analysis, and none lasted more than 24 weeks. Studies comparing different drugs found no consistent difference in the effect on inflammatory or noninflammatory lesion counts. There was no difference in efficacy over time, which might have happened if resistance had occurred. There was also no benefit to higher doses.

Simonart T, Dramaix M, De Maertelaer V. Efficacy of tetracyclines in the treatment of acne vulgaris: a review. Br J Dermatol. 2008;158(2):208-216.

Half of patients with optic neuritis will develop MS after 15 years

Clinical question How many patients with optic neuritis will develop multiple sclerosis (MS)?

Bottom line After 15 years of follow up, 50% of patients with optic neuritis went on to develop MS. Patients with 1 or more white matter lesions on MRI have the greatest risk of developing MS. (Level of evidence = 1b–)

Synopsis The Optic Neuritis Treatment Trial was a randomized controlled trial of steroids versus placebo in 389 adult patients without MS who had acute unilateral optic neuritis. The authors used standard criteria for the diagnosis of MS. In addition to the original episode of optic neuritis, a patient had to have a second new neurologic deficit attributable to CNS demyelination lasting at least 24 hours and separated by at least 4 weeks from the initial event. Recurrent episodes of optic neuritis did not count in the diagnostic criteria for MS. At the beginning of the study, each patient underwent a standardized assessment that included MRI of the brain. Most of the patients were white (85%) and female (77%), with an average age of 39 years. After 15 years, 50% of the patients (95% CI, 44%-56%) developed MS, most in the first 5 years. The risk of developing MS was highly correlated to the number of lesions found on the initial MRI. Twenty-five percent of patients with no lesions developed MS (18%-32%), whereas 72% of those with at least one lesion developed MS (63%-81%). Although the researchers used statistical methods that take into account the patients who dropped out, a significant limitation of the study is that after 15 years, the researchers could only account for 142 of the original 389 patients.

Optic Neuritis Study Group. Multiple sclerosis risk after optic neuritis: final optic neuritis treatment trial follow-up. Arch Neurol. 2008;65(6):727-732.

Pharmacist-assisted Web-based care improves hypertension control

Clinical question Can a pharmacist-assisted Web-based care program improve hypertension control?

Bottom line A pharmacist-assisted management program including home BP monitoring and regular Web site communication resulted in a higher rate of adequate BP control in hypertensive adults than usual office-based care or home BP monitoring and Web site communication alone. (Level of evidence = 1b)

Synopsis Effective efforts to improve BP control in hypertensive patients are urgently needed. These investigators identified 778 adults, aged 25 to 75 years, with Internet access and uncontrolled hypertension (systolic pressure from 141 to 199 mm Hg and/or diastolic pressure from 91 to 109 mm Hg) and no other coexisting serious disease. Eligible subjects were randomly assigned (concealed allocation) to either usual care with their individual clinician; home BP monitoring and Web-site training; or home BP monitoring and Web-site training plus pharmacist-assisted care management. Web-site access and training included usual care plus e-mail communication with individual clinicians, medication refills, lab information, and patient education tools. Pharmacist-assisted care consisted of active individual-based, online medication adjustment using nationally accepted hypertension guidelines. Individuals assessing outcomes remained blind to treatment group assignment. Complete follow-up occurred for 94% of patients at 12 months and all analyses were by intention to treat. Adequate BP control (<140/90 mm Hg) occurred significantly more often in the home BP monitoring/Web-site training plus pharmacist-assisted care group compared to the home BP monitoring/Web-site training and usual care groups (56% vs 36%, 31%, respectively; number needed to treat = 5, range 3-7). There was no significant difference in the rate of adequate BP control between the usual care and home BP monitoring/Web-site training group.

Green BB, Cook AJ, Ralston JD, et al. Effectiveness of home blood pressure monitoring, Web communication, and pharmacist care on hypertension control: a randomized controlled trial. JAMA. 2008;299(24):2857-2867.

Rhythm control is not better than rate control in AF with heart failure

Clinical question What is the best strategy for managing atrial fibrillation (AF) in patients with heart failure?

Bottom line Rhythm control is no better than rate control for patients with atrial fibrillation, even if they have left ventricular dysfunction. (Level of evidence = 1b)

Synopsis Previous studies have consistently shown no benefit to rhythm control over rate control in patients with AF, provided they were anticoagulated. This study looked at the important subset of patients with AF who also have left ventricular dysfunction. In this study, researchers recruited 1,376 patients with a left ventricular ejection fraction of less than 35% and an episode of AF lasting at least 6 hours; or requiring cardioversion within the past 6 months; or an episode lasting at least 10 minutes within the past 6 months and a history of cardioversion. Patients with persistent AF for more than 12 months were excluded. Their mean age was 66 years and 82% were men. Groups were fairly well balanced at the start of the study—although there were more men in the rate control group—and analysis was by intention to treat. The study was not masked and allocation did not appear to have been concealed. Follow-up was good, with 94% of patients completing follow-up or dying, and a median follow-up of survivors of 47 months. Most patients in the rhythm control group were taking amiodarone, and 90% of patients received an ACE inhibitor or angiotensin receptor blocker, and 90% were anticoagulated. Crossovers occurred in both directions: 21% from rhythm to rate (for inability to maintain sinus rhythm) and 10% from rate to rhythm (for worsening heart failure). There was no difference in the rates of cardiovascular death (27% for rhythm vs 25% for rate control) or all-cause mortality (32% vs 33%).

Roy D, Talajic M, Nattel S, et al; Atrial Fibrillation and Congestive Heart Failure Investigators. Rhythm control versus rate control for atrial fibrillation and heart failure. N Engl J Med. 2008;358(25):2667-2677.

Motor cortex stimulation may improve chronic pain

Clinical question Does motor cortex stimulation improve chronic pain?

Bottom line The reporting of this systematic review limits the conclusions, but it appears that motor cortex stimulation decreases pain in patients with chronic pain. The inclusion of lower-quality studies and the incomplete reporting makes it difficult to determine if the improvement is clinically important. (Level of evidence = 2a–)

Synopsis The authors searched several databases for prospective studies that evaluated the effectiveness of motor cortex stimulation in patients with chronic pain. Additionally, the authors tried to find unpublished studies. The authors don’t describe independent selection of the included studies, study quality assessment, or data extraction. They included 22 studies (327 patients) of invasive brain stimulation and 11 studies (274 patients) of noninvasive stimulation. In other words, these were all small studies. Some of the studies were open-label trials, a design that tends to make the intervention look better. The authors report that pain was significantly reduced by 9.4% using a visual analog scale. They also provide a great deal of data about the proportion of responders in the various studies, but fail to define what constitutes a response. They also fail to report the response rate in the control groups. The response rate is greater in the invasive studies than in the noninvasive studies, but because we don’t know the control rate, we don’t know how much better these interventions really are.

Lima MC, Fregni F. Motor cortex stimulation for chronic pain: systematic review and meta-analysis of the literature. Neurology. 2008;70(24):2329-2337.