Metformin extended release (XR) formulation appears to cause a small but significant decrease in body mass index (BMI) in non-diabetic obese adolescents when combined with a lifestyle intervention program, according to a recent study.

Researchers conducted a randomised study in 77 obese adolescents aged 13 to 18 years. Patients received a lifestyle intervention program, consisting of physical activity and diet, and were randomised to receive either 1 daily dose of metformin XR 2,000 mg (n = 39) or placebo (n = 38) for 48 weeks. Participants were monitored for an additional 48 weeks.

Metformin XR had a small but statistically significant impact on BMI over the initial 52 weeks of the study. The average BMI increased by 0.2 in the placebo group and decreased by 0.9 in the metformin XR group. The BMI difference between the groups persisted for 12 to 24 weeks after cessation of study drug. Thereafter, the mean BMI in the metformin group increased toward that in the control group.

Metformin was safe and tolerated in this population. These results indicated that metformin may have an important role in the treatment of adolescent obesity, wrote the authors.

Longer-term studies will be needed to define the effects of metformin treatment on obesity-related disease risk in this population, the authors concluded.

Adapted from: Archives of Pediatrics & Adolescent Medicine, Feb 2010

In treating visceral leishmaniasis (kala-azar), a single dose of liposomal amphotericin B is as effective as a standard 15-infusion course of amphotericin B deoxycholate, according to findings from a study in India. India accounts for at least 50% of the world's cases.

With liposomal amphotericin B, patients can be discharged home 24 hours after the infusion. With amphotericin B deoxycholate, a 29-day hospital stay is required. Not surprisingly, the former approach is less expensive than the latter.

As reported in The New England Journal of Medicine for February 11, Dr. Shyam Sundar, from Banaras Hindu University, Varanasi, and colleagues assessed 6-month cure rates in 412 patients who were randomized in a 3:1 ratio to receive liposomal amphotericin B or amphotericin B deoxycholate.

Liposomal amphotericin B was given in a single infusion at a dose of 10 mg per kg of body weight. Amphotericin B deoxycholate was given every other day at a dose of 1 mg/kg, for a total of 15 infusions.

The 6-month cure rate in the liposomal therapy group was 95.7%, which is similar to the 96.3% rate in the conventional therapy group.

Infusion-associated fever or rigors occurred in 40% of patients who had liposomal therapy and in 64% of those given standard therapy. Two percent of liposomal therapy patients had increased anemia or thrombocytopenia; 19% of standard therapy patients had increased anemia and 2% had hypokalemia.

Neither treatment was associated with serious adverse effects, and no more than 1% of patients in each group had nephrotoxicity or hepatotoxicity.

A single-dose regimen of liposomal amphotericin B is effective and apparently non-inferior to treatment with amphotericin B deoxycholate, the authors concluded.

Moreover, the single 10-mg dose of liposomal amphotericin B per kg was not associated with any safety concerns in adults or children, and compliance was guaranteed.

Pregabalin may be of significant help to certain patients with fibromyalgia, according to an analysis of clinical trial reports.

Those people with fibromyalgia who do well with pregabalin usually do very well, but not everyone with fibromyalgia will benefit from it, said researchers.

Researchers studied data from 5 randomized trials involving 3808 patients. Data from 4 trials with standard designs were pooled in an intention-to-treat analysis.

Pregabalin doses ranged from 150 to 600 mg per day, and the standard trials lasted from 8 to 14 weeks. Compared to placebo, pregabalin significantly improved pain, sleep scores, and other symptoms.

There was a dose-response relationship only in patients who had at least 50% pain relief. That degree of relief was obtained by only 24% of the people taking pregabalin at the higher 450 and 600 mg doses. While applicable only to a minority, this is an important outcome for those people who achieve it, said researchers.

Overall, the rates of serious adverse events were low and roughly similar with pregabalin and placebo.

The fifth trial, which had a randomized withdrawal design, began with a 6-week open-label phase in which there was no substantial difference compared to the conventionally designed trials in the proportion of patients who benefited from pregabalin.

In that trial, responders in the open-label phase who continued to show response at 14 weeks were likely to do so for 26 weeks.

There are other analyses that could do more, particularly efficacy analysis at the level of the individual patient, said researchers.

Rifampicin plus vancomycin may be better than vancomycin alone for treating nosocomial methicillin-resistant Staphylococcus aureus (MRSA) pneumonia, reported researchers.

Their trial results suggested that patients with nosocomial MRSA pneumonia should receive vancomycin plus rifampicin if the liver function is acceptable (or) vancomycin alone if the patient is receiving other important medication that is subject to significant drug interaction with rifampicin. If the first line fails, the next option is linezolid, said researchers.

Researchers randomly assigned 93 patients to treatment with either vancomycin (1 g IV every 12 hours) plus oral rifampin (300 mg twice daily) or vancomycin alone.

Ten patients were later found not to have MRSA or were resistant to rifampicin, leaving 83 patients (including 41 in the combination therapy group) in the modified intent-to-treat population and 64 patients (30 in the combination group) in the per-protocol population.

In the modified intent-to-treat analysis, clinical cure rates on day 14 (the primary outcome) were 53.7% (22/41) in the rifampicin-vancomycin group and 31.0% (13/42) in the vancomycin-only group (p=0.047), the authors reported.

In the per-protocol population, clinical cure rates on day 14 were 63.3% (19/30) in the rifampicin-vancomycin group and 38.2% (13/34) in the vancomycin-only group (p=0.079).

Mortality rates on day 28 did not differ between the groups, the researchers note, but the mortality rate on day 60 was lower in the rifampicin-vancomycin group (26.8%) than in the vancomycin-only group (50.0%, p=0.042).

The microbiological eradication rates did not differ significantly between the treatment groups, although the rate was lower when rifampin resistance emerged during treatment.

There were 11 drug-related adverse events in the rifampicin-vancomycin group and 6 in the vancomycin-only group (p=ns). The most common adverse event in the rifampin group was an elevated serum bilirubin level, which developed in 13%.

The US Food and Drug Administration (FDA) has recently approved an expanded indication for olmesartan medoxomil for the treatment of hypertension in pediatric patients aged 6 to16 years. The angiotensin II receptor blocker previously was reserved for use in adults.

The prevalence of pediatric hypertension has been increasing since the late 1980s, in parallel with increases in children's weight. Treatment is important because the condition represents an independent risk factor for adult hypertension and is associated with early markers of cardiovascular disease.

The approval was based on data from a randomized, double-blind study of pediatric patients (n = 302; 112 black and 190 mixed racial heritage) with hypertension of predominantly essential origin. Patients who weighed from 20 to less than 35 kg were randomly assigned to receive 2.5 or 20 mg of olmesartan once daily; those who weighed 35 kg or more were randomly assigned to a daily dose of 5 or 40 mg. After 3 weeks, patients were reassigned to continued olmesartan therapy or placebo.

Results of the initial dose-response phase showed that olmesartan significantly reduced both systolic and diastolic blood pressure in a weight-adjusted dose-dependent manner. Overall, the 2 dose levels of olmesartan (low and high) significantly reduced systolic blood pressure by 6.6 and 11.9 mm Hg from the baseline, respectively. These reductions in systolic blood pressure included both drug and placebo effect.

During the randomized withdrawal to placebo phase, mean systolic and diastolic blood pressure at trough were significantly lower in patients continuing olmesartan therapy than in those withdrawn to placebo (Δ, 3.2 mm Hg and 2.8 mm Hg, respectively). As observed in adult populations, blood pressure reductions were smaller in black patients.

Pediatric use of olmesartan was well-tolerated; adverse events were similar to those reported in adult studies, with dizziness most commonly reported (incidence, 3%).

Pediatric dosing of olmesartan is based on body weight. The recommended starting and maintenance doses for patients weighing from 20 to less than 35 kg are 10 mg and 20 mg once daily, respectively; patients weighing 35 kg or greater should receive an adult starting dose of 20 mg once daily and be maintained at a daily dose of 20 to 40 mg. An extemporaneous suspension may be prepared for children unable to swallow tablets.