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Digoxin-furosemide reduces viral load, diameter of cutaneous warts4/11/2019
Topical ionic contraviral therapy decreased the size of cutaneous warts caused by human papillomavirus virus (HPV) by a mean of 3 mm, a significant improvement compared with placebo, in a proof-of-concept study, Dr. Melanie Rijsbergen and her associates reported in the British Journal of Dermatology.wisepoqder Furosemide powder

The mean HPV load also declined by 94% in warts treated with the treatment, a combination of digoxin and furosemide in a topical gel, Dr. Rijsbergen of the Center for Human Drug Research, Leiden, the Netherlands, and her coauthors wrote.

“It has been shown that DNA viruses, such as HPV, rely on potassium influx ... for replication. The cardiac glycoside digoxin and loop diuretic furosemide both inhibit potassium influx by interacting with the cell membrane ion cotransporters,” they said, noting that in 2006, an in vitro study found that “the inhibitory effect on DNA replication was most potent when digoxin and furosemide were combined.”

The placebo-controlled phase 2a trial randomized 80 patients with at least two plantar or common warts to one of four arms: digoxin 0.125% plus furosemide 0.125%; digoxin 0.125%; furosemide 0.125%; or placebo applied once a day for 42 consecutive days. A subset of 20 warts underwent histopathology and immunohistochemistry. In all, 139 warts were treated.
Patients were a mean of 26 years old and had developed warts a mean of 6 years before study onset. They had a mean of three warts each; about half were common and half were plantar.

In an analysis of all treated warts, each active treatment conferred a significant benefit, compared with placebo. The combination treatment was the most effective, with a mean diameter reduction of 3 mm. Warts exposed to digoxin alone or furosemide alone showed a mean reduction of about 2 mm.

At the study’s end, primary wart clearance rates were similar in all treatment groups – around 15%. None of the primary warts in the placebo group cleared. Common warts were more responsive to treatment than were plantar warts (24%-27% vs. 8%-15%). “The increased treatment resistance of plantar warts was previously described and seems to be mainly due to callus formation resulting in a decrease in cutaneous permeability of a drug,” the authors wrote.

The HPV viral load decreased by 94% in warts exposed to the combination therapy – a significant benefit, compared with placebo.There were no discontinuations because of adverse events, and no serious adverse events related to treatment. There was no topical irritation associated with the treatment.One author is an employee of Cutanea Life Sciences, which funded the study. Dr. Rijsbergen and the remaining authors declared no financial conflicts.

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Budesonide-formoterol reliever therapy outperforms maintenance plus 4/11/2019
Data from the PRACTICAL study showed that budesonide-formoterol reliever therapy in a single inhaler for patients with mild to moderate asthma was associated with a 31% reduction in the risk for severe exacerbations, as compared with maintenance budesonide plus terbutaline reliever therapy.wisepoqder Formoterol powder

“The budesonide-formoterol reliever regimen in mild to moderate asthma is based on the proven efficacy of the budesonide-formoterol maintenance and reliever regimen in moderate to severe asthma,” Richard Beasley, DSc, from the Medical Research Institute of New Zealand and the Capital and Coast District Health Board, wrote in an email to Healio Pulmonology. “This regimen has the potential to overcome the problem of underuse of inhaled steroids in asthma by using the reliever as its vehicle for administration.”
Investigators conducted the open-label, parallel-group, superiority trial at 15 primary care or hospital-based clinical trial units and primary care practices in New Zealand. They randomly assigned 890 adults aged 18 to 75 years with asthma to reliever therapy with one inhalation of budesonide 200 g–formoterol 6 g (Symbicort Turbuhaler, AstraZeneca) as needed or maintenance budesonide 200 g (Pulmicort Turbuhaler, AstraZeneca) twice daily plus two inhalations of terbutaline 250 g (Bricanyl Turbuhaler, AstraZeneca; not available in the U.S.) as needed.

All patients were using short-acting beta-agonists for symptom relief with or without maintenance low to moderate doses of inhaled corticosteroids during the previous 12 weeks. The study included six visits over 52 weeks and the primary outcome was the number of severe exacerbations per patient per year.

Fewer exacerbations

The final analysis included 885 patients. Results showed that the rate of severe asthma exacerbations was lower in the as-needed budesonide-formoterol group than in the maintenance budesonide plus as-needed terbutaline group (relative rate = 0.69; 95% CI, 0.48-1), as was the rate of combined moderate and severe asthma exacerbations (relative rate = 0.7; 95% CI, 0.51-0.95). Both time to first severe exacerbation and time to first moderate or severe exacerbation were longer with budesonide-formoterol vs. maintenance budesonide plus as-needed terbutaline, the researchers noted.

The most common adverse event in both treatment groups was nasopharyngitis, occurring in 35% of patients receiving as-needed budesonide-formoterol and 32% of those receiving maintenance budesonide plus as-needed terbutaline.

“This is the first independent study showing that budesonide-formoterol reliever therapy outperforms maintenance inhaled corticosteroid and [short-acting beta-agonist (SABA)] reliever therapy in mild to moderate asthma in reducing severe exacerbation risk,” Beasley said. “Taken together with the three earlier studies of budesonide-formoterol reliever therapy in mild asthma published in The New England Journal of Medicine, and the studies of the budesonide-formoterol maintenance and reliever regimen in moderate to severe asthma, there is now strong evidence that budesonide-formoterol outperforms SABA therapy across the spectrum of asthma severity.”

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