An exploratory, prospective, open-label trial of ingenol mebutate gel 0.05% for the treatment of external anogenital warts.

BACKGROUND: Anogenital warts (AGW) can cause physical discomfort and decreased quality of life. Recent case reports suggest that ingenol mebutate gel might be an effective treatment of AGW. OBJECTIVE: To explore primarily the safety, and secondarily the efficacy of ingenol mebutate gel 0.05% in patients with AGW. METHODS: This was an exploratory, open-label, 1-arm trial of ingenol mebutate gel 0.05% administered up to three times to patients with AGW. Safety was assessed by occurrence and severity of local skin reactions (LSRs) and treatment-related adverse events (AEs). Efficacy was assessed by complete clearance and reduction in AGW count 14 days after last treatment, and recurrence 12 weeks after clearance. RESULTS: Of 41 patients enrolled, 40 received treatment and 26 completed the trial. Patients had a median AGW count of 11.0 and AGW duration of 3.0 years at baseline. All patients experienced transient LSRs following treatment with a maximum composite LSR score of 7.5 (on a scale from 0 to 18). A total of 93% of patients reported treatment-related AEs, most frequently pain (85%) and procedural complications (35%) due to smearing of the gel. 78% of patients took mild analgesics for the pain, typically for 1-2 days following treatment. The majority of AEs were of moderate-to-severe intensity. Seventeen of 39 patients (43.6%) had complete clearance 14 days after last treatment, and AGW count was reduced by 90.9%. There was a tendency towards lower clearance rate in patients with longer duration of AGW. Eight of 14 patients (57.1%) had AGW recurrence 12 weeks after clearance. CONCLUSION: Ingenol mebutate gel was associated with a high number of AEs and withdrawals due to painful local and adjacent skin reactions. Furthermore, it showed promising efficacy in reducing AGW despite a difficult-to-treat population. Optimization of the formulation is warranted to improve the safety profile of the treatment.

Poor validity of the routine diagnosis of necrotising enterocolitis in preterm infants at discharge.

AIM: Necrotising enterocolitis contributes considerably to the mortality of preterm infants, but most questions remain unsolved after decades of extensive research. This Danish study investigated the validity of necrotising enterocolitis diagnoses at discharge according to Bell's staging system. METHODS: We conducted a retrospective single-centre cohort study of 714 preterm infants with a gestational age of less than 30 weeks born in 2006-2013. The infants were diagnosed with necrotising enterocolitis according to Bell's stages 2-3 at discharge and in retrospect by an expert panel, which served as our gold standard. RESULTS: The sensitivity of necrotising enterocolitis diagnosed at discharge was 0.72-0.75 depending on whether spontaneous intestinal perforation was included as necrotising enterocolitis or not. The positive predictive value of the diagnosis was 0.49-0.61. The incidence was significantly higher when diagnosed at discharge than when diagnosed by the expert panel (11.1 versus 9.0%, p = 0.03). The mortality rate for infants who were underdiagnosed at discharge was 50.0%, and it was 25.8% for infants who were overdiagnosed (p = 0.10). CONCLUSION: We found poor validity for the discharge diagnosis of necrotising enterocolitis. In future, a better way of defining the disease is needed for large-scale epidemiologic research.

Bronchiolitis obliterans after allo-SCT: clinical criteria and treatment options.

Bronchiolitis obliterans (BO) following allogeneic haematopoietic SCT (HSCT) is a serious complication affecting 1.7-26% of the patients, with a reported mortality rate of 21-100%. It is considered a manifestation of chronic graft-versus-host disease, but our knowledge of aetiology and pathogenesis is still limited. Diagnostic criteria are being developed, and will allow more uniform and comparable research activities between centres. At present, no randomised controlled trials have been completed that could demonstrate an effective treatment. Steroids in combination with other immunosuppressive drugs still constitute the backbone of the treatment strategy, and results from our and other centres suggest that monthly infusions of high-dose pulse i.v. methylprednisolone (HDPM) might stabilise the disease and hinder progression. This article provides an overview of the current evidence regarding treatment options for BO and presents the treatment results with HDPM in a paediatric national HSCT-cohort.

Cure of peptic gastric ulcer associated with eradication of Helicobacter pylori. Finnish Gastric Ulcer Study Group.

The effect of Helicobacter pylori eradication on ulcer healing and the relapse rate were investigated in a multicentre trial of 239 gastric ulcer patients. Patients with H pylori positive gastric ulcer were randomly assigned to one of three groups: (A) 10 days' treatment with metronidazole and eight weeks' treatment with colloidal bismuth subcitrate (CBS) (84 patients); (B) 10 days' treatment with metronidazole placebo and eight weeks with CBS (73 patients); or (C) ranitidine (82 patients). At 12 weeks in 210 patients, gastric ulcer was present in three (9%) of 35 H pylori negative patients, and in 45 (26%) of 175 H pylori positive patients (p < 0.05). Results after one year of follow up were available for 205 patients. Between 12 and 52 weeks, two (7%) ulcer relapses occurred in 29 H pylori negative patients and in 60 (47%) of 128 H pylori positive patients (p < 0.001). After two weeks of open triple therapy (CBS 120 mg four times daily, amoxicillin 500 mg four times daily, and metronidazole 400 mg three times daily), given to the patients with ulcer relapse, only one (an NSAID user) of 55 successfully treated patients had an ulcer relapse during the one year follow up. Healing of gastric ulcer is rapid and recurrence is infrequent after successful H pylori eradication. H pylori eradication changes the natural history of the gastric ulcer disease.