Massimo Milani

Sublingual immunotherapy efficacy in patients with atopic dermatitis and house dust mites sensitivity: a prospective pilot study.

ABSTRACT Background: Specific subcutaneous immunotherapy (SCIT) with house dust mite (HDM) preparation has recently been shown to improve eczema in patients with atopic dermatitis (AD). So far, there is less data regarding efficacy and safety of specific sublingual immunotherapy (SLIT) in patients with AD. Study aim: To evaluate in an open non-controlled, non-randomized pilot trial the effect of SLIT with HDM allergen extracts preparation (SLITone, ALK Abellò Italy) on SCORAD in adult patients with mild–moderate AD. Patients and methods: 86 Subjects (53 females and 33 males) between 3 and 60 years of age with AD and IgE-proved (Class > 2) HDM sensitization were enrolled after their informed consent in the trial. Exclusion criteria were severe asthma and treatment with systemic or high potent topical corticosteroids or immunosuppressant agents. Patients were treated with SLIT (Dermatophagoides pteronyssinus and Dermatophagoides farinae extracts: SLITone, ALK-Abellò) for at least 12 months. SCORAD was evaluated at baseline and after 12 months of treatment. Results: Baseline SCORAD value, mean ± SD, was 43.3 ± 13.7 (range 15–84). After 1 year of SLIT, mean ± SD, SCORAD value was reduced to 23.7 ± 13.3 (range: 0–65) (p = 0.0001; unpaired t-test vs. baseline). This was a 46% reduction in SCORAD in comparison with baseline value. A significant improvement, defined as a SCORAD reduction of > 30%, was observed in 51 out of 86 patients (59%). In 5 patients (5.8%) SCORAD values did not change at the end of the observation period. In 30 patients (35%) the SCORAD reduction after SIT was ≤ 30% in comparison with baseline. Total and specific IgE serum levels were significantly (p = 0.001) reduced after SLIT. No severe adverse events were observed during the trial. Conclusion: In this open non-controlled trial SLIT with HDM extracts in patients with mild to moderate AD was effective in reducing the SCORAD after 1 year of SLIT treatment. In addition the treatment was very well tolerated. Treatment with SLIT, furthermore, has allowed a gradual and relevant reduction of concomitant therapies with topical corticosteroids or immunosuppressants. Present results require further controlled trials in order to confirm the potential clinical benefit of SLIT in this clinical setting.

Efficacy and safety of a new clobetasol propionate 0.05% foam in alopecia areata: a randomized, double‐blind placebo‐controlled trial

Background  Clinical efficacy of topical corticosteroids in alopecia areata (AA) is still controversial. Positive clinical results have been obtained using ointments with occlusive dressing but this approach has a low patient compliance. Recently, a new topical formulation (thermophobic foam: Versafoam®) of clobetasol propionate 0.05% has been introduced on the market (Olux®, Mipharm, Milan, Italy) (CF). This formulation is easy to apply. After application to the skin the foam quickly evaporates without residues and it has a good patient compliance. In vitro studies have also shown that this formulation enhances the delivery of the active compound through the skin.

Efficacy of betamethasone valerate mousse in comparison with standard therapies on scalp psoriasis: an open, multicentre, randomized, controlled, cross-over study on 241 patients

Background  The scalp is a common area for plaque psoriasis. Corticosteroid‐based lotions are the most widely used therapy in this clinical setting. A new formulation of betamethasone valerate 0·12% in a thermophobic, low‐residue foam vehicle (Bettamousse™, Mipharm, Italy; BVM) is available for the treatment of scalp dermatoses.

Thromboxane antagonism and cough induced by angiotensin- converting-enzyme inhibitor

BACKGROUND The increased prostaglandin synthesis that might follow stimulation of the arachidonic acid cascade by angiotensin-converting-enzyme inhibition (ACE-I) has been suggested to underlie the appearance of cough on ACE-I treatment. We investigated whether the prostanoid thromboxane was involved. METHODS Nine patients with essential hypertension who had cough after enalapril 20 mg once a day (coughers) were treated, while continuing the enalapril, in a double-blind crossover study with placebo or picotamide, 600 mg twice daily. Picotamide is a platelet antiaggregant that acts through both inhibition of thromboxane synthase and thromboxane-receptor antagonism. Thirteen hypertensive patients with no history of ACE-I-induced cough were also treated with enalapril and served as controls. Cough frequency was measured by a visual analogue scale and by a daily cough diary. 24 h urinary recovery of 11-dehydro-thromboxane-B2 and 6-keto-PGF1 alpha were measured to assess any changes in endoperoxide metabolism during the study periods. FINDINGS 11-dehydro-thromboxane-B2 (TXB2) recovery was significantly reduced by picotamide, which led to the disappearance of cough in eight patients within 72 h. Picotamide urinary recovery data suggested incomplete absorption in the non-responder. At baseline and after rechallenge with enalapril, 11-dehydro-TXB2 excretion was in the same range in the controls and in the coughers, but the latter showed significantly lower excretion of 6-keto-PGF1 alpha, and their ratio of 11-dehydroTXB2 to 6-keto-PGF1 alpha was twice that of the controls (1.40 [95% CI 0.86-1.95] vs 0.61 [0.37-0.84]). INTERPRETATION A thromboxane antagonist is effective in ACE-I-induced cough. An imbalance between thromboxane and prostacyclin may represent a marker of patients susceptible to ACE-I-induced cough.

Effect of Fluvastatin on Lipids and Fibrinolysis in Coronary Artery Disease

This randomized, double-blind, placebo-controlled study shows that 20-week fluvastatin treatment induces beneficial changes in the lipid panel and a shift in the fibrinolytic pathway toward activation through a decrease in tissue plasminogen activator antigen. Fluvastatin treatment causes no variation in lipoprotein(a) circulating levels.

Efficacy of betamethasone valerate foam formulation in comparison with betamethasone dipropionate lotion in the treatment of mild-to-moderate alopecia areata : a multicenter, prospective, randomized, controlled, investigator-blinded trial

Background Betamethasone valerate foam (BVF) is a new topical corticosteroid formulation. In scalp psoriasis patients BVF has induced a significantly greater clinical improvement in comparison with corticosteroid lotions. No data are available to date regarding the efficacy and safety of BVF in mild‐to‐moderate alopecia areata (AA).

Evaluation of the efficacy and tolerability of oral terbinafine (Daskil®) in patients with seborrhoeic dermatitis. A multicentre, randomized, investigator-blinded, placebo-controlled trial

Background Previous uncontrolled trials have suggested that oral terbinafine, an antimycotic allylamine compound, could be useful in the treatment of seborrhoeic dermatitis.

Efficacy of the combination of 2 g oral tinidazole and acidic buffering vaginal gel in comparison with vaginal clindamycin alone in bacterial vaginosis: a randomized, investigator-blinded, controlled trial

OBJECTIVE To evaluate the efficacy of tinidazole (T) (Trimonase, Mipharm, Italy) and an acidic vaginal gel (Miphil) (M) in comparison with vaginal clindamycin (CL) (Cleocin Pharmacia Upjohn) in BV. DESIGN A multicentre, randomised, investigator-blinded, controlled trial. POPULATION AND METHODS 64 women with BV were enrolled. Thirty-two were allocated to receive oral T 2g, single dose, and 32 were assigned to CL 2% for 7 consecutive days. After week 1, T group were treated with an acidic vaginal gel, 2g every 3 days, for additional 3 weeks, whereas CL group did not received any additional treatment. Patients were evaluated at week 1 and 4. Vaginal pH, the BV-blue test (Gryphus Diagnostics, USA) and the whiff test were performed at baseline and at week 4. MAIN OUTCOMES MEASURES Clinical cure rate; normalisation of vaginal pH (pH<4.5); and laboratory cure rate (defined as a clinical cure rate and a negative results of BV-blue and whiff test). RESULTS At baseline, vaginal pH values were (mean+/-S.D.) 5.4+/-0.7 and 5.3+/-0.5 in T and CL groups, respectively. Six patients (2 in T group and 4 in CL group) withdrew from the study due to side effects. At week 1, the clinical cure rates were 84% in both T and CL treated group (P=N.S.). At week 4, clinical cure rates were 94% in T+M group and 77% in CL group (P=N.S.). The laboratory cure rates were 81% in T+M group and 59% in CL group (P<0.04). Vaginal pH normalisation (i.e. pH <4.5) was achieved in 78% and in 38% of T+M and CL groups, respectively (P<0.0007). CONCLUSIONS In the short term, 2g single oral dose tinidazole was at least as effective as 7-day of vaginal clindamycin. The sequential treatment of tinidazole and acidic vaginal gel was superior to vaginal clindamycin in lowering vaginal pH and achieving a higher laboratory tests normalization rate at 1-month follow-up.

D-dimer before chemotherapy might predict venous thromboembolism.

To see whether D-Dimer levels can identifying patients at high risk of venous thrombotic events and establish the best benefit/risk-of-bleeding ratio. Current guidelines do not recommend routine prophylaxis against venous thromboembolism (VTE) in cancer patients receiving chemotherapy, but the risk increases about 6.5-fold because of this treatment. D-dimer was measured at baseline in 124 cancer patients scheduled for their first chemotherapy. VTE events, including symptomatic episodes of deep vein thrombosis or pulmonary embolism or both, were recorded during the first 6 months of therapy, and asymptomatic deep vein thrombosis was revealed by compression ultrasonography at baseline and after 90 and 180 days. During follow-up, there were 11 episodes of VTE (8.9%). Mean D-dimer values were higher in patients with VTE (2195 ± 1382 vs. 695 ± 1039 ng/ml, (P < 0.001). On grouping D-dimer values in tertiles, only 2.4% (confidence interval, 0.9–5.7%) in the first (<262 ng/ml) and second tertiles (262–650 ng/ml) suffered a deep vein thrombosis/pulmonary embolism event as compared with 22% (confidence interval, 9–34%) in the third (>650 ng/dl) (P = 0.003). The VTE-free interval was significantly shorter in the third tertile than in the first (P = 0.0218, log–rank test; relative risk for third vs. first tertile, 11.0; 95% confidence interval, 1.4–81.3; P = 0.0033). Multivariate analysis found that only baseline D-dimer concentrations were correlated with the subsequent development of VTE. Baseline D-dimer values in cancer patients scheduled for chemotherapy might be used to select those at low risk of VTE, most likely to be safe without prophylaxis.

C-reactive protein in hypertensive disorders in pregnancy

Hypertension is the most frequent medical complication of pregnancy. A recent report demonstrates the flogistic pathogenesis of pregnancy-induced hypertension. Because C-reactive protein (CRP) is a marker of inflammation, it can be used in the differential diagnosis of hypertensive disorders of pregnancy. A total of 322 pregnant women at 24 to 32 weeks’ gestation were enrolled. The control group (A) comprised 190 women. Sixty-three women had preeclampsia (PE, group B), 31 women presented transient hypertension (TH, group C), 19 had HELLP syndrome (HS, group D) and 19 had chronic hypertension (CH, group E). CRP serum concentrations were significantly higher in groups B, C, and D in comparison with the group A. In the whole population, systolic and diastolic pressure value inversely correlate with weight at delivery and weeks of gestation at delivery. CPR levels in patients with PE and HS inversely correlate with birth weight and gestational week at delivery. Normal plasma levels of CRP may be an important marker of differential diagnosis between TH and CH. In TH, PE, and HS, CRP levels were higher than in the control and CH groups, suggesting that inflammation may be the common pathogenetic cause of TH and PE. Finally CRP levels in preeclampsia are believed to correlate with preeclamptic process severity.