A Direct Aspiration, First Pass Technique (ADAPT) versus Stent Retrievers for Acute Stroke Therapy: An Observational Comparative Study.

BACKGROUND AND PURPOSE: Mechanical thrombectomy with stent retrievers is now the standard therapy for selected patients with ischemic stroke. The technique of A Direct Aspiration, First Pass Technique for the Endovascular Treatment of Stroke (ADAPT) appears promising with a high rate of recanalization. We compared ADAPT versus stent retrievers (the Solitaire device) for efficacy and safety as a front-line endovascular procedure. MATERIALS AND METHODS: We analyzed 243 consecutive patients with large intracranial artery occlusions of the anterior circulation, treated within 6 hours with mechanical thrombectomy by either ADAPT or the Solitaire stent. Th primary outcome was complete recanalization (modified TICI ≥ 2b); secondary outcomes included complication rates and procedural and clinical outcomes. RESULTS: From November 2012 to June 2014, 119 patients were treated with stent retriever (Solitaire FR) and 124 by using the ADAPT with Penumbra reperfusion catheters. The median baseline NIHSS score was the same for both groups (Solitaire, 17 [interquartile range, 11-21] versus ADAPT, 17 [interquartile range, 12-21]). Time from groin puncture to recanalization (Solitaire, 50 minutes [range, 25-80 minutes] versus ADAPT, 45 minutes [range, 27-70 minutes], P = .42) did not differ significantly. However, compared with the Solitaire group, patients treated with ADAPT achieved higher final recanalization rates (82.3% versus 68.9%; adjusted relative risk, 1.18; 95% CI, 1.02-1.37; P = .022), though differences in clinical outcomes between the cohorts were not significant. Use of an adjunctive device was more frequent in the ADAPT group (45.2% versus 13.5%, P < .0001). The rate of embolization in new territories or symptomatic hemorrhage did not differ significantly between the 2 groups. CONCLUSIONS: Front-line ADAPT achieved higher recanalization rates than the Solitaire device. Further randomized controlled trials are warranted to define the best strategy for mechanical thrombectomy.

Impact of thrombolysis in acute ischaemic stroke without occlusion: an observational comparative study.

BACKGROUND AND PURPOSE: The impact of intravenous recombinant tissue plasminogen activator (IV-rtPA) in patients with acute ischaemic stroke (AIS) but no arterial occlusion is currently a matter of debate. This study aimed to assess functional outcome of such patients with respect to IV-rtPA use. METHODS: A retrospective case-control analysis was performed comparing the outcome of AIS patients without arterial occlusion with or without IV-rtPA use. Patients were selected from prospective consecutive observational registries of five European university hospitals. The primary study outcome was excellent outcome at 3 months after stroke, as defined by a modified Rankin Scale (mRS) 0-1. RESULTS: A total of 488 patients without arterial occlusion documented by angiography were included in the present study; 300 received IV-rtPA and 188 did not. No between-group difference was found for excellent outcome before and after adjustment for baseline characteristics (adjusted odds ratio for no IV-rtPA use 0.79, 95% confidence interval 0.51-1.24, P = 0.31). Similar results were found for favourable outcome (defined as a 90-day mRS of 0-2) whereas a higher rate of early neurological improvement was found in IV-rtPA-treated patients (adjusted odds ratio 1.99; 95% confidence interval 1.29-3.07, P = 0.002). Sensitivity analyses yielded similar results. CONCLUSIONS: Our study suggests that AIS patients without visible arterial occlusion treated with IV-rtPA may have no better outcome at 3 months than those untreated. However, only a randomized controlled trial would provide a definitive answer about the impact of rtPA in acute stroke patients without occlusion. Until then, these patients should be treated by rtPA as recommended.

[Pupil-sparing painful oculomotor neuropathy due to a carotico-cavernous aneurysm]. / Ophtalmoplégie extrinsèque pure douloureuse du nerf moteur oculaire commun révélant un anévrysme de la carotide.

INTRODUCTION: In third cranial nerve palsy, the lack of mydriasis evokes a noncompressive mechanism. Case report. We report a case of a slightly painful, pure extrinsic third-nerve palsy, complete except for the partial ptosis secondary to the compression by an intracavernous carotid aneurysm. Percutaneous endovascular embolization was followed by complete regression of the palsy within 4 weeks. The pupil may have been spared by the mechanism of compression after the separation of the pupillomotor and extrinsic fibers or the ischemia of the third nerve by its arterial trunk lesion. CONCLUSION: This case report underlines that brain radiological explorations are necessary in some third-nerve pupil-sparing palsies.

Desloratadine 5 mg once daily improves the quality of life of patients with chronic idiopathic urticaria.

BACKGROUND: Chronic urticaria is known to debilitate a person's quality of life via sleep disruption, itching lesions, fatigue, social isolation, energy loss and emotional/sexual difficulties. Once-daily desloratadine significantly improved the signs and symptoms of CIU. OBJECTIVE: Assess the effect of desloratadine 5 mg once daily on the quality of life of patients suffering of chronic idiopathic urticaria (CIU). Study population One-hundred twenty-one consecutive patients with CIU present for at least 6 weeks prior to inclusion and with a current flare of at least 3 weeks, were included in the study in 24 Belgian centres. RESULTS: The mean dermatology life quality index (DLQI) significantly decreased from baseline to day 7 and further to day 42. Sixty per cent and 77% of patients had a clinically significant change (i.e. a decrease of at least 2 points) at day 7 or day 42, respectively, as compared with that of day 0. Change in pruritus and size of the hives significantly correlated with the change in the score of the quality of life. One-third of patients experienced complete relief whereas in 1 of 10 patients no effect was experienced. CONCLUSIONS: Desloratadine significantly improves the quality of life of patients with chronic idiopathic urticaria as reflected by the dermatology life quality index (DLQI).

A prospective multicenter study of the efficacy and tolerability of cryopreserved allogenic human keratinocytes to treat venous leg ulcers.

Allogeneic human keratinocyte cultures have been used to treat burn wounds, donor sites, and chronic skin ulcers with some success. Cryopreservation of these cultures allows for the production of large standardized batches that are readily available for use. The aim of the study presented in this report was to study effects of cryopreserved cultured allogenic human keratinocytes (CryoCeal) on chronic lower extremity wounds. Parameters were measured to study efficacy, tolerability, pain associated with chronic wounds, and quality of life of patients. Twenty-seven patients with hard-to-heal venous leg ulcers received a maximum of 9 applications of CryoCeal in a prospective, uncontrolled multicenter study lasting 48 weeks. Eleven out of 27 patients (41%; 95% CI: 22%-61%) had complete wound closure within 24 weeks (1 week). The time required for complete wound closure in these 11 patients ranged from 4.1 to 24.9 weeks. Only 1 patient had recurrence of the ulcer at 48 weeks. Local (wound) pain scores decreased from a mean of 2.5 at baseline to 0.9 at week 24. Fifty percent of the patients attained a pain score of 0 after 12 weeks and remained stable at this score until the end of the study. Overall, the patient quality of life was better at week 24, compared to baseline values. The treatment was well tolerated, and wound infection was the most frequently occurring adverse event.

Clobetasol propionate shampoo 0.05% and calcipotriol solution 0.005%: a randomized comparison of efficacy and safety in subjects with scalp psoriasis.

BACKGROUND: Scalp involvement in psoriatic patients represents a common issue. Treatment of the hairy skin requires adequate pharmaceutical formulations; hence, a new specific shampoo formulation of clobetasol propionate 0.05% was developed by Galderma R&D, Inc. METHODS: For this multicenter, randomized, investigator-masked, parallel group study, 151 subjects with moderate to severe scalp psoriasis were randomized to 4 weeks of treatment with clobetasol propionate shampoo or calcipotriol solution. RESULTS: Clobetasol propionate demonstrated significantly superior efficacy to calcipotriol solution (total severity score: mean difference 0.51, 95% CI 0.05-0.97, p = 0.028; global severity score: mean difference 0.43, 95% CI 0.08-0.78, p = 0.016). Adverse events were more common in the calcipotriol group than in the clobetasol propionate shampoo group. Telangiectasia and skin atrophy did not differ significantly between treatments; however, a burning sensation was significantly more common in the calcipotriol solution group. CONCLUSIONS: Short contact therapy of scalp psoriasis with this new shampoo formulation of clobetasol propionate was significantly more effective and better tolerated than calcipotriol solution for the treatment of scalp psoriasis.

A new calcipotriol/betamethasone dipropionate formulation (Daivobet) is an effective once-daily treatment for psoriasis vulgaris.

BACKGROUND: Topical corticosteroids and calcipotriol have been used separately for many years to treat psoriasis. A new combination ointment has been formulated, which contains both calcipotriol and the corticosteroid betamethasone dipropionate. OBJECTIVE: To compare the combination ointment with betamethasone dipropionate ointment, calcipotriol ointment and ointment vehicle in patients with psoriasis vulgaris. METHODS: 1,603 patients were randomised to one of the 4 double-blind treatments used once daily for 4 weeks. RESULTS: The mean percentage change in the PASI at the end of treatment was -71.3 (combination), -57.2 (betamethasone), -46.1 (calcipotriol) and -22.7 (vehicle). The mean difference of combination minus betamethasone was -14.2 (95% CI: -17.6 to -10.8, p < 0.001), of combination minus calcipotriol -25.3 (95% CI: -28.7 to -21.9, p < 0.001) and of combination minus vehicle -48.3 (95% CI: -53.2 to -43.4, p < 0.001). 6.0% of patients (combination) reported local adverse reactions compared to 4.9% (betamethasone), 11.4% (calcipotriol) and 13.6% (vehicle). CONCLUSION: Calcipotriol/betamethasone dipropionate combination ointment used once daily is well tolerated and more effective than either active constituent used alone.

A new calcipotriol/betamethasone formulation with rapid onset of action was superior to monotherapy with betamethasone dipropionate or calcipotriol in psoriasis vulgaris.

In this study, we compared a new combination ointment containing both calcipotriol and betamethasone dipropionate with betamethasone dipropionate ointment (Diprosone) and calcipotriol ointment (Daivonex) in patients with psoriasis vulgaris; 1106 patients were randomized to twice daily double-blind treatment with combination, betamethasone dipropionate or calcipotriol for 4 weeks. Patients then received twice daily calcipotriol, unblinded, for a further 4 weeks. Mean percentage change in PASI at end of the double-blind phase was -74.4 (combination group), -61.3 (betamethasone group) and -55.3 (calcipotriol group). Mean difference (95% Cl) combination-betamethasone was -13.1 (-16.9 to -9.3, p < 0.001) and for combination-calcipotriol -19.0 (-22.8 to -15.2, p <0.001). The differences in PASI were also statistically significant after 1 week. In the double-blind phase, 8.1% of patients (combination) reported lesional/ perilesional adverse reactions compared to 4.7% (betamethasone) and 12.0% (calcipotriol). In the combination group, mean PASI at the end of the double-blind phase was 2.5, and at end of the unblinded phase 3.6, compared with 3.9 and 4.1 (betamethasone) and 4.4 and 3.7 (calcipotriol). Calcipotriol/betamethasone combination is more effective and has a more rapid onset of action than either active constituent used alone, and is well tolerated. It is safe to transfer patients from combination to calcipotriol, with maintenance of clinical effect.

A multicentre, single-blind, randomized comparison of a fixed clindamycin phosphate/tretinoin gel formulation (Velac) applied once daily and a clindamycin lotion formulation (Dalacin T) applied twice daily in the topical treatment of acne vulgaris.

BACKGROUND: A successful phase III pilot study compared the efficacy and safety of a fixed clindamycin 1%/tretinoin 0.025% gel formulation (CTG; Velac gel) applied once daily and a clindamycin 1% lotion formulation (CLN; Dalacin T lotion) applied twice daily in the treatment of moderate to severe acne vulgaris. OBJECTIVES: We aimed to follow up this study. METHODS: The two treatment regimens were compared in a multicentre, single-blind, randomized 12-week investigation of patients with moderate to severe acne vulgaris. RESULTS: At week 12, the mean percentage reduction in non-inflamed lesions (open and closed comedones) was greater in the CTG group compared with the CLN group (P = 0.05). Absolute reductions in open and closed comedones were also greater in the CTG group, consistent with the comedolytic activity of tretinoin. There was a significantly greater absolute reduction in inflamed lesions (pustules, papules and nodules) from baseline to both end-point (last observed efficacy outcome; P = 0.043) and week 12 (P = 0.018) in the CTG group compared with the CLN group. Evaluation of the calculated overall acne severity score, considering all five lesion subtypes, demonstrated a significantly greater mean percentage reduction in the CTG group compared with the CLN group, both at end-point (P = 0.01) and at week 12 (P < 0.01). The more subjective assessment of overall acne severity according to the Cook scale also demonstrated a significantly greater mean reduction in the CTG group than the CLN group after 12 weeks of therapy (P = 0.007). CTG had a more rapid effect on the onset of improvement compared with CLN; a 50% reduction in total lesion counts by day 60 was found in 77% of patients on CTG compared with 56% receiving CLN (P = 0.003). This was largely due to the reduction in open comedone counts (P = 0. 0006). For all other variables, CTG was at least as effective as CLN. Both treatments were well tolerated. CONCLUSIONS: A single daily topical application of Velac gel was superior to Dalacin T lotion applied twice daily in reducing overall acne scores, and was faster acting. The simpler dosing regimen of Velac gel and its rapid effect are likely to have a positive effect on both patient compliance and cost.

Factors influencing pain outcome in herpes zoster: an observational study with valaciclovir. Valaciclovir International Zoster Assessment Group (VIZA).

AIM OF THE STUDY: An observational study with valaciclovir was conducted to assess clinical outcome in herpes zoster, especially pain and associated neurological signs and symptoms in relation to a series of demographic and disease characteristics discernible at presentation. The safety and acceptability of valaciclovir for treatment of zoster was assessed in a wide variety of primary care and clinic referral settings. METHODS: In total, 1897 immunocompetent adults with clinically diagnosed, localized acute herpes zoster were enrolled in this international, open-label study of valaciclovir. All subjects received treatment with oral valaciclovir (1000 mg three times daily) for 7 days from entry to the study and were asked to record the presence of zoster-associated pain and abnormal sensations throughout treatment and 6 months' follow-up. They were seen frequently in clinic to verify subjective assessments and for evaluation of rash healing. Safety and tolerability were assessed by adverse event monitoring. RESULTS: Overall, 1191 subjects (63%) were aged > or = 50 years, and 203 (11%) had ophthalmic zoster. Cessation of zoster-associated pain was significantly faster in the younger age group; median times to loss of zoster-associated pain were 23 days and 9 days in the > or = 50 and < 50 years age groups, respectively. Similarly, abnormal sensations resolved significantly more rapidly in the younger subjects; the median duration of abnormal sensations was 31 days in the > or = 50 year olds and 16 days in those aged < 50 years. In cases of ophthalmic zoster, the rate of pain resolution was not different from those with zoster in other dermatomes (median duration of pain 18 vs. 16 days). However, abnormal sensations persisted significantly longer in subjects with ophthalmic zoster than in those with zoster at other sites (47 vs. 22 days). In addition to advancing age, subjects suffering moderate to severe prodromal pain or acute pain during the rash phase were at significantly greater risk of zoster-associated pain and abnormal sensations persisting for longer. Subjects with concomitant neurological disorders were also more likely to develop prolonged abnormal sensations. Valaciclovir treatment was well tolerated, and adverse events were rare and generally mild. CONCLUSION: This study confirmed the prognostic importance of advancing age and the intensity of prodromal or acute pain as risk factors for prolonged zoster-associated pain and persisting abnormal sensations in the affected dermatome. Ophthalmic zoster and pre-existing neurological disorders are also identified as highly significant risk factors for prolonged abnormal sensations in herpes zoster.

Short-term itraconazole versus terbinafine in the treatment of tinea pedis or manus.

A total of 304 patients with a clinical diagnosis of palmar-type tinea pedis or manus and a positive mycologic examination were recruited into this double-blind, randomized, multicenter, phase III study. Patients were randomized to receive either oral itraconazole 200 mg twice daily (in the morning and evening) for 7 days, followed by placebo for 7 days (n = 153), or placebo in the morning and oral terbinafine 250 mg in the evening for 14 days (n = 151). At the first visit and 1, 2, and 6 weeks after the start of the study, signs and symptoms were assessed clinically, and scales were taken for mycologic assessments (microscopy and culture). At weeks 1, 2, and 6, the effectiveness of therapy was evaluated globally and given a rating of healed (absence of signs and symptoms), marked improvement (> or = 50% clinical improvement), considerable residual lesions (< 50% clinical improvement), no change, or worsened. The primary efficacy parameter was the mycologic cure rate at the follow-up end-point (week 6). The tolerability of the study medications was assessed at weeks 1 and 2. Adverse events were recorded at weeks 1, 2, and 6. Routine hematologic and biochemical tests were performed at the start of the study and after 1 week of treatment. No significant differences were seen in the baseline patient characteristics between the two groups. The rate of mycologic cure (negative microscopy and culture test result) was 79% in the itraconazole group and 80% in the terbinafine group at the follow-up end-point. The analysis of the 90% confidence interval for the difference between the treatment groups (-7.1, 5.4) and the outcome of the Blackwelder test (for two one-sided tests, P = 0.013 and P = 0.029) showed the two treatments to be equivalent. The results of the global evaluations of the efficacy in the two treatment groups are shown in Table 1. The rate of clinical response (healed or markedly improved) was 93% in the itraconazole group and 91% in the terbinafine group at the follow-up end-point. The analysis of the 90% confidence interval for the difference between the two groups (-2.5, 5.7) and the outcome of the Blackwelder test (for two one-sided tests, P = 0.004 and P < 0.001) showed the two treatments to be equivalent. The severity of the clinical signs and symptoms decreased from the baseline to the treatment end-point and from the treatment end-point to the follow-up end-point in both groups. At the double-blind treatment period end-point (week 2), the tolerability of the study medication was rated as very good or good in more than 97% of patients. During treatment, 21 of 153 patients (14%) in the itraconazole group and 28 of 151 patients (19%) in the terbinafine group reported adverse events. During follow-up, one patient in the itraconazole group and two in the terbinafine group reported adverse events. The most frequent events were headache, abdominal pain, nausea, vomiting, and hypertriglyceridemia. Two patients in the itraconazole group and four in the terbinafine group withdrew because of adverse events. Severe adverse events were reported by one patient in the itraconazole group and five in the terbinafine group. Serious adverse events were reported by two patients in the terbinafine group, although these were probably not drug related. No clinically relevant changes in laboratory variables were observed.

Itraconazole therapy is effective for pedal onychomycosis caused by some nondermatophyte molds and in mixed infection with dermatophytes and molds: a multicenter study with 36 patients.

BACKGROUND: Onychomycosis of the toenail caused by nondermatophyte molds alone or in combination with dermatophytes is difficult to eradicate with standard antifungal therapy. OBJECTIVE: Our purpose was to determine the effectiveness of itraconazole in the treatment of toenail onychomycosis caused by molds alone or in combination with dermatophytes. METHODS: We treated 36 patients with this drug given as continuous dosing (100 or 200 mg/ day) for 6 to 20 weeks or as a 1-week pulse dosing (200 mg twice daily for 1 week per month) for two to four pulses. RESULTS: Patients with toenail onychomycosis with the following organisms were treated: Aspergillus spp. (eight patients), Fusarium spp. (four patients), Scopulariopsis brevicaulis (23 patients), and Alternaria spp. (one patient). Nineteen patients had onychomycosis with a mixed origin. At follow-up, 12 months after therapy was initiated, clinical and mycologic cure was achieved in 15 of 17 patients (88%) with onychomycosis caused by a single mold. In patients with mixed infection, a clinical cure was obtained in 16 of 19 patients (84%) and a mycologic cure in 13 of 19 patients (68%). CONCLUSION: Itraconazole appears to be effective and safe for the treatment of toenail onychomycosis caused by some nondermatophyte molds alone or in combination with dermatophytes.

[Painful nodular and plantar erythema in children]. / Erythème nodulaire plantaire douloureux de l'enfant.

INTRODUCTION: According to our knowledge, only twenty-three similar cases have been reported in the literature. Possible hypotheses for localised painful red nodules on the feet in children include erythema nodosum, neutrophilic eccrine hidradenitis, traumatic plantar urticaria, vasculitis and cold panniculitis. CASE REPORT: We report a typical case of painful erythematous plantar nodules of the child. A 13-yr-old boy was first seen by a paediatrician for intermittent fever. The fever was associated with red, painful nodules on the soles. He was unable to walk. Routine blood chemistry parameters were within normal limits. Histopathologic examination of lesional skin revealed an image of septal and lobular panniculitis with vasculitis. Direct immunofluorescence study was not contributive. With proper antibiotic therapy, pain resolved within one week while fever and nodules cleared within two weeks. DISCUSSION: Briefly, this observation concerns a child disease occurring as painful erythematous plantar nodules. The lesions are spontaneously resolutive and the children are in good health. Our observation should constitute a supplementary group with the same classical symptoms of nodular plantar painful erythema of the child but moreover accompanied by a septal and lobular panniculitis with vasculitis at the histological examination. Further studies are necessary to verify these hypotheses.

Antifungal pulse therapy for onychomycosis. A pharmacokinetic and pharmacodynamic investigation of monthly cycles of 1-week pulse therapy with itraconazole.

BACKGROUND AND DESIGN: In the treatment of onychomycosis, oral therapies have generally been given as a continuous-dosing regimen. For example, the suggested dose of itraconazole for the treatment of onychomycosis has thus far been 200 mg/d for 3 months. Based on the advances in our understanding of the pharmacokinetics of itraconazole, we investigated the efficacy and nail kinetics of intermittent pulse-dosing therapy with oral itraconazole in patients who were suffering from onychomycosis. Fifty patients with confirmed onychomycosis of the toenails, predominantly Trichophyton rubrum, were recruited and randomly assigned to three (n = 25) or four (n = 25) pulses of 1-week itraconazole therapy (200 mg twice daily for each month). Clinical and mycological evaluation of the infected toenails, and determination of the drug levels in the distal nail ends of the fingernails and toenails, were performed at the end of each month up to month 6 and then every 2 months up to 1 year. RESULTS: In the three-pulse treatment group, the mean concentration of itraconazole in the distal ends of the toenails ranged from 67 (month 1) to 471 (month 6) ng/g, and in the distal ends of the fingernails, it ranged from 103 (month 1) to 424 (month 6) ng/g. At month 11, the drug was still present in the distal ends of the toenails at an average concentration of 186 ng/g. The highest individual concentrations of 1064 and 1166 ng/g were reached at month 6 for toenails and fingernails, respectively. At end-point follow-up, toenails in 84% of the patients were clinically cured with a negative potassium hydroxide preparation and culture in 72% and 80% of the patients, respectively. In the four-pulse treatment group, the mean concentration of itraconazole in the distal ends of the toenails ranged from 32 (month 1) to 623 (month 8) ng/g, and in the distal ends of the fingernails, it ranged from 42 (month 1) to 380 (month 6) ng/g. The highest individual concentrations of 1549 and 946 ng/g were reached at month 7 for toenails and at month 9 for fingernails, respectively. At month 12, the drug was still present in the distal ends of the toenails at an average concentration of 196 ng/g. At end-point follow-up, toenails in 76% of the patients were clinically cured with a negative potassium hydroxide preparation and culture in 72% and 80% of the patients, respectively. There were no significant intergroup differences between the three- and four-pulse treatment groups for the primary efficacy parameters. The drug was well tolerated with no significant side effects in either patient group. CONCLUSIONS: Following pulse therapy with itraconazole (400 mg/d given for 1 week each month for 3 to 4 months), the drug has been detected in the distal ends of nails after the first pulse, and it has reached therapeutic concentrations with further therapy. After stopping the last pulse, the drug remains in the nail plate at levels above 300 ng/g for several months. Clinical cure rates between 76% and 84% and negative mycological examination findings between 72% and 80%, respectively, were observed in toenail onychomycosis. The data suggest that pulse therapy with itraconazole is an effective and safe treatment option for onychomycosis.