Safety and Efficacy of Escalating Doses of Ingenol Mebutate for Field Treatment of Actinic Keratosis on the Full Face, Full Balding Scalp, or Chest.

Background: Actinic keratosis (AK) can affect large skin areas. Ingenol mebutate (IngMeb) gel (0.015% and 0.05%) is approved for topical treatment of AK in a single contiguous area of ~25 cm2.

Objective: The study sought to determine the maximum tolerated dose (MTD), efficacy, and tolerability of IngMeb applied to AK on a contiguous area less than equal to 250 cm2.

Methods: Part 1 determined the MTD of IngMeb at 7 concentrations for 2 or 3 days. Part 2 assessed efficacy and tolerability at the MTD and one dose lower for 2 or 3 days vs vehicle.

Results: Four dosing regimens with an acceptable benefit-to-risk ratio were identified: 0.018% and 0.027% once daily for 2 or 3 days. Complete clearance at 8 weeks was achieved by 21.3% to 39.1% of IngMeb-treated patients vs 0% to 3.2% treated with vehicle. Composite local skin response scores peaked on the day after the last application, rapidly declined, and were near baseline at 2 weeks. Adverse events were predominantly mild or moderate.

Limitations: The study evaluated a limited number of doses in a population of only white patients.

Conclusion: IngMeb gel was effective and well tolerated as field treatment of AK on the full face, full scalp, and up to 250 cm2 on the chest.

J Drugs Dermatol. 2017;16(5):438-444.

Ingenol mebutate gel for actinic keratosis.

BACKGROUND: Actinic keratosis is a common precursor to sun-related squamous-cell carcinoma. Treating actinic keratoses and the surrounding skin area (i.e., field therapy) can eradicate clinical and subclinical actinic keratoses. Topical field therapy currently requires weeks or months of treatment. We investigated the efficacy and safety of a new topical field therapy for actinic keratosis, ingenol mebutate gel (0.015% for face and scalp and 0.05% for trunk and extremities). METHODS: In four multicenter, randomized, double-blind studies, we randomly assigned patients with actinic keratoses on the face or scalp or on the trunk or extremities to receive ingenol mebutate or placebo (vehicle), self-applied to a 25-cm(2) contiguous field once daily for 3 consecutive days for lesions on the face or scalp or for 2 consecutive days for the trunk or extremities. Complete clearance (primary outcome) was assessed at 57 days, and local reactions were quantitatively measured. RESULTS: In a pooled analysis of the two trials involving the face and scalp, the rate of complete clearance was higher with ingenol mebutate than with placebo (42.2% vs. 3.7%, P<0.001). Local reactions peaked at day 4, with a mean maximum composite score of 9.1 on the local-skin-response scale (which ranges from 0 to 4 for six types of reaction, yielding a composite score of 0 to 24, with higher numbers indicating more severe reactions), rapidly decreased by day 8, and continued to decrease, approaching baseline scores by day 29. In a pooled analysis of the two trials involving the trunk and extremities, the rate of complete clearance was also higher with ingenol mebutate than with placebo (34.1% vs. 4.7%, P<0.001). Local skin reactions peaked between days 3 and 8 and declined rapidly, approaching baseline by day 29, with a mean maximum score of 6.8. Adverse events were generally mild to moderate in intensity and resolved without sequelae. CONCLUSIONS: Ingenol mebutate gel applied topically for 2 to 3 days is effective for field treatment of actinic keratoses. (Funded by LEO Pharma; ClinicalTrials.gov numbers, NCT00742391, NCT00916006, NCT00915551, and NCT00942604.).

Imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: two phase 3, multicenter, randomized, double-blind, placebo-controlled studies.

BACKGROUND: Imiquimod 3.75% and 2.5% creams were studied for the treatment of actinic keratosis (AK) of the full face or balding scalp, to determine comparable efficacy and tolerability to imiquimod 5% cream. METHODS: In two identical multicenter, randomized, double-blind, placebo controlled studies. Adult subjects with 5 to 20 visible lesions, or palpable AKs in an area that exceeded 25 cm² on either the face or balding scalp were randomized to imiquimod 3.75%, 2.5% or vehicle cream (1:1:1) applied once daily for two 2-week treatment cycles, with a 2-week, no-treatment interval between cycles. Efficacy was assessed 8 weeks posttreatment (End of Study Visit [EOS]). Primary efficacy was rate of complete clearance of AK lesions. Secondary efficacy endpoints were rate of partial clearance at EOS (≥ 75% reduction in number of AK lesions compared to baseline) and median percent decrease from baseline lesion count. Safety assessments included visual assessment of local skin reactions (LSRs), number and duration of study treatment rest periods required due to intolerant LSRs, adverse events (AEs) and clinical laboratory tests. RESULTS: Overall 479 patients were randomized to imiquimod 3.75%, 2.5%, or vehicle. Complete clearance rates were 35.6%, 30.6%, and 6.3% respectively (both P<.001 versus vehicle). The difference in complete clearance rates (imiquimod minus vehicle) was 29.3% and 24.3%, respectively. Partial clearance rates were 59.4%, 48.1%, and 22.6% respectively (both P<.001 versus vehicle). Median % reductions in AK lesions were 81.8%, 71.8%, and 25.0% respectively (P<.001 versus vehicle). All primary and secondary efficacy endpoints were greater in Study 1. Photodamage in the treatment area was 'much improved' with imiquimod 3.75%. Both active creams were well tolerated with few treatment-related discontinuations. CONCLUSIONS: In two well-controlled Phase 3 studies, both imiquimod 3.75% and 2.5% creams were more effective than vehicle and well tolerated when administered daily as a 2-week on/off/on regimen to treat AK. Reduction in AK lesions was comparable to that reported with imiquimod 5% with fewer local AEs.

Efficacy and safety of ingenol mebutate 0.015% gel after cryosurgery of actinic keratosis: 12-month results.

INTRODUCTION: Recurrence rates of actinic keratosis (AK) lesions after cryosurgery are high, and this treatment does not address field cancerization. We investigated the efficacy and safety of field treatment of AKs with ingenol mebutate gel following cryosurgery. METHODS: In this phase 3, randomized, double-blind, vehicle-controlled study (NCT01541553), patients ≥18 years with four to eight clinically typical, visible, discrete AKs within a contiguous 25-cm2 treatment area on the face or scalp underwent cryosurgery followed 3 weeks later by once-daily ingenol mebutate 0.015% or vehicle gel for 3 consecutive days. Endpoints included complete clearance at week 11 and safety and efficacy over 12 months. RESULTS: In 329 randomized patients, complete clearance rates were greater with ingenol mebutate than vehicle (week 11: 60.5% vs 49.4%; P=.04; month 12: 30.5% vs 18.5%; P=.01). Fewer patients experienced the emergence of new lesions with ingenol mebutate than with vehicle (38.9% vs 51.9%; P =.02). At month 12, mean percentage reduction of AKs was higher with ingenol mebutate than with vehicle (68.2% vs 54.1%; P =.002). The probability of remaining free of lesions was sustained longer with ingenol mebutate compared with vehicle gel: 78% vs 68% at 6 months; 64% vs 57% at 9 months; 55% vs 40% at month 12, respectively. Ingenol mebutate 0.015% gel was well tolerated and no unexpected adverse events occurred; all adverse events resolved within 2 weeks of starting treatment. CONCLUSIONS: Field treatment with ingenol mebutate 0.015% gel following cryosurgery significantly enhanced clearance of baseline lesions, and was well tolerated. Furthermore, ingenol mebutate 0.015% gel following cryosurgery reduced development of new lesions in the treated field.

Efficacy and safety of ingenol mebutate 0.015% gel 3 weeks after cryosurgery of actinic keratosis: 11-week results.

INTRODUCTION: Cryosurgery is the most common treatment for actinic keratosis (AK) in the United States. Efficacy with cryosurgery is variable, and is a modality for treating individual, visible lesions while failing to treat subclinical lesions. METHODS: FIELD Study 1 (NCT01541553) is a phase 3, multicenter, randomized, double-blind study that evaluated the short- (11-week) and long- (12-month) term efficacy and safety of sequential AK treatment using cryosurgery with liquid nitrogen followed by ingenol mebutate gel, versus cryosurgery followed by vehicle. RESULTS: Overall, 329 patients were randomized to ingenol mebutate 0.015% gel (n=167) or vehicle (n=162) 3 weeks after cryosurgery. Baseline characteristics were balanced across groups. At week 11, complete clearance rate (100%) in the treatment area was higher for ingenol mebutate gel compared with vehicle (60.5% vs 49.4%, respectively; P=.04). Mean percentage reduction in number of AKs versus baseline was also numerically higher for ingenol mebutate gel (82.7% vs 75.6%). A general reduction from baseline lesion count was observed 3 weeks after cryosurgery. Treatment after cryosurgery was well tolerated. CONCLUSIONS: Short-term (11-week) AK clearance rates on the face or scalp with ingenol mebutate gel after cryosurgery were higher than with cryosurgery alone.

British societies guideline on the management of emergencies in implantable left ventricular assist device recipients in transplant centres.

An implantable left ventricular assist device (LVAD) is indicated as a bridge to transplantation or recovery in the United Kingdom (UK). The mechanism of action of the LVAD results in a unique state of haemodynamic stability with diminished arterial pulsatility. The clinical assessment of an LVAD recipient can be challenging because non-invasive blood pressure, pulse and oxygen saturation measurements may be hard to obtain. As a result of this unusual situation and complex interplay between the device and the native circulation, resuscitation of LVAD recipients requires bespoke guidelines. Through collaboration with key UK stakeholders, we assessed the current evidence base and developed guidelines for the recognition of clinical deterioration, inadequate circulation and time-critical interventions. Such guidelines, intended for use in transplant centres, are designed to be deployed by those providing immediate care of LVAD patients under conditions of precipitous clinical deterioration. In summary, the Joint British Societies and Transplant Centres LVAD Working Group present the UK guideline on management of emergencies in implantable LVAD recipients for use in advanced heart failure centres. These recommendations have been made with a UK resuscitation focus but are widely applicable to professionals regularly managing patients with implantable LVADs.

Clinical findings using ingenol mebutate gel to treat actinic keratoses.

Actinic keratosis (AK) is a common ultraviolet light-induced skin lesion found on sun-exposed skin areas generally in older, fair-skinned people. It is part of a disease continuum observed in photodamaged skin that may lead to invasive squamous cell carcinoma. The presence of AK is associated with an increased risk of all skin cancers, as it is visible evidence of the carcinogenic effects of cumulative ultraviolet exposure. AKs are treated with lesion- and field-directed methods. Field-directed methods treat both the visible and subclinical lesions present in photodamaged skin, but treatment regimens are often lengthy and associated with poor tolerability because of vigorous local inflammatory reactions. Ingenol mebutate gel was recently approved by the Food and Drug Administration for topical treatment of AK. It induces cell death preferentially in transformed keratinocytes and promotes an inflammatory response that kills remaining tumor cells. In human studies, ingenol mebutate achieved high clearance rates of AK on the trunk or extremities and face or scalp after once-daily application for 2 or 3 consecutive daily treatments, when measured by complete or partial clearance of lesions. The localized inflammatory skin responses were generally mild to moderate and resolved in approximately 2 weeks on the face or scalp and 4 weeks on the trunk or extremities.

Imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: two phase 3 multicenter, randomized, double-blind, placebo-controlled studies.

BACKGROUND: Imiquimod 3.75% and 2.5% creams were studied for the treatment of actinic keratosis (AK) of the full face or balding scalp, to determine comparable efficacy and tolerability to imiquimod 5% cream. METHODS: In two identical multicenter, randomized, double-blind, placebo controlled studies. Adult subjects with 5 to 20 visible lesions, or palpable AKs in an area that exceeded 25 cm² on either the face or balding scalp were randomized to imiquimod 3.75%, 2.5% or vehicle cream (1:1:1) applied once daily for two 2-week treatment cycles, with a 2-week, no-treatment interval between cycles. Efficacy was assessed 8 weeks posttreatment (End of Study Visit [EOS]). Primary efficacy was rate of complete clearance of AK lesions. Secondary efficacy endpoints were rate of partial clearance at EOS (≥ 75% reduction in number of AK lesions compared to baseline) and median percent decrease from baseline lesion count. Safety assessments included visual assessment of local skin reactions (LSRs), number and duration of study treatment rest periods required due to intolerant LSRs, adverse events (AEs) and clinical laboratory tests. RESULTS: Overall 479 patients were randomized to imiquimod 3.75%, 2.5%, or vehicle. Complete clearance rates were 35.6%, 30.6%, and 6.3% respectively (both P<.001 versus vehicle). The difference in complete clearance rates (imiquimod minus vehicle) was 29.3% and 24.3%, respectively. Partial clearance rates were 59.4%, 48.1%, and 22.6% respectively (both P<.001 versus vehicle). Median % reductions in AK lesions were 81.8%, 71.8%, and 25.0% respectively (-<.001 versus vehicle). All primary and secondary efficacy endpoints were greater in Study 1. Photodamage in the treatment area was 'much improved' with imiquimod 3.75%. Both active creams were well tolerated with few treatment-related discontinuations. CONCLUSIONS: In two well-controlled Phase 3 studies, both imiquimod 3.75% and 2.5% creams were more effective than vehicle and well tolerated when administered daily as a 2-week on/off/on regimen to treat AK. Reduction in AK lesions was comparable to that reported with imiquimod 5% with fewer local AEs.

Complete clearance is sustained for at least 12 months after treatment of actinic keratoses of the face or balding scalp via daily dosing with imiquimod 3.75% or 2.5% cream.

OBJECTIVE: Assess long-term, sustained, complete clearance of actinic keratoses after treatment with imiquimod 3.75% or 2.5% cream using two two-week or three-week cycles of daily dosing. METHODS: Adults with five to 20 baseline actinic keratoses who achieved complete clearance at the eight-week post-treatment visit in four phase 3 placebo-controlled treatment studies were followed for an additional 12 months. RESULTS: For imiquimod 3.75% and 2.5% cream, respectively, complete clearance was sustained for 12 months in 17/42 (40.5%) and 13/39 (33.3%) subjects from the two-week cycle studies, and in 23/48 (47.9%) and 16/37 (43.2%) subjects from the three-week cycle studies. There were no safety concerns during the follow-up. CONCLUSION: In subjects with a median of eight to nine baseline actinic keratoses who achieved complete clearance after treatment of the full face or balding scalp with topical imiquimod 3.75% cream, complete clearance of all lesions (baseline, recurrent or new) was sustained in ≥ 40 percent of subjects for at least 14 months after the last dose. Clinicaltrials.gov identifier NCT00668733.

Evidence-Based Consensus Recommendations for the Evolving Treatment of Patients with High-Risk and Advanced Cutaneous Squamous Cell Carcinoma.

Cutaneous squamous cell carcinoma is the second most common skin cancer in the United States. Currently, there is no standardized management approach for patients with cutaneous squamous cell carcinoma who develop metastatic or locally advanced disease and are not candidates for curative surgery or curative radiation. To address this issue, the Expert Cutaneous Squamous Cell Carcinoma Leadership program convened an expert steering committee to develop evidence-based consensus recommendations on the basis of a large, structured literature review. Consensus was achieved through modified Delphi methodology. The steering committee included five dermatologists, three medical oncologists, two head and neck surgeons, one radiation oncologist, and a patient advocacy group representative. The steering committee aligned on the following clinical topics: diagnosis and identification of patients considered not candidates for surgery; staging systems and risk stratification in cutaneous squamous cell carcinoma; the role of radiation therapy, surgery, and systemic therapy in the management of advanced disease, with a focus on immunotherapy; referral patterns; survivorship care; and inclusion of the patient's perspective. Consensus was achieved on 34 recommendations addressing 12 key clinical questions. The Expert Cutaneous Squamous Cell Carcinoma Leadership steering committee's evidence-based consensus recommendations may provide healthcare professionals with practically oriented guidance to help optimize outcomes for patients with advanced cutaneous squamous cell carcinoma.

Imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: results of two placebo-controlled studies of daily application to the face and balding scalp for two 2-week cycles.

BACKGROUND: The approved imiquimod 5% cream regimen for treating actinic keratoses requires a long treatment time and is limited to a small area of skin. OBJECTIVE: We sought to evaluate imiquimod 2.5% and 3.75% for short-course treatment of the full face or balding scalp. METHODS: In two identical studies, adults with 5 to 20 lesions were randomized to placebo, imiquimod 2.5%, or imiquimod 3.75% (1:1:1). Up to two packets (250 mg each) were applied per dose once daily for two 2-week treatment cycles, with a 2-week, no-treatment interval between cycles. Efficacy was assessed at 8 weeks posttreatment. RESULTS: A total of 479 patients were randomized to placebo, or imiquimod 2.5% or 3.75%. Complete and partial clearance (> or =75% lesion reduction) rates were 6.3% and 22.6% for placebo, 30.6% and 48.1% for imiquimod 2.5%, and 35.6% and 59.4% for imiquimod 3.75%, respectively (P < .001 vs placebo, each; P = .047, 3.75% vs 2.5% for partial clearance). Median reductions from baseline in lesion counts were 25.0% for placebo, 71.8% for imiquimod 2.5%, and 81.8% for imiquimod 3.75% (P < .001, each active vs placebo; P = .048 3.75% vs 2.5%). There were few treatment-related discontinuations. Patient rest period rates were 0% for placebo, 6.9% for imiquimod 2.5%, and 10.6% for imiquimod 3.75%. LIMITATIONS: Local pharmacologic effects of imiquimod, including erythema, may have limited concealment of treatment assignment in some patients. CONCLUSIONS: Both imiquimod 2.5% and 3.75% creams were more effective than placebo and were well tolerated when administered daily as a 2-week on/off/on regimen to treat actinic keratoses.

Long-term mortality after primary percutaneous coronary intervention for high-risk myocardial infarction.

BACKGROUND: Primary percutaneous coronary intervention (PPCI) has evolved, including the introduction of stents and platelet glycoprotein IIb/IIIa receptor inhibitors (GPI). The effects of these changes and other variables on long-term survival for a single-centre service were studied. METHODS: A prospective database of clinical and angiographic variables were kept for patients treated with PPCI in Waikato Hospital from 1996 to 2006 (n=527). This was analysed with long-term mortality data. Survival was recorded using Kaplan-Meier curves. Multivariate analysis of factors at presentation, including ethnicity was performed. RESULTS: 5, 8 & 10-year survival rates were 76.5% (n=274), 72.7% (n=125) & 71.0% (n=19) respectively. Increased stent (42.8% vs. 84.1%, p<0.001) and GPI (39.6% vs. 73.3%, p<0.001) use was seen between early and late stages of the study. Stent use was associated with greater 5-year survival (80.5% vs. 70.8%, p=0.02), but GPI use was not. Multivariate analysis showed stent use independently predicted reduced mortality. Age, Maori ethnicity, renal failure and cardiogenic shock predicted higher mortality. CONCLUSIONS: Survival after PPCI remains high long-term. Stent and GPI use significantly increased. Stent, but not GPI, use was associated with improved survival. Maori ethnicity was under-represented in the study and is associated with worse long-term outcomes after myocardial infarction (MI).

Randomized, placebo-controlled study of a new botulinum toxin type a for treatment of glabellar lines: efficacy and safety.

BACKGROUND: A new botulinum toxin type A (BoNT-A) has been assessed in the United States for treatment of glabellar lines. In April 2009, the US FDA approved the Biologics License Application for a new US formulation of BoNT-A (Dysport [abobotulinum toxin A]; Medicis Aesthetics Inc., Scottsdale, AZ). OBJECTIVE: To compare efficacy and safety of a single treatment of BoNT-A with placebo in subjects with moderate to severe glabellar lines. METHODS AND MATERIALS: One hundred fifty-eight subjects with moderate to severe glabellar lines were randomized 2:1 to receive 50 U of BoNT-A (n=105) or placebo (n=53). Responders were defined as having no or mild glabellar lines at 30 days posttreatment according to investigator and subject assessments (co-primary endpoint) using the validated Glabellar Line Scale Score at maximum frown. Subject diaries were used to document onset of effect. When conducting the research, the authors conformed to the ethical guidelines of the 1975 Declaration of Helsinki. RESULTS: According to investigator assessment, the proportion of responders to BoNT-A at Day 30 was 89.5%, versus 7.5% for placebo (p<.001); according to subject assessment, the proportion of responders was 75.7%, versus 9.8% for placebo (p<.001). CONCLUSION: A single treatment with BoNT-A (50 U) was significantly superior to placebo in the correction of moderate to severe glabellar lines, with comparable tolerability.

Rapid Aspirin Desensitization is Safe and Feasible in Patients With Stable and Unstable Coronary Artery Disease: A Single-Center Experience.

AIMS: There are limited data on aspirin (ASA) desensitization for patients with coronary disease. We present our experience with a rapid nurse-led oral desensitization regimen in patients with aspirin sensitivity undergoing coronary angiography. METHODS: This single-center retrospective observational study includes patients with a history of ASA sensitivity undergoing coronary angiography with intent to perform percutaneous coronary intervention (PCI). RESULTS: Between January 2012 and January 2017, 24 patients undergoing coronary angiography for stable coronary disease (7 cases) or acute coronary syndromes (non-ST-segment myocardial infarction [NSTEMI; 8 cases], STEMI [9 cases]) underwent aspirin desensitization having reported previous reactions to aspirin. At initial presentation, previous sensitivity reactions were reported as: mucocutaneous reactions in 17 patients (urticaria in 3 [13%], nonurticarial rash in 6 [25%], angio-oedema in 8 [33%]), respiratory sensitivity in 4 (17%), and systemic anaphylactoid reactions in 3 (13%). Seventeen (71%) patients underwent PCI. Desensitization was acutely successful in 22 (92%) patients and unsuccessful in 2 (8%) patients who both had a single short-lived episode of acute bronchospasm treated successfully with nebulized salbutamol. Fifteen successfully desensitized patients completed 12 months of aspirin; no patient had recurrent hypersensitivity reaction. Aspirin was stopped prior to 12 months in 7 patients (replaced by warfarin [1 case], no antiplatelet or single antiplatelet clinically indicated and clopidogrel chosen [4 cases], patient choice without evidence of recurrent hypersensitivity [1 case], and death due to cardiogenic shock following STEMI [1 case]). CONCLUSION: A rapid aspirin desensitization protocol is safe and effective across a broad spectrum of hypersensitivity reactions and clinical presentations.

Primary percutaneous balloon pericardiotomy for malignant pericardial effusion.

OBJECTIVES: Pericardial effusion associated with malignancy is a life-threatening complication of late-stage disease. While simple drainage is effective in relieving the symptoms, reaccumulation of effusion may cause further symptomatic episodes, often during a period when overall patient management is focused on improving the quality of remaining life. Over a 16-year period, we have adopted a strategy of managing such patients with balloon pericardiotomy as the initial preferred treatment. The results are described and compared to alternative management strategies. METHODS: A retrospective analysis of patients who presented with symptomatic, malignant pericardial effusion, their management, procedural complication rates, and the need for further therapy for the same condition was made. Survival, reaccumulation rates, and readmissions after the index procedure were recorded and compared. RESULTS: Forty-three patients were treated for malignant pericardial effusion. Balloon pericardiotomy was the primary treatment in 27/43 patients, simple drainage in 14/43, and surgery in 2/43. Reaccumulation rates between balloon pericardiotomy and simple aspiration (7.4% vs. 14.3%, respectively, P = 0.48) and complication rates (7.4% vs. 7.1%, respectively, P = 0.98) were not statistically different. Survival following intervention was driven by the underlying pathology and was poor, with overall median survival of 56 days. CONCLUSIONS: Balloon pericardiotomy, as initial management of symptomatic malignant pericardial effusions, allows a definitive procedure to be performed at presentation. This can be achieved with low complication rates, similar to treatment by simple drainage.

Modified single-sling myocutaneous island pedicle flap: series of 61 reconstructions.

BACKGROUND: Bilevel undermining above and below the transverse nasalis muscle in the construction of a myocutaneous island pedicle flap produces a bilateral or unilateral muscular sling with exceptional vascular supply for reconstruction of defects on the distal nose. We present further modification of the single-sling myocutaneous island pedicle flap that expands its application to a wide variety of nasal defects and further defines its usefulness in nasal reconstruction. METHODS: A series of 61 consecutive myocutaneous island pedicle flap reconstructions performed after Mohs surgery between March 2005 and July 2006 are presented. Flap modifications are presented, and advantages and limitations are discussed. RESULTS: Flap modifications introduce additional reach and rotational mobility to the flap that permit extension of the flap to defects on the nasal tip and distal ala. CONCLUSION: Modifications of the bilevel approach to the single-sling nasalis myocutaneous island pedicle flap further define its practicality in nasal reconstruction and expand its application to a variety of nasal defects.

Imiquimod 2.5% and 3.75% Cream for the Treatment of Photodamage: A Meta-analysis of Efficacy and Tolerability in 969 Randomized Patients.

Background: Ad-hoc reports within clinical studies of imiquimod for the treatment of actinic keratosis (AK) have suggested the drug can improve both skin texture and overall signs of photodamage. Objective: We sought to assess the efficacy and tolerability of imiquimod 3.75% and 2.5% cream for the treatment of photodamage in patients with AK of the full face or balding scalp. Methods: A meta-analysis of four identical multicenter, randomized, double-blind, vehicle-controlled studies was conducted. The studies included a total of 969 adult subjects (aged 33-91 years) with 5 to 20 visible lesions or palpable AKs in an area exceeding 25cm2 on either the face or balding scalp. Patients were randomized to imiquimod 3.75%, imiquimod 2.5%, or vehicle cream (1:1:1). Up to two packets (250mg each) were applied per dose once daily for two two-week treatment cycles, separated by a two-week no-treatment interval. Photodamage improvement was assessed at study end based on subjects' baseline assessments using a seven-point scale. Local skin reactions were recorded throughout the study. Results: Combined Investigator's Global Integrated Photodamage (IGIP) score was "significantly" or "much" improved in 57.6 percent (n=175) of patients treated with imiquimod 2.5% cream and in 69.6 percent (n=208) of patients treated with imiquimod 3.75% cream versus in 25.7 percent (n=76) of patients treated with the vehicle. Mean IGIP scores at end of study were 1.67, 1.98, and 0.73, respectively (both actives P<0.0001 versus vehicle). Conclusion: Both imiquimod 2.5% and 3.75% creams showed a positive effect on photodamage when compared with the vehicle cream.

Outcomes after culprit-only percutaneous coronary intervention for multivessel disease during ST-segment elevation myocardial infarction: a comparison of registry and clinical trial outcomes.

BACKGROUND: The PRAMI and CvLPRIT trials support preventive percutaneous coronary intervention (PCI) for multivessel coronary disease found during ST-segment elevation myocardial infarction (STEMI). We assess our real-world experience of the management of multivessel disease identified during primary PCI (PPCI) in a large UK regional centre. PATIENTS AND METHODS: All STEMI patients who underwent culprit-only PPCI during the study period (August 2011 to August 2013) were retrospectively assessed for eligibility to each trial. The two resulting groups were designated as the 'observational' cohorts. Primary outcomes were then determined and compared with the culprit-only revascularisation cohorts from the respective published randomized controlled trials (RCTs). RESULTS: A total of 1143 consecutive cases were presented during the study period. Of these, 343 would have been suitable for inclusion to PRAMI and were included in the 'observational PRAMI' cohort; 196 patients were included in the 'observational CvLPRIT' cohort.The 'observational PRAMI' cohort experienced fewer primary outcome events (13.1 vs. 22.9%), cardiac deaths (0.6 vs. 4.3%) and nonfatal myocardial infarctions (3.5 vs. 8.7%) than the culprit-only PCI PRAMI cohort (n=231); there were significantly more diabetics (P=0.022) and anterior STEMI initial presentations in the culprit-only PCI PRAMI cohort. Primary outcomes were comparable to those of the preventive PCI PRAMI cohort.The 'observational CvLPRIT' cohort showed no significant difference in primary outcomes over 12 months (16.8 vs. 21.2%), but significantly lower all-cause mortality (2 vs. 6.9%) than the culprit-only PCI CvPLRIT cohort (n=146). The 30-day event rates were similar to the preventive PCI arm; the 12-month events were better than the nonpreventive, but not as good as the preventive RCT cohorts. CONCLUSION: Outcomes from culprit-only primary PCI for multivessel disease in patients selected by the RCT criteria from an all-comers population representing real-life experience are better than those published in the two main RCTs. The RCTs may have selected a high-risk population for study exaggerating the benefits of preventive PCI.

Surgical revision.

Even the best surgeons must confront scars and complications that are aesthetically unacceptable and need revision. With careful assessment of the scar, various scar revision techniques can be applied to create an aesthetically pleasing result.