Treatments for Moderate-to-Severe Acne Vulgaris: A Systematic Review and Network Meta-analysis.

BACKGROUND: Multiple treatment options exist for the management of moderate-to-severe acne. However, the comparative effectiveness (efficacy/safety) of moderate-to-severe acne treatments has not been systematically examined. METHODS: A systematic literature review (SLR) was conducted to identify randomized controlled trials of ≥4 weeks of treatment (topical, oral, physical, or combinations) for moderate-to-severe facial acne in patients aged ≥9 years. Efficacy outcomes included: percentage of patients achieving ≥2-grade reduction from baseline and “clear” or “almost clear” for global severity score (treatment success); absolute change in inflammatory (ILs reduction); and noninflammatory lesion counts (NILs reduction). A random-effects network meta-analysis (NMA) was conducted for the efficacy outcomes. Treatments were ranked with posterior rank plots and surface under cumulative ranking values.  Results: Eighty-five studies were included in the SLR/NMA. Topical triple-agent fixed-dose combination (FDC) gel (clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1%) and combinations of double-agent fixed-dose topical treatments with oral antibiotics (TOA3) consistently ranked in the top 3 treatments. Topical triple-agent FDC gel was numerically superior to TOA3 for treatment success (log-odds ratios: 1.84 [95% credible interval (CrI) 1.36 to 2.29]) and 1.69 (95% CrI: 1.01 to 2.32) vs placebo/vehicle). TOA3 was numerically superior to topical triple-agent FDC gel for reduction of ILs (mean difference: -8.21 [-10.33 to -6.13]) and -10.40 [-13.44 to -7.14] vs placebo/vehicle) and NILs (mean difference: -13.41 [-16.69 to -10.32] and -17.74 [-22.56 to -12.85] vs placebo/vehicle). CONCLUSIONS: Based on this SLR/NMA, topical triple-agent FDC gel was the most efficacious and safe treatment for moderate-to-severe acne. J Drugs Dermatol. 2024;23(4):     doi:10.36849/JDD.8148.

Derivation and validation of risk prediction for posttraumatic stress symptoms following trauma exposure.

BACKGROUND: Posttraumatic stress symptoms (PTSS) are common following traumatic stress exposure (TSE). Identification of individuals with PTSS risk in the early aftermath of TSE is important to enable targeted administration of preventive interventions. In this study, we used baseline survey data from two prospective cohort studies to identify the most influential predictors of substantial PTSS. METHODS: Self-identifying black and white American women and men (n = 1546) presenting to one of 16 emergency departments (EDs) within 24 h of motor vehicle collision (MVC) TSE were enrolled. Individuals with substantial PTSS (⩾33, Impact of Events Scale - Revised) 6 months after MVC were identified via follow-up questionnaire. Sociodemographic, pain, general health, event, and psychological/cognitive characteristics were collected in the ED and used in prediction modeling. Ensemble learning methods and Monte Carlo cross-validation were used for feature selection and to determine prediction accuracy. External validation was performed on a hold-out sample (30% of total sample). RESULTS: Twenty-five percent (n = 394) of individuals reported PTSS 6 months following MVC. Regularized linear regression was the top performing learning method. The top 30 factors together showed good reliability in predicting PTSS in the external sample (Area under the curve = 0.79 ± 0.002). Top predictors included acute pain severity, recovery expectations, socioeconomic status, self-reported race, and psychological symptoms. CONCLUSIONS: These analyses add to a growing literature indicating that influential predictors of PTSS can be identified and risk for future PTSS estimated from characteristics easily available/assessable at the time of ED presentation following TSE.

Atrial Tachyarrhythmias and Stroke: Temporal Relationship and Stroke Subtypes.

BACKGROUND AND PURPOSE: Research into the temporal relationship between atrial tachyarrhythmias (atrial tachycardia [AT] and atrial fibrillation [AF]) and stroke has produced conflicting findings. Systematic categorization of stroke subtypes may help clarify the discussion. OBJECTIVES: The objective of the study was to examine the presence and timing of AT/AF in relation to ischemic stroke subtypes, categorized as either cardioembolic (CE) or non-CE. METHODS: Consecutive patients presenting to the Austin Hospital with acute stroke from 2012 to 2019 and a cardiac implantable electronic device (CIED) were identified. Using a case-control design, the temporal proximity of AT/AF episodes in the 90 days prior to stroke was compared in the CE and non-CE stroke groups. RESULTS: 5,591 patients presented to the Austin Hospital with acute stroke from 2012 to 2019, of whom 31 patients with an ischemic stroke and a CIED with ≥90 days of monitoring were identified. Twelve strokes were adjudicated as CE and 19 as non-CE by a stroke neurologist. Six of the 12 CE stroke patients (50%) experienced AT/AF within 30 days preceding their stroke, while none of the 19 non-CE stroke patients recorded any AT/AF in the same period (p = 0.001). Four CE stroke patients (33%) had no AT/AF preceding their strokes at any time. The odds ratio for CE stroke was highest (39; 95% confidence interval [CI]: 1.92-791.5) when AT/AF occurred in the 30 days prior, declining to 20.65 (95% CI: 1.00-427.66) and 6.07 (95% CI: 0.94-39.04) in the subsequent 31-60- and 61-90-day windows, respectively. CONCLUSIONS: CE strokes were associated with a significantly higher proportion of preceding AT/AF compared with non-CE strokes. These findings support a potential temporal relationship between AT/AF and CE stroke and demonstrate that stroke subtyping can better characterize the relationship between AF and ischemic stroke. However, this study's findings are limited by its sample size and small number of informative cases.

Late recurrence of atrial fibrillation and flutter in patients referred for elective electrical cardioversion.

Aim    The primary aim was to ascertain long-term rates of atrial fibrillation (AF) recurrence in this all-comer patient population undergoing elective electrical cardioversion (DCR). Secondary aims included procedural DCR success, clinical predictors of long-term maintenance of sinus rhythm (SR) and AF related hospitalizations.Material and Methods    A retrospective cohort study was conducted. Consecutive patients (n=316) undergoing elective DCR were included.Results    Successful immediate reversion to SR was attained in 266 (84 %) of patients. 224 (84 %) patients were followed up for a median period of 3.5 years (IQR 2.7-4.3). Most patients (150 [67 %]) had recurrence of AF / flutter at a median time of 240 days. Clinical predictors of AF recurrence included a history of AF (HR 0.63, p=0.038) and a dilated left atrium (HR 4.13, p=0.048). Maintenance of SR was associated with fewer unplanned hospitalizations for AF (HR 3.25, p<0.01).Conclusion    There was high procedural success post DCR. However, long-term rates of AF recurrence were high, and AF recurrences were associated with increased hospitalizations. These findings underscore the importance of clinical vigilance and multi-modal management as part of a comprehensive and effective rhythm control strategy.

High anatomical accuracy of a novel high-resolution wide-band dielectric imaging system in cryoballoon-based ablation.

PURPOSE: Recently, a novel cardiac imaging system based on a wide-band dielectric technology (KODEX-EPD) was introduced to guide catheter ablation. The aim of the study was to evaluate this 3D wide-band dielectric imaging system (WDIS) during cryoballoon (CB)-based atrial fibrillation (AF) ablation focusing on accuracy of pulmonary vein (PV)-anatomy. METHODS: In consecutive patients with symptomatic AF, CB-based ablation was performed in conjunction with the 3D WDIS. Selective PV-angiographies were performed, and 3D anatomy of the left atrium (LA) and PVs using the 3D WDIS was created. The ostial diameters of the ipsilateral right-sided and left-sided PVs and ostial diameters of the right-/left-sided upper/lower PVs demonstrated by selective angiographies were analyzed and compared to 3D WDIS-based PV visualization. RESULTS: In 65 patients (42/65 (65%) male, age 65 ± 9 years, 29/65 (45%) paroxysmal AF) a total of 260 PVs were identified. Median ostial PV-diameters for the ipsilateral left- and right-sided PVs were 38 [34; 43] and 37 [34; 40.3] mm when assessed fluoroscopically and 40 [35.7; 43] and 39 [35.0; 43] mm as demonstrated by 3D WDIS. There was no statistically significant difference between both methods regarding PV-diameter measurements. KODEX-EPD overestimated fluoroscopy measurements by 1.08 mm (95% limits of agreement of -1.93 mm and 4.1 mm). CONCLUSION: The novel wide-band dielectric 3D-imaging system is feasible to create high-resolution images of cardiac structures during CB ablation procedures and accurately visualizes PV-anatomy.

Outcome of cardiac tamponades in interventional electrophysiology.

AIMS: The aim of this study was to analyse tamponades following electrophysiological procedures regarding frequency and mortality in a high-volume centre and to identify independent predictors for severe tamponades. METHODS AND RESULTS: We performed a retrospective study on 34 982 consecutive patients undergoing diagnostic electrophysiological studies or catheter ablation of cardiac arrhythmias. The combined endpoint was defined as severe tamponade. Criteria for severe tamponade included surgical repair, repeat pericardiocentesis, cardiopulmonary resuscitation, intrahospital death or death during follow-up, and thrombo-embolic events or complications due to therapeutic management. Multivariate analysis was performed to identify independent predictors for severe tamponade. A total of 226 tamponades were identified. Overall frequency of tamponades was 0.6%. Procedures requiring epicardial approach had the highest rate of tamponades (9.4%). Twenty-nine patients with tamponade underwent surgery (12.8% of all tamponades and 21.4% of tamponades during epicardial procedures). Overall tamponade-related mortality was 0.03% (9 deaths). Fifty-six patients (24.8%) experienced severe tamponade. Independent risk factors for severe tamponades were endocardial ablation of ventricular tachycardia, epicardial approach, balloon device ablation, high aspiration volume during pericardiocentesis and structural heart disease. CONCLUSION: The frequency of tamponades is strongly dependent on the type of procedure performed. Overall tamponade-related mortality was low but significantly higher in patients undergoing epicardial procedures. Surgical backup should be considered for patients undergoing complex ventricular tachycardia ablation and left atrial ablation procedures.

Halobetasol 0.01%/Tazarotene 0.045% Lotion for Moderate-to-Severe Psoriasis: Pooled Phase 3 Analysis of Males and Females.

BACKGROUND: Previous results from two phase 3 studies demonstrated efficacy and safety of fixed combination halobetasol propionate 0.01%/tazarotene 0.045% (HP/TAZ) lotion in participants with moderate-to-severe plaque psoriasis. This post hoc analysis evaluated sex-specific efficacy and safety of HP/TAZ lotion. METHODS: In two randomized, double-blind, phase 3 studies, participants were randomized (2:1) to receive HP/TAZ or vehicle lotion once daily for 8 weeks. Male and female participants were evaluated separately in this pooled analysis. Efficacy assessments included treatment success (at least 2­grade improvement in Investigator's Global Assessment [IGA] score and score of clear/almost clear), impact on individual signs of psoriasis, and affected Body Surface Area (BSA). RESULTS: The analysis included 272 males (HP/TAZ, n=175; vehicle, n=97) and 146 females (HP/TAZ, n=101; vehicle, n=45). Significantly more participants achieved overall treatment success at week 8 with HP/TAZ versus vehicle in both male (38.4% vs 9.8%) and female (44.5% vs 9.9%) subgroups (P<0.001, both). Erythema, plaque elevation, and scaling were also reduced by week 8 in both males and females, with significantly more HP/TAZ-treated participants achieving at least 2­grade improvement in each sign of psoriasis than vehicle-treated participants (P<0.001 each, both groups). Mean reductions in affected BSA were significantly greater with HP/TAZ versus vehicle lotion in both males and females (P≤0.001, both). The most frequent treatment-related adverse events were contact dermatitis, pruritis, and application site pain (each 4.0%) in females and contact dermatitis (7.6%) in males. CONCLUSION: HP/TAZ lotion was highly effective and safe in both males and females with moderate-to-severe psoriasis over 8 weeks of once-daily use. J Drugs Dermatol. 2020;19(5): doi:10.36849/JDD.2020.5021.

Halobetasol Propionate 0.01%/Tazarotene 0.045% Lotion for Moderate-to-Severe Psoriasis: Pooled Phase 3 Analysis of Lower Extremities.

Background: Plaque psoriasis can occur in all body regions, with the trunk and extremities among the most commonly affected areas. A fixed combination halobetasol propionate 0.01%/tazarotene 0.045% (HP/TAZ) lotion demonstrated efficacy and safety in patients with moderate-to-severe localized plaque psoriasis. This analysis evaluated patients where a psoriatic target lesion was identified on the leg. Methods: In two phase 3, multicenter, double-blind studies, participants were randomized (2:1) to receive HP/TAZ or vehicle lotion once-daily for 8 weeks. This pooled, post hoc analysis included a subset of participants who had a leg target lesion (HP/TAZ, n=148; vehicle, n=71). Efficacy assessments included treatment success (≥2-grade improvement) in psoriasis signs (erythema, plaque elevation, scaling) on the leg target lesion, and overall treatment outcomes, including overall treatment success (≥2-grade improvement in Investigator's Global Assessment [IGA] score and score of clear/almost clear), affected Body Surface Area (BSA), and IGAxBSA composite score. Results: Psoriasis signs were reduced by week 8, with more HP/TAZ treated participants achieving treatment success for erythema (41.6%), plaque elevation (58.5%), and scaling (59.5%) on the leg compared with vehicle (12.5%, 19.2%, and 21.0%, respectively; P<0.001 all). Significantly more participants achieved overall treatment success at week 8 with HP/TAZ versus vehicle (36.4% vs 10.4%; P<0.001). The HP/TAZ group also had a greater mean reduction in affected BSA and IGAxBSA score versus vehicle (P<0.001, both). The most frequently reported treatment-related adverse event (incidence, ≥3%) with HP/TAZ was contact dermatitis. Conclusions: HP 0.01%/TAZ 0.045% lotion was associated with significant reductions in disease severity and good tolerability following 8 weeks of treatment in patients where a psoriatic target lesion was identified on the leg. J Drugs Dermatol. 2020;19(4):389-396. doi:10.36849/JDD.2020.4958.

Miniaturized implantable cardiac monitor with a long sensing vector (BIOMONITOR III): Insertion procedure assessment, sensing performance, and home monitoring transmission success.

BACKGROUND: Implantable Cardiac Monitors (ICMs) are used for long-term monitoring of arrhythmias. BIOMONITOR III is a novel ICM with a miniaturized profile, long sensing vector due to a flexible antenna, simplified implantation with a dedicated insertion tool for pocket formation and ICM placement in a single step, and daily automatic Home Monitoring (HM) function. METHODS: In 47 patients undergoing BIOMONITOR III insertion for any ICM indication, 16 investigators at 10 Australian sites assessed handling characteristics of the insertion tool, R-wave amplitudes, noise burden, P-wave visibility, and HM transmission success. Patients were followed for 1 month. RESULTS: All 47 attempted insertions were successful. Median time from skin incision to removal of the insertion tool after ICM insertion was 39 s (IQR 19-65) and to wound closure and cleaning was 4.7 min (IQR 3.5-7.8). All aspects of the insertion tool were rated as "good" or "excellent" in ≥97.9% and "fair" in ≤2.1% of patients, except for "force needed for tunnelling" (91.5% good/excellent, 8.5% fair). Based on HM data, R-waves in the first month were stable at 0.70 ± 0.37 mV. Median noise burden (disabling automatic rhythm evaluation) was 0.19% (IQR 0.00-0.93), equivalent to 2.7 min (IQR 0.0-13.4) per day. In HM-transmitted ECG strips with regular sinus rhythm, P-waves were visible in 89 ± 24% of heart cycles. Patient-individual automatic Home Monitoring transmission success was 98.0% ± 5.5%. CONCLUSIONS: The novel ICM performed well in all aspects studied, including fast insertion, reliable R-wave sensing, good P-wave visibility, and highly successful HM transmissions.

Predictors of ManuScript Rejection sYndrome (MiSeRY): a cohort study.

OBJECTIVES: To assess whether specific factors predict the development of ManuScript Rejection sYndrome (MiSeRY) in academic physicians. DESIGN: Prospective pilot study; participants self-administered a questionnaire about full manuscript submissions (as first or senior author) rejected at least once during the past 5 years. SETTING: Single centre (tertiary institution). PARTICIPANTS: Eight academic physician-authors. MAIN OUTCOME MEASURES: Duration of grief. MiSeRY was pre-specified as prolonged grief (grief duration longer than the population median). RESULTS: Eight participants provided data on 32 manuscripts with a total of 93 rejections (median, two rejections per manuscript; interquartile range [IQR], 1-3 rejections per manuscript). Median age at rejection was 37 years (IQR, 33-45 years); 86% of 80 rejections involved male authors (86%), 56 of the authors providing data about these rejections were first authors (60%). The median journal impact factor was 5.9 (IQR, 5.2-17). In 48 cases of rejection (52%), pre-submission expectations of success had been high, and in 54 cases (58%) the manuscripts had been sent for external review. Median grief duration was 3 hours (IQR, 1-24 h). Multivariate analysis indicated that higher pre-submission expectation (adjusted odds ratio [aOR], 5.0; 95% CI, 1.5-18), first author status (aOR, 9.5; 95% CI, 1.1-77), and external review (aOR, 19.0; 95% CI 2.9-126) were independent predictors of MiSeRY. CONCLUSIONS: To help put authors out of their MiSeRY, journal editors could be more selective in the manuscripts they send for external review. Tempering pre-submission expectations and mastering the Coping and reLaxing Mechanisms (CaLM) of senior colleagues are important considerations for junior researchers.

Efficacy, Safety, and Tolerability of a Halobetasol 0.01% /Tazarotene 0.045% Fixed Combination in the Treatment of Severe Localized Plaque Psoriasis: Post Hoc Analysis of Two Phase III Randomized Controlled Trials

Background: The use of topical therapy is a key component in the management of almost all psoriasis patients. Topicals are considered first-line therapy for mild disease and are having an increasing role in moderate or severe psoriasis as an integral part of combination therapy. Halobetasol has been shown be effective in moderate or severe localized plaque psoriasis, and tazarotene affords important effects on epidermal hyperproliferation that may be important in more severe disease. Objective: To investigate the efficacy, safety and tolerability of a once-daily application of a fixed combination halobetasol propionate 0.01% and tazarotene 0.045% (HP/TAZ) lotion in comparison with its vehicle in patients with severe localized plaque psoriasis (as defined by an Investigator Global Assessment (IGA) of 4 and Body Surface Area (BSA) of 3%-12%. Methods: Post hoc analysis of two multicenter, randomized, double-blind, vehicle-controlled phase 3 studies. Sixty-two patients with severe localized psoriasis (mean BSA 7.4) randomized (2:1) to receive HP/TAZ lotion or vehicle, once-daily for 8 weeks, with a 4-week posttreatment follow-up. Efficacy assessments included treatment success (defined as at least a 2-grade improvement from baseline in the IGA score and a score of 'clear' or 'almost clear'), impact on individual signs of psoriasis (erythema, plaque elevation, and scaling) at the target lesion, BSA, reduction in mean baseline IGAxBSA and achievement of a clinically meaningful response (number of patients who achieved at least a 75% improvement in IGAxBSA). Safety and treatment emergent adverse events (TEAEs) were evaluated throughout. Results: By week 8, 34.8% of patients were treatment successes compared with 0.0% on vehicle (P=0.004). HP/TAZ lotion was also significantly superior in reducing psoriasis signs and symptoms and improving BSA. At week 8, 47.4% (erythema), 66.4% (plaque elevation), and 65.4% (scaling) subjects achieved at least a 2-grade improvement, compared with 14.0% (P=0.016), 14.8% (P<0.001) and 14.7% (P<0.001) respectively with vehicle. Patients treated with HP/TAZ lotion achieved a 32.8% reduction in baseline mean BSA, compared with a 39.6% increase with vehicle (P=0.013). HP/TAZ lotion achieved a statistically significant superior reduction in mean IGAxBSA compared to vehicle from week 2 (P<0.001 versus vehicle). By week 8, almost half of the patients treated with HP/TAZ lotion achieved a clinically meaningful response (IGAxBSA-75) and a 52.9% reduction in mean IGAxBSA score compared with a 17.5% increase in those patients treated with vehicle (P<0.001). One patient (2.6%) treated with HP/TAZ lotion discontinued due to AE. Most frequently reported treatment related AEs were application site pain (7.9%), contact dermatitis (5.3%) and pruritus (5.3%). Conclusions: HP/TAZ lotion provides significantly greater efficacy than vehicle that is both rapid and sustained, in patients with severe localized plaque psoriasis, with good tolerability and safety over 8 weeks' once-daily use. J Drugs Dermatol. 2019;18(10):1012-1018.

Halobetasol 0.01% Lotion in the Treatment of Moderate-to-Severe Plaque Psoriasis of the Lower Extremities

Background: Psoriasis is a chronic, immune-mediated disease that varies widely in its clinical expression. Topical corticosteroids (TCS) are the mainstay of treatment. Long-term safety remains a concern, limiting use, and posttreatment flare is common. Recently data were reported on the use of halobetasol propionate (HP) 0.01% lotion in moderate or severe localized plaque psoriasis, once-daily for 8 weeks. In addition, a 2-week label-restricted study reported comparable efficacy to HP 0.05% cream. Data evaluating efficacy in specific locations has not been reported and while psoriasis commonly affects lower extremities treatment can be more problematic and burden of disease heightened. Objective: To investigate the efficacy of a once-daily application of HP 0.01% lotion in comparison with its vehicle in patients with moderate-to-severe plaque psoriasis of the lower extremities. Methods: A post hoc analysis of two multicenter, randomized, double-blind, vehicle-controlled phase 3 studies in moderate or severe psoriasis. Subjects (N=234) where the leg was identified as the target lesion were randomized (2:1 ratio) to receive HP 0.01% lotion or vehicle, once-daily for 8 weeks. Efficacy assessments included treatment success (defined as at least a 2-grade improvement from baseline) in each individual sign of psoriasis (erythema, plaque elevation, and scaling) at the target lesion (leg) and overall treatment outcomes including at least a 2-grade improvement from baseline in the Investigator Global Assessment (IGA) score, and 'clear' or 'almost clear', improvement in Body Surface Area (BSA) and reduction in IGAxBSA. Quality of Life (QoL) was assessed using the Dermatology Life Quality Index (DLQI) at baseline, week 4, 8, and 12. Results: At the end of the 8-week treatment period, more than half of subjects had achieved treatment success, with 52.1%, 55.5%, and 58.2% of subjects achieving at least a 2-grade reduction in erythema, plaque elevation and scaling severity on the leg, compared with 15.7% and 22.9%, and 22.2% of those treated with vehicle (P<0.001). In addition, overall treatment success (IGA) was achieved in 37.1% of these subjects who had been treated with HP 0.01% lotion compared with 8.4% treated with vehicle (P<0.001); with a corresponding 34.2% reduction in baseline BSA and 50.5% change in mean baseline IGAxBSA (both P<0.001 versus vehicle). Overall, a clinically relevant improvement in QoL was achieved by week 4; by week 8 37.7% of subjects where the leg was the target lesion had a clinically meaningful improvement in disease severity (IGAxBSA-75). Conclusions: In conclusion, halobetasol propionate 0.01% lotion provides statistically significant efficacy following 8 weeks' therapy compared with vehicle in subjects where the leg was identified as the target lesion, with clinically relevant improvements in QoL and more than a third of subjects achieving a clinically meaningful result. J Drugs Dermatol. 2019;18(10):1029-1036.

Efficacy of a Once-Daily Fixed Combination Halobetasol (0.01%) and Tazarotene (0.045%) Lotion in the Treatment of Localized Moderate-to-Severe Plaque Psoriasis

Recently, clinical data on 8 weeks' once-daily treatment of localized moderate-to-severe psoriasis with a novel fixed combination halobetasol propionate 0.01%/tazarotene 0.045% (HP/TAZ) lotion were published.1,2 HP/TAZ lotion was significantly more effective than individual active ingredients or vehicle, based on improvements in Investigator's Global Assessment (IGA), body surface area (BSA) involvement, and signs and symptoms of psoriasis (erythema, plaque elevation, and scaling) at the target lesion as well as a synergistic benefit over individual active ingredients, and good tolerability.

Higher contact force, energy setting, and impedance rise during radiofrequency ablation predicts charring: New insights from contact force-guided in vivo ablation.

INTRODUCTION: Higher contact force (CF) theoretically increases the risk of blood charring, diminishing lesion formation. We aimed to investigate the relationship between CF, impedance change, and char formation during pulmonary vein isolation (PVI). METHODS: CF was assessed during PVI in 65 patients. Radiofrequency ablation (RFA) with power-controlled mode was applied in the point-by-point manner. The RFA were divided into five groups: group A (CF < 10 g), group B (10 g ≤ CF < 20 g), group C (20 g ≤ CF < 30 g), group D (30 g ≤ CF < 40 g), and group E (CF ≥ 40 g). Gradual impedance rise (gIR) was defined as >5 Ω increase during each 10-second period of RFA. Catheter tip was assessed for charring during, and at the end of each procedure. RESULTS: In total, 2,064 applications were analyzed. During 0-10 seconds, impedance was significantly decreased in groups with higher CF (P < 0.05). During 10-20 seconds, an impedance decrease was not significantly different among the five groups. During 20-30 seconds, mean impedance increased in group E. A gIR was noted at least once during RFA in 63 patients (97%). The incidence of gIR during RFA after 20 seconds was significantly higher in groups D and E (77/504 [15.3%] vs. 90/1560 [5.8%], P < 0.001). Charring occurred in 8 of 65 (12%) patients. A gIR after 20 seconds was significantly associated with a higher incidence of macroscopic charring (6/20 [30%] vs. 2/45 [4%], P < 0.01). CONCLUSIONS: gIR was noted with higher applied CFs after 20 seconds of RFA. This impedance rise may be avoided by keeping the applied CF under 26.9 g with negative predictive value of 95%. Our data suggested that gIR may be related to the incidence of charring.

Insights into ablation of persistent atrial fibrillation: Lessons from 6-year clinical outcomes.

INTRODUCTION: Ablation of persistent atrial fibrillation (AF) is a potential treatment option for symptomatic patients. We sought to evaluate the critical role of circumferential pulmonary vein isolation (CPVI) in the ablation of persistent AF. METHODS AND RESULTS: A total of 341 ablation procedures were performed in 174 consecutive patients with persistent AF. CPVI was performed in all patients, additional ablation was only performed if electrical cardioversion failed after CPVI. During a median follow-up (FU) of 89 (63; 89) months, stable sinus rhythm was documented in 42/170 (25%) patients after a single procedure and in 111/164 (68%) patients after 1.9 ± 1.1 procedures. Stable SR was achieved in 40/75 (53%) patients in whom only CPVI was performed during the index and repeat procedures and in 71/89 (79%) patients with CPVI plus additional ablation. The main predictor for ablation success was duration of persistent AF before the index procedure (P < 0.001, HR ± CI: 1.608 [1.034, 1.103]). Responders to CPVI during the initial procedure had a significantly better multiple-procedure outcome after 42 months of FU compared to CPVI nonresponders (P  =  0.0365). Conversion during the index procedure had no impact on clinical outcomes (P  =  0.0903). Persistent AF regressed to paroxysmal AF in 16% of patients. CONCLUSIONS: We demonstrate a 25% single- and 68% multiple-procedure success in patients with persistent AF, while stable SR was achieved in 53% of patients with pure CPVI during all procedures and in 79% of patients with CPVI plus additional ablation. Only duration of persistent AF before ablation had a statistically significant impact on ablation outcome.

Long-term follow up of 3 T MRI-detected brain lesions after percutaneous catheter-based left atrial appendage closure.

BACKGROUND: Left atrial appendage closure (LAAC) for stroke prevention is an increasingly performed intervention. AIMS: This prospective study aims to evaluate the incidence of long-term magnetic resonance imaging (MRI)-detected brain lesions as well as potential changes of neurocognitive function after percutaneous LAAC. METHODS: Brain MRI at 3 T was performed within 24 hr before and after LAAC. A follow-up MRI was carried out after three months. Neuro-cognitive examination using the National Institutes of Health Stroke Scale (NIHSS) score and the Montreal Cognitive Assessment (MoCA) Test was performed. RESULTS: Successful device implantation was achieved in all 25 patients (age 74.6 ± 10.2 years, male = 17) using the Amulet (n = 20), Occlutech (n = 3), or a Lambre (n = 2) device. In 12/25 (48%) patients, acute brain lesions (ABL) were detected after LAAC. A three-month follow-up MRI was performed in seven patients, and no new ABLs were seen. In 5/7 (71%) patients, there were no residual changes from the ABLs detectable. However, the FLAIR sequence was still positive in two patients. After LAAC, there were no significant differences in the MoCA-test (mean 24.3 ± 4.5 vs. 23.5 ± 4.5; P = 0.1) and the NIHSS-score (mean 0.9 ± 1.6 vs. 1.2 ± 1.8; P = 0.1). This was the same at the three-month follow-up (MoCA-test 23.5 ± 4.5 vs. 23.8 ± 2.7; P = 0.3; NIHSS-score 1.2 ± 1.8 vs. 1.0 ± 0.8; P = 0.4). CONCLUSION: While new MRI-detected brain lesions are commonly observed after percutaneous LAAC, ABLs were no longer detectable in 71% of the patients at the three-month follow-up. There were no significant changes in neurocognitive function after LAAC and at the three-month follow-up.

Cryoballoon ablation in the elderly: one year outcome and safety of the second-generation 28mm cryoballoon in patients over 75 years old.

Aims: The efficacy of the second-generation cryoballoon (CB) ablation in patients with atrial fibrillation (AF) has been demonstrated previously. Data on the efficacy of CB ablation in elderly patients is missing. The aim of this study was to evaluate the long-term success rate of pulmonary vein isolation (PVI) in patients ≥75 years vs. <75 years using the second-generation 28mm CB. Methods and results: Eighty patients [n = 40 ≥75 years (Group 1); n = 40 <75 years (Group 2)] with paroxysmal [n = 37 (46%) or persistent (n = 43 (54%)] AF were included. Median follow-up was 12 [6;18] months (Group 1 vs. 13 [6;27]) months (Group 2; P = 0.8). PVI was performed in all patients using cryoablation. Follow-up was obtained using 24h-Holter monitoring or via an implanted loop recorder or pacemaker. CHA2DS2VASc-Score (Group 1: 4 [4;5] vs. Group 2: 2 [1;3], P < 0.001) and HASBLED-Score (Group 1: 2 [2;3] and Group 2: 2 [1;3], (P = 0.009)) differed significantly between the two groups. Mean fluoroscopy time was 22.9 [16.3;31.9] in Group 1 and 24.5 [19.1;30.6] in Group 2 (P = 0.75), and mean procedure time was 125 min [105;151] in Group 1 and 130.5 min [117.5;147.3] in Group 2 (P = 0.66). Arrhythmia recurrence was similar in Group 1 and Group 2 (12/40 (30%) vs. 10/40 (25%) (P = 0.62). One transient ischaemic attack occurred in Group 2. No further major complications were documented in this patients cohort. Conclusion: CB ablation in patients ≥75 years has favourable success rates and similar complication rates compared with patients <75 years.

Pulmonary vein stenosis or occlusion after catheter ablation of atrial fibrillation: long-term comparison of drug-eluting versus large bare metal stents.

Aims: Pulmonary vein stenosis or occlusion (PVS/O) following catheter ablation of atrial fibrillation is a rare but potentially severe complication. Treatment options include angioplasty with or without stent implantation, but data on outcome and optimal treatment strategy are limited. We report long-term results after catheter-based treatment of patients with symptomatic PVS/O. Methods and results: Retrospective analysis was performed in patients undergoing pulmonary vein (PV) angiography for suspected PVS/O. All patients with PVS/O were treated with balloon angioplasty and implantation of a coronary drug-eluting stent (DES) or a peripheral large-diameter bare metal stent (LD-BMS). A total of 25 high-degree PVS/Os in 19 patients were treated. Nine PVs were treated with angioplasty and DES implantation and 16 with angioplasty and LD-BMS implantation. The ostial PV diameter was not different in the DES and LD-BMS groups (10.2 ± 2.5 mm vs. 11.1 ± 1.9 mm, P = 0.34), but the PV/stent diameter ratio was significantly lower in the former (0.43 ± 0.13 vs. 0.82 ± 0.13, P < 0.0001). Angiographic stent restenosis was observed at a median of 539 (interquartile range 99-774) days in 9 of 23 (39%) treated PVs. The restenosis rate in the LD-BMS group was only one-third of that in the DES group [3/14 (21%) vs. 6/9 (67%), respectively; P = 0.08]. Conclusion: The use of LD-BMS for the treatment of PVS/O was associated with an acceptable long-term outcome. Coronary DES implantation resulted in a high rate of restenosis and should therefore not be performed. Larger trials are needed to confirm our findings.

Safety and efficacy of a fixed combination of halobetasol and tazarotene in the treatment of moderate-to-severe plaque psoriasis: Results of 2 phase 3 randomized controlled trials.

BACKGROUND: Topical corticosteroids are the mainstay of psoriasis treatment, with long-term safety considerations limiting their use. Combining them with tazarotene may optimize their efficacy and minimize safety and tolerability concerns. OBJECTIVE: To investigate the safety and efficacy of halobetasol propionate 0.01% plus tazarotene 0.045% (HP/TAZ) lotion in moderate-to-severe plaque psoriasis. METHODS: Two multicenter, randomized, double-blind, vehicle-controlled phase 3 studies (N = 418) were conducted. Subjects were randomized (2:1) to HP/TAZ lotion or vehicle once daily for 8 weeks with a 4-week follow-up. The primary efficacy assessment end point was treatment success (at least a 2-grade improvement from baseline in Investigator's Global Assessment score and a score of clear or almost clear). Safety and treatment-emergent adverse events were evaluated throughout. RESULTS: HP/TAZ lotion demonstrated statistically significant superiority over vehicle within as few as 2 weeks. By week 8, 35.8% (study 1) and 45.3% (study 2) of subjects were treatment successes compared with 7.0% and 12.5% of those treated with vehicle (P < .001). HP/TAZ lotion was also superior in reducing signs and symptoms of psoriasis and body surface area affected by psoriasis. The most frequently reported treatment-related adverse events were contact dermatitis (6.3%), application site pain (2.6%), and pruritus (2.2%). LIMITATIONS: Studies did not include subjects with more than 12% of their body surface area affected by psoriasis. CONCLUSIONS: HP/TAZ lotion was associated with significant reductions in the severity of the clinical signs of psoriasis, with no safety concerns.

Is Severity of Disease a Prognostic Factor for Cure Following Treatment of Onychomycosis?

BACKGROUND: Onychomycosis is a common disease that remains a difficult disorder to treat despite the introduction of new topical agents; and not all patients are cured. Clinical experience leads us to suggest a number of host-related factors can affect the chance of cure, but studies supporting these observations are currently lacking. Although many studies, particularly on topical agents, rely on severity classification when selecting patients for inclusion, a pilot study was unable to demonstrate any prognostic value of the extension of nail involvement. In addition, no universal severity classification exists, and most studies do not report prognostic factors. OBJECTIVE: To investigate the efficacy of efinaconazole topical solution, 10% in patients with mild-to-moderate onychomycosis and determine the impact of baseline severity on treatment outcome. METHODS: Post hoc pooled analysis of two identical, multicenter, randomized, double-blind, vehicle-controlled studies in 1655 patients aged 18-70 years with a clinical and mycological diagnosis of mild-to-moderate dermatophyte toenail onychomycosis (20-50% clinical involvement). Patients were randomized (3:1) to efinaconazole 10% solution or vehicle, once-daily for 48 weeks, with 4-week post treatment follow-up. Efficacy criteria included clear nail (0% target nail plate involvement), almost clear nail (≤5% target nail plate involvement), and clinical treatment success (≤10% target nail plate involvement) at week 52. For the post hoc analysis, patients were classified as mild (20%-29% nail involvement), moderate (30%-39%), and moderately severe (40%-50%) at baseline. RESULTS: Overall, 25%, 23%, and 52% of patients had mild, moderate, or moderately severe disease at baseline. Baseline nail involvement did not appear to predict treatment outcomes. The proportion of patients with mild disease who had a clear nail progressively reduced by week 36 (58%) and week 48 (41%), and even further by week 52 (37%). Of the 237 patients treated with efinaconazole who were 'clear' at week 52, 37%, 24%, and 39% had mild, moderate or moderately severe disease respectively at baseline. The majority of patients (N=634) saw at least a 50% improvement in their target toenail by week 52. Almost half of these patients (N=312, 49.2%) were moderately severe at baseline. CONCLUSIONS: This post hoc analysis supports previous data showing good efficacy of efinaconazole in mild onychomycosis. The relative contribution to overall efficacy results at week 52 of patients with moderate or moderately severe disease was unexpected for a topical therapy, and warrants further study, especially as they represent the majority of patients enrolled in the two studies. It is possible that comparable efficacy can be achieved in these more severe patients with longer treatment courses, or follow-up. J Drugs Dermatol. 2018;17(2):175-178.