Guselkumab demonstrates long-term efficacy and maintenance of treatment response post-withdrawal in systemic-treatment naïve patients and non-responders to fumaric acid esters: Results from parts II and III of a randomised, active-comparator-controlled phase IIIb trial (POLARIS).

BACKGROUND: The anti-interleukin-23 antibody guselkumab demonstrated favourable Week 24 efficacy and safety over fumaric acid esters (FAE) in systemic-treatment naïve patients with moderate-to-severe plaque psoriasis (study part I). OBJECTIVES: Part II: compare a) sustainability of treatment responses (Weeks 24-32) in guselkumab- and FAE-treated patients and b) treatment responses (Weeks 32-56) in patients treated with guselkumab, FAE, and FAE non-responders switching to guselkumab. Part III: investigate the maintenance of response through Week 100 in patients withdrawn from guselkumab at Week 56. METHODS: At Week 0, systemic-treatment naïve patients were randomised 1:1 to guselkumab (GUS) or FAE as per label. At Week 32, patients with PASI75 response (r) continued assigned treatment (GUSr-GUS; FAEr-FAE), whereas non-responders (nr) received guselkumab (FAEnr-GUS; GUSnr-GUS). Guselkumab-treated patients with Week 56 PASI90 response were withdrawn (w) and followed until loss of response or Week 100. RESULTS: At Week 32, 98.2% (54/55) of guselkumab- and 41.2% (14/34) of FAE-treated patients were PASI75 responders. At Week 56, 90.7%, 50.0% and 80.0% of GUSr-GUS, FAEr-FAE and FAEnr-GUS patients, respectively, achieved a PASI90 response; 72.2%, 28.6% and 45.0%, respectively, achieved a DLQI score 0/1. At Week 100, 44 weeks post-withdrawal, 47.2% (17/36) and 25.0% (3/12) of GUS-GUSw and FAE-GUSw patients, respectively, maintained PASI score ≤5. Overall, the adverse event and discontinuation rates were lower for guselkumab than FAE. CONCLUSIONS: In these exploratory analyses, guselkumab, as a first-line systemic treatment or second-line systemic treatment in FAE non-responders, was associated with long-term clinical efficacy up to Week 100, including a withdrawal period.

PrabotulinumtoxinA vs OnabotulinumtoxinA for the Treatment of Adult Males With Moderate to Severe Glabellar Lines: Post-hoc Analyses of the Phase III Clinical Study Data.

BACKGROUND: Despite a growing interest among men in cosmetic procedures such as botulinum toxin, comparator clinical trial data in this population are limited. OBJECTIVES: The authors sought to compare the efficacy and safety of prabotulinumtoxinA and onabotulinumtoxinA for the treatment of males with moderate to severe glabellar lines. METHODS: Post-hoc analyses were performed on the subpopulation of male patients treated with either a single dose of 20 U prabotulinumtoxinA (n = 25) or 20 U onabotulinumtoxinA (n = 31) in the EVB-003 Phase III glabellar line clinical study. One key efficacy endpoint was the proportion of responders with a ≥1-point improvement from baseline at maximum frown on the 4-point Glabellar Line Scale. RESULTS: Compared with onabotulinumtoxinA-treated males, the percentages of responders who had a ≥1-point improvement on the Glabellar Line Scale at maximum frown were higher at all postbaseline time points for prabotulinumtoxinA-treated males (P > 0.05 at all visits) by an absolute overall mean difference of 10.1% across all visits. Similar trends were observed for efficacy endpoints based on global aesthetic improvement and subject satisfaction. PrabotulinumtoxinA-treated males had a higher incidence of treatment-related headache and eyelid ptosis. CONCLUSIONS: The percentages of patients who met the definition of a responder were higher at almost all time points examined for prabotulinumtoxinA-treated males. Despite the high level of consistency across all measures, differences between the 2 treatment groups did not reach statistical significance. Further study is warranted to establish if these post-hoc analyses observations are reproducible in a larger male patient population.

Efficacy and safety of N-acetyl-GED-0507-34-LEVO gel in patients with moderate-to severe facial acne vulgaris: a phase IIb randomized double-blind, vehicle-controlled trial.

BACKGROUND: Preliminary in vitro and in vivo studies have supported the efficacy of the peroxisome proliferator-activated receptor-γ (PPARγ) modulator N-acetyl-GED-0507-34-LEVO (NAC-GED) for the treatment of acne-inducing sebocyte differentiation, improving sebum composition and controlling the inflammatory process. OBJECTIVES: To evaluate the efficacy and safety of NAC-GED (5% and 2%) in patients with moderate-to-severe facial acne vulgaris. METHODS: This double-blind phase II randomized controlled clinical trial was conducted at 36 sites in Germany, Italy and Poland. Patients aged 12-30 years with facial acne, an Investigator Global Assessment (IGA) score of 3-4, and an inflammatory and noninflammatory lesion count of 20-100 were randomized to topical application of the study drug (2% or 5%) or placebo (vehicle), once daily for 12 weeks. The co-primary efficacy endpoints were percentage change from baseline in total lesion count (TLC) and IGA success at week 12; the safety endpoints were adverse events (AEs) and serious AEs. This study was registered with EudraCT (2018-003307-19). RESULTS: Between Q1 in 2019 and Q1 in 2020 450 patients [n = 418 (92·9%) IGA 3; n = 32 (7·1%) IGA 4] were randomly assigned to NAC-GED 5% (n = 150), NAC-GED 2% (n = 150) or vehicle (n = 150). The percentage change in TLC reduction was statistically significantly higher in both the NAC-GED 5% [-57·1%, 95% confidence interval (CI) -60·8 to -53·4; P < 0·001] and NAC-GED 2% (-44·7%, 95% CI -49·1 to -40·1; P < 0·001) groups compared with vehicle (-33·9%, 95% CI -37·6 to -30·2). A higher proportion of patients treated with NAC-GED 5% experienced IGA success (45%, 95% CI 38-53) vs. the vehicle group (24%, 95% CI 18-31; P < 0·001). The IGA success rate was 33% in the NAC-GED 2% group (P = not significant vs. vehicle). The percentage of patients who had one or more AEs was 19%, 16% and 19% in the NAC-GED 5%, NAC-GED 2% and vehicle groups, respectively. CONCLUSIONS: The topical application of NAC-GED 5% reduced TLC, increased the IGA success rate and was safe for use in patients with acne vulgaris. Thus, NAC-GED, a new PPARγ modulator, showed an effective clinical response. What is already known about this topic? Acne vulgaris, one of the most common dermatological diseases, affects more than 85% of adolescents. There is a medical need for innovative and safe treatment of acne vulgaris. The peroxisome proliferator-activated receptor-γ (PPARγ) is involved in lipid metabolism and specifically in cell differentiation, sebum production and the inflammatory reaction. What does this study add? N-acetyl-GED-0507-34-LEVO (NAC-GED 5%), a PPARγ modulator, significantly improves acne manifestations in patients with moderate-to-severe acne and is safe and well tolerated. The results suggest that the PPARγ receptor is a novel therapeutic target for acne. The results provide a basis for a large phase III trial to assess the effectiveness and safety profile of NAC-GED in combating a disease that afflicts 80-90% of adolescents.

Self-efficacy, burnout and academic success in nursing students: A counterfactual mediation analysis.

AIM: To test the mediating role of burnout in the relationship between self-efficacy and academic success in nursing students. DESIGN: This was a cross-sectional secondary analysis of longitudinal research aimed at exploring the academic success of nursing students. METHODS: We enrolled a convenience sample of nursing students attending 21 Italian baccalaureate nursing degree programmes. Data were collected from 2014 to the 2018-2019 academic year. We analysed the wave of data collected during the third year of the programme. The measurements were the Academic Nurse Self-Efficacy scale (ANSEs) and the Scale of Work Burnout (SWEBO). A mediation analysis with a counterfactual approach was performed. RESULTS: The participants (n = 556) had a median age of 20 years (IQR 19-22) and the majority was female [70.5% (392/556)]. Academic success was reached by 51.97% (289/556) of the students. The findings reveal a significant direct effect of self-efficacy on academic success and also a significant indirect effect of this relationship via burnout. CONCLUSION: The mechanism by which self-efficacy influences academic performance in nursing students is more complex than a simple direct relationship. Universities should consider screening students for variables affecting academic success to decrease academic costs and increase ranking systems classification. IMPACT: Nurses' professors should be engaged in strategies to promote self-efficacy. The area of intervention should be structured both during classes and internships, in tandem with the mentor and the clinical nurse.

Molecular Cross-Talk between Gravity- and Light-Sensing Mechanisms in Euglena gracilis.

Euglena gracilis is a photosynthetic flagellate. To acquire a suitable position in its surrounding aquatic environment, it exploits light and gravity primarily as environmental cues. Several physiological studies have indicated a fine-tuned relationship between gravity sensing (gravitaxis) and light sensing in E. gracilis. However, the underlying molecular mechanism is largely unknown. The photoreceptor photoactivated adenylyl cyclase (PAC) has been studied for over a decade. Nevertheless, no direct/indirect interaction partner (upstream/downstream) has been reported for PAC. It has been shown that a specific protein, kinase A (PKA), showed to be involved in phototaxis and gravitaxis. The current study reports the localization of the specific PKA and its relationship with PAC.

Bimekizumab Self-Injection Devices: Two Multicenter, Randomized, Open-Label Studies on Self-Administration by Patients With Psoriasis.

BACKGROUND: Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A. OBJECTIVES: To assess patients' ability to self-inject bimekizumab subcutaneously using a 1 mL safety syringe or auto-injector. METHODS: DV0002 and DV0006 were sub-studies of BE BRIGHT, a multicenter, phase 3 open-label extension study. Patients with moderate to severe plaque psoriasis received bimekizumab 320 mg (2x160 mg injections) every 4 or 8 weeks and were randomized 1:1 to the safety syringe or the auto-injector. The ability of patients to safely and effectively self-inject bimekizumab was assessed at 8 weeks (primary endpoint) and immediately after self-injection training at Baseline (secondary endpoint). Patient experience was evaluated using the pain visual analog scale (VAS; 0–100 mm; 100 being worst pain), and the Self-Injection Assessment Questionnaire (SIAQ; 0–10; 10 being most positive experience). RESULTS: All evaluable patients in DV0002 (n=125) and DV0006 (n=86) safely and effectively self-injected bimekizumab at Week 8. All evaluable patients in DV0002 who used the safety syringe (n=64) and 97.1% (n=66/68) who used the auto-injector, as well as all evaluable DV0006 patients (n=88) also self-injected bimekizumab safely and effectively at Baseline. Median VAS scores were low (range: 7.0–20.0), and median pre-injection and post-injection SIAQ scores were high (range: 5.8–10.0 and 7.1–10.0, respectively) across both devices, sub-studies, and timepoints. CONCLUSIONS: Both devices provide a safe and effective option for patients to self-administer bimekizumab. Furthermore, patients reported a positive self-injection experience. TRIAL REGISTRATION: NCT03766685 J Drugs Dermatol. 2022;21(2):162-171. doi:10.36849/JDD.6274THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.

Rhinoceros-related delayed traumatic diaphragmatic rupture.

Animal-related injuries should be analyzed based on the behavior and anatomy of the attacking animal. Rhinoceros-related injuries in humans are extremely rare. Hereby, we report a life-threatening traumatic diaphragmatic hernia in a woman who presented three years after a rhinoceros gored her chest. A 47-year-old lady presented with abdominal pain, bilious vomiting and obstipation of one-day duration. She had recurrent attacks of colicky abdominal pain for a week before that. The patient gave the history of being admitted to the ICU three years before, after being gored by a rhinoceros into her chest while working as a veterinary assistant in the zoo. On examination, the abdomen was distended but soft and lax. Bowel sounds were exaggerated. Abdominal x-rays showed multiple air-fluid levels. A gastrographin follow through study hold up in the small bowel and did not reach the colon after seven hours. Abdominal and chest CT scan showed the splenic colonic flexure to be located in the left chest through a left diaphragmatic hernia. Urgent laparotomy showed a healthy splenic flexure of the colon that herniated through a 4 cm postero-lateral defect in the left diaphragm. The colon was reduced, and the defect was repaired with non-absorbable sutures. Postoperative recovery was smooth. The patient was discharged home 10 days after the surgery. Rhinoceros-related injuries in humans are extremely rare. Life-threatening traumatic diaphragmatic herniation may be delayed for few years. High index of suspicion is needed for its diagnosis.

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Single-Dose, Phase III, Non-Inferiority Study Comparing PrabotulinumtoxinA and OnabotulinumtoxinA for the Treatment of Moderate to Severe Glabellar Lines in Adult Patients.

BACKGROUND: PrabotulinumtoxinA is a 900-kDa botulinum toxin type A produced by Clostridium botulinum. OBJECTIVES: The authors sought to investigate the efficacy and safety of prabotulinumtoxinA compared to onabotulinumtoxinA and placebo for the treatment of glabellar lines. METHODS: This was a 150-day, multicenter, double-blind, controlled, single-dose Phase III study. Adult patients (n = 540) with moderate to severe glabellar lines at maximum frown as assessed by the investigator on the validated 4-point Glabellar Line Scale (0 = no lines, 1 = mild, 2 = moderate, 3 = severe), who also felt that their glabellar lines had an important psychological impact, were enrolled. Patients were randomized 5:5:1 to receive a single treatment (0.1 mL injected into each of 5 glabellar sites) of 20 U prabotulinumtoxinA (n = 245), 20 U onabotulinumtoxinA (n = 246), or placebo (n = 49). The primary efficacy endpoint was the proportion of responders (patients with a Glabellar Line Scale score of 0 or 1 at maximum frown by investigator assessment) on day 30. RESULTS: Responder rates for the primary efficacy endpoint were 87.2%, 82.8%, and 4.2% in the prabotulinumtoxinA, onabotulinumtoxinA, and placebo groups, respectively. The absolute difference between prabotulinumtoxinA and onabotulinumtoxinA groups was 4.4% (95% confidence interval [-1.9, 10.8]). Given that the lower bound of the 95% confidence interval for the difference was less than -10.0%, noninferiority of prabotulinumtoxinA vs onabotulinumtoxinA was concluded. Five patients (3 prabotulinumtoxinA, 1.2%; 1 onabotulinumtoxinA, 0.4%; 1 placebo, 2.0%) experienced serious adverse events, none of which were study drug related. CONCLUSIONS: A single treatment of 20 U prabotulinumtoxinA was safe and effective and noninferior to 20 U onabotulinumtoxinA for the treatment of moderate to severe glabellar lines.

Using Probability for Pathological Complete Response (pCR) as a Decision Support Marker for Neoadjuvant Chemotherapy in HER2 Negative Breast Cancer Patients - a Survey Among Physicians.

BACKGROUND: In women with early breast cancer, a pathological complete response (pCR) after neoadjuvant chemotherapy is reported to be associated with an improvement of the survival. The aim of this survey among physicians was to investigate whether the probability of achieving pCR in patients with a hormone receptor-positive, HER2-negative disease encourages physicians to recommend neoadjuvant chemotherapy. METHODS: The study was conducted via an online survey that was sent to 493 physicians, who were either known as members of national guideline committees, heads of breast cancer centers, being high recruiters in clinical trials or leading a private practice. Participants were asked about a specific case that should resemble patients for whom it is unclear, whether they should be treated with chemotherapy. RESULTS: 113 (24.5%) physicians participated at the survey, out of which 96.5% had a work experience of more than 10 years and 94.7% were board certified in their specialty. A total of 84.1% would consider pCR for a decision concerning neoadjuvant chemotherapy. With regard to the pCR probability, 2.7 and 10.6% of the participants demanded at least a pCR rate of 5 and 10%, respectively, while 25.7% were satisfied with 20% probability, and another 25.7% with a pCR rate of 30%. CONCLUSIONS: The vast majority of the long-term experienced physicians would embrace the implementation of a further method such as the prediction of pCR probability in clinical routine to support decision making regarding the necessity of neoadjuvant chemotherapy. The cut-off of around 30% pCR probability seems to be a realizable rate to distinguish patient groups.

S3-Leitlinie zur Therapie der Psoriasis vulgaris Update - Kurzfassung Teil 2 - Besondere Patientengruppen und spezielle Behandlungssituationen.

Die deutsche Psoriasis-Leitlinie zur Behandlung der Psoriasis vulgaris wurde unter Verwendung der GRADE-Methodik aktualisiert. Die Leitlinie wurde aufbauend auf einer systematischen Literaturrecherche (letzte Update-Recherche am 01.12.2016) entwickelt und in einem formalen Konsensus- und Freigabeverfahren verabschiedet. Der zweite Teil dieser Kurzfassung stellt die Empfehlungen zum Tuberkulose-Screening vor und unter Therapie, zur Therapieauswahl bei Kinderwunsch, Schwangerschaft und Stillzeit, vorliegender Gelenkbeteiligung sowie zum Umgang mit Impfungen dar. Zudem werden die Empfehlungen zur Therapieauswahl bei Komorbidität mit Hepatitis und Leberfunktionseinschränkungen, HIV, Tumorerkrankungen, Erkrankungen aus dem neurologischen und psychiatrischen Formenkreis, koronarer Herzkrankheit und Herzinsuffizienz, Diabetes mellitus, Niereninsuffizienz sowie chronisch entzündlicher Darmerkrankung dargestellt.

S3 Guideline for the treatment of psoriasis vulgaris, update - Short version part 2 - Special patient populations and treatment situations.

The German guideline for the treatment of psoriasis vulgaris was updated using GRADE methodology. The guideline is based on a systematic literature review completed on December 1, 2016, and on a formal consensus and approval process. The second part of this short version of the guideline covers the following special patient populations and treatment situations: tuberculosis screening before and during psoriasis treatment, choice of psoriasis treatment for individuals wishing to have children, as well as during pregnancy and breast-feeding, and patients with joint involvement and vaccinations. In addition, recommendations on the choice of treatment are presented for patients with the following comorbidities: hepatitis and other hepatic impairment, HIV, malignancies, neurological and psychiatric disorders, ischemic heart disease and congestive heart failure, diabetes mellitus, renal impairment and inflammatory bowel disease.

S3 Guideline for the treatment of psoriasis vulgaris, update - Short version part 1 - Systemic treatment.

The German guideline for the treatment of psoriasis vulgaris was updated using GRADE methodology. The guideline is based on a systematic literature review completed on December 1, 2016, and on a formal consensus and approval process. The first section of this short version of the guideline covers systemic treatment options considered relevant by the expert panel and approved in Germany at the time of the consensus conference (acitretin, adalimumab, apremilast, cyclosporine, etanercept, fumaric acid esters, infliximab, methotrexate, secukinumab and ustekinumab). Detailed information is provided on the management and monitoring of the included treatment options.

An 18-Month Follow-up, Randomized Comparison of Effectiveness and Safety of Two Hyaluronic Acid Fillers for Treatment of Moderate Nasolabial Folds.

BACKGROUND: Hyaluronic acid (HA) filler injection is a popular nonsurgical aesthetic procedure. OBJECTIVE: To compare the effectiveness and safety of 2 hyaluronic acid fillers (HAEC and HARES) for treatment of moderate nasolabial folds (NLFs). MATERIALS AND METHODS: This was an evaluator- and subject-blinded split-face study. HAEC or HARES was randomly assigned to the left or right NLF at baseline. Retreatment was performed after 9 months; follow-up extended to 18 months after baseline (9 months after retreatment). Effectiveness assessments included the Wrinkle Severity Rating Scale (WSRS) and subject preference. Safety assessments included adverse events (AEs) and local tolerability symptoms recorded by subjects during 3 weeks after treatment. RESULTS: HAEC was noninferior to HARES measured as mean change from baseline in WSRS score at 6 months. Mean WSRS score change from baseline was similar between products up to 18 months. A majority of subjects (>70%) were still responders at 18 months (after retreatment at 9 months). The volume required at retreatment was approximately two-thirds of that at baseline. There was no difference in subject preference between products. Both fillers were well tolerated and associated with few treatment-related AEs. CONCLUSION: HAEC and HARES were effective and well tolerated for treatment of moderate NLFs.