Psoriasis improvements and inflammatory biomarker normalization with secukinumab: the randomized ObePso-S study.

BACKGROUND: The IL-17A inhibitor secukinumab has demonstrated consistent efficacy and safety in patients with moderate-to-severe plaque psoriasis, with normalization of molecular and histopathologic psoriasis markers. OBJECTIVE: To investigate treatment effects of secukinumab on clinical signs and psoriatic inflammation markers over 52 weeks in patients with psoriasis. METHODS: In the ObePso-S study (NCT03055494), patients with psoriasis were randomized 2:1 to receive secukinumab 300 mg (n = 54) or placebo (n = 28), stratified by body weight (<90 or ≥90 kg), for 52 weeks. At Week 12, patients receiving placebo were switched to secukinumab. Psoriasis Area and Severity Index improvement of 90% (PASI90) and Investigator's Global Assessment modified 2011 0/1 responses were assessed at Weeks 12 and 52. Immunohistochemistry for keratin 16 (K16) and gene expression profiles were evaluated in lesional and non-lesional skin biopsies collected at baseline, Week 12, and Week 52. RESULTS: Of patients receiving secukinumab, 55.8% and 59.6% achieved PASI90 at Weeks 12 and 52, respectively. K16 was absent in 93.1% of Week 12 PASI90 responders and 93.6% of Week 52 PASI90 responders, which mirrored the down-regulated expression of psoriatic inflammation. Week 52 PASI90 non-responders experienced regression of clinical and inflammatory marker responses toward baseline levels. Lower control of inflammatory gene expression at Week 12 was associated with suboptimal clinical responses at Week 52. CONCLUSION: Sustained clinical responses with secukinumab were associated with rapid and sustained normalization of K16 and inflammatory gene expression in most patients. Molecular anti-inflammatory effects of secukinumab at Week 12 were associated with clinical responses at Week 52.

Building Moral Resiliency Through the Nurse Education and Support Team Initiative.

BACKGROUND: Findings from 3 nurse-led research studies conducted in a large pediatric institution resulted in a call to action to support intensive and progressive care nurses experiencing moral and ethical challenges. OBJECTIVE: To evaluate the feasibility of and satisfaction with implementation of a Nurse Education and Support Team (NEST) coach role. METHODS: An interdisciplinary work group identified solutions for just-in-time support, including a new NEST coach role. This role was implemented in January 2017 to provide peer-to-peer support for nurses. The NEST coaches provide coverage 5 days per week in 4 intensive care units and 1 progressive care unit. Feasibility of the role was evaluated by assessing the number, type, length, and outcome of NEST coach consultations. Staff satisfaction was evaluated 6 months and 1.5 years after implementation. RESULTS: A total of 6262 NEST coach consultations occurred across the units from January 2017 through November 2019. At both evaluation periods, more than 85% of respondents indicated that they were satisfied with their interactions with the NEST coach and nearly 80% indicated that they would seek consultation again. CONCLUSIONS: Pediatric intensive and progressive care nurses experience many challenges in their practice environments. The innovative NEST coach role enabled access to just-in-time support and guidance through morally and ethically challenging situations. As evidenced by the number of consultations and the positive staff response, intensive and progressive care nurses have embraced and integrated the NEST coach role into their culture and practice.

A Randomized Placebo-Controlled Trial of Secukinumab on Aortic Vascular Inflammation in Moderate-to-Severe Plaque Psoriasis (VIP-S).

Psoriasis, a chronic immune-mediated disease, is associated with an increased risk of cardiovascular events and mortality. Secukinumab selectively neutralizes IL-17A and has reported high efficacy with a favorable safety profile in various psoriatic disease manifestations. Subsequent to the 12-week randomized, placebo-controlled, double-blind treatment period, patients with moderate-to-severe psoriasis received secukinumab for 40 weeks. Vascular inflammation using 18F-2-fluorodeoxyglucose-positron emission tomography/computed tomography imaging and blood-based cardiometabolic was assessed at week 0, 12, and 52. The difference in change in aortic inflammation from baseline to week 12 for secukinumab (n = 46) versus placebo (n = 45) was -0.053 (95% confidence interval = -0.169 to 0.064; P= 0.37). Small increases in total cholesterol, low-density lipoprotein, and low-density lipoprotein particles, but no changes in markers of inflammation, adiposity, insulin resistance, or predictors of diabetes, were observed with secukinumab treatment compared with placebo. At week 52, reductions in TNF-α (P= 0.0063) and ferritin (P= 0.0354), and an increase in fetuin-A (P= 0.0024), were observed with secukinumab treatment compared with baseline. No significant changes in aortic inflammation or markers of advanced lipoprotein characterization, adiposity, or insulin resistance were observed with secukinumab treatment compared with baseline. Secukinumab exhibited a neutral impact on aortic vascular inflammation and biomarkers of cardiometabolic disease after 52 weeks of treatment.

The effect of secukinumab on moderate-to-severe scalp psoriasis: Results of a 24-week, randomized, double-blind, placebo-controlled phase 3b study.

BACKGROUND: Moderate-to-severe scalp psoriasis has not been evaluated in prospective trials of patients without moderate-to-severe body psoriasis. OBJECTIVE: Evaluate the efficacy and safety of secukinumab in moderate-to-severe scalp psoriasis. METHODS: In this 24-week, double-blind, phase 3b study, 102 patients were randomized 1:1 to subcutaneous secukinumab 300 mg or placebo at baseline, weeks 1, 2, and 3, and then every 4 weeks from week 4 to 20. The primary efficacy variable was 90% improvement of Psoriasis Scalp Severity Index (PSSI 90) score from baseline to week 12. RESULTS: At week 12, PSSI 90 (secukinumab 300 mg vs placebo, 52.9% vs 2.0%) and Investigator's Global Assessment modified 2011 scalp responses of 0 or 1 (secukinumab 300 mg vs placebo, 56.9% vs 5.9%) were significantly greater with secukinumab 300 mg than placebo (P < .001 for both). In addition, significantly more patients achieved complete clearance of scalp psoriasis at week 12 with secukinumab 300 mg than placebo (35.3% vs 0%; P < .001). The median time to 50% reduction in PSSI score was 3.29 weeks with secukinumab 300 mg. The safety profile of secukinumab was consistent with previous phase 3 studies. LIMITATIONS: There was no active comparator arm. CONCLUSION: Secukinumab is efficacious and well-tolerated for patients with extensive moderate-to-severe scalp psoriasis.

Switching From Donepezil to Rivastigmine Is Well Tolerated: Results of an Open-Label Safety and Tolerability Study.

Background: Transitioning patients between cholinesterase inhibitors was thought to require a washout period to avoid cholinergic toxicity; however, evidence suggests that abrupt discontinuation of donepezil may lead to cognitive decline. We evaluated the safety and tolerability of an immediate switch from donepezil to rivastigmine.Method: This is an analysis of the safety and tolerability data from the first 28 days of an open-label, multicenter, prospective trial, conducted from August 2002 to August 2003, in which patients satisfying NINCDS-ADRDA criteria for probable Alzheimer's disease were administered rivastigmine 1.5 mg b.i.d. within 24 to 36 hours of donepezil discontinuation. Results are compared with adverse event rates from a retrospective analysis of a pivotal, placebo-controlled trial examining patients not previously treated with a cholinesterase inhibitor.Results: Fifty-eight of 61 patients completed the first 28 days, with no suspected drug-related discontinuations during this period. Incidence of overall gastrointestinal adverse events at day 7 was 8.2%, and at day 28 was 11.5%. The corresponding rate for rivastigmine-treated patients in the retrospective analysis of the pivotal trial for day 7 was 3.3%.Conclusion: These study results suggest that transitioning patients from donepezil to rivastigmine without a washout period is safe and well tolerated.

Therapeutic boundary issues in working with childhood sexual-abuse survivors.

The article describes a study of therapists involved in treating survivors of childhood sexual abuse. The authors focus on what induces participants to change their usual therapeutic boundaries. Through qualitative research utilizing extensive interviews, written questionnaires, and a focus-group discussion, the authors gathered information from therapists related to situations that influence them to change their own boundaries. Emergent themes are discussed and the information is integrated with the authors' experience of supervision and psychotherapy. Concern for client safety is the commonly recurrent issue that pushes therapists to change their boundaries. Other intense feelings, such as resentment of the client, worry about the client's feelings, a wish to connect and imbue hope are also strong influences. Self-disclosure boundaries of the therapist are challenged by the wish to balance power within the relationship. Supervision provides an opportunity to examine what influences therapists to make subtle boundary shifts before they become harmful boundary crossings.