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Introduction: Treating plaque psoriasis (PsO) with guselkumab (GUS) promotes skin clearance and is associated with improvements in health-related quality of life (HRQoL), anxiety, and depression. It is unclear whether improvements in patient-reported outcomes are due to resolution of skin symptoms or the direct result of GUS treatment. Methods: Two phase 3, placebo- and active-comparator-controlled studies randomized patients with moderate-to-severe PsO to GUS, placebo (crossing over to GUS at week 16), or adalimumab. Post hoc mediation analyses examined direct and indirect effects of GUS, versus adalimumab, on Dermatology Life Quality Index (DLQI) or Hospital Anxiety and Depression Scale (HADS) after adjusting for indirect effects mediated by skin clearance, evaluated via Psoriasis Area and Severity Index (PASI), to determine the direct effect of GUS on dermatology HRQoL, depression, and anxiety. Results: Compared with adalimumab, the natural direct effect (NDE) of GUS on change in DLQI from baseline was − 2.04 (P < 0.001), using PASI improvement as a mediator, indicating 89.2% of the total treatment effect was due to direct effects of GUS; using PASI 90 as a mediator, NDE of GUS was − 1.43 (P < 0.001), with 62.2% of the total treatment effect attributed to direct effects of GUS. Compared with adalimumab, 25.5% of change in HADS anxiety score was mediated through PASI improvement (NDE − 0.74; P = 0.002), indicating 74.5% of the total effect was independent of PASI improvement. Similarly, 24% of treatment effect was mediated through PASI 90 (NDE − 0.76; P = 0.002). Comparable proportions of the total improvement in HADS depression scores were due to direct and indirect effects of GUS mediated through PASI improvement (direct, 50.2%; indirect, 49.8%) or PASI 90 (direct, 59.5%; indirect, 40.5%). Conclusions: GUS-mediated improvements in anxiety, depression, and overall HRQoL are not solely mediated by resolution of PsO signs, suggesting GUS use has a potential direct effect on anxiety and depression. [ABSTRACT FROM AUTHOR]

Introduction: Secukinumab has demonstrated sustained long-term efficacy with a favourable safety profile in various manifestations of psoriatic disease. We investigated effectiveness and safety of secukinumab, other biologics and conventional systemic therapies in patients with chronic plaque psoriasis in a real-world setting. Methods: REALIA was a non-interventional, multicentre, prospective, parallel group study. Eligible patients were ≥ 18 years old with chronic plaque psoriasis commencing a new treatment with a biologic agent or conventional systemic therapies. Results: At baseline, 541 patients were divided into three cohorts based on treatment initiated: conventional systemics (173), secukinumab (184) and other biologics (184). A significantly higher proportion of patients achieved almost clear to clear skin based on physician's judgement in secukinumab versus conventional systemics at month 3 (64.7% versus 22.8%, P < 0.001) and month 6 (61.8% versus 20.8%, P < 0.001). At month 12, clear to almost clear skin was achieved by 52.1% of the patients in secukinumab versus 35.8% in conventional systemics (P = 0.066). The proportion of patients achieving Psoriasis Area Severity Index (PASI) 90 on conventional systemics, secukinumab and other biologics was 18.8%, 59.7% and 40.0% at month 3 and 35.3%, 60.8% and 50.0% at month 12, respectively. Secukinumab patients showed significantly higher change in PASI total score from baseline versus conventional systemics at month 3 {least squares [LS] mean [standard error (SE)]: −14.49 [0.648] versus −8.48 [1.149], P < 0.001} and numerically higher [LS mean (SE): −13.60 (0.475) versus −10.84 (1.733), P = 0.122] at month 12. The proportion of patients with Dermatology Life Quality Index 0/1 score on conventional systemics, secukinumab and other biologics was 22.6%, 65.0% and 41.6% at month 3 and 32.0%, 63.5% and 41.3% at month 12, respectively. Safety profile was comparable across cohorts. Conclusions: Secukinumab is effective and well tolerated in patients with chronic plaque psoriasis in a real-world setting in an Asia-Pacific and Middle East population, and these results are in agreement with clinical outcomes of secukinumab reported in randomised clinical trials. Trial registration number: 170803-001645. [ABSTRACT FROM AUTHOR]

Background: Guselkumab effectively treats moderate-to-severe psoriasis. Objectives: Results of continuous guselkumab treatment through 4 years from VOYAGE 2 are presented. Methods: At baseline, 992 patients were randomized to receive guselkumab 100 mg every 8 weeks, placebo, or adalimumab 40 mg every 2 weeks. Placebo-treated patients crossed over to guselkumab at week 16. Weeks 28–76 incorporated randomized withdrawal, and all patients received open-label guselkumab through to week 204. Efficacy was analyzed using pre-specified treatment failure rules (patients were considered nonresponders after discontinuing due to lack of efficacy, worsening of psoriasis, or use of a prohibited treatment). There was no missing data imputation after treatment failure rules. Safety was analyzed through 4 years. Results: The proportions of guselkumab-treated patients who achieved and maintained designated clinical responses at weeks 100 and 204, respectively, were as follows: at least a 75% improvement in Psoriasis Area and Severity Index from baseline (PASI 75): 94.1% and 92.3%; PASI 90: 79.1% and 79.7%; PASI 100: 48.4% and 51.0%; Investigator's Global Assessment (IGA) score of 0/1: 83.1% and 81.9%; IGA score of 0: 52.7% and 52.7%; Dermatology Life Quality Index score of 0/1: 70.2% and 69.1%; Psoriasis Symptoms and Signs Diary (PSSD) symptom score of 0: 35.7% and 39.7%; PSSD sign score of 0: 22.0% and 27.2%; ≥ 5% improvement in Short Form-36 (SF-36) physical component score: 48.8% and 45.0%; ≥ 5% improvement in SF-36 mental component score: 45.1% and 43.2%; Hospital Anxiety and Depression Score (HADS)-anxiety score ≥ 8: 22.9% and 21.7%; and HADS-depression score ≥ 8: 16.6% and 21.0%. Similar findings were reported for the adalimumab → guselkumab group. No new safety signals were identified. Conclusions: High efficacy levels were maintained from week 100 through to week 204 with continuous guselkumab treatment, across multiple endpoints, in VOYAGE 2. Guselkumab was well tolerated. Clinical Trial Registration: NCT02207244. [ABSTRACT FROM AUTHOR]

Background: Health-related quality of life (HRQoL) may be markedly impaired in patients with moderate-to-severe psoriasis.Objectives: Our objectives were to compare improvements in Dermatology Life Quality Index (DLQI) and Psoriasis Symptoms and Signs Diary (PSSD) scores between patients receiving guselkumab compared with placebo or adalimumab and to correlate these improvements with skin clearance.Methods: Pooled phase III VOYAGE 1 and VOYAGE 2 data were evaluated through week 24. At baseline, patients were randomized to guselkumab 100 mg, placebo, or adalimumab 40 mg. At week 16, patients receiving placebo switched to guselkumab. Assessment measures included DLQI percent change from baseline, DLQI 0/1, DLQI minimal clinically important difference (MCID), individual domain scores, PSSD symptoms and signs score = 0, DLQI association with PSSD, Investigator's Global Assessment (IGA), and Psoriasis Area and Severity Index (PASI).Results: Significantly greater improvements from baseline DLQI were observed with guselkumab versus placebo (weeks 8 and 16) and versus adalimumab (week 24; p < 0.001). The proportion of patients achieving DLQI 0/1 ("no impact") at week 24 was higher with guselkumab than with adalimumab (58.9 vs. 40.2%; p < 0.001), and more patients attained a ≥ 4-point reduction in DLQI (MCID) at this timepoint (p < 0.001). Changes in individual DLQI domains were significantly greater for patients receiving guselkumab than for those receiving adalimumab, and among patients with individual baseline domain scores = 3 or 6 (severest impact), more guselkumab recipients than those receiving adalimumab achieved a score = 0 across all domains at week 24. DLQI 0/1 scores were associated with a PSSD symptom or sign score = 0 (no impact) and greater improvement of PASI and IGA (week 24).Conclusions: Pooled VOYAGE 1/VOYAGE 2 data demonstrated that guselkumab was superior to adalimumab in improving HRQoL, which was associated with greater skin clearance.Clinical Trial Registration: NCT02207231 and NCT02207244. [ABSTRACT FROM AUTHOR]

Central venous catheters that have been in place for a long time can become fixed to the vein wall, making them impossible to pull out. Leaving them in situ is undesirable because of the risk that they could act as a nidus for thrombosis. Moreover, inserting new catheters alongside the old ones might compromise flow in the superior vena cava, further predisposing to thrombosis. Surgical removal is likewise undesirable, as this would necessitate thoracotomy with the attendant risks. We describe a novel technique, which we were able to use to remove retained long-term hemodialysis catheters in a patient who needed new catheters and who would have been a high-risk candidate for surgery. The right internal jugular vein was punctured adjacent to the site of insertion and a guide wire was used to form a snare, which was passed around the catheters and used to saw through the fibrous attachments to the vein wall. The midsection of one catheter could not be freed but the snare was used to cut off the proximal and distal ends, which could then be removed, the latter via the femoral vein. New catheters were then inserted via the left internal jugular vein. This technique enabled successful catheter extraction and replacement in a patient who would have been a poor candidate for cardiothoracic surgery. [ABSTRACT FROM AUTHOR]

Chylothorax carries significant mortality and morbidity. Patients with high-output chylothorax have traditionally been managed by surgical treatment if nonoperative management has proved unsuccessful. Newer, more recent percutaneous techniques used to treat chylothorax are safer and less invasive than surgery. We present three cases that have been successfully managed using these percutaneous techniques. [ABSTRACT FROM AUTHOR]

Objectives: To study the change in outcome for patients admitted to an intensive care unit following the establishment of a team of resident medical staff and a change from an "open" to a "closed" organisational format.Design: Database review of prospectively collected data.Setting: Intensive care unit of a postgraduate teaching hospital.Subjects: 1134 admissions to the intensive care unit over a 3-year period, of whom 476 (42%) followed elective surgery.Main Outcome Measure: Hospital mortality corrected for illness severity by using the APACHE II scoring system.Results: Crude hospital mortality fell from 28% before the changes to 20% afterwards (P = 0.01). With correction for case-mix factors, the probability of death after the changes was reduced by almost half (OR 0.51; CI 0.32, 0.82, P = 0.005).Conclusion: A "closed" format of organisation of the delivery of care may result in improved outcomes for patients admitted to intensive care units. [ABSTRACT FROM AUTHOR]