Evaluation of the efficacy and safety of amustaline/glutathione pathogen-reduced RBCs in complex cardiac surgery: the Red Cell Pathogen Inactivation (ReCePI) study-protocol for a phase 3, randomized, controlled trial.

BACKGROUND: Red blood cell (RBC) transfusion is a critical supportive therapy in cardiovascular surgery (CVS). Donor selection and testing have reduced the risk of transfusion-transmitted infections; however, risks remain from bacteria, emerging viruses, pathogens for which testing is not performed and from residual donor leukocytes. Amustaline (S-303)/glutathione (GSH) treatment pathogen reduction technology is designed to inactivate a broad spectrum of infectious agents and leukocytes in RBC concentrates. The ReCePI study is a Phase 3 clinical trial designed to evaluate the efficacy and safety of pathogen-reduced RBCs transfused for acute anemia in CVS compared to conventional RBCs, and to assess the clinical significance of treatment-emergent RBC antibodies. METHODS: ReCePI is a prospective, multicenter, randomized, double-blinded, active-controlled, parallel-design, non-inferiority study. Eligible subjects will be randomized up to 7 days before surgery to receive either leukoreduced Test (pathogen reduced) or Control (conventional) RBCs from surgery up to day 7 post-surgery. The primary efficacy endpoint is the proportion of patients transfused with at least one study transfusion with an acute kidney injury (AKI) diagnosis defined as any increased serum creatinine (sCr) level ≥ 0.3 mg/dL (or 26.5 µmol/L) from pre-surgery baseline within 48 ± 4 h of the end of surgery. The primary safety endpoints are the proportion of patients with any treatment-emergent adverse events (TEAEs) related to study RBC transfusion through 28 days, and the proportion of patients with treatment-emergent antibodies with confirmed specificity to pathogen-reduced RBCs through 75 days after the last study transfusion. With ≥ 292 evaluable, transfused patients (> 146 per arm), the study has 80% power to demonstrate non-inferiority, defined as a Test group AKI incidence increase of no more than 50% of the Control group rate, assuming a Control incidence of 30%. DISCUSSION: RBCs are transfused to prevent tissue hypoxia caused by surgery-induced bleeding and anemia. AKI is a sensitive indicator of renal hypoxia and a novel endpoint for assessing RBC efficacy. The ReCePI study is intended to demonstrate the non-inferiority of pathogen-reduced RBCs to conventional RBCs in the support of renal tissue oxygenation due to acute anemia and to characterize the incidence of treatment-related antibodies to RBCs.

On the Biochemistry and Biophysics of Living Cell Formation.

A description is given of a sequence of events which would have led to the appearance of the organic compounds and living cells present on Earth, one of which is human cells. The evolutionary events involved are proposed as having taken place in phosphate ion-dominated aqueous pools formed in regions associated with volcanoes. The mechanism involved the unique molecular structure variations and chemical properties of polyphosphoric acid and compounds of this acid producing urea as the first organic compound formed on Earth and derivatives of urea giving rise to DNA and RNA. The occurrence of the process in present times is considered possible.

Lifestyle behaviors among Canadian nurses working night shifts in the COVID-19 era: a pilot study.

Abstract: Working night shifts has been associated with negative mental health consequences such as depression, anxiety, and sleep problems. The objectives of this study were to determine the lifestyle behaviors (prevalence of nicotine, caffeine, cannabis, sleep-promoting medication, and alcohol use) and the association between job stress, sleep quality, anxiety, and depression among registered nurses working night shifts in the Canadian province of Saskatchewan in the COVID-19 era. Twenty-two registered nurses ranging from ages 25-65 that work permanent or rotating night shifts participated in an online survey from April 11th to July 15th, 2022. The results showed a strong positive association between sleep disturbance, and depression r (19) = 0.50, [p = 0.029, 95% CI, 0.06, 0.78]. A positive correlation was found between higher levels of reported anxiety and sleep disturbance r (19) = 0.69, [p = 0.001, 95% CI, 0.34, 0.87]. There was a positive correlation between depression and occupational exhaustion r (17) = 0.56, [p = 0.021, 95% CI, 0.10, 0.82]. Anxiety was significantly related to occupational exhaustion r (17) = 0.65, [p = 0.005, 95% CI, 0.24, 0.86] and depersonalization r (17) = 0.52, [p = 0.005, 95% CI, 0.06, 0.80], but not significantly related to personal accomplishment r (17) = -0.34, [p = 0.185, 95% CI, -0.70, 0.17]. In conclusion, a sample of Canadian nurses working night shifts in the province of Saskatchewan during the COVID-19 pandemic showed a significant positive relationship among sleep disturbance, anxiety, and depression. Furthermore, most nurses reported using at least one or more of the following substances: sleep-promoting medication, nicotine, alcohol, and cannabis.

Perioperative outcomes of women with and without class III obesity undergoing hysterectomy for endometrioid endometrial cancer: A population-based study.

OBJECTIVE: Population-based data on perioperative complications among women with endometrial cancer and severe obesity are lacking. We evaluated 30-day complication rates among women with and without class III obesity (body mass index ≥ 40 kg/m2) undergoing primary surgical management for endometrioid endometrial cancer (EEC), and how outcomes differed according to surgical approach (open vs. minimally invasive). METHODS: We performed a retrospective population-based cohort study of women with EEC undergoing hysterectomy in Ontario, Canada, between 2006 and 2015. We evaluated perioperative complications in the whole cohort, and in a 1:1 matched analysis using hard and propensity score matching to ensure similar distributions of patient, tumour, provider and institution-level factors between women with and without class III obesity (identified using a surgical billing code). The primary outcome of interest was the 30-day perioperative complication rate. RESULTS: 12,112 women met inclusion criteria; 2697 (22.3%) had class III obesity. We matched 2320 (86%) women with class III obesity to those without. The composite complication rate was significantly higher among women with class III obesity (23.2% vs. 18.4%, standardized mean difference [SMD] = 0.12), primarily due to wound infection/disruption (12.1% vs. 6.2%). There was no difference in outcomes for women with and without class III obesity when a minimally invasive approach was used. CONCLUSIONS: Wound infection/disruption was increased for women with class III obesity compared to women without. Otherwise, perioperative complications were similar between the matched pairs. When minimally invasive approaches were used, women with class III obesity had a similar risk of complications as women without obesity.

Human body cell membranes and antigen control.

The variables involved in the initiation and operation of the human immune system are considered. It is shown that the number of variations associated with disease and other detrimental conditions exceeds the number of lymphocyte cells available for control of these conditions. It is proposed that the immune system functions by changes in the ionic strength of metabolic fluids which in turn control the formation and stability of cell membranes. The application of these conditions to the control of bacterial, virus particle and other antigens is detailed. Observations supporting the proposals are presented.

Changes in auditory thalamus neural firing patterns after acoustic trauma in rats.

Tinnitus is an abnormal phantom perception associated with cochlear trauma, and is thought to cause changes in the rates and patterns of firing neurons in the central auditory pathway. Recent studies have suggested a key role for the auditory thalamus, the medial geniculate nucleus (MGN), in the generation of tinnitus as it may serve a gating function for information en route to cortex. Dysfunctional gating would lead to abnormal activity reaching cortex and hence inappropriate perception, tinnitus, would occur. In this study we compared spontaneous MGN firing rates and burst firing parameters in Wistar rats with and without behavioural evidence of tinnitus following an acoustic trauma. Data were also compared with animals subjected to sham surgery and at an early time-point (2 weeks) after acoustic trauma. Acoustic trauma resulted in a temporary but not a permanent threshold loss and no differences were found in spontaneous firing rate between any of the groups. However, acoustic trauma, whether resulting in tinnitus or not, was accompanied by a significant decrease in the percentage of neurons showing burst firing. In bursting neurons, the number of spikes occurring in a burst and the number of burst per minutes was also significantly reduced compared to the sham group. Our results show that in our rat model without permanent threshold loss, elevated spontaneous firing rates are not associated with acoustic trauma and/or tinnitus and that burst firing parameters are associated with acoustic trauma but are not a neural signature for tinnitus.

Measurement of rivaroxaban concentrations demonstrates lack of clinical utility of a PT, dPT and APTT test in estimating levels.

INTRODUCTION: Rivaroxaban concentrations were measured in 127 inpatient samples using an HPLC-MS/MS assay. METHODS: We compared this measurement with a calibrated anti-Xa assay and performed PT, aPTT and dilute PT tests to assess the value of clot-based assays in clinical decision-making. RESULTS: The correlation between the anti-Xa assay and the HPLC-MS/MS at therapeutic concentrations was strong (R2  = 0.98). The PT, RecombiPlasTin 2G, and aPTT, Actin FS, showed a linear dose-response but poor correlation (R2  = 0.32 and 0.44, respectively) and at dilutions of 1 in 150 to 1 in 750 the dilute PT assay also showed poor correlation with rivaroxaban concentrations measured by specific assays. A normal PT or aPTT alone did not identify a likely safe rivaroxaban concentration to allow surgery or invasive procedures, but the combination of normal PT and aPTT identified a group of patients with rivaroxaban levels less than 90 ng/mL. Combined normal PT and aPTT had specificity and sensitivity of 0.97 (95% CI 0.92-0.99) and 0.37 (95% CI 0.1-0.74) for a rivaroxaban concentration < 32 ng/mL. CONCLUSIONS: The PT and aPTT show poor correlation with rivaroxaban levels measured by calibrated anti-Xa and HPLC-MS/MS assays. A normal combined PT and APTT identified low rivaroxaban levels with high specificity but lacked sensitivity. The dPT assay at several dilutions could not be used to quantify rivaroxaban in clinical samples. The utility of these PT, aPTT and dilute PT assays in a clinical setting is very limited, and results generated must be interpreted with caution.

Metabolic iodine and tumours.

PURPOSE: Purpose of the work is to highlight a possible connection between metabolic iodine and natural tumour control. METHOD: Method adopted is to use information available in the literature. RESULT: Result indicated a means of the purpose being attained. CONCLUSION: Conclusion drawn is that a tumour control method derives from the relationship studied.

Surgery for diverticular disease results in a higher hernia rate compared to colorectal cancer: a population-based study from Ontario, Canada.

BACKGROUND: Incisional hernias are a well described complication of abdominal surgery. Previous studies identified malignancy and diverticular disease as risk factors. We compared incisional hernia rates between colon resection for colorectal cancer (CRC) and diverticular disease (DD). STUDY DESIGN: We performed a retrospective, population-based, matched cohort study. Provincial databases were linked through the Institute for Clinical Evaluative Sciences. These databases include all patients registered under the universal Ontario Health Insurance Plan. Patients aged 18-105 undergoing open colon resection, without ostomy formation between April 1, 2002 and March 31, 2009, were included. We excluded those with previous surgery, hernia, obstruction, and perforation. The primary outcomes were surgery for hernia repair, or diagnosis of hernia in clinic. RESULTS: We identified 4660 cases of DD. These were matched 2:1 by age and gender to 8933 patients with CRC for a total of 13,593. At 5 years, incisional hernias occurred in 8.3% of patients in the CRC cohort, versus 13.1% of those undergoing surgery for DD. After adjusting for important confounders (comorbidity score, wound infection, age, diabetes, prednisone and chemotherapy), hernias were still more likely in patients with DD [HR 1.58, 95% Confidence Interval (CI) 1.43-1.76, P < 0.001]. The only significant covariate was wound infection (HR 1.63, 95% CI 1.43-1.87, P < 0.001). CONCLUSION: Our study found that incisional hernias occur more commonly in patients with DD than CRC.

Proposed biochemistry of Parkinson's and Alzheimer's diseases.

The formation of brain compounds linked to Parkinson's and Alzheimer's brain diseases are described. Metabolic mechanisms involved in the control of reacting biochemicals are detailed. Relationships are established between the biochemical reactions, biochemical control mechanisms and the onset of Parkinson's, Alzheimer's. Treatments based on these relationships are proposed.

Metastatic ductal carcinoma of the breast to the thyroid gland diagnosed with fine needle aspiration: A case report with emphasis on morphologic and immunophenotypic features.

Metastases to the thyroid are uncommon [<0.2% of thyroid fine needle aspirations (FNA)]. Of metastases to the thyroid, breast carcinoma is relatively common. The diagnosis of metastasis to the thyroid has important therapeutic and prognostic implications. To our knowledge, a morphologic and immunophenotypic comparison of metastatic ductal carcinoma of the breast and primary thyroid carcinomas has not been reported. Here, we report the case of a 37-year-old female with a history of metastatic ductal carcinoma of the breast (modified Bloom-Richardson grade 2; ER+, PgR+, HER2+) diagnosed 6 years prior. She developed hoarseness, prompting a CT scan. Multiple thyroid nodules were found, including a 1.5 cm hypoechoic, solid, irregularly-shaped nodule. On FNA, cells were arranged singly and in crowded groups, varied in size and degree of pleomorphism, and exhibited rare nuclear grooves, inconspicuous nucleoli, and rare intracytoplasmic lumina with no nuclear pseudoinclusions or colloid (Figs. 1A and B). These findings raised the differential of papillary thyroid carcinoma (Fig. 1C), follicular neoplasm (Fig. 1D), medullary carcinoma (Fig. 1E), parathyroid (Fig. 1F), and metastatic breast carcinoma. Immunostaining for GATA-3 (+), ER (+), PAX-8 (-), and TTF-1 (-) was consistent with metastatic breast carcinoma (Fig. 2). We conclude that metastatic breast carcinoma to the thyroid may morphologically mimic primary thyroid carcinoma on FNA; a panel of immunomarkers, such as GATA-3, hormonal marker(s), PAX-8, and TTF-1, may be useful in some cases. GATA-3 immunostaining for metastatic breast carcinoma was helpful in our case and has not been previously reported in a thyroid metastasis sampled by FNA. Diagn. Cytopathol. 2016;44:530-534. © 2016 Wiley Periodicals, Inc.

Comparison of two leukocytapheresis protocols in a case of idiopathic hypereosinophilic syndrome.

BACKGROUND: Hypereosinophilic syndrome (HEOS) is rare, and the efficacy of leukocytapheresis in this context is unclear. We here report the successful treatment of a patient with idiopathic HEOS with four leukocytapheresis procedures using two protocols. CASE: A 4-year-old female presented with cardiac and respiratory dysfunction, and WBC of 225 K/µL with 96% eosinophils. Leukocytapheresis was started after initiation of methylprednisolone and hydroxyurea. She received two leukocytapheresis with polymorphonuclear cell (PMN) protocol, followed by initiation of imatinib therapy, then two leukocytapheresis with mononuclear cell (MNC) protocol. After the fourth leukocytapheresis, her WBC decreased to 69 K/µL with 82% eosinophils. She was discharged on hospital day 21 under stable condition with WBC of 22 K/µL with 86% eosinophils. WBC count and eosinophil percentage continued to decrease, and were 6.4 K/µL and 52% by 2 weeks and 3.9 K/µL and 4.9% by 3 months after discharge, respectively. FINDINGS: WBC and absolute eosinophil (aEO) counts decreased by an average of 29.0 and 30.4% per leukocytapheresis, respectively. Normalized to estimated blood volume, procedures with PMN and MNC protocols changed, on average, WBC by -10.7 and -12.1%, aEO by -10.4 and -13.4%, platelet by -8.1 and -19.2%, and fluid balance by -129 and -47 mL, respectively. CONCLUSION: Leukocytapheresis was effective in decreasing WBC and aEO counts in HEOS, with PMN and MNC protocols achieving similar reductions. However, PMN protocol resulted in greater negative fluid balance and MNC protocol resulted in greater platelet loss. J. Clin. Apheresis 31:481-489, 2016. © 2015 Wiley Periodicals, Inc.

Severing corneal nerves in one eye induces sympathetic loss of immune privilege and promotes rejection of future corneal allografts placed in either eye.

Less than 10% of corneal allografts undergo rejection even though HLA matching is not performed. However, second corneal transplants experience a threefold increase in rejection, which is not due to prior sensitization to histocompatibility antigens shared by the first and second transplants since corneal grafts are selected at random without histocompatibility matching. Using a mouse model of penetrating keratoplasty, we found that 50% of the initial corneal transplants survived, yet 100% of the subsequent corneal allografts (unrelated to the first graft) placed in the opposite eye underwent rejection. The severing of corneal nerves that occurs during surgery induced substance P (SP) secretion in both eyes, which disabled T regulatory cells that are required for allograft survival. Administration of an SP antagonist restored immune privilege and promoted graft survival. Thus, corneal surgery produces a sympathetic response that permanently abolishes immune privilege of subsequent corneal allografts, even those placed in the opposite eye and expressing a completely different array of foreign histocompatibility antigens from the first corneal graft.

Maintenance plasma exchange treatment for muscle specific kinase antibody positive myasthenia gravis patients.

BACKGROUND: Anti-muscle specific kinase antibody positive myasthenia gravis (MuSK MG) is often characterized by a relatively severe and progressive course, refractoriness to standard myasthenia gravis (MG) medications, and an increased risk of myasthenic crisis. We report here successful management of three MuSK MG patients using maintenance therapeutic plasma exchange (TPE) treatment for up to 4.5 years. MATERIALS: The study was a 5-year retrospective review of all MG patients treated with TPE between 2008 and 2013 at University of Michigan. Inclusion criteria of MuSK MG were positive for anti-MuSK antibodies and a diagnosis of MuSK MG by staff neurologists. Patient data included age, gender, diagnostic testing results, medications, and the dates and response to TPE treatments. RESULTS: A total of 153 MG patients underwent at least one course of TPE between 2008 and 2013. A total of 12 patients (7.8%) were positive for anti-MuSK antibodies. Patients were predominantly female (83.3%) and a median age of onset was 46-years old. Three MuSK MG patients were successfully managed with maintenance TPE. CONCLUSION: Maintenance TPE may be an effective option for MuSK MG patients. The key of successful maintenance treatment at our institution has been to tailor the TPE frequency for each individual, and to modify the treatment interval in conjunction with medical management.

A case of extravascular hemolysis with Tk-activation.

KEY CLINICAL MESSAGE: A 50-year-old female with ovarian cancer for 4 years presented with abdominal pain. She started antibiotics for possible infection, and developed extravascular hemolysis. All antigen detection tests were negative, but lectin panel suggested Tk-activation. Additional laboratory testing in conjunction with blood bank is essential to investigate rare cause of hemolysis.

The development of tumor cell characteristics.

The origins of the characteristics associated with cells from both benign and malignant (cancer) tumors are proposed. It is shown that these deviant cells can originate as the result of the failure of the normal biochemical control of the formation of DNA and RNA. This change in characteristics is proposed as occurring in regions of metabolism where fluid movement is altered becoming restricted and giving rise to both physical and chemical changes in the associated cells. Treatment of cancerous cells based on the compounds with properties related to the cellular compounds involved in the control of nucleic acids is proposed.

Hyperactivity following unilateral hearing loss in characterized cells in the inferior colliculus.

Hyperactivity (increased spontaneous firing rates) following cochlear trauma and hearing loss has been well documented in the inferior colliculus (IC). This hyperactivity is associated with frequency regions in the IC that are closely related to regions of peripheral hearing loss. In other auditory nuclei, notably cochlear nucleus, hyperactivity has been shown to be more prevalent in particular cell types but this has not been investigated in the IC. Single-neuron spontaneous firing rates were recorded in the IC of animals after acoustic trauma (10-kHz tone at 124dB for 2h) and in sham surgery controls. Single-neuron recordings were made 2weeks later. Evoked responses to ipsi- and contralateral sound were used for classification. Classifications were based on peri-stimulus time histograms, input-output functions, frequency response areas and monaural/binaural responses. Results showed increased spontaneous firing rates in the IC following trauma, in regions corresponding to the frequencies at which there was peripheral hearing loss (12-20kHz). Most response categories, with the exception of cells showing an onset response classification, showed a significantly increased average spontaneous firing rate. These data suggest that hyperactivity in the IC is not confined to a particular response type in contrast to findings in the cochlear nucleus. This may be the result of factors intrinsic to the IC, or because of convergent input to the IC from a range of other auditory structures.

Improvement in aspects of sleep with etanercept and optional adjunctive topical therapy in patients with moderate-to-severe psoriasis: results from the PRISTINE trial.

BACKGROUND: Impaired sleep in patients with moderate-to-severe psoriasis and improvement on therapy has not been widely studied. OBJECTIVE: Quantify baseline aspects of sleep and improvement in patients with psoriasis receiving etanercept (ETN) when allowed concomitant topical medications (PRISTINE study). METHODS: Patients with moderate-to-severe psoriasis were randomized to 50 mg ETN once weekly (QW/QW) or 50 mg ETN twice weekly (BIW/QW) for weeks 1-12, followed by 50 mg QW for weeks 13-24; a broad range of topical therapies were permitted during weeks 13-24. Sleep impairment was measured by the Medical Outcomes Study (MOS) sleep questionnaire Index II (population norm = 25.8; minimum clinically important difference = 5.1); quality of life (QoL) measures included Dermatology Life Quality Index (DLQI), EuroQoL 5 Dimension (EQ-5D) Utility Index and Visual Analogue Scale (VAS) and Functional Activity in Chronic Therapy-Fatigue (FACIT-Fatigue). ancova and Fisher's exact test or chi-squared tests were used for between-group testing. RESULTS: Mean baseline MOS-Sleep scores were 34.0 for both groups indicating impairment (N = 270; QW/QW n = 137; BIW/QW n = 133, approximately 64% had impaired sleep). At week 12 of treatment, MOS-Sleep scores improved to 30.8 and 30.1, and at week 24, to 28.4 and 28.2 respectively. Poor sleep was significantly associated with clinically important problems in EQ-5D utility, VAS and FACIT-Fatigue; sleep improvement was associated with improved EQ-5D utility and FACIT-Fatigue (P < 0.001). CONCLUSION: This study confirms that most patients with moderate-to-severe psoriasis have impaired sleep which is associated with impaired QoL. Treatment with etanercept significantly improved sleep, with most improvement occurring before a broad range of topicals were allowed. Sleep improvement was associated with improved QoL.

Verification of proton range, position, and intensity in IMPT with a 3D liquid scintillator detector system.

PURPOSE: Intensity-modulated proton therapy (IMPT) using spot scanned proton beams relies on the delivery of a large number of beamlets to shape the dose distribution in a highly conformal manner. The authors have developed a 3D system based on liquid scintillator to measure the spatial location, intensity, and depth of penetration (energy) of the proton beamlets in near real-time. METHODS: The detector system consists of a 20 × 20 × 20 cc liquid scintillator (LS) material in a light tight enclosure connected to a CCD camera. This camera has a field of view of 25.7 by 19.3 cm and a pixel size of 0.4 mm. While the LS is irradiated, the camera continuously acquires images of the light distribution produced inside the LS. Irradiations were made with proton pencil beams produced with a spot-scanning nozzle. Pencil beams with nominal ranges in water between 9.5 and 17.6 cm were scanned to irradiate an area of 10 × 10 cm square on the surface of the LS phantom. Image frames were acquired at 50 ms per frame. RESULTS: The signal to noise ratio of a typical Bragg peak was about 170. Proton range measured from the light distribution produced in the LS was accurate to within 0.3 mm on average. The largest deviation seen between the nominal and measured range was 0.6 mm. Lateral position of the measured pencil beam was accurate to within 0.4 mm on average. The largest deviation seen between the nominal and measured lateral position was 0.8 mm; however, the accuracy of this measurement could be improved by correcting light scattering artifacts. Intensity of single proton spots were measured with precision ranging from 3 % for the smallest spot intensity (0.005 MU) to 0.5 % for the largest spot (0.04 MU). CONCLUSIONS: Our LS detector system has been shown to be capable of fast, submillimeter spatial localization of proton spots delivered in a 3D volume. This system could be used for beam range, intensity and position verification in IMPT.

Self-reported health outcomes in patients with psoriasis and psoriatic arthritis randomized to two etanercept regimens.

BACKGROUND: Moderate/severe psoriasis combined with psoriatic arthritis (PsA) impairs health-related quality of life (QoL). Etanercept, a fully human tumour necrosis factor-α receptor fusion protein, is approved for treatment of both diseases. OBJECTIVE: To compare patient-reported health outcomes (PROs) of two etanercept regimens in patients with moderate/severe psoriasis and PsA. METHODS: In this randomized, double-blind, multicenter study, participants received etanercept 50 mg twice weekly (BIW; n = 379) or 50 mg weekly (QW; n = 373) for 12 weeks and open-label etanercept 50 mg QW for 12 additional weeks. PROs included: the EuroQOL-5D (EQ-5D), which measures general health status and consists of the utility index measuring five dimensions of health, and a visual analogue scale (VAS) allowing patients to assess health status; the Dermatology Life Quality Index (DLQI), which measures the impact of skin disease on QoL; the Health Assessment Questionnaire-Disability Index (HAQ-DI), an assessment of physical function; the Hospital Anxiety and Depression Scale (HADS), which screens for anxiety and depression symptoms; and individual questions on general health, disease activity, fatigue, itching, joint pain and morning stiffness. RESULTS: At baseline, patients reported QoL worse than that seen in many chronic medical conditions. Significant within-group improvements in each PRO occurred from baseline to Week 12 (P < 0.001) in both groups and were maintained at Week 24; DLQI, EQ-5D, HAQ-DI and self assessments improved significantly (P < 0.001) from baseline as early as Week 3. At Week 12, but not Week 24, improvement in DLQI, itching and psoriasis activity was greater in the BIW arm (P ≤ 0.004). Improvements in other PROs were always similar between groups. CONCLUSIONS: Greater improvements in PROs specific to skin disorders were seen with etanercept BIW than QW at Week 12, but not at Week 24. Both etanercept regimens led to sustained PRO improvements, starting as early as Week 3.