Reproducibility of T1ρ and T2 quantification in a multi-vendor multi-site study.

OBJECTIVE: To evaluate the multi-vendor multi-site reproducibility of two-dimensional (2D) multi-echo spin-echo (MESE) T2 mapping (product sequences); and to evaluate the longitudinal reproducibility of three-dimensional (3D) magnetization-prepared angle-modulated partitioned k-space spoiled gradient echo snapshots (MAPSS) T1ρ and T2 mapping (research sequences), and 2D MESE T2 mapping, separated by 6 months, in a multi-vendor multi-site setting. METHODS: Phantoms and volunteers (n = 5 from each site, n = 20 in total) were scanned on four 3 T magnetic resonance (MR) systems from four sites and three vendors (Siemens, General Electric, and Phillips). Two traveling volunteers (3 knees) scanned at all 4 sites at baseline and 6-month follow-up. Data was transferred to one site for centralized processing. Coefficients of variation (CVs) were calculated to evaluate reproducibility. RESULTS: For baseline 2D MESE T2 measures, average CV were 0.37-2.45% (intra-site) and 5.96% (inter-site) for phantoms, and 3.15-8.49% (intra-site) and 14.16% (inter-site) for volunteers. For longitudinal phantom data, intra-site CVs were 1.42-3.48% for 3D MAPSS T1ρ, 1.77-3.56% for 3D MAPSS T2, and 1.02-2.54% for 2D MESE T2. For the longitudinal volunteer data, the intra-site CVs were 2.60-4.86% for 3D MAPSS T1ρ, 3.33-7.25% for 3D MAPSS T2, and 3.11-8.77% for 2D MESE T2. CONCLUSION: This study demonstrated excellent intra-site reproducibility of 2D MESE T2 imaging, while its inter-site variation was slightly higher than 3D MAPSS T2 imaging (10.06% as previously reported). This study also showed excellent reproducibility of longitudinal T1ρ and T2 cartilage quantification, in a multi-vendor multi-site setting for both product 2D MESE T2 and 3D MAPSS T1p/T2 research sequences.

A combined experimental and computational approach to evaluate microclimate control at the support surface interface.

Temperature and humidity conditions at the interface between a support surface and the skin, termed microclimate, has been implicated in the development of pressure ulcers. Support surface technologies have been developed to control microclimate conditions, although only a few standard test methods exist to evaluate their performance. This study describes a combined experimental-computational approach to analyzing microclimate control systems. The study used a modified physical model protocol to evaluate two specific support surface systems involving a spacer fabric cover with i) no air flow and ii) an active fan. The physical model deposited moisture at a controlled rate for 25 min, and the microclimate conditions under the model and the surrounding area were monitored for 24 h. Using the experimental data as boundary conditions, a finite element model was developed using mass transport principles, which was calibrated using experimental results. Model inputs included mass density and mass diffusivity, resulting in an estimated absolute humidity change over time. The physical model tests revealed distinct differences between the support surfaces with and without active airflow, with the former having little effect on local humidity levels (RH>75% for 24hr). By contrast, there was a spatial and temporal change in microclimate with the active fan, with sensors positioned towards the source of airflow reaching ambient conditions within 24hr. The computational model was refined to produce comparable results with respect to both the spatial distribution of microclimate and the change in values over time. The combined experimental and computation approach was able to distinguish distinct difference in microclimate change between two support surface designs. The approach could enable the efficient evaluation of different mattress design principles to aid decision making for personalized support surface solutions, for the prevention of pressure ulcers.

Immune profiling of lupus miliaris disseminatus faciei and successful management with anti-tumour necrosis factor therapy.

Lupus miliaris disseminatus faciei (LMDF) is a chronic inflammatory dermatosis of unknown aetiology, most often seen in young adults. Although many treatments for LMDF exist, treatment guidelines have not been developed, and response to therapy is generally unpredictable. We present the results of transcriptomic analysis of LMDF lesional skin, which revealed a variety of differentially expressed genes linking LMDF to alterations in innate and adaptive T helper 1 immunity. Immunohistochemical analysis was also performed, identifying similar changes in T-cell immune responses. Given evidence for increased tumour necrosis factor (TNF) pathway activity, our patient, who had previously been refractory to multiple treatments, was initiated on TNF inhibitor therapy with excellent response. This characterization of the LMDF immune response may lead to improved treatment of this condition.

Cultivating a communities of practice for colorectal cancer screening in northern Canada.

BACKGROUND: Knowledge management systems such as a Communities of Practice (CoP) can improve healthcare processes but are challenging in complex multidisciplinary systems, and guidance on methods to establish a CoP are needed. This case illustrates the use of early stakeholder engagement and Nominal Group Technique (NGT) to cultivate a CoP in a complex multidisciplinary system: colorectal cancer screening in northern Canada. METHODS: Stakeholders in the Northwest Territories, Canada were recruited and co-designed a workshop with authors to introduce CoP concepts and identify priorities. At the workshop NGT was used to identify and prioritize gaps in process, practice, and evidence for the CoP to focus on. An anonymous polling system was used to obtain workshop participants' feedback on the process. RESULTS: The co-design process integrated stakeholders' perspectives in developing a workshop. Using NGT, the gap analysis identified 23 areas of focus for the CoP, among which, the highest priorities were identified: communication between clinicians and with patients, and identification of screening eligibility in the electronic medical record. Participants found the process to be useful, educational, and interesting. There was unanimous interest in moving forward with developing a CoP. CONCLUSION: A co-designed workshop and NGT were useful in laying the foundation for a CoP in a complex multidisciplinary environment. POLICY STATEMENT: This case shows the utility of a co-designed workshop and NGT in starting a CoP: a knowledge management system that would provide critical insight into colorectal cancer screening policies for the region.

Implementing a one-day testing model improves timeliness of workup for patients with lung cancer.

Background: Patients with lung cancer often experience stressful delays throughout the diagnostic phase of care. To address that situation, our multidisciplinary team created a "Navigation Day," during which patients partake in a single-day visit that comprises nurse-led teaching, social work, smoking cessation counselling, symptom control, and dedicated test slots for integrated positron-emission tomography and computed tomography (pet/ct), pulmonary function tests (pfts), and magnetic resonance imaging (mri) of the brain. We evaluated the effects of that program on wait times and patient satisfaction. Methods: Patients with a suspicion of lung cancer on chest ct imaging referred during 3 time periods were reviewed: 1 year before launch of the Navigation Day, 1 year post-launch, and 2 years post-launch. Patients were further stratified according to concordance of their test date with a Navigation Day date. Mean wait times for pet/ct, pfts, and mri brain were calculated for each group. Patient satisfaction was measured using a standardized provincial survey. The Student t-test and analysis of variance were used to assess for significance. Results: After implementation, mean wait times in the first year improved to 9.2 days from 15.5 days for pet/ct (p < 0.0001), to 9.6 days from 15.7 days for pfts (p < 0.0001), and to 10.2 days from 16.0 days for mri brain (p < 0.0001). Patients who used a dedicated test slot experienced the shortest wait times, at 5.8 days for pet/ct, 5.8 days for pfts, and 6.3 days for mri brain (p < 0.0001). Those improvements were sustained at 2 years post-launch. Patient satisfaction in the categories of assistance, emotional support, and clarity remained high post-launch. Conclusions: Navigation Day significantly improved the timeliness of diagnostic testing services in patients with suspected lung cancer.

The effect of surgery report cards on improving radical prostatectomy quality: the SuRep study protocol.

BACKGROUND: The goal of radical prostatectomy is to achieve the optimal balance between complete cancer removal and preserving a patient's urinary and sexual function. Performing a wider excision of peri-prostatic tissue helps achieve negative surgical margins, but can compromise urinary and sexual function. Alternatively, sparing peri-prostatic tissue to maintain functional outcomes may result in an increased risk of cancer recurrence. The objective of this study is to determine the effect of providing surgeons with detailed information about their patient outcomes through a surgical report card. METHODS: We propose a prospective cohort quasi-experimental study. The intervention is the provision of feedback to prostate cancer surgeons via surgical report cards. These report cards will be distributed every 3 months by email and will present surgeons with detailed information, including urinary function, erectile function, and surgical margin outcomes of their patients compared to patients treated by other de-identified surgeons in the study. For the first 12 months of the study, pre-operative, 6-month, and 12-month patient data will be collected but there will be no report cards distributed to surgeons. This will form the pre-feedback cohort. After the pre-feedback cohort has completed accrual, surgeons will receive quarterly report cards. Patients treated after the provision of report cards will comprise the post-feedback cohort. The primary comparison will be post-operative function of the pre-feedback cohort vs. post-feedback cohort. The secondary comparison will be the proportion of patients with positive surgical margins in the two cohorts. Outcomes will be stratified or case-mix adjusted, as appropriate. Assuming a baseline potency of 20% and a baseline continence of 70%, 292 patients will be required for 80% power at an alpha of 5% to detect a 10% improvement in functional outcomes. Assuming 30% of patients may be lost to follow-up, a minimum sample size of 210 patients is required in the pre-feedback cohort and 210 patients in the post-feedback cohort. DISCUSSION: The findings from this study will have an immediate impact on surgeon self-evaluation and we hypothesize surgical report cards will result in improved overall outcomes of men treated with radical prostatectomy.

Low but not high frequency of intermittent hypoxia suppresses endothelium-dependent, oxidative stress-mediated contractions in carotid arteries of obese mice.

Obstructive sleep apnea is characterized by intermittent hypoxia (IH) during sleep and predisposes to endothelial dysfunction. Obesity is a major risk factor for the occurrence of sleep apnea. The present study compared the functional impact of low- (IH10; 10 hypoxic events/h) and high-frequency (IH60; 60 hypoxic events/h) IH for 4 wk on endothelial function in male C57BL/6 mice with or without high-fat (HF) diet-induced obesity. Mean arterial blood pressure (tail cuff method) was increased in obese mice after IH60 exposure, i.e., HF + IH60 group. The serum levels of the oxidative stress marker malondialdehyde were augmented in lean IH60 and HF groups, with a further increase in HF + IH60 but a reduction in HF + IH10 mice compared with the HF group. Vascular responsiveness was assessed as changes in isometric tension in isolated arteries. Relaxations to the endothelium-dependent vasodilator acetylcholine were impaired in HF + IH60 aortae. Endothelium-dependent contractions (EDC; response to acetylcholine in the presence of the nitric oxide synthase inhibitor l-NAME) in carotid arteries were augmented in the HF group, but this HF-induced augmentation was suppressed by low-frequency IH exposure. The addition of apocynin (antioxidant) reduced EDC in HF and HF + IH60 groups but not in HF + IH10 group. In conclusion, these findings suggest that exposure of obese mice to mild IH exerts preconditioning-like suppression of endothelium-dependent and oxidative stress-mediated contractions. When IH severity increases, this suppression diminishes and endothelial dysfunction accelerates. NEW & NOTEWORTHY The present study demonstrates, for the first time, that low-frequency intermittent hypoxia may exert a preconditioning-like suppression of oxidative stress-induced endothelium-dependent contractions in mice with diet-induced obesity. This relative suppression was diminished as intermittent hypoxia became more severe, and a deleterious effect on endothelial function emerged.

Regional process redesign of lung cancer care: a learning health system pilot project.

BACKGROUND: The Ottawa Hospital (toh) defined delay to timely lung cancer care as a system design problem. Recognizing the patient need for an integrated journey and the need for dynamic alignment of providers, toh used a learning health system (lhs) vision to redesign regional diagnostic processes. A lhs is driven by feedback utilizing operational and clinical information to drive system optimization and innovation. An essential component of a lhs is a collaborative platform that provides connectivity across silos, organizations, and professions. METHODS: To operationalize a lhs, we developed the Ottawa Health Transformation Model (ohtm) as a consensus approach that addresses process barriers, resistance to change, and conflicting priorities. A regional Community of Practice (cop) was established to engage stakeholders, and a dedicated transformation team supported process improvements and implementation. RESULTS: The project operationalized the lung cancer diagnostic pathway and optimized patient flow from referral to initiation of treatment. Twelve major processes in referral, review, diagnostics, assessment, triage, and consult were redesigned. The Ottawa Hospital now provides a diagnosis to 80% of referrals within the provincial target of 28 days. The median patient journey from referral to initial treatment decreased by 48% from 92 to 47 days. CONCLUSIONS: The initiative optimized regional integration from referral to initial treatment. Use of a lhs lens enabled the creation of a system that is standardized to best practice and open to ongoing innovation. Continued transformation initiatives across the continuum of care are needed to incorporate best practice and optimize delivery systems for regional populations.

Time-resolved fluorescence spectroscopy for the diagnosis of oral lichen planus.

BACKGROUND: Lichen planus (LP) is a T-cell mediated autoimmune disorder of unknown aetiology that affects the skin, nails, oral and genital mucous membranes. Conventionally, oral LP (OLP) is diagnosed through clinical assessment and histopathological confirmation by oral biopsy. AIM: To explore the use of time-resolved fluorescence spectroscopy (TRFS) to detect fluorescence lifetime changes between lesional OLP and perilesional normal mucosa. METHODS: In this pilot study, measurements of lesional and perilesional buccal and mouth floor mucosa were conducted in vivo with a TRFS system. Histopathological findings were consistent with OLP in 8 out of 10 patients biopsied. Two patients with histopathological diagnoses of frictional hyperkeratosis and oral candidiasis, respectively, were excluded from the study. RESULTS: Our preliminary data show that lifetime values in the 360-560 nm spectral range indicate a significant differentiation between normal and diseased tissue. In contrast to the standard oral biopsy procedure, this technique is noninvasive, painless, time-efficient and safe. CONCLUSIONS: Future studies are needed to better elucidate the diagnostic capability of TRFS and to further explore the sources of fluorescence contrast. This pilot study suggests that, based on fluorescence lifetime parameters, TRFS is a very promising technology for the development of a novel OLP diagnostic technique.

Randomized Clinical Trial of 12% and 38% Silver Diamine Fluoride Treatment.

This 30-mo randomized clinical trial compared the effectiveness of 2 concentrations (12% or 38%) of silver diamine fluoride (SDF) and 2 periodicity of application (once or twice a year) in arresting cavitated dentin caries in primary teeth. Children aged 3 to 4 y who had at least 1 active cavitated caries lesion were enrolled and randomly allocated into 4 groups for intervention. Group 1 had 12% SDF applied annually (every 12 mo), group 2 had 12% SDF applied semiannually (every 6 mo), group 3 had 38% SDF applied annually, and group 4 had 38% SDF applied semiannually. Clinical examinations were performed semiannually in kindergarten by a single examiner to investigate whether the SDF-treated caries became arrested. A total of 888 children with 4,220 decayed tooth surfaces received SDF application at baseline, and 799 (90.0%) children with 3,790 surfaces (89.8%) were evaluated at the 30-mo examination. The caries arrest rates were 55.2%, 58.6%, 66.9%, and 75.7% for groups 1, 2, 3, and 4, respectively ( P < 0.001). Caries treated with 38% SDF had a higher chance of becoming arrested than those treated with 12% SDF (odds ratio [OR], 1.98; 95% confidence interval [CI], 1.51-2.60, P < 0.001). The interaction between frequency of SDF application and visible plaque index (VPI) score was significant ( P = 0.017). Among those children who received annual SDF application, children with a higher VPI score had a lower chance to have their caries become arrested (OR, 0.59, 95% CI, 0.49-0.72). In conclusion, SDF at a concentration of 38% is more effective than that of 12% in arresting active caries in primary teeth. For children with poor oral hygiene, caries arrest rate of SDF treatment can be increased by increasing the frequency of application from annually to semiannually ( ClinicalTrials.gov NCT02385474).

Waist circumference at five common measurement sites in normal weight and overweight adults: which site is most optimal?

The aim of this study was to determine (i) if adults would measure their own waist circumference (WC), (ii) which WC site(s) are the most intuitive and easy to measure and (iii) if measurement accuracy and association between WC and blood pressure differs across five measurement sites. Participants (n = 198) measured their WC first with no instruction and then using visual instructions for the iliac crest, last rib, midpoint, minimal waist and umbilicus. Without instruction, men most commonly measured their WC at the umbilicus and iliac crest, while women measured their WC at the umbilicus and minimal WC. Both men and women reported the minimal waist and umbilicus to be moderately easier to self-measure compared to the other sites (P < 0.05). Prevalence of abdominal obesity varied significantly by gender and measurement site, especially for females (normal weight: 0-18%; overweight: 51-79%). Measurement site did not influence accuracy of WC self-measurement or the association between WC and blood pressure (P > 0.05). A universal WC landmark is needed. From these results, there does not appear to be a clear clinical advantage in terms of blood pressure or practical advantage of measuring one WC site over another. However, the umbilicus may be the most intuitive and easy to measure.

OV21/PETROC: a randomized Gynecologic Cancer Intergroup phase II study of intraperitoneal versus intravenous chemotherapy following neoadjuvant chemotherapy and optimal debulking surgery in epithelial ovarian cancer.

Background: The purpose of this multistage, adaptively, designed randomized phase II study was to evaluate the role of intraperitoneal (i.p.) chemotherapy following neoadjuvant chemotherapy (NACT) and optimal debulking surgery in women with epithelial ovarian cancer (EOC). Patients and methods: We carried out a multicenter, two-stage, phase II trial. Eligible patients with stage IIB-IVA EOC treated with platinum-based intravenous (i.v.) NACT followed by optimal (<1 cm) debulking surgery were randomized to one of the three treatment arms: (i) i.v. carboplatin/paclitaxel, (ii) i.p. cisplatin plus i.v./i.p. paclitaxel, or (iii) i.p. carboplatin plus i.v./i.p. paclitaxel. The primary end point was 9-month progressive disease rate (PD9). Secondary end points included progression-free survival (PFS), overall survival (OS), toxicity, and quality of life (QOL). Results: Between 2009 and 2015, 275 patients were randomized; i.p. cisplatin containing arm did not progress beyond the first stage of the study after failing to meet the pre-set superiority rule. The final analysis compared i.v. carboplatin/paclitaxel (n = 101) with i.p. carboplatin, i.v./i.p. paclitaxel (n = 102). The intention to treat PD9 was lower in the i.p. carboplatin arm compared with the i.v. carboplatin arm: 24.5% (95% CI 16.2% to 32.9%) versus 38.6% (95% CI 29.1% to 48.1%) P = 0.065. The study was underpowered to detect differences in PFS: HR PFS 0.82 (95% CI 0.57-1.17); P = 0.27 and OS HR 0.80 (95% CI 0.47-1.35) P = 0.40. The i.p. carboplatin-based regimen was well tolerated with no reduction in QOL or increase in toxicity compared with i.v. administration alone. Conclusion: In women with stage IIIC or IVA EOC treated with NACT and optimal debulking surgery, i.p. carboplatin-based chemotherapy is well tolerated and associated with an improved PD9 compared with i.v. carboplatin-based chemotherapy. Clinical trial number: clinicaltrials.gov, NCT01622543.

Adverse Effects of Silver Diamine Fluoride Treatment among Preschool Children.

This randomized clinical trial aimed to compare the adverse effects and parental satisfaction following the different regimes of silver diamine fluoride (SDF) treatment among preschool children. A total of 888 preschool children who had active dentin caries received different SDF application regimes: group 1, 12% SDF applied annually; group 2, 12% SDF applied semiannually; group 3, 38% SDF applied annually; and group 4, 38% SDF applied semiannually. Information on adverse effects-including tooth or gum pain, gum swelling, gum bleaching, and systemic toxicity-was collected through a parent-reported questionnaire within 1 wk after every SDF or placebo application. Information of parental satisfaction on children's dental appearance was collected at baseline and 30-mo examination. At the 30 mo, 799 children (90%) remained in the study. No acute systemic illness or major adverse effect was reported. No differences of all minor adverse effects among the 4 groups were found ( P > 0.05). Overall, prevalence of tooth and gum pain as perceived by patients and reported by parents was 6.6%, while gum swelling and gum bleaching were 2.8% and 4.7%, respectively. Blackening of carious lesions was common among all groups, with 36.7%, 49.5%, 65.6% and 76.3% in groups 1 to 4, respectively (χ2 test, P < 0.001). The proportion of parents who were satisfied with their children's dental appearance in groups 1 to 4 was as follows: 67.6%, 61.5%, 70.8%, and 62.3%, respectively (χ2 test, P > 0.05). Based on parental reporting, SDF does not cause acute systemic illness. Tooth or gum pain, gum swelling, and gum bleaching were uncommon and not significantly different among the study groups. Parental satisfaction with children's dental appearance was similar among all groups. The use of SDF following the study protocol for caries arrest is safe for preschool children. Collecting information on parental satisfaction and adverse effects is beneficial for dental professionals when deciding to adopt SDF treatment for preschool children (ClinicalTrials.gov NCT02385474).

Prothrombin complex concentrate for emergent reversal of warfarin: an international survey of hospital protocols.

For emergent warfarin reversal, four-factor prothrombin complex concentrates (4FPCCs) are recommended by many international guidelines. We surveyed international clinical sites including members of the Biomedical Excellence for Safer Transfusion (BEST) Collaborative. Most sites have emergent warfarin reversal protocols (53% use PCC, 25% use PCC+ plasma and 2% use plasma alone); however, variation between adjusted dosing and fixed dosing was observed.