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Abstract Background and Aim Patients with inflammatory bowel disease (IBD) requiring infliximab frequently spend hours to attend treatment. Through quality improvement (QI) methodology, we aimed to shorten the time spent in the biologics infusion center using the accelerated infusion protocol and describe patient outcomes, safety, and associated cost savings. Methods From September 2018 through December 2019, eligible IBD patients receiving infliximab were recruited. We implemented interventions including the accelerated infusion protocol, and modifying collection location of infliximab. Statistical process control charts were created. Patients' clinical outcome and cost savings data were analyzed using descriptive statistics and Pearson's chi‐square. Results During the study period, a total of 60 patients with IBD receiving infliximab were recruited. A total of 315 infusions were administered—152 were under accelerated infusion protocol and 163 under standard protocol. The mean infliximab infusion time was reduced by 47%, from 2.4 h (142 ± 14 min) to 1.2 h (75 ± 10 min) (142 min vs 75 min, P

Background: Returning home from the hospital for palliative-focused care is a common transition, but the process can be emotionally distressing and logistically challenging for patients and caregivers. While interventions exist to aid in the transition, none have been developed in partnership with patients and caregivers., Objective: To undergo the initial stages of codesign to create an intervention (Advancing the Care Experience for patients receiving Palliative care as they Transition from hospital to Home [ACEPATH]) to improve the experience of hospital-to-home transitions for adult patients receiving palliative care and their caregiver(s)., Methods: The codesign process consisted of (1) the development of codesign workshop (CDW) materials to communicate key findings from prior research to CDW participants; (2) CDWs with patients, caregivers and healthcare providers (HCPs); and (3) low-fidelity prototype testing to review CDW outputs and develop low-fidelity prototypes of interventions. HCPs provided feedback on the viability of low-fidelity prototypes., Results: Three patients, seven caregivers and five HCPs participated in eight CDWs from July 2022 to March 2023. CDWs resulted in four intervention prototypes: a checklist, quick reference sheets, a patient/caregiver workbook and a transition navigator role. Outputs from CDWs included descriptions of interventions and measures of success. In April 2023, the four prototypes were presented in four low-fidelity prototype sessions to 20 HCPs. Participants in the low-fidelity prototype sessions provided feedback on what the interventions could look like, what problems the interventions were trying to solve and concerns about the interventions., Conclusion: Insights gained from this codesign work will inform high-fidelity prototype testing and the eventual implementation and evaluation of an ACEPATH intervention that aims to improve hospital-to-home transitions for patients receiving a palliative approach to care., Patient or Public Contribution: Patients and caregivers with lived experience attended CDWs aimed at designing an intervention to improve the transition from hospital to home. Their direct involvement aligns the intervention with patients' and caregivers' needs when transitioning from hospital to home. Furthermore, four patient/caregiver advisors were engaged throughout the project (from grant writing through to manuscript writing) to ensure all stages were patient- and caregiver-centred., (© 2024 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Background and Methods: We conducted a population-based, retrospective cohort study of first-time emergency department (ED) visits in adolescents and young adults (AYA) due to alcohol and compared mortality to AYA with nonalcohol ED visits between 2009 and 2015 using standardized all-cause mortality ratios (age, sex, income, and rurality). We described the cause of death for AYA and examined the association between clinical factors and mortality rates in the alcohol cohort using proportional hazard models., Results: A total of 71,776 AYA had a first-time ED visit due to alcohol (56.1% male, mean age 20.7 years) between 2009 and 2015, representing 3.3% of the 2,166,838 AYA with an ED visit in this time period. At 1 year, there were 2396 deaths, 248 (10.3%) following an ED visit related to alcohol. First-time alcohol ED visits were associated with a threefold higher risk in mortality at 1 year (0.35% vs. 0.10%, adjusted hazard ratio [aHR] 3.07, 95% confidence interval [CI] 2.69-3.51). Mortality was associated with age 25-29 years (aHR 3.88, 95% CI 2.56-5.86), being male (aHR 1.98, 95% CI 1.49-2.62), having a history of mental health or substance use (aHR 3.22, 95% CI 1.64-6.32), cause of visit being withdrawal/dependence (aHR 2.81, 95% CI 1.96-4.02), and having recurrent ED visits (aHR 1.97, 95% CI 1.27-3.05). Trauma (42.7%), followed by poisonings from drugs other than opioids (38.3%), and alcohol (28.6%) were the most common contributing causes of death., Conclusion: Incident ED visits due to alcohol in AYA are associated with a high risk of 1-year mortality, especially in young adults, those with concurrent mental health or substance use disorders, and those with a more severe initial presentation. These findings may help inform the need and urgency for follow-up care in this population., (© 2023 The Authors. Academic Emergency Medicine published by Wiley Periodicals LLC on behalf of Society for Academic Emergency Medicine.)

Coincidental with the intensified regulatory and industry focus on the design and conduct of human absorption, metabolism, and excretion (hAME) studies in the past 12 months, we have recently completed our 500th cohort involving radiolabeled test item administration to humans. Here, we build upon a recent industry white paper in this journal 1 and share some of our own experiences as a Contract Research Organization based upon collaborations with numerous pharma companies and their differing approaches to design and timing, to add further context to the discussion regarding hAME studies and the pivotal role that drug metabolism and pharmacokinetics plays. In this article, we explore how both changing relationships within the industry and shifting regulatory guidelines are impacting strategies, and compare EU and US pre-study approval requirements, before evaluating the trends from over 500 studies conducted at our global facilities conducted over more than 30 years. We conclude with a review of how improved technical capabilities and strategies are influencing the design and conduct of hAME studies, before speculating on some of the driving factors which may shape the direction they take in the future., (© 2023 The Authors. Clinical Pharmacology & Therapeutics © 2023 American Society for Clinical Pharmacology and Therapeutics.)

Objective: This study aimed to identify colorectal cancer (CRC) diagnostic pathways and describe patients in those pathway groups., Methods: This was a cross-sectional study of CRC patients in Ontario, Canada, diagnosed 2009-2012 that used linked administrative data at ICES. We used cluster analysis on 11 pathway variables characterising patient presentation, symptoms, procedures and referrals. We assessed associations between patient- and disease-related characteristics and diagnostic pathway group. We further characterised the pathways by diagnostic interval and number of related physician visits., Results: Six diagnostic pathways were identified, with three adhering to provincial diagnostic guidelines: screening (N = 4494), colonoscopy (N = 10,066) and imaging plus colonoscopy (N = 3427). Non-adherent pathways were imaging alone (N = 2238), imaging and emergency presentation (N = 2849) and no pre-diagnostic workup (N = 887). Patients in adherent pathways were younger, had fewer comorbidities, lived in less deprived areas and had earlier stage disease. The median diagnostic interval length varied across pathways from 12 to 126 days, correlating with the number of CRC-related visits., Conclusions: This study demonstrated substantial variations in real-world CRC diagnostic pathways and 25% were diagnosed through non-adherent pathways. Those patients were older, had more comorbid disease and had higher stage cancer. Further research needs to identify and describe the reasons for divergent diagnostic processes., (© 2022 John Wiley & Sons Ltd.)

Background: Colonoscopy is a key resource used to diagnose colorectal cancer (CRC). This study evaluated the relationship between colonoscopy availability and the length of the CRC diagnostic interval., Methods: This is a cross-sectional study of CRC patients diagnosed in Ontario, Canada, in 2008-2012. We used administrative health data to characterise colonoscopist density, private colonoscopy clinic access, distance to the closest colonoscopist and the diagnostic interval, defined as the time from patients' first cancer-related healthcare encounter to their cancer diagnosis date. We used multivariable quantile regression to evaluate the association between colonoscopy availability and the diagnostic interval, modelling the median and 90th percentile., Results: The median diagnostic interval was 84 days (90th percentile 323 days). The diagnostic interval was longer in patients residing in areas with lower colonoscopists density or private clinic access (adjusted median difference = 9 and 19 days, respectively), with evidence of effect modification by symptom status. Increased distance to a colonoscopist was associated with a longer diagnostic interval in asymptomatic patients, but a shorter diagnostic interval in symptomatic patients (adjusted median difference = 29 and -25 days, respectively)., Conclusions: This study demonstrated that reduced colonoscopy resource availability is associated with longer diagnostic intervals for CRC patients., (© 2019 John Wiley & Sons Ltd.)

Delayed diagnosis of breast cancer can adversely impact patient outcomes. To better understand this issue, we conducted a scoping review of literature from 1996 to 2015 that examined predictors of delayed presentation and diagnosis among women with breast cancer symptoms. We performed searches to identify studies of predictors of the time from symptom onset to first presentation (the patient interval), first presentation to diagnosis (the diagnostic interval) and symptom onset to diagnosis (the total interval) among women with breast cancer symptoms. Two reviewers independently reviewed and abstracted the findings of these studies. Of the 22 studies included in this review, 16 examined predictors of the patient interval, six examined predictors of the diagnostic interval and four examined predictors of the total interval. A total of 116 predictors were examined; three had evidence of an association with a less timely diagnosis: not disclosing symptoms to others, non-lump breast symptoms and African American ethnicity. Improving awareness of atypical breast cancer symptoms and encouraging disclosure could improve the timeliness of a breast cancer diagnosis. Access concerns for vulnerable groups need to be addressed. Future research should be more purposeful in its choice of predictors, possibly through the use of established conceptual frameworks., (© 2016 John Wiley & Sons Ltd.)

The relationship between bone mineral mass and cumulative dose of corticosteroids (CDC) was investigated in 42 children and adolescents treated for Hodgkin disease (HD; n = 22) and non-Hodgkin lymphoma (NHL; n = 20). The median age at the time of the study was 24.1 years for HD survivors and 14.1 years for NHL survivors. Dual-energy X-ray absorptiometry [bone mineral density of the lumbar spine (LS-BMD) expressed as Z-scores] and peripheral quantitative computed tomography at the distal radius [trabecular volumetric BMD (vBMD-trab)] were undertaken. Osteopenia (Z-score < -1.00) was found in 9/22 patients with HD and 10/20 with NHL, while 34% (HD = 6, NHL = 8) had a vBMD-trab below the normal range. The CDC correlated inversely with LS-BMD Z-score (r =-0.41, P = 0.007). There was a statistically significantly higher vBMD-trab in patients who received low (1-4 g/m(2)) compared with high (>or=20 g/m(2)) CDC (P = 0.031). Treatment of malignant lymphoma with high CDC is a risk factor for development of osteopenia.

The assembly and resorption of the extracellular matrix in the physis of the growth plate are poorly understood. By examining isolated fetal growth plate chondrocytes in culture and using immunochemical methods we show that type II collagen, proteoglycan aggrecan, and type IX collagen are assembled into a matrix that is initially enriched in type II collagen over proteoglycan and type IX collagen. When compared to the content of the COL2 domain in the alpha(1)(IX) chain it is evident that the majority ( 90%) of type IX molecules lack the NC4 domain unlike in articular cartilage. During matrix assembly the molar ratio of type II/COL2 of alpha(1)(IX) varied from 25:1 to 2.5:1. Following expression of the hypertrophic phenotype (initiation of type X collagen synthesis) there are parallel changes in both collagen and proteoglycan contents (inversely related to collagenase cleavage of type II collagen). The NC4 domain is then selectively, rapidly and irreversibly removed as mineralization is initiated, leaving the alpha(1)(IX) chain COL2 domain. Subsequently as mineralization progresses type II and type IX collagen (COL2 domain), but not the proteoglycan aggrecan, are resorbed coincident with a markedly increased cleavage of type II collagen by collagenase as mineral is deposited in the matrix. This study, therefore reveals a carefully orchestrated series of events in matrix assembly and resorption that prepares the extracellular matrix for mineralization., (Copyright 2000 Wiley-Liss, Inc.)