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BackgroundIncreases in patient needs can strain hospital resources, which may worsen care quality and outcomes. This systematic literature review sought to understand whether hospital capacity strain is associated with worse health outcomes for hospitalized patients and to evaluate benefits and harms of health system interventions to improve care quality during times of hospital capacity strain.MethodsParallel searches were conducted in MEDLINE, CINAHL, the Cochrane Library, and reference lists from 1999-2015. Two reviewers assessed study eligibility. We included English-language studies describing the association between capacity strain (high census, acuity, turnover, or an indirect measure of strain such as delayed admission) and health outcomes or intermediate outcomes for children and adults hospitalized in highly developed countries. We also included studies of health system interventions to improve care during times of capacity strain. Two reviewers extracted data and assessed risk of bias using the Newcastle-Ottawa Score for observational studies and the Cochrane Collaboration Risk of Bias Assessment Tool for experimental studies.ResultsOf 5,702 potentially relevant studies, we included 44 observational and 8 experimental studies. There was marked heterogeneity in the metrics used to define capacity strain, hospital settings, and overall study quality. Mortality increased during times of capacity strain in 18 of 30 studies and in 9 of 12 studies in intensive care unit settings. No experimental studies were randomized, and none demonstrated an improvement in health outcomes after implementing the intervention. The pediatric literature is very limited; only six observational studies included children. There was insufficient study homogeneity to perform meta-analyses.DiscussionIn highly developed countries, hospital capacity strain is associated with increased mortality and worsened health outcomes. Evidence-based solutions to improve outcomes during times of capacity strain are needed.

Metastatic prostate cancer is incurable, and new therapeutic targets and drugs are urgently needed. Viral infections are associated with several cancer types, but a link between viruses and prostate oncogenesis has not been established. Only recently, an association between human cytomegalovirus (CMV) seropositivity and increased risk of prostate cancer mortality was demonstrated. Here, we show that CMV infection is common in the normal prostate epithelium and in prostate tumor tissue, with 70–92% of tumors being infected. Additionally, we report that commonly studied prostate cancer cell lines are CMV infected. Loss‐of‐function experiments demonstrate that CMV promotes cell survival, proliferation, and androgen receptor signaling, identifying it as a therapeutic target in castration‐sensitive and castration‐resistant prostate cancer. Several anti‐CMV pharmaceutical compounds in clinical use inhibited cell expansion in prostate cancer models both in vitro and in vivo. We conclude that CMV is common in prostate cancer, promotes core prostate cancer cell programs, and can be inhibited by well‐tolerated drugs. These findings motivate investigation into potential clinical benefits of CMV inhibition in the treatment of prostate cancer. Human cytomegalovirus infection is common in normal prostate epithelium, prostate tumor tissue, and prostate cancer cell lines. CMV promotes cell survival, proliferation, and androgen receptor signaling. Anti‐CMV pharmaceutical compounds in clinical use inhibited cell expansion in prostate cancer models in vitro and in vivo, motivating investigation into potential clinical benefits of CMV inhibition in the treatment of prostate cancer.

ObjectiveThe Epi-IBD cohort is a prospective population-based inception cohort of unselected patients with inflammatory bowel disease from 29 European centres covering a background population of almost 10 million people. The aim of this study was to assess the 5-year outcome and disease course of patients with Crohn’s disease (CD).DesignPatients were followed up prospectively from the time of diagnosis, including collection of their clinical data, demographics, disease activity, medical therapy, surgery, cancers and deaths. Associations between outcomes and multiple covariates were analysed by Cox regression analysis.ResultsIn total, 488 patients were included in the study. During follow-up, 107 (22%) patients received surgery, while 176 (36%) patients were hospitalised because of CD. A total of 49 (14%) patients diagnosed with non-stricturing, non-penetrating disease progressed to either stricturing and/or penetrating disease. These rates did not differ between patients from Western and Eastern Europe. However, significant geographic differences were noted regarding treatment: more patients in Western Europe received biological therapy (33%) and immunomodulators (66%) than did those in Eastern Europe (14% and 54%, respectively, P<0.01), while more Eastern European patients received 5-aminosalicylates (90% vs 56%, P<0.05). Treatment with immunomodulators reduced the risk of surgery (HR: 0.4, 95% CI 0.2 to 0.6) and hospitalisation (HR: 0.3, 95% CI 0.2 to 0.5).ConclusionDespite patients being treated early and frequently with immunomodulators and biological therapy in Western Europe, 5-year outcomes including surgery and phenotype progression in this cohort were comparable across Western and Eastern Europe. Differences in treatment strategies between Western and Eastern European centres did not affect the disease course. Treatment with immunomodulators reduced the risk of surgery and hospitalisation.

Background: Data on direct and indirect annual costs for inflammatory bowel disease (IBD) patients treated with vedolizumab are limited. Objectives: To evaluate the total annual direct healthcare costs and indirect costs among IBD patients treated with vedolizumab. Design: A prospective observational multicentre study involving 286 patients with Crohn’s disease (CD; n = 169) or ulcerative colitis (UC; n = 117) who started vedolizumab therapy during 2015–2017 at 21 hospitals across Sweden. Methods: Data on direct and indirect costs were collected during a 3-year follow-up period. Direct costs were measured as healthcare resource utilization including medication, hospital admissions and hospital-based outpatient visits. Indirect societal costs were measured as production losses from sick leave and disability pension. Data were obtained from the Swedish Quality Register for IBD and through linkage with national registers. Data are presented both for patients who continued treatment throughout the follow-up period and for patients who discontinued treatment (CD: n = 83; UC: n = 48). Results: The mean annual direct follow-up cost was €24,305 for all IBD patients, €24,873 for CD patients and €23,484 for UC patients (p = 0.24). No difference was observed between men and women (€24,506 vs €24,080; p = 0.87). Direct costs were similar in patients who continued vedolizumab for the entire study period (€24,401) and those who discontinued treatment (€24,192; p = 0.12). Medication was the primary driver of direct costs (64%), followed by hospital admissions (19%) and outpatient care (17%). Mean indirect costs were lower among patients who continued vedolizumab (€3044) than among those who stopped the treatment (€8927; p < 0.01). Increased direct costs were associated with perianal disease and high baseline disease activity in CD, and concurrent use of immunomodulators in UC. Conclusion: Patients treated with vedolizumab in Swedish clinical practice represent a group with high direct costs, primarily due to medication expenses. However, indirect costs were significantly lower than in previous reports. Plain language summary Healthcare use and productivity loss in inflammatory bowel disease patients treated with vedolizumab: results from the Swedish SVEAH study Inflammatory bowel disease (IBD) is a chronic idiopathic inflammatory disorder of the gastrointestinal tract. The two main types of IBD are Crohn’s disease and ulcerative colitis. IBD causes significant illness and can lead to complications like bowel blockages, fistulas, infections, and cancer, which create a heavy economic burden on society and healthcare. Vedolizumab is a biological treatment that was approved for treating IBD in 2014. A previous Swedish study, called the SVEAH study, showed that vedolizumab is effective in routine care. However, the cost of vedolizumab is higher than that of conventional therapies, costing over €10,000 per treatment year, depending on the country, healthcare system, and dosage. The purpose of this study was to examine healthcare costs and productivity losses, such as sick leave, in patients treated with vedolizumab. To do this, we used the Swedish personal identification number to collect data from Swedish health registers for the participants in the SVEAH study. We found that the average healthcare cost per patient was €24,305. Medication was the largest contributor to direct costs (64%), followed by hospital admissions (19%) and outpatient care (17%). Direct healthcare costs were similar for patients who continued vedolizumab throughout the study (€24,401) and those who stopped treatment (€24,192). However, productivity losses were lower for patients who continued vedolizumab (€3,044) than for those who stopped treatment (€8,927). High disease activity and the presence of perianal disease, such as abscesses or fistulas, were linked to higher costs in Crohn’s disease. Patients with ulcerative colitis who used immunomodulators alongside vedolizumab also had higher costs.

AbstractObjectiveCreate an easy‐to‐use pediatric out‐of‐hospital cardiac arrest (OHCA)‐specific chart review tool to reliably detect severe adverse safety events (ASEs) in the prehospital care of children with OHCA. MethodsWe revised our previously validated pediatric prehospital adverse event detection system (PEDS) tool, used to evaluate ASEs in the prehospital care of children during emergent calls, to create an OHCA‐specific chart review tool. We developed decision support for reviewers, reviewer training, and a dedicated section for chart data abstraction. We randomly selected 28 charts for independent review by 2 expert reviewers who determined the presence or absence of a severe ASE for each care episode and identified the domain of care and preventability for each ASE. We calculated inter‐rater agreement in the assessment of the presence or absence of a severe ASE using Gwet's first‐order agreement coefficient (AC1). ResultsThe PEDS‐OHCA chart review tool has 6 sections, with a minimum of 70 and maximum of 667 total possible fields. We found inter‐rater agreement of 0.83 (95% confidence interval, 0.63–0.99) between our 2 reviewers for the overall detection of a severe ASE and an average time to complete of 8 minutes (range, 2–25 minutes). Inter‐rater agreement in the detection of a severe ASE in each individual domain ranged from 0.36 to 0.96. ConclusionsThe PEDS‐OHCA is the first chart review tool to systematically evaluate the safety and quality of EMS care for children with OHCA. This tool may help improve understanding of the quality of EMS care for children with OHCA, which is essential to improving outcomes.

Background Real‐world data on clinical outcomes of ustekinumab in ulcerative colitis are lacking. Objective To assess short‐ and long‐term clinical outcomes of ustekinumab in ulcerative colitis. Methods Adult ulcerative colitis patients without previous colectomy starting ustekinumab treatment up until 11 December 2020 were identified through the Swedish Inflammatory Bowel Disease Register (SWIBREG). Prospectively recorded data were extracted from the SWIBREG. The primary outcome was persistence to ustekinumab 16 weeks after treatment initiation. Secondary outcomes included drug persistence beyond week 16, clinical remission (defined as a patient‐reported Mayo rectal bleeding subscore = 0 and stool frequency subscore ≤1), biochemical remission (defined as faecal‐calprotectin <250 μg/g) and changes in health‐related quality of life (HRQoL), as measured by the Short Health Scale (SHS). Logistic regression was used to identify potential predictors of ustekinumab persistence at 16 weeks. Results Of the 133 patients with ulcerative colitis, only three were naïve to biologics and tofacitinib. The persistence rates of ustekinumab were 115/133 (86%) at 16 weeks and 89/133 (67%) at last follow‐up, that is, after a median follow‐up of 32 (interquartile range 19–56) weeks. The clinical remission rates were 17% at 16 weeks and 32% at the last follow‐up. The corresponding rates for biochemical remission were 14% and 23%. The median faecal‐calprotectin concentration decreased from 740 μg/g at baseline to 98 μg/g at the last follow‐up (p < 0.01, n = 37). Improvement was seen in each dimension of the SHS between baseline and last follow‐up (p < 0.01 for each dimension, n = 46). Male sex was associated with ustekinumab persistence at 16 weeks (adjusted odds ratio = 4.00, 95% confidence interval: 1.35–11.83). Conclusion In this nationwide real‐world cohort of ulcerative colitis patients with prior drug failures, including other biologics and tofacitinib, ustekinumab was associated with high drug persistence rates and improvements in clinical, biochemical and HRQoL measures.

PurposeThere is a need for diagnostic and prognostic biosignatures to improve long-term outcomes in inflammatory bowel disease (IBD). Here, we describe the establishment of the Swedish Inception Cohort in IBD (SIC-IBD) and demonstrate its potential for the identification of such signatures.ParticipantsPatients aged ≥18 years with gastrointestinal symptoms who were referred to the gastroenterology unit due to suspected IBD at eight Swedish hospitals between November 2011 and March 2021 were eligible for inclusion.Findings to dateIn total, 367 patients with IBD (Crohn’s disease, n=142; ulcerative colitis, n=201; IBD-unclassified, n=24) and 168 symptomatic controls were included. In addition, 59 healthy controls without gastrointestinal symptoms were recruited as a second control group. Biospecimens and clinical data were collected at inclusion and in patients with IBD also during follow-up to 10 years. Levels of faecal calprotectin and high-sensitivity C-reactive protein were higher in patients with IBD compared with symptomatic controls and healthy controls. Preliminary results highlight the potential of serum protein signatures and autoantibodies, as well as results from faecal markers, to differentiate between IBD and symptomatic controls in the cohort. During the first year of follow-up, 37% (53/142) of the patients with Crohn’s disease, 24% (48/201) with ulcerative colitis and 4% (1/24) with IBD-U experienced an aggressive disease course.Future plansWe have established an inception cohort enabling ongoing initiatives to collect and generate clinical data and multi-omics datasets. The cohort will allow analyses for translation into candidate biosignatures to support clinical decision-making in IBD. Additionally, the data will provide insights into mechanisms of disease pathogenesis.

IntroductionEfforts to improve the quality of emergency medical services (EMS) care for adults with out-of-hospital cardiac arrest (OHCA) have led to improved survival over time. Similar improvements have not been observed for children with OHCA, who may be at increased risk for preventable adverse safety events during prehospital care. The purpose of this study is to identify patient and organisational factors that are associated with adverse safety events during the EMS care of paediatric OHCA.Methods and analysisThis is a large multisite EMS study in the USA consisting of chart reviews and agency surveys to measure, characterise and evaluate predictors of our primary outcome severe adverse safety events in paediatric OHCA. Using the previously validated Paediatric prehospital adverse Event Detection System tool, we will review EMS charts for 1500 children with OHCA from 2013 to 2019 to collect details of each case and identify severe adverse safety events (ASEs). Cases will be drawn from over 40 EMS agencies in at least five states in geographically diverse areas of the USA. EMS agencies providing charts will also be invited to complete an agency survey to capture organisational characteristics. We will describe the frequency and proportion of severe ASEs in paediatric OHCA across geographic regions and clinical domains, and identify patient and EMS organisational characteristics associated with severe ASEs using logistic regression.Ethics and disseminationThis study has been approved by the Oregon Health & Science University Institutional Review Board (IRB Approval# 00018748). Study results will be disseminated through scientific publications and presentations, and to EMS leaders and staff through local EMS medical directors, quality and training officers and community engagement activities.

Background: Prospectively and systematically collected real-world data on vedolizumab are scarce. We aimed to assess the long-term clinical effectiveness of vedolizumab in inflammatory bowel disease (IBD). Methods: This study was a prospective, observational, multicentre study. Overall, 286 patients with active IBD were included (Crohn’s disease, n = 169; ulcerative colitis, n = 117). The primary outcomes were clinical response at week 12 and clinical remission at week 52, based on the Harvey Bradshaw Index and the partial Mayo Clinic score. Secondary outcomes included clinical remission at week 12, clinical response at week 52, corticosteroid-free clinical remission at week 52, changes in biochemical measures, and health-related quality of life (HRQoL). Results: At baseline, 88% of the patients were exposed to anti-TNF and 41% of the patients with Crohn’s disease had undergone ⩾1 surgical resection. At week 12, clinical response was 27% and remission 47% in Crohn’s disease; corresponding figures in ulcerative colitis were 52% and 34%. Clinical response, remission and corticosteroid-free remission at week 52 were 22%, 41% and 40% in Crohn’s disease and 49%, 47% and 46% in ulcerative colitis, respectively. A statistically significant decrease in median faecal-calprotectin and C-reactive protein was observed at 12 and 52 weeks in patients with Crohn’s disease and ulcerative colitis. The HRQoL measures Short Health Scale and EuroQol 5-Dimensions improved in both Crohn’s disease and ulcerative colitis patients (p < 0.001). Clinical disease activity at baseline was inversely associated with clinical remission at week 52. Conclusion: Vedolizumab proved effective for the treatment of refractory IBD in clinical practice.

Background: Real-world data on long-term outcomes of vedolizumab (VDZ) are scarce. Objective: To assess long-term outcomes (up to 3 years) of VDZ in treating inflammatory bowel disease (IBD). Design: A nationwide, prospective multicentre extension of a Swedish observational study on VDZ assessing Effectiveness And Healthcare resource utilization in patients with IBD (SVEAH). Methods: After re-consent, data of patients with Crohn’s disease (CD) (n = 68) and ulcerative colitis (UC) (n = 46) treated with VDZ were prospectively recorded using an electronic case report form integrated with the Swedish IBD Register (SWIBREG). The primary outcome was clinical remission (defined as Harvey–Bradshaw Index ⩽4 in CD and partial Mayo score ⩽2 in UC) at 104 and 156 weeks in patients with a response and/or remission 12 weeks after starting VDZ. Secondary outcomes included health-related quality of life (HRQoL) and biochemical outcomes. Results: VDZ continuation rates were high at weeks 104 and 156, 88% and 84%, respectively, for CD and 87% and 78%, respectively, for UC. Of the 53 CD patients with a response/remission at 12 weeks, 40 (75%) patients were in remission at 104 weeks and 42 (79%) patients at 156 weeks. For UC, these numbers were 25/31 (81%) and 22/31 (71%), respectively. Improvements were seen in the Short Health Scale (p < 0.01 for each dimension; CD, n = 51; UC, n = 33) and the EuroQol 5-Dimensions, 5-levels index value (p < 0.01; CD, n = 39; UC, n = 30). Median plasma-C-reactive protein concentrations (mg/L) decreased from 5 at baseline to 4 in CD (p = 0.01, n = 53) and from 5 to 4 in UC (p = 0.03, n = 34) at 156 weeks. Correspondingly, median faecal-calprotectin (µg/g) decreased from 641 to 114 in CD patients (p < 0.01, n = 26) and from 387 to 37 in UC patients (p = 0.02, n = 17). Conclusion: VDZ demonstrated high continuation rates and was associated with improvements in clinical outcomes, HRQoL measures and inflammatory markers at 2 and 3 years after treatment initiation in this prospective national SVEAH extension study. Registration: ENCePP registration number: EUPAS22735.