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The editorial independence of biomedical journals allows flexibility to meet a wide range of research interests. However, it also is a barrier for coordination between journals to solve challenging issues such as racial bias in the scientific literature. A standardized tool to screen for racial bias could prevent the publication of racially biased papers. Biomedical journals would maintain editorial autonomy while still allowing comparable data to be collected and analyzed across journals. A racially diverse research team carried out a three-phase study to generate and test a racial bias assessment tool for biomedical research. Phase 1, an in-depth, structured literature search to identify recommendations, found near complete agreement in the literature on addressing race in biomedical research. Phase 2, construction of a framework from those recommendations, provides the major innovation of this paper. The framework includes three dimensions of race: 1) context, 2) tone and terminology, and 3) analysis, which are the basis for the Race Equity Vetting Instrument for Editorial Workflow (REVIEW) tool. Phase 3, pilot testing the assessment tool, showed that the REVIEW tool was effective at flagging multiple concerns in widely criticized articles. This study demonstrates the feasibility of the proposed REVIEW tool to reduce racial bias in research. Next steps include testing this tool on a broader sample of biomedical research to determine how the tool performs on more subtle examples of racial bias. [ABSTRACT FROM AUTHOR]

Background: STEM education providers increasingly use complex intervention models to redress persistent under-representation in STEM sectors. These intervention models require robust evaluation to determine their effectiveness. The study examines a complex, sustained intervention intended to build science capital in young people aged 11–15 over 3 years, which drew on science capital theory and related research to inform intervention design and evaluation. When evaluation results differed from those anticipated, process evaluation supported authors to interpret these findings. By outlining challenges faced in the evaluation of a complex, sustained STEM outreach intervention, this paper addresses critique that outreach programmes focus too often on short-term and positive findings. Results: Intervention outcomes were assessed using a quantitative questionnaire adapted from science capital research, issued to pupils at the intervention's baseline (2015), midpoint (2017) and endpoint (2019). Adopting a cohort-based model, the 2015 questionnaire collected a baseline for the Year 7 intervention group (children aged 11–12, N = 464), and established baseline comparator groups for Year 9 (children aged 13–14, N = 556) and Year 11 (children aged 15–16, N = 342). The Year 7 intervention group was re-evaluated again in 2017 when in Year 9 (N = 556), and in 2019 when in Year 11 (N = 349). Analysis explored differences in science capital between the intervention and comparator groups and identified lower composite science capital scores and greater proportions of low- and medium-science capital in the intervention group when compared with the two comparator groups. A rationale for this emerged from the subsequent process evaluation. Conclusions: This study's main contribution is the provision of nuanced insight into the evaluation of STEM interventions for use by others evaluating in similar circumstances, particularly those adopting sustained or complex delivery models. This paper concludes that assessing the effectiveness of complex interventions cannot rely on quantitative evaluation of outcomes alone. Process evaluation can complement quantitative instruments and aid interventions to better understand variability and interpret results. While this study highlights the value of science capital when designing intervention models, it also illustrates the inherent challenges of using an outcome measure of 'building science capital', and quantifying levels over an intervention's course. [ABSTRACT FROM AUTHOR]

Objective: Although previous epidemiological studies have demonstrated that serum uric acid (SUA) is associated with major depressive disorder (MDD), these analyses are prone to biases. Here, we applied the Mendelian Randomization approach to determine whether SUA is causally associated with MDD.Methods: We conducted a meta-analysis to evaluate the relationship between SUA and MDD, then applied summary data from the Global Urate Genetics Consortium and the Psychiatric Genomics Consortium to estimate their causal effect using a two-sample bidirectional Mendelian Randomization (MR) analysis. Thereafter, the causal effect was further researched using genetic risk scores (GRS) as instrumental variables (IVs).Results: Results of a meta-analysis of articles comprising 6975 and 13,589 MDD patients and controls, respectively, revealed that SUA was associated with MDD (SMD = -0.690, 95% CI: -0.930 to -0.440, I2 = 97.4%, P < 0.001). In addition, the five MR methods revealed no causal relationship existed between SUA and MDD, which corroborated the results obtained via the GRS approach.Conclusion: This paper found little evidence that this association between SUA and MDD is casual. Genetically, there was no significant causal association between SUA and MDD. [ABSTRACT FROM AUTHOR]

To solve the problem of regional water system evaluation, this paper proposes a system efficiency evaluation method based on the game cross-efficiency model and conducts an empirical analysis. First, autopoiesis is introduced as the theoretical basis. The characteristics of the authigenic system are combined with a regional water system, and the connotation and characteristics of the regional water system are defined. Second, based on the competitive relationship between regional water systems, the existing game crossover efficiency model is improved. A crossover efficiency model of other games is proposed to evaluate the efficiency of regional water systems. Then, the Pearl River Delta urban agglomeration is selected as the research object. The effects of four systematic evaluation methods based on the DEA method are compared horizontally to find the optimal system efficiency evaluation method. Finally, the characteristics of the regional water system in the Pearl River Delta are systematically analysed through the evaluation results, and the present situation of the regional water system is fully explained. [ABSTRACT FROM AUTHOR]

This paper presents a specific approach in the field of evaluating the effects of publicly supported R&D activities: the BETA approach. Initially developed for application to large technology procurement/agency driven public R&D programmes, it has been adapted to a larger range of programmes supporting science and technology. The BETA approach consists of identifying and retrospectively measuring, at the micro-level via direct interviews, the impact of different types of learning processes triggered by participation in R&D. A further adaptation to the specific case of research infrastructures was conducted in the frame of the EvaRIO project. It also dealt with learning processes from an ex post and micro-level perspective, but covered a wider variety of activities and actors over time, leading to a broader view of effects. Based on 30 years of impact evaluation experience, we argue that the revised BETA approach, despite its focus on the economic dimension of impacts, is at the intersection between different strands of evaluation research. The dual nature of the BETA approach is examined along several dimensions including an output versus process perspective, project versus organization scope, qualitative versus quantitative investigation, contribution versus attribution issues, private profitability versus public value perspective, etc. We show that the BETA-EvaRIO method can be used to complement other evaluation methodologies and can be considered as bridging among them, or can be seen as a single, specific approach. [ABSTRACT FROM AUTHOR]

Objectives: Digital breast tomosynthesis (DBT) plus digital mammography (DM) in screening is problematic due to increased radiation by the double exposure. Synthesised two-dimensional mammography (s2D) calculated from DBT datasets at no additional dose appears a sensible alternative compared to adding DM. This systematic review and meta-analysis focuses on screening performance outcomes in women screened with DBT plus s2D compared to DM alone.Methods: PubMed was searched from January 1, 2010, to September 2, 2020. Studies comparing DBT plus s2D to DM alone in breast cancer screening were included. Pooled risk ratios (RR) were estimated for cancer detection rates (CDR), recall rates, interval cancer rates (ICR), biopsy rates, and positive predictive values for recalls (PPV-1), for biopsies recommended (PPV-2), and for biopsies performed (PPV-3). Sensitivity analyses were performed using the leave-one-out approach. Risk of bias (RoB) was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool.Results: Twelve papers covering 414,281 women were included from 766 records identified. CDR is increased ([RR, 95% CI] 1.35, 1.20-1.52), recall rates are decreased (0.79, 0.64-0.98), and PPV-1 is increased (1.69, 1.45-1.96) when using DBT plus s2D compared to DM alone. ICR and biopsy rates did not differ, but PPV-2 respectively PPV-3 increased with DBT plus s2D (1.57, 1.08-2.28 respectively 1.36, 1.17-1.58). Overall RoB of studies was assessed to be low.Conclusion: Results show improved diagnostic outcomes with DBT plus s2D compared to DM alone and underline the value of DBT in combination with s2D in breast cancer screening.Key Points: • DBT plus s2D is associated with higher CDR, lower recall rates, and a higher PPV-1 compared to DM alone in breast cancer screening. • No differences in biopsy rates were found between screening modalities, but PPV-2 and PPV-3 were higher in women screened with DBT plus s2D compared to DM alone. • We identified inconsistent results of ICR in two studies comparing DBT plus s2D to DM alone-resulting in no differences when pooling ICR in meta-analysis. [ABSTRACT FROM AUTHOR]

Purpose: Age, sex, and type of fracture have traditionally been described as prognostic factors for proximal humeral fractures (PHFs). Some non-medical patient-related factors may play a role in the outcome. This paper evaluates the association of comorbidities and socioeconomic factors with clinical outcomes for PHF.Methods: A total of 217 patients with PHF were evaluated according to Neer's classification with X-ray. Comorbidities were assessed through the Charlson comorbidity index and, non-medical patient-related factors were determined with a 52-item questionnaire concerning personal behaviors such as social activities, family support, economic solvency, and leisure-time activities. The clinical outcome was assessed with the Constant-Murley Score (CMS), with a minimum 1-year follow-up. The minimal clinically relevant difference for the CMS was set at 10 points. A multivariable analysis was performed to adjust for comorbidities and non-medical patient-related factors, such as age, sex, fracture classification, and treatment.Results: One hundred and eighty-three patients completed the initial research protocol, while 126 of them completed the 1-year follow-up. The mean age was 71.6 years (SD ± 13.3), and 79.3% of the patients were women. In the bivariable analysis, age and comorbidities were correlated with the CMS (correlation coefficient: - 0.34 [- 0.49, 0.17] and 0.35 [0.18, 0.50], respectively), as well as non-medical patient-related factors and the fracture pattern (p value ANOVA < 0.001). In the multivariable regression model, the effects of considering oneself socially active, without economic problems, and self-sufficient were associated with a higher CMS than the effect of the fracture pattern (beta coefficient: 11.69 [6.09-17.30], 15.54 [8.32-22.75], and 10.61 [3.34-17.88], respectively).Conclusion: Socioeconomic status had a higher impact on functional outcomes than fracture pattern in patients with PHF. [ABSTRACT FROM AUTHOR]

Due to rapid developments in machine learning, and in particular neural networks, a number of new methods for time-to-event predictions have been developed in the last few years. As neural networks are parametric models, it is more straightforward to integrate parametric survival models in the neural network framework than the popular semi-parametric Cox model. In particular, discrete-time survival models, which are fully parametric, are interesting candidates to extend with neural networks. The likelihood for discrete-time survival data may be parameterized by the probability mass function (PMF) or by the discrete hazard rate, and both of these formulations have been used to develop neural network-based methods for time-to-event predictions. In this paper, we review and compare these approaches. More importantly, we show how the discrete-time methods may be adopted as approximations for continuous-time data. To this end, we introduce two discretization schemes, corresponding to equidistant times or equidistant marginal survival probabilities, and two ways of interpolating the discrete-time predictions, corresponding to piecewise constant density functions or piecewise constant hazard rates. Through simulations and study of real-world data, the methods based on the hazard rate parametrization are found to perform slightly better than the methods that use the PMF parametrization. Inspired by these investigations, we also propose a continuous-time method by assuming that the continuous-time hazard rate is piecewise constant. The method, named PC-Hazard, is found to be highly competitive with the aforementioned methods in addition to other methods for survival prediction found in the literature. [ABSTRACT FROM AUTHOR]

Identification of pediatric patients with acute myeloid leukemia (AML) candidates to receive allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission (CR1) is still a matter of debate. Currently, transplantation is reserved to patients considered at high risk of relapse based on cytogenetics, molecular biology, and minimal residual disease (MRD) assessment. However, no randomized clinical trial exists in the literature comparing transplantation with other types of consolidation therapy. Here, we provide an up-to-date meta-analysis of studies comparing allo-HSCT in CR1 with chemotherapy alone as a post-remission treatment in high-risk pediatric AML. The literature search strategy identified 10 cohorts from 9 studies performing as-treated analysis. The quantitative synthesis showed improved overall survival (OS) (relative risk, 1.15; 95% confidence interval [CI], 1.06-1.24; P = 0.0006) and disease-free survival (relative risk, 1.31; 95% CI, 1.17-1.47; P = 0.0001) in the allo-HSCT group, with increased relapse rate in the chemotherapy group (relative risk, 1.26; 95% CI, 1.07-1.49; P = 0.006). Sensitivity analysis including prospective studies alone and excluding studies that reported the comparison only on intermediate-risk patients confirmed the benefit of allo-HSCT on OS. Further research should focus on individualizing allo-HSCT indications based on molecular stratification and MRD monitoring. [ABSTRACT FROM AUTHOR]

Background: This study aims to assess the rate at which screening colonoscopy is performed on patients younger or older than the age range specified in national guidelines, or at shorter intervals than recommended. Such non-indicated use of the procedure is considered low-value care, or overuse. This study is the first systematic review of the rate of non-indicated completed screening colonoscopy in the USA.Methods: PubMed and Embase were queried for relevant studies on overuse of screening colonoscopy published from January 1, 2002, until January 23, 2019. English-language studies that were conducted for screening colonoscopy after 2001 for average-risk patients were included. Studies must have followed national guidelines for detecting rates of overuse. We followed methods outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the reporting recommendations of the Meta-analysis of Observational Studies in Epidemiology group (MOOSE).Results: A total of 772 papers were reviewed for inclusion; 42 were reviewed in full text. Of those reviewed, six studies met eligibility criteria, including a total of 459,503 colonoscopies of which 242,756 were screening colonoscopies. The rate of overuse ranged credibly from 17 to 25.7%.Discussion: This study demonstrates that screening colonoscopy is regularly performed in the USA more often, and in populations older or younger, than recommended by national guidelines. Such overuse wastes resources and places patients at unnecessary risk of harm. Efforts to reduce non-indicated screening colonoscopy are needed. [ABSTRACT FROM AUTHOR]

Objective: The prevalence of anemia has remained high among Indian adolescent girls over the past decade, despite the ongoing iron and folic acid (IFA) supplementation program. This study was conducted to assess the impact of daily supplementation of a package of IFA with vitamin B12 on hemoglobin levels among adolescent girls.Methods: A community-based cluster-randomized trial was conducted in the rural block of Faridabad District, Haryana, India in the year 2017. A total of 760 adolescent girls in the age group of 12-19 years with mild and moderate anemia were selected from government schools. Daily-supervised administration of iron and folic acid was conducted for 90 days: experimental group-IFA (iron (60 mg), folic acid (500) mcg), and cyanocobalamin (1000 mcg), control group-IFA and placebo. Hemoglobin, serum ferritin, and vitamin B12 levels were assessed at baseline and endline.Results: Two-hundred adolescent girls completed 90 doses of daily supplementation. The mean hemoglobin (experimental group: 1.3 ± 1.0 g/dL, control group: 1.6 ± 1.2 g/dL, P = 0.004) and ferritin levels (experimental group: 18.6 ± 31.5 ng/mL, control group: 18.8 ± 35.0 ng/mL, P = 0.188) increased in both the control and experiment groups. Serum vitamin B12 deficiency significantly reduced to 2.5% in the experimental group and ferritin deficiency alleviated in more than 96% of the girls post intervention.Conclusions: Daily supplementation of IFA with/without vitamin B12 for 90 days eliminated iron, vitamin B12 deficiency and reduced the overall proportion of anemia by 53.5%. However, addition of vitamin B12 to IFA supplementation had no impact on improving the hemoglobin levels among adolescent girls. The present study does not recommend provision of vitamin B12 for prevention and treatment of anemia in this population group. [ABSTRACT FROM AUTHOR]

Swallowing disorder is one of the most common postoperative complications for oral cancer patients and seriously influences quality of life. Limited attention has been paid to evaluating swallowing training measures in postoperative oral cancer patients. This study systematically reviewed swallowing training measures for these patients. A comprehensive search strategy was undertaken across various databases for studies published between database inception and 15 June 2021. Raters independently judged titles, abstracts and full articles for selection according to inclusion and exclusion criteria. The included literature was evaluated for quality and data were extracted. Meta-analyses were conducted using RevMan 5.3. Ten intervention studies (four randomized controlled trials and six quasi-experimental studies) involving 588 patients were identified. Across the studies, most started in the early postoperative stage; however, there were differences in starting time, training time and duration, and type of training. We summarized four training methods: oral exercise, oral sensory stimulation, compensatory strategies and protective airway manoeuvres. The meta-analysis indicated that swallowing training could improve patients' swallowing function and quality of life in the short term, but the long-term effects were not obvious. Swallowing training mostly occurred in the early postoperative period and training measures were often used in combination. The timing, frequency and content of interventions varied between studies, and the effectiveness of any single measure was unclear. High-quality randomized controlled trials are necessary to study the efficacy and clinical applicability of various training measures, to provide a theoretical basis for their optimal selection and to develop a standardized training programme for postoperative oral cancer patients. [ABSTRACT FROM AUTHOR]

Background/objectives: Continuous positive airway pressure (CPAP) concomitant with weight loss is a recommended treatment approach for adults with moderate-severe obstructive sleep apnoea (OSA) and obesity. This requires multiple synchronous behaviour changes. The aim of this study was to examine the effectiveness of a 6-month lifestyle intervention and to determine whether the timing of starting a weight loss attempt affects weight change and trajectory after 12 months in adults newly diagnosed with moderate-severe OSA and treated at home with overnight CPAP.Methods: Using a stepped-wedge design, participants were randomised to commence a six-month lifestyle intervention between one and six-months post-enrolment, with a 12-month overall follow-up. Adults (n = 60, 75% males, mean age 49.4 SD 10.74 years) newly diagnosed with moderate-severe OSA and above a healthy weight (mean BMI 34.1 SD 4.8) were recruited.Results: After 12 months, exposure to the intervention (CPAP and lifestyle) resulted in a 3.7 (95% CI: 2.6 to 4.8, p < 0.001) kg loss of weight compared to the control condition (CPAP alone). Timing of the weight loss attempt made no difference to outcomes at 12 months. When exposed to CPAP only (control period) there was no change in body weight (Coef, [95% CI] 0.03, [-0.3 to 0.36], p = 0.86).Conclusions: The lifestyle intervention resulted in a modest reduction in body weight, while timing of commencement did not impact the degree of weight loss at 12 months. These findings support the recommendation of adjunctive weight-loss interventions within six-months of starting CPAP. [ABSTRACT FROM AUTHOR]

Background: Health information exchange (HIE) notifications when patients experience cross-system acute care encounters offer an opportunity to provide timely transitions interventions to improve care across systems.Objective: To compare HIE notification followed by a post-hospital care transitions intervention (CTI) with HIE notification alone.Design: Cluster-randomized controlled trial with group assignment by primary care team.Patients: Veterans 65 or older who received primary care at 2 VA facilities who consented to HIE and had a non-VA hospital admission or emergency department visit between 2016 and 2019.Interventions: For all subjects, real-time HIE notification of the non-VA acute care encounter was sent to the VA primary care provider. Subjects assigned to HIE plus CTI received home visits and telephone calls from a VA social worker for 30 days after arrival home, focused on patient activation, medication and condition knowledge, patient-centered record-keeping, and follow-up.Measures: Primary outcome: 90-day hospital admission or readmission.Secondary Outcomes: emergency department visits, timely VA primary care team telephone and in-person follow-up, patients' understanding of their condition(s) and medication(s) using the Care Transitions Measure, and high-risk medication discrepancies.Key Results: A total of 347 non-VA acute care encounters were included and assigned: 159 to HIE plus CTI and 188 to HIE alone. Veterans were 76.9 years old on average, 98.5% male, 67.8% White, 17.1% Black, and 15.1% other (including Hispanic). There was no difference in 90-day hospital admission or readmission between the HIE-plus-CTI and HIE-alone groups (25.8% vs. 20.2%, respectively; risk diff 5.6%; 95% CI - 3.3 to 14.5%, p = .25). There was also no difference in secondary outcomes.Conclusions: A care transitions intervention did not improve outcomes for veterans after a non-VA acute care encounter, as compared with HIE notification alone. Additional research is warranted to identify transitions services across systems that are implementable and could improve outcomes. [ABSTRACT FROM AUTHOR]

Objectives: Intravenous application of contrast media is part of a wide spectrum of diagnostic procedures for better imaging quality. Clinical avoidance of contrast-enhanced imaging is an ever-present quandary in patients with impaired kidney function. The objective of this study was to estimate the risk for acute kidney injury (AKI), dialysis and mortality among patients undergoing contrast-enhanced CT compared to propensity score-matched controls (i.e. contrast-unenhanced CT). Selected cohort studies featured high-risk patients with advanced kidney disease and critical illness.Methods: This review was designed to conform to the Preferred Reporting Items in Systematic Reviews and Meta-Analysis (PRISMA) guidelines. PubMed was searched from August 2021 to November 2021 for all-language articles without date restriction. A random-effects model (DerSimonian and Laird method) was used for meta-analysis.Results: Twenty-one articles were included, comprising data of 169,455 patients. The overall risk of AKI was similar in the contrast-enhanced and unenhanced groups (OR: 0.97 [95% CI: 0.85; 1.11], p = 0.64), regardless of baseline renal function and underlying disease. Substantial heterogeneity was detected (I2 = 90%, p ≤ 0.0001). Multivariable logistic regression identified hypertension (p = 0.03) and estimated glomerular filtration rate (eGFR) ≤ 30 mL/min/1.73 m2 (p = 0.0001) as factors associated with greater risk of post-contrast AKI.Conclusions: Based on propensity score-matched pairs obtained from 21 cohort studies, we found no evidence for increased risk for AKI, dialysis or mortality after contrast-enhanced CT among patients with eGFR ≥ 45 mL/min/1.73 m2. In congruence with the emerging evidence in the literature, caution should be exercised in patients with hypertension and eGFR ≤ 30 mL/min/1.73 m2.Key Points: • The application of contrast media for medical imaging is not associated with higher odds for AKI, induction of renal replacement therapy, or mortality. Many comorbidities traditionally associated with greater risk for acute kidney injury do not appear to predispose for renal decline after contrast media exposure. • Underlying hypertension and eGFR less than or equal to 30 mL/min/1.73 m2 seem to predispose for post-contrast acute kidney injury. • Propensity score matching cannot account for unmeasured influences on AKI incidence, which needs to be addressed in the interpretation of results. [ABSTRACT FROM AUTHOR]

Introduction: There is considerable variation in the practice of ventral hernia repair (VHR). Consequently, both short- and long-term outcomes are different. We report the first multicenter data from India on the variations in procedures and short-term outcomes after ventral hernia repair.Methods: A prospective study was planned under the aegis of the Indian Association of Gastrointestinal Endo Surgeons (IAGES). Participating surgeons prospectively recorded the data of patients who underwent VHR from January 21, 2021, to April 20, 2021. Patients were followed for 3-6 months.Results: Data from 648 patients were analyzed for demographics, hernia characteristics, technical variations, and outcomes. 375 (57.8%) were primary hernias (PH) and 273 (42.15%) were incisional hernias (IH), of which 63 (9.7%) were recurrent hernias. In the PH group, there were 171 minimal access (MAS) and 170 open repair. In descending order of frequency, there were 111 (32.6%) open onlay, 83 (24.3%) intraperitoneal onlay meshplasty (IPOM) Plus, 36 (10.6%) IPOM, 35 (10.3%) suture repair, 22 (6.5%) endoscopic Rives Stoppa (eRS), 11 (3.2%) open RS, 11 (3.2%) TAPP, 7 (2%) hybrid, 6 (1.8%) open preperitoneal, 19 (5.6%) others. There were 3.73% seroma, 3.2% SSI, 0% 90-day readmission, 0% recurrence, and 0.3% mortality. In the IH group, 164 patients underwent open repair and 104 MAS repair. In descending order of frequency, there were 90 (33.6%) open onlay, 47 (17.5%) IPOM Plus, 38 (14.1%) open sublay, 28 (10.4%) IPOM, 12 (4.5%) Transversus Abdominis Release (TAR), 11 (4.1%) suture repair, 9 (3.4%) open preperitoneal, 7 (2.6%) hybrid, 6 (2.2%) TAPP, 5 (1.9%) eRS, 4 (1.5%) TARM, 3 (1.1%) endoscopic TAR (eTAR), and 8 (3%) others. There were 13.92% seroma, 4.4% hematoma, 9.5% SSI, 1.1% mesh explantation, 0.4% wound sinus, 2.2% 90-day readmission, 0% recurrence, and 1.1% mortality.Conclusion: Onlay meshplasty is the commonest procedure in India both in PH and IH. IPOM/IPOM plus is the second commonest procedure. TAR is the preferred component separation technique. Complication rates were comparable to published literature.Trial Registration: The study was registered with Clinical Trial Registry of India. CTRI number-CTRI/2021/01/030435. [ABSTRACT FROM AUTHOR]

Background: Black patients in the USA are disproportionately affected by chronic pain, yet there are few interventions that address these disparities.Objective: To determine whether a walking-focused, proactive coaching intervention aimed at addressing contributors to racial disparities in pain would improve chronic pain outcomes among Black patients compared to usual care.Design: Randomized controlled trial with masked outcome assessment ( Clinicaltrials.gov : NCT01983228).Participants: Three hundred eighty Black patients at the Atlanta VA Health Care System with moderate to severe chronic back, hip, or knee pain.Intervention: Six telephone coaching sessions over 8-14 weeks, proactively delivered, using action planning and motivational interviewing to increase walking, or usual care.Main Measures: Primary outcome was a 30% improvement in pain-related physical functioning (Roland Morris Disability Questionnaire [RMDQ]) over 6 months among Black patients, using intention-to-treat. Secondary outcomes were improvements in pain intensity and interference, depression, anxiety, global impression of change in pain, and average daily steps.Key Results: The intervention did not produce statistically significant effects on the primary outcome (at 6 months, 32.4% of intervention participants had 30% improvement on the RMDQ vs. 24.7% of patients in usual care; aOR=1.61, 95% CI, 0.94 to 2.77), nor on other secondary outcomes assessed at 6 months, with the exception that intervention participants reported more favorable changes in pain relative to usual care (mean difference=-0.54, 95% CI, -0.85 to -0.23). Intervention participants also experienced a significant reduction in pain intensity and pain interference over 3 months (mean difference=-0.55, 95% CI, -0.88 to -0.22).Conclusions: A novel intervention to improve chronic pain among Black patients did not produce statistically significant improvements on the primary outcome relative to usual care. More intensive efforts are likely required among this population, many of whom were economically disadvantaged and had mental health comorbidities and physical limitations.Trial Registration: Clinicaltrials.gov Identifier: NCT01983228. [ABSTRACT FROM AUTHOR]

Objectives: To determine the performance of diagnostic algorithm of adding hepatobiliary phase (HBP) images in Gd-EOB-DTPA-enhanced MRI for the detection of hepatocellular carcinoma (HCC) measuring up to 3 cm in patients with chronic liver disease.Methods: We searched multiple databases from inception to April 10, 2020, to identify studies on using Gd-EOB-DTPA-enhanced MRI for the diagnostic accuracy of HCC (≤ 3 cm) in patients with chronic liver disease. The diagnostic algorithm of Gd-EOB-DTPA-enhanced MRI with HBP for HCC was defined as a nodule showing hyperintensity during arterial phase and hypointensity during the portal venous, delayed, or hepatobiliary phases. For gadoxetic acid-enhanced MRI without HBP, the diagnostic criteria were a nodule showing arterial enhancement and hypointensity on the portal venous or delayed phases. The data were extracted to calculate summary estimates of sensitivity, specificity, diagnostic odds ratio, likelihood ratio, and summary receiver operating characteristic (sROC) by using a bivariate random-effects model.Results: Twenty-nine studies with 2696 HCC lesions were included. Overall Gd-EOB-DTPA-enhanced MRI with HBP had a sensitivity of 87%, specificity of 92%, and the area under the sROC curve of 95%. The summary sensitivity of Gd-EOB-DTPA-enhanced MRI with HBP was significantly higher than that without HBP (84% vs 68%, p = 0.01).Conclusion: Gd-EOB-DTPA-enhanced MRI with HBP showed higher sensitivity than that without HBP and had comparable specificity for diagnosis of HCC in patients with chronic liver disease.Key Points: • Hypointensity on HBP is a major feature for diagnosis of HCC. • Extending washout appearance to the transitional or hepatobiliary phase on Gd-EOB-DTPA provides favorable sensitivity and comparable specificity for diagnosis HCC. • The summary sensitivity of gadoxetic acid-enhanced MRI with HBP was significantly higher than that without HBP (84% vs 68%, p = 0.01) for diagnosis of HCC in patients with chronic liver disease. [ABSTRACT FROM AUTHOR]

Objectives: The multicenter study aimed to explore the relationship between the growth pattern of liver metastases on preoperative MRI and early recurrence in patients with colorectal cancer liver metastases (CRCLM) after surgery.Methods: A total of 348 CRCLM patients from 3 independent centers were enrolled, including 130 patients with 339 liver metastases in the primary cohort and 218 patients in validation cohorts. Referring to the gross classification of hepatocellular carcinoma (HCC), the growth pattern of each liver metastasis on MRI was classified into four types: rough, smooth, focal extranodular protuberant (FEP), and nodular confluent (NC). Disease-free survival (DFS) curve was constructed using the Kaplan-Meier method.Results: In primary cohort, 42 (12.4%) of the 339 liver metastases were rough type, 237 (69.9%) were smooth type, 29 (8.6%) were FEP type, and 31 (9.1%) were NC type. Those patients with FEP- and/or NC-type liver metastases had shorter DFS than those without such metastases (p < 0.05). However, there were no significant differences in DFS between patients with rough- and smooth-type liver metastases and those without such metastases. The patients with FEP- and/or NC-type liver metastases also had shorter DFS than those without such metastases in two external validation cohorts. In addition, 40.5% of high-risk-type (FEP and NC) liver metastases converted to low-risk types (rough and smooth) after neoadjuvant chemotherapy.Conclusion: The FEP- and NC-type liver metastases were associated with early recurrence, which may facilitate the clinical treatment of CRCLM patients.Key Points: • In the primary cohort, patients with FEP- and NC-type metastases had shorter disease-free survival (DFS) and a higher intrahepatic recurrence rate than patients without such metastases in the liver. • In the primary cohort, there were no significant differences in DFS or intrahepatic recurrence rate between patients with rough- and smooth-type metastases and those without such metastases in the liver. • High-risk patients had shorter DFS and a higher intrahepatic recurrence rate than low-risk patients in primary and external validation cohorts. [ABSTRACT FROM AUTHOR]

Over the past decade, there has been rapid growth in the evidence for programs to prevent or reduce intimate partner violence (IPV)-the most common form of men's violence against women. IPV interventions targeting heterosexual couples have shown significant impact. However, our understanding of how these interventions achieve their impacts on violence-the mechanisms through which change occurs-remains limited. Using data from two follow-up rounds of a randomized controlled trial of the Bandebereho intervention in Rwanda, we constructed conceptually driven structural equation models to represent the processes by which hypothesized mediating variables linked treatment assignment to IPV. We found significant differences in the expected direction between the intervention and control participants on all mediating variables, including men's alcohol use, communication frequency, emotional closeness, frequency of quarreling, and men's attitudes related to gender and violence. Several mechanisms-more positive couple dynamics including emotional closeness and communication frequency; men's gender-equitable attitudes; men's alcohol use-accounted for the largest proportions of the effect of assignment to the Bandebereho intervention on IPV. Overall, our findings highlight that no one particular component is driving the reductions in violence; instead, the multiple components and pathways account for the intervention's effects, suggesting that the holistic nature of the intervention may be integral to its positive impact. The Bandebereho trial from which data was used in this analysis was registered on ClinicalTrials.gov prior to completion ( NCT02694627 ). [ABSTRACT FROM AUTHOR]

Mentoring is considered an evidence-based practice for violence prevention. This study presents a partial replication of the Take Charge! program implemented in partnership with Big Brothers Big Sisters of America (BBBS). One hundred and eighty-eight early adolescents (M age = 12.87; 61.17% male) who were treated for peer-related assault injury in two urban mid-Atlantic emergency departments were randomly assigned to receive a mentor from two BBBS affiliates. Mentors and organization staff were trained in the Take Charge! violence prevention curriculum, which had previously shown evidence of efficacy. Intent-to-treat analyses showed statistically significant improvements in conflict avoidance self-efficacy for the intervention group at 9 months and reductions in fighting at 21 months, but an increase in parental report of aggression at 9 months. Complier average causal effect models revealed evidence of an additional effect for reduced problem behavior at 21 months for intervention adolescents who received a mentor. No effects were found for youth-reported aggression, retaliatory attitudes, deviance acceptance, or commitment to learning. Sensitivity analyses suggested increased aggressive behavior for adolescents in the intervention group who did not receive a mentor (i.e., non-compliers). These findings extend the evidence-base for Take Charge! as a violence prevention curriculum for youth already engaged in violence to "real-world" implementation settings. However, they also suggest that challenges associated with providing youth with mentors can be consequential and that additional supports may be needed for these youth/parents. Clinical trials number: clinicaltrials.gov NCT01770873. [ABSTRACT FROM AUTHOR]

Aim: The combination of cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitors plus endocrine therapy (ET) improved the survival outcomes and became the standard of care in the treatment of metastatic hormone-positive breast cancer. However, these combinations increased the risk of neutropenia compared with ET alone. While the infection-related mortalities did not seem to be increased, the exact risk of infections with CDK 4/6 inhibitor and ET combinations is relatively understudied. Therefore, we performed a meta-analysis of CDK 4/6 inhibitor clinical trials to assess the infection risk of adding CDK4/6 inhibitors to ET.Material and Method: We systemically searched the PubMed database for relevant clinical trials. For each study, all grade and grade 3 or higher infections, upper respiratory tract infections (URTI), urinary tract infections (UTI), pneumonia, and febrile neutropenia rates were recorded whenever available. The hazard ratios (HR) with a 95% confidence interval (CI) of infection risk were calculated via the generic inverse-variance method with a random-effects model.Results: Nine eligible studies were included in the analyses (MONALEESA-2,3,7, MONARCH-2,3, MONARCH plus, PALOMA-1,2,3). In the meta-analysis of these studies, CDK 4/6 inhibitors plus ET arms were associated with increased all grade infections (HR 1.77, 95% CI 1.56-2.01, p < 0.00001), grade 3 or higher infections, (HR 1.77, 95% CI 1.28-2.43, p = 0.0005), UTIs (HR 1.59, 95% CI 1.19-2.12, p = 0.002), and febrile neutropenia (HR 4.28, 95% CI 1.73-10.62, p = 0.002).Conclusion: In this meta-analysis, we observed that adding CDK4/6 inhibitors to ET significantly increased the risk of all grade, grade 3 or higher infections, and urinary tract infections. We propose that closer follow-up for infections should be considered for metastatic breast cancer patients using CDK 4/6 inhibitors. This may help clinicians to recognize infections earlier which prevents early death from infection. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether ultrasound-guided umbilical venous catheter (UVC) insertion (US group) reduced the rate of malpositioning of the catheter tip compared to the standard method of insertion (SD group).Methods: In this open-label, randomized, controlled trial, neonates admitted to NICU within the first week of life were randomly assigned to the US group (n = 26) or SD group (n = 27). Neonates with major congenital anomalies of the thorax and abdomen were excluded. The primary outcome was the rate of malpositioning of the catheter tip.Results: The rate of malpositioning of the catheter tip was observed in a significantly lower number of neonates in the US group as compared to the SD group (11/26, 42.3% vs. 20/27, 74%; RR = 0.57, 95% CI: 0.34 to 0.94, p = 0.019). As more of the UVCs were positioned optimally in the first attempt in the US group than SD group, the need for repeated attempts at catheter repositioning was reduced, resulting in reduced procedure time (minutes) [mean (SD), 23.96 (6.42) vs. 30 (1.83); mean difference 6.04 (95% CI: 3.46 to 8.62), p = 0.005]. This also led to a reduction in the additional X-ray exposure in the US group (n = 11) compared to the SD group (n = 20) [95% CI: 3.12 to 44.26; p = 0.020].Conclusion: Ultrasound-guided UVC insertion significantly reduced the rate of catheter tip malposition. It also reduced the number of attempts at catheter manipulation, procedure time, and X-ray exposures. With adequate training, it could be incorporated into routine bedside practice during UVC insertion for optimum placement.Trial Registration: Clinical Trial Registry of India ( www.ctri.nic.in ) CTRI/2021/03/031894. [ABSTRACT FROM AUTHOR]

Introduction: This MONONOFU trial subgroup analysis evaluates the efficacy of lasmiditan across patient and migraine characteristics in Japanese patients with migraine.Methods: MONONOFU trial was a multicenter, randomized, double-blind, placebo-controlled study. The patients were randomly assigned in a 3:7:6:7 ratio to receive lasmiditan 50 mg, 100 mg, 200 mg, or placebo for a single migraine attack within 4 h of pain onset. Efficacy of lasmiditan vs placebo was evaluated at 2 h post dose for proportion of patients with headache pain freedom. Efficacy was assessed across patient characteristics (age, sex, body weight, cardiovascular risk factors (CVRF), and comorbidity of tension-type headache), migraine disease characteristics (history of migraine with aura, migraine prevention therapy, triptan response, and triptan use or nonuse), and migraine attack characteristics (headache severity, aggressive headache, attack during perimenstrual period, time to dosing, time of dosing, experienced treatment-emergent adverse event (TEAE) of dizziness, and experienced TEAE of somnolence). Logistic regression was used; all subgroup analyses were not analyzed with multiplicity-adjusted statistical tests.Results: Treatment-by-subgroup interactions (by each arm) were not significant (p ≥ 0.05) for pain freedom at 2 h post dose across all patient subgroups and lasmiditan doses, except for CVRF (100 mg and 200 mg), migraine with aura (50 mg), triptan response (50 mg), and time to dosing (200 mg). Treatment-by-subgroup interactions (by overall) were not significant (p ≥ 0.05) for pain freedom at 2 h post dose across all patient subgroups, except for CVRFs. Higher proportions of patients were pain free at 2 h post dose when treated with lasmiditan (50 mg, 100 mg, and 200 mg) versus placebo, irrespective of most patient characteristics, migraine disease characteristics, and migraine attack characteristics.Conclusion: Although few interactions were observed, lasmiditan could be a promising acute treatment option in a wide range of Japanese patients with migraine, as efficacy is not generally influenced by patient and migraine characteristics. [ABSTRACT FROM AUTHOR]

Introduction: Lasmiditan is the first 5-HT1F receptor agonist with potential to address the huge unmet medical needs for the treatment of migraine in China. The CENTURION study was the first phase 3 study of lasmiditan in Caucasian and Chinese patients with migraine. This post hoc analysis further demonstrates the safety profile of lasmiditan in the Chinese population and was urgently needed.Methods: Patients were randomized 1:1:1 to lasmiditan 200 mg lasmiditan 100 mg, or a control group. The incidence of treatment-emergent adverse events (TEAEs), their severity, and incidence by treated attacks for frequently reported TEAEs (≥ 5%) were evaluated. The duration, onset, and relationship of efficacy with very common TEAEs (≥ 10%) was analyzed.Results: A total of 281 Chinese patients were included in this post hoc analysis. No deaths and no study drug-related treatment emergent serious adverse events (TESAEs) were reported. The incidence of at least one TEAE was higher in patients receiving lasmiditan 200 mg (73.9%) and 100 mg (66.3%) versus placebo (26.6%). TEAEs were generally mild or moderate in severity, and the incidence of frequently reported TEAEs was generally highest during the first attack. Very common TEAEs with lasmiditan included dizziness, asthenia, somnolence, muscular weakness, fatigue, and nausea. The duration of dizziness was longest during the first attack. There were no cardio-cerebrovascular ischemic events and serotonin syndrome. The presence of very common TEAEs (except nausea), and severe dizziness, did not appear to have a negative influence on the efficacy.Conclusion: In the Chinese population of the CENTURION study, most of the TEAEs were neurologic, of mild or moderate severity, and self-limiting. The distribution of frequently reported TEAEs at the first attack differed from the primary cohort, while the overall safety profile of lasmiditan in the Chinese population was generally consistent with the CENTURION primary cohort. No new safety concerns were observed in the Chinese population.Trial Registration: NCT03670810. [ABSTRACT FROM AUTHOR]

This study aimed to compare the effects of extracorporeal shockwave therapy (ESWT) and high-intensity laser therapy (HILT) on pain, grip strength, and function in patients with lateral epicondylalgia. This prospective randomized controlled study included 42 patients (22 women and 20 men, mean age: 37) divided into 3 groups. The first group received physiotherapy (n = 14), the second received physiotherapy combined with ESWT (n = 14), and the third received physiotherapy combined with HILT (n = 14). All participants underwent 10 physiotherapy sessions for 2 weeks, 5 sessions per week. In addition to physiotherapy, the ESWT group received 4 ESWT sessions, 2 sessions per week, and the HILT group received 4 HILT sessions, 2 sessions per week. The outcomes were pain intensity as assessed by Visual Analog Scale, grip strength by hand dynamometer, and function by the Duruoz Hand Index and Patient-Rated Tennis Elbow Evaluation-Turkish version questionnaire. The participants were assessed at the beginning of the study (T1/week 0), at the end of treatment (T2/2nd week), and at follow-up (T3/6th week). At follow-up (T3), a significant improvement was observed in all outcomes compared to baseline (T1) in all groups (P < 0.05). Inter-group comparison of the mean differences between baseline and end values showed that the HILT group was superior in all outcomes (P < 0.05). This study showed that physiotherapy alone combined with ESWT and HILT positively affected the treatment of lateral epicondylalgia. Physiotherapy combined with HILT was found to be the most effective for improving pain, grip strength, and function. Clinical trial number: NCT674325. [ABSTRACT FROM AUTHOR]

Purpose: To investigate potential associations between preoperative MRI findings and patient reported outcome measures (PROMs) after surgery for lumbar spinal stenosis (LSS).Methods: The NORDSTEN trial included 437 patients. We investigated the association between preoperative MRI findings such as morphological grade of stenosis (Schizas grade), quantitative grade of stenosis (dural sac cross-sectional area), disc degeneration (Pfirrmann score), facet joint tropism and fatty infiltration of the multifidus muscle, and improvement in patient reported outcome measures (PROMs) 2 years after surgery. We dichotomized each radiological parameter into a moderate or severe category. PROMs i.e., Oswestry Disability Index (ODI), Zurich Claudication Questionnaire (ZCQ) and Numeric rating scale (NRS) for back and leg pain were collected before surgery and at 2 year follow-up. In the primary analysis, we investigated the association between MRI findings and ODI score (dichotomized to ≥ 30% improvement or not). In the secondary analysis, we investigated the association between MRI findings and the mean improvement on the ODI-, ZCQ- and NRS scores. We used multivariable regression models adjusted for patients' gender, age, smoking status and BMI.Results: The primary analysis showed that severe disc degeneration (Pfirrmann score 4-5) was significantly associated with less chance of achieving a 30% improvement on the ODI score (OR 0.54, 95% CI 0.34, 0.88). In the secondary analysis, we detected no clinical relevant associations.Conclusion: Severe disc degeneration preoperatively suggest lesser chance of achieving 30% improvement in ODI score after surgery for LSS. Other preoperative MRI findings were not associated with patient reported outcome. [ABSTRACT FROM AUTHOR]

Background/objectives: Self-reported digestive intolerance to dairy foods is common. As dairy can be an important source of dietary protein, this study aimed to identify whether milk protein digestion is compromised in individuals with digestive intolerance.Subjects/methods: Adult women (n = 40) were enroled in this double-blinded, randomised cross-over trial, with digestive symptoms characterised using a lactose challenge and self-reported digestive symptom questionnaire. Participants were classified as either lactose intolerant (LI, n = 10), non-lactose dairy intolerant (NLDI, n = 20) or dairy tolerant (DT, n = 10). In a randomised sequence, participants consumed three different kinds of milk (750 ml); conventional milk (CON), a2 Milk™ (A2M), and lactose-free conventional milk (LF-CON). Circulatory plasma amino acid (AA) concentrations were measured at baseline and every 30 min until 3 h post-ingestion.Results: In all participants across all milk types, plasma AA concentrations (AUC0-180) increased after milk ingestion with no significant differences in responses observed between milk types or participants (P > 0.05), with the exception of the suppressed lysine response in the DT group following A2M ingestion, relative to the other two groups and milk types (P < 0.05).Conclusion: Milk protein digestion, as determined by circulatory AAs, is largely unaffected by dairy- and lactose- intolerances. [ABSTRACT FROM AUTHOR]

Hemophagocytic lymphohistiocytosis (HLH) is a heterogeneous, life-threatening clinical syndrome. There are scarce data on the quality of care in HLH or data comparing treatment patterns and outcomes between different triggers. We aimed to examine quality-of-care indicators and outcomes in adults with various HLH triggers. In this multi-centre retrospective cohort study of adult HLH in the province of Alberta, Canada (1999-2019), we examined quality indicators including diagnostic testing, time to diagnosis and treatment and trigger identification. We also compared treatment regimens and outcomes across HLH triggers. Logistic regression was used to identify predictors of etoposide use. Overall survival (OS) was estimated using the Kaplan-Meier method. We identified 97 patients; 66 (68%) were male. Triggers included malignancy (36%), infection (35%), autoimmune disease (21%) and idiopathic/others (8%). Specialized tests such as sCD25 (53%) and natural killer degranulation assay (19%) were under-performed, as were testing for infectious triggers. Etoposide was administered in only 33 (34%). Neutropenia, hyperbilirubinemia and hyperferritinemia, but not age, sex and comorbidities, were significant predictors of etoposide use. At median follow-up of 32 months, median OS was 18.8 months. Worse OS was seen in malignancy-associated and idiopathic HLH (log-rank P < 0.001). Our study showed low rates of specialized testing such as sCD25 and a low rate of etoposide use. Development of a standardized provincial protocol has the potential to improve quality of care in adult HLH. [ABSTRACT FROM AUTHOR]

Introduction: Electrocardiogram (ECG) monitoring is an important tool to detect and mitigate the risk of potentially fatal drug-induced QT prolongation and remains fundamental in supporting the quality use of high-risk QT interval prolonging medicines.Objective: The aim of this systematic review was to determine the prevalence of baseline and/or follow-up ECG use in adult patients taking high-risk QT interval prolonging medicines in clinical practice.Methods: CINAHL, Cochrane Library, Embase, PubMed, EThOS, OpenGrey and Proquest were searched for studies in adults that reported ECG use at baseline and/or at follow-up in relation to the initiation of a high-risk QT interval prolonging medicine in any clinical setting; either hospital or non-hospital. Two reviewers independently assessed the methodological quality of included studies. Proportional meta-analysis was conducted with all studies reporting baseline ECG use, before medicine initiation, and follow-up ECG use, within 30 days of medicine initiation.Results: There was variability in baseline ECG use according to the practice setting. The prevalence of baseline ECG use for high-risk QT interval prolonging medicines was moderate to high in the hospital setting at 75.1% (95% CI 64.3-84.5); however, the prevalence of baseline ECG use was low in the non-hospital setting at 33.7% (95% CI 25.8-42.2). The prevalence of follow-up ECG use was low to moderate in the hospital setting at 39.2% (95% CI 28.2-50.8) and could not be determined for the non-hospital setting.Conclusions: The use of ECG monitoring for high-risk QT interval prolonging medicines is strongly influenced by the clinical practice setting. Baseline ECG use occurs more in the hospital setting in comparison to the non-hospital setting. There is lower use of follow-up ECG in comparison to baseline ECG. [ABSTRACT FROM AUTHOR]

Backgrond and Objective: Crohn's disease (CD) is a chronic inflammatory bowel disease that affects a wide age range. Hence, CD patients receive a variety of drugs over their life beyond those used for CD itself. The changes to the integrity of the intestine and its drug metabolising enzymes and transporters (DMETs) can alter the oral bioavailability of drugs. However, there are other changes in systems parameters determining the fate of drugs in CD, and understanding these is essential for dose adjustment in patients with CD.Methods: The current analysis gathered all the available clinical data on the kinetics of drugs in CD (by March 2021), focusing on orally administered small molecule drugs. A meta-analysis of the systems parameters affecting oral drug pharmacokinetics was conducted. The systems information gathered on intestine, liver and blood proteins and other physiological parameters was incorporated into a physiologically based pharmacokinetic (PBPK) platform to create a virtual population of CD patients, with a view for guiding dose adjustment in the absence of clinical data in CD.Results: There were no uniform trends in the reported changes in reported oral bioavailability. The nature of the drug as well as the formulation affected the direction and magnitude of variation in kinetics in CD patients relative to healthy volunteers. Even for the same drug, the reported changes in exposure varied, possibly due to a lack of distinction between the activity states of CD. The highest alteration was seen with S-verapamil and midazolam, 8.7- and 5.3-fold greater exposure, respectively, in active CD patients relative to healthy volunteers. Only one report was available on liver DMETs in CD, and indicated reduced CYP3A4 activity. In a number of reports, mRNA expression of DMETs in the ileum and colon of CD patients was measured, focussing on P-glycoprotein (p-gp) transporter and CYP3A4 enzyme, and showed contradictory results. No data were available on protein expression in duodenum and jejunum despite their dominant role in oral drug absorption.Conclusion: There are currently inadequate dedicated clinical or quantitative proteomic studies in CD to enable predictive PBPK models with high confidence and adequate verification. The PBPK models for CD with the available systems parameters were able to capture the major physiological influencers and the gaps to be filled by future research. Quantification of DMETs in the intestine and the liver in CD is warranted, alongside well-defined clinical drug disposition studies with a number of index drugs as biomarkers of changes in DMETs in these patients, to avoid large-scale dedicated studies for every drug to determine the effects of disease on the drug's metabolism and disposition and the consequential safety and therapeutic concerns. [ABSTRACT FROM AUTHOR]

Background: Telepsychiatry Collaborative Care (TCC) and Telepsychiatry/Telepsychology Enhanced Referral (TER) expand the reach of specialty mental health services to underserved populations.Objective: Assess clinical predictors of treatment engagement for complex psychiatric conditions in TCC-in which remote specialists consult with primary care teams via an onsite care manager who also provides brief psychotherapy-and TER, in which remote specialists provide direct telehealth treatment.Design: A randomized pragmatic trial from twenty-four primary care clinics without onsite psychiatrists or psychologists.Participants: A total of 1,004 adult patients screened positive for posttraumatic stress disorder (PTSD)and/or bipolar disorder were randomized to receive TCC or TER for 1 year.Main Measures: Psychotherapy engagement was measured by the number of sessions completed, and pharmacotherapy engagement by the medication adherence item from the Schizophrenia Care and Assessment Program Health Questionnaire (SCAP-HQ).Key Results: Engagement in TCC psychotherapy visits was greater compared to TER. There was no association between the PTSD symptom severity and treatment engagement. The internal state scale (ISS) activation subscale, an indicator of mania, was associated with reduced odds of initiating psychotherapy (odds ratio [OR] = 0.70; 95% CI, 0.59 to 0.84) but not the number of sessions attended once psychotherapy started. The Drug Abuse Screening Test-10(DAST-10) score was associated with receipt of fewer psychotherapy sessions (incidence ratio rate [IRR] = 0.88; 95% CI, 0.81 to 0.95). The number of physical health comorbidities was associated with greater engagement in psychotherapy (IRR = 1.11, 95% CI, 1.03 to 1.19) and pharmacotherapy (OR = 1.54; 95% CI, 1.27 to 1.87). None of the findings varied by intervention group.Conclusions: Both teleintegrated and telereferral care offer an opportunity to treat patients with complex psychiatric conditions. While there was no difference in clinical characteristics predicting engagement, onsite care managers engaged patients in more psychotherapy sessions than remote therapists.Trial Registration: ClinicalTrials.gov Identifier: NCT02738944. [ABSTRACT FROM AUTHOR]

Objective: To develop a quantitative Response Evaluation Criteria in Solid Tumors (qRECIST) for evaluating response to neoadjuvant therapy (nT) in ESCCs relying on multiparametric (mp) MRI.Methods: Patients with cT2-T4a/N0-N3/M0 ESCC undergoing pre-nT and post-nT esophageal mpMRI before radical resection were prospectively included. Images were reviewed by two experienced radiologists. qRECIST was redefined using four methods including conventional criterion (cRECIST) and three model-dependent RECIST relying on quantitative MRI measurements at pre-nT, post-nT, and delta pre-post nT, respectively. Pathological tumor regression grades (TRGs) were used as a reference standard. The rates of agreement between four qRECIST methods and TRGs were determined with a Cronbach's alpha test, area under the curve (AUC), and a diagnostic odds ratio meta-analysis.Results: Ninety-one patients were enrolled. All four methods revealed high inter-reader agreements between the two radiologists, with a Kappa coefficient of 0.96, 0.87, 0.88, and 0.97 for cRECIST, pre-nT RECIST, post-nT RECIST, and delta RECIST, respectively. Among them, delta RECIST achieved the highest overall agreement rate (67.0% [61/91]) with TRGs, followed by post-nT RECIST (63.8% [58/91]), cRECIST (61.5% [56/91]), and pre-nT RECIST (36.3% [33/91]). Especially, delta RECIST achieved the highest accuracy (97.8% [89/91]) in distinguishing responders from non-responders, with 97.3% (34/35) for responders and 98.2% (55/56) for non-responders. Post-nT RECIST achieved the highest accuracy (93.4% [85/91]) in distinguishing complete responders from non-pCRs, with 77.8% (11/18) for pCRs and 94.5% (69/73) for non-pCRs.Conclusion: The qRECIST with mpMRI can assess treatment-induced changes and may be used for early prediction of response to nT in ESCC patients.Key Points: • Quantitative mpMRI can reliably assess tumor response, and delta RECIST model had the best performance in evaluating response to nT in ESCCs, with an AUC of 0.98, 0.95, 0.80, and 0.82 for predicting TRG0, TRG1, TRG2, and TRG3, respectively. • In distinguishing responders from non-responders, the rate of agreement between delta RECIST and pathology was 97.3% (34/35) for responders and 98.2% (55/56) for non-responders, resulting in an overall agreement rate of 97.8% (89/91). • In distinguishing pCRs from non-pCR, the rate of agreement between MRI and pathology was 77.8% (11/18) for pCRs and 94.5% (69/73) for non- pCRs, resulting in an overall agreement rate of 91.2% (83/91). [ABSTRACT FROM AUTHOR]

Objectives: To compare patient satisfaction, procedural variables, and safety with transradial access (TRA) and transfemoral access (TFA) in patients undergoing transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC).Materials and Methods: From February 2019 to August 2021, 130 patients undergoing TACE for HCC were randomly allocated to the TRA (n = 65) or TFA (n = 65) group. Vascular closure devices were not used after TFA-TACE. All patients completed the post-catheterization questionnaire and 8-item Short-Form Health Survey 1 day after TACE.Results: Technical success rate, crossover rate, contrast agent dose, fluoroscopy time, procedure time, air kerma, dose-area product, length of hospital stay, and total cost were similar between the two groups (all p > 0.05). The incidence and severity of adverse events were also similar between the two groups (all p > 0.05). However, overall discomfort, difficulty going to the bathroom, difficulty feeding or self-caring, difficulty walking, general health, physical function, role physical function, social function, mental health, and role emotional function were better in the TRA group than in the TFA group (all p < 0.001). Consequently, more patients preferred the current access for their next procedure in the TRA group than in the TFA group (90.8% vs. 24.6%; p < 0.001).Conclusion: In patients undergoing TACE for HCC, using TRA instead of TFA can improve patient satisfaction without compromising procedural variables and safety.Key Points: • Transradial access (TRA) enabled early ambulation after transarterial chemoembolization (TACE), resulting in significant increase in activities of daily living and health-related quality of life (HRQoL) compared to transfemoral access (TFA) when vascular closure devices were not used. • Procedural variables (contrast agent dose, fluoroscopy time, procedure time, air kerma, dose-area product, length of hospital stay, and total cost) were not significantly different between patients who received TRA-TACE and TFA-TACE. • The incidence and severity of adverse events were similar between patients who received TRA-TACE and TFA-TACE. [ABSTRACT FROM AUTHOR]

Emergency shelters are a core component of homeless service systems that address immediate basic needs. Service bans, which refer to temporary or permanent disallowances from a program or organization, are an underresearched phenomenon that can leave people experiencing homelessness without needed supports. This exploratory study examined the factors associated with shelter bans among people experiencing homelessness using secondary data from two Canadian studies: (1) a multisite randomized controlled trial of Housing First (At Home/Chez Soi Demonstration Project) and (2) a cross-sectional survey of youth experiencing homelessness across Canada (2019 Without a Home-National Youth Homelessness Survey). The two datasets were analyzed separately using logistic regression models with similar predictors to maximize the comparability of the results. Participants who experienced homelessness at an earlier age and had recent criminal justice system involvement were more likely to have shelter bans in both datasets. Impaired impulse control, more chronic medical conditions and living in Toronto were associated with increased likelihood of shelter bans in the At Home/Chez Soi dataset, whereas more adverse childhood experiences, physical violence victimization, engagement in survival sex behaviours and longer current episodes of homelessness were significant predictors of bans in the Without A Home dataset. Overall, the findings suggest that victimization and criminalization during homelessness may increase the risk of shelter loss from bans and further exclusion. The observed regional differences also highlight the potential limits of individual-level predictors. Further research is needed on shelter ban outcomes, as well as how capacity limits and organizational policies affect banning decisions. [ABSTRACT FROM AUTHOR]

Background: Recent studies have proved the importance of intact lateral trochanteric wall, thus buttressing/fixing the broken lateral trochanteric wall irrespective of the implant, is likely to improve the alignment and outcome. We compared the outcome of lateral wall buttressing by trochanteric buttress plate (TBP) supplemented to proximal femoral nailing versus proximal femoral nailing alone in patients of broken lateral wall intertrochanteric fractures.Material and Method: Sixty patients of intertrochanteric factures (IT) of femur with broken lateral wall were randomized into group A or B and were treated with either proximal femoral nail (PFN) alone or proximal femoral nail augmented with trochanteric buttress plate (PFN + TBP), respectively. The TBP plate used was primarily fixed to proximal femur via 8 mm hip screw and 6.4 mm antirotation screw of the PFN. Operative time, blood loss, radiation exposure, quality of reduction, functional outcome, union time, and complications were compared.Result: The mean age was 60.03 + 7.60 (range 42 to 70 years), with male to female ratio of 4:1 and left to right ratio of approximately 1:1. The mean follow up in the series was 16.2 months (range 13 to 36 months). Mean duration of surgery, mean intra-operative blood loss, and mean number of exposures in group A (PFN alone) were 64.88 + 12.24 min (48 to 88), 93 + 1.18 ml (60 to 120), and 32.13 (24 to 46) and in group B (PFN with TBP plate) were 91.86 + 12.78 min (70 to 122 min), 144.8 + 3.6 ml (116 to 208 ml), and 56.6 (38 to 112), respectively. Twenty-five patients and 28 patients in groups A and B respectively achieved score of 4 Chang quality reduction. Mean union time was 13.4 weeks in group A whereas in group B was 11.6 weeks. Mean HHS score in group A was 87.86 with 90% patients in comparison to 94.13 and 97% cases having excellent to good results in group B. In group A, 24 patients, while 29 patients in group B, had excellent to good results. Four patients had hip pain, four had impingement of screws, two had screw migration, three had Z/reverse effect, and four patients had shortening of more than 1 cm in group A. In group B, only one patient had impingement and none of the patient had hip pain, infection, implant failure, Z effect, or shortening.Conclusion: The lateral trochanteric wall in IT fractures is significantly important, and when the lateral wall is broken, it can lead to poor results. TBP plate which is applied laterally on femur along with nail and fixing the plate with hip screw and antirotational screw provides faster union, early weight bearing, better reduction, and so better hip functions. TBP can be used successfully to augment, fix, or buttress the lateral trochanteric wall giving excellent to good results but at the cost of surgical time, blood loss, and radiation exposure. [ABSTRACT FROM AUTHOR]

Introduction: We sought to identify and characterize distinct responder profiles among osteoarthritis (OA) subjects treated with tanezumab, nonsteroidal anti-inflammatory drugs (NSAIDs), or placebo.Methods: Subject-level data were derived from three randomized, double-blind, placebo- or NSAID-controlled trials of tanezumab in subjects with moderate-to-severe OA. Subjects received subcutaneous tanezumab (2.5 mg, n = 1527; 5 mg, n = 1279) every 8 weeks, oral NSAIDs (n = 994) daily, or placebo (n = 513). Group-based trajectory modeling (GBTM, an application of finite mixture statistical modeling that uses response trajectory to identify and summarize complex patterns in longitudinal data) was used to identify subgroups of subjects following similar patterns of response in each treatment arm, based on daily pain intensity scores from baseline through Week 16. We then examined whether subject-related variables were associated with any of the subgroups using multinomial logistic regression.Results: A three-subgroup/four-inflection point trajectory model was selected based on clinical and statistical considerations. The subgroups were high responders (substantial pain improvement and a large majority of members achieved ≥ 30% improvement before Week 16), medium responders (gradual pain improvement and a majority of members achieved ≥ 30% improvement by Week 16), and non-responders (little to no pain improvement over 16 weeks). Across all treatments, fluctuation in pain intensity in the week prior to treatment was consistently associated with treatment response. Other variables were positively (age, body mass index, days of rescue medication use) or negatively (severity of disease based on Kellgren-Lawrence grading) associated with response but effects were small and/or varied across treatments.Conclusions: Across all treatments, GBTM identified three subgroups of subjects that were characterized by extent of treatment response (high, medium, and non-responders). Similar analyses (e.g., grouping of subjects based on response trajectory and identification of subgroup-related variables) in other studies of OA could inform clinical trial design and/or treatment approaches. (NCT02697773; NCT02709486; NCT02528188). [ABSTRACT FROM AUTHOR]

Objectives: To develop and validate an optimal model based on the 1-mm-isotropic-3D contrast-enhanced StarVIBE MRI sequence combined with clinical risk factors for predicting survival in patients with esophageal squamous cell carcinoma (ESCC).Methods: Patients with ESCC at our institution from 2015 to 2017 participated in this retrospective study based on prospectively acquired data, and were randomly assigned to training and validation groups at a ratio of 7:3. Random survival forest (RSF) and variable hunting methods were used to screen for radiomics features and LASSO-Cox regression analysis was used to build three models, including clinical only, radiomics only and combined clinical and radiomics models, which were evaluated by concordance index (CI) and calibration curve. Nomograms and decision curve analysis (DCA) were used to display intuitive prediction information.Results: Seven radiomics features were selected from 434 patients, combined with clinical features that were statistically significant to construct the predictive models of disease-free survival (DFS) and overall survival (OS). The combined model showed the highest performance in both training and validation groups for predicting DFS ([CI], 0.714, 0.729) and OS ([CI], 0.730, 0.712). DCA showed that the net benefit of the combined model and of the clinical model is significantly greater than that of the radiomics model alone at different threshold probabilities.Conclusions: We demonstrated that a combined predictive model based on MR Rad-S and clinical risk factors had better predictive efficacy than the radiomics models alone for patients with ESCC.Key Points: • Magnetic resonance-based radiomics features combined with clinical risk factors can predict survival in patients with ESCC. • The radiomics nomogram can be used clinically to predict patient recurrence, DFS, and OS. • Magnetic resonance imaging is highly reproducible in visualizing lesions and contouring the whole tumor. [ABSTRACT FROM AUTHOR]

Background: Neurodegenerative genes are critical in neuronal loss in Parkinson's disease (PD). We performed a systematic meta-analysis including all the studies published on PD risk related to genes encoding enzymes vital for dopamine metabolism and neuron survival.Methods: We included neurodegeneration-related genes which were divided into four groups according to their functions: main enzymes in dopamine metabolism, receptors and transporters for dopamine or other metabolites, neuroprotective factors for dopaminergic neurons, and genes associated with dopaminergic neurons survival reported in other neurological diseases. We collected original articles from PubMed, Embase, and Web of Science databases. Revman 5.3 software was used to analyze data. The allele model (AM) was used to test the effect size of the effect allele between the case group and the control group and secondary analysis using the dominant model (DM) and recessive model (RM) to analyze the contributions from heterozygote and homozygote to the allele risk. Odds ratio (OR) and 95% confidence interval (CI) were used to present the pooled results.Results: We included 31 variants in 20 genes for the final pooled analysis. Consequently, SLC6A4/5-HTT HTTLPR, BDNF rs56164415, FGF20 rs1721100, PARK16 rs823128, rs823156, rs947211, APOE e2, A2M rs669, RIT2 rs12456492, MAPT intron 9 H1H2, and STH rs62063857 variants were statistically associated with PD risk while researched variants in COMT, DBH, MAO, DAT/SLC6A3, DRD2, GRIN2B, GSK3β, ATP13A2, LINGO1, PICALM, and GRN were not related to PD risk.Conclusion: Several variants from neurodegeneration-related genes are associated with PD risk, which may help deepen the understanding of PD pathogenesis and improve clinical treatment strategies. [ABSTRACT FROM AUTHOR]

We aimed to describe characteristics and management of children with comorbidities attending European emergency departments (EDs) with fever. MOFICHE (Management and Outcome of Fever in children in Europe) is a prospective multicentre study (12 European EDs, 8 countries). Febrile children with comorbidities were compared to those without in terms of patient characteristics, markers of disease severity, management, and diagnosis. Comorbidity was defined as a chronic underlying condition that is expected to last > 1 year. We performed multivariable logistic regression analysis, displaying adjusted odds ratios (aOR), adjusting for patient characteristics. We included 38,110 patients, of whom 5906 (16%) had comorbidities. Most common comorbidities were pulmonary, neurologic, or prematurity. Patients with comorbidities more often were ill appearing (20 versus 16%, p < 0.001), had an ED-Paediatric Early Warning Score of > 15 (22 versus 12%, p < 0.001), or a C-reactive protein > 60 mg/l (aOR 1.4 (95%CI 1.3-1.6)). They more often required life-saving interventions (aOR 2.7, 95% CI 2.2-3.3), were treated with intravenous antibiotics (aOR 2.3, 95%CI 2.1-2.5), and were admitted to the ward (aOR 2.2, 95%CI 2.1-2.4) or paediatric intensive care unit (PICU) (aOR 5.5, 95% CI 3.8-7.9). They were more often diagnosed with serious bacterial infections (aOR 1.8, 95%CI 1.7-2.0), including sepsis/meningitis (aOR 4.6, 95%CI 3.2-6.7). Children most at risk for sepsis/meningitis were children with malignancy/immunodeficiency (aOR 14.5, 8.5-24.8), while children with psychomotor delay/neurological disease were most at risk for life-saving interventions (aOR 5.3, 4.1-6.9) or PICU admission (aOR 9.7, 6.1-15.5).Conclusions: Our data show how children with comorbidities are a population at risk, as they more often are diagnosed with bacterial infections and more often require PICU admission and life-saving interventions.What Is Known: • While children with comorbidity constitute a large part of ED frequent flyers, they are often excluded from studies.What Is New: • Children with comorbidities in general are more ill upon presentation than children without comorbidities. • Children with comorbidities form a heterogeneous group; specific subgroups have an increased risk for invasive bacterial infections, while others have an increased risk of invasive interventions such as PICU admission, regardless of the cause of the fever. [ABSTRACT FROM AUTHOR]

Background: Whether to conduct enteral ecoimmunonutrition (EEIN) in patients undergoing hepatectomy remains controversial. This study aimed to systematically explore the efficacy and safety of EEIN in patients undergoing hepatectomy.Subject: We performed searches in the Embase, PubMed, Medline, Cochrane Library, Chinese Scientific Journal Database (VIP), Chinese National Knowledge Infrastructure (CNKI) and Wanfang databases.Results: A total of 9 randomized controlled trials (705 patients) were included. The meta-analysis revealed a significantly shorter time to first postoperative flatus (h) (MD, -14.60; 95% CI, -16.06~-13.15; P < 0.00001); lower levels of alanine aminotransferase (µmol/L) (MD, -22.26; 95% CI, -28.42~-16.10; P < 0.00001), aspartate transaminase (µmol/L) (MD, -53.79; 95% CI, -57.37~-50.21; P < 0.00001), total bilirubin (µmol/L) (MD, -16.28; 95% CI, -17.77~-14.79; P < 0.00001), direct bilirubin (µmol/L) (MD, -8.77; 95% CI, -9.65~-7.88; P < 0.00001), endotoxin (ng/L) (MD, -0.78; 95% CI, -0.88~-0.68; P < 0.00001), tumor necrosis factor-α (pg/ml) (MD, -79.69; 95% CI, -99.90~-59.49; P < 0.00001), and interleukin-6 (pg/ml) (MD, -46.29; 95% CI, -50.24~-42.34; P < 0.00001); and higher levels of immunoglobulin A (g/L) (MD, 0.24; 95% CI, 0.14~0.35; P < 0.00001), immunoglobulin G (g/L) (MD, 1.52; 95% CI, 1.22~1.82; P < 0.00001), and immunoglobulin M (g/L) (MD, 0.12; 95% CI, 0.05~0.20; P = 0.0007) in the EEIN group than in the enteral or parenteral nutrition (EN/PN) groups.Conclusion: Enteral ecoimmunonutrition support in patients undergoing hepatectomy may effectively protect liver function, reduce serum endotoxin levels and inflammatory factors, improve the immune function of patients, and promote the recovery of postoperative gastrointestinal function, which is worthy of clinical application. [ABSTRACT FROM AUTHOR]

Objective: Hospital-onset stroke (HOS) is associated with poorer outcomes than community-onset stroke (COS). Previous studies have variably documented patient characteristics and outcome measures; here, we compare in detail characteristics, management and outcomes of HOS and COS.Methods: A total of 1656 men (mean age ± SD = 73.1 years ± 13.2) and 1653 women (79.3 years ± 13.0), with data prospectively collected (2014-2016) from the Sentinel Stroke National Audit Programme, were admitted with acute stroke in four UK hyperacute stroke units (HASU). Associations between variables were examined by chi-squared tests and multivariable logistic regression (COS as reference).Results: There were 272 HOS and 3037 COS patients with mean ages of 80.2 years ± 12.5 and 76.4 years ± SD13.5 and equal sex distribution. Compared to COS, HOS had higher proportions ≥ 80 years (64.0% vs 46.4%), congestive heart failure (16.9% vs 4.9%), atrial fibrillation (25.0% vs 19.7%) and pre-stroke disability (9.6% vs 5.1%), and similar history of stroke, hypertension, diabetes, stroke type and severity of stroke. After age, sex and co-morbidities adjustments, HOS had greater risk of pneumonia: OR (95%CI) = 1.9 (1.3-2.6); malnutrition: OR = 2.2 (1.7-2.9); immediate thrombolysis complications: OR = 5.3 (1.5-18.2); length of stay on HASU > 3 weeks: OR = 2.5 (1.8-3.4); post-stroke disability: OR = 1.8 (1.4-2.4); and in-hospital mortality: OR = 1.8 (1.2-2.4), as well as greater support at discharge including palliative care: OR = 1.9 (1.3-2.8); nursing care: OR = 2.0 (1.3-4.0), help for daily living activities: OR = 1.6 (1.1-2.2); and joint-care planning: OR = 1.5 (1.1-1.9).Conclusions: This detailed analysis of underlying differences in subject characteristics between patients with HOS or COS and adverse consequences provides further insights into understanding poorer outcomes associated with HOS. [ABSTRACT FROM AUTHOR]

Purpose: Behavioral interventions have been used with breast cancer survivors (BCS) in cancer pain management and post-treatment quality of life (QOL) studies. We studied the effects of an anti-inflammatory dietary intervention on QOL in BCS.Methods: One hundred fifty-three overweight and obese (body mass index [BMI] ≥ 25 kg/m2), early stage (0-III), English-speaking BCS who had completed all cancer treatment 2 or more months prior to enrollment were recruited into a two-arm randomized controlled trial with a 2 (group) by 3 (time) repeated measures design. Intervention components included six monthly food-preparation workshops and twelve motivational interviewing telephone calls. Endpoints included the Perceived Stress Scale (PSS), the Functional Assessment of Cancer Therapy-General (FACT-G) and Breast Cancer (FACT-B), and the Center for Epidemiologic Studies Depression Scale (CES-D). Repeated measures analysis using PROC MIXED in SAS version 9.4 was used.Results: On repeated measures analysis (intent to treat), there were no differences between groups on any of the QOL outcomes except the PSS total scores. These were significantly different in the intervention group (IG; n = 76) compared to control group (CG; n = 77), showing a main effect of assignment but no effect of time and no interaction effects.Conclusion: There was an impact on QOL as measured by the PSS between groups. The intervention reduced perceived stress at 6-month follow-up, but the effects dissipated by 12 months. Sources and stress and stress reduction should be a focus of future studies. Future research should also identify appropriate QOL measures that are sensitive to changes brought about by behavioral interventions. [ABSTRACT FROM AUTHOR]

Background: CRC-PIPAC prospectively assessed repetitive oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy (PIPAC-OX) as a palliative monotherapy (i.e., without concomitant systemic therapy in between subsequent procedures) for unresectable colorectal peritoneal metastases (CPM). The present study explored patient-reported outcomes (PROs) during trial treatment.Methods: In this single-arm phase 2 trial in two tertiary centers, patients with isolated unresectable CPM received 6-weekly PIPAC-OX (92 mg/m2). PROs (calculated from EQ-5D-5L, and EORTC QLQ-C30 and QLQ-CR29) were compared between baseline and 1 and 4 weeks after the first three procedures using linear mixed modeling with determination of clinical relevance (Cohen's D ≥ 0.50) of statistically significant differences.Results: Twenty patients underwent 59 procedures (median 3 [range 1-6]). Several PROs solely worsened 1 week after the first procedure (index value - 0.10, p < 0.001; physical functioning - 20, p < 0.001; role functioning - 27, p < 0.001; social functioning - 18, p < 0.001; C30 summary score - 16, p < 0.001; appetite loss + 15, p = 0.007; diarrhea + 15, p = 0.002; urinary frequency + 13, p = 0.004; flatulence + 13, p = 0.001). These PROs returned to baseline at subsequent time points. Other PROs worsened 1 week after the first procedure (fatigue + 23, p < 0.001; pain + 29, p < 0.001; abdominal pain + 32, p < 0.001), second procedure (fatigue + 20, p < 0.001; pain + 21, p < 0.001; abdominal pain + 20, p = 0.002), and third procedure (pain + 22, p < 0.001; abdominal pain + 22, p = 0.002). Except for appetite loss, all changes were clinically relevant. All analyzed PROs returned to baseline 4 weeks after the third procedure.Conclusions: Patients receiving repetitive PIPAC-OX monotherapy for unresectable CPM had clinically relevant but reversible worsening of several PROs, mainly 1 week after the first procedure.Trial Registration: Clinicaltrials.gov: NCT03246321; Netherlands trial register: NL6426. [ABSTRACT FROM AUTHOR]

Objective: To test the hypothesis that ICG fluorescence cholangiography (ICG-FC) helps to identify critical structures during laparoscopic cholecystectomy (LC) and hence reduce biliary injuries and conversions. In LC, biliary injury and conversion often happen if the biliary anatomy is misidentified.Methods: This was a single-center randomized controlled trial from 2017 to 2019. Patients with acute cholecystitis requiring LC were assessed for eligibility for the trial. Patients in the trial were randomized to undergo either conventional LC (conventional arm) or LC with ICG-FC (ICG arm). Conversion rate and biliary injury incidence were outcome measures.Results: Totally 92 patients participated (46 patients in each arm). The median age was 61 years in both arms (p = 0.472). The conventional arm had 22 men and 24 women; the ICG arm had 24 men and 22 women (p = 0.677). The two arms were comparable in all perioperative parameters. The time from ICG injection to surgery was 67 (16-1150) min. Both arms had an 8.7% conversion rate (p = 1.000). The median operative time was 140.5 min in the conventional arm and 149.5 min in the ICG arm (p = 0.086). The complication rate was 15.2% in the former and 10.9% in the latter (p = 0.536), and both had a 2.2% bile leakage rate. The median hospital stay was 3.5d in the former and 4.0d in the latter (p = 0.380).Conclusion: ICG-FC did not make any difference in conversion or complication rate. Its routine use in LC is questionable. However, it may be helpful in difficult cholecystectomies and may be used as an adjunct.Trial Registration: The trial was registered with the Institutional Review Board of University of Hong Kong/Hospital Authority Hong Kong West Cluster ( http://www.med.hku.hk/en/research/ethics-and-integrity/human-ethics ).Registration Number: UW17-492. [ABSTRACT FROM AUTHOR]

Background: The use of 3D technique compared to high-resolution 2D-4K-display technique has been shown to optimize spatial orientation and surgical performance in laparoscopic surgery. Since women make up an increasing amount of medical students and surgeons, this study was designed to investigate whether one gender has a greater benefit from using a 3D compared to a 4K-display system.Methods: In a randomized cross-over trial, the surgical performance of male and female medical students (MS), non-board certified surgeons (NBCS), and board certified surgeons (BCS) was compared using 3D- vs. 4K-display technique at a minimally invasive training parkour with multiple surgical tasks and repetitions.Results: 128 participants (56 women, 72 men) were included. Overall parkour time in seconds was 3D vs. 4K for all women 770.7 ± 31.9 vs. 1068.1 ± 50.0 (p < 0.001) and all men 664.5 ± 19.9 vs. 889.7 ± 31.2 (p < 0.001). Regarding overall mistakes, participants tend to commit less mistakes while using the 3D-vision system, showing 10.2 ± 1.1 vs. 13.3 ± 1.3 (p = 0.005) for all women and 9.6 ± 0.7 vs. 12.2 ± 1.0 (p = 0.001) for all men. The benefit of using a 3D system, measured by the difference in seconds, was for women 297.3 ± 41.8 (27.84%) vs. 225.2 ± 23.3 (25.31%) for men (p = 0.005). This can be confirmed in the MS group with 327.6 ± 65.5 (35.82%) vs. 249.8 ± 33.7 (32.12%), p = 0.041 and in the NBCS group 359 ± 52.4 (28.25%) vs. 198.2 ± 54.2 (18.62%), p = 0.003. There was no significant difference in the BCS group.Conclusion: 3D laparoscopic display technique optimizes surgical performance compared to the 2D-4K technique for both women and men. The greatest 3D benefit was found for women with less surgical experience. As a possible result of surgical education, this gender specific difference disappears with higher grade of experience. Using a 3D-vision system could facilitate surgical apprenticeship, especially for women. [ABSTRACT FROM AUTHOR]

Background: Enhanced recovery after surgery (ERAS) programs influence morbidity rates and length of stay after colorectal surgery (CRS), and may also impact major complications and anastomotic leakage rates. A prospective multicenter observational study to investigate the interactions between ERAS program adherence and early outcomes after elective CRS was carried out.Methods: Prospective enrolment of patients submitted to elective CRS with anastomosis in 18 months. Adherence to 21 items of ERAS program was measured upon explicit criteria in every case. After univariate analysis, independent predictors of primary endpoints [major morbidity (MM) and anastomotic leakage (AL) rates] were identified through logistic regression analyses including all significant variables, presenting odds ratios (OR).Results: Institutional ERAS protocol was declared by 27 out of 38 (71.0%) participating centers. Median overall adherence to ERAS program items was 71.4%. Among 3830 patients included in the study, MM and AL rates were 4.7% and 4.2%, respectively. MM rates were independently influenced by intra- and/or postoperative blood transfusions (OR 7.79, 95% CI 5.46-11.10; p < 0.0001) and standard anesthesia protocol (OR 0.68, 95% CI 0.48-0.96; p = 0.028). AL rates were independently influenced by male gender (OR 1.48, 95% CI 1.06-2.07; p = 0.021), intra- and/or postoperative blood transfusions (OR 4.29, 95% CI 2.93-6.50; p < 0.0001) and non-standard resections (OR 1.49, 95% CI 1.01-2.22; p = 0.049).Conclusions: This study disclosed wide room for improvement in compliance to several ERAS program items. It failed to detect any significant association between institutionalization and/or adherence rates to ERAS program with primary endpoints. These outcomes were independently influenced by gender, intra- and postoperative blood transfusions, non-standard resections, and standard anesthesia protocol. [ABSTRACT FROM AUTHOR]

Background and Aim: Vascular calcification is one of the most prevalent disorders in pediatric hemodialysis patients that eventually lead to cardiovascular morbidity. Vitamin K2 was investigated in adults in previous studies and showed favorable effects on calcification markers. Our aim in this study was to evaluate the efficacy and safety of vitamin K2 and cholecalciferol on the calcification regulators in pediatric patients.Methods: A prospective, randomized and controlled trial was conducted on sixty hemodialysis pediatric patients who were divided to four groups; Group 1: administered 100 µg of vitamin K2 (MK-7); Group 2: administered 10 µg of native vitamin D; Group 3: administered 100 µg of vitamin K2 (MK-7) in addition 10 µg of native vitamin D, and Group 4: administered the standard therapy only. The duration of supplementation was 4 months. In addition to a group of healthy normal control of age and sex-matched.Results: At the end of the study period, serum levels of FGF23, dp-uc-MGP, and uc-OC were measured. It was found that serum levels of dp-uc-MGP, uc-OC, and FGF23 were significantly higher (p < 0.05) in the hemodialysis patients as compared to the healthy normal control. After 4 months, group 3 revealed the most significant decrease in dp-uc-MGP, uc-OC as compared to the other groups. However, there was no change in FGF23.Conclusion: Vitamin K2 and native vitamin D showed a beneficial effect on calcification regulators in pediatric hemodialysis patients.Trial Registration: clinical trial.gov (NCT04145492). [ABSTRACT FROM AUTHOR]

Background/objective: Morning consumption of a single dose of high-energy oral nutritional supplement (ONS) in females with a lower BMI displaces some of the food eaten at breakfast but increases overall daily energy intake. This study investigated the effectiveness of ONS intake in the late afternoon and for longer duration.Subjects/methods: Twenty-one healthy females (mean ± SD, age 25 ± 5 years; BMI 18.7 ± 1.2 kg/m2) participated in a randomised, crossover study with two experimental trials. In the afternoon of days 1-5, participants consumed either ONS (2.510 MJ) or low-energy PLACEBO drink (0.377 MJ) and recorded food eaten at home. On day six, energy intake was measured during buffet meals, and energy expenditure, appetite measurements and blood samples were collected throughout the day.Result: Over the 5-day period, in the ONS trial energy intake from evening meals was lower (ONS, 2.7 ± 0.25 MJ; Placebo, 3.6 ± 0.25 MJ, P = 0.01) but averaged total daily energy intake was higher (ONS, 9.2 ± 0.3 MJ; PLACEBO, 8.2 ± 0.4 MJ, P = 0.03). On day six, energy intake, appetite scores, plasma GLP-1 and PYY, and energy expenditure were not significantly different between the two trials but fasting insulin concentration and HOMAIR, were higher (P < 0.05) and insulin sensitivity score based on fasting insulin and TAG lower (P < 0.05) in ONS trial.Conclusion: Late afternoon consumption of ONS for five consecutive days by females with a lower BMI has only a partial and short-lived energy intake suppression and thus increases daily energy intake but reduces insulin sensitivity. [ABSTRACT FROM AUTHOR]

Objective: We developed a detailed imaging phenotype of the cerebral complications in critically ill patients with infective endocarditis (IE) and determine whether any specific imaging pattern could impact prognostic information.Methods: One hundred ninety-two patients admitted to the intensive care units of seven tertiary centers with severe, definite left IE and neurological complications were included. All underwent cerebral imaging few days after admission to define the types of lesions, their volumes, and their locations using voxel-based lesion-symptom mapping (VLSM). We employed uni- and multi-variate logistic regression analyses to explore the associations among imaging features and other prognostic variables and the 6-month modified Rankin Scale (mRS) score.Results: Ischemic lesions were the most common lesions (75%; mean volume, 15.3 ± 33 mL) followed by microbleeds (50%; mean number, 4 ± 7.5), subarachnoidal hemorrhages (20%), hemorrhagic strokes (16%; mean volume, 14.6 ± 21 mL), and hemorrhagic transformations (10%; mean volume, 5.6 ± 11 mL). The volume of hemorrhagic transformations, the severity of leukopathy, and the compromises of certain locations on the motor pathway from the VLSM were associated with a poor 6-month mRS score on univariate analyses. However, upon multivariate analyses, no such specific imaging pattern independently predicted the mRS; this was instead influenced principally by age (OR = 1.03 [1.004-1.06]) and cardiac surgery status (OR = 0.06 [0.02-0.16]) in the entire cohort, and by age (OR = 1.04 [1.01-1.08]) and Staphylococcus aureus status (OR = 2.86 [1.19-6.89]) in operated patients.Conclusions: In a cohort of severely ill IE patients with neurological complications, no specific imaging pattern could be highlighted as a reliable predictor of prognosis. [ABSTRACT FROM AUTHOR]