The effect of repeated concussions on clinical and neurocognitive symptom severity in different contact sports.

INTRODUCTION: The potential consequences of repeated concussions in sport are well documented. However, it remains unclear whether the cumulative impact of sports-related concussions differs between different contact sports. Therefore, the aim of the current study was to investigate the cumulative effects of sports-related concussions on clinical and neurocognitive health in different contact sports. MATERIALS AND METHODS: In a prospective multicenter study, we examined 507 (74 females) active professional athletes between 18 and 40 years of age from five different contact sports (soccer, handball, American football, basketball, and ice hockey). Data collection involved concussion history, clinical symptom evaluation, neurocognitive assessment, and the collection of other sports-related information. Composite scores were built for clinical symptoms (such as neck pain and balance disturbances) and for neurocognitive symptoms (such as memory and attention impairments). RESULTS: Athletes having suffered 3+ concussions in the past showed disproportionally higher clinical symptom severity than athletes with less than three concussions across all sports. The level of clinical symptom burden in athletes with 3+ concussions indicated mild impairment. The number of past concussions did not affect neurocognitive performance. DISCUSSION: Repeated sports-related concussions appear to have a cumulative impact on clinical-but not cognitive-symptom severity. Although clinical symptom burden in athletes with 3+ concussions in the past was not alarmingly high yet in our sample, increased caution should be advised at this point. Despite few exceptions, results are similar for different contact sports, suggesting a similar multidisciplinary concussion management across all types of sport.

Effectiveness of an 11-week exercise intervention for patients with hip or knee osteoarthritis: results of a quasi-experimental pragmatic trial.

OBJECTIVE: To assess the effectiveness of exercise and education in addition to standard care (SC) compared to SC alone in patients with hip or knee osteoarthritis (OA) during 24 months follow-up. DESIGN: We conducted a quasi-experimental pragmatic clinical trial in care centers of a health insurance company. Overall, 1,030 subjects with hip and/or knee OA were included. The intervention group was recruited from clients participating in a hip/knee training (HKT, n = 515) in addition to SC. The control group (CO, n = 515) receiving SC only was recruited from the insurance database. HKT comprised 8 group sessions (1/week) of exercise and education, complemented by a 11-week structured home-exercise program (2/week). Primary endpoints were change of joint-related pain and function (WOMAC Index, score 0-10) after 3 months. Secondary endpoints related to follow-ups at 6, 12 and 24 months. All patient reported outcome measures were analyzed using linear mixed models (LMMs) investigating a time x treatment effect. A multivariable cox proportional hazards regression model was used to identify differences of joint replacement during follow-up between groups. RESULTS: LMMs revealed statistically significant differences in favor of HKT for the primary outcomes WOMAC pain = 0.47 (CI 0.27-0.66; Effect Size (ES) = 0.22, p < 0.001) and WOMAC function = 0.27 (CI 0.11-0.44; ES = 0.13, p < 0.001). HKT was superior to CO for 6, 12, and 24 months as well (ES < 0.2, p ≤ 0.006). HKT was inferior regarding the first incidence of hip or knee AJR during follow-up in comparison to CO (adjusted hazard ratio, HR = 1.57; CI 1.08-2.30; p = 0.020). CONCLUSIONS: This trial demonstrated short-, mid- and long-term superiority of exercise versus control. However, differences were smaller than those reported in previous efficacy trials, raising questions regarding clinical importance. Responder analysis will follow to identify possible predictors for patient responsiveness on an individual level. Further studies should investigate the frequency and reasons for joint replacement following exercise therapy. TRIAL REGISTRATION: German Clinical Trial Register (DRKS00009251). Registered 10 September 2015.

Bisphenol A in German watersheds: Part II. FlowEQ model-based characterization of sources and current and future conditions.

Increasing scientific and regulatory concern regarding environmental concentrations of bisphenol A (BPA) increases the need to understand the sources and sinks of this chemical. We developed a coupled flow network/fugacity-based fate and transport model to assess the contribution of different emissions sources to the concentration of BPA in surface water in Germany. The model utilizes BPA loadings and sinks, BPA physicochemical properties, a water flow network, environmental characteristics, and fugacity equations. The model considers industrial emissions, leaching from BPA-containing articles, wastewater treatment and bypass events, and emissions from landfills. The model also considers different scenarios that account for changes in the usage profile of BPA. Model predictions compare favorably to measured surface water concentrations, with the modeled concentrations generally falling within the range of measured values. Model scenarios that consider reductions in BPA usage due to government-mandated restrictions and voluntary reductions in usage predict falling BPA concentrations that are consistent with the most recent monitoring data. Model predictions of the contributions from different usage scenarios and wastewater treatment methods can be used to assess the efficacy of different restrictions and waste handling strategies to support efforts to evaluate the costs and benefits associated with actions aimed at reducing BPA levels in the environment. This feature of the model is of particular importance, given current efforts to update the regulations regarding BPA usage in the EU. The model indicates that as the current restriction on BPA in thermal paper works through the paper recycling process, BPA concentrations will continue to decrease. Other actions, such as upgrades to the stormwater and wastewater infrastructure to minimize the frequency of storm-related bypasses, are predicted to provide more meaningful reductions than additional restrictions on usage. Integr Environ Assess Manag 2024;20:226-238. © 2023 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Bisphenol A in surface waters in Germany: Part I. Reassessment of sources and emissions pathways for FlowEQ modeling.

Bisphenol A (BPA) enters the environment through various industrial and consumer-related pathways. Industrial sources include BPA manufacturing and secondary industrial uses such as the manufacturing of polymers and other substances based on or containing BPA. However, secondary sources and emissions to the environment, such as those related to the consumer use of articles containing BPA, may be more important than industrial emissions. Although readily biodegradable, BPA is widely distributed in various environmental compartments and living organisms. It is still not well understood which specific sources and pathways are responsible for releasing BPA into the environment. Therefore, we developed FlowEQ, a coupled flow network and fugacity-based fate and transport model for the assessment of BPA in surface water. The work is divided into two parts. In Part I, inputs needed to support the modeling and model validation were collected. Bisphenol A was measured at 23 wastewater treatment plants (WWTPs) and 21 landfills in Germany. In addition, the BPA content of 132 consumer articles from 27 article classes was analyzed. Bisphenol A concentrations in WWTPs ranged from 0.33 to 910 µg L-1 in influents and from less than 0.01 to 0.65 µg L-1 in effluents, resulting in removal efficiencies of 13%-100%. Average BPA concentrations in landfill leachate ranged from less than 0.01 to approximately 1400 µg L-1 . Bisphenol A concentrations measured in consumer articles varied significantly by type, ranging from less than 0.5 µg kg-1 in printing inks up to 1 691 700 µg kg-1 in articles made from recycled polyvinyl chloride (PVC). These concentrations were combined with information on use, leaching, and contact with water to develop estimates of loadings. Together with the results of the FlowEQ modeling presented in Part II, this assessment improves our understanding of the sources and emission pathways of BPA in surface water. The model considers various sources of BPA and can estimate future surface water concentrations of BPA based on changes in use. Integr Environ Assess Manag 2024;20:211-225. © 2023 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Effects of an online information tool on post-traumatic stress disorder in relatives of intensive care unit patients: a multicenter double-blind, randomized, placebo-controlled trial (ICU-Families-Study).

PURPOSE: Intensive care unit (ICU) hospitalization is challenging for the family members of the patients. Most family members report some level of anxiety and depression, sometimes even resulting in post-traumatic stress disorder (PTSD). An association has been reported between lack of information and PTSD. This study had three aims: to quantify the psychological burden of family members of critically ill patients, to explore whether a website with specific information could reduce PTSD symptoms, and to ascertain whether a website with information about intensive care would be used. METHOD: A multicenter double-blind, randomized, placebo-controlled trial was carried out in Austria and Switzerland. RESULTS: In total, 89 members of families of critically ill patients (mean age 47.3 ± 12.9 years, female n = 59, 66.3%) were included in the study. 46 relatives were allocated to the intervention website and 43 to the control website. Baseline Impact of Event Scale (IES) score was 27.5 ± 12.7. Overall, 50% showed clinically relevant PTSD symptoms at baseline. Mean IES score for the primary endpoint (~ 30 days after inclusion, T1) was 24 ± 15.8 (intervention 23.9 ± 17.9 vs. control 24.1 ± 13.5, p = 0.892). Hospital Anxiety and Depression Scale (HADS - Deutsch (D)) score at T1 was 12.2 ± 6.1 (min. 3, max. 31) and did not differ between groups. Use of the website differed between the groups (intervention min. 1, max. 14 vs. min. 1, max. 3; total 1386 "clicks" on the website, intervention 1021 vs. control 365). Recruitment was prematurely stopped in February 2020 due to coronavirus disease 2019 (COVID-19). CONCLUSION: Family members of critically ill patients often have significant PTSD symptoms and online information on critical illness did not result in reduced PTSD symptoms.

Galectin-3, Acute Kidney Injury and Myocardial Damage in Patients With Acute Heart Failure.

BACKGROUND: Galectin-3, a biomarker of inflammation and fibrosis, can be associated with renal and myocardial damage and dysfunction in patients with acute heart failure (AHF). METHODS AND RESULTS: We retrospectively analyzed 790 patients with AHF who were enrolled in the AKINESIS study. During hospitalization, patients with galectin-3 elevation (> 25.9 ng/mL) on admission more commonly had acute kidney injury (assessed by KDIGO criteria), renal tubular damage (peak urine neutrophil gelatinase-associated lipocalin [uNGAL] > 150 ng/dL) and myocardial injury (≥ 20% increase in the peak high-sensitivity cardiac troponin I [hs-cTnI] values compared to admission). They less commonly had ≥ 30% reduction in B-type natriuretic peptide from admission to last measured value. In multivariable linear regression analysis, galectin-3 was negatively associated with estimated glomerular filtration rate and positively associated with uNGAL and hs-cTnI. Higher galectin-3 was associated with renal replacement therapy, inotrope use and mortality during hospitalization. In univariable Cox regression analysis, higher galectin-3 was associated with increased risk for the composite of death or rehospitalization due to HF and death alone at 1 year. After multivariable adjustment, higher galectin-3 levels were associated only with death. CONCLUSIONS: In patients with AHF, higher galectin-3 values were associated with renal dysfunction, renal tubular damage and myocardial injury, and they predicted worse outcomes.

Implications of worsening renal function before hospitalization for acute heart failure.

AIMS: Kidney function changes dynamically during AHF treatment, but risk factors for and consequences of worsening renal function (WRF) at hospital admission are uncertain. We aimed to determine the significance of WRF at admission for acute heart failure (AHF). METHODS AND RESULTS: We evaluated a subgroup of 406 patients from The Acute Kidney Injury Neutrophil gelatinase-associated lipocalin Evaluation of Symptomatic heart failure Study (AKINESIS) who had serum creatinine measurements available within 3 months before and at the time of admission. Admission WRF was primarily defined as a 0.3 mg/dL or 50% creatinine increase from preadmission. Alternative definitions evaluated were a ≥0.5 mg/dL creatinine increase, ≥25% glomerular filtration rate decrease, and an overall change in creatinine. Predictors of admission WRF were evaluated. Outcomes evaluated were length of hospitalization, a composite of adverse in-hospital events, and the composite of death or HF readmission at 30, 90, and 365 days. Biomarkers' prognostic ability for these outcomes were evaluated in patients with admission WRF. One-hundred six patients (26%) had admission WRF. These patients had features of more severe AHF with lower blood pressure, higher BUN, and lower serum sodium concentrations at admission. Higher BNP (odds ratio [OR] per doubling 1.16-1.28, 95% confidence interval [CI] 1.00-1.55) and lower diastolic blood pressure (OR 0.97-0.98, 95% CI 0.96-0.99) were associated with a higher odds for the three definitions of admission WRF. The primary WRF definition was not associated with a longer hospitalization, but alternative WRF definitions were (1.3 to 1.6 days longer, 95% CI 1.0-2.2). WRF across definitions was not associated with a higher odds of adverse in-hospital events or a higher risk of death or HF readmission. In the subset of patients with WRF, biomarkers were not prognostic for any outcome. CONCLUSIONS: Admission WRF is common in AHF patients and is associated with an increased length of hospitalization, but not adverse in-hospital events, death, or HF readmission. Among those with admission WRF, biomarkers did not risk stratify for adverse events.

Comparison of a Group-/Home-Based and a Weight-Machine-Based Exercise Training for Patients with Hip or Knee Osteoarthritis-A Secondary Analysis of Two Trial Interventions in a Real-World Context.

This study aimed to compare an individual weight-machine-based strengthening program (MbT) with a group-/homebased training offering strengthening/functional exercises (GHT) in a general health care setting. A total of 657 participants (GHT = 521, MbT = 136) suffering from hip/knee OA were included and analysed with a pre-post design (baseline (T0)/3-months (T1)). Primary outcomes were pain and physical functioning (Western Ontario and McMaster Universities Osteoarthritis Index, range 0-10). Additionally, adherence and perceived patient benefit were measured (T1). Data were analysed with linear mixed models (time, treatment, baseline pain/physical impairment severity) adjusted for patient characteristics. No significant between-group differences in pain reduction/functional improvements (time*treatment*baseline pain/physical impairment severity, pain/function: n.s.; time*treatment, pain: p = 0.884, function: p = 0.067). Within-group improvements were dependent on baseline severity: Higher severity levels demonstrated larger changes from baseline. Perceived patient-benefit (very high to high, GHT: 78%, MbT: 92%) and exercise adherence (Dropouts T1: GHT: 27.8%, MbT: 16.2%; adherence to supervised sessions: GHT: 89%, MbT: 92%) was slightly better in the MbT. In summary, both MbT and GHT, showed positive results for patients with at least moderate disease symptoms. Findings for physical functioning, perceived patient-benefit, exercise adherence hint towards a superiority of MbT. Individual preferences should be considered when prescribing exercise therapy. Trial registration: (1) German Clinical Trial Register DRKS00009251. Registered 10 September 2015. (2) German Clinical Trial Register DRKS00009257. Registered 11 September 2015.

Decongestion, kidney injury and prognosis in patients with acute heart failure.

BACKGROUND: In patients with acute heart failure (AHF), the development of worsening renal function with appropriate decongestion is thought to be a benign functional change and not associated with poor prognosis. We investigated whether the benefit of decongestion outweighs the risk of concurrent kidney tubular damage and leads to better outcomes. METHODS: We retrospectively analyzed data from the AKINESIS study, which enrolled AHF patients requiring intravenous diuretic therapy. Urine neutrophil gelatinase-associated lipocalin (uNGAL) and B-type natriuretic peptide (BNP) were serially measured during the hospitalization. Decongestion was defined as ≥30% BNP decrease at discharge compared to admission. Univariable and multivariable Cox models were assessed for one-year mortality. RESULTS: Among 736 patients, 53% had ≥30% BNP decrease at discharge. Levels of uNGAL and BNP at each collection time point had positive but weak correlations (r ≤ 0.133). Patients without decongestion and with higher discharge uNGAL values had worse one-year mortality, while those with decongestion had better outcomes regardless of uNGAL values (p for interaction 0.018). This interaction was also significant when the change in BNP was analyzed as a continuous variable (p < 0.001). Although higher peak and discharge uNGAL were associated with mortality in univariable analysis, only ≥30% BNP decrease was a significant predictor after multivariable adjustment. CONCLUSIONS: Among AHF patients treated with diuretic therapy, decongestion was generally not associated with kidney tubular damage assessed by uNGAL. Kidney tubular damage with adequate decongestion does not impact outcomes; however, kidney injury without adequate decongestion is associated with a worse prognosis.

Decongestion discriminates risk for one-year mortality in patients with improving renal function in acute heart failure.

AIMS: Improving renal function (IRF) is paradoxically associated with worse outcomes in acute heart failure (AHF), but outcomes may differ based on response to decongestion. We explored if the relationship of IRF with mortality in hospitalized AHF patients differs based on successful decongestion. METHODS AND RESULTS: We evaluated 760 AHF patients from AKINESIS for the relationship between IRF, change in B-type natriuretic peptide (BNP), and 1-year mortality. IRF was defined as a ≥20% increase in estimated glomerular filtration rate (eGFR) relative to admission. Adequate decongestion was defined as a ≥40% decrease in last measured BNP relative to admission. IRF occurred in 22% of patients who had a mean age of 69 years, 58% were men, 72% were white, and median admission eGFR was 49 mL/min/1.73 m2 . IRF patients had more severe heart failure reflected by lower admission eGFR, higher blood urea nitrogen, lower systolic blood pressure, lower sodium, and higher use of inotropes. IRF patients had higher 1-year mortality (25%) than non-IRF patients (15%) (P < 0.01). However, this relationship differed by BNP trajectory (P-interaction = 0.03). When stratified by BNP change, non-IRF patients and IRF patients with decreasing BNP had lower 1-year mortality than either non-IRF and IRF patients without decreasing BNP. However, in multivariate analysis, IRF was not associated with mortality [adjusted hazard ratio (HR) 1.0, 95% confidence interval (CI) 0.7-1.5] while BNP was (adjusted HR 0.5, 95% CI 0.3-0.7). When IRF was evaluated as transiently occurring or persisting at discharge, again only BNP change was significantly associated with mortality. CONCLUSION: Improving renal function is associated with mortality in AHF but not independent of other variables and congestion status. Achieving adequate decongestion, as reflected by lower BNP, in AHF is more strongly associated with mortality than IRF.

Adult patient access to electronic health records.

BACKGROUND: To support patient-centred care, healthcare organisations increasingly offer patients access to data stored in the institutional electronic health record (EHR). OBJECTIVES: Primary objective 1. To assess the effects of providing adult patients with access to electronic health records (EHRs) alone or with additional functionalities on a range of patient, patient-provider, and health resource consumption outcomes, including patient knowledge and understanding, patient empowerment, patient adherence, patient satisfaction with care, adverse events, health-related quality of life, health-related outcomes, psychosocial health outcomes, health resource consumption, and patient-provider communication. Secondary objective 1. To assess whether effects of providing adult patients with EHR access alone versus EHR access with additional functionalities differ among patient groups according to age, educational level, or different status of disease (chronic or acute). SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, and Scopus in June 2017 and in April 2020. SELECTION CRITERIA: Randomised controlled trials and cluster-randomised trials of EHR access with or without additional functionalities for adults with any medical condition. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. MAIN RESULTS: We included 10 studies with 78 to 4500 participants and follow-up from 3 to 24 months. Nine studies assessed the effects of EHR with additional functionalities, each addressing a subset of outcomes sought by this review. Five studies focused on patients with diabetes mellitus, four on patients with specific diseases, and one on all patients. All studies compared EHR access alone or with additional functionalities plus usual care versus usual care only. No studies assessing the effects of EHR access alone versus EHR access with additional functionalities were identified. Interventions required a variety of data within the EHR, such as patient history, problem list, medication, allergies, and lab results. In addition to EHR access, eight studies allowed patients to share self-documented data, seven offered individualised disease management functions, seven offered educational disease-related information, six supported secure communication, and one offered preventive reminders. Only two studies were at low or unclear risk of bias across domains. Meta-analysis could not be performed, as participants, interventions, and outcomes were too heterogeneous, and most studies presented results based on different adjustment methods or variables. The quality of evidence was rated as low or very low across outcomes. Overall differences between intervention and control groups, if any, were small. The relevance of any small effects remains unclear for most outcomes because in most cases, trial authors did not define a minimal clinically important difference. Overall, results suggest that the effects of EHR access alone and with additional functionalities are mostly uncertain when compared with usual care. Patient knowledge and understanding: very low-quality evidence is available from one study, so we are uncertain about effects of the intervention on patient knowledge about diabetes and blood glucose testing. Patient empowerment: low-quality evidence from three studies suggests that the intervention may have little or no effect on patient empowerment measures. Patient adherence: low-quality evidence from two studies suggests that the intervention may slightly improve adherence to the process of monitoring risk factors and preventive services. Effects on medication adherence are conflicting in two studies; this may or may not improve to a clinically relevant degree. Patient satisfaction with care: low-quality evidence from three studies suggests that the intervention may have little or no effect on patient satisfaction, with conflicting results. Adverse events: two small studies reported on mortality; one of these also reported on serious and other adverse events, but sample sizes were too small for small differences to be detected. Therefore, low-quality evidence suggests that the intervention may have little to no effect on mortality and other adverse events. Health-related quality of life: only very low-quality evidence from one study is available. We are uncertain whether the intervention improves disease-specific quality of life of patients with asthma. Health-related outcomes: low-quality evidence from eight studies suggests that the intervention may have little to no effect on asthma control, glycosylated haemoglobin (HbA1c) levels, blood pressure, low-density lipoprotein or total cholesterol levels, body mass index or weight, or 10-year Framingham risk scores. Low-quality evidence from one study suggests that the composite scores of risk factors for diabetes mellitus may improve slightly with the intervention, but there is uncertainty about effects on ophthalmic medications or intraocular pressure. Psychosocial health outcomes: no study investigated psychosocial health outcomes in a more than anecdotal way. Health resource consumption: low-quality evidence for adult patients in three studies suggests that there may be little to no effect of the intervention on different measures of healthcare use. Patient-provider communication: very low-quality evidence is available from a single small study, and we are uncertain whether the intervention improves communication measures, such as the number of messages sent. AUTHORS' CONCLUSIONS: The effects of EHR access with additional functionalities in comparison with usual care for the most part are uncertain. Only adherence to the process of monitoring risk factors and providing preventive services as well as a composite score of risk factors for diabetes mellitus may improve slightly with EHR access with additional functionalities. Due to inconsistent terminology in this area, our search may have missed relevant studies. As the overall quality of evidence is very low to low, future research is likely to change these results. Further trials should investigate the impact of EHR access in a broader range of countries and clinical settings, including more patients over a longer period of follow-up, as this may increase the likelihood of detecting effects of the intervention, should these exist. More studies should focus on assessing outcomes such as patient empowerment and behavioural outcomes, rather than concentrating on health-related outcomes alone. Future studies should distinguish between effects of EHR access only and effects of additional functionalities, and investigate the impact of mobile EHR tools. Future studies should include information on usage patterns, and consider the potential for widening health inequalities with implementation of EHR access. A taxonomy for EHR access and additional functionalities should be developed to promote consistency and comparability of outcome measures, and facilitate future reviews by better enabling cross-study comparisons.

Relation of Decongestion and Time to Diuretics to Biomarker Changes and Outcomes in Acute Heart Failure.

Prompt treatment may mitigate the adverse effects of congestion in the early phase of heart failure (HF) hospitalization, which may lead to improved outcomes. We analyzed 814 acute HF patients for the relationships between time to first intravenous loop diuretics, changes in biomarkers of congestion and multiorgan dysfunction, and 1-year composite end point of death or HF hospitalization. B-type natriuretic peptide (BNP), high sensitivity cardiac troponin I (hscTnI), urine and serum neutrophil gelatinase-associated lipocalin, and galectin 3 were measured at hospital admission, hospital day 1, 2, 3 and discharge. Time to diuretics was not correlated with the timing of decongestion defined as BNP decrease ≥ 30% compared with admission. Earlier BNP decreases but not time to diuretics were associated with earlier and greater decreases in hscTnI and urine neutrophil gelatinase-associated lipocalin, and lower incidence of the composite end point. After adjustment for confounders, only no BNP decrease at discharge was significantly associated with mortality but not the composite end point (p = 0.006 and p = 0.062, respectively). In conclusion, earlier time to decongestion but not the time to diuretics was associated with better biomarker trajectories. Residual congestion at discharge rather than the timing of decongestion predicted a worse prognosis.

Agreement in Risk of Bias Assessment Between RobotReviewer and Human Reviewers: An Evaluation Study on Randomised Controlled Trials in Nursing-Related Cochrane Reviews.

PURPOSE: RobotReviewer is a machine learning system for semi-automated assistance in risk of bias assessment. The tools's performance in randomized controlled trials (RCTs) in the field of nursing remains unknown. We aimed therefore to evaluate the agreement in risk of bias assessment between RobotReviewer and human reviewers. DESIGN: Evaluation study using a retrospective diagnostic design. METHODS: We used RobotReviewer as the index test and human reviewers' risk of bias assessment reported in Cochrane reviews as the reference test. A convenience sample of electronically available English-language full texts of RCTs included in Cochrane reviews with nurs* in the title were eligible for inclusion. In this context, we assessed random sequence generation, allocation concealment, and blinding (personnel or participants and assessors) corresponding to Cochrane risk of bias version 2011. Two independent research teams performed and double-checked data extraction and analysis. We calculated sensitivity, specificity, receiver operating characteristic (ROC) curve, the area under the ROC curve, predictive values, observed percentage of agreement, and Cohen's kappa (including confidence intervals, if applicable). FINDINGS: The selection process yielded 190 RCTs published between 1958 and 2016 in 23 Cochrane reviews published between 2000 and 2018. Missing assessments of risk of bias domains in Cochrane reviews or RobotReviewer yielded varying sample sizes per risk of bias domain. Sensitivity ranged from 0.44 to 0.88 and specificity from 0.48 to 0.95. Positive predictive value was highest for allocation concealment (0.79) and lowest for blinding assessors (0.25). Cohen's kappa was moderate for randomization (0.52), allocation concealment (0.60), and for blinding of personnel/patients (0.43). Blinding of outcome assessors had only slight agreement (0.04). CONCLUSIONS: This is the first evaluation of risk of bias assessment by RobotReviewer in RCTs included in nursing-related Cochrane reviews. It yielded a moderate degree of agreement with human reviewers for randomization and allocation concealment, and an adequate sensitivity for detecting low risk of selection bias. CLINICAL RELEVANCE: Based on our results, using the RobotReviewer for risk of bias assessment in RCTs can be supportive in some risk of bias domains. However, human reviewers should supervise the semi-automated assessment process.

Potential Utility of Cardiorenal Biomarkers for Prediction and Prognostication of Worsening Renal Function in Acute Heart Failure.

BACKGROUND: Multiple different pathophysiologic processes can contribute to worsening renal function (WRF) in acute heart failure. METHODS AND RESULTS: We retrospectively analyzed 787 patients with acute heart failure for the relationship between changes in serum creatinine and biomarkers including brain natriuretic peptide, high sensitivity cardiac troponin I, galectin 3, serum neutrophil gelatinase-associated lipocalin, and urine neutrophil gelatinase-associated lipocalin. WRF was defined as an increase of greater than or equal to 0.3 mg/dL or 50% in creatinine within first 5 days of hospitalization. WRF was observed in 25% of patients. Changes in biomarkers and creatinine were poorly correlated (r ≤ 0.21) and no biomarker predicted WRF better than creatinine. In the multivariable Cox analysis, brain natriuretic peptide and high sensitivity cardiac troponin I, but not WRF, were significantly associated with the 1-year composite of death or heart failure hospitalization. WRF with an increasing urine neutrophil gelatinase-associated lipocalin predicted an increased risk of heart failure hospitalization. CONCLUSIONS: Biomarkers were not able to predict WRF better than creatinine. The 1-year outcomes were associated with biomarkers of cardiac stress and injury but not with WRF, whereas a kidney injury biomarker may prognosticate WRF for heart failure hospitalization.

Urine E-cadherin: A Marker for Early Detection of Kidney Injury in Diabetic Patients.

Diabetic nephropathy (DN) is the main reason for end-stage renal disease. Microalbuminuria as the non-invasive available diagnosis marker lacks specificity and gives high false positive rates. To identify and validate biomarkers for DN, we used in the present study urine samples from four patient groups: diabetes without nephropathy, diabetes with microalbuminuria, diabetes with macroalbuminuria and proteinuria without diabetes. For the longitudinal validation, we recruited 563 diabetic patients and collected 1363 urine samples with the clinical data during a follow-up of 6 years. Comparative urinary proteomics identified four proteins Apolipoprotein A-I (APOA1), Beta-2-microglobulin (B2M), E-cadherin (CDH1) and Lithostathine-1-alpha (REG1A), which differentiated with high statistical strength (p < 0.05) between DN patients and the other groups. Label-free mass spectrometric quantification of the candidates confirmed the discriminatory value of E-cadherin and Lithostathine-1-alpha (p < 0.05). Immunological validation highlighted E-cadherin as the only marker able to differentiate significantly between the different DN stages with an area under the curve (AUC) of 0.85 (95%-CI: [0.72, 0.97]). The analysis of the samples from the longitudinal study confirmed the prognostic value of E-cadherin, the critical increase in urinary E-cadherin level was measured 20 ± 12.5 months before the onset of microalbuminuria and correlated significantly (p < 0.05) with the glomerular filtration rate measured by estimated glomerular filtration rate (eGFR).

Short-term prognostic implications of serum and urine neutrophil gelatinase-associated lipocalin in acute heart failure: findings from the AKINESIS study.

AIMS: Kidney impairment has been associated with worse outcomes in acute heart failure (AHF), although recent studies challenge this association. Neutrophil gelatinase-associated lipocalin (NGAL) is a novel biomarker of kidney tubular injury. Its prognostic role in AHF has not been evaluated in large cohorts. The present study aimed to determine if serum NGAL (sNGAL) or urine NGAL (uNGAL) is superior to creatinine for predicting short-term outcomes in AHF. METHODS AND RESULTS: The study was conducted in an international, multicentre, prospective cohort consisting of 927 patients with AHF. Admission and peak values of sNGAL, uNGAL and uNGAL/urine creatinine (uCr) ratio were compared to admission and peak serum creatinine (sCr). The composite endpoints were death, initiation of renal replacement therapy, heart failure (HF) readmission and any emergent HF-related outpatient visit within 30 and 60 days, respectively. The mean age of the cohort was 69 years and 62% were male. The median length of stay was 6 days. The composite endpoint occurred in 106 patients and 154 patients within 30 and 60 days, respectively. Serum NGAL was more predictive than uNGAL and the uNGAL/uCr ratio but was not superior to sCr [area under the curve: admission sNGAL 0.61, 95% confidence interval (CI) 0.55-0.67, and 0.59, 95% CI 0.54-0.65; peak sNGAL: 0.60, 95% CI 0.54-0.66, and 0.57, 95% CI 0.52-0.63; admission sCr: 0.60, 95% CI 0.54-0.64, and 0.59, 95% CI 0.53-0.64; peak sCr: 0.61, 95% CI 0.55-0.67, and 0.59, 95% CI 0.54-0.64, at 30 and 60 days, respectively]. NGAL was not predictive of the composite endpoint in multivariate analysis. CONCLUSIONS: Serum NGAL outperformed uNGAL but neither was superior to admission or peak sCr for predicting adverse events.

B-type natriuretic peptide trend predicts clinical significance of worsening renal function in acute heart failure.

AIMS: In acute heart failure (AHF), relationships between changes in B-type natriuretic peptide (BNP) and worsening renal function (WRF) and its prognostic implications have not been fully determined. We investigated the relationship between WRF and a decrease in BNP with in-hospital and 1-year mortality in AHF. METHODS AND RESULTS: The Acute Kidney Injury NGAL Evaluation of Symptomatic heart faIlure Study (AKINESIS) was a prospective, international, multicentre study of AHF patients. Severe WRF (sWRF) was a sustained increase of ≥44.2 µmol/L (0.5 mg/dL) or ≥50% in creatinine, non-severe WRF (nsWRF) was a non-sustained increase of ≥26.5 µmol/L (0.3 mg/dL) or ≥50% in creatinine, and WRF with clinical deterioration was nsWRF with renal replacement therapy, inotrope use, or mechanical ventilation. Decreased BNP was defined as a ≥30% reduction in the last measured BNP compared to admission BNP. Among 814 patients, the incidence of WRF was not different between patients with or without decreased BNP (nsWRF: 33% vs. 31%, P = 0.549; sWRF: 11% vs. 9%, P = 0.551; WRF with clinical deterioration: 8% vs. 10%, P = 0.425). Decreased BNP was associated with better in-hospital and 1-year mortality regardless of WRF, while WRF was associated with worse outcomes only in patients without decreased BNP. In multivariate Cox regression analysis, decreased BNP, sWRF, and WRF with clinical deterioration were significantly associated with 1-year mortality. CONCLUSIONS: Decreased BNP was associated with better in-hospital and long-term outcomes. WRF was only associated with adverse outcomes in patients without decreased BNP.

Effects of Adult Patient Portals on Patient Empowerment and Health-Related Outcomes: A Systematic Review.

Patient portals are offered by health care organizations to facilitate health information sharing and patient empowerment and support patient-centered care. The aim of this systematic review is to assess the effect of patient portals on patient empowerment and health-related outcomes. After a systematic literature search, ten randomized controlled trials (RCTs) were included in this review. Of these, seven RCTs were conducted in the United States., two in Canada, and one in Japan. Study characteristics, risk of bias, and outcomes were extracted. varied in terms of intervention, included patients, and outcome. Most studies found no or only a small, clinically non-relevant effect of patient portals. The review showed that future research should develop a taxonomy to describe patient portal functionalities to facilitate the aggregation of evidence.

Utility of Urine Neutrophil Gelatinase-Associated Lipocalin for Worsening Renal Function during Hospitalization for Acute Heart Failure: Primary Findings of the Urine N-gal Acute Kidney Injury N-gal Evaluation of Symptomatic Heart Failure Study (AKINESIS).

BACKGROUND: Worsening renal function (WRF) during acute heart failure (AHF) occurs frequently and has been associated with adverse outcomes, though this association has been questioned. WRF is now evaluated by function and injury. We evaluated whether urine neutrophil gelatinase-associated lipocalin (uNGAL) is superior to creatinine for prediction and prognosis of WRF in patients with AHF. METHODS AND RESULTS: We performed a multicenter, international, prospective cohort of patients with AHF requiring IV diuretics. The primary outcome was whether uNGAL predicted development of WRF, defined as a sustained increase in creatinine of 0.5 mg/dL or ≥50% above first value or initiation of renal replacement therapy, within the first 5 days. The main secondary outcome was a composite of in-hospital adverse events. We enrolled 927 patients (mean 68.5 years of age, 62% men). The primary outcome occurred in 72 patients (7.8%). The first, peak and the ratio of uNGAL to urine creatinine (area under curves (AUC) ≤ 0.613) did not have diagnostic utility over the first creatinine (AUC 0.662). There were 235 adverse events in 144 patients. uNGAL did not predict (AUCs ≤ 0.647) adverse clinical events better than creatinine (AUC 0.695). CONCLUSIONS: uNGAL was not superior to creatinine for predicting WRF or adverse in-hospital outcomes and cannot be recommended for WRF in AHF.

The effect of Therapeutic Touch on Back Pain in Adults on a Neurological Unit: An Experimental Pilot Study.

BACKGROUND: Chronic back pain affects many aspects of everyday life and is a common reason for medical visits, leading to high direct and indirect health care costs. Innovative and cost-effective nonpharmacologic pain management methods should be promoted to ensure adequate treatment. AIMS: The aim of this pilot study was to investigate the pain-relieving effect of Therapeutic Touch in adult neurologic patients with back pain. DESIGN: A pretest-post-test randomized controlled trial. SETTINGS: A university hospital in Austria. PARTICIPANTS/SUBJECTS: Patients with back pain diagnosis (N = 29) on hospital admission. METHODS: A pilot study was conducted for 3 months. The control group (n = 14) received the pharmacologic pain management recommended by the World Health Organization; patients in the intervention group (n = 15) received additionally four Therapeutic Touch treatments on 4 consecutive days. The Quebec Back Pain Disability Scale and the Numeric Pain Rating Scale were used as outcome measures to evaluate activity domains affected by back pain and pain intensity. RESULTS: Pain improvement was found in the intervention group according to the mean score of the Quebec Back Pain Disability Scale (day 1: 72.53, standard deviation [SD] ± 14.10; day 4: 39.47, SD ± 8.77; p < .001). The Numerical Pain Rating Scale score averaged 4.33 points (SD ± 2.09) on the first day and 2.47 points (SD ± 1.12) on the fourth day. The long-term effect of Therapeutic Touch was significant and indicated a major effect (Pillai's trace = .641, F(3.12) = 7.1, p = .005, ηp2 = .641). CONCLUSIONS: Therapeutic Touch seems to be a noninvasive nursing intervention for back pain management to provide more professional patient care.