Nursing documentation and its relationship with perceived nursing workload:a mixed-methods study among community nurses

BACKGROUND: The time that nurses spent on documentation can be substantial and burdensome. To date it was unknown if documentation activities are related to the workload that nurses perceive. A distinction between clinical documentation and organizational documentation seems relevant. This study aims to gain insight into community nurses’ views on a potential relationship between their clinical and organizational documentation activities and their perceived nursing workload. METHODS: A convergent mixed-methods design was used. A quantitative survey was completed by 195 Dutch community nurses and a further 28 community nurses participated in qualitative focus groups. For the survey an online questionnaire was used. Descriptive statistics, Wilcoxon signed-ranked tests, Spearman’s rank correlations and Wilcoxon rank-sum tests were used to analyse the survey data. Next, four qualitative focus groups were conducted in an iterative process of data collection - data analysis - more data collection, until data saturation was reached. In the qualitative analysis, the six steps of thematic analysis were followed. RESULTS: The majority of the community nurses perceived a high workload due to documentation activities. Although survey data showed that nurses estimated that they spent twice as much time on clinical documentation as on organizational documentation, the workload they perceived from these two types of documentation was comparable. Focus-group participants found organizational documentation particularly redundant. Furthermore, the survey indicated that a perceived high workload was not related to actual time spent on clinical documentation, while actual time spent on organizational documentation was related to the perceived workload. In addition, the survey showed no associations between community nurses’ perceived workload and the user-friendliness of electronic health records. Yet focus-group participants did point towards the impact of limited user-friendliness on their perceived workload. Lastly, there was no association between the perceived workload and whether the nursing process was central in the electronic health records. CONCLUSIONS: Community nurses often perceive a high workload due to clinical and organizational documentation activities. Decreasing the time nurses have to spend specifically on organizational documentation and improving the user-friendliness and intercommunicability of electronic health records appear to be important ways of reducing the workload that community nurses perceive

Towards the integration and development of a cross-European research network and infrastructure:the DEterminants of DIet and Physical ACtivity (DEDIPAC) Knowledge Hub

To address major societal challenges and enhance cooperation in research across Europe, the European Commission has initiated and facilitated ‘joint programming’. Joint programming is a process by which Member States engage in defining, developing and implementing a common strategic research agenda, based on a shared vision of how to address major societal challenges that no Member State is capable of resolving independently. Setting up a Joint Programming Initiative (JPI) should also contribute to avoiding unnecessary overlap and repetition of research, and enable and enhance the development and use of standardised research methods, procedures and data management. The Determinants of Diet and Physical Activity (DEDIPAC) Knowledge Hub (KH) is the first act of the European JPI ‘A Healthy Diet for a Healthy Life’. The objective of DEDIPAC is to contribute to improving understanding of the determinants of dietary, physical activity and sedentary behaviours. DEDIPAC KH is a multi-disciplinary consortium of 46 consortia and organisations supported by joint programming grants from 12 countries across Europe. The work is divided into three thematic areas: (I) assessment and harmonisation of methods for future research, surveillance and monitoring, and for evaluation of interventions and policies; (II) determinants of dietary, physical activity and sedentary behaviours across the life course and in vulnerable groups; and (III) evaluation and benchmarking of public health and policy interventions aimed at improving dietary, physical activity and sedentary behaviours. In the first three years, DEDIPAC KH will organise, develop, share and harmonise expertise, methods, measures, data and other infrastructure. This should further European research and improve the broad multi-disciplinary approach needed to study the interactions between multilevel determinants in influencing dietary, physical activity and sedentary behaviours. Insights will be translated into more effective interventions and policies for the promotion of healthier behaviours and more effective monitoring and evaluation of the impacts of such intervention

Prevention of severe infectious complications after colorectal surgery using oral non-absorbable antimicrobial prophylaxis:results of a multicenter randomized placebo-controlled clinical trial

BACKGROUND: Surgical site infections (SSIs) are common complications after colorectal surgery. Oral non-absorbable antibiotic prophylaxis (OAP) can be administered preoperatively to reduce the risk of SSIs. Its efficacy without simultaneous mechanical cleaning is unknown. METHODS: The Precaution trial was a double-blind, placebo-controlled randomized clinical trial conducted in six Dutch hospitals. Adult patients who underwent elective colorectal surgery were randomized to receive either a three-day course of preoperative OAP with tobramycin and colistin or placebo. The primary composite endpoint was the incidence of deep SSI or mortality within 30 days after surgery. Secondary endpoints included both infectious and non-infectious complications at 30 days and six months after surgery. RESULTS: The study was prematurely ended due to the loss of clinical equipoise. At that time, 39 patients had been randomized to active OAP and 39 to placebo, which reflected 8.1% of the initially pursued sample size. Nine (11.5%) patients developed the primary outcome, of whom four had been randomized to OAP (4/39; 10.3%) and five to placebo (5/39; 12.8%). This corresponds to a risk ratio in the intention-to-treat analysis of 0.80 (95% confidence interval (CI) 0.23-2.78). In the per-protocol analysis, the relative risk was 0.64 (95% CI 0.12-3.46). CONCLUSIONS: Observational data emerging during the study provided new evidence for the effectiveness of OAP that changed both the clinical and medical ethical landscape for infection prevention in colorectal surgery. We therefore consider it unethical to continue randomizing patients to placebo. We recommend the implementation of OAP in clinical practice and continuing monitoring of infection rates and antibiotic susceptibilities. TRIAL REGISTRATION: The PreCaution trial is registered in the Netherlands Trial Register under NL5932 (previously: NTR6113) as well as in the EudraCT register under 2015-005736-17

Predictive Performance of a Gentamicin Pharmacokinetic Model in Term Neonates with Perinatal Asphyxia Undergoing Controlled Therapeutic Hypothermia

Background:Model validation procedures are crucial when population pharmacokinetic (PK) models are used to develop dosing algorithms and to perform model-informed precision dosing. We have previously published a population PK model describing the PK of gentamicin in term neonates with perinatal asphyxia during controlled therapeutic hypothermia (TH), which showed altered gentamicin clearance during the hypothermic phase dependent on gestational age and weight. In this study, the predictive performance and generalizability of this model were assessed using an independent data set of neonates with perinatal asphyxia undergoing controlled TH.Methods:The external data set contained a subset of neonates included in the prospective observational multicenter PharmaCool Study. Predictive performance was assessed by visually inspecting observed-versus-predicted concentration plots and calculating bias and precision. In addition, simulation-based diagnostics, model refitting, and bootstrap analyses were performed.Results:The external data set included 323 gentamicin concentrations of 39 neonates. Both the model-building and external data set included neonates from multiple centers. The original gentamicin PK model predicted the observed gentamicin concentrations with adequate accuracy and precision during all phases of controlled TH. Model appropriateness was confirmed with prediction-corrected visual predictive checks and normalized prediction distribution error analyses. Model refitting to the merged data set (n = 86 neonates with 935 samples) showed accurate estimation of PK parameters.Conclusions:The results of this external validation study justify the generalizability of the gentamicin dosing recommendations made in the original study for neonates with perinatal asphyxia undergoing controlled TH (5 mg/kg every 36 or 24 h with gestational age 36-41 and 42 wk, respectively) and its applicability in model-informed precision dosing.</p

Predictive Performance of a Gentamicin Pharmacokinetic Model in Term Neonates with Perinatal Asphyxia Undergoing Controlled Therapeutic Hypothermia

Background:Model validation procedures are crucial when population pharmacokinetic (PK) models are used to develop dosing algorithms and to perform model-informed precision dosing. We have previously published a population PK model describing the PK of gentamicin in term neonates with perinatal asphyxia during controlled therapeutic hypothermia (TH), which showed altered gentamicin clearance during the hypothermic phase dependent on gestational age and weight. In this study, the predictive performance and generalizability of this model were assessed using an independent data set of neonates with perinatal asphyxia undergoing controlled TH.Methods:The external data set contained a subset of neonates included in the prospective observational multicenter PharmaCool Study. Predictive performance was assessed by visually inspecting observed-versus-predicted concentration plots and calculating bias and precision. In addition, simulation-based diagnostics, model refitting, and bootstrap analyses were performed.Results:The external data set included 323 gentamicin concentrations of 39 neonates. Both the model-building and external data set included neonates from multiple centers. The original gentamicin PK model predicted the observed gentamicin concentrations with adequate accuracy and precision during all phases of controlled TH. Model appropriateness was confirmed with prediction-corrected visual predictive checks and normalized prediction distribution error analyses. Model refitting to the merged data set (n = 86 neonates with 935 samples) showed accurate estimation of PK parameters.Conclusions:The results of this external validation study justify the generalizability of the gentamicin dosing recommendations made in the original study for neonates with perinatal asphyxia undergoing controlled TH (5 mg/kg every 36 or 24 h with gestational age 36-41 and 42 wk, respectively) and its applicability in model-informed precision dosing.</p

The effect of sex on the efficacy and safety of dual antithrombotic therapy with dabigatran versus triple therapy with warfarin after PCI in patients with atrial fibrillation (a RE-DUAL PCI subgroup analysis and comparison to other dual antithrombotic therapy trials)

BACKGROUND: The RE‐DUAL PCI trial demonstrated that in patients with nonvalvular atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI), dual therapy with dabigatran and a P2Y(12) inhibitor, either clopidogrel or ticagrelor, reduced the risk of bleeding without an increased risk of thromboembolic events as compared to triple therapy with warfarin in addition to a P2Y(12) inhibitor and aspirin. What remains unclear is whether this effect is consistent between males and females undergoing PCI. HYPOTHESIS: The reduction in risk of bleeding without increased risk of thromboembolic events with dual therapy with dabigatran and a P2Y(12) inhibitor in comparison to triple therapy with warfarin, a P2Y(12) inhibitor and aspirin is consistent in females and males. METHODS: The primary safety endpoint was the first International Society on Thrombosis and Hemostasis (ISTH) major bleeding event (MBE) or clinically relevant non‐major bleeding event (CRNMBE). The efficacy endpoint was the composite of death, thromboembolic event (stroke, myocardial infarction, and systemic embolism) or unplanned revascularization. Cox proportional hazard regression analyses were applied to calculate corresponding hazard ratios and interaction p values for each endpoint. RESULTS: A total of 655 women and 2070 men were enrolled. The risk of major or CRNM bleeding was lower with both dabigatran 110 mg dual therapy and dabigatran 150 mg dual therapy compared with warfarin triple therapy in female and male patients (for 110 mg: females: HR 0.69, 95% CI 0.47–1.01, males: HR 0.46, 95% CI 0.37–0.59, interaction p value: 0.084 and for 150 mg: females HR 0.74, 95% CI 0.48–1.16, males HR 0.71, 95% CI 0.56–0.90, interaction p value: 0.83). There was also no detectable difference in the composite efficacy endpoint of death, thromboembolic events or unplanned revascularization between dabigatran dual therapy and warfarin triple therapy, with no statistically significant interaction between sex and treatment (interaction p values: 0.73 and 0.72, respectively). CONCLUSIONS: Consistent with the overall study results, the risk of bleeding was lower with dabigatran 110 mg and 150 mg dual therapy compared with warfarin triple therapy, and risk of thromboembolic events was comparable with warfarin triple therapy independent of the patient's sex

Prevention of severe infectious complications after colorectal surgery using preoperative orally administered antibiotic prophylaxis (PreCaution):Study protocol for a randomized controlled trial

BACKGROUND: Colorectal surgery is frequently complicated by surgical site infections (SSIs). The most important consequences of SSIs are prolonged hospitalization, an increased risk of surgical reintervention and an increase in mortality. Perioperative intravenously administered antibiotic prophylaxis is the standard of care to reduce the risk of SSIs. In the last few decades, preoperative orally administered antibiotics have been suggested as additional prophylaxis to further reduce the risk of infection, but are currently not part of routine practice in most hospitals. The objective of this study is to evaluate the efficacy of a preoperative orally administered antibiotic prophylaxis (Pre-OP) in addition to intravenously administered perioperative antibiotic prophylaxis to reduce the incidence of deep SSIs and/or mortality after elective colorectal surgery. METHODS/DESIGN: The PreCaution trial is designed as a multicenter, double-blind, randomized, placebo-controlled clinical trial that will be carried out in The Netherlands. Adult patients who are scheduled for elective colorectal surgery are eligible to participate. In total, 966 patients will be randomized to receive the study medication. This will either be Pre-OP, a solution that consists of tobramycin and colistin sulphate, or a placebo solution. The study medication will be administered four times daily during the 3 days prior to surgery. Perioperative intravenously administered antibiotic prophylaxis will be administered to all patients in accordance with national infection control guidelines. The primary endpoint of the study is the cumulative incidence of deep SSIs and/or mortality within 30 days after surgery. Secondary endpoints include both infectious and non-infectious complications of colorectal surgery, and will be evaluated 30 days and/or 6 months after surgery. DISCUSSION: To date, conclusive evidence on the added value of preoperative orally administered antibiotic prophylaxis in colorectal surgery is lacking. The PreCaution trial should determine the effects of orally administered antibiotics in preventing infectious complications in elective colorectal surgery. TRIAL REGISTRATION: Netherlands Trial Register, ID: NTR6113 . Registered on 11 October 2016; EudraCT 2015-005736-17

In Silico Ascription of Gene Expression Differences to Tumor and Stromal Cells in a Model to Study Impact on Breast Cancer Outcome

Breast tumors consist of several different tissue components. Despite the heterogeneity, most gene expression analyses have traditionally been performed without prior microdissection of the tissue sample. Thus, the gene expression profiles obtained reflect the mRNA contribution from the various tissue components. We utilized histopathological estimations of area fractions of tumor and stromal tissue components in 198 fresh-frozen breast tumor tissue samples for a cell type-associated gene expression analysis associated with distant metastasis. Sets of differentially expressed gene-probes were identified in tumors from patients who developed distant metastasis compared with those who did not, by weighing the contribution from each tumor with the relative content of stromal and tumor epithelial cells in their individual tumor specimen. The analyses were performed under various assumptions of mRNA transcription level from tumor epithelial cells compared with stromal cells. A set of 30 differentially expressed gene-probes was ascribed solely to carcinoma cells. Furthermore, two sets of 38 and five differentially expressed gene-probes were mostly associated to tumor epithelial and stromal cells, respectively. Finally, a set of 26 differentially expressed gene-probes was identified independently of cell type focus. The differentially expressed genes were validated in independent gene expression data from a set of laser capture microdissected invasive ductal carcinomas. We present a method for identifying and ascribing differentially expressed genes to tumor epithelial and/or stromal cells, by utilizing pathologic information and weighted t-statistics. Although a transcriptional contribution from the stromal cell fraction is detectable in microarray experiments performed on bulk tumor, the gene expression differences between the distant metastasis and no distant metastasis group were mostly ascribed to the tumor epithelial cells of the primary breast tumors. However, the gene PIP5K2A was found significantly elevated in stroma cells in distant metastasis group, compared to stroma in no distant metastasis group. These findings were confirmed in gene expression data from the representative compartments from microdissected breast tissue. The method described was also found to be robust to different histopathological procedures

Expression profiling of blood samples from an SU5416 Phase III metastatic colorectal cancer clinical trial: a novel strategy for biomarker identification

BACKGROUND: Microarray-based gene expression profiling is a powerful approach for the identification of molecular biomarkers of disease, particularly in human cancers. Utility of this approach to measure responses to therapy is less well established, in part due to challenges in obtaining serial biopsies. Identification of suitable surrogate tissues will help minimize limitations imposed by those challenges. This study describes an approach used to identify gene expression changes that might serve as surrogate biomarkers of drug activity. METHODS: Expression profiling using microarrays was applied to peripheral blood mononuclear cell (PBMC) samples obtained from patients with advanced colorectal cancer participating in a Phase III clinical trial. The PBMC samples were harvested pre-treatment and at the end of the first 6-week cycle from patients receiving standard of care chemotherapy or standard of care plus SU5416, a vascular endothelial growth factor (VEGF) receptor tyrosine kinase (RTK) inhibitor. Results from matched pairs of PBMC samples from 23 patients were queried for expression changes that consistently correlated with SU5416 administration. RESULTS: Thirteen transcripts met this selection criterion; six were further tested by quantitative RT-PCR analysis of 62 additional samples from this trial and a second SU5416 Phase III trial of similar design. This method confirmed four of these transcripts (CD24, lactoferrin, lipocalin 2, and MMP-9) as potential biomarkers of drug treatment. Discriminant analysis showed that expression profiles of these 4 transcripts could be used to classify patients by treatment arm in a predictive fashion. CONCLUSIONS: These results establish a foundation for the further exploration of peripheral blood cells as a surrogate system for biomarker analyses in clinical oncology studies

Gene Expression Programs in Response to Hypoxia: Cell Type Specificity and Prognostic Significance in Human Cancers

BACKGROUND: Inadequate oxygen (hypoxia) triggers a multifaceted cellular response that has important roles in normal physiology and in many human diseases. A transcription factor, hypoxia-inducible factor (HIF), plays a central role in the hypoxia response; its activity is regulated by the oxygen-dependent degradation of the HIF-1α protein. Despite the ubiquity and importance of hypoxia responses, little is known about the variation in the global transcriptional response to hypoxia among different cell types or how this variation might relate to tissue- and cell-specific diseases. METHODS AND FINDINGS: We analyzed the temporal changes in global transcript levels in response to hypoxia in primary renal proximal tubule epithelial cells, breast epithelial cells, smooth muscle cells, and endothelial cells with DNA microarrays. The extent of the transcriptional response to hypoxia was greatest in the renal tubule cells. This heightened response was associated with a uniquely high level of HIF-1α RNA in renal cells, and it could be diminished by reducing HIF-1α expression via RNA interference. A gene-expression signature of the hypoxia response, derived from our studies of cultured mammary and renal tubular epithelial cells, showed coordinated variation in several human cancers, and was a strong predictor of clinical outcomes in breast and ovarian cancers. In an analysis of a large, published gene-expression dataset from breast cancers, we found that the prognostic information in the hypoxia signature was virtually independent of that provided by the previously reported wound signature and more predictive of outcomes than any of the clinical parameters in current use. CONCLUSIONS: The transcriptional response to hypoxia varies among human cells. Some of this variation is traceable to variation in expression of the HIF1A gene. A gene-expression signature of the cellular response to hypoxia is associated with a significantly poorer prognosis in breast and ovarian cancer