| 1. |
- KC, Ashish, 1982-, et al.
(author)
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Effect of a scaled-up neonatal resuscitation quality improvement package on intrapartum-related mortality in Nepal : A stepped-wedge cluster randomized controlled trial
- 2019
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In: PLoS Medicine. - : PUBLIC LIBRARY SCIENCE. - 1549-1277 .- 1549-1676. ; 16:9
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Journal article (peer-reviewed)abstract
- Background Improving quality of intrapartum care will reduce intrapartum stillbirth and neonatal mortality, especially in resource-poor settings. Basic neonatal resuscitation can reduce intrapartum stillbirth and early neonatal mortality, if delivered in a high-quality health system, but there is a dearth of evidence on how to scale up such evidence-based interventions. We evaluated the scaling up of a quality improvement (QI) package for neonatal resuscitation on intrapartum-related mortality (intrapartum stillbirth and first day mortality) at hospitals in Nepal. Methods and findings We conducted a stepped-wedge cluster randomized controlled trial in 12 hospitals over a period of 18 months from April 14, 2017, to October 17, 2018. The hospitals were assigned to one of four wedges through random allocation. The QI package was implemented in a stepped-wedge manner with a delay of three months for each step. The QI package included improving hospital leadership on intrapartum care, building health workers' competency on neonatal resuscitation, and continuous facilitated QI processes in clinical units. An independent data collection system was set up at each hospital to gather data on mortality through patient case note review and demographic characteristics of women using semi-structured exit interviews. The generalized linear mixed model (GLMM) and multivariate logistic regression were used for analyses. During this study period, a total of 89,014 women-infant pairs were enrolled. The mean age of the mother in the study period was 24.0 +/- 4.3 years, with 54.9% from disadvantaged ethnic groups and 4.0% of them illiterate. Of the total birth cohort, 54.4% were boys, 16.7% had gestational age less than 37 weeks, and 17.1% had birth weight less than 2,500 grams. The incidence of intrapartum-related mortality was 11.0 per 1,000 births during the control period and 8.0 per 1,000 births during the intervention period (adjusted odds ratio [aOR], 0.79; 95% CI, 0.69-0.92; p = 0.002; intra-cluster correlation coefficient [ICC], 0.0286). The incidence of early neonatal mortality was 12.7 per 1,000 live births during the control period and 10.1 per 1,000 live births during the intervention period (aOR, 0.89; 95% CI, 0.78-1.02; p = 0.09; ICC, 0.1538). The use of bag-and-mask ventilation for babies with low Apgar score (<7 at 1 minute) increased from 3.2% in the control period to 4.0% in the intervention period (aOR, 1.52; 95% CI, 1.32-1.77, p = 0.003). There were two major limitations to the study; although a large sample of women-infant pairs were enrolled in the study, the clustering reduced the power of the study. Secondly, the study was not sufficiently powered to detect reduction in early neonatal mortality with the number of clusters provided. Conclusion These results suggest scaled-up implementation of a QI package for neonatal resuscitation can reduce intrapartum-related mortality and improve clinical care. The QI intervention package is likely to be effective in similar settings. More implementation research is required to assess the sustainability of QI interventions and quality of care.
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| 2. |
- KC, Ashish, 1982, et al.
(author)
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Effect of a scaled-up neonatal resuscitation quality improvement package on intrapartum-related mortality in Nepal: A stepped-wedge cluster randomized controlled trial.
- 2019
-
In: PLoS medicine. - : Public Library of Science (PLoS). - 1549-1676 .- 1549-1277. ; 16:9
-
Journal article (peer-reviewed)abstract
- Improving quality of intrapartum care will reduce intrapartum stillbirth and neonatal mortality, especially in resource-poor settings. Basic neonatal resuscitation can reduce intrapartum stillbirth and early neonatal mortality, if delivered in a high-quality health system, but there is a dearth of evidence on how to scale up such evidence-based interventions. We evaluated the scaling up of a quality improvement (QI) package for neonatal resuscitation on intrapartum-related mortality (intrapartum stillbirth and first day mortality) at hospitals in Nepal.We conducted a stepped-wedge cluster randomized controlled trial in 12 hospitals over a period of 18 months from April 14, 2017, to October 17, 2018. The hospitals were assigned to one of four wedges through random allocation. The QI package was implemented in a stepped-wedge manner with a delay of three months for each step. The QI package included improving hospital leadership on intrapartum care, building health workers' competency on neonatal resuscitation, and continuous facilitated QI processes in clinical units. An independent data collection system was set up at each hospital to gather data on mortality through patient case note review and demographic characteristics of women using semi-structured exit interviews. The generalized linear mixed model (GLMM) and multivariate logistic regression were used for analyses. During this study period, a total of 89,014 women-infant pairs were enrolled. The mean age of the mother in the study period was 24.0 ± 4.3 years, with 54.9% from disadvantaged ethnic groups and 4.0% of them illiterate. Of the total birth cohort, 54.4% were boys, 16.7% had gestational age less than 37 weeks, and 17.1% had birth weight less than 2,500 grams. The incidence of intrapartum-related mortality was 11.0 per 1,000 births during the control period and 8.0 per 1,000 births during the intervention period (adjusted odds ratio [aOR], 0.79; 95% CI, 0.69-0.92; p = 0.002; intra-cluster correlation coefficient [ICC], 0.0286). The incidence of early neonatal mortality was 12.7 per 1,000 live births during the control period and 10.1 per 1,000 live births during the intervention period (aOR, 0.89; 95% CI, 0.78-1.02; p = 0.09; ICC, 0.1538). The use of bag-and-mask ventilation for babies with low Apgar score (<7 at 1 minute) increased from 3.2% in the control period to 4.0% in the intervention period (aOR, 1.52; 95% CI, 1.32-1.77, p = 0.003). There were two major limitations to the study; although a large sample of women-infant pairs were enrolled in the study, the clustering reduced the power of the study. Secondly, the study was not sufficiently powered to detect reduction in early neonatal mortality with the number of clusters provided.These results suggest scaled-up implementation of a QI package for neonatal resuscitation can reduce intrapartum-related mortality and improve clinical care. The QI intervention package is likely to be effective in similar settings. More implementation research is required to assess the sustainability of QI interventions and quality of care.ISRCTN30829654.
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| 3. |
- KC, Ashish, 1982-, et al.
(author)
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Scaling up quality improvement intervention for perinatal care in Nepal (NePeriQIP); study protocol of a cluster randomised trial
- 2017
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In: BMJ Global Health. - : BMJ. - 2059-7908. ; 2:3
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Journal article (peer-reviewed)abstract
- INTRODUCTION: Nepal Perinatal Quality Improvement Project (NePeriQIP) intends to scale up a quality improvement (QI) intervention for perinatal care according to WHO/National guidelines in hospitals of Nepal using the existing health system structures. The intervention builds on previous research on the implementation of Helping Babies Breathe-quality improvement cycle in a tertiary healthcare setting in Nepal. The objective of this study is to evaluate the effect of this scaled-up intervention on perinatal health outcomes.METHODS/DESIGN: Cluster-randomised controlled trial using a stepped wedged design with 3 months delay between wedges will be conducted in 12 public hospitals with a total annual delivery rate of 60 000. Each wedge will consist of 3 hospitals. Impact will be evaluated on intrapartum-related mortality (primary outcome), overall neonatal mortality and morbidity and health worker's performance on neonatal care (secondary outcomes). A process evaluation and a cost-effectiveness analysis will be performed to understand the functionality of the intervention and to further guide health system investments will also be performed.DISCUSSION: In contexts where resources are limited, there is a need to find scalable and sustainable implementation strategies for improved care delivery. The proposed study will add to the scarce evidence base on how to scale up interventions within existing health systems. If successful, the NePeriQIP model can provide a replicable solution in similar settings where support and investment from the health system is poor, and national governments have made a global pledge to reduce perinatal mortality.TRIAL REGISTRATION NUMBER: ISRCTN30829654.
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| 4. |
- Brunell, Olivia, et al.
(author)
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Exploration of factors affecting parent-infant closeness and separation in hospitals in Nepal : a qualitative study
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Other publication (other academic/artistic)abstract
- Aim: Closeness is crucial for the physical, emotional and social well-being of both parent and child. Though the benefits of closeness are proven for stable and unstable newborns, separation often remains standard, especially for small or sick newborns. We aimed to explore factors affecting closeness and separation of parents and newborns in hospitals in Nepal. Method: A qualitative design was used. Data was collected by individual interviews with 10 health care workers from labor rooms, post-natal wards or sick newborn care units/neonatal intensive care units, in five referral hospitals in Nepal. Data was analyzed using an inductive thematic approach. Results: Three main themes were generated, 1) Hospital resources, 2) In-hospital practices and attitudes, and 3) Parental-newborn relationships and social factors. Keeping the newborns spatially close to their mothers, offering a comfortable environment, and privacy were thought to enhance closeness, while heavy workload and lack of workforce hampered efforts to enhance closeness. Routines and rules separated parents and newborns, while actions and attitudes among health care workers strengthened closeness. Parental involvement, and the influence of various social aspects such as education, cultural beliefs and gender discrimination, were discussed.Conclusion: Though closeness was considered important, separation was common due to limited resources and existing rules and routines in the hospitals. Introducing small, low-cost changes in the wards, like offering a comfortable place to sit, can help keep the parents close and lessen the workload for health care workers. To avoid separation, hospital rules and practices should be changed, and the parents should be supported to take on the role of primary caregivers, with medical support from health care workers. There are traditions and cultural beliefs in society that hampers parental-infant closeness and gender discrimination remains a problem.
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| 5. |
- Church, Timothy W., et al.
(author)
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AKAP79 enables calcineurin to directly suppress protein kinase A activity
- 2021
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In: eLIFE. - : eLIFE SCIENCES PUBL LTD. - 2050-084X. ; 10
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Journal article (peer-reviewed)abstract
- Interplay between the second messengers cAMP and Ca2+ is a hallmark of dynamic cellular processes. A common motif is the opposition of the Ca2+-sensitive phosphatase calcineurin and the major cAMP receptor, protein kinase A (PKA). Calcineurin dephosphorylates sites primed by PKA to bring about changes including synaptic long-term depression (LTD). AKAP79 supports signaling of this type by anchoring PKA and calcineurin in tandem. In this study, we discovered that AKAP79 increases the rate of calcineurin dephosphorylation of type II PKA regulatory subunits by an order of magnitude. Fluorescent PKA activity reporter assays, supported by kinetic modeling, show how AKAP79-enhanced calcineurin activity enables suppression of PKA without altering cAMP levels by increasing PKA catalytic subunit capture rate. Experiments with hippocampal neurons indicate that this mechanism contributes toward LTD. This non-canonical mode of PKA regulation may underlie many other cellular processes.
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| 6. |
- Eriksson, Olivia, PhD, 1971-, et al.
(author)
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Combining hypothesis- and data-driven neuroscience modeling in FAIR workflows
- 2022
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In: eLIFE. - : eLife Sciences Publications, Ltd. - 2050-084X. ; 11
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Research review (peer-reviewed)abstract
- Modeling in neuroscience occurs at the intersection of different points of view and approaches. Typically, hypothesis-driven modeling brings a question into focus so that a model is constructed to investigate a specific hypothesis about how the system works or why certain phenomena are observed. Data-driven modeling, on the other hand, follows a more unbiased approach, with model construction informed by the computationally intensive use of data. At the same time, researchers employ models at different biological scales and at different levels of abstraction. Combining these models while validating them against experimental data increases understanding of the multiscale brain. However, a lack of interoperability, transparency, and reusability of both models and the workflows used to construct them creates barriers for the integration of models representing different biological scales and built using different modeling philosophies. We argue that the same imperatives that drive resources and policy for data - such as the FAIR (Findable, Accessible, Interoperable, Reusable) principles - also support the integration of different modeling approaches. The FAIR principles require that data be shared in formats that are Findable, Accessible, Interoperable, and Reusable. Applying these principles to models and modeling workflows, as well as the data used to constrain and validate them, would allow researchers to find, reuse, question, validate, and extend published models, regardless of whether they are implemented phenomenologically or mechanistically, as a few equations or as a multiscale, hierarchical system. To illustrate these ideas, we use a classical synaptic plasticity model, the Bienenstock-Cooper-Munro rule, as an example due to its long history, different levels of abstraction, and implementation at many scales.
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| 7. |
- Eriksson, Olivia, PhD, 1971-, et al.
(author)
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e-Science in Scandinavia
- 2018
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In: Informatik-Spektrum. - : Springer Science and Business Media LLC. - 0170-6012 .- 1432-122X. ; 41:6, s. 398-404
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Journal article (peer-reviewed)
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| 8. |
- Eriksson, Olivia, PhD, 1971-, et al.
(author)
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Sensitivity Approximation by the Peano-Baker Series
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Other publication (other academic/artistic)abstract
- In this paper we develop a new method for numerically approximating sensitivitiesin parameter-dependent ordinary differential equations (ODEs). Our approach,intended for situations where the standard forward and adjoint sensitivity analysisbecome too computationally costly for practical purposes, is based on the PeanoBaker series from control theory. We give a representation, using this series, for thesensitivity matrix S of an ODE system and use the representation to construct anumerical method for approximating S. We prove that, under standard regularityassumptions, the error of our method scales as O(∆t2max), where ∆tmax is the largesttime step used when numerically solving the ODE. We illustrate the performanceof the method in several numerical experiments, taken from both the systemsbiology setting and more classical dynamical systems. The experiments show thesought-after improvement in running time of our method compared to the forwardsensitivity approach. For example, in experiments involving a random linear system,the forward approach requires roughly √n longer computational time, where n isthe dimension of the parameter space, than our proposed method.
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| 9. |
- Eriksson, Olivia, PhD, 1971-, et al.
(author)
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Side Chain-Positioning as an Integer Programming Problem.
- 2001
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In: Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics). - Berlin, Heidelberg : Springer Nature. ; , s. 128-141
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Conference paper (peer-reviewed)abstract
- An important aspect of homology modeling and protein design algorithms is the correct positioning of protein side chains on a fixed backbone. Homology modeling methods are necessary to complement large scale structural genomics projects. Recently it has been shown that in automatic protein design it is of the uttermost importance to find the global solution to the side chain positioning problem [1]. If a suboptimal solution is found the difference in free energy between different sequences will be smaller than the error of the side chain positioning. Several different algorithms have been developed to solve this problem. The most successful methods use a discrete representation of the conformational space. Today, the best methods to solve this problem, are based on the dead end elimination theorem. Here we introduce an alternative method. The problem is formulated as a linear integer program. This programming problem can then be solved by efficient polynomial time methods, using linear programming relaxation. If the solution to the relaxed problem is integral it corresponds to the global minimum energy conformation (GMEC). In our experimental results, the solution to the relaxed problem has always been integral.
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| 10. |
- Eriksson, Olivia, 1971-
(author)
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Simplicity within Complexity : Understanding dynamics of cellular networks by model reduction
- 2008
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Doctoral thesis (other academic/artistic)abstract
- Cellular networks composed of interactions between genes, proteins and metabolites, determines the behavioural repertoire of the cell. Recent developments in high-throughput experimental techniques and computational methods allow static descriptions of these networks on a genome scale. There are also several dynamical mathematical models characterizing small subnetworks of the cell such as a signaling cascade or cell division. These networks exhibit a considerable complexity, and mathematical analysis are therefore essential in order to uncover the underlying dynamical core driving the systems. A core description can reveal the relative functional contributions of the various molecular interactions and goes to the heart of what kind of computations biological circuits perform. Partially successful methodologies toward this end includes bifurcation analysis, which only considers a small number of dimensions, and large-scale computer simulations. In this thesis we explore a third route utilizing the inherent biological structure and dynamics of the network as a tool for model simplification. Using the well studied cell cycle, as a model system, we observe that the this network can be divided into dynamical modules displaying a switch-like behaviour. This allows a transformation into a piecewise linear system with delay, the subsequent use of tools from linear systems theory and finally a core dynamical description. Analytical expressions capturing important cell cycle features such as cell mass, as well as necessary constraints for cell cycle oscillations, are thereby retrieved. Finally we use the dynamical core together with large-scale simulations in order to study the balance between robustness and sensitivity. It appears that biological features such as switches, modularity and robustness provide a means to reformulate intractable mathematical problems into solvable ones, as biology appears to suggest a path of simplicity within the realm of mathematical complexity.
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