Instantaneous monitoring of heart beat dynamics during anesthesia and sedation

Anesthesia-induced altered arousal depends on drugs having their effect in specific brain regions. These effects are also reflected in autonomic nervous system (ANS) outflow dynamics. To this extent, instantaneous monitoring of ANS outflow, based on neurophysiological and computational modeling, may provide a more accurate assessment of the action of anesthetic agents on the cardiovascular system. This will aid anesthesia care providers in maintaining homeostatic equilibrium and help to minimize drug administration while maintaining antinociceptive effects. In previous studies, we established a point process paradigm for analyzing heartbeat dynamics and have successfully applied these methods to a wide range of cardiovascular data and protocols. We recently devised a novel instantaneous nonlinear assessment of ANS outflow, also suitable and effective for real-time monitoring of the fast hemodynamic and autonomic effects during induction and emergence from anesthesia. Our goal is to demonstrate that our framework is suitable for instantaneous monitoring of the ANS response during administration of a broad range of anesthetic drugs. Specifically, we compare the hemodynamic and autonomic effects in study participants undergoing propofol (PROP) and dexmedetomidine (DMED) administration. Our methods provide an instantaneous characterization of autonomic state at different stages of sedation and anesthesia by tracking autonomic dynamics at very high time-resolution. Our results suggest that refined methods for analyzing linear and nonlinear heartbeat dynamics during administration of specific anesthetic drugs are able to overcome nonstationary limitations as well as reducing inter-subject variability, thus providing a potential real-time monitoring approach for patients receiving anesthesia

Municipal solid waste sampling, quantification and seasonal characterization for power evaluation: Energy potential and statistical modelling

Municipal Solid Waste (MSW) streams of Ilorin was characterized for four months in each season: May to August 2016, representing wet season; and November 2016 to February 2017 representing dry season. Thirty-two samples of 240 L bin volume of MSW were collected randomly, from heaps of wastes at Lasoju/ Eyenkorin for each season. The samples were manually sorted on the metallic (screening) table (1.5 m × 3 m with 10 mm × 10 mm surface mesh). Nine combustible waste fractions, out of the nineteen waste components characterized, were considered for laboratory analysis. Proximate analysis revealed averages of 57% and 55% fixed carbon content for wet and dry seasons respectively. Ultimate analysis gave 29 and 29.2% total carbon content for wet and dry seasons respectively. Models were developed to ascertain the correlation between the physicochemical properties and the heating values of the waste fractions. The MSW predicted for the dry season was 158 tons/day, with generation rate of 0.15 kg/capita/person, heating value of 29 MJ/kg, energy and power potentials of 890.2 MWh and 11.27 MW, respectively. MSW for wet season was 210 tons/day, with 0.02 kg/ capita/day, heating value of 26 MJ/kg, energy and power potentials of 1.1 GWh and 1.06 GW, respectively

Neuroimmune activation and increased brain aging in chronic pain patients after the COVID-19 pandemic onset

The COVID-19 pandemic has exerted a global impact on both physical and mental health, and clinical populations have been disproportionally affected. To date, however, the mechanisms underlying the deleterious effects of the pandemic on pre-existing clinical conditions remain unclear. Here we investigated whether the onset of the pandemic was associated with an increase in brain/blood levels of inflammatory markers and MRI-estimated brain age in patients with chronic low back pain (cLBP), irrespective of their infection history. A retrospective cohort study was conducted on 56 adult participants with cLBP (28 ‘Pre-Pandemic’, 28 ‘Pandemic’) using integrated Positron Emission Tomography/ Magnetic Resonance Imaging (PET/MRI) and the radioligand [11C]PBR28, which binds to the neuroinflammatory marker 18 kDa Translocator Protein (TSPO). Image data were collected between November 2017 and January 2020 (‘Pre-Pandemic’ cLBP) or between August 2020 and May 2022 (‘Pandemic’ cLBP). Compared to the Pre-Pandemic group, the Pandemic patients demonstrated widespread and statistically significant elevations in brain TSPO levels (P =.05, cluster corrected). PET signal elevations in the Pandemic group were also observed when 1) excluding 3 Pandemic subjects with a known history of COVID infection, or 2) using secondary outcome measures (volume of distribution -VT- and VT ratio - DVR) in a smaller subset of participants. Pandemic subjects also exhibited elevated serum levels of inflammatory markers (IL-16; P <.05) and estimated BA (P <.0001), which were positively correlated with [11C]PBR28 SUVR (r’s ≥ 0.35; P’s < 0.05). The pain interference scores, which were elevated in the Pandemic group (P <.05), were negatively correlated with [11C]PBR28 SUVR in the amygdala (r = −0.46; P<.05). This work suggests that the pandemic outbreak may have been accompanied by neuroinflammation and increased brain age in cLBP patients, as measured by multimodal imaging and serum testing. This study underscores the broad impact of the pandemic on human health, which extends beyond the morbidity solely mediated by the virus itself

What Are the Contextual Enablers and Impacts of Using Digital Technology to Extend Maternal and Child Health Services to Rural Areas? Findings of a Qualitative Study From Nigeria

Background: Strengthening health systems to improve access to maternity services remains challenging for Nigeria due partly to weak and irregular in-service training and deficient data management. This paper reports the implementation of digital health tools for video training (VTR) of health workers and digitization of health data at scale, supported by satellite communications (SatCom) technology and existing 3G mobile networks. Objective: To understand whether, and under what circumstances using digital interventions to extend maternal, newborn and child health (MNCH) services to remote areas of Nigeria improved standards of healthcare delivery. Methods: From March 2017 to March 2019, VTR and data digitization interventions were delivered in 126 facilities across three states of Nigeria. Data collection combined documents review with 294 semi-structured interviews of stakeholders across four phases (baseline, midline, endline, and 12-months post-project closedown) to assess acceptability and impacts of digital interventions. Data was analyzed using a framework approach, drawing on a modified Technology Acceptance Model to identify factors that shaped technology adoption and use. Results: Analysis of documents and interview transcripts revealed that a supportive policy environment, and track record of private-public partnerships facilitated adoption of technology. The determinants of technology acceptance among health workers included ease of use, perceived usefulness, and prior familiarity with technology. Perceptions of impact suggested that at the micro (individual) level, repeated engagement with clinical videos increased staff knowledge, motivation and confidence to perform healthcare roles. At meso (organizational) level, better-trained staff felt supported and empowered to provide respectful healthcare and improved management of obstetric complications, triggering increased use of MNCH services. The macro level saw greater use of reliable and accurate data for policymaking. Conclusions: Simultaneous and sustained implementation of VTR and data digitization at scale enabled through SatCom and 3G mobile networks are feasible approaches for supporting improvements in staff confidence and motivation and reported MNCH practices. By identifying mechanisms of impact of digital interventions on micro, meso, and macro levels of the health system, the study extends the evidence base for effectiveness of digital health and theoretical underpinnings to guide further technology use for improving MNCH services in low resource settings. Trial Registration: ISRCTN32105372

Neuro-immune signatures in chronic low back pain subtypes

We recently showed that patients with different chronic pain conditions (such as chronic low back pain, fibromyalgia, migraine, and Gulf War Illness) demonstrated elevated brain and/or spinal cord levels of the glial marker 18 kDa translocator protein, which suggests that neuroinflammation might be a pervasive phenomenon observable across multiple etiologically heterogeneous pain disorders. Interestingly, the spatial distribution of this neuroinflammatory signal appears to exhibit a degree of disease specificity (e.g. with respect to the involvement of the primary somatosensory cortex), suggesting that different pain conditions may exhibit distinct “neuroinflammatory signatures”. To further explore this hypothesis, we tested whether neuroinflammatory signal can characterize putative etiological subtypes of chronic low back pain patients based on clinical presentation. Specifically, we explored neuroinflammation in patients whose chronic low back pain either did or did not radiate to the leg (i.e. “radicular” vs. “axial” back pain). Fifty-four chronic low back pain patients, twenty-six with axial back pain (43.7 ± 16.6 y.o. [mean±SD]) and twenty-eight with radicular back pain (48.3 ± 13.2 y.o.), underwent PET/MRI with [11C]PBR28, a second-generation radioligand for the 18 kDa translocator protein. [11C]PBR28 signal was quantified using standardized uptake values ratio (validated against volume of distribution ratio; n = 23). Functional MRI data were collected simultaneously to the [11C]PBR28 data 1) to functionally localize the primary somatosensory cortex back and leg subregions and 2) to perform functional connectivity analyses (in order to investigate possible neurophysiological correlations of the neuroinflammatory signal). PET and functional MRI measures were compared across groups, cross-correlated with one another and with the severity of “fibromyalgianess” (i.e. the degree of pain centralization, or “nociplastic pain”). Furthermore, statistical mediation models were employed to explore possible causal relationships between these three variables. For the primary somatosensory cortex representation of back/leg, [11C]PBR28 PET signal and functional connectivity to the thalamus were: 1) higher in radicular compared to axial back pain patients, 2) positively correlated with each other and 3) positively correlated with fibromyalgianess scores, across groups. Finally, 4) fibromyalgianess mediated the association between [11C]PBR28 PET signal and primary somatosensory cortex-thalamus connectivity across groups. Our findings support the existence of “neuroinflammatory signatures” that are accompanied by neurophysiological changes, and correlate with clinical presentation (in particular, with the degree of nociplastic pain) in chronic pain patients. These signatures may contribute to the subtyping of distinct pain syndromes and also provide information about inter-individual variability in neuro-immune brain signals, within diagnostic groups, that could eventually serve as targets for mechanism-based precision medicine approaches

The pandemic brain: Neuroinflammation in non-infected individuals during the COVID-19 pandemic

While COVID-19 research has seen an explosion in the literature, the impact of pandemic-related societal and lifestyle disruptions on brain health among the uninfected remains underexplored. However, a global increase in the prevalence of fatigue, brain fog, depression and other “sickness behavior”-like symptoms implicates a possible dysregulation in neuroimmune mechanisms even among those never infected by the virus. We compared fifty-seven ‘Pre-Pandemic’ and fifteen ‘Pandemic’ datasets from individuals originally enrolled as control subjects for various completed, or ongoing, research studies available in our records, with a confirmed negative test for SARS-CoV-2 antibodies. We used a combination of multimodal molecular brain imaging (simultaneous positron emission tomography / magnetic resonance spectroscopy), behavioral measurements, imaging transcriptomics and serum testing to uncover links between pandemic-related stressors and neuroinflammation. Healthy individuals examined after the enforcement of 2020 lockdown/stay-at-home measures demonstrated elevated brain levels of two independent neuroinflammatory markers (the 18 kDa translocator protein, TSPO, and myoinositol) compared to pre-lockdown subjects. The serum levels of two inflammatory markers (interleukin-16 and monocyte chemoattractant protein-1) were also elevated, although these effects did not reach statistical significance after correcting for multiple comparisons. Subjects endorsing higher symptom burden showed higher TSPO signal in the hippocampus (mood alteration, mental fatigue), intraparietal sulcus and precuneus (physical fatigue), compared to those reporting little/no symptoms. Post-lockdown TSPO signal changes were spatially aligned with the constitutive expression of several genes involved in immune/neuroimmune functions. This work implicates neuroimmune activation as a possible mechanism underlying the non-virally-mediated symptoms experienced by many during the COVID-19 pandemic. Future studies will be needed to corroborate and further interpret these preliminary findings

Impact of using eHealth tools to extend health services to rural areas of Nigeria: protocol for a mixed-method, non-randomised cluster trial

Introduction: eHealth solutions that use internet and related technologies to deliver and enhance health services and information are emerging as novel approaches to support healthcare delivery in sub-Saharan Africa. Using digital technology in this way can support cost-effectiveness of care delivery and extend the reach of services to remote locations. Despite the burgeoning literature on eHealth approaches, little is known about the effectiveness of eHealth tools for improving the quality and efficiency of health systems functions or client outcomes in resource-limited countries. eHealth tools including satellite communications are currently being implemented at scale, to extend health services to rural areas of Nigeria, in Ondo and Kano States and the Federal Capital Territory. This paper shares the protocol for a 2-year project (‘EXTEND’) that aims to evaluate the impact of eHealth tools on health system functions and health outcomes. Methodology and analysis: This multisite, mixed-method evaluation includes a non-randomised, cluster trial design. The study comprises three phases—baseline, midline and endline evaluations—that involve: (1) process evaluation of video training and digitisation of health data interventions; (2) evaluation of contextual influences on the implementation of interventions; and (3) impact evaluation of results of the project. A convergent mixed-method model will be adopted to allow integration of quantitative and qualitative findings to achieve study objectives. Multiple quantitative and qualitative datasets will be repeatedly analysed and triangulated to facilitate better understanding of impact of eHealth tools on health worker knowledge, quality and efficiency of health systems and client outcomes. Ethics and dissemination: Ethics approvals were obtained from the University of Leeds and three States’ Ministries of Health in Nigeria. All data collected for this study will be anonymised and reports will not contain information that could identify respondents. Study findings will be presented to Ministries of Health at scientific conferences and published in peer-reviewed journals. Trial registration number: ISRCTN32105372; Pre-results

Stakeholder perspectives and requirements to guide the development of digital technology for palliative cancer services: a multi-country, cross-sectional, qualitative study in Nigeria, Uganda and Zimbabwe

Introduction: Coverage of palliative care in low and middle-income countries is very limited, and global projections suggest large increases in need. Novel approaches are needed to achieve the palliative care goals of Universal Health Coverage. This study aimed to identify stakeholders’ data and information needs and the role of digital technologies to improve access to and delivery of palliative care for people with advanced cancer in Nigeria, Uganda and Zimbabwe. Methods: We conducted a multi-country cross-sectional qualitative study in sub-Saharan Africa. In-depth qualitative stakeholder interviews were conducted with N = 195 participants across Nigeria, Uganda and Zimbabwe (advanced cancer patients n = 62, informal caregivers n = 48, health care professionals n = 59, policymakers n = 26). Verbatim transcripts were subjected to deductive and inductive framework analysis to identify stakeholders needs and their preferences for digital technology in supporting the capture, transfer and use of patient-level data to improve delivery of palliative care. Results: Our coding framework identified four main themes: i) acceptability of digital technology; ii) current context of technology use; iii) current vision for digital technology to support health and palliative care, and; iv) digital technologies for the generation, reporting and receipt of data. Digital heath is an acceptable approach, stakeholders support the use of secure data systems, and patients welcome improved communication with providers. There are varying preferences for how and when digital technologies should be utilised as part of palliative cancer care provision, including for increasing timely patient access to trained palliative care providers and the triaging of contact from patients. Conclusion: We identified design and practical challenges to optimise potential for success in developing digital health approaches to improve access to and enhance the delivery of palliative cancer care in Nigeria, Uganda and Zimbabwe. Synthesis of findings identified 15 requirements to guide the development of digital health approaches that can support the attainment of global health palliative care policy goals

Understanding data and information needs for palliative cancer care to inform digital health intervention development in Nigeria, Uganda and Zimbabwe: protocol for a multicountry qualitative study

Introduction: Palliative care is a clinically and cost‐effective component of cancer services in sub-Saharan Africa (SSA). Despite the significant need for palliative cancer care in SSA, coverage remains inadequate. The exploration of digital health approaches could support increases in the quality and reach of palliative cancer care services in SSA. However, there is currently a lack of any theoretical underpinning or data to understand stakeholder drivers for digital health components in this context. This project addresses this gap through engaging with key stakeholders to determine data and information needs that could be supported through digital health interventions. Methods and analysis: This is a multicountry, cross-sectional, qualitative study conducted in Nigeria, Uganda and Zimbabwe. In-depth interviews will be conducted in patients with advanced cancer (n=20), caregivers (n=15), health professionals (n=20) and policy-makers (n=10) in each of the three participating countries. Data from a total of 195 interviews will transcribed verbatim and translated into English before being imported into NVivo software for deductive framework analysis. The analysis will seek to understand the acceptability and define mechanisms of patient-level data capture and usage via digital technologies. Ethics and dissemination: Ethics approvals have been obtained from the Institutional Review Boards of University of Leeds (Ref: MREC 18–032), Research Council of Zimbabwe (Ref: 03507), Medical Research Council of Zimbabwe (Ref: MRCZ/A/2421), Uganda Cancer Institute (Ref: 19–2018), Uganda National Council of Science and Technology (Ref: HS325ES) and College of Medicine University of Lagos (Ref: HREC/15/04/2015). The project seeks to determine optimal mechanisms for the design and development of subsequent digital health interventions to support development, access to, and delivery of palliative cancer care in SSA. Dissemination of these findings will occur through newsletters and press releases, conference presentations, peer-reviewed journals and social media. Trial registration number: ISRCTN1572771

Anaesthesia and PET of the Brain

Although drugs have been used to administer general anaesthesia for more than a century and a half, relatively little was known until recently about the molecular and cellular effects of the anaesthetic agents and the neurobiology of anaesthesia. Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) studies have played a valuable role in improving this knowledge. PET studies using 11C-flumazenil binding have been used to demonstrate that the molecular action of some, but not all, of the current anaesthetic agents is mediated via the GABAA receptor. Using different tracers labelled with 18F, 11C and 15O, PET studies have shown the patterns of changes in cerebral metabolism and blood flow associated with different intravenous and volatile anaesthetic agents. Within classes of volatile agents, there are minor variations in patterns. More profound differences are found between classes of agents. Interestingly, all agents cause alterations in the blood flow and metabolism of the thalamus, providing strong support for the hypothesis that the anaesthetic agents interfere with consciousness by interfering with thalamocortical communication.</p