State transition modeling of complex monitored health data

This article considers the analysis of complex monitored health data, where often one or several signals are reflecting the current health status that can be represented by a finite number of states, in addition to a set of covariates. In particular, we consider a novel application of a non-parametric state intensity regression method in order to study time-dependent effects of covariates on the state transition intensities. The method can handle baseline, time varying as well as dynamic covariates. Because of the non-parametric nature, the method can handle different data types and challenges under minimal assumptions. If the signal that is reflecting the current health status is of continuous nature, we propose the application of a weighted median and a hysteresis filter as data pre-processing steps in order to facilitate robust analysis. In intensity regression, covariates can be aggregated by a suitable functional form over a time history window. We propose to study the estimated cumulative regression parameters for different choices of the time history window in order to investigate short- and long-term effects of the given covariates. The proposed framework is discussed and applied to resuscitation data of newborns collected in Tanzania

A prospective observational study on newborn resuscitation in a high-resource setting

Bakgrunn: Omkring åtte prosent av verdens nyfødte har behov for pustehjelp for å klare overgangen fra intra- til ekstrauterint liv. Nøyaktig forekomst er usikker og varierer antagelig mellom ulike settinger, men resuscitering av nyfødte er likevel en av de vanligste akuttbehandlinger i sykehus rundt om i verden. Internasjonale retningslinjer for nyfødtresuscitering skal sikre lik og optimal behandling av syke nyfødte. Imidlertid er kunnskapsgrunnlaget for internasjonale retningslinjer mangelfullt, og baserer seg i stor grad på prekliniske studier uten sikker forankring i den kliniske hverdagen. Pustestøtte ansees som det viktigste tiltaket, og retningslinjer presiserer at overtrykksventilering bør starte innen ett minutt fra fødsel hos barn som ikke puster selv. Lav hjertefrekvens kan indikere behov for pustestøtte, og ved eventuelle tiltak vil rask bedring i hjertefrekvens indikere at behandlingen er effektiv. Retningslinjer anbefaler derfor tidlig vurdering av barnets hjertefrekvens, og at hjertefrekvens overvåkes under resuscitering ved hjelp av pulsoksymetri (PO) eller elektrokardiografi (EKG). Likevel finnes det lite kunnskap om hva som faktisk er normal hjertefrekvens de første minuttene etter fødsel, og man vet ikke hvilken metode som mest effektivt overvåker barnets hjertefrekvens under resuscitering. T-stykke ventilator er blitt et vanlig apparat for å gi luftveisstøtte til nyfødte. Forskning på bruk av disse apparatene under resuscitering i hovedsak utprøvd på premature nyfødte. Resultater fra forskning på nyfødtresuscitering danner et viktig grunnlag for videre utvikling av evidensbaserte anbefalinger. Mål: Mål for dette prosjektet var å i) studere forekomst av, karakteristika ved, og utfall av nyfødtresuscitering på kort sikt i en høyressurs setting, ii) studere etterlevelsen av retningslinjer for nyfødtresuscitering og undersøke hvor effektivt PO og EKG er til å overvåke hjertefrekvens under resuscitering, iii) beskrive normal hjertefrekvens hos friske nyfødte etter vaginal forløsning og sen avnavling, og iv) beskrive hvilke trykk og volum som leveres ved overtrykksventilering av ikke-pustende nyfødte til termin, når man bruker en T-stykke ventilator. Metode: Denne sammenstillingen bygger på fire prospektive observasjonsstudier. Alle studiene er utført ved Stavanger Universitetssjukehus. Studie I benyttet seg av rapporteringsskjema og videofilming over 12 måneder for å registrere og analysere tiltak ved nyfødtresuscitering. Vi registrerte forekomst av overtrykksventilering, kontinuerlig positivt luftveistrykk (CPAP), intubasjon, hjertekompresjoner og intravenøs administrasjon av adrenalin. Utfall etter resuscitering ble hentet fra elektroniske pasientjournaler. I studie II brukte vi videofilmer fra resuscitering av ikke-pustende barn ≥ 34 gestasjonsuker sammen med PO og/eller EKG-signal fra pasientmonitor. Vi målte tid fra fødsel til vurdering av hjerterytme og tid til oppstart av overtrykksventilering. Videre målte vi tid til pålitelig signal fra PO og EKG. I studie III målte vi hjertefrekvens de første fem minuttene etter fødsel hos friske, vaginalforløste terminbarn med sen avnavling, ved hjelp av en nyutviklet hjertefrekvensmåler med tørrelektrode-EKG (NeoBeat). Vi brukte ‘locally estimated scatterplot smoothing’ for å beregne og tegne percentiler. I studie IV brukte vi en ventilasjonsmonitor for å måle og analysere venilasjonsparametre under overtrykksventilering av terminbarn etter fødsel med T-stykke ventilator som var innstilt etter internasjonale anbefalinger (30/5 cmH2O). Vi analyserte de første 100 innblåsingene i hver resuscitering, og delte dem inn i tidlig (1.-20. innblåsing) og sen (21.-100. innblåsing) fase. Vi brukte ‘general estimating equations’ for å analysere assosiasjoner mellom tidalvolum og topptrykk, innblåsingstid og ventilasjonsfrekvens. Resultat: I studie I inkluderte vi 4693 nyfødte. Av disse ble 291 (6.2%) behandlet med pustehjelp eller annen støtte umiddelbart etter fødsel. Antall nyfødte som ble behandlet med overtrykksventilering, CPAP, intubasjon, brystkompresjoner og intravenøs administrasjon av adrenalin var henholdsvis 170 (3.6%), 121 (2.6%), 19 (0.4%), ti (0.2%), og tre (0.1%). Median (IQR) varighet av overtrykksventilasjon var 106 (54-221) sekunder. 63% av de resusciterte nyfødte ≥34 gestasjonsuker ble igjen hos foreldre etter resusciteringen. I studie II analyserte vi resusciteringer av 104 nyfødte som ikke pustet etter fødsel. I bare 35% av tilfellene ble hjertefrekvens vurdert (ved palpasjon eller auskultasjon) og overtrykksventilering startet innen 60 sekunder etter fødsel. Tiden fra fødsel til vurdering av hjertefrekvens og oppstart av overtrykksventilering var henholdsvis 70 (47-118) og 78 (42-118) sekunder. Tiden fra fødsel til pålitelig registrering av hjertefrekvens fra PO og EKG var henholdsvis 348 (217-524) og 174 (105-227) sekunder (p<0.001). Tiden fra PO måler eller EKG elektroder ble festet på barnet og til pålitelig registrering av hjertefrekvens var henholdsvis 199 (77-352) og 16 (11-22) sekunder (p<0.001). I studie III målte vi hjertefrekvens etter fødsel hos 898 friske nyfødte terminbarn. Hjertefrekvensen økte raskt fra 123 (98-147) slag per minutt ved 5 sekunders alder til 175 (157-189) slag per minutt ved 61 sekunders alder. I studie IV analyserte vi venilasjonsparametre under resuscitering av 129 nyfødte terminbarn. Topptrykket var 30 (28-31) mbar i tidlig fase og 30 (27-31) mbar i sen fase. Tidalvolum var 4.5 (1.6-7.8) ml/kg i tidlig fase og 5.7 (2.2-9.8) ml/kg i sen fase. Innblåsingstid på mer enn 0.41 sekunder i tidlig fase og 0.50 sekunder i sen fase var assosiert med de høyeste tidalvolumene. Ventilasjonsfrekvens på mer enn 32 innblåsinger per minutt i tidlig fase og 41 innblåsinger i per minutt i sen fase var assosiert med reduserte tidalvolum. Konklusjon: Nyfødtresuscitering forekom hyppig i denne høyressurs-settingen. De fleste nyfødte responderte raskt på luftveisstøtte. Etterlevelsen av gjeldende retningslinjer var dårlig. Under resuscitering av nyfødte ble pålitelig overvåkning av hjertefrekvens etablert raskere med EKG enn med PO. Vi har presentert percentiler for normal hjertefrekvens etter fødsel hos friske vaginalforløste terminbarn etter sen avnavling. Når man ventilerte nyfødte terminbarn ved hjelp av en T-stykke ventilator ble det levert stabile topptrykk, men det var vesentlig variasjon i tidalvolum. Innblåsingstid på omtrent 0.5 sekunder og ventilasjonsfrekvens på 30-40 innblåsinger i minuttet var assosiert med det høyeste tidalvolumet.Background: An estimated eight percent of newborns globally need respiratory support at birth to make the transition from intra- to extra uterine life. Although these estimates are uncertain, and presumably vary between settings, newborn resuscitation remains one of the most commonly occurring emergencies in the hospital. Resuscitation guidelines should ensure optimal treatment of compromised newborns; however, there is a general lack of evidence to support the different treatment recommendations. Existing knowledge is in large part derived from pre-clinical studies, and the transferability to real-world resuscitations is uncertain. Guidelines highlight support of breathing as the single most important task during newborn resuscitation, and positive pressure ventilation (PPV) should be initiated within the first minute of life in apnoeic newborns. Furthermore, guidelines acknowledge the newborn heart rate as an important factor to guide resuscitative interventions, and recommend continuous heart rate monitoring during resuscitation by either pulse oximetry (PO) or electrocardiography (ECG). However, there is limited data on the normal heart rate in healthy newborns, and the optimal method for monitoring heart rate during newborn resuscitation remains unknown. The flow driven T-piece resuscitator is a widely used device for respiratory support at birth. However, research into its ventilation performance during resuscitation is limited to premature newborns. Studies on newborn resuscitations provide important feedback to support the process of evolving evidence based resuscitation guidelines. Aim: The aim of this thesis was to i) study the incidence, characteristics and short-term outcomes in newborn resuscitation in a high-resource setting, ii) study compliance with resuscitation algorithms and efficacy of PO versus ECG as heart rate monitoring during resuscitation, iii) describe the normal heart rate in vaginally delivered healthy term newborns after delayed cord clamping, and iv) describe delivered pressures and tidal volumes during positive pressure ventilation of apnoeic term newborns with a T-piece resuscitator. Method: This thesis consists of four prospective observational studies. All studies were conducted at Stavanger University Hospital in Norway. Study I used incident report forms and video recordings to register and analyse resuscitative interventions during a period of 12 months. We recorded the incidence of PPV, continuous positive airway pressure (CPAP), intubation, chest compressions and intravenous administration of adrenaline. From electronic patient records we extracted short-term outcomes after resuscitation. In study II, we combined video recordings of resuscitations with PO and ECG signals from the patient monitor, to analyse guideline compliance and efficacy of heart rate monitoring in newborns ≥34 weeks of gestation receiving PPV after birth. We recorded the time from birth to initiation of PPV and time from birth to initial heart rate assessment by palpation or stethoscope. We compared time to accurate heart rate monitoring between PO and 3-lead ECG. For study III, we used a novel dry electrode ECG heart rate meter (NeoBeat, Laerdal Medical, Stavanger, Norway) to record physiological newborn heart rate in healthy vaginally born newborns after delayed cord clamping the first five minutes after birth. Heart rate centiles were drawn using a local regression model. In study IV we combined video recordings of resuscitations and a respiratory function monitor to record and analyse ventilation parameters during PPV of apnoeic term newborns after birth, using a T-piece resuscitator at standard internationally recommended settings of 30/5 cmH2O. We analysed the first 100 inflations from each resuscitation, and divided them into an early (inflation 1-20) and a late (inflation 21-100) phase. We applied general estimating equations to analyse the association between delivered tidal volumes, and peak inflating pressure, inflation time, and inflation rate. Results: Study I included 4693 newborns. Of those, 291 (6.2%) received interventions after birth. The incidence of PPV, CPAP (only), intubation, chest compressions, and intravenous administration of adrenaline were 170 (3.6%), 121 (2.6%), 19 (0.4%), ten (0.2%), and three (0.1%), respectively. Median (IQR) duration of PPV was 106 (54-221) seconds. 63% of newborns ≥34 weeks of gestation were returned to parental care immediately after resuscitation. For study II, we analysed video- and heart rate recordings of 104 resuscitations. Initial heart rate assessment (stethoscope or palpation) and initiation of PPV were achieved within 60 seconds for 35% of the resuscitated newborns. The time from birth to initial heart rate assessment and initiation of PPV was 70 (47-118) and 78 (42-118) seconds, respectively. Time from birth to provision of a reliable heart rate signal was 348 (217-524) seconds for PO, and 174 (105-227) seconds for ECG (p<0.001). Time from sensor application to a reliable heart rate signal was 199 (77-352) seconds for PO, and 16 (11-22) seconds for ECG (p<0.001). In study III, we recorded heart rates from five seconds to five minutes in 898 healthy, vaginally delivered term newborns. Following birth, the heart rate increased rapidly from 123 (98-147) beats per minute at five seconds after birth to 175 (157-189) beats per minute at 61 seconds after birth. In study IV we analysed ventilation parameters from the resuscitation of 129 term newborns. PIP was 30 (28-31) mbar in the early phase and 30 (27-31) mbar in the late phase. Tidal volume was 4.5 (1.6-7.8) ml/kg in the early phase and 5.7 (2.2-9.8) ml/kg in the late phase. Inflation times exceeding 0.41 seconds in the early phase and 0.50 seconds in the late phase were associated with the highest delivered tidal volumes. Inflation rates exceeding 32 per minute during the early phase and 41 per minute in the late phase were associated with a decrease in tidal volumes. Conclusion: The need of resuscitative interventions after birth was frequent in this high-resource setting, and most newborns responded quickly to airway support. The adherence to guidelines was poor. ECG provided a reliable heart rate signal significantly faster than PO during newborn resuscitation. We presented normal heart rate centiles in vaginally delivered term newborns after delayed cord clamping. When ventilating apnoeic newborns at birth with a T-piece resuscitator, there was a consistent delivery of PIP, however, tidal volumes varied substantially. Inflation time of approximately 0.5 seconds and rates of approximately 30-40 per minute were associated with the highest delivered tidal volumes.Doktorgradsavhandlin

A case study of technology transfer: Cardiology

Research advancements in cardiology instrumentation and techniques are summarized. Emphasis is placed upon the following techniques: (1) development of electrodes which show good skin compatibility and wearer comfort; (2) contourography - a real time display system for showing the results of EKGs; (3) detection of arteriosclerosis by digital computer processing of X-ray photos; (4) automated, noninvasive systems for blood pressure measurement; (5) ultrasonoscope - a noninvasive device for use in diagnosis of aortic, mitral, and tricuspid valve disease; and (6) rechargable cardiac pacemakers. The formation of a biomedical applications team which is an interdisciplinary team to bridge the gap between the developers and users of technology is described

Optical imaging and spectroscopy for the study of the human brain: status report.

This report is the second part of a comprehensive two-part series aimed at reviewing an extensive and diverse toolkit of novel methods to explore brain health and function. While the first report focused on neurophotonic tools mostly applicable to animal studies, here, we highlight optical spectroscopy and imaging methods relevant to noninvasive human brain studies. We outline current state-of-the-art technologies and software advances, explore the most recent impact of these technologies on neuroscience and clinical applications, identify the areas where innovation is needed, and provide an outlook for the future directions

Optical imaging and spectroscopy for the study of the human brain: status report

This report is the second part of a comprehensive two-part series aimed at reviewing an extensive and diverse toolkit of novel methods to explore brain health and function. While the first report focused on neurophotonic tools mostly applicable to animal studies, here, we highlight optical spectroscopy and imaging methods relevant to noninvasive human brain studies. We outline current state-of-the-art technologies and software advances, explore the most recent impact of these technologies on neuroscience and clinical applications, identify the areas where innovation is needed, and provide an outlook for the future directions

Metabolomics, Oxidative, and Nitrosative Stress in the Perinatal Period

Studies focusing on the perinatal period face unique challenges, yet research in this area is extremely important, as this period of life is highly delicate and adverse events might have a long-lasting impact. With the advent of powerful high-resolution and high-throughput analytical methods, researchers have started to successfully develop and implement novel approaches in this area. New insights have great potential to be translated into novel diagnostic tools, as well as alternative preventive and treatment approaches. This book collects a series of timely review and original research articles focusing on metabolomic, oxidative, and nitrosative stress in the perinatal period.We would like to thank all involved authors for their high-quality contributions and their commitment to the publication of this work and hope that this book will be a useful resource for students, scientists, and doctors working in this specific area of application

Optical imaging and spectroscopy for the study of the human brain: status report

This report is the second part of a comprehensive two-part series aimed at reviewing an extensive and diverse toolkit of novel methods to explore brain health and function. While the first report focused on neurophotonic tools mostly applicable to animal studies, here, we highlight optical spectroscopy and imaging methods relevant to noninvasive human brain studies. We outline current state-of-the-art technologies and software advances, explore the most recent impact of these technologies on neuroscience and clinical applications, identify the areas where innovation is needed, and provide an outlook for the future directions. Keywords: DCS; NIRS; diffuse optics; functional neuroscience; optical imaging; optical spectroscop

Aerospace medicine and biology: A continuing bibliography with indexes

This bibliography lists 223 reports, articles, and other documents introduced into the NASA scientific and technical information system in December, 1988