title: The relationship between cerebral oxygen saturation changes and postoperative cognitive dysfunction in elderly patients after coronary artery bypass graft surgery. Cerebral near infrared spectroscopy oximetry in extremely preterm infants: phase II randomised clinical trial Early CPAP versus surfactant in extremely preterm infants. Extending the CONSORT statement to randomized trials of nonpharmacologic treatment: explanation and elaboration. The SafeBoosC Phase II Randomised Clinical Trial: A Treatment Guideline for Targeted Near-Infrared-Derived Cerebral Tissue Oxygenation versus Standard Treatment in Extremely Preterm Infants A comparison of near‐infrared spectroscopy and jugular bulb oximetry in comatose patients resuscitated from a cardiac arrest Fusing Randomized Trials With Big Data: The Key to Self-learning Health Care Systems? Comparison between cerebral tissue oxygenation index measured by near-infrared spectroscopy and venous jugular bulb saturation in children Surveillance protocol for the detection of intracranial abnormalities in premature neonates. The SafeBoosC II randomized trial: treatment guided by near-infrared spectroscopy reduces cerebral hypoxia without changing early biomarkers of brain injury Clinical use of cerebral oximetry in extremely preterm infants is feasible. A phase II randomized clinical trial on cerebral near-infrared spectroscopy plus a treatment guideline versus treatment as usual for extremely preterm infants during the first three days of life (SafeBoosC): study protocol for a randomized controlled trial Contradicted and initially stronger effects in highly cited clinical research. Preoperative Cerebral Oxygen Saturation and Clinical Outcomes in Cardiac Surgery Monitoring Brain Oxygen Saturation During Coronary Bypass Surgery: A Randomized, Prospective Study Avoiding hyperoxia in infants ⩽1250 g is associated with improved short- and long-term outcomes Cerebral oxygen desaturation predicts cognitive decline and longer hospital stay after cardiac surgery. Continuous Monitoring of Cerebral Oxygen Saturation in Elderly Patients Undergoing Major Abdominal Surgery Minimizes Brain Exposure to Potential Hypoxia Cerebral Oximetry Monitoring to Maintain Normal Cerebral Oxygen Saturation during High-risk Cardiac Surgery: A Randomized Controlled Feasibility Trial Cerebral Oxygen Saturation to Guide Oxygen Delivery in Preterm Neonates for the Immediate Transition after Birth: A 2-Center Randomized Controlled Pilot Feasibility Trial. Measurement of cerebral oxygenation state in anaesthetized children using the INVOS 5100 cerebral oximeter. Patent ductus arteriosus: to treat or not to treat? Influence of Reported Study Design Characteristics on Intervention Effect Estimates From Randomized, Controlled Trials
abstract: OBJECTIVE The aim of this study was to evaluate the predictive value of cerebral regional oxygen saturation ( rSO(2 ) ) in the occurrence of postoperative cognitive dysfunction ( POCD ) in elderly patients undergoing coronary artery bypass graft ( CABG ) surgery .  DESIGN A prospect i ve study . SETTING University hospital . PARTICIPANTS A total of 61 patients ( 84 % male ) with a mean age of 70.39 ± 4.69 on a waiting list for CABG surgery were enrolled in the study . INTERVENTION A  complete neurocognitive evaluation was performed 1 day before surgery as well as 4 to 7 days and 1 month after surgery . During surgery , rSO(2 ) was monitored continuously . MEASUREMENTS AND MAIN RESULTS POCD was defined as a reduction of 1 st and ard deviation on 2 or more neuropsychologic indices . Forty-six patients ( 80.7 % ) developed early POCD , and 23 ( 38.3 % ) showed late POCD . Patients whose rSO(2 ) decreased to less than 50 % during the surgery experienced more POCD 4 to 7 days after surgery ( p = 0.04 ) . In addition , a decrease of more than 30 % from the patient 's baseline rSO(2 ) was associated with POCD 1 month after surgery ( p = 0.03 ) . CONCLUSION Intraoperative cerebral oxygen desaturation is associated with early and late POCD in elderly patients . Cerebral oximetry is a promising tool in the prediction of subtle neuropsychologic deficits and further studies are needed Objective To determine if it is possible to stabilise the cerebral oxygenation of extremely preterm infants monitored by cerebral near infrared spectroscopy ( NIRS ) oximetry . Design Phase II r and omised , single blinded , parallel clinical trial . Setting Eight tertiary neonatal intensive care units in eight European countries . Participants 166 extremely preterm infants born before 28 weeks of gestation : 86 were r and omised to cerebral NIRS monitoring and 80 to blinded NIRS monitoring .  The only exclusion criterion was a decision not to provide life support . Interventions Monitoring of cerebral oxygenation using NIRS in combination with a dedicated treatment guideline during the first 72 hours of life ( experimental ) compared with blinded NIRS oxygenation monitoring with st and ard care ( control ) . Main outcome measures The primary outcome measure was the time spent outside the target range of 55 - 85 % for cerebral oxygenation multiplied by the mean absolute deviation , expressed in % hours ( burden of hypoxia and hyperoxia ) . One hour with an oxygenation of 50 % gives 5%hours of hypoxia . Secondary outcomes were all cause mortality at term equivalent age and a brain injury score assessed by cerebral ultrasonography . R and omisation Allocation sequence 1:1 with block sizes 4 and 6 in r and om order concealed for the investigators . The allocation was stratified for gestational age ( < 26 weeks or ≥26 weeks ) . Blinding Cerebral oxygenation measurements were blinded in the control group . All outcome assessors were blinded to group allocation . Results The 86 infants r and omised to the NIRS group had a median burden of hypoxia and hyperoxia of 36.1%hours ( interquartile range 9.2 - 79.5%hours ) compared with 81.3 ( 38.5 - 181.3 ) % hours in the control group , a reduction of 58 % ( 95 % confidence interval 35 % to 73 % , P<0.001 ) . In the experimental group the median burden of hypoxia was 16.6 ( interquartile range 5.4 - 68.1 ) % hours , compared with 53.6 ( 17.4 - 171.3 ) % hours in the control group ( P=0.0012 ) . The median burden of hyperoxia was similar between the groups : 1.2 ( interquartile range 0.3 - 9.6 ) % hours in the experimental group compared with 1.1 ( 0.1 - 23.4 ) % hours in the control group ( P=0.98 ) . We found no statistically significant differences between the two groups at term corrected age . No severe adverse reactions were associated with the device . Conclusions Cerebral oxygenation was stabilised in extremely preterm infants using a dedicated treatment guideline in combination with cerebral NIRS monitoring . Trial registration Clinical Trial.gov NCT01590316 BACKGROUND There are limited data to inform the choice between early treatment with continuous positive airway pressure ( CPAP ) and early surfactant treatment as the initial support for extremely-low-birth-weight infants . METHODS We performed a r and omized , multicenter trial , with a 2-by-2 factorial design , involving infants who were born between 24 weeks 0 days and 27 weeks 6 days of gestation . Infants were r and omly assigned to intubation and surfactant treatment ( within 1 hour after birth ) or to CPAP treatment initiated in the delivery room , with subsequent use of a protocol -driven limited ventilation strategy . Infants were also r and omly assigned to one of two target ranges of oxygen saturation . The primary outcome was death or bronchopulmonary dysplasia as defined by the requirement for supplemental oxygen at 36 weeks ( with an attempt at withdrawal of supplemental oxygen in neonates who were receiving less than 30 % oxygen ) . RESULTS A total of 1316 infants were enrolled in the study . The rates of the primary outcome did not differ significantly between the CPAP group and the surfactant group ( 47.8 % and 51.0 % , respectively ; relative risk with CPAP , 0.95 ; 95 % confidence interval [ CI ] , 0.85 to 1.05 ) after adjustment for gestational age , center , and familial clustering . The results were similar when bronchopulmonary dysplasia was defined according to the need for any supplemental oxygen at 36 weeks ( rates of primary outcome , 48.7 % and 54.1 % , respectively ; relative risk with CPAP , 0.91 ; 95 % CI , 0.83 to 1.01 ) . Infants who received CPAP treatment , as compared with infants who received surfactant treatment , less frequently required intubation or postnatal corticosteroids for bronchopulmonary dysplasia ( P<0.001 ) , required fewer days of mechanical ventilation ( P=0.03 ) , and were more likely to be alive and free from the need for mechanical ventilation by day 7 ( P=0.01 ) . The rates of other adverse neonatal outcomes did not differ significantly between the two groups . CONCLUSIONS The results of this study support consideration of CPAP as an alternative to intubation and surfactant in preterm infants . ( Clinical Trials.gov number , NCT00233324 . Adequate reporting of r and omized , controlled trials ( RCTs ) is necessary to allow accurate critical appraisal of the validity and applicability of the results . The CONSORT ( Consoli date d St and ards of Reporting Trials ) Statement , a 22-item checklist and flow diagram , is intended to address this problem by improving the reporting of RCTs . However , some specific issues that apply to trials of nonpharmacologic treatments ( for example , surgery , technical interventions , devices , rehabilitation , psychotherapy , and behavioral intervention ) are not specifically addressed in the CONSORT Statement . Furthermore , considerable evidence suggests that the reporting of nonpharmacologic trials still needs improvement . Therefore , the CONSORT group developed an extension of the CONSORT Statement for trials assessing nonpharmacologic treatments . A consensus meeting of 33 experts was organized in Paris , France , in February 2006 , to develop an extension of the CONSORT Statement for trials of nonpharmacologic treatments . The participants extended 11 items from the CONSORT Statement , added 1 item , and developed a modified flow diagram . To allow adequate underst and ing and implementation of the CONSORT extension , the CONSORT group developed this elaboration and explanation document from a review of the literature to provide examples of adequate reporting . This extension , in conjunction with the main CONSORT Statement and other CONSORT extensions , should help to improve the reporting of RCTs performed in this field Near-infrared spectroscopy-derived regional tissue oxygen saturation of haemoglobin ( rStO2 ) reflects venous oxygen saturation . If cerebral metabolism is stable , rStO2 can be used as an estimate of cerebral oxygen delivery . The SafeBoosC phase II r and omised clinical trial hypothesises that the burden of hypo- and hyperoxia can be reduced by the combined use of close monitoring of the cerebral rStO2 and a treatment guideline to correct deviations in rStO2 outside a predefined target range . Aims : To describe the rationale for and content of this treatment guideline . Methods : Review of the literature and assessment of the quality of evidence and the grade of recommendation for each of the interventions . Results and Conclusions : A clinical intervention algorithm based on the main determinants of cerebral perfusion-oxygenation changes during the first hours after birth was generated . The treatment guideline is presented to assist neonatologists in making decisions in relation to cerebral oximetry readings in preterm infants within the SafeBoosC phase II r and omised clinical trial . The evidence grade s were relatively low and the guideline can not be recommended outside a research setting One cause of cerebral damage in comatose patients resuscitated from a cardiac arrest is cerebral ischaemia occurring during the postresuscitation period . Near‐infrared spectroscopy has been advocated as a useful monitor of brain oxygenation , but data on clinical use in comatose postarrest patients are not available . Therefore , we compared regional oxygen saturation measured with the INVOS 3100 with global oxygen saturation measured using jugular bulb oximetry in 10 comatose patients successfully resuscitated from an out‐of‐hospital cardiac arrest . Our data show that , in most patients , there is a significant difference between the two methods . The INVOS 3100 over‐read at low jugular bulb saturations ( < 60 % ) and under‐read at high jugular bulb saturations ( ≥ 60 % ) . During hypoventilation we found a significant increase in regional oxygen saturation . This increase was significantly correlated with the rise in cerebral blood flow and cardiac index , indicating that regional oxygen saturation is influenced by both cerebral and extracerebral components . We conclude that regional cerebral oxygen saturation measured with the INVOS 3100 can not be compared with global cerebral oxygen saturation measured with jugular bulb oximetry in comatose patients resuscitated from a cardiac arrest . This may be due to characteristics of the INVOS 3100 or to the distribution of cerebral blood flow after cardiac arrest R and omized clinical trials ( RCTs ) have revolutionized medicine by providing evidence on the efficacy and safety of drugs , devices , and procedures . Today , more than 40 000 RCTs are reported annually , their quality continues to increase , and oversight mechanisms ensure adequate protection of participants . However , RCTs have at least 4 related problems : ( 1 ) they are too expensive and difficult ; ( 2 ) their findings are too broad ( average treatment effect not representative of benefit for any given individual ) and too narrow ( trial population and setting not representative of general practice ) ; ( 3 ) r and omizing patients can make patients and physicians uncomfortable , especially when comparing different types of existing care ; and ( 4 ) there are often long delays before RCT results diffuse into practice . The new alternative is “ big data . ” Because medical care is increasingly digitized in electronic health record ( EHR ) data sets and linked biological and genetic data banks , proponents suggest that health care systems are at the dawn of an era in which a patient ’s prognosis and optimal therapy will be generated from rapid analysis of these data sets using sophisticated machinelearning strategies . The information is relatively inexpensive , generated as a by-product of patient care ( overcoming the cost problem ) , and both specific to individuals ( ie , adequately narrow ) and , en masse , descriptive of the entire delivery system ( ie , adequately broad ) . No individuals are r and omized , so the ethical issues appear less complex . The richness and immediacy of these new data could allow tailored treatment decisions in real time , overcoming delays in knowledge translation . As such , although the RCT remains the gold st and ard for evaluation of experimental therapies , big data is proposed as a better approach for the broad swath of comparative effectiveness questions that arise in clinical practice . Indeed , the Institute of Medicine envisions big data as the engine for so-called learning health care systems.1 Yet big data is not a replacement for the RCT . The singular beauty of the RCT is the strength of causal inference that arises from r and om assignment . All known and unknown factors that can influence outcome , other than the treatment assignment , are distributed r and omly— and , if r and omization is effective , evenly — among the groups . Thus , any statistical difference in outcome between groups can be attributed to the assigned interventions . In contrast , big data exploits variation that may appear r and om but is not in fact r and omized . For example , big data may compare patients who did or did not receive a particular drug and then attempt to determine the extent to which any difference in patient outcome may be related to receiving the drug . However , for all the allure of inexpensive access to massive amounts of data , the Achilles ’ heel is lack of causal inference . No matter how detailed the measurement and how sophisticated the adjustment for all known variables , big data can not eliminate unmeasured factors coincident with a particular treatment assignment that could explain an apparent change in outcome .2 Thus , each approach has complementary strengths : RCTs offer causal inference , and big data offers the potential for low-cost , high-volume , nuanced answers with immediate feedback . Rather than debate which is better , the greatest promise may come from fusing them Objective To compare the cerebral tissue oxygenation index ( TOI ) measured by near-infrared spectroscopy ( NIRS ) with venous oxygen saturation in the jugular bulb ( SjO2 ) during elective cardiac catheterization in children . Design and setting Prospect i ve observational clinical study in a catheterization laboratory for pediatric cardiology . Patients Sixty children with congenital heart defects admitted to the catheterization laboratory . Measurements and results TOI measured noninvasively by NIRS was compared to SjO2 measured in the jugular bulb during cardiac catheterization . Patients were divided into two groups regarding body weight : below ( n=29 ) and above 10 kg ( n=31 ) . Linear regression analysis and Pearson ’s correlation coefficient were calculated . Bl and -Altman analysis , sensitivity , and specificity calculation for spatially resolved near-infrared spectroscopy with a cutoff level of 60 % were performed . Simultaneously measured values for SjO2 ( 67.3±9.8 % , 40–84.1 % ) and TOI ( 65.7±7.2 % , 39–80 % ) showed a significant correlation ; the correlation in children weighing under 10 kg was stronger in children weighing over 10 kg . Bl and -Altman analysis showed a mean bias of −1.8 % with limits of agreement between 11.7 % and −15.3 % for all children . Sensitivity and specificity of the SRS method were 46 % and 91 % , respectively , for all children and 53 % and 83 % respectively in infants weighing under 10 kg . Conclusions The results demonstrate that despite a significant correlation , sensitivity of spatially resolved spectroscopy is poor , and it is question able whether TOI can be used reliably to detect low SjO2 OBJECTIVE To determine the optimal timing of cranial ultrasound scans ( USs ) for identifying preterm neonates weighing less than 1500 g at birth who develop intracranial complications of prematurity . DESIGN / SETTING Observational study at an urban county hospital . METHODS Serial USs from neonates with less than 1500-g birth weight ( BW ) admitted to the neonatal intensive care unit between January 1995 and December 1996 were review ed by a pediatric neuroradiologist in a blinded r and om manner . RESULTS Two hundred forty-eight neonates ( 78 % ) underwent at least 3 USs , 32 ( 10 % ) had 2 USs  and 37 ( 12 % ) only 1 US . The initial US was normal in 156 neonates ( 49 % ) and abnormal in 161 ( 57 % ) . The principal abnormalities included intraventricular hemorrhage ( IVH ) ( n = 74 ) , periventricular echogenicity ( PVE ) ( n = 68 ) , ventriculomegaly ( n = 7 ) , and solitary cysts ( n = 9 ) . Severe IVH ( n = 17 ) occurred in 13 ( 11.4 % ) of 114 neonates at less than 1000-g BW and 4 ( 5 % ) of 79 neonates of BW 1000 to 1250 g. In 11 cases ( 65 % ) , the severe IVH was clinical ly unsuspected . For neonates weighing less than 1000 g , IVH was diagnosed by days 3 to 5 in 10 ( 77 % ) of 13 , by days 10 to 14 in 11 ( 84 % ) of 13 , and by day 28 in all neonates ; for neonates 1001 to 1250 g , IVH was diagnosed in 1 ( 24 % ) of 4 by days 3 to 5 , 2 ( 50 % ) of 4 by days 10 to 14 , and 3 ( 75 % ) of 4 by day 28 . One infant 's condition was diagnosed on routine US before discharge from the hospital . Cystic periventricular leukomalacia ( PVL ) was noted in 9 neonates ; in 4 of the 9 cases , increased PVE was present on the initial US and cyst formation was obvious by the second US . For 4 neonates ( 3 with BW < 1000 g ) , all routine USs were negative and cystic PVL was noted on the predischarge US in these cases . Nonobstructive ventriculomegaly in the absence of IVH or cystic PVL was observed in 14 neonates . In 6 , it was noted on the initial screening US ; in 4 of the cases , it evolved after the third screening US . Two hundred fifty-six neonates had a US before discharge from the hospital ; 181 ( 72 % ) were normal and 75 ( 28 % ) abnormal . Nine significant lesions were identified by the US before discharge from the hospital ( ie , severe IVH [ n = 1 ] , cystic PVL [ n = 4 ] , and ventriculomegaly [ n = 4 ] ) . CONCLUSIONS The following screening protocol is recommended : ( 1 ) Neonates of less than 1000-g BW : initial US on days 3 to 5 ( should identify at least 75 % of cases of IVH and some PVE abnormalities ) ; second US on days 10 to 14 ( should detect at least 84 % of IVH and identify early hydrocephalus and early cyst formation ) ; third scan on day 28 ( should detect all cases of IVH , as well as assess PVE and ventricular size ) ; and final scan before discharge from the hospital ( should detect approximately 20 % of significant late-onset lesions ) . ( 2 ) Neonates of 1000- to 1250-g BW : initial US at days 3 to 5 ( should detect at least 40 % of significant abnormalities ) ; a second scan at day 28 ( should detect at least 70 % of significant abnormalities ) ; and a predischarge scan ( should detect all late-onset significant lesions ) . ( 3 ) Neonates of 1251- to 1500-g BW : an initial scan at days 3 to 5 ; and a second scan before discharge from the hospital if the clinical course is complicated . Arch Pediatr Adolesc Med . 2000;154:822 - Background : The SafeBoosC phase II multicentre r and omized clinical trial investigated the benefits and harms of monitoring cerebral oxygenation by near-infrared spectroscopy ( NIRS ) combined with an evidence -based treatment guideline vs. no NIRS data and treatment as usual in the control group during the first 72 h of life . The trial demonstrated a significant reduction in the burden of cerebral hypoxia in the experimental group . We now report the blindly assessed and analyzed treatment effects on electroencephalographic ( EEG ) outcomes ( burst rate and spectral edge frequency 95 % ( SEF95 ) ) and blood biomarkers of brain injury ( S100β , brain fatty acid-binding protein , and neuroketal ) . Methods : One hundred and sixty-six extremely preterm infants were r and omized to either experimental or control group .  EEG was recorded at 64 h of age and blood sample s were collected at 6 and 64 h of age . Results : One hundred and thirty-three EEGs were evaluated . The two groups did not differ regarding burst rates ( experimental 7.2 vs. control 7.7 burst/min ) or SEF95 ( experimental 18.1 vs. control 18.0 Hz ) . The two groups did not differ regarding blood S100β , brain fatty acid-binding protein , and neuroketal concentrations at 6 and 64 h ( n = 123 participants ) . Conclusion : Treatment guided by NIRS  reduced the cerebral burden of hypoxia without affecting EEG or the selected blood biomarkers INTRODUCTION The research programme Safeguarding the Brains of our smallest Children ( SafeBoosC ) aims to test the benefits and harms of cerebral near-infrared spectroscopy ( NIRS ) oximetry in infants born before 28 weeks of gestation . In a phase II trial , infants will be r and omised to visible cerebral NIRS oximetry with pre-specified treatment guidelines compared to st and ard care with blinded NIRS-monitoring . The primary outcome is duration multiplied with the extent outside the normal range of regional tissue oxygen saturation of haemoglobin ( rStO2 ) of 55 to 85 % in percentage hours ( burden ) . This study was a pilot of the Visible -Oximetry Group . MATERIAL AND METHODS This was an observational study including ten infants . RESULTS The median gestational age was 26 weeks+three days , and the median start-up time was 133 minutes after delivery .  The median recording time was 69.7 hours , mean rStO2 was 64.2±4.5 % , median burden of hyper- and hypoxia was 30.3 % hours ( range 2.8 - 112.3 ) . Clinical staff responded to an out of range value 29 times -- only once to values above 85 % . In comparison , there were 83 periods of more than ten minutes with an rStO2 below 55 % and four episodes with an rStO2 above 85 % . These periods accounted for 72 % of the total hypoxia burden . A total of 18 of the 29 interventions were adjustments of FiO2 which in 13 of the 18 times result ed in an out-of-range SpO2 . Two infants suffered second-degree burns from the sensor . Five infants died . In all cases , this was unrelated to NIRS monitoring and treatment . CONCLUSION The intervention of early cerebral NIRS monitoring proved feasible , but prolonged periods of hypoxia went untreated . Thus , a revision of the treatment guideline and an alarm system is required . FUNDING The Elsass Foundation funded the present study . TRIAL REGISTRATION Clinical trials.gov : NCT01530360 Background Every year in Europe about 25,000 infants are born extremely preterm . These infants have a 20 % mortality rate , and 25 % of survivors have severe long-term cerebral impairment . Preventative measures are key to reduce mortality and morbidity in an extremely preterm population . The primary objective of the SafeBoosC phase II trial is to examine if it is possible to stabilize the cerebral oxygenation of extremely preterm infants during the first 72 hours of life through the application of cerebral near-infrared spectroscopy ( NIRS ) oximetry and implementation of an clinical treatment guideline based on intervention thresholds of cerebral regional tissue saturation rStO2 . Methods / Design SafeBoosC is a r and omized , blinded , multinational , phase II clinical trial . The inclusion criteria are : neonates born more than 12 weeks preterm ; decision to conduct full life support ; parental informed consent ; and possibility to place the cerebral NIRS oximeter within 3 hours after birth . The infants will be r and omized into one of two groups . Both groups will have a cerebral oximeter monitoring device placed within three hours of birth . In the experimental group , the cerebral oxygenation reading will supplement the st and ard treatment using a predefined treatment guideline . In the control group , the cerebral oxygenation reading will not be visible and the infant will be treated according to the local st and ards . The primary outcome is the multiplication of the duration and magnitude of rStO2 values outside the target ranges of 55 % to 85 % , that is , the ‘ burden of hypoxia and hyperoxia ’ expressed in ‘ % hours ’ . To detect a 50 % difference between the experimental and control group in % hours , 166 infants in total must be r and omized . Secondary outcomes are mortality at term date , cerebral ultrasound score , and interburst intervals on an amplitude-integrated electroencephalogram at 64 hours of life and explorative outcomes include neurodevelopmental outcome at 2 years corrected age , magnetic resonance imaging at term , blood biomarkers at 6 and 64 hours after birth , and adverse events . Discussion Cerebral oximetry guided interventions have the potential to improve neurodevelopmental outcome in extremely preterm infants . It is a logical first step to test if it is possible to reduce the burden of hypoxia and hyperoxia . Trial registration Clinical Trial.gov , CONTEXT Controversy and uncertainty ensue when the results of clinical research on the effectiveness of interventions are subsequently contradicted . Controversies are most prominent when high-impact research is involved . OBJECTIVES To underst and how frequently highly cited studies are contradicted or find effects that are stronger than in other similar studies and to discern whether specific characteristics are associated with such refutation over time . DESIGN All original clinical research studies published in 3 major general clinical journals or high-impact-factor specialty journals in 1990 - 2003 and cited more than 1000 times in the literature were examined . MAIN OUTCOME MEASURE The results of highly cited articles were compared against subsequent studies of comparable or larger sample size and similar or better controlled design s. The same analysis was also performed comparatively for matched studies that were not so highly cited . RESULTS Of 49 highly cited original clinical research studies , 45 cl aim ed that the intervention was effective .  Of these , 7 ( 16 % ) were contradicted by subsequent studies , 7 others ( 16 % ) had found effects that were stronger than those of subsequent studies , 20 ( 44 % ) were replicated , and 11 ( 24 % ) remained largely unchallenged . Five of 6 highly-cited nonr and omized studies had been contradicted or had found stronger effects vs 9 of 39 r and omized controlled trials ( P = .008 ) . Among r and omized trials , studies with contradicted or stronger effects were smaller ( P = .009 ) than replicated or unchallenged studies although there was no statistically significant difference in their early or overall citation impact . Matched control studies did not have a significantly different share of refuted results than highly cited studies , but they included more studies with " negative " results . CONCLUSIONS Contradiction and initially stronger effects are not unusual in highly cited research of clinical interventions and their outcomes . The extent to which high citations may provoke contradictions and vice versa needs more study . Controversies are most common with highly cited nonr and omized studies , but even the most highly cited r and omized trials may be challenged and refuted over time , especially small ones Background : The current study was design ed to determine the relation between  preoperative cerebral oxygen saturation ( Sco2 ) , variables of cardiopulmonary function , mortality , and morbidity in a heterogeneous cohort of cardiac surgery patients . Methods : In this study , 1,178 consecutive patients scheduled for on-pump surgery were prospect ively studied . Preoperative Sco2 , demographics , N-terminal pro-B-type natriuretic peptide , high-sensitive troponin T , clinical outcomes , and 30-day and 1-yr mortality were recorded . Results : Median additive EuroSCORE  was 5 ( range : 0–19 ) . Thirty-day and 1-yr mortality and major morbidity ( at least two major complications and /or a high-dependency unit stay of at least 10 days ) were 3.5 % , 7.7 % , and 13.3 % , respectively . Median minimal preoperative oxygen supplemented Sco2 ( Sco2min-ox ) was 64 % ( range : 15–92 % ) . Sco2min-ox was correlated ( all : P value < 0.0001 ) with N-terminal pro-B-type natriuretic peptide ( & rgr ; : −0.35 ) , high-sensitive troponin T ( & rgr ; : −0.28 ) , hematocrit ( & rgr ; : 0.34 ) , glomerular filtration rate ( & rgr ; : 0.19 ) , EuroSCORE ( & tgr ; : 0.20 ) , and left ventricular ejection fraction class ( & tgr ; : 0.12 ) . Thirty-day nonsurvivors had a lower Sco2min-ox than survivors ( median 58 % [ 95 % CI , 50.7–62 % ] vs. 64 % [ 95 % CI , 64–65 % ] ; P < 0.0001 ) . Receiver-operating curve analysis of Sco2min-ox and 30-day mortality revealed an area-under-the-curve of 0.71 ( 95 % CI , 0.68–0.73 % ; P < 0.0001 ) in the total cohort and an area-under-the-curve of 0.77 ( 95 % CI , 0.69–0.86 % ; P < 0.0001 ) in patients  with a EuroSCORE more than 10 . Logistic regression based on different EuroSCORE categories ( 0–2 ; 3–5 , 6–10 , > 10 ) , Sco2min-ox , and duration of cardiopulmonary bypass showed that a Sco2min-ox equal or less than 50 % is an independent risk factor for 30-day and 1-yr mortality . Conclusions : Preoperative Sco2 levels are reflective of the severity of cardiopulmonary dysfunction , associated with short- and long-term mortality and morbidity , and may add to preoperative risk stratification in patients undergoing cardiac surgery BACKGROUND : Cerebral deoxygenation is associated with various adverse systemic outcomes . We hypothesized , by using the brain as an index organ , that interventions to improve cerebral oxygenation would have systemic benefits in cardiac surgical patients . METHODS : Two-hundred coronary artery bypass patients were r and omized to either intraoperative cerebral regional oxygen saturation ( rSO2 ) monitoring with active display and treatment intervention protocol ( intervention , n = 100 ) , or underwent blinded rSO2 monitoring ( control , n = 100 ) . Predefined clinical outcomes were assessed by a blinded observer . RESULTS : Significantly more patients in the control group demonstrated prolonged cerebral desaturation ( P = 0.014 ) and longer duration in the intensive care unit ( P = 0.029 ) versus intervention patients . There was no difference in overall incidence of adverse complications , but significantly more control patients had major organ morbidity or mortality ( death , ventilation > 48 h , stroke , myocardial infa rct ion , return for re-exploration ) versus intervention group patients ( P = 0.048 ) . Patients experiencing major organ morbidity or mortality had lower baseline and mean rSO2 , more cerebral desaturations and longer lengths of stay in the intensive care unit and postoperative hospitalization , than patients without such complications . There was a significant ( r2 = 0.29 ) inverse correlation between intraoperative rSO2 and duration of postoperative hospitalization in patients requiring ≥10 days postoperative length of stay . CONCLUSION : Monitoring cerebral rSO2 in coronary artery bypass patients avoids profound cerebral desaturation and is associated with significantly fewer incidences of major organ dysfunction Objective : To determine the rate and severity of short- and long-term morbidity in very low birth weight infants treated before and after the implementation of a change in clinical practice design ed to avoid hyperoxia . Methods : Analysis of a prospect ively collected data base of all infants ⩽1250 g admitted to two Emory University NICU 's from January 2000 to December 2004 . A change in practice was instituted in January 2003 with the objective of avoiding hyperoxia in preterm infants with target O2 saturation ( SpO2 ) at 93 to 85 % ( Period II ) . Before the change in practice , SpO2 high alarms were set at 100 % and low alarms at 92 % ( Period I ) . Statistical analysis included bivariate analyses and multivariate logistic regression comparing outcomes between the two periods . Results : From January 2000 to December 2004 , 502 infants met enrollment criteria and 202 ( 40 % ) were born in period II , after change in SpO2 targets . Birth weight , gestational age and survival were similar between both periods . The rates for any retinopathy of prematurity , supplemental oxygen at 36 weeks post-conceptional age and the use of steroids for chronic lung disease were significantly lower in the infants born in Period II . There was no difference in the rates of necrotizing enterocolitis , intraventricular hemorrhage and periventricular leukomalacia . At 18 months corrected age ( CA ) , the infants treated during Period II had a higher Mental Developmental Index ( MDI ) scores ( 80.2±18.3 vs 89.2±18.5 ; P 0.02 ) and similar Psychomotor Developmental Index ( PDI ) scores ( 83.9±18.6 vs 89.4±17.2 ; P 0.08 ) than those treated during Period I. The proportion of infants with an MDI or a PDI less than 70 was similar between the periods . Conclusions : The change in practice to avoid hyperoxia is associated with a significant decrease in neonatal morbidity and does not have a detrimental effect on developmental outcomes at 18 months CA BACKGROUND Previous studies have reported an 11 % to 75 % incidence of postoperative cognitive decline among cardiac surgery patients . The INVOS Cerebral Oximeter ( Somanetics Corp , Troy , MI ) is a Food and Drug Administration approved device that measures regional cerebral oxygen ( rSo(2 ) ) saturation . The purpose of this study is to examine whether decreased rSo(2 ) predicts cognitive decline and prolonged hospital stay after coronary artery bypass grafting ( CABG ) . METHODS The rSo(2 ) was monitored intraoperatively in a cohort of primary CABG patients . Patients were prospect ively r and omized to a blinded control group or an unblinded intervention group . Cognitive function was assessed preoperatively , postoperatively , and at 3 months using a battery of st and ardized neurocognitive tests . Cognitive decline was defined as a decrease of one st and ard deviation or more in performance on at least one neurocognitive measure . The rSo(2 ) desaturation score was calculated by multiplying rSo(2 ) below 50 % by time ( seconds ) . Multivariate logistic regression models were used to assess cognitive decline and hospital stay . The change in cognitive performance was also assessed using a multivariate linear regression model . RESULTS Patients with rSo(2 ) desaturation score greater than 3,000%-second had a significantly higher risk of early postoperative cognitive decline [ p = 0.024 ] . Patients with rSo(2 ) desaturation score greater than 3,000%-second also had a near threefold increased risk of prolonged hospital stay ( > 6 days ) [ p = 0.007 ] . CONCLUSIONS Intraoperative cerebral oxygen desaturation is significantly associated with an increased risk of cognitive decline and prolonged hospital stay after CABG Elderly patients are more prone than younger patients to develop cerebral desaturation because of the reduced physiologic reserve that accompanies aging . To evaluate whether monitoring cerebral oxygen saturation ( rSO2 ) minimizes intraoperative cerebral desaturation , we prospect ively monitored rSO2 in 122 elderly patients undergoing major abdominal surgery with general anesthesia .  Patients were r and omly allocated to an intervention group ( the monitor was visible and rSO2 was maintained at ≥75 % of preinduction values ; n = 56 ) or a control group ( the monitor was blinded and anesthesia was managed routinely ; n = 66 ) . Cerebral desaturation ( rSO2 reduction < 75 % of baseline ) was observed in 11 patients of the treatment group ( 20 % ) and 15 patients of the control group ( 23 % ) ( P = 0.82 ) . Mean ( 95 % confidence intervals ) values of mean rSO2 were higher ( 66 % [ 64%–68 % ] ) and the area under the curve below 75 % of baseline ( AUCrSO22 < 75 % of baseline ) was lower ( 0.4 min% [ 0.1–0.8 min% ] ) in patients of the treatment group than in patients of the control group ( 61 % [ 59%–63 % ] and 80 min% [ 2–144 min% ] , respectively ; P = 0.002 and P = 0.017 ) . When considering only patients developing intraoperative cerebral desaturation , a lower Mini Mental State Elimination ( MMSE ) score was observed at the seventh postoperative day in the control group ( 26 [ 25–30 ] ) than in the treatment group ( 28 [ 26–30 ] ) ( P = 0.02 ) , with a significant correlation between the AUCrSO2 < 75 % of baseline and postoperative decrease in MMSE score from preoperative values ( r2= 0.25 , P = 0.01 ) . Patients of the control group with intraoperative cerebral desaturation also experienced a longer time to postanesthesia care unit ( PACU ) discharge ( 47 min [ 13–56 min ] ) and longer hospital stay ( 24 days [ 7–53 ] days ) compared with patients of the treatment group ( 25 min [ 15–35 min ] and 10 days [ 7–23 days ] , respectively ; P = 0.01 and P = 0.007 ) . Using rSO2 monitoring to manage anesthesia in elderly patients undergoing major abdominal surgery reduces the potential exposure of the brain to hypoxia ; this might be associated with decreased effects on cognitive function and shorter PACU and hospital stay Background : Cerebral oxygen desaturation during cardiac surgery has been associated with adverse perioperative outcomes . Before a large multicenter r and omized controlled trial ( RCT ) on the impact of preventing desaturations on perioperative outcomes , the authors undertook a r and omized prospect i ve , parallel-arm , multicenter feasibility RCT to determine whether an intervention algorithm could prevent desaturations . Methods : Eight Canadian sites r and omized 201 patients between April 2012 and October 2013 . The primary outcome was the success rate of reversing cerebral desaturations below 10 % relative to baseline in the intervention group . Anesthesiologists were blinded to the cerebral saturation values in the control group . Intensive care unit personnel were blinded to cerebral saturation values for both groups . Secondary outcomes included the area under the curve of cerebral desaturation load , enrolment rates , and a 30-day follow-up for adverse events . Results : Cerebral desaturations occurred in 71 ( 70 % ) of the 102 intervention group patients and 56 ( 57 % ) of the 99 control group patients ( P = 0.04 ) . Reversal was successful in 69 ( 97 % ) of the intervention group patients . The mean cerebral desaturation load ( SD ) in the operating room was smaller for intervention group patients compared with control group patients ( 104 [ 217 ] % .min vs. 398 [ 869 ] % .min , mean difference , −294 ; 95 % CI , −562 to −26 ; P = 0.03 ) . This was also true in the intensive care unit ( P = 0.02 ) . There were no differences in adverse events between the groups . Conclusions : Study sites were successful in reversal of desaturation , patient recruitment , r and omization , and follow-up in cardiac surgery , supporting the feasibility of conducting a large multicenter RCT OBJECTIVE To assess if monitoring of cerebral regional tissue oxygen saturation ( crSO2 ) using near-infrared spectroscopy ( NIRS ) to guide respiratory and supplemental oxygen support reduces burden of cerebral hypoxia and hyperoxia in preterm neonates during resuscitation after birth . STUDY DESIGN Preterm neonates < 34(+0 ) weeks of gestation were included in a prospect i ve r and omized controlled pilot feasibility study at 2 tertiary level neonatal intensive care units . In a NIRS-visible group , crSO2 monitoring in addition to pulse oximetry was used to guide respiratory and supplemental oxygen support during the first 15 minutes after birth . In a NIRS-not-visible group , only pulse oximetry was used . The primary outcomes were burden of cerebral hypoxia ( < 10th percentile ) or hyperoxia ( > 90th percentile ) measured in % minutes crSO2 during the first 15 minutes after birth . Secondary outcomes were all cause of mortality and /or cerebral injury and neurologic outcome at term age . Allocation sequence was 1:1 with block-r and omization of 30 preterm neonates at each site . RESULTS In the NIRS-visible group burden of cerebral hypoxia in % minutes , crSO2 was halved , and the relative reduction was 55.4 % ( 95 % CI 37.6 - 73.2 % ; P = .028 ) . Cerebral hyperoxia was observed in NIRS-visible group in 3 neonates with supplemental oxygen and in NIRS-not-visible group in 2 . Cerebral injury rate and neurologic outcome at term age was similar in both groups . Two neonates died in the NIRS-not-visible group and none in the NIRS-visible group . No severe adverse reactions were observed . CONCLUSIONS Reduction of burden of cerebral hypoxia during immediate transition and resuscitation after birth is feasible by crSO2 monitoring to guide respiratory and supplemental oxygen support . TRIAL REGISTRATION Clinical Trials.gov : NCT02017691 BACKGROUND Near-infrared spectroscopy is a developing technique for monitoring cerebral oxygenation during anaesthesia . The aim of this study was to evaluate absolute values of cerebral oxygenation during stable anaesthesia conditions in otherwise healthy children using the recently introduced INVOS 5100 cerebral oximeter with a paediatric and adult sensor and to compare them with values obtained from the NIRO 300 oximeter . METHODS Thirty paediatric surgical patients ( aged 0.23 - 15.97 years ) were studied during general anaesthesia with tracheal intubation and controlled ventilation .  Comparative measurements of cerebral oxygenation were performed on the forehead with two probes within 10 min under stable cardiorespiratory and anaesthesia conditions . Cerebral oxygenation values ( rSO2 ) obtained from the paediatric and adult INVOS 5100 sensors were compared with the tissue oxygenation index ( TOI ) obtained from the NIRO 300 cerebral oximeter using 4- and 5-cm emitter-detector separation . RESULTS Cerebral rSO2 values and the TOI values both showed a large range of cerebral oxygenation in the children studied ( rSO2 : 59 - 95 % , TOI : 48 - 85 % ) . Cerebral rSO2 values measured by the INVOS 5100 , particularly with the paediatric sensor , were significantly higher than the TOI values obtained from the NIRO 300 ( P < 0.0001 ) . Agreement between the INVOS and NIRO oximeter was poor . CONCLUSION The large range and the poor agreement of cerebral oxygenation values between the two oximeters makes it difficult to define a normal value . Cerebral oxygenation readings by these monitors , based on one single point measurement during anaesthesia , should be viewed with caution . Actually , there may be little indication for routine use of such monitoring during general anaesthesia Persistent patency of the ductus arteriosus in the preterm infant is associated with numerous morbidities , including higher rates of bronchopulmonary dysplasia and increased mortality . These strong associations have led to widespread use of cyclooxygenase inhibitors and surgical ligation to achieve ductal closure in the expectation that closing the ductus will reduce these complications . Each of these interventions has its own associated adverse effects . Neither individual r and omised controlled trials nor meta-analyses of those trials have been able to demonstrate long-term benefits of these treatments despite their efficacy in inducing ductal closure and reducing the need for ductal ligation . Despite the potential shortcomings of those trials , they provide substantial cumulative evidence that early , routine treatment to close a persistently patent ductus arteriosus in preterm infants does not improve outcomes and should therefore be ab and oned . Future trials of these interventions for patent ductus management should address different questions . Persistence of ductal patency should be considered a sign of rather than a direct cause of the several morbidities with which it is clearly associated . Practitioners should tolerate ductal patency and learn to manage its causes and consequences rather than focusing on achievement of ductal closure Published evidence suggests that aspects of trial design lead to biased intervention effect estimates , but findings from different studies are inconsistent . This study combined data from 7 meta-epidemiologic studies and removed overlaps to derive a final data set of 234 unique meta-analyses containing 1973 trials . Outcome measures were classified as " mortality , " " other objective , " " or subjective , " and Bayesian hierarchical models were used to estimate associations of trial characteristics with average bias and between-trial heterogeneity . Intervention effect estimates seemed to be exaggerated in trials with inadequate or unclear ( vs. adequate ) r and om-sequence generation ( ratio of odds ratios , 0.89 [ 95 % credible interval { CrI } , 0.82 to 0.96 ] ) and with inadequate or unclear ( vs. adequate ) allocation concealment ( ratio of odds ratios , 0.93 [ CrI , 0.87 to 0.99 ] ) . Lack of or unclear double-blinding ( vs. double-blinding ) was associated with an average of 13 % exaggeration of intervention effects ( ratio of odds ratios , 0.87 [ CrI , 0.79 to 0.96 ] ) , and between-trial heterogeneity was increased for such studies ( SD increase in heterogeneity , 0.14 [ CrI , 0.02 to 0.30 ] ) . For each characteristic , average bias and increases in between-trial heterogeneity were driven primarily by trials with subjective outcomes , with little evidence of bias in trials with objective and mortality outcomes . This study is limited by incomplete trial reporting , and findings may be confounded by other study design characteristics . Bias associated with study design characteristics may lead to exaggeration of intervention effect estimates and increases in between-trial heterogeneity in trials reporting subjectively assessed outcomes
target: The only eligible r and omised clinical trial did not demonstrate any consistent effects of NIRS plus a guideline on the assessed clinical outcomes .
  The trial was , however , only powered to detect difference in cerebral oxygenation , not morbidities or mortality .
background: BACKGROUND Cerebral injury and long-term neurodevelopmental impairment is common in extremely preterm infants .
  Cerebral near-infrared spectroscopy ( NIRS ) enables continuous estimation of cerebral oxygenation .
  This diagnostic method coupled with appropriate interventions if NIRS is out of normal range ( that is cerebral oxygenation within the 55 % to 85 % range ) may offer benefits without causing more harms .
  Therefore , NIRS coupled with appropriate responses to abnormal findings on NIRS needs assessment in a systematic review of r and omised clinical trials and quasi-r and omised studies .
  OBJECTIVES To evaluate the benefits and harms of interventions that attempt to alter cerebral oxygenation guided by cerebral NIRS monitoring in order to prevent cerebral injury , improve neurological outcome , and increase survival in preterm infants born more than 8 weeks preterm .