A Bedside Method for Measuring Effects of a Sedative Drug on Cerebral Function in Newborn Infants.

BACKGROUND: Data on the cerebral effects of analgesic and sedative drugs are needed for the development of safe and effective treatments during neonatal intensive care. Electroencephalography (EEG) is an objective, but interpreter-dependent method for monitoring cortical activity. Quantitative computerized analyses might reveal EEG changes otherwise not detectable. METHODS: EEG registrations were retrospectively collected from 21 infants (mean 38.7 gestational weeks; range 27-42) who received dexmedetomidine during neonatal care. The registrations were transformed into computational features and analyzed visually, and with two computational measures quantifying relative and absolute changes in power (range EEG; rEEG) and cortico-cortical synchrony (activation synchrony index; ASI), respectively. RESULTS: The visual assessment did not reveal any drug effects. In rEEG analyses, a negative correlation was found between the baseline and the referential frontal (rho = 0.612, p = 0.006) and parietal (rho = -0.489, p = 0.035) derivations. The change in ASI was negatively correlated to baseline values in the interhemispheric (rho = -0.753; p = 0.001) and frontal comparisons (rho = -0.496; p = 0.038). CONCLUSION: Cerebral effects of dexmedetomidine as determined by EEG in newborn infants are related to cortical activity prior to DEX administration, indicating that higher brain activity levels (higher rEEG) during baseline links to a more pronounced reduction by DEX. The computational measurements indicate drug effects on both overall cortical activity and cortico-cortical communication. These effects were not evident in visual analysis.

Clonidine for pain in non-ventilated infants.

BACKGROUND: Critically ill newborn infants undergo a variety of painful procedures or experience a variety of painful conditions during their early life in the neonatal unit. In the critically ill paediatric and neonatal population, clonidine is prescribed as an adjunct to opioids or benzodiazepines aiming to reduce the doses of these drugs that are required for analgesia or sedation, or to facilitate weaning from mechanical ventilation. It has been shown that clonidine premedication might have a positive effect on postoperative pain in children. OBJECTIVES: To assess the benefit and harms of clonidine for the prevention or treatment of procedural pain; postoperative pain; or pain associated with clinical conditions in non-ventilated neonates. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the CENTRAL, MEDLINE via PubMed, Embase, and CINAHL to December 2018. We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. We ran an updated search from 1 January 2018 to 11 March 2020 in CENTRAL via CRS Web, MEDLINE via Ovid, and CINAHL via EBSCOhost. SELECTION CRITERIA: Randomised controlled trials, quasi-randomised controlled trials, and cluster trials comparing clonidine to placebo or no treatment, opioids, paracetamol, dexmedetomidine, or non-pharmacological pain-reducing interventions for the management of procedural pain, postoperative pain, and pain associated with clinical conditions in preterm and term newborns. DATA COLLECTION AND ANALYSIS: Two review authors independently planned to extract data (e.g. number of participants, birth weight, gestational age, modality of administration, and dose of clonidine) and assess the risk of bias (e.g. adequacy of randomisation, blinding, completeness of follow-up). The primary outcome considered was pain: for procedural pain, the mean values of each analgesia scale assessed during the procedure and at one to two hours after the procedure; for postoperative pain and for pain associated with clinical conditions, the mean values of each analgesia scale assessed at 30 minutes, three hours, and 12 hours after the administration of the intervention. We planned to use the GRADE approach to assess the quality of evidence. MAIN RESULTS: Our search strategy yielded 3383 references. Two review authors independently assessed all references for inclusion. We did not find any completed studies for inclusion. We excluded three trials where clonidine was administered for spinal anaesthesia. AUTHORS' CONCLUSIONS: We did not find any studies that met our inclusion criteria and hence there is no evidence to recommend or refute the use of clonidine for the prevention or treatment of procedural or postoperative pain, or pain associated with clinical conditions in neonates.

Improved infrastructure and support needed for paediatric clinical trials in Sweden.

AIM: There is a lack of authorised medicines for paediatric patients and improved drug development is necessary. The aim of this study was to evaluate the need for infrastructure and support for paediatric clinical trials in Sweden. METHODS: A web-based survey was sent to doctors and nurses involved in the care of neonates, children and adolescents assessing the current situation and future needs for paediatric clinical trials in Sweden. Questions regarding premises, competence, organisation, support for paediatric clinical trials and Good Clinical Practice Training were addressed. RESULTS: In total, 137 individuals responded to the survey (109 doctors and 28 nurses). Overall, 61% of the respondents had previous experience of paediatric clinical trials. Some respondents had access to trial units, but only 34% had used the trial unit for support. Half of the responders were interested in recurrent paediatric Good Clinical Practice training. Doctors responded that clinical work often had to be prioritised and emphasised the need for research time. CONCLUSION: This study clearly shows the commitment for clinical trials among doctors and nurses involved in paediatric care in Sweden, but also that administrative, logistic and economic support in a sustainable setting and an expanded national collaboration are needed.

Individual variations in fentanyl pharmacokinetics and pharmacodynamics in preterm infants.

AIM: Fentanyl pharmacokinetics and pharmacodynamics are lacking in preterm infants. Our aim was to study these and their relation with a new formulation of fentanyl 5 µg/mL for procedural pain. METHODS: Preterm infants were given 0.5 (n = 20, median gestational age 26.5; range 23.3-34.1 weeks) and 2 µg/kg (n = 8, 27.4; 25.3-30.7 weeks) fentanyl, respectively, before skin-breaking procedures or tracheal intubation. Blood samples were collected after ten minutes, two, four, eight and 24 hours. Physiologic parameters were monitored and pain scores assessed. RESULTS: The median fentanyl concentrations were 0.18, 0.15, 0.15 and 0.57, 0.37, 0.35 ng/mL at 15-31 minutes, two and four hours and the half-lives were 1.6 to 20.5 or 4.1 to 32.6 hours for the low- and high-dose groups, respectively. A significant correlation was seen between weight at study inclusion and half-life (Spearman's r = -0.9, p < 0.001), volume of distribution (r = -0.8, p < 0.01) and clearance (r = -0.9, p < 0.01) in the low-dose group (n = 9). Pain assessment results were not correlated to pharmacokinetic variables. Fentanyl was well tolerated. CONCLUSION: The inter-individual variation of fentanyl pharmacokinetics is large in preterm infants, and the dose of 0.5 µg/kg seems not effective for skin-breaking procedures.

Swedish consensus reached on recording, interpretation and reporting of neonatal continuous simplified electroencephalography that is supported by amplitude-integrated trend analysis.

Continuous monitoring of electroencephalography (EEG), with a focus on amplitude-integrated EEG (aEEG), has been used in neonatal intensive care for decades. A number of systems have been suggested for describing and quantifying aEEG patterns. Extensive full-montage EEG monitoring is used in specialised intensive care units. The American Clinical Neurophysiology Society published recommendations for defining and reporting EEG findings in critically ill adults and infants. Swedish neonatologists and clinical neurophysiologists collaborated to optimise simplified neonatal continuous aEEG and EEG recordings based on these American documents. CONCLUSION: This paper describes the Swedish consensus document produced by those meetings.

Clonidine for sedation and analgesia for neonates receiving mechanical ventilation.

BACKGROUND: Although routine administration of pharmacologic sedation or analgesia during mechanical ventilation in preterm neonates is not recommended, its use in clinical practice remains common. Alpha-2 agonists, mainly clonidine and dexmedetomidine, are used as adjunctive (or alternative) sedative agents alongside opioids and benzodiazepines. Clonidine has not been systematically assessed for use in neonatal sedation during ventilation. OBJECTIVES: To assess whether clonidine administered to term and preterm newborn infants receiving mechanical ventilation reduces morbidity and mortality rates. To compare the intervention versus placebo, no treatment, and dexmedetomidine; and to assess the safety of clonidine infusion for potential harms.To perform subgroup analyses according to gestational age; birth weight; administration method (infusion or bolus therapy); dose, duration, and route of clonidine administration; and pharmacologic sedation as a co-intervention. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 12) in the Cochrane Library, MEDLINE via PubMed (1966 to January 10, 2017), Embase (1980 to January 10, 2017), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to January 10, 2017). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomized controlled trials and quasi-randomized trials. SELECTION CRITERIA: We searched for randomized controlled trials, quasi-randomized controlled trials, and cluster trials comparing clonidine versus placebo, no treatment, or dexmedetomidine administered to term and preterm newborns receiving mechanical ventilation via an endotracheal tube. DATA COLLECTION AND ANALYSIS: For the included trial, two review authors independently extracted data (e.g. number of participants, birth weight, gestational age, all-cause death during initial hospitalization, duration of respiratory support, sedation scale, duration of hospital stay) and assessed risk of bias (e.g. adequacy of randomization, blinding, completeness of follow-up). This review considered primary outcomes of all-cause neonatal death, all-cause death during initial hospitalization, and duration of mechanical ventilation in days. MAIN RESULTS: One trial, which included 112 infants, met the inclusion criteria for this review. Term newborn infants on mechanical ventilation with the need for continuous analgesia and sedation with fentanyl and midazolam were eligible for enrollment during the first 96 hours of ventilation. Study authors administered clonidine 1 µg/kg/h or placebo on day 4 after intubation.We found no differences between the two groups in all-cause death during hospitalization (risk ratio [RR] 0.69, 95% confidence interval [CI] 0.12 to 3.98). The quality of the evidence supporting these findings is low owing to imprecision of the estimates (one study; few events). The median (interquartile range) duration of mechanical ventilation was 7.1 days (5.7 to 9.1 days) in the clonidine group and 5.8 days (4.9 to 7.9 days) in the placebo group, respectively (P = 0.070). Among secondary outcomes, we found no differences in terms of duration of stay in the intensive care unit. Sedation scale values (COMFORT) and analgesia scores (Hartwig) during the first 72 hours of infusion of study medication were lower in the clonidine group than in the placebo group. AUTHORS' CONCLUSIONS: At present, evidence is insufficient to show the efficacy and safety of clonidine for sedation and analgesia in term and preterm newborn infants receiving mechanical ventilation.

Genetic Predisposition to Poor Opioid Response in Preterm Infants: Impact of KCNJ6 and COMT Polymorphisms on Pain Relief After Endotracheal Intubation.

BACKGROUND: Single-nucleotide polymorphisms in genes involved in pain control might predispose to exaggerated sensitivity or difference in opioid analgesic effect. The relevance of the KCNJ6 -1250G>A (rs6517442, c.-1787G>A) and the catecholamine-O-methyltransferase (COMT) c.472G>A (rs4680, ValMet) single-nucleotide polymorphisms were studied in preterm infants needing intubation and randomized to a premedication strategy including remifentanil (n = 17) or morphine (n = 17). METHODS: Pain was scored with Astrid Lindgren and Lund Children's Hospital Pain Assessment Scale every 30 minutes for 6 hours. The pain relief provided by the opioids was compared between the different KCNJ6 and COMT genotypes. RESULTS: Infants homozygous for the KCNJ6 -1250A allele had an increased duration after intubation to achieve a score indicating no pain compared with infants with the A/G or G/G genotypes (182 ± 30, 109 ± 29, and 60 ± 21 minutes, respectively; Logrank = 7.5, P = 0.006). Similarly, the duration was increased in individuals with the COMT Val/Val alleles compared with Val/Met and Met/Met (285 ± 37, 137 ± 25, and 63 ± 15 minutes, respectively; Logrank = 14.4, P = 0.0021). Cox proportional hazards analysis confirmed that the variation in both genes was independently associated with susceptibility to respond to therapy. CONCLUSION: We conclude that the KCNJ6 -1250A and COMT Val alleles are predisposing preterm newborns to diminished opioid-induced pain relief.

The relationship between strategic control and conscious structural knowledge in artificial grammar learning.

We address Jacoby's (1991) proposal that strategic control over knowledge requires conscious awareness of that knowledge. In a two-grammar artificial grammar learning experiment all participants were trained on two grammars, consisting of a regularity in letter sequences, while two other dimensions (colours and fonts) varied randomly. Strategic control was measured as the ability to selectively apply the grammars during classification. For each classification, participants also made a combined judgement of (a) decision strategy and (b) relevant stimulus dimension. Strategic control was found for all types of decision strategy, including trials where participants claimed to lack conscious structural knowledge. However, strong evidence of strategic control only occurred when participants knew or guessed that the letter dimension was relevant, suggesting that strategic control might be associated with - or even causally requires - global awareness of the nature of the rules even though it does not require detailed knowledge of their content.

Metacognition and Reading: Comparing Three Forms of Metacognition in Normally Developing Readers and Readers with Dyslexia.

Metacognition refers to 'cognition about cognition' and includes metacognitive knowledge, strategies and experiences (Efklides, 2008; Flavell, 1979). Research on reading has shown that better readers demonstrate more metacognitive knowledge than poor readers (Baker & Beall, 2009), and that reading ability improves through strategy instruction (Gersten, Fuchs, Williams, & Baker, 2001). The current study is the first to specifically compare the three forms of metacognition in dyslexic (N = 22) versus normally developing readers (N = 22). Participants read two factual texts, with learning outcome measured by a memory task. Metacognitive knowledge and skills were assessed by self-report. Metacognitive experiences were measured by predictions of performance and judgments of learning. Individuals with dyslexia showed insight into their reading problems, but less general knowledge of how to approach text reading. They more often reported lack of available reading strategies, but groups did not differ in the use of deep and surface strategies. Learning outcome and mean ratings of predictions of performance and judgments of learning were lower in dyslexic readers, but not the accuracy with which metacognitive experiences predicted learning. Overall, the results indicate that dyslexic reading and spelling problems are not generally associated with lower levels of metacognitive knowledge, metacognitive strategies or sensitivity to metacognitive experiences in reading situations.

Development and psychometric properties of the Swedish ALPS-Neo pain and stress assessment scale for newborn infants.

AIM: To validate and evaluate the psychometric properties of the ALPS-Neo, a new pain assessment scale created for the continuous evaluation of pain and stress in preterm and sick term infants. METHODS: A unidimensional scale for continuous pain, Astrid Lindgren Children's Hospital Pain Scale (ALPS 1), was developed further to assess continuous pain and stress in infants treated in the neonatal intensive care unit (NICU). The pain scale includes observations of five behaviours. A manual was created, clarifying the scoring criteria. An internal and an external panel assessed face validity. Psychometric properties were evaluated in three different steps. Inter-rater reliability was estimated from video-based assessments (n = 625) using weighted kappa statistics (test I). Inter-rater reliability was further evaluated in test II (n = 125) and test III (n = 96) by real-time assessments using the intraclass correlation coefficient (ICC) and Cronbach's alpha. RESULTS: The final inter-rater reliability (test III) was assessed as good with ICC 0.91 for the total score and 0.62-0.81 for the five items. Cronbach's alpha showed 0.95 for the total score. CONCLUSION: ALPS-Neo is a new assessment tool for optimising the management of pain and stress in newborn infants in the NICU. It has proved easy to implement and user-friendly, permitting fast, reliable observations with high inter-rater reliability.

Premedication for intubation with morphine causes prolonged depression of electrocortical background activity in preterm infants.

BACKGROUND: Sedative and analgesic medications are used in critically ill newborns, but little is known about their effects on electrocortical activity in preterm infants. We hypothesized that morphine might induce prolonged neurodepression, independent of blood pressure, as compared with rapid sequence induction/intubation(RSI). METHODS: Of 34 infants enrolled in a randomized controlled trial (RCT) comparing RSI (including thiopental 2-3 mg/kg and remifentantil 1 mcg/kg) with morphine (0.3 mg/kg) as premedication for intubation, 28 infants (n = 14 + 14; median gestational age 26.1 wk and postnatal age 138 h) had continuous two-channel amplitude-integrated electroencephalogram (aEEG/EEG) and blood pressure monitoring during 24 h after the intubation. Thirteen infants not receiving any additional medication constituted the primary study group. Visual and quantitative analyses of aEEG/EEG and blood pressure were performed in 3-h epochs. RESULTS: RSI was associated with aEEG/EEG depression lasting <3 h. Morphine premedication resulted in aEEG/EEG depression with more discontinuous background and less developed cyclicity for 24 h, and during the first 9 h, interburst intervals (IBI) were significantly increased as compared with those of RSI treatment. The difference was not related to blood pressure. CONCLUSION: Premedication with morphine is associated with prolonged aEEG/EEG depression independent of blood pressure changes and may not be optimal for short procedures.

Early single-channel aEEG/EEG predicts outcome in very preterm infants.

AIM: To characterize early amplitude-integrated electroencephalogram (aEEG) and single-channel EEG (aEEG/EEG) in very preterm (VPT) infants for prediction of long-term outcome. PATIENTS: Forty-nine infants with median (range) gestational age of 25 (22-30) weeks. METHODS: Amplitude-integrated electroencephalogram/EEG recorded during the first 72 h and analysed over 0-12, 12-24, 24-48 and 48-72 h, for background pattern, sleep-wake cycling, seizures, interburst intervals (IBI) and interburst percentage (IB%). In total, 2614 h of single-channel EEG examined for seizures. Survivors were assessed at 2 years corrected age with a neurological examination and Bayley Scales of Infant Development-II. Poor outcome was defined as death or survival with neurodevelopmental impairment. Good outcome was defined as survival without impairment. RESULTS: Thirty infants had good outcome. Poor outcome (n = 19) was associated with depressed aEEG/EEG already during the first 12 h (p = 0.023), and with prolonged IBI and higher IB% at 24 h. Seizures were present in 43% of the infants and associated with intraventricular haemorrhages but not with outcome. Best predictors of poor outcome were burst-suppression pattern [76% correctly predicted; positive predictive value (PPV) 63%, negative predictive value (NPV) 91%], IBI > 6 sec (74% correctly predicted; PPV 67%, NPV 79%) and IB% > 55% at 24 h age (79% correctly predicted; PPV 72%, NPV 80%). In 35 infants with normal cerebral ultrasound during the first 3 days, outcome was correctly predicted in 82% by IB% (PPV 82%, NPV 83%). CONCLUSION: Long-term outcome can be predicted by aEEG/EEG with 75-80% accuracy already at 24 postnatal hours in VPT infants, also in infants with no early indication of brain injury.

Rapid sequence induction is superior to morphine for intubation of preterm infants: a randomized controlled trial.

OBJECTIVES: To compare rapid sequence intubation (RSI) premedication with morphine for intubation of preterm infants. STUDY DESIGN: Preterm infants needing semi-urgent intubation were enrolled to either RSI (glycopyrrolate, thiopental, suxamethonium, and remifentanil, n = 17) or atropine and morphine (n = 17) in a randomized trial. The main outcome was "good intubation conditions" (score ≤10 assessed with intubation scoring), and secondary outcomes were procedural duration, physiological and biochemical variables, amplitude-integrated electroencephalogram, and pain scores. RESULTS: Infants receiving RSI had superior intubation conditions (16/17 versus 1/17, P < .001), the median (IQR) intubation score was 5 (5-6) compared with 12 (10.0-13.5, P < .001), and a shorter procedure duration of 45 seconds (35-154) compared with 97 seconds (49-365, P = .031). The morphine group had prolonged heart rate decrease (area under the curve, P < .009) and mean arterial blood pressure increase (area under the curve, P < .005 and %change: mean ± SD 21% ± 23% versus -2% ± 22%, P < .007) during the intubation, and a subsequent lower mean arterial blood pressure 3 hours after the intubation compared with baseline (P = .033), concomitant with neurophysiologic depression (P < .001) for 6 hours after. Plasma cortisol and stress/pain scores were similar. CONCLUSION: RSI with the drugs used can be implemented as medication for semi-urgent intubation in preterm infants. Because of circulatory changes and neurophysiological depression found during and after the intubation in infants given morphine, premedication with morphine should be avoided.

Measuring strategic control in artificial grammar learning.

In response to concerns with existing procedures for measuring strategic control over implicit knowledge in artificial grammar learning (AGL), we introduce a more stringent measurement procedure. After two separate training blocks which each consisted of letter strings derived from a different grammar, participants either judged the grammaticality of novel letter strings with respect to only one of these two grammars (pure-block condition), or had the target grammar varying randomly from trial to trial (novel mixed-block condition) which required a higher degree of conscious flexible control. Random variation in the colour and font of letters was introduced to disguise the nature of the rule and reduce explicit learning. Strategic control was observed both in the pure-block and mixed-block conditions, and even among participants who did not realise the rule was based on letter identity. This indicated detailed strategic control in the absence of explicit learning.

Working Under the Gun: A Theoretical Analysis of Stressors Associated With the Re-negotiation of Norms and Control of Work Tasks During COVID-19.

The COVID-19 pandemic has led many of the world's nations to impose numerous preventive and mitigative measures to increase social distance, including various forms of home isolation and quarantine. A central premise for the current paper is that the COVID-19 situation is likely to constitute a massive re-negotiation of social and organizational norms, which may lead to psychological distress at the individual, family and interpersonal level. Virtually overnight, people have to re-define what is expected and deemed appropriate by a given group member in a certain social setting. This goes for all kinds of general social interaction, such as societal, even multinational medical demands on social distancing. Simultaneously it also goes for a sudden, gargantuan re-division of labor in a complex global system. We provide a theoretical analysis of the potential consequences of re-negotiation of norms from the perspective of four sets of psychological theory: Theory of professions; organizational strategic crisis responses; the job-demands-resources model; and theories addressing the interplay between norm violations and psychological distance. From these theories we derive three suggestions that the discussion centers around: (1) The COVID-19 situation leads to a massive re-negotiation of norms related to work, (2) The COVID-19 situation diffuses the demarcation between the various professional arenas and the private sphere, and this diffusion enhances the stress associated with norm conflict, and (3) Norm conflicts are enhanced by digitalization. Our discussion centers on potential stressors associated with the renegotiation of norms, and also includes a few suggestions for practice. For each theoretical suggestion, we give examples of how the suggestion may manifest itself with respect to (a) the work task, (b) the individual's relationship to their leader and/or organization, and (c) interpersonal relationships. We finally point to some theoretical and applied implications.

The use and reporting of neonatal pain scales: a systematic review of randomized trials.

ABSTRACT: The burden of pain in newborn infants has been investigated in numerous studies, but little is known about the appropriateness of the use of pain scales according to the specific type of pain or infant condition. This systematic review aimed to evaluate the reporting of neonatal pain scales in randomized trials. A systematic search up to March 2019 was performed in Embase, PubMed, PsycINFO, CINAHL, Cochrane Library, Scopus, and Luxid. Randomized and quasirandomized trials reporting neonatal pain scales were included. Screening of the studies for inclusion, data extraction, and quality assessment was performed independently by 2 researchers. Of 3718 trials found, 352 with 29,137 infants and 22 published pain scales were included. Most studies (92%) concerned procedural pain, where the most frequently used pain scales were the Premature Infant Pain Profile or Premature Infant Pain Profile-Revised (48%), followed by the Neonatal Infant Pain Scale (23%). Although the Neonatal Infant Pain Scale is validated only for acute pain, it was also the second most used scale for ongoing and postoperative pain (21%). Only in a third of the trials, blinding for those performing the pain assessment was described. In 55 studies (16%), pain scales that were used lacked validation for the specific neonatal population or type of pain. Six validated pain scales were used in 90% of all trials, although not always in the correct population or type of pain. Depending on the type of pain and population of infants included in a study, appropriate scales should be selected. The inappropriate use raises serious concerns about research ethics and use of resources.

Measuring "intuition" in the SRT generation task.

We address some concerns related to the use of post-trial attribution judgments, originally developed for artificial grammar learning (AGL), during the version of the serial reaction time (SRT) task used by Fu, Dienes, and Fu (2010). In particular, intuition attributions, which are central to Fu et al.'s arguments, seem problematic: This attribution is likely to be made when stimuli contain several competing sources of information to which subjective feelings could be attributed. The interpretation of intuition attributions in Fu et al.'s SRT generation task is problematic because the procedure involved a 2-element sequence where items varied only in position. In our view, responses categorised as intuitions might have been a variety of guess response where neither judgement knowledge nor structural knowledge were conscious. The results would then be compatible with previous findings showing that people can control the use of unconscious structural knowledge even when judgement knowledge is unconscious.

Why Metacognition Is Not Always Helpful.

In many situations, actively engaging in metacognition may improve cognitive achievement and subjective well-being. However, the potential disadvantages of metacognitive engagement are only rarely communicated in metacognition research. In this paper, I outline three ways in which metacognition may reduce cognitive achievement and psychological well-being. First, metacognition may sometimes actively interfere with task performance. Second, the costs of engaging in metacognitive strategies may under certain circumstances outweigh its benefits. Third, metacognitive judgments or feelings involving a negative self-evaluation may detract from psychological well-being. The main contribution of this paper is to integrate findings from different research traditions in order to illustrate the three suggested ways in which metacognition may be unhelpful. An implication of this overview is that although metacognition is most often beneficial to cognitive achievement and subjective well-being, one should bear in mind that it may also have the opposite effect. It is important for researchers and practitioners to take this potential downside of metacognition into account. Practitioners might find it useful to consider the following three questions that relate to my aforementioned claims: Is the nature of the task such that metacognition could interfere with performance? Is the cognitive demand required by the metacognitive strategy disproportionally large compared to its potential usefulness to cognitive achievement? Does metacognition lead to an unhelpful comparison of oneself to others? The same considerations should be kept in mind when researchers and practitioners communicate the potential implications of research findings in metacognition research to audiences within and beyond the research community.

Opioids and alpha-2-agonists for analgesia and sedation in newborn infants: protocol of a systematic review.

BACKGROUND: Hospitalized newborn infants may require analgesia and sedation either for the management of procedural pain, during or after surgery, and other painful conditions. The benefits and harms of opioids administered at different doses and routes of administration have been reported in numerous trials and systematic reviews. The use of alpha-2-agonists such as clonidine and dexmedetomidine in newborn infants is more recent, and they might be prescribed to reduce the total amount of opioids which are thought to have more side effects. Moreover, alpha-2-agonists might play an important role in the management of agitation and discomfort. METHODS: We will conduct a systematic review and meta-analysis on the use of opioids, alpha-2-agonists, or the combination of both drugs. We will include randomized controlled trials to assess benefits and harms and observational studies to assess adverse events and pharmacokinetics; preterm and term infants; studies on any opioids or alpha-2-agonists administered for any indication and by any route except spinal, intraosseous, or administration for nerve blocks and wound infusions. The use of opioids or alpha-2-agonists will be compared to no intervention; placebo with normal saline or other non-sedative, non-analgesic drug; control with oral sugar solution or non-pharmacological intervention; same drug of different dose or route; or a different drug (not limiting to opioids and alpha-2-agonists) or combinations of such drugs. The primary outcomes for this review will be all-cause mortality during initial hospitalization and hypotension requiring medical therapy. We will conduct a search in the following databases: The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE, Embase, and CINAHL. Two review authors will independently screen records for inclusion, undertake data abstraction using a data extraction form and assess the risk of bias of all included trials using the Cochrane "Risk of bias" tool. DISCUSSION: This systematic review will summarize and update our knowledge about neonatal analgesia and sedation including pharmacokinetics/pharmacodynamics, and provide a platform for developing evidence-based guidelines that we can immediately apply to our clinical practice. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2020 CRD42020170852.

Thiopental pharmacokinetics in newborn infants: a case report of overdose.

UNLABELLED: Thiopental may be used for sedation before intubation in newborn infants. A boy, born at 33 weeks of gestation (gw); birth weight 2435 g, was prescribed thiopental 3 mg/kg before intubation. He developed temporary hypotension and oxygen desaturation, and remained unconscious for longer than expected with a suppressed electroencephalography for 48 h. Serum thiopental concentration was 82, 59, 42 and 32 micromol/L after 20 min and 6, 24 and 68 h respectively. Serum concentrations from five newborn infants at the same time points after intubation with the same thiopental dose were used as reference values, and indicated a 10-fold overdose in the index case. The cause of the overdose could not be identified. The infant recovered; cerebral magnetic resonance imaging at the age of 42 gw and psychomotor development at 2 years were normal. These results show that thiopental concentrations are variable in neonates and there is a high risk of dosage error as no specific paediatric formulation is available. CONCLUSION: Well-designed procedures and continuous education are required to prevent errors and adverse events during drug delivery to newborn infants. To develop a safe method of administration for thiopental, an extended pharmacokinetic and pharmacodynamic study in neonates is warranted.