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1.  Head injury (moderate to severe): reducing cerebral oedema 
BMJ Clinical Evidence  2015;2015:1210.
Introduction
Head injury in young adults is often associated with motor vehicle accidents, violence, and sports injuries. In older adults, it is often associated with falls. Severe head injury can lead to secondary brain damage from cerebral ischaemia resulting from hypotension, hypercapnia, and raised intracranial pressure. Severity of brain injury is assessed using the Glasgow Coma Scale (GCS). While about one quarter of people with severe brain injury (GCS score less than 8) will make a good recovery, about one third will die, and one fifth will have severe disability or be in a vegetative state.
Methods and outcomes
We conducted a systematic overview and aimed to answer the following clinical question: What are the effects of interventions to reduce cerebral oedema in people with moderate to severe head injury as defined by GCS? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2014 (BMJ Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview).
Results
At this update, searching of electronic databases retrieved 306 studies. After deduplication and removal of conference abstracts, 209 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 161 studies and the further review of 48 full publications. Of the 48 full articles evaluated, two systematic reviews and four RCTs were added at this update. We performed a GRADE evaluation for six PICO combinations.
Conclusions
In this systematic overview, we categorised the efficacy for three interventions, based on information relating to the effectiveness and safety of decompressive craniectomy, hypertonic saline compared with mannitol, and hypertonic saline compared with placebo (normal saline).
Key Points
Head injury in young adults is often associated with motor vehicle accidents, violence, and sports injuries. In older adults, it is often associated with falls. This overview covers moderate to severe head injury. Severe head injury can lead to secondary brain damage from cerebral ischaemia resulting from hypotension, hypercapnia, and raised intracranial pressure (ICP).Poor outcome correlates with low post-resuscitation Glasgow Coma Scale (GCS) score, older age, eye pupil abnormalities, hypoxia or hypotension before definitive treatment, traumatic subarachnoid haemorrhage, and inability to control ICP.Severity of brain injury is assessed using the GCS. While about one quarter of people with severe brain injury (GCS score <8) will make a good recovery, about one third will die, and one fifth will have severe disability or be in a vegetative state.
There is no high-quality evidence of benefit from any treatment in reducing cerebral oedema in people with moderate to severe head injury. Despite this, most clinicians implement various combinations of treatments. The evidence is also lacking for treatments aimed at reducing an elevated ICP, a complication of severe head injury and harbinger of a poor prognosis.
Decompressive craniectomy may be beneficial in improving ICP control. However, the evidence for decompressive craniectomy improving patient outcomes is inconclusive.
Hypertonic saline seems no more effective than placebo (normal saline) at reducing mortality or neurological disability in people with moderate to severe head injury and cerebral oedema.
Hypertonic saline and mannitol may be equally effective in people with mild to moderate head injury and cerebral oedema; however, the evidence is limited.
PMCID: PMC4643751
2.  Proceedings of the 14th annual conference of INEBRIA 
Holloway, Aisha S. | Ferguson, Jennifer | Landale, Sarah | Cariola, Laura | Newbury-Birch, Dorothy | Flynn, Amy | Knight, John R. | Sherritt, Lon | Harris, Sion K. | O’Donnell, Amy J. | Kaner, Eileen | Hanratty, Barbara | Loree, Amy M. | Yonkers, Kimberly A. | Ondersma, Steven J. | Gilstead-Hayden, Kate | Martino, Steve | Adam, Angeline | Schwartz, Robert P. | Wu, Li-Tzy | Subramaniam, Geetha | Sharma, Gaurav | McNeely, Jennifer | Berman, Anne H. | Kolaas, Karoline | Petersén, Elisabeth | Bendtsen, Preben | Hedman, Erik | Linderoth, Catharina | Müssener, Ulrika | Sinadinovic, Kristina | Spak, Fredrik | Gremyr, Ida | Thurang, Anna | Mitchell, Ann M. | Finnell, Deborah | Savage, Christine L. | Mahmoud, Khadejah F. | Riordan, Benjamin C. | Conner, Tamlin S. | Flett, Jayde A. M. | Scarf, Damian | McRee, Bonnie | Vendetti, Janice | Gallucci, Karen Steinberg | Robaina, Kate | Clark, Brendan J. | Jones, Jacqueline | Reed, Kathryne D. | Hodapp, Rachel M. | Douglas, Ivor | Burnham, Ellen L. | Aagaard, Laura | Cook, Paul F. | Harris, Brett R. | Yu, Jiang | Wolff, Margaret | Rogers, Meighan | Barbosa, Carolina | Wedehase, Brendan J. | Dunlap, Laura J. | Mitchell, Shannon G. | Dusek, Kristi A. | Gryczynski, Jan | Kirk, Arethusa S. | Oros, Marla T. | Hosler, Colleen | O’Grady, Kevin E. | Brown, Barry S. | Angus, Colin | Sherborne, Sidney | Gillespie, Duncan | Meier, Petra | Brennan, Alan | de Vargas, Divane | Soares, Janaina | Castelblanco, Donna | Doran, Kelly M. | Wittman, Ian | Shelley, Donna | Rotrosen, John | Gelberg, Lillian | Edelman, E. Jennifer | Maisto, Stephen A. | Hansen, Nathan B. | Cutter, Christopher J. | Deng, Yanhong | Dziura, James | Fiellin, Lynn E. | O’Connor, Patrick G. | Bedimo, Roger | Gibert, Cynthia | Marconi, Vincent C. | Rimland, David | Rodriguez-Barradas, Maria C. | Simberkoff, Michael S. | Justice, Amy C. | Bryant, Kendall J. | Fiellin, David A. | Giles, Emma L. | Coulton, Simon | Deluca, Paolo | Drummond, Colin | Howel, Denise | McColl, Elaine | McGovern, Ruth | Scott, Stephanie | Stamp, Elaine | Sumnall, Harry | Vale, Luke | Alabani, Viviana | Atkinson, Amanda | Boniface, Sadie | Frankham, Jo | Gilvarry, Eilish | Hendrie, Nadine | Howe, Nicola | McGeechan, Grant J. | Ramsey, Amy | Stanley, Grant | Clephane, Justine | Gardiner, David | Holmes, John | Martin, Neil | Shevills, Colin | Soutar, Melanie | Chi, Felicia W. | Weisner, Constance | Ross, Thekla B. | Mertens, Jennifer | Sterling, Stacy A. | Shorter, Gillian W. | Heather, Nick | Bray, Jeremy | Cohen, Hildie A. | McPherson, Tracy L. | Adam, Cyrille | López-Pelayo, Hugo | Gual, Antoni | Segura-Garcia, Lidia | Colom, Joan | Ornelas, India J. | Doyle, Suzanne | Donovan, Dennis | Duran, Bonnie | Torres, Vanessa | Gaume, Jacques | Grazioli, Véronique | Fortini, Cristiana | Paroz, Sophie | Bertholet, Nicolas | Daeppen, Jean-Bernard | Satterfield, Jason M. | Gregorich, Steven | Alvarado, Nicholas J. | Muñoz, Ricardo | Kulieva, Gozel | Vijayaraghavan, Maya | Adam, Angéline | Cunningham, John A. | Díaz, Estela | Palacio-Vieira, Jorge | Godinho, Alexandra | Kushir, Vladyslav | O’Brien, Kimberly H. M. | Aguinaldo, Laika D. | Sellers, Christina M. | Spirito, Anthony | Chang, Grace | Blake-Lamb, Tiffany | LaFave, Lea R. Ayers | Thies, Kathleen M. | Pepin, Amy L. | Sprangers, Kara E. | Bradley, Martha | Jorgensen, Shasta | Catano, Nico A. | Murray, Adelaide R. | Schachter, Deborah | Andersen, Ronald M. | Rey, Guillermina Natera | Vahidi, Mani | Rico, Melvin W. | Baumeister, Sebastian E. | Johansson, Magnus | Sinadinovic, Christina | Hermansson, Ulric | Andreasson, Sven | O’Grady, Megan A. | Kapoor, Sandeep | Akkari, Cherine | Bernal, Camila | Pappacena, Kristen | Morley, Jeanne | Auerbach, Mark | Neighbors, Charles J. | Kwon, Nancy | Conigliaro, Joseph | Morgenstern, Jon | Magill, Molly | Apodaca, Timothy R. | Borsari, Brian | Hoadley, Ariel | Scott Tonigan, J. | Moyers, Theresa | Fitzgerald, Niamh M. | Schölin, Lisa | Barticevic, Nicolas | Zuzulich, Soledad | Poblete, Fernando | Norambuena, Pablo | Sacco, Paul | Ting, Laura | Beaulieu, Michele | Wallace, Paul George | Andrews, Matthew | Daley, Kate | Shenker, Don | Gallagher, Louise | Watson, Rod | Weaver, Tim | Bruguera, Pol | Oliveras, Clara | Gavotti, Carolina | Barrio, Pablo | Braddick, Fleur | Miquel, Laia | Suárez, Montse | Bruguera, Carla | Brown, Richard L. | Capell, Julie Whelan | Paul Moberg, D. | Maslowsky, Julie | Saunders, Laura A. | McCormack, Ryan P. | Scheidell, Joy | Gonzalez, Mirelis | Bauroth, Sabrina | Liu, Weiwei | Lindsay, Dawn L. | Lincoln, Piper | Hagle, Holly | Wallhed Finn, Sara | Hammarberg, Anders | Andréasson, Sven | King, Sarah E. | Vargo, Rachael | Kameg, Brayden N. | Acquavita, Shauna P. | Van Loon, Ruth Anne | Smith, Rachel | Brehm, Bonnie J. | Diers, Tiffiny | Kim, Karissa | Barker, Andrea | Jones, Ashley L. | Skinner, Asheley C. | Hinman, Agatha | Svikis, Dace S. | Thacker, Casey L. | Resnicow, Ken | Beatty, Jessica R. | Janisse, James | Puder, Karoline | Bakshi, Ann-Sofie | Milward, Joanna M. | Kimergard, Andreas | Garnett, Claire V. | Crane, David | Brown, Jamie | West, Robert | Michie, Susan | Rosendahl, Ingvar | Andersson, Claes | Gajecki, Mikael | Blankers, Matthijs | Donoghue, Kim | Lynch, Ellen | Maconochie, Ian | Phillips, Ceri | Pockett, Rhys | Phillips, Tom | Patton, R. | Russell, Ian | Strang, John | Stewart, Maureen T. | Quinn, Amity E. | Brolin, Mary | Evans, Brooke | Horgan, Constance M. | Liu, Junqing | McCree, Fern | Kanovsky, Doug | Oberlander, Tyler | Zhang, Huan | Hamlin, Ben | Saunders, Robert | Barton, Mary B. | Scholle, Sarah H. | Santora, Patricia | Bhatt, Chirag | Ahmed, Kazi | Hodgkin, Dominic | Gao, Wenwu | Merrick, Elizabeth L. | Drebing, Charles E. | Larson, Mary Jo | Sharma, Monica | Petry, Nancy M. | Saitz, Richard | Weisner, Constance M. | Young-Wolff, Kelly C. | Lu, Wendy Y. | Blosnich, John R. | Lehavot, Keren | Glass, Joseph E. | Williams, Emily C. | Bensley, Kara M. | Chan, Gary | Dombrowski, Julie | Fortney, John | Rubinsky, Anna D. | Lapham, Gwen T. | Forray, Ariadna | Olmstead, Todd A. | Gilstad-Hayden, Kathryn | Kershaw, Trace | Dillon, Pamela | Weaver, Michael F. | Grekin, Emily R. | Ellis, Jennifer D. | McGoron, Lucy | McGoron, Lucy
doi:10.1186/s13722-017-0087-8
PMCID: PMC5606215
3.  Review of commonly used age‐based weight estimates for paediatric drug dosing in relation to the pharmacokinetic properties of resuscitation drugs 
AIM:
To study which weight estimate calculation used in paediatric resuscitation results in optimal drug dosing; Advanced Paediatric and Life Support (APLS) or the UK Resuscitation Council age‐based formula.
Method
Commonly used drugs used in paediatric resuscitation were selected and a literature search conducted for each drug's pharmacokinetic properties, concentrating on the volume of distribution (Vd).
Hydrophobic drugs have a higher Vd than hydrophilic drugs as they distribute preferentially to fat mass (FM). The larger the Vd, the higher the initial dose required to achieve therapeutic plasma concentrations.
Actual body weight (ABW) estimates are a good indicator of Vd for hydrophobic drugs as they correlate well with FM. Ideal body weight (IBW) estimates may be a better indicator of Vd for hydrophilic drugs, as they correlate better with lean body mass. This highlights potential variation between ABW and IBW, which may result in toxic or sub‐therapeutic dosing.
Results
The new APLS formulae give higher estimates of expected weight for a wider age range. This may be a more accurate reflection of ABW due to increasing prevalence of obesity in children. The UK Resuscitation Council's formula appears to result in a lower estimate of weight, which may relate more closely to IBW.
Conclusion
The main drugs used in paediatric resuscitation are hydrophilic, thus the APLS formulae may result in too much being given. Therefore the UK Resuscitation Council's single formula may be preferred. In addition, a single formula may minimize error in the context of a child of unknown weight requiring administration of emergency resuscitation drugs.
doi:10.1111/bcp.12876
PMCID: PMC4834587  PMID: 26714256
paediatric; pharmacokinetic; resuscitation; volume of distribution; weight
4.  Prioritising the care of critically ill children: a pilot study using SCREEN reduces clinic waiting times 
BMJ Global Health  2016;1(1):e000036.
Objective
In low-resource settings, childhood mortality secondary to delays in triage and treatment remains high. This paper seeks to evaluate the impact of the novel Sick Children Require Emergency Evaluation Now (SCREEN) tool on the waiting times of critically ill children who present for care to primary healthcare clinics in Cape Town, South Africa.
Methods
We used a pre/postevaluation study design to calculate the median waiting times of all children who presented to four randomly chosen clinics for 5 days before, and 5 days after, the implementation of SCREEN.
Findings
The SCREEN programme resulted in statistical and clinically significant reductions in waiting times for children with critical illness to see a professional nurse (2 hours 45 min to 1 hour 12 min; p<0.001). There was also a statistically significant reduction in the proportion of children who left without being seen by a professional nurse (25.8% to 18.48%; p<0.001).
Conclusions
SCREEN is a novel programme that uses readily available laypersons, trained to make a subjective assessment of children arriving at primary healthcare centres, and provides a low cost, simple methodology to prioritise children and reduce waiting times in low-resource healthcare clinics.
doi:10.1136/bmjgh-2016-000036
PMCID: PMC5321329
5.  Pathways to Care for Critically Ill or Injured Children: A Cohort Study from First Presentation to Healthcare Services through to Admission to Intensive Care or Death 
PLoS ONE  2016;11(1):e0145473.
Purpose
Critically ill or injured children require prompt identification, rapid referral and quality emergency management. We undertook a study to evaluate the care pathway of critically ill or injured children to identify preventable failures in the care provided.
Methods
A year-long cohort study of critically ill and injured children was performed in Cape Town, South Africa, from first presentation to healthcare services until paediatric intensive care unit (PICU) admission or emergency department death, using expert panel review of medical records and caregiver interview. Main outcomes were expert assessment of overall quality of care; avoidability of severity of illness and PICU admission or death and the identification of modifiable factors.
Results
The study enrolled 282 children, 252 emergency PICU admissions, and 30 deaths. Global quality of care was graded good in 10% of cases, with half having at least one major impact modifiable factor. Key modifiable factors related to access to care and identification of the critically ill, assessment of severity, inadequate resuscitation, and delays in decision making and referral. Children were transferred with median time from first presentation to PICU admission of 12.3 hours. There was potentially avoidable severity of illness in 185 (74%) of children, and death prior to PICU admission was avoidable in 17/30 (56.7%) of children.
Conclusions
The study presents a novel methodology, examining quality of care across an entire system, and highlighting the complexity of the pathway and the modifiable events amenable to interventions, that could reduce mortality and morbidity, and optimize utilization of scarce critical care resources; as well as demonstrating the importance of continuity and quality of care.
doi:10.1371/journal.pone.0145473
PMCID: PMC4712128  PMID: 26731245
6.  Systematic Review and Meta-Analysis of Outcomes after Cardiopulmonary Arrest in Childhood 
PLoS ONE  2015;10(6):e0130327.
Background
Cardiopulmonary arrest in children is an uncommon event, and often fatal. Resuscitation is often attempted, but at what point, and under what circumstances do continued attempts to re-establish circulation become futile? The uncertainty around these questions can lead to unintended distress to the family and to the resuscitation team.
Objectives
To define the likely outcomes of cardiopulmonary resuscitation in children, within different patient groups, related to clinical features.
Data Sources
MEDLINE, MEDLINE in-Process & Other non-Indexed Citations, EMBASE, Cochrane database of systematic reviews and Cochrane central register of trials, Database of Abstracts of Reviews of Effects (DARE), the Health Technology Assessment database, along with reference lists of relevant systematic reviews and included articles.
Study Eligibility Criteria
Prospective cohort studies which derive or validate a clinical prediction model of outcome following cardiopulmonary arrest.
Participants and Interventions
Children or young people (aged 0 – 18 years) who had cardiopulmonary arrest and received an attempt at resuscitation, excluding resuscitation at birth.
Study Appraisal and Synthesis Methods
Risk of bias assessment developed the Hayden system for non-randomised studies and QUADAS2 for decision rules. Synthesis undertaken by narrative, and random effects meta-analysis with the DerSimonian-Laird estimator.
Results
More than 18,000 episodes in 16 data sets were reported. Meta-analysis was possible for survival and one neurological outcome; others were reported too inconsistently. In-hospital patients (average survival 37.2% (95% CI 23.7 to 53.0%)) have a better chance of survival following cardiopulmonary arrest than out-of-hospital arrests (5.8% (95% CI 3.9% to 8.6%)). Better neurological outcome was also seen, but data were too scarce for meta-analysis (17% to 71% ‘good’ outcomes, compared with 2.8% to 3.2%).
Limitation
Lack of consistent outcome reporting and short-term neurological outcome measures limited the strength of conclusions that can be drawn from this review.
Conclusions and Implications of Key Findings
There is a need to collaboratively, prospectively, collect potentially predictive data on these rare events to understand more clearly the predictors of survival and long-term neurological outcome.
Systematic Review Registration Number
PROSPERO 2013:CRD42013005102
doi:10.1371/journal.pone.0130327
PMCID: PMC4479568  PMID: 26107958
7.  A novel multipatient intranasal diamorphine spray for use in acute pain in children: pharmacovigilance data from an observational study 
Emergency Medicine Journal : EMJ  2014;32(4):269-273.
Objectives
To establish the safety of an intranasal diamorphine (IND) spray in children.
Design
An open-label, single-dose pharmacovigilance trial.
Setting
Emergency departments in eight UK hospitals.
Participants
Children aged 2–16 years with a fracture or other trauma.
Outcome measures
Adverse events (AE) specifically related to nasal irritation, respiratory and central nervous system depression.
Results
226 patients received 0.1 mg/kg IND. No serious or severe AEs occurred. The incidence of treatment-emergent AEs (TEAEs) was 26.5% (95% CI 20.9% to 32.8%), 93% being mild. 89% were related to treatment, all being known effects of the drug or route of administration except for three events in two patients. 20.4% (95% CI 15.3% to 26.2%) patients reported nasal irritation, all mild except one moderate and one ‘unknown’ severity. No respiratory depression was reported. Three AEs related to reduced Glasgow Coma Score (GCS) occurred, all mild.
Conclusions
There were no safety concerns raised during the conduct of the study. In addition to expected side effects, IND can cause mild nasal irritation in a proportion of patients.
European Union Drug Regulating Authorities Clinical Trial No
2009-014982-16.
doi:10.1136/emermed-2013-203226
PMCID: PMC4392188  PMID: 24406329
8.  Linked randomised controlled trials of face-to-face and electronic brief intervention methods to prevent alcohol related harm in young people aged 14–17 years presenting to Emergency Departments (SIPS junior) 
BMC Public Health  2015;15:345.
Background
Alcohol is a major global threat to public health. Although the main burden of chronic alcohol-related disease is in adults, its foundations often lie in adolescence. Alcohol consumption and related harm increase steeply from the age of 12 until 20 years. Several trials focusing upon young people have reported significant positive effects of brief interventions on a range of alcohol consumption outcomes. A recent review of reviews also suggests that electronic brief interventions (eBIs) using internet and smartphone technologies may markedly reduce alcohol consumption compared with minimal or no intervention controls.
Interventions that target non-drinking youth are known to delay the onset of drinking behaviours. Web based alcohol interventions for adolescents also demonstrate significantly greater reductions in consumption and harm among ‘high-risk’ drinkers; however changes in risk status at follow-up for non-drinkers or low-risk drinkers have not been assessed in controlled trials of brief alcohol interventions.
Design and methods
The study design comprises two linked randomised controlled trials to evaluate the effectiveness and cost-effectiveness of two intervention strategies compared with screening alone. One trial will focus on high-risk adolescent drinkers attending Emergency Departments (Eds) and the other will focus on those identified as low-risk drinkers or abstinent from alcohol but attending the same ED.
Our primary (null) hypothesis is similar for both trials: Personalised Feedback and Brief Advice (PFBA) and Personalised Feedback plus electronic Brief Intervention (eBI) are no more effective than screening alone in alcohol consumed at 12 months after randomisation as measured by the Time-Line Follow-Back 28-day version. Our secondary (null) hypothesis relating to economics states that PFBA and eBI are no more cost-effective than screening alone.
In total 1,500 participants will be recruited into the trials, 750 high-risk drinkers and 750 low-risk drinkers or abstainers. Participants will be randomised with equal probability, stratified by centre, to either a screening only control group or one of the two interventions: single session of PFBA or eBI. All participants will be eligible to receive treatment as usual in addition to any trial intervention. Individual participants will be followed up at 6 and 12 months after randomisation.
Discussion
The protocol represents an ambitious innovative programme of work addressing alcohol use in the adolescent population.
Trial registration
ISRCTN45300218. Registered 5th July 2014.
doi:10.1186/s12889-015-1679-4
PMCID: PMC4394590  PMID: 25886178
Adolescents; SBI; eBI; Emergency Department
9.  Improving the Manchester Triage System for Pediatric Emergency Care: An International Multicenter Study 
PLoS ONE  2014;9(1):e83267.
Objectives
This multicenter study examines the performance of the Manchester Triage System (MTS) after changing discriminators, and with the addition use of abnormal vital sign in patients presenting to pediatric emergency departments (EDs).
Design
International multicenter study
Settings
EDs of two hospitals in The Netherlands (2006–2009), one in Portugal (November–December 2010), and one in UK (June–November 2010).
Patients
Children (<16years) triaged with the MTS who presented at the ED.
Methods
Changes to discriminators (MTS 1) and the value of including abnormal vital signs (MTS 2) were studied to test if this would decrease the number of incorrect assignment. Admission to hospital using the new MTS was compared with those in the original MTS. Likelihood ratios, diagnostic odds ratios (DORs), and c-statistics were calculated as measures for performance and compared with the original MTS. To calculate likelihood ratios and DORs, the MTS had to be dichotomized in low urgent and high urgent.
Results
60,375 patients were included, of whom 13% were admitted. When MTS 1 was used, admission to hospital increased from 25% to 29% for MTS ‘very urgent’ patients and remained similar in lower MTS urgency levels. The diagnostic odds ratio improved from 4.8 (95%CI 4.5–5.1) to 6.2 (95%CI 5.9–6.6) and the c-statistic remained 0.74. MTS 2 did not improve the performance of the MTS.
Conclusions
MTS 1 performed slightly better than the original MTS. The use of vital signs (MTS 2) did not improve the MTS performance.
doi:10.1371/journal.pone.0083267
PMCID: PMC3893080  PMID: 24454699
10.  Normal ranges of heart rate and respiratory rate in children from birth to 18 years: a systematic review of observational studies 
Lancet  2011;377(9770):1011-1018.
Summary
Background
Although heart rate and respiratory rate are routinely measured in children in acute settings, current reference ranges are not evidence-based. The aim of this study is to derive new centile charts for heart rate and respiratory rate using systematic review data from existing studies, and to compare these with existing international ranges.
Methods
We searched MEDLINE, EMBASE, and CINAHL to April 2009, and reference lists to identify studies which had measured heart rate and/or respiratory rate in normal children between birth and 18 years of age. We used a non-parametric kernel regression method to create centile charts for heart rate and respiratory rate with respect to age. We compared existing reference ranges with those derived from the centile charts.
Findings
We included 69 studies, 59 of which provided data on the heart rate of 143,346 children, and 20 on the respiratory rate of 3,881 children. Our new centile charts demonstrate the decline in respiratory rate from birth to early adolescence, with the steepest decline apparent in infants under two years; decreasing from a median of 44 breaths/minutes at birth to 26 breaths/minute at the age of two. The heart rate centile chart demonstrates a small peak at one month of age. The median heart rate increases from 127 beats/minute at birth to a maximum of 145 beats/minute at approximately one month of age, before decreasing to 113 beats/minute by the age of two. Comparison of the centile charts with existing published reference ranges for heart rate and respiratory rate show marked disagreement with the centile charts, with limits from published ranges frequently exceeding the 99th and 1st centiles, or crossing the median.
Interpretation
Our review shows that existing international guidelines for heart rate and respiratory rate in children are not based on evidence. We have created new centile charts based on a systematic review of studies which have measured these vital signs in normal children. Clinical and resuscitation guidelines should be updated in the light of these evidence-based reference ranges.
Funding
Research funded by the National Institute for Health Research programme grant for applied research ‘Development and implementation of new diagnostic processes and technologies in primary care’. SF was funded by the Engineering and Physical Sciences Research Council and the National Institute for Health Research Biomedical Research Centre Programme.
doi:10.1016/S0140-6736(10)62226-X
PMCID: PMC3789232  PMID: 21411136
children; heart rate; respiratory rate; normal; centiles; ranges
11.  Head injury (moderate to severe) 
BMJ Clinical Evidence  2010;2010:1210.
Introduction
Head injury in young adults is often associated with motor vehicle accidents, violence, and sports injuries. In older adults it is often associated with falls. Severe head injury can lead to secondary brain damage from cerebral ischaemia resulting from hypotension, hypercapnia, and raised intracranial pressure. Severity of brain injury is assessed using the Glasgow Coma Scale (GCS). While about one quarter of people with severe brain injury (GCS score less than 8) will make a good recovery, about one third will die, and one fifth will have severe disability or be in a vegetative state.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of interventions to reduce complications of moderate to severe head injury as defined by Glasgow Coma Scale? We searched: Medline, Embase, The Cochrane Library, and other important databases up to November 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 17 systematic reviews, RCTs, or observational studies that met our inclusion criteria.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics, anticonvulsants, corticosteroids, hyperventilation, hypothermia, and mannitol.
Key Points
Head injury in young adults is often associated with motor vehicle accidents, violence, and sports injuries. In older adults it is often associated with falls. This review covers only moderate to severe head injury. Severe head injury can lead to secondary brain damage from cerebral ischaemia resulting from hypotension, hypercapnia, and raised intracranial pressure.Poor outcome correlates with low post-resuscitation Glasgow Coma Scale (GCS) score, older age, eye pupil abnormalities, hypoxia or hypotension before definitive treatment, traumatic subarachnoid haemorrhage, and inability to control intracranial pressure.Severity of brain injury is assessed using the GCS. While about one quarter of people with severe brain injury (GCS score less than 8) will make a good recovery, about one third will die, and one fifth will have severe disability or be in a vegetative state.
There is no strong evidence of benefit from any treatment in reducing the complications of moderate to severe head injury. Despite this, most clinicians implement various combinations of treatments discussed here.
Hyperventilation and mannitol are frequently used to lower intracranial pressure. Anticonvulsants, barbiturates, antibiotics, and hypothermia are less commonly implemented. Evidence on hyperventilation, mild hypothermia, and mannitol has been inconclusive. Carbamazepine and phenytoin may reduce early seizures in people with head injury, but they have not been shown to reduce late seizures, neurological disability, or death.Barbiturates have not been shown to be effective in reducing intracranial pressure or in preventing adverse neurological outcomes after head injury.Prophylactic antibiotics have not been shown to reduce the risk of death or meningitis in people with skull fracture.
CAUTION: Corticosteroids have been shown to increase mortality when used acutely in people with head injury. One large RCT (the CRASH trial) found that death from all causes and severe disability at 6 months were more likely in people with head injury given methylprednisolone infusion than in those given placebo. Corticosteroids are no longer used in the treatment of head injuries.
PMCID: PMC3217652  PMID: 21418686
13.  Teaching children basic life support skills 
BMJ : British Medical Journal  2007;334(7605):1174.
Can improve outcomes but implementation needs to be earlier and more widespread
doi:10.1136/bmj.39218.422650.80
PMCID: PMC1889961  PMID: 17556433
15.  Head injury (moderate to severe) 
BMJ Clinical Evidence  2007;2007:1210.
Introduction
Head injury in young adults is often associated with motor vehicle accidents, violence, and sports injuries. In older adults it is often associated with falls. Severe head injury can lead to secondary brain damage from cerebral ischaemia resulting from hypotension, hypercapnia, and raised intracranial pressure. Severity of brain injury is assessed using the GCS. While about a quarter of people with severe brain injury (GCS score less than 8) will make a good recovery, about a third will die, and a fifth will have severe disability or be in a vegetative state.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of interventions to reduce complications of moderate to severe head injury as defined by Glasgow Coma Scale? We searched: Medline, Embase, The Cochrane Library and other important databases up to April 2007 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 17 systematic reviews, RCTs, or observational studies that met our inclusion criteria.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics, anticonvulsants, corticosteroids, hyperventilation, hypothermia, and mannitol.
Key Points
Head injury in young adults is often associated with motor vehicle accidents, violence, and sports injuries. In older adults it is often associated with falls. This review covers moderate to severe head injury only. Severe head injury can lead to secondary brain damage from cerebral ischaemia resulting from hypotension, hypercapnia, and raised intracranial pressure.Poor outcome correlates with low post-resuscitation Glasgow Coma Scale (GCS) score, older age, eye pupil abnormalities, hypoxia or hypotension before definitive treatment, traumatic subarachnoid haemorrhage, and inability to control intracranial pressure.Severity of brain injury is assessed using the GCS. While about a quarter of people with severe brain injury (GCS score less than 8) will make a good recovery, about a third will die, and a fifth will have severe disability or be in a vegetative state.
There is no strong evidence of benefit from any treatment in reducing the complications of moderate to severe head injury. Despite this, most clinicians implement various combinations of treatments discussed here.
Hyperventilation and mannitol are frequently used to lower intracranial pressure. Anticonvulsants, barbiturates, antibiotics, and hypothermia are less commonly implemented. Evidence on hyperventilation, mild hypothermia, and mannitol has been inconclusive. Carbamazepine and phenytoin may reduce early seizures in people with head injury, but have not been shown to reduce late seizures, neurological disability, or death.Barbiturates have not been shown to be effective in reducing intracranial pressure or in preventing adverse neurological outcomes after head injury.Prophylactic antibiotics have not been shown to reduce the risks of death or meningitis in people with skull fracture.
CAUTION: Corticosteroids have been shown to increase mortality when used acutely in people with head injury. One large RCT (the CRASH trial) found that death from all causes and severe disability at 6 months were more likely in people with head injury given methylprednisolone infusion than in those given placebo. Corticosteroids are no longer used in the treatment of head injuries.
PMCID: PMC2943769  PMID: 19450357
18.  The role of healthcare delivery in the outcome of meningococcal disease in children: case-control study of fatal and non-fatal cases 
BMJ : British Medical Journal  2005;330(7506):1475.
Objective To determine whether suboptimal management in hospital could contribute to poor outcome in children admitted with meningococcal disease.
Design Case-control study of childhood deaths from meningococcal disease, comparing hospital care in fatal and non-fatal cases.
Setting National statistics and hospital records.
Subjects All children under 17 years who died from meningococcal disease (cases) matched by age with three survivors (controls) from the same region of the country.
Main outcome measures Predefined criteria defined optimal management. A panel of paediatricians blinded to the outcome assessed case records using a standardised form and scored patients for suboptimal management.
Results We identified 143 cases and 355 controls. Departures from optimal (per protocol) management occurred more frequently in the fatal cases than in the survivors. Multivariate analysis identified three factors independently associated with an increased risk of death: failure to be looked after by a paediatrician, failure of sufficient supervision of junior staff, and failure of staff to administer adequate inotropes. Failure to recognise complications of the disease was a significant risk factor for death, although not independently of absence of paediatric care (P = 0.002). The odds ratio for death was 8.7 (95% confidence interval 2.3 to 33) with two failures, increasing with multiple failures.
Conclusions Suboptimal healthcare delivery significantly reduces the likelihood of survival in children with meningococcal disease. Improved training of medical and nursing staff, adherence to published protocols, and increased supervision by consultants may improve the outcome for these children and also those with other life threatening illnesses.
PMCID: PMC558454  PMID: 15976421

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