Validating Signs and Symptoms From An Actual Mass Casualty Incident to Characterize An Irritant Gas Syndrome Agent (IGSA) Exposure: A First Step in The Development of a Novel IGSA Triage Algorithm.

CONTRIBUTION TO EMERGENCY NURSING PRACTICE: • Chemical exposures daily pose a significant threat to life. Rapid assessment by first responders/emergency nurses is required to reduce death and disability. Currently, no informatics tools for Irritant Gas Syndrome Agents (IGSA) exposures exist to process victims efficiently, continuously monitor for latent signs/symptoms, or make triage recommendations. • This study uses actual patient data from a chemical incident to characterize and validate signs/symptoms of an IGSA Syndrome. Validating signs/symptoms is the first step in developing new emergency department informatics tools with the potential to revolutionize the process by which emergency nurses manage triage victims of chemical incidents. ABSTRACTINTRODUCTION: Chemical exposures can pose a significant threat to life. Rapid assessment by first responders/emergency nurses is required to reduce death and disability. Currently, no informatics tools for irritant gas syndrome agents (IGSA) exposures exist to process victims efficiently, continuously monitor for latent signs/symptoms, or make triage recommendations. This study describes the first step in developing ED informatics tools for chemical incidents: validation of signs/symptoms that characterize an IGSA syndrome. METHODS: Data abstracted from 146 patients treated for chlorine exposure in one emergency department during a 2005 train derailment and 152 patients not exposed to chlorine (a comparison group) were mapped to 93 possible signs/symptoms within 2 tools (WISER and CHEMM-IST) designed to assist emergency responders/emergency nurses with managing hazardous material exposures. Inferential statistics (χ2/Fisher's exact test) and diagnostics tests were used to examine mapped signs/symptoms of persons who were and were not exposed to chlorine. RESULTS: Three clusters of signs/symptoms are statistically associated with an IGSA syndrome (P < .01): respiratory (shortness of breath, wheezing, coughing, and choking); chest discomfort (tightness, pain, and burning), and eye, nose and/or throat (pain, irritation, and burning). The syndrome requires the presence of signs/symptoms from at least 2 of these clusters. The latency period must also be considered for exposed/potentially exposed persons. DISCUSSION: This study uses actual patient data from a chemical incident to characterize and validate signs/symptoms of an IGSA syndrome. Validating signs/symptoms is the first step in developing new ED informatics tools with the potential to revolutionize the process by which emergency nurses manage triage victims of chemical incidents.

Antiemetic medication for prevention and treatment of chemotherapy-induced nausea and vomiting in childhood.

BACKGROUND: Nausea and vomiting remain a problem for children undergoing treatment for malignancies despite new antiemetic therapies. Optimising antiemetic regimens could improve quality of life by reducing nausea, vomiting, and associated clinical problems. This is an update of the original systematic review. OBJECTIVES: To assess the effectiveness and adverse events of pharmacological interventions in controlling anticipatory, acute, and delayed nausea and vomiting in children and young people (aged less than 18 years) about to receive or receiving chemotherapy. SEARCH METHODS: Searches included the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS, PsycINFO, conference proceedings of the American Society of Clinical Oncology, International Society of Paediatric Oncology, Multinational Association of Supportive Care in Cancer, and ISI Science and Technology Proceedings Index from incept to December 16, 2014, and trial registries from their earliest records to December 2014. We examined references of systematic reviews and contacted trialists for information on further studies. We also screened the reference lists of included studies. SELECTION CRITERIA: Two review authors independently screened abstracts in order to identify randomised controlled trials (RCTs) that compared a pharmacological antiemetic, cannabinoid, or benzodiazepine with placebo or any alternative active intervention in children and young people (less than 18 years) with a diagnosis of cancer who were to receive chemotherapy. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted outcome and quality data from each RCT. When appropriate, we undertook meta-analysis. MAIN RESULTS: We included 34 studies that examined a range of different antiemetics, used different doses and comparators, and reported a variety of outcomes. The quality and quantity of included studies limited the exploration of heterogeneity to narrative approaches only.The majority of quantitative data related to the complete control of acute vomiting (27 studies). Adverse events were reported in 29 studies and nausea outcomes in 16 studies.Two studies assessed the addition of dexamethasone to 5-HT3 antagonists for complete control of vomiting (pooled risk ratio (RR) 2.03; 95% confidence interval (CI) 1.35 to 3.04). Three studies compared granisetron 20 mcg/kg with 40 mcg/kg for complete control of vomiting (pooled RR 0.93; 95% CI 0.80 to 1.07). Three studies compared granisetron with ondansetron for complete control of acute nausea (pooled RR 1.05; 95% CI 0.94 to 1.17; 2 studies), acute vomiting (pooled RR 2.26; 95% CI 2.04 to 2.51; 3 studies), delayed nausea (pooled RR 1.13; 95% CI 0.93 to 1.38; 2 studies), and delayed vomiting (pooled RR 1.13; 95% CI 0.98 to 1.29; 2 studies). No other pooled analyses were possible.Narrative synthesis suggests that 5-HT3 antagonists are more effective than older antiemetic agents, even when these agents are combined with a steroid. Cannabinoids are probably effective but produce frequent side effects. AUTHORS' CONCLUSIONS: Our overall knowledge of the most effective antiemetics to prevent chemotherapy-induced nausea and vomiting in childhood is incomplete. Future research should be undertaken in consultation with children, young people, and families that have experienced chemotherapy and should make use of validated, age-appropriate measures. This review suggests that 5-HT3 antagonists are effective in patients who are to receive emetogenic chemotherapy, with granisetron or palonosetron possibly better than ondansetron. Adding dexamethasone improves control of vomiting, although the risk-benefit profile of adjunctive steroid remains uncertain.

A validation study of 5 triage systems using data from the 2005 Graniteville, South Carolina, chlorine spill.

INTRODUCTION: Lack of outcomes-based research results in uncertainty about the effectiveness of any of the current triage systems in determining priority of care during actual chemical disasters. The purpose of this study was to determine whether the level of injury severity extrapolated from 5 triage systems correlated with actual injury severity outcomes of victims exposed to a chlorine disaster. METHODS: Using secondary data analysis, data for 631 victims were merged, de-identified, and analyzed. Using logic models from the triage systems, the actual injury severity was compared with the extrapolated injury severity classifications. RESULTS: Analysis showed weak to modest correlations between the extrapolated injury severity triage outcome classifications and the actual injury severity outcomes (Spearman correlation range 0.38 to 0.71, P < .0001). There was slight to fair agreement between the extrapolated injury severity triage outcome classifications and the actual injury severity outcomes (weighted κ = - 0.23 to 0.42). DISCUSSION: The extrapolated injury severity triage outcome categories from the 5 triage systems did not agree with the actual injury severity categories. Oxygen saturation measured by pulse oximetry provides early indications and is very predictive of outcome severity in incidents involving irritant chemical exposures such as chlorine, and should be a part of a mass casualty protocol for any irritant chemical incident. Additional research is needed to identify the most sensitive clinical measures for triaging victims of toxic inhalation disasters.

The experience of long-term opiate maintenance treatment and reported barriers to recovery: a qualitative systematic review.

BACKGROUND/AIM: To inform understanding of the experience of long-term opiate maintenance and identify barriers to recovery. METHODS: A qualitative systematic review. RESULTS: 14 studies in 17 papers, mainly from the USA (65%), met inclusion criteria, involving 1,088 participants. Studies focused on methadone prescribing. Participants reported stability; however, many disliked methadone. Barriers to full recovery were primarily 'inward focused'. CONCLUSION: This is the first review of qualitative literature on long-term maintenance, finding that universal service improvements could be made to address reported barriers to recovery, including involving ex-users as positive role models, and increasing access to psychological support. Treatment policies combining harm minimisation and abstinence-orientated approaches may best support individualised recovery.

Manipulation of drugs to achieve the required dose is intrinsic to paediatric practice but is not supported by guidelines or evidence.

BACKGROUND: A lack of age-appropriate formulations can make it difficult to administer medicines to children. A manipulation of the dosage form may be required to achieve the required dose. This study aimed to describe medicines that are manipulated to achieve the required dose in paediatric practice. METHOD: A structured, undisguised observational study and postal survey. The observational study investigated drug manipulations occurring in clinical practice across three sites. The questionnaire, administered to a sample of paediatric nurses throughout the UK, surveyed manipulations conducted and nurses' experiences and views. RESULTS: The observational study identified 310 manipulations, of which 62% involved tablets, 21% were intravenous drugs and 10% were sachets. Of the 54 observed manipulations 40 involved tablets with 65% of the tablets being cut and 30% dispersed to obtain a smaller dose. 188 manipulations were reported by questionnaire respondents, of these 46% involved tablets, 12% were intravenous drugs, and 12% were nebuliser solutions. Manipulations were predominantly, but not exclusively, identified in specialist clinical areas with more highly dependent patients. Questionnaire respondents were concerned about the accuracy of the dose achieved following manipulations and the lack of practice guidance. CONCLUSION: Manipulations to achieve the required dose occur throughout paediatric in-patient settings. The impact of manipulations on the efficacy of the drugs, the accuracy of the dose and any adverse effects on patients is not known. There is a need to develop evidence-based guidance for manipulations of medicines in children.

The manipulation of drugs to obtain the required dose: systematic review.

AIM: To describe the development of a systematic review protocol that maps the evidence relating to drug manipulations conducted to obtain the required dose. This process included defining a search strategy and methods to assess the quality and to synthesize the evidence retrieved. BACKGROUND: Economic constraints mean that marketed formulations may not meet the needs of all patients. Consequently, it is sometimes necessary to manipulate marketed products with the aim of obtaining the required dose. Most clinical practice appears to be guided by ad hoc approaches and informal literature reviews. METHODS: This systematic review protocol has been designed to identify the evidence available on drug manipulation. The review aims to identify what evidence is available and where the gaps appear in the current evidence. This report describes the challenges of developing a systematic review in an area that potentially involves many drugs and considers outcomes other than effectiveness. In particular, searches required the use of non-specific terms and the iterative development of a complex search strategy. The development of quality assessment criteria is also described. Funding commenced in April 2009. DISCUSSION: The systematic review described here will capture a broad selection of research about drug manipulations and may also be of interest to those conducting reviews in broad remit subject areas that are not easy to define using accepted terminology.

Audit to monitor the uptake of national mouth care guidelines for children and young people being treated for cancer.

PURPOSE: The aim of this study is to review current oral care practices in children being treated for cancer against audit criteria derived from national guidelines, and to compare findings with data from a baseline survey carried out in 2002 prior to implementation of the national guidelines. METHODS: A telephone survey was carried out of all 21 haematology-oncology (HO) centres and seven bone marrow transplant (BMT) units within the UK Children's Cancer Study Group focusing on key audit themes of: availability of evidence-based guidelines, oral and dental care prior to and during cancer treatment, oral assessment, prevention and treatment of oral complications. RESULTS: The national guidelines were used in 19/25 (76%) settings that employed written guidelines. There was little variation in advice given to patients/parents on basic oral hygiene, and this advice was commensurate with guideline recommendations. Inconsistencies in oral care assessment, reported at baseline, remained commonplace across the majority of settings. In only 10/21 HO centres, it was usual practice for children to undergo dental assessment prior to commencing cancer treatment, indicating no improvement since baseline survey. Few therapies outside of the guideline recommendations were being used. The routine use of preventive nystatin, not recommended in the guideline, had significantly decreased from baseline (by 40%). CONCLUSIONS: Uptake of national guidelines by HO/BMT settings was good however certain oral care practices fell short of the guideline recommendations. Routine dental checks need to be embedded in practice. Further consideration is needed as to how oral assessment might be used more effectively in informing treatment.

Antiemetic medication for prevention and treatment of chemotherapy induced nausea and vomiting in childhood.

BACKGROUND: Nausea and vomiting are still a problem for children undergoing treatment for malignancies despite new antiemetic therapies. Optimising antiemetic regimens could improve quality of life by reducing nausea, vomiting and associated clinical problems. OBJECTIVES: To assess the effectiveness and adverse events of pharmacological interventions in controlling anticipatory, acute and delayed nausea and vomiting in children and young people (aged < 18 years) about to receive/receiving chemotherapy. SEARCH STRATEGY: Searches included CENTRAL, MEDLINE, EMBASE and LILACS, trial registries from their earliest records to February 2008, and ASCO, MASCC and SIOP conference proceedings from 2001 to 2007. We examined references of systematic reviews and contacted trialists for information on further studies. SELECTION CRITERIA: Two authors independently screened abstracts to identify randomised controlled trials (RCTs) that compared a pharmacological antiemetic, cannabinoid or benzodiazepine with placebo or any alternative active intervention in children and young people (< 18 years) with a diagnosis of cancer who were to receive chemotherapy. DATA COLLECTION AND ANALYSIS: Two authors independently extracted outcome and quality data from each RCT. When appropriate, we undertook meta-analysis. MAIN RESULTS: We included 28 studies which examined a range of different antiemetics, used different doses and comparators, and reported a variety of outcomes. The quality and quantity of included studies limited the exploration of heterogeneity to narrative approaches only.The majority of quantitative data related to the complete control of acute vomiting (22 studies). Adverse events were reported in 24 studies and nausea outcomes in 10 studies.The addition of dexamethasone to 5-HT(3) antagonists was assessed in two studies for complete control of vomiting (pooled relative risk (RR) 2.03; 95% CI 1.35 to 3.04). Three studies compared granisetron 20 mcg/kg with 40 mcg/kg for complete control of vomiting (pooled RR 0.93; 95% CI 0.80 to 1.07). No other pooled analyses were possible.Narrative synthesis suggests 5-HT(3) antagonists are more effective than older antiemetic agents even when combined with a steroid. Cannabinoids are probably effective but produce frequent side effects. AUTHORS' CONCLUSIONS: Our overall knowledge of the most effective antiemetics to prevent chemotherapy-induced nausea and vomiting in childhood is incomplete. Future research should be undertaken in consultation with children, young people and families that have experienced chemotherapy and should make use of validated, age-appropriate measures. This review suggests that 5-HT(3) antagonists with dexamethasone added are effective in patients who are to receive highly emetogenic chemotherapy although the risk-benefit profile of additional steroid remains uncertain.

International electronic health record-derived COVID-19 clinical course profiles: the 4CE consortium.

We leveraged the largely untapped resource of electronic health record data to address critical clinical and epidemiological questions about Coronavirus Disease 2019 (COVID-19). To do this, we formed an international consortium (4CE) of 96 hospitals across five countries (www.covidclinical.net). Contributors utilized the Informatics for Integrating Biology and the Bedside (i2b2) or Observational Medical Outcomes Partnership (OMOP) platforms to map to a common data model. The group focused on temporal changes in key laboratory test values. Harmonized data were analyzed locally and converted to a shared aggregate form for rapid analysis and visualization of regional differences and global commonalities. Data covered 27,584 COVID-19 cases with 187,802 laboratory tests. Case counts and laboratory trajectories were concordant with existing literature. Laboratory tests at the time of diagnosis showed hospital-level differences equivalent to country-level variation across the consortium partners. Despite the limitations of decentralized data generation, we established a framework to capture the trajectory of COVID-19 disease in patients and their response to interventions.

Safety and efficacy of 2% chlorhexidine gluconate aqueous versus 2% chlorhexidine gluconate in 70% isopropyl alcohol for skin disinfection prior to percutaneous central venous catheter insertion in preterm neonates: the ARCTIC randomised-controlled feasibility trial protocol.

INTRODUCTION: Catheter-related sepsis is one of the most dangerous complications of neonatal intensive care and is associated with significant morbidity and mortality. Use of catheter-care 'bundles' has reduced the incidence of catheter-related sepsis, although individual components have not been well studied. Better evidence is needed to guide selection of the most appropriate antiseptic solution for skin disinfection in preterm neonates. This study will inform the feasibility and design of the first randomised controlled trial to examine the safety and efficacy of alcohol-based versus aqueous-based chlorhexidine antiseptic formulations for skin disinfection prior to percutaneous central venous catheterisation in preterm neonates. The antiseptics to be compared are 2% chlorhexidine gluconate (CHG) aqueous and 2% CHG in 70% isopropyl alcohol. METHODS AND ANALYSIS: The Antiseptic Randomised Controlled Trial for Insertion of Catheters (ARCTIC) is a two-centre randomised-controlled feasibility trial. At least 100 preterm infants born at <34 weeks' gestation and due to undergo percutaneous insertion of a central venous catheter will be randomly allocated to receive prior skin disinfection with one of the two antiseptic solutions. Outcomes include: i) recruitment and retention rates; ii) completeness of data collection; iii) numbers of enrolled infants meeting case definitions for definite catheter-related sepsis, catheter-associated sepsis and catheter colonisation and iv) safety outcomes of skin morbidity scores recorded daily from catheter insertion until 48 hours post removal. The key feasibility metrics will be reported as proportions with 95% CIs. Estimated prevalence of catheter colonisation will allow calculation of sample size for the large-scale trial. The data will inform whether it will be feasible to progress to a large-scale trial. ETHICS AND DISSEMINATION: ARCTIC has been approved by the National Health Service Health Research Authority National Research Ethics Service Committee East of England (Cambridge South) (IRAS ID 163868), was adopted onto the National Institute of Health Research Clinical Research Network portfolio (CPMS ID 19899) and is registered with an International Standard Randomised Control Trials Number (ISRCTN: 82571474; Pre-results) and European Clinical Trials Database number 2015-000874-36. Dissemination plans include presentations at scientific conferences, scientific publications and sharing of the findings with parents via the support of Bliss baby charity. TRIAL REGISTRATION NUMBER: ISRCTN82571474; Pre-results.

Designing and executing a functional exercise to test a novel informatics tool for mass casualty triage.

OBJECTIVE: The testing of informatics tools designed for use during mass casualty incidents presents a unique problem as there is no readily available population of victims or identical exposure setting. The purpose of this article is to describe the process of designing, planning, and executing a functional exercise to accomplish the research objective of validating an informatics tool specifically designed to identify and triage victims of irritant gas syndrome agents. MATERIALS AND METHODS: During a 3-year time frame, the research team and partners developed the Emergency Department Informatics Computational Tool and planned a functional exercise to test it using medical records data from 298 patients seen in 1 emergency department following a chlorine gas exposure in 2005. RESULTS: The research team learned valuable lessons throughout the planning process that will assist future researchers with developing a functional exercise to test informatics tools. Key considerations for a functional exercise include contributors, venue, and information technology needs (ie, hardware, software, and data collection methods). DISCUSSION: Due to the nature of mass casualty incidents, testing informatics tools and technology for these incidents is challenging. Previous studies have shown a functional exercise as a viable option to test informatics tools developed for use during mass casualty incidents. CONCLUSION: Utilizing a functional exercise to test new mass casualty management technology and informatics tools involves a painstaking and complex planning process; however, it does allow researchers to address issues inherent in studying informatics tools for mas casualty incidents.

Meta-analysis of diagnostic test studies using individual patient data and aggregate data.

A meta-analysis of diagnostic test studies provides evidence-based results regarding the accuracy of a particular test, and usually involves synthesizing aggregate data (AD) from each study, such as the 2 by 2 tables of diagnostic accuracy. A bivariate random-effects meta-analysis (BRMA) can appropriately synthesize these tables, and leads to clinical results, such as the summary sensitivity and specificity across studies. However, translating such results into practice may be limited by between-study heterogeneity and that they relate to some 'average' patient across studies.In this paper we describe how the meta-analysis of individual patient data (IPD) from diagnostic studies can lead to clinical results more tailored to the individual patient. We develop IPD models that extend the BRMA framework to include study-level covariates, which help explain the between-study heterogeneity, and also patient-level covariates, which allow one to assess the effect of patient characteristics on test accuracy. We show how the inclusion of patient-level covariates requires a careful separation of within-study and across-study accuracy-covariate effects, as the latter are particularly prone to confounding. Our models are assessed through simulation and extended to allow IPD studies to be combined with AD studies, as IPD are not always available for all studies. Application is made to 23 studies assessing the accuracy of ear thermometers for diagnosing fever in children, with 16 IPD and 7 AD studies. The models reveal that between-study heterogeneity is partly explained by the use of different measurement devices, but there is no evidence that being an infant modifies diagnostic accuracy.

Data Capture and Analysis of Signs and Symptoms in a Chemically Exposed Population.

This manuscript provides a practical case study to demonstrate data collection from paper-based medical records so that the occurrence of specific signs/symptoms indicative of a chemical exposure can be studied.

Validation of a novel irritant gas syndrome triage algorithm.

OBJECTIVE: Our objective was to validate a novel irritant gas syndrome agent (IGSA) triage algorithm for use in an emergency department (ED). We assessed efficiency, accuracy, and precision of our IGSA triage algorithm based on signs/symptoms of actual patients. DESIGN: After characterizing the signs/symptoms of an actual IGSA exposure event, we developed and validated the IGSA triage algorithm using a simulated computer exercise to compare the IGSA triage algorithm to the preferred hospital triage algorithm, the Emergency Severity Index (ESI). SETTING: This study was a simulated computer exercise using surveys developed in Research Electronic Data Capture software. Nurse volunteers simulated triaging 298 patients. PARTICIPANTS: Patient data included 146 patients treated during the disaster as well as 152 unexposed patients. Twenty-six nurse volunteers were assigned to triage the patients using one of the algorithms in the simulated computer exercise. MAIN OUTCOME MEASURE(S): The precision of the IGSA triage algorithm was 0.82 (confidence interval [CI] 0.78-0.85) and ESI 0.73 (CI 0.69-0.77). Weighted κ for ESI and IGSA accuracy for exposed patients was 0.32 (95% CI 0.26-0.37) and 0.81 (95% CI 0.77-0.85), respectively. RESULTS: The IGSA triage algorithm was more accurate and precise than the ESI algorithm for triaging patients exposed to an irritant gas. CONCLUSIONS: This study validates the IGSA triage algorithm as the basis for the development of a prototype software application to quickly identify victims of a chemical disaster and triage patients efficiently and accurately with the potential to dramatically improve the processing of patients in EDs.

Smoking cessation for substance misusers: A systematic review of qualitative studies on participant and provider beliefs and perceptions.

INTRODUCTION: Smoking prevalence among those in substance misuse treatment remains much higher than the general population, despite evidence for effective cessation interventions that do not negatively impact substance misuse outcomes. This systematic review summarises qualitative data on barriers and facilitators to smoking cessation for people in substance misuse treatment, participants' and providers' perceptions about effects of smoking cessation on substance misuse treatment, timing of intervention delivery and aspects of interventions perceived to be effective. METHODS: Systematic review of qualitative studies and thematic synthesis of published qualitative data. RESULTS: 10939 records and 132 full texts were screened. 22 papers reporting on 21 studies were included. Key themes identified were: strong relationships between smoking and other substance misuse; environmental influences; motivation; mental health; aspects of interventions perceived to be effective/ineffective; barriers and facilitators to intervention implementation; smoking bans/restrictions; and relationships with professionals. Many service users were motivated toward smoking cessation but were not offered support. Some felt interventions should be delivered after substance misuse treatment, whilst others felt concurrent/dual interventions would be beneficial, due to strong associations between smoking and other substances. Treatment providers felt they lacked training and resources for supporting smoking cessation, and were concerned about impact on substance misuse outcomes. CONCLUSIONS: Many substance misusers who also smoke are motivated to quit but perceive a lack of support from professionals. Additional training and resources are required to enable professionals to provide the support needed. More research is required to develop enhanced packages of care for this deprived group of smokers.

Relationship between the Mediterranean dietary pattern and musculoskeletal health in children, adolescents, and adults: systematic review and evidence map.

CONTEXT: An understanding of the modifiable effects of diet on bone and skeletal muscle mass and strength over the life course will help inform strategies to reduce age-related fracture risk. The Mediterranean diet is rich in nutrients that may be important for optimal musculoskeletal health. The aim of this systematic review was to investigate the relationship between a Mediterranean diet and musculoskeletal outcomes (fracture, bone density, osteoporosis, sarcopenia) in any age group. Ten electronic databases were searched. Randomized controlled trials and prospective cohort studies that investigated a traditional Mediterranean diet, published in any language, were eligible. Studies using other designs or other definitions of the Mediterranean diet were collated separately in an evidence map. Details on study design, methods, population, dietary intervention or exposure, length of follow-up, and effect on or association with musculoskeletal outcomes were extracted. The search yielded 1738 references. Data from eligible randomized controlled trials (n = 0) and prospective cohort studies (n = 3) were synthesized narratively by outcome for the systematic review. Two of these studies reported on hip fracture incidence, but results were contradictory. A third study found no association between the Mediterranean diet and sarcopenia incidence. Overall, the systematic review and evidence map demonstrate a lack of research to understand the relationship between the Mediterranean diet and musculoskeletal health in all ages. PROSPERO registration number IDCRD42016037038.

A systematic review of the use of dosage form manipulation to obtain required doses to inform use of manipulation in paediatric practice.

This study sought to determine whether there is an evidence base for drug manipulation to obtain the required dose, a common feature of paediatric clinical practice. A systematic review of the data sources, PubMed, EMBASE, CINAHL, IPA and the Cochrane database of systematic reviews, was used. Studies that considered the dose accuracy of manipulated medicines of any dosage form, evidence of safety or harm, bioavailability, patient experience, tolerability, contamination and comparison of methods of manipulation were included. Case studies and letters were excluded. Fifty studies were eligible for inclusion, 49 of which involved tablets being cut, split, crushed or dispersed. The remaining one study involved the manipulation of suppositories of one drug. No eligible studies concerning manipulation of oral capsules or liquids, rectal enemas, nebuliser solutions, injections or transdermal patches were identified. Twenty four of the tablet studies considered dose accuracy using weight and/or drug content. In studies that considered weight using adapted pharmacopoeial specifications, the percentage of halved tablets meeting these specifications ranged from 30% to 100%. Eighteen studies investigated bioavailability, pharmacokinetics or clinical outcomes following manipulations which included nine delayed or modified release formulations. In each of these nine studies the entirety of the dosage form was administered. Only one of the 18 studies was identified where drugs were manipulated to obtain a proportion of the dosage form, and that proportion administered. The five studies that considered patient perception found that having to manipulate the tablets did not have a negative impact on adherence. Of the 49 studies only two studies reported investigating children. This review yielded limited evidence to support manipulation of medicines for children. The results cannot be extrapolated between dosage forms, methods of manipulation or between different brands of the same drug.

In a systematic review, infrared ear thermometry for fever diagnosis in children finds poor sensitivity.

BACKGROUND AND OBJECTIVES: To investigate sensitivity and specificity of infrared ear thermometry compared to rectal thermometry to detect fever in children. METHODS: Systematic review of studies comparing rectal and infrared ear temperatures in children. RESULTS: Sensitivity and specificity estimates were highly heterogeneous, and displayed an inverse relationship suggestive of a threshold effect, due in part to the different offsets used to obtain adjusted tympanic temperatures depending on the ear thermometer mode. To account for this threshold effect, results from each study were summarized as a diagnostic odds ratio (DOR). These varied extensively across studies, suggesting that heterogeneity between study estimates is not fully explained by the threshold effect. Pooled estimates of sensitivity and specificity from random effects models were 63.7% (95% CI 55.6%, 71.8%) and 95.2% (95% CI 93.5%, 96.9%), respectively. CONCLUSION: Pooled estimates of measures of diagnostic accuracy from these studies suggest that infrared ear thermometry would fail to diagnose fever in three or four out of every 10 febrile children (with fever defined by a rectal temperature of 38 degrees C or above). These findings support our previous concerns about the use of infrared ear thermometers in situations where a failure to detect fever has serious implications.

An efficient approach for surveillance of childhood diabetes by type derived from electronic health record data: the SEARCH for Diabetes in Youth Study.

OBJECTIVE: To develop an efficient surveillance approach for childhood diabetes by type across 2 large US health care systems, using phenotyping algorithms derived from electronic health record (EHR) data. MATERIALS AND METHODS: Presumptive diabetes cases <20 years of age from 2 large independent health care systems were identified as those having ≥1 of the 5 indicators in the past 3.5 years, including elevated HbA1c, elevated blood glucose, diabetes-related billing codes, patient problem list, and outpatient anti-diabetic medications. EHRs of all the presumptive cases were manually reviewed, and true diabetes status and diabetes type were determined. Algorithms for identifying diabetes cases overall and classifying diabetes type were either prespecified or derived from classification and regression tree analysis. Surveillance approach was developed based on the best algorithms identified. RESULTS: We developed a stepwise surveillance approach using billing code-based prespecified algorithms and targeted manual EHR review, which efficiently and accurately ascertained and classified diabetes cases by type, in both health care systems. The sensitivity and positive predictive values in both systems were approximately ≥90% for ascertaining diabetes cases overall and classifying cases with type 1 or type 2 diabetes. About 80% of the cases with "other" type were also correctly classified. This stepwise surveillance approach resulted in a >70% reduction in the number of cases requiring manual validation compared to traditional surveillance methods. CONCLUSION: EHR data may be used to establish an efficient approach for large-scale surveillance for childhood diabetes by type, although some manual effort is still needed.