Developments in the Design, Conduct, and Reporting of Child Health Trials.

To identify priority areas to improve the design, conduct, and reporting of pediatric clinical trials, the international expert network, Standards for Research (StaR) in Child Health, was assembled and published the first 6 Standards in Pediatrics in 2012. After a recent review summarizing the 247 publications by StaR Child Health authors that highlight research practices that add value and reduce research "waste," the current review assesses the progress in key child health trial methods areas: consent and recruitment, containing risk of bias, roles of data monitoring committees, appropriate sample size calculations, outcome selection and measurement, and age groups for pediatric trials. Although meaningful change has occurred within the child health research ecosystem, measurable progress is still disappointingly slow. In this context, we identify and review emerging trends that will advance the agenda of increased clinical usefulness of pediatric trials, including patient and public engagement, Bayesian statistical approaches, adaptive designs, and platform trials. We explore how implementation science approaches could be applied to effect measurable improvements in the design, conducted, and reporting of child health research.

Practice variation in urine collection methods among pre-toilet trained children with suspected urinary tract infection: a systematic review.

BACKGROUND: Urinary tract infections (UTIs) are a common cause of acute illness among infants and young children. There are numerous methods for collecting urine in children who are not toilet trained. This review examined practice variation in the urine collection methods for diagnosing UTI in non-toilet-trained children. METHODS: A systematic review was completed by searching MEDLINE (Ovid), Embase (Ovid), CENTRAL (Ovid), PsycInfo (Ovid), CINAHL (EBSCO), and JBI (Ovid) from January 1, 2000 until October 9, 2021 and updated on May 24, 2023. Studies were included if they were conducted in an acute care facility, examined pre-toilet trained children, and compared one urine collection method with another for relevant health care outcomes (such as length of stay in an ED, or re-visits or readmissions to the ED) or provider satisfaction. Two independent reviewers screened the identified articles independently, and those included in the final analysis were assessed for quality and bias using the Newcastle-Ottawa Scale. RESULTS: Overall, 2535 articles were reviewed and 8 studies with a total of 728 children were included in the final analysis. Seven studies investigated the primary outcome of interest, practice variation in urine collection methods to diagnose a UTI. The seven studies that investigated novel methods of urine collection concluded that there were improved health care outcomes compared to conventional methods. Novel methods include emerging methods that are not captured yet captured in clinical practice guidelines including the use of ultrasound guidance to aid existing techniques. Three studies which investigated healthcare provider satisfaction found preference to novel methods of urine collection. CONCLUSIONS: There is significant practice variation in the urine collection methods within and between countries. Further research is needed to better examine practice variation among clinicians and adherence to national organizations and societies guidelines. PROSPERO registration number CRD42021267754.

Assessment of Usefulness of Randomized Control Trials in Child Health Research Published in 2007 and 2017.

OBJECTIVE: To examine how clinical usefulness in pediatric research with randomized controlled trials (RCTs) has changed over a 10-year period via a research usefulness tool composed of unique clinical usefulness criteria. STUDY DESIGN: We leveraged a pre-existing sample of child health RCTs published in 2007, used by our team in a previous study. Using the same methods, a research librarian executed a literature search in the Cochrane Central Register of Controlled Trials for the 2017 cohort. We included the first 300 eligible citations from the randomly ordered list for each year, creating two cohorts of 300 publications each, 1 in 2007 and 1 in 2017. Each publication was analyzed and data regarding primary and secondary outcomes, as well as 11 unique criteria of clinical usefulness, were extracted. Each publication was then graded using a tool created by our research team. After quality review, statistical analysis was then performed. RESULTS: Six hundred pediatric RCT publications were included in this review. The mean score increased from 6.07 in 2007 to 9.20 in 2017 (P < .001). Usefulness factors that saw the largest increase in reporting were context placement, funding statements, and conflict of interest statements, while patient centeredness, value for money, and raw data availability remained infrequently reported. CONCLUSION: Our results demonstrate that clinical usefulness of pediatric research improved over this 10-year period, but there are still areas that need a great deal of improvement in order to maximize clinical usefulness and reduce research waste.

Readiness of emergency departments for pediatric patients and pediatric mortality: a systematic review.

BACKGROUND: Most children who need emergency care visit general emergency departments and urgent care centres; the weighted pediatric readiness score (WPRS) is currently used to evaluate emergency departments' readiness for pediatric patients. The aim of this study was to determine whether a higher WPRS was associated with decreased mortality and improved health care outcomes and utilization. METHODS: We conducted a systematic review of cohort and cross-sectional studies on emergency departments that care for children (age ≤ 21 yr). We searched MEDLINE (Ovid), Embase (Ovid), the Cochrane Library (Wiley), CINAHL (EBSCO), Global Health (Ovid) and Scopus from inception until July 29, 2022. Articles identified were screened for inclusion by 2 independent reviewers. The primary outcome was mortality, and the secondary outcomes were health care outcomes and utilization. We used the Newcastle-Ottawa Scale to assess for quality and bias of the included studies. The I 2 statistic was calculated to quantify study heterogeneity. RESULTS: We identified 1789 articles. Eight articles were included in the final analysis. Three studies showed an inverse association between highest WPRS quartile and pediatric mortality (pooled odds ratio [OR] 0.45, 95% confidence interval [CI] 0.26 to 0.78; I 2 = 89%, low certainty of evidence) in random-effects meta-analysis. Likewise, 1 study not included in the meta-analysis also reported an inverse association with a 1-point increase in WPRS (OR 0.93, 95% CI 0.88 to 0.98). One study reported that the highest WPRS quartile was associated with shorter length of stay in hospital (ß -0.36 days, 95% CI -0.61 to -0.10). Three studies concluded that the highest WPRS quartile was associated with fewer interfacility transfers. The certainty of evidence is low for mortality and moderate for the studied health care outcomes and utilization. INTERPRETATION: The data suggest a potential inverse association between the WPRS of emergency departments and mortality risk in children. More studies are needed to refute or confirm these findings. PROTOCOL REGISTRATION: PROSPERO-CRD42020191149.

Nebulised hypertonic saline solution for acute bronchiolitis in infants.

BACKGROUND: Airway oedema (swelling) and mucus plugging are the principal pathological features in infants with acute viral bronchiolitis. Nebulised hypertonic saline solution (≥ 3%) may reduce these pathological changes and decrease airway obstruction. This is an update of a review first published in 2008, and updated in 2010, 2013, and 2017. OBJECTIVES: To assess the effects of nebulised hypertonic (≥ 3%) saline solution in infants with acute bronchiolitis. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE Daily, Embase, CINAHL, LILACS, and Web of Science on 13 January 2022. We also searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov on 13 January 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs using nebulised hypertonic saline alone or in conjunction with bronchodilators as an active intervention and nebulised 0.9% saline or standard treatment as a comparator in children under 24 months with acute bronchiolitis. The primary outcome for inpatient trials was length of hospital stay, and the primary outcome for outpatients or emergency department (ED) trials was rate of hospitalisation. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, data extraction, and assessment of risk of bias in included studies. We conducted random-effects model meta-analyses using Review Manager 5. We used mean difference (MD), risk ratio (RR), and their 95% confidence intervals (CI) as effect size metrics. MAIN RESULTS: We included six new trials (N = 1010) in this update, bringing the total number of included trials to 34, involving 5205 infants with acute bronchiolitis, of whom 2727 infants received hypertonic saline. Eleven trials await classification due to insufficient data for eligibility assessment. All included trials were randomised, parallel-group, controlled trials, of which 30 were double-blinded. Twelve trials were conducted in Asia, five in North America, one in South America, seven in Europe, and nine in Mediterranean and Middle East regions. The concentration of hypertonic saline was defined as 3% in all but six trials, in which 5% to 7% saline was used. Nine trials had no funding, and five trials were funded by sources from government or academic agencies. The remaining 20 trials did not provide funding sources. Hospitalised infants treated with nebulised hypertonic saline may have a shorter mean length of hospital stay compared to those treated with nebulised normal (0.9%) saline or standard care (mean difference (MD) -0.40 days, 95% confidence interval (CI) -0.69 to -0.11; 21 trials, 2479 infants; low-certainty evidence). Infants who received hypertonic saline may also have lower postinhalation clinical scores than infants who received normal saline in the first three days of treatment (day 1: MD -0.64, 95% CI -1.08 to -0.21; 10 trials (1 outpatient, 1 ED, 8 inpatient trials), 893 infants; day 2: MD -1.07, 95% CI -1.60 to -0.53; 10 trials (1 outpatient, 1 ED, 8 inpatient trials), 907 infants; day 3: MD -0.89, 95% CI -1.44 to -0.34; 10 trials (1 outpatient, 9 inpatient trials), 785 infants; low-certainty evidence). Nebulised hypertonic saline may reduce the risk of hospitalisation by 13% compared with nebulised normal saline amongst infants who were outpatients and those treated in the ED (risk ratio (RR) 0.87, 95% CI 0.78 to 0.97; 8 trials, 1760 infants; low-certainty evidence). However, hypertonic saline may not reduce the risk of readmission to hospital up to 28 days after discharge (RR 0.83, 95% CI 0.55 to 1.25; 6 trials, 1084 infants; low-certainty evidence). We are uncertain whether infants who received hypertonic saline have a lower number of days to resolution of wheezing compared to those who received normal saline (MD -1.16 days, 95% CI -1.43 to -0.89; 2 trials, 205 infants; very low-certainty evidence), cough (MD -0.87 days, 95% CI -1.31 to -0.44; 3 trials, 363 infants; very low-certainty evidence), and pulmonary moist crackles (MD -1.30 days, 95% CI -2.28 to -0.32; 2 trials, 205 infants; very low-certainty evidence). Twenty-seven trials presented safety data: 14 trials (1624 infants; 767 treated with hypertonic saline, of which 735 (96%) co-administered with bronchodilators) did not report any adverse events, and 13 trials (2792 infants; 1479 treated with hypertonic saline, of which 416 (28%) co-administered with bronchodilators and 1063 (72%) hypertonic saline alone) reported at least one adverse event such as worsening cough, agitation, bronchospasm, bradycardia, desaturation, vomiting and diarrhoea, most of which were mild and resolved spontaneously (low-certainty evidence). AUTHORS' CONCLUSIONS: Nebulised hypertonic saline may modestly reduce length of stay amongst infants hospitalised with acute bronchiolitis and may slightly improve clinical severity score. Treatment with nebulised hypertonic saline may also reduce the risk of hospitalisation amongst outpatients and ED patients. Nebulised hypertonic saline seems to be a safe treatment in infants with bronchiolitis with only minor and spontaneously resolved adverse events, especially when administered in conjunction with a bronchodilator. The certainty of the evidence was low to very low for all outcomes, mainly due to inconsistency and risk of bias.

Glucocorticoids for croup in children.

BACKGROUND: Glucocorticoids are the mainstay for the treatment of croup. The existing evidence demonstrates that glucocorticoids are effective in the treatment of croup in children. However, updating the evidence on their clinical relevance in croup is imperative. This is an update to a review first published in 1999, and updated in 2004, 2011, and 2018. OBJECTIVES: To investigate the effects and safety of glucocorticoids in the treatment of croup in children aged 18 years and below. SEARCH METHODS: We searched the Cochrane Library, which includes the Cochrane Central Register of Controlled Trials (CENTRAL; 2022 Issue 9), Ovid MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Ovid MEDLINE (1946 to 4 March 2022), Embase (Ovid) (1974 to 4 March 2022). We also searched the WHO ICTRP and ClinicalTrials.gov on 4 March 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in children (aged 18 years and below) with croup. We assessed the effect of glucocorticoids compared to the following: placebo, any other pharmacologic agents, any other glucocorticoids, any combination of other glucocorticoids, given by different modes of administration, or given in different doses. The included studies must have assessed at least one of our primary outcomes (defined as the change in croup score or return visits, (re)admissions to the hospital or both) or secondary outcomes (defined as the length of stay in hospital or emergency departments, patient improvement, use of additional treatments, or adverse events). DATA COLLECTION AND ANALYSIS: Review authors independently extracted data, with another review author verified. We entered the data into Review Manager 5 for meta-analysis. Two review authors independently assessed studies for risk of bias using the Cochrane risk of bias tool. Two review authors assessed the certainty of the evidence for the primary outcomes using the GRADE approach. MAIN RESULTS: This updated review includes 45 RCTs with a total of 5888 children, an increase of two RCTs with 1323 children since the last update. We also identified one ongoing study and one study awaiting classification. We assessed most studies (98%) as at high or unclear risk of bias.  Any glucocorticoid compared to placebo  Compared to placebo, glucocorticoids may result in greater reductions in croup score after two hours (standardised mean difference (SMD) -0.65, 95% confidence interval (CI) -1.13 to -0.18; 7 RCTs, 426 children; low-certainty evidence); six hours (SMD -0.76, 95% CI -1.12 to -0.40; 11 RCTs, 959 children; low-certainty evidence); and 12 hours (SMD -1.03, 95% CI -1.53 to -0.53; 8 RCTs, 571 children; low-certainty evidence). The evidence for change in croup score after 24 hours is very uncertain (SMD -0.86, 95% CI -1.40 to -0.31; 8 RCTs, 351 children; very low-certainty evidence).  One glucocorticoid compared to another glucocorticoid There was little to no difference between prednisolone and dexamethasone for reduction in croup score at two-hour post-baseline score (SMD 0.06, 95% CI -0.06 to 0.18; 1 RCT, 1231 children; high-certainty evidence). There was likely little to no difference between prednisolone and dexamethasone for reduction in croup score at six-hour post-baseline score (SMD 0.21, 95% CI -0.21 to 0.62; 1 RCT, 99 children; moderate-certainty evidence). However, dexamethasone probably reduced the return visits or (re)admissions for croup by almost half (risk ratio (RR) 0.55, 95% CI 0.28 to 1.11; 4 RCTs, 1537 children; moderate-certainty evidence), and showed a 28% reduction in the use of supplemental glucocorticoids as an additional treatment (RR 0.72, 95% CI 0.53 to 0.97; 2 RCTs, 926 children).  Dexamethasone given in different doses Compared to 0.15 mg/kg, 0.60 mg/kg dexamethasone probably reduced the severity of croup as assessed by the croup scoring scale at 24-hour postbaseline score (SMD 0.63, 95% CI 0.16 to 1.10; 1 RCT, 72 children; moderate-certainty evidence); however, this was not the case at two hours (SMD -0.27, 95% CI -0.76 to 0.22; 2 RCTs, 861 children; high-certainty evidence). There was probably no reduction at six hours (SMD -0.45, 95% CI -1.26 to 0.35; 3 RCTs, 178 children; moderate-certainty evidence), and the evidence at 12 hours is very uncertain (SMD -0.60, 95% CI -4.39 to 3.19; 2 RCTs, 113 children; very low-certainty evidence). There was little to no difference between doses of dexamethasone in return visits or (re)admissions of children or both (RR 0.91, 95% CI 0.71 to 1.17; 3 RCTs, 949 children; high-certainty evidence) or length of stay in the hospital or emergency department (mean difference 0.12, 95% CI -0.32 to 0.56; 2 RCTs, 892 children). The need for additional treatments, such as epinephrine (RR 0.78, 95% CI 0.34 to 1.75; 2 RCTs, 885 children); intubation (risk difference 0.00, 95% CI -0.00 to 0.00; 2 RCTs, 861 children); or use of supplemental glucocorticoids (RR 0.77, 95% CI 0.51 to 1.15; 2 RCTs, 617 children), also did not differ between doses of dexamethasone.  There were moderate to high levels of heterogeneity in the analyses for most comparisons. Adverse events were observed for some of the comparisons reported in the review. AUTHORS' CONCLUSIONS: The evidence that glucocorticoids reduce symptoms of croup at two hours, shorten hospital stays, and reduce the rate of return visits or (re)admissions has not changed in this update. A smaller dose of 0.15 mg/kg of dexamethasone may be as effective as the standard dose of 0.60 mg/kg. More RCTs are needed to strengthen the evidence for effectiveness of low-dose dexamethasone at 0.15 mg/kg to treat croup.

Evaluation of baseline pediatric readiness of emergency departments in Manitoba, Canada.

BACKGROUND: Data on the readiness of the general emergency departments (EDs) in Canada to care for children requiring emergency care are limited. Recent evidence suggests an inverse association between pediatric readiness of the general ED and mortality. OBJECTIVES: To assess the baseline pediatric readiness of the general EDs in the province of Manitoba, Canada, to care for acutely ill and injured children. METHODS: This was a cross-sectional survey study conducted between 2019 and 2020. We used a validated pediatric readiness research checklist to obtain information on the six domains of the general EDs in Manitoba in the fiscal year 2019. A general ED that managed acutely ill patients (0-17th birthday), except for psychiatric cases (up to the 18th birthday), was defined as eligible. We performed a descriptive analysis using the weighted pediatric readiness score (WPRS) based on a 100-point scale. The factors associated with the total WPRS were examined in linear regression models. RESULTS: Of the 42 eligible general EDs, 34 centers participated with a participation rate of 81%. However, only 27 general EDs plus one specialized children ED (28, 67%) completed the survey. The overall median WPRS (/100) attained by the general EDs was 52.34 (interquartile range [IQR] = 10.44). The only specialized children ED in Manitoba achieved a score of 89.75. Over half (15, 55.6%) of the general EDs scored 50 or more. The mean volume of the general ED that participated was 4010.9 (± SD 2137.2) pediatric general ED visits/year. The average scores attained in the domains such as coordination of patient care, general ED staffing and training, and quality improvement were low across the five Regional Health Authorities. The general ED volume was directly associated with the total WPRS, regression coefficient, ß = 0.24 (95% CI 0.04-0.44). Neither the capacity of the general ED to receive pediatric patients from a nursing station, ß = - 0.07 (95% CI - 0.28-0.14), nor the capacity to admit pediatric patients that visited the general ED, ß = - 0.03 (- 0.23-0.17) was associated with the total WPRS. CONCLUSIONS: The pediatric readiness of the general EDs across Manitoba is comparable to other Canadian region, yet some domains need to be improved.

Serum ferritin and incident cardiometabolic diseases in Scottish adults.

BACKGROUND: Iron stores, estimated as ferritin levels, and type 2 diabetes (T2D) have been associated previously, while findings regarding coronary heart disease (CHD) and cerebrovascular disease (CEVD) are still inconclusive. No study has focused on simultaneous evaluation of associations between iron stores and the above cardiometabolic diseases (CMD) in the same population. We aim to evaluate the association between serum ferritin and risk of T2D, CHD and CEVD in Scottish population over a wide range of ferritin levels. METHODS: Longitudinal study in 6,497 participants of the 1995 and 1998 Scottish health surveys, who were followed-up until 2011. Cox regression models were conducted adjusting for age, sex/menopausal status, fibrinogen, GGT levels, smoking, alcohol consumption, total cholesterol, HDL-cholesterol, blood pressure, and BMI. Ferritin was used as continuous (sex/menopausal status-specific Z score) and categorical variable (sex/menopausal status-specific quartiles, quintiles and sextiles). RESULTS: During follow-up, 4.9% of the participants developed T2D, 5.3% CHD, and 2.3% CEVD. By using ferritin quartiles, serum ferritin was positively associated with T2D, CHD and CEVD but only the association with T2D remained after adjustment for covariates [Quartile 4 v. 1: adjusted HR 95% CI 1.59 (1.10-2.34); P = 0.006]. When ferritin sextiles were used (6 v. 1), the ferritin-CEVD association became slightly stronger and significant [adjusted HR 95% CI 2.08 (1.09-3.94); P = 0.024]. CONCLUSIONS: Iron stores relate differently to each CMD. Serum ferritin levels were positively and independently associated with incident T2D, and with incident CEVD if higher cut-off points for high ferritin levels were considered.

Implementation strategies in emergency management of children: A scoping review.

BACKGROUND: Implementation strategies are vital for the uptake of evidence to improve health, healthcare delivery, and decision-making. Medical or mental emergencies may be life-threatening, especially in children, due to their unique physiological needs when presenting in the emergency departments (EDs). Thus, practice change in EDs attending to children requires evidence-informed considerations regarding the best approaches to implementing research evidence. We aimed to identify and map the characteristics of implementation strategies used in the emergency management of children. METHODS: We conducted a scoping review using Arksey and O'Malley's framework. We searched four databases [Medline (Ovid), Embase (Ovid), Cochrane Central (Wiley) and CINAHL (Ebsco)] from inception to May 2019, for implementation studies in children (≤21 years) in emergency settings. Two pairs of reviewers independently selected studies for inclusion and extracted the data. We performed a descriptive analysis of the included studies. RESULTS: We included 87 studies from a total of 9,607 retrieved citations. Most of the studies were before and after study design (n = 68, 61%) conducted in North America (n = 63, 70%); less than one-tenth of the included studies (n = 7, 8%) were randomized controlled trials (RCTs). About one-third of the included studies used a single strategy to improve the uptake of research evidence. Dissemination strategies were more commonly utilized (n = 77, 89%) compared to other implementation strategies; process (n = 47, 54%), integration (n = 49, 56%), and capacity building and scale-up strategies (n = 13, 15%). Studies that adopted capacity building and scale-up as part of the strategies were most effective (100%) compared to dissemination (90%), process (88%) and integration (85%). CONCLUSIONS: Studies on implementation strategies in emergency management of children have mostly been non-randomized studies. This review suggests that 'dissemination' is the most common strategy used, and 'capacity building and scale-up' are the most effective strategies. Higher-quality evidence from randomized-controlled trials is needed to accurately assess the effectiveness of implementation strategies in emergency management of children.

P value and Bayesian analysis in randomized-controlled trials in child health research published over 10 years, 2007 to 2017: a methodological review protocol.

BACKGROUND: There is an unresolved debate about the reliability of the interpretation of P value. Some investigators have suggested that an alternative Bayesian method is preferred in conducting health research. As randomized-controlled trials (RCTs) are important in generating research evidence, we decided to investigate the extent, if any, the inferential statistical framework in published RCTs in child health research have changed over 10 years. We aim to examine the change in P value and Bayesian analysis in RCTs in child health research papers published from 2007 to 2017. METHODS: We will search the Cochrane Central Register of Controlled Trials (Wiley) to identify relevant citations. We will leverage a pre-existing sample of child health RCTs published in 2007 (n=300) used in our previous study of reporting quality of pediatric RCTs. Using the same strategy and study selection methods, we will identify a comparable random sample of child health RCTs published in 2017 (n=300). Eligible studies will include RCTs in health research among individuals aged 21 years and below. One reviewer will select studies for inclusion and extract the data and another reviewer will verify these. Disagreements will be resolved by a discussion between reviewers or by involving another reviewer. We will perform a descriptive analysis of 2007 and 2017 samples and analyze the results using both the frequentist and Bayesian methods. We will present specific characteristics of the clinical trials from 2007 and 2017 in tabular and graphical forms. We will report the difference in the proportion of P value and Bayesian analysis between 2007 and 2017 to assess the 10-year change. Clustering around P values of significance, if observed, will be reported. DISCUSSION: This review will present the difference in the proportion of trials that reported on P value and Bayesian analysis between 2007 and 2017 to assess the 10-year change. The implications for future clinical research will be discussed and this research work will be published in a peer-reviewed journal. This review has the potential to help inform the need for a change in the methodological approach from the null hypothesis significance test to Bayesian methods. SYSTEMATIC REVIEW REGISTRATION: Open Science Framework https://osf.io/aj2df.

Implementation strategies in emergency management of children: a scoping review protocol.

BACKGROUND: Behavior change is not simple, and the introduction of guidelines or protocols does not mean that they will be followed. As such, implementation strategies are vital for the uptake and sustainability of changes in medical protocols. Medical or mental emergencies may be life-threatening, especially in children due to their unique physiological needs. In emergency departments (EDs), where timely decisions are often made, practice change requires thoughtful considerations regarding the best approaches to implementation. As there are many studies reporting on a wide variety of implementation strategies in the emergency management of children in EDs, we aim to identify and map the characteristics of these studies. METHODS: We will conduct a scoping review to identify various implementation strategies in the emergency management of children using the Arksey and O'Malley framework. We will search MEDLINE (Ovid), Embase (Ovid), Cochrane Central (Wiley), and CINAHL (Ebsco), from inception to May 29, 2019, for implementation studies among the pediatric population (≤ 21 years) in a pediatric emergency setting. Two pairs of reviewers will independently select studies for inclusion and extract the data. We will perform a descriptive, narrative analysis of the characteristics of the identified implementation strategies. DISCUSSION: We will present specific characteristics and outcome measures of all included studies in a tabular form. The results of this review are expected to help identify and characterize successful implementation strategies in the emergency management of children in EDs. SYSTEMATIC REVIEW REGISTRATION: Open Science Framework https://osf.io/h6jv2.

Determinants of hospitalizations for pneumonia among Finnish drug users.

OBJECTIVE: The study examined the determinants of being hospitalized for pneumonia in a large cohort of drug users. METHODS: Information of 4817 clients seeking treatment for illicit drug use was linked with the Finnish hospital discharge register to identify those who were hospitalized with main/primary diagnoses of pneumonia during 1997-2013. Cox regression models were used to examine the association between age, gender, homelessness, and route of drug administration of the primary drug at initial clinical consultation and pneumonia hospitalization. Findings were presented as adjusted hazard ratios and 95% confidence intervals. RESULTS: There were 354 persons diagnosed with pneumonia, with a total of 522 hospitalizations at the end of 2013. The univariate Cox models revealed that being over 44 years of age, male gender, homelessness, and intravenous drug use at initial clinical consultation increased the risk of being hospitalized for pneumonia. In the fully adjusted multivariate model, being over 44 years was the strongest factor independently associated with pneumonia hospitalization (adjusted hazard ratio: 2.67, 95% confidence interval: 1.56-4.57, p < 0.001), followed by homelessness (adjusted hazard ratio: 1.75, 95% confidence interval: 1.38-2.22, p < 0.001) and intravenous drug use (adjusted hazard ratio: 1.27, 95% confidence interval: 1.01-1.59, p = 0.041). Of the 354 clients hospitalized for pneumonia, 31.9% (n = 113) were rehospitalized within 30 days of being discharged. One-third of the reasons for the 30-day rehospitalization were pneumonia-related. CONCLUSION: Vaccination, measures addressing housing instability, safe injecting and good hygienic practices, and treating underlying drug use problems could help to reduce morbidity for pneumonia in this cohort.

Diabetes hospitalizations and deaths in a cohort of treatment-seeking illicit drug users.

BACKGROUND: Studies on diabetes among illicit drug users are scarce in Finland. This study aimed to describe hospitalization and death due to diabetes among treatment-seeking illicit drug users. METHODS: Information of 4817 treatment-seeking drug users (3365 men and 1452 women) aged 11-65 years (mean 24.5 years) was linked to the Finnish national hospital discharge register and the national death registry to identify those clients who were hospitalized or died from diabetes mellitus during 1997-2013. RESULTS: Fifty-three persons (42 men and 11 women) had primary diagnoses of diabetes, with a total of 146 hospitalizations (121 among men and 25 among women). The total length of stay among men (1183 days) far exceeded those of women (138 days). Overall, type 1 diabetes was the main contributor to hospitalizations (67%, n = 98/146). The proportion of Type 1 diabetes with complications was 31% in men (n = 37/121) and 44% in women (n = 11/25). All cases of deaths due to diabetes (n = 7) occurred in men. CONCLUSION: Diabetes hospitalizations were mainly due to Type 1 diabetes. Longer length of hospital stay was observed in men, and all diabetes deaths occurred among men. Male drug users and drug users in general would require more support to reduce morbidity and mortality due to diabetes.

Serum adiponectin/Ferritin ratio in relation to the risk of type 2 diabetes and insulin sensitivity.

AIMS: Body iron inhibits the metabolism of adiponectin, an insulin sensitizing adipokine. We investigated the relationships of baseline and average of 4-year change in values of serum adiponectin (sA), serum ferritin (sF) and sA/sF ratio on type 2 diabetes (T2D) risk and insulin sensitivity (Matsuda ISI) and secretion (disposition index; DI30). METHODS: Prospective analyses were conducted in participants with impaired glucose tolerance of the Finnish Diabetes Prevention Study (n = 516) recruited in 1993-1998. Cox and linear regression analyses were used to investigate the associations of sA, sF and sA/sF ratio, as continuous variables, with incident T2D, Matsuda ISI, and DI30. RESULTS: During the mean follow-up of 8.2 years, 157 incident T2D cases occurred (intervention group, n = 65 and control group, n = 92). In adjusted models, baseline sA and sA/sF ratio were inversely associated with T2D risk (HR = 0.49, 95% CI 0.31-0.76, P = 0.002 and HR = 0.83, 95% CI 0.70-0.99, P = 0.044, respectively). Furthermore, a direct association was observed with Matsuda ISI (ß=0.13, 95% CI 0.03-0.22, P = 0.009, for sA and ß=0.04, 95% CI 0.01-0.07, P = 0.035, for sA/sF ratio) during the average 4-year follow-up. The changes in sA and sA/sF ratio were also inversely associated with T2D risk (HR = 0.36, 95% CI 0.20-0.63, P < 0.001 and HR = 0.76, 95% CI 0.62-0.92, P = 0.006, respectively), and directly with Matsuda ISI (ß=0.27, 95% CI 0.17-0.38, P < 0.001, for sA and ß=0.07, 95% CI 0.03-0.11, P < 0.001, for sA/sF ratio). No consistent associations were found with DI30. CONCLUSIONS: Baseline levels and changes during the follow-up in sA and sA/sF ratio are related to T2D risk and insulin sensitivity.

Association between route of illicit drug administration and hospitalizations for infective endocarditis.

OBJECTIVE: This study examined the association between the route of drug administration and being hospitalized for infective endocarditis among 4817 treatment-seeking illicit drug users in Finland. METHODS: Cox regression models were used to examine the association between the route of drug administration and infective endocarditis hospitalization, adjusted for age, gender, and homelessness. Cases of infective endocarditis as a primary/main diagnosis were tracked using the 10th version of the International Classification of Disease code I33. RESULTS: In all, 47 persons had a primary diagnosis of infective endocarditis. These 47 persons contributed a total of 95 hospitalizations and their total length of hospital stay was 1393 days. There was a statistically significant difference in hospitalizations between injectors and non-injectors (Log-Rank test p = 0.018). Univariate Cox model showed that injectors had higher hazard or risk for infective endocarditis hospitalization compared to non-injectors (hazard ratio: 2.04, 95% confidence interval: 1.12-3.73, p = 0.020). After adjusting for age, gender, and homelessness in the multivariate model, the elevated hazard among injectors compared to non-injectors remained statistically significant with adjusted hazard ratio of 2.12 (95% confidence interval: 1.11-4.07, p = 0.024). CONCLUSION: The study findings suggested a need to boost harm reduction measures targeting high-risk injecting and other health behaviors among injecting drug users in order to reduce their hospitalizations for infective endocarditis.

Midwives perceptions of partner presence in childbirth pain alleviation in Nigeria hospitals.

OBJECTIVE: partner presence in the labour room can influence childbirth pain outcomes and maternal well-being. We examined midwives' perception of the use of partner presence in the management of childbirth pain in Nigerian hospitals. DESIGN: a descriptive cross-sectional quantitative study. SETTING: maternity units of four hospitals in Abuja, Nigeria, Jun.-Dec., 2014. PARTICIPANTS: 100 midwives selected through convenience sampling. MEASUREMENTS: data collected using the Abuja Instrument for Midwives (AIM) questionnaire underwent frequency, correlation, and content analysis. FINDINGS: most midwives felt partner presence contributed to pain relief and were willing to allow partner presence as an intervention for childbirth pain. However, only every fourth midwife reported using partner presence as a pain management intervention. KEY CONCLUSION: partner presence is perceived as contributing to pain relief and is a non-pharmacological technique reported to be utilised by midwives for pain management during childbirth. However, Nigeria suffers from poor utilisation of partner presence as a pain management intervention during childbirth. IMPLICATION FOR PRACTICE: information from this study can improve midwifery practice and aid further research regarding midwives' attitudes, knowledge and usage of partner presence in pain management during childbirth.

Gender difference in type 2 diabetes and the role of body iron stores.

Background Studies of gender difference in type 2 diabetes have been inconclusive. We investigated gender difference in type 2 diabetes and the contribution of body iron, as assessed by serum ferritin to this difference. Methods We performed cross-sectional ( n = 1707) and prospective ( n = 1506) analyses in males and females aged 53-73 years in 1998-2001. Type 2 diabetes diagnosis was determined by questionnaire, blood glucose measurements and record linkage to type 2 diabetes registers. Gender difference in type 2 diabetes and serum ferritin contribution to the difference was examined in multivariable logistic and Cox regression models. Gender difference in fasting plasma glucose and insulin and homeostasis model assessment of insulin resistance was examined in linear regression analysis. Results In the cross-sectional analysis, a total of 201 type 2 diabetes cases were observed (males = 111 [55.2%] vs. female = 90 [44.8%], P = 0.032), and in adjusted models, males had higher odds of type 2 diabetes (OR = 1.61, 95% CI 1.10 to 2.34); higher fasting plasma glucose (ß = 0.28, 95% CI 0.15 to 0.41), fasting plasma insulin (ß = 0.73, 95% CI 0.26 to 1.19) and homeostasis model assessment of insulin resistance (ß = 0.11, 95% CI 0.04 to 0.17). In the prospective analysis, males had increased risk of type 2 diabetes (HR = 1.46, 95% CI 1.03 to 2.07). With serum ferritin introduction (100 µg/L, log-transformed) into the models, the type 2 diabetes prevalence (OR = 1.35, 95% CI 0.91 to 1.99) and incidence (HR = 1.38, 95% CI 0.96 to 1.97) were appreciably attenuated. Conclusions These data suggest a gender difference in type 2 diabetes, with a higher prevalence and increased type 2 diabetes risk in males. Body iron explains about two-fifths and one-fifth of the gender difference in type 2 diabetes prevalence and incidence, respectively.

Serum hepcidin concentrations and type 2 diabetes.

Hepcidin is a peptide hormone with both paracrine and endocrine functions that help in maintaining body iron stores. Type 2 diabetes (T2D) is one of the sequelae of excess body iron stores; thus, iron regulatory hormone hepcidin may have a direct or at least an indirect role in the aetiopathogenesis of T2D. Both human and animal studies at molecular and genetic levels have attempted to establish a role for hepcidin in the development of T2D, and a few epidemiologic studies have also showed a link between hepcidin and T2D at population level, but the findings are still inconclusive. Recent data have suggested different pathways in which hepcidin could be associated with T2D with much emphasis on its primary or secondary role in insulin resistance. Some of the suggested pathways are via transcription modulator of hepcidin (STAT3); ferroportin 1 expression on the cells involved in iron transport; transmembrane protease 6 enzyme; and pro-inflammatory cytokines, interleukin (IL)-1, IL-6, tumor necrosis factor-α and IL-10. This review briefly reports the existing evidence on the possible links between hepcidin and T2D and concludes that more data are needed to confirm or refute hepcidin's role in the development of T2D. Examining this role could provide a further evidence base for iron in the aetiopathogenesis of T2D.

Serum ferritin and glucose homeostasis: change in the association by glycaemic state.

BACKGROUND: Data on the association between body iron and glucose homeostasis by the three glycaemic states are scarce. Thus, we investigated the association between body iron as assessed by a serum ferritin concentration and glucose homeostasis using homeostasis model assessment (HOMA) of insulin resistance (HOMA-IR) and beta cell function (HOMA-BcF) in different glycaemic states. METHODS: A cross-sectional analysis was conducted in 2541 men aged 42-60 years in 1984-1989 in the Kuopio Ischemic Heart Disease Risk Factor Study. Subjects were classified into the three glycaemic states, normoglycaemia, prediabetes and type 2 diabetes (T2D), by fasting plasma glucose measurements and the information collected at study visit. The association between serum ferritin quartiles and HOMA-IR and HOMA-BcF for each glycaemic state was examined by analysis of covariance and linear regression analysis. RESULTS: The mean age and serum ferritin concentrations were 53.1 years (standard deviation = 5.7, range = 42.0-61.3 years) and 166.2 µg/L (standard deviation = 141.7, range = 11-960 µg/L), respectively. After multivariable adjustments, a weak and direct association was observed between serum ferritin quartiles and HOMA-IR in normoglycaemia (P-trend = 0.001) but a direct association in prediabetes (P-trend = 0.007) and in T2D (P-trend = 0.078). In HOMA-BcF, the association was weak and direct in normoglycaemia (P-trend = 0.003), direct in prediabetes (P-trend = 0.005) and inverse in T2D (P-trend = 0.105). Strongest associations were observed in prediabetes (ß = 0.25, 95% confidence interval = 0.14-0.36 and P = 0.004 in HOMA-IR; ß = 0.23, 95% confidence interval = 0.15-0.31 and P = 0.008 in HOMA-BcF) after a 100-µg/L increase in serum ferritin (log-transformed). CONCLUSIONS: These data suggest that both the strength and the direction of the association between body iron stores and glucose homeostasis are dependent on the glycaemic state of the population.