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1.  In-service training for health professionals to improve care of seriously ill newborns and children in low-income countries 
Background
A variety of in-service emergency care training courses are currently being promoted as a strategy to improve the quality of care provided to seriously ill newborns and children in low-income countries. Most courses have been developed in high-income countries. However, whether these courses improve the ability of health professionals to provide appropriate care in low-income countries remains unclear. This is the first update of the original review.
Objectives
To assess the effects of in-service emergency care training on health professionals' treatment of seriously ill newborns and children in low-income countries.
Search methods
For this update, we searched the Cochrane Database of Systematic Reviews, part of The Cochrane Library (http://www.cochranelibrary.com); MEDLINE, Ovid SP; EMBASE, Ovid SP; the Cochrane Central Register of Controlled Trials (CENTRAL), part of The Cochrane Library (http://www.cochranelibrary.com) (including the Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register); Science Citation Index and Social Sciences Citation Index, Institute for Scientific Information (ISI) Web of Knowledge/Science and eight other databases. We performed database searches in February 2015. We also searched clinical trial registries, websites of relevant organisations and reference lists of related reviews. We applied no date, language or publication status restrictions when conducting the searches.
Selection criteria
Randomised trials, non-randomised trials, controlled before and after studies and interrupted-time-series studies that compared the effects of in-service emergency care training versus usual care were eligible for inclusion. We included only hospital-based studies and excluded community-based studies. Two review authors independently screened and selected studies for inclusion.
Data collection and analysis
Two review authors independently extracted data and assessed study risk of bias and confidence in effect estimates (certainty of evidence) for each outcome using GRADE (Grades of Recommendation, Assessment, Development and Evaluation). We described results and presented them in GRADE tables.
Main results
We identified no new studies in this update. Two randomised trials (which were included in the original review) met the review eligibility criteria. In the first trial, newborn resuscitation training compared with usual care improved provider performance of appropriate resuscitation (trained 66% vs usual care 27%, risk ratio 2.45, 95% confidence interval (CI) 1.75 to 3.42; moderate certainty evidence) and reduced inappropriate resuscitation (trained mean 0.53 vs usual care 0.92, mean difference 0.40, 95% CI 0.13 to 0.66; moderate certainty evidence). Effect on neonatal mortality was inconclusive (trained 28% vs usual care 25%, risk ratio 0.77, 95% CI 0.40 to 1.48; N = 27 deaths; low certainty evidence). Findings from the second trial suggest that essential newborn care training compared with usual care probably slightly improves delivery room newborn care practices (assessment of breathing, preparedness for resuscitation) (moderate certainty evidence).
Authors' conclusions
In-service neonatal emergency care courses probably improve health professionals' treatment of seriously ill babies in the short term. Further multi-centre randomised trials evaluating the effects of in-service emergency care training on long-term outcomes (health professional practice and patient outcomes) are needed.
PLAIN LANGUAGE SUMMARY
In-service training for health professionals to improve care of seriously ill newborns and children in low-income countries
What question was the review asking?
This is the first update of the original Cochrane review, whose objective was to find out whether additional emergency care training programmes can improve the ability of health workers in poor countries to care for seriously ill newborns and children admitted to hospitals. Researchers at The Cochrane Collaboration searched for all studies that could answer this question and found two relevant studies.
What are the key messages?
The review authors suggest that giving health professionals in poor countries additional training in emergency care probably improves their ability to care for seriously ill newborns. We need additional high-quality studies, including studies in which health professionals are trained to care for seriously ill older children.
Background: training health professionals to care for seriously ill babies and children
In poor countries, many babies and children with serious illnesses die even though they have been cared for in hospitals. One reason for this may be that health workers in these countries often are not properly trained to offer the care that these children need.
In poor countries, children often become seriously ill because of conditions such as pneumonia, meningitis and diarrhoea, and may need emergency care. For newborn babies, the most common reason for emergency care is too little oxygen to the baby during birth. If this goes on for too long, the person delivering the baby has to help the baby breathe, and sometimes has to get the baby's heart rate back to normal. This is called neonatal resuscitation.
Neonatal resuscitation is a skilled task, and the health worker needs proper training. As babies need to be resuscitated quickly, the health worker needs to know how to prepare for this before the baby is born. For instance, he or she needs to know how to prepare the room and proper equipment. Health workers in poor countries often do not have these skills, and these babies are likely to die. Babies can also be harmed if the health worker does not resuscitate the baby correctly.
Several training programmes have been developed to teach health workers how to give emergency care to seriously ill babies and children. But most of these have been developed and tested in wealthy countries, and we don't know whether they would work in poor countries.
What happens when health professionals in poor countries are given extra training?
The review authors found two relevant studies. These studies compared the practices of health professionals who had been given extra training in the care of newborns with the practices of health professionals who did not receive extra training.
In the first study, nurses at a maternity hospital in Kenya completed a one-day training course on how to resuscitate newborn babies. This course was adapted from the UK Resuscitation Council, and it included lectures and practical training. The study suggests that after these training courses:
health professionals are probably more likely to resuscitate newborn babies correctly (moderate certainty of the evidence); and
newborn babies may be less likely to die while being resuscitated (low certainty of the evidence).
In the second study, doctors, nurses and midwives in five Sri Lankan hospitals were given a four-day training course on how to prepare for and provide care for newborns. This course was adapted from the World Health Organization (WHO) Training Modules on Essential Newborn Care and Breastfeeding, and included lectures, demonstrations, hands-on training and small group discussions. This study suggests that after these training courses:
health professionals probably are more likely to be well prepared to resuscitate newborn babies (moderate certainty of the evidence).
Unfortunately, the two studies followed up with health professionals for only two to three months after they received training. We therefore don't know if the benefits of the training courses lasted over time.
The review authors found no studies that looked at the effects of training programmes on the care of older children.
How up-to-date is this review?
Review authors searched for studies that had been published up to February 2015.
doi:10.1002/14651858.CD007071.pub3
PMCID: PMC4463987  PMID: 25968066
2.  Immediate fluid management of children with severe febrile illness and signs of impaired circulation in low-income settings: a contextualised systematic review 
BMJ Open  2014;4(4):e004934.
Objective
To evaluate the effects of intravenous fluid bolus compared to maintenance intravenous fluids alone as part of immediate emergency care in children with severe febrile illness and signs of impaired circulation in low-income settings.
Design
Systematic review of randomised controlled trials (RCTs), and observational studies, including retrospective analyses, that compare fluid bolus regimens with maintenance fluids alone. The primary outcome measure was predischarge mortality.
Data sources and synthesis
We searched PubMed, The Cochrane Library (to January 2014), with complementary earlier searches on, Google Scholar and Clinical Trial Registries (to March 2013). As studies used different clinical signs to define impaired circulation we classified patients into those with signs of severely impaired circulation, or those with any signs of impaired circulation. The quality of evidence for each outcome was appraised using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Findings are presented as risk ratios (RRs) with 95% CIs.
Results
Six studies were included. Two were RCTs, one large trial (n=3141 children) from a low-income country and a smaller trial from a middle-income country. The remaining studies were from middle-income or high-income settings, observational, and with few participants (34–187 children).
Severely impaired circulation
The large RCT included a small subgroup with severely impaired circulation. There were more deaths in those receiving bolus fluids (20–40 mL/kg/h, saline or albumin) compared to maintenance fluids (2.5–4 mL/kg/h; RR 2.40, 95% CI 0.84 to 6.88, p=0.054, 65 participants, low quality evidence). Three additional observational studies, all at high risk of confounding, found mixed effects on mortality (very low quality evidence).
Any signs of impaired circulation
The large RCT included children with signs of both severely and non-severely impaired circulation. Overall, bolus fluids increased 48 h mortality compared to maintenance fluids with an additional 3 deaths per 100 children treated (RR 1.45, 95% CI 1.13 to 1.86, 3141 participants, high quality evidence). In a second small RCT from India, no difference in 72 h mortality was detected between children who received 20–40 mL/kg Ringers lactate over 15 min and those who received 20 mL over 20 min up to a maximum of 60 mL/kg over 1 h (147 participants, low quality evidence). In one additional observational study, resuscitation consistent with Advanced Paediatric Life Support (APLS) guidelines, including fluids, was not associated with reduced mortality in the small subgroup with septic shock (very low quality evidence).
Signs of impaired circulation, but not severely impaired
Only the large RCT allowed an analysis for children with some signs of impaired circulation who would not meet the criteria for severe impairment. Bolus fluids increased 48 h mortality compared to maintenance alone (RR 1.36, 95% CI 1.05 to 1.76, high quality evidence).
Conclusions
Prior to the publication of the large RCT, the global evidence base for bolus fluid therapy in children with severe febrile illness and signs of impaired circulation was of very low quality. This large study provides robust evidence that in low-income settings fluid boluses increase mortality in children with severe febrile illness and impaired circulation, and this increased risk is consistent across children with severe and less severe circulatory impairment.
doi:10.1136/bmjopen-2014-004934
PMCID: PMC4010848  PMID: 24785400
Paediatrics
3.  Evidence review of hydroxyurea for the prevention of sickle cell complications in low-income countries 
Archives of Disease in Childhood  2013;98(11):908-914.
Hydroxyurea is widely used in high-income countries for the management of sickle cell disease (SCD) in children. In Kenyan clinical guidelines, hydroxyurea is only recommended for adults with SCD. Yet many deaths from SCD occur in early childhood, deaths that might be prevented by an effective, disease modifying intervention. The aim of this review was to summarise the available evidence on the efficacy, effectiveness and safety of hydroxyurea in the management of SCD in children below 5 years of age to support guideline development in Kenya. We undertook a systematic review and used the Grading of Recommendations Assessment, Development and Evaluation system to appraise the quality of identified evidence. Overall, available evidence from 1 systematic review (n=26 studies), 2 randomised controlled trials (n=354 children), 14 observational studies and 2 National Institute of Health reports suggest that hydroxyurea may be associated with improved fetal haemoglobin levels, reduced rates of hospitalisation, reduced episodes of acute chest syndrome and decreased frequency of pain events in children with SCD. However, it is associated with adverse events (eg, neutropenia) when high to maximum tolerated doses are used. Evidence is lacking on whether hydroxyurea improves survival if given to young children. Majority of the included studies were of low quality and mainly from high-income countries. Overall, available limited evidence suggests that hydroxyurea may improve morbidity and haematological outcomes in SCD in children aged below 5 years and appears safe in settings able to provide consistent haematological monitoring.
doi:10.1136/archdischild-2012-302387
PMCID: PMC3812872  PMID: 23995076
Genetics; Haematology
4.  Topical Umbilical Cord Care for Prevention of Infection and Neonatal Mortality 
Umbilical cord care varies often reflecting community or health-worker beliefs. We undertook a review of current evidence on topical umbilical cord care. Study quality was assessed using the Grading of Recommendations, Assessment, Development and Evaluation system, and a meta-analysis was conducted for comparable trials. Available moderate-quality to high-quality evidence indicate that cord cleansing with 4% chlorhexidine may reduce the risk of neonatal mortality and sepsis (omphalitis) in low-resource settings.
doi:10.1097/INF.0b013e3182783dc3
PMCID: PMC3785148  PMID: 23076382
cord care; chlorhexidine; neonatal mortality; sepsis; neonates
5.  Comparison of Alternative Evidence Summary and Presentation Formats in Clinical Guideline Development: A Mixed-Method Study 
PLoS ONE  2013;8(1):e55067.
Background
Best formats for summarising and presenting evidence for use in clinical guideline development remain less well defined. We aimed to assess the effectiveness of different evidence summary formats to address this gap.
Methods
Healthcare professionals attending a one-week Kenyan, national guideline development workshop were randomly allocated to receive evidence packaged in three different formats: systematic reviews (SRs) alone, systematic reviews with summary-of-findings tables, and ‘graded-entry’ formats (a ‘front-end’ summary and a contextually framed narrative report plus the SR). The influence of format on the proportion of correct responses to key clinical questions, the primary outcome, was assessed using a written test. The secondary outcome was a composite endpoint, measured on a 5-point scale, of the clarity of presentation and ease of locating the quality of evidence for critical neonatal outcomes. Interviews conducted within two months following completion of trial data collection explored panel members’ views on the evidence summary formats and experiences with appraisal and use of research information.
Results
65 (93%) of 70 participants completed questions on the prespecified outcome measures. There were no differences between groups in the odds of correct responses to key clinical questions. ‘Graded-entry’ formats were associated with a higher mean composite score for clarity and accessibility of information about the quality of evidence for critical neonatal outcomes compared to systematic reviews alone (adjusted mean difference 0.52, 95% CI 0.06 to 0.99). There was no difference in the mean composite score between SR with SoF tables and SR alone. Findings from interviews with 16 panelists indicated that short narrative evidence reports were preferred for the improved clarity of information presentation and ease of use.
Conclusions
Our findings suggest that ‘graded-entry’ evidence summary formats may improve clarity and accessibility of research evidence in clinical guideline development.
Trial Registration
Controlled-Trials.com ISRCTN05154264
doi:10.1371/journal.pone.0055067
PMCID: PMC3555827  PMID: 23372813
6.  The “Child Health Evidence Week” and GRADE grid may aid transparency in the deliberative process of guideline development 
Journal of Clinical Epidemiology  2012;65(9-10):962-969.
Objective
To explore the evidence translation process during a 1-week national guideline development workshop (“Child Health Evidence Week”) in Kenya.
Study Design and Setting
Nonparticipant observational study of the discussions of a multidisciplinary guideline development panel in Kenya. Discussions were aided by GRADE (Grading of Recommendations Assessment, Development, and Evaluation) grid.
Results
Three key thematic categories emerged: 1) “referral to other evidence to support or refute the proposed recommendations;” 2) “assessment of the presented research evidence;” and 3) “assessment of the local applicability of evidence.” The types of evidence cited included research evidence and anecdotal evidence based on clinician experiences. Assessment of the research evidence revealed important challenges in the translation of evidence into recommendations, including absence of evidence, low quality or inconclusive evidence, inadequate reporting of key features of the management under consideration, and differences in panelists’ interpretation of the research literature. A broad range of factors with potential to affect local applicability of evidence were discussed.
Conclusion
The process of the “Child Health Evidence Week” combined with the GRADE grid may aid transparency in the deliberative process of guideline development, and provide a mechanism for comprehensive assessment, documentation, and reporting of multiple factors that influence the quality and applicability of guideline recommendations.
doi:10.1016/j.jclinepi.2012.03.004
PMCID: PMC3413881  PMID: 22742914
Clinical practice guidelines; Evidence; Knowledge translation; Transparency; GRADE; Pediatrics
7.  Getting to grips with GRADE—perspective from a low-income setting 
Journal of clinical epidemiology  2011;64(7):708-710.
doi:10.1016/j.jclinepi.2010.07.016
PMCID: PMC3319275  PMID: 21316192
8.  Experience developing national evidence-based clinical guidelines for childhood pneumonia in a low-income setting - making the GRADE? 
BMC Pediatrics  2012;12:1.
Background
The development of evidence-based clinical practice guidelines has gained wide acceptance in high-income countries and reputable international organizations. Whereas this approach may be a desirable standard, challenges remain in low-income settings with limited capacity and resources for evidence synthesis and guideline development. We present our experience using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach for the recent revision of the Kenyan pediatric clinical guidelines focusing on antibiotic treatment of pneumonia.
Methods
A team of health professionals, many with minimal prior experience conducting systematic reviews, carried out evidence synthesis for structured clinical questions. Summaries were compiled and distributed to a panel of clinicians, academicians and policy-makers to generate recommendations based on best available research evidence and locally-relevant contextual factors.
Results
We reviewed six eligible articles on non-severe and 13 on severe/very severe pneumonia. Moderate quality evidence suggesting similar clinical outcomes comparing amoxicillin and cotrimoxazole for non-severe pneumonia received a strong recommendation against adopting amoxicillin. The panel voted strongly against amoxicillin for severe pneumonia over benzyl penicillin despite moderate quality evidence suggesting clinical equivalence between the two and additional factors favoring amoxicillin. Very low quality evidence suggesting ceftriaxone was as effective as the standard benzyl penicillin plus gentamicin for very severe pneumonia received a strong recommendation supporting the standard treatment.
Conclusions
Although this exercise may have fallen short of the rigorous requirements recommended by the developers of GRADE, it was arguably an improvement on previous attempts at guideline development in low-income countries and offers valuable lessons for future similar exercises where resources and locally-generated evidence are scarce.
doi:10.1186/1471-2431-12-1
PMCID: PMC3268095  PMID: 22208358
9.  Effect of a multi-faceted quality improvement intervention on inappropriate antibiotic use in children with non-bloody diarrhoea admitted to district hospitals in Kenya 
BMC Pediatrics  2011;11:109.
Background
There are few reports of interventions to reduce the common but irrational use of antibiotics for acute non-bloody diarrhoea amongst hospitalised children in low-income settings. We undertook a secondary analysis of data from an intervention comprising training of health workers, facilitation, supervision and face-to-face feedback, to assess whether it reduced inappropriate use of antibiotics in children with non-bloody diarrhoea and no co-morbidities requiring antibiotics, compared to a partial intervention comprising didactic training and written feedback only. This outcome was not a pre-specified end-point of the main trial.
Methods
Repeated cross-sectional survey data from a cluster-randomised controlled trial of an intervention to improve management of common childhood illnesses in Kenya were used to describe the prevalence of inappropriate antibiotic use in a 7-day period in children aged 2-59 months with acute non-bloody diarrhoea. Logistic regression models with random effects for hospital were then used to identify patient and clinician level factors associated with inappropriate antibiotic use and to assess the effect of the intervention.
Results
9, 459 admission records of children were reviewed for this outcome. Of these, 4, 232 (44.7%) were diagnosed with diarrhoea, with 130 of these being bloody (dysentery) therefore requiring antibiotics. 1, 160 children had non-bloody diarrhoea and no co-morbidities requiring antibiotics-these were the focus of the analysis. 750 (64.7%) of them received antibiotics inappropriately, 313 of these being in the intervention hospitals vs. 437 in the controls. The adjusted logistic regression model showed the baseline-adjusted odds of inappropriate antibiotic prescription to children admitted to the intervention hospitals was 0.30 times that in the control hospitals (95%CI 0.09-1.02).
Conclusion
We found some evidence that the multi-faceted, sustained intervention described in this paper led to a reduction in the inappropriate use of antibiotics in treating children with non-bloody diarrhoea.
Trial registration
International Standard Randomised Controlled Trial Number Register ISRCTN42996612
doi:10.1186/1471-2431-11-109
PMCID: PMC3314405  PMID: 22117602
10.  Quality of hospital care for sick newborns and severely malnourished children in Kenya: A two-year descriptive study in 8 hospitals 
Background
Given the high mortality associated with neonatal illnesses and severe malnutrition and the development of packages of interventions that provide similar challenges for service delivery mechanisms we set out to explore how well such services are provided in Kenya.
Methods
As a sub-component of a larger study we evaluated care during surveys conducted in 8 rural district hospitals using convenience samples of case records. After baseline hospitals received either a full multifaceted intervention (intervention hospitals) or a partial intervention (control hospitals) aimed largely at improving inpatient paediatric care for malaria, pneumonia and diarrhea/dehydration. Additional data were collected to: i) examine the availability of routine information at baseline and their value for morbidity, mortality and quality of care reporting, and ii) compare the care received against national guidelines disseminated to all hospitals.
Results
Clinical documentation for neonatal and malnutrition admissions was often very poor at baseline with case records often entirely missing. Introducing a standard newborn admission record (NAR) form was associated with an increase in median assessment (IQR) score to 25/28 (22-27) from 2/28 (1-4) at baseline. Inadequate and incorrect prescribing of penicillin and gentamicin were common at baseline. For newborns considerable improvements in prescribing in the post baseline period were seen for penicillin but potentially serious errors persisted when prescribing gentamicin, particularly to low-birth weight newborns in the first week of life. Prescribing essential feeds appeared almost universally inadequate at baseline and showed limited improvement after guideline dissemination.
Conclusion
Routine records are inadequate to assess newborn care and thus for monitoring newborn survival interventions. Quality of documented inpatient care for neonates and severely malnourished children is poor with limited improvement after the dissemination of clinical practice guidelines. Further research evaluating approaches to improving care for these vulnerable groups is urgently needed. We also suggest pre-service training curricula should be better aligned to help improve newborn survival particularly.
doi:10.1186/1472-6963-11-307
PMCID: PMC3236590  PMID: 22078071
newborns; child malnutrition; quality of health care
11.  What clinical signs best identify severe illness in young infants aged 0–59 days in developing countries? A systematic review 
Archives of disease in childhood  2011;96(11):1052-1059.
Despite recent overall improvement in the survival of under-five children worldwide, mortality among young infants remains high, and accounts for an increasing proportion of child deaths in resource-poor settings. In such settings, clinical decisions for appropriate management of severely ill infants have to be made on the basis of presenting clinical signs, and with limited or no laboratory facilities. This review summarises the evidence from observational studies of clinical signs of severe illnesses in young infants aged 0–59 days, with a particular focus on defining a minimum set of best predictors of the need for hospital-level care. Available moderate to high quality evidence suggests that, among sick infants aged 0–59 days brought to a health facility, the following clinical signs—alone or in combination—are likely to be the most valuable in identifying infants at risk of severe illness warranting hospital-level care: history of feeding difficulty, history of convulsions, temperature (axillary) ≥37.5°C or <35.5°C, change in level of activity, fast breathing/respiratory rate ≥60 breaths per minute, severe chest indrawing, grunting and cyanosis.
doi:10.1136/adc.2010.186049
PMCID: PMC3081806  PMID: 21220263
12.  Treatment of African children with severe malaria - towards evidence-informed clinical practice using GRADE 
Malaria Journal  2011;10:201.
Background
Severe malaria is a major contributor of deaths in African children up to five years of age. One valuable tool to support health workers in the management of diseases is clinical practice guidelines (CPGs) developed using robust methods. A critical assessment of the World Health Organization (WHO) and Kenyan paediatric malaria treatment guidelines with quinine was undertaken, with a focus on the quality of the evidence and transparency of the shift from evidence to recommendations.
Methods
Systematic reviews of the literature were conducted using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool to appraise included studies. The findings were used to evaluate the WHO and Kenyan recommendations for the management of severe childhood malaria.
Results
The WHO 2010 malaria guidance on severe malaria in children, which informed the Kenyan guidelines, only evaluated the evidence on one topic on paediatric care using the GRADE tool. Using the GRADE tool, this work explicitly demonstrated that despite the established use of quinine in the management of paediatric cases of severe malaria for decades, low or very low quality evidence of important outcomes, but not critical outcomes such as mortality, have informed national and international guidance on the paediatric quinine dosing, route of administration and adverse effects.
Conclusions
Despite the foreseeable shift to artesunate as the primary drug for treatment of severe childhood malaria, the findings reported here reflect that the particulars of quinine therapeutics for the management of severe malaria in African children have historically been a neglected research priority. This work supports the application of the GRADE tool to make transparent recommendations and to inform advocacy efforts for a greater research focus in priority areas in paediatric care in Africa and other low-income settings.
doi:10.1186/1475-2875-10-201
PMCID: PMC3152530  PMID: 21777441
13.  A Multifaceted Intervention to Implement Guidelines and Improve Admission Paediatric Care in Kenyan District Hospitals: A Cluster Randomised Trial 
PLoS Medicine  2011;8(4):e1001018.
Philip Ayieko and colleagues report the outcomes of a cluster-randomized trial carried out in eight Kenyan district hospitals evaluating the effects of a complex intervention involving improved training and supervision for clinicians. They found a higher performance of hospitals assigned to the complex intervention on a variety of process of care measures, as compared to those receiving the control intervention.
Background
In developing countries referral of severely ill children from primary care to district hospitals is common, but hospital care is often of poor quality. However, strategies to change multiple paediatric care practices in rural hospitals have rarely been evaluated.
Methods and Findings
This cluster randomized trial was conducted in eight rural Kenyan district hospitals, four of which were randomly assigned to a full intervention aimed at improving quality of clinical care (evidence-based guidelines, training, job aides, local facilitation, supervision, and face-to-face feedback; n = 4) and the remaining four to control intervention (guidelines, didactic training, job aides, and written feedback; n = 4). Prespecified structure, process, and outcome indicators were measured at baseline and during three and five 6-monthly surveys in control and intervention hospitals, respectively. Primary outcomes were process of care measures, assessed at 18 months postbaseline.
In both groups performance improved from baseline. Completion of admission assessment tasks was higher in intervention sites at 18 months (mean = 0.94 versus 0.65, adjusted difference 0.54 [95% confidence interval 0.05–0.29]). Uptake of guideline recommended therapeutic practices was also higher within intervention hospitals: adoption of once daily gentamicin (89.2% versus 74.4%; 17.1% [8.04%–26.1%]); loading dose quinine (91.9% versus 66.7%, 26.3% [−3.66% to 56.3%]); and adequate prescriptions of intravenous fluids for severe dehydration (67.2% versus 40.6%; 29.9% [10.9%–48.9%]). The proportion of children receiving inappropriate doses of drugs in intervention hospitals was lower (quinine dose >40 mg/kg/day; 1.0% versus 7.5%; −6.5% [−12.9% to 0.20%]), and inadequate gentamicin dose (2.2% versus 9.0%; −6.8% [−11.9% to −1.6%]).
Conclusions
Specific efforts are needed to improve hospital care in developing countries. A full, multifaceted intervention was associated with greater changes in practice spanning multiple, high mortality conditions in rural Kenyan hospitals than a partial intervention, providing one model for bridging the evidence to practice gap and improving admission care in similar settings.
Trial registration
Current Controlled Trials ISRCTN42996612
Please see later in the article for the Editors' Summary
Editors' Summary
Background
In 2008, nearly 10 million children died in early childhood. Nearly all these deaths were in low- and middle-income countries—half were in Africa. In Kenya, for example, 74 out every 1,000 children born died before they reached their fifth birthday. About half of all childhood (pediatric) deaths in developing countries are caused by pneumonia, diarrhea, and malaria. Deaths from these common diseases could be prevented if all sick children had access to quality health care in the community (“primary” health care provided by health centers, pharmacists, family doctors, and traditional healers) and in district hospitals (“secondary” health care). Unfortunately, primary health care facilities in developing countries often lack essential diagnostic capabilities and drugs, and pediatric hospital care is frequently inadequate with many deaths occurring soon after admission. Consequently, in 1996, as part of global efforts to reduce childhood illnesses and deaths, the World Health Organization (WHO) and the United Nations Children's Fund (UNICEF) introduced the Integrated Management of Childhood Illnesses (IMCI) strategy. This approach to child health focuses on the well-being of the whole child and aims to improve the case management skills of health care staff at all levels, health systems, and family and community health practices.
Why Was This Study Done?
The implementation of IMCI has been evaluated at the primary health care level, but its implementation in district hospitals has not been evaluated. So, for example, interventions designed to encourage the routine use of WHO disease-specific guidelines in rural pediatric hospitals have not been tested. In this cluster randomized trial, the researchers develop and test a multifaceted intervention designed to improve the implementation of treatment guidelines and admission pediatric care in district hospitals in Kenya. In a cluster randomized trial, groups of patients rather than individual patients are randomly assigned to receive alternative interventions and the outcomes in different “clusters” of patients are compared. In this trial, each cluster is a district hospital.
What Did the Researchers Do and Find?
The researchers randomly assigned eight Kenyan district hospitals to the “full” or “control” intervention, interventions that differed in intensity but that both included more strategies to promote implementation of best practice than are usually applied in Kenyan rural hospitals. The full intervention included provision of clinical practice guidelines and training in their use, six-monthly survey-based hospital assessments followed by face-to-face feedback of survey findings, 5.5 days training for health care workers, provision of job aids such as structured pediatric admission records, external supervision, and the identification of a local facilitator to promote guideline use and to provide on-site problem solving. The control intervention included the provision of clinical practice guidelines (without training in their use) and job aids, six-monthly surveys with written feedback, and a 1.5-day lecture-based seminar to explain the guidelines. The researchers compared the implementation of various processes of care (activities of patients and doctors undertaken to ensure delivery of care) in the intervention and control hospitals at baseline and 18 months later. The performance of both groups of hospitals improved during the trial but more markedly in the intervention hospitals than in the control hospitals. At 18 months, the completion of admission assessment tasks and the uptake of guideline-recommended clinical practices were both higher in the intervention hospitals than in the control hospitals. Moreover, a lower proportion of children received inappropriate doses of drugs such as quinine for malaria in the intervention hospitals than in the control hospitals.
What Do These Findings Mean?
These findings show that specific efforts are needed to improve pediatric care in rural Kenya and suggest that interventions that include more approaches to changing clinical practice may be more effective than interventions that include fewer approaches. These findings are limited by certain aspects of the trial design, such as the small number of participating hospitals, and may not be generalizable to other hospitals in Kenya or to hospitals in other developing countries. Thus, although these findings seem to suggest that efforts to implement and scale up improved secondary pediatric health care will need to include more than the production and dissemination of printed materials, further research including trials or evaluation of test programs are necessary before widespread adoption of any multifaceted approach (which will need to be tailored to local conditions and available resources) can be contemplated.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001018.
WHO provides information on efforts to reduce global child mortality and on Integrated Management of Childhood Illness (IMCI); the WHO pocket book “Hospital care for children contains guidelines for the management of common illnesses with limited resources (available in several languages)
UNICEF also provides information on efforts to reduce child mortality and detailed statistics on child mortality
The iDOC Africa Web site, which is dedicated to improving the delivery of hospital care for children and newborns in Africa, provides links to the clinical guidelines and other resources used in this study
doi:10.1371/journal.pmed.1001018
PMCID: PMC3071366  PMID: 21483712
14.  Mini-review: Management of Hypoglycaemia in Children Aged 0–59 Months 
Journal of tropical pediatrics  2009;56(4):227-234.
Summary
Hypoglycaemia is associated with poor prognosis in many severe childhood illnesses especially in sub-Saharan Africa where the prevalence of malaria, diarrhoea and malnutrition remains high. Uncertainty, however, still persists regarding the significance, definition and management of childhood hypoglycaemia. As a step towards defining optimal, evidence-based diagnostic and management criteria, we (i) reviewed the evidence underlying current recommendations for the management of hypoglycaemia, and (ii) analysed a large set of data on blood glucose levels and associated outcomes of paediatric admissions in a rural hospital over an 11-year period. Current definitions and treatment protocols for hypoglycaemia are based on observational data and expert opinion. Future large pragmatic randomized trials would help define optimal treatment thresholds. Emerging evidence suggests that sublingual sugar is a feasible and effective therapy for correction of hypoglycaemia, and should be considered where intravenous glucose is delayed or impossible.
doi:10.1093/tropej/fmp109
PMCID: PMC2948531  PMID: 19933785
hypoglycaemia; glucose; dextrose; newborn; children
15.  Caffeine for the management of apnea in preterm infants 
International health  2009;1(2):190-195.
Summary
Considerable uncertainty persists regarding the efficacy and safety of methylxanthines (caffeine, theophylline – in intravenous form named aminophylline) for the prevention and treatment of infant apnea. To help inform national guideline development in Kenya we undertook structured literature searches to identify current evidence on caffeine therapy for infant apnea. Available evidence shows that caffeine is as effective as intravenous theophylline (aminophylline), but is safer and easier to give and has better therapeutic properties. It is therefore recommended for the treatment of apnea of prematurity. Caffeine is also the preferred drug if clinicians plan to provide apnea prophylaxis. As prematurity is likely to result in more than 1 million deaths a year, mostly in resource-poor settings, greater efforts need to be made to ensure interventions such as caffeine, currently unavailable in countries such as Kenya, are made more widely available.
doi:10.1016/j.inhe.2009.09.005
PMCID: PMC2912513  PMID: 20676238
Infant; Apnea; Prematurity; Caffeine
16.  In-service training for health professionals to improve care of the seriously ill newborn or child in low and middle-income countries (Review) 
Background
A variety of emergency care training courses based on developed country models are being promoted as a strategy to improve the quality of care of the seriously ill newborn or child in developing countries. Clear evidence of their effectiveness is lacking.
Objectives
To investigate the effectiveness of in-service training of health professionals on their management and care of the seriously ill newborn or child in low and middle-income settings.
Search strategy
We searched The Cochrane Register of Controlled Trials (CENTRAL), the Specialised Register of the Cochrane EPOC group (both up to May 2009), MEDLINE (1950 to May 2009), EMBASE (1980 to May 2009), CINAHL (1982 to March 2008), ERIC / LILACS / WHOLIS (all up to October 2008), and ISI Science Citation Index Expanded and ISI Social Sciences Citation Index (both from 1975 to March 2009). We checked references of retrieved articles and reviews and contacted authors to identify additional studies.
Selection criteria
Randomised controlled trials (RCTs), cluster-randomised trials (CRTs), controlled clinical trials (CCTs), controlled before-after studies (CBAs) and interrupted time series studies (ITSs) that reported objectively measured professional practice, patient outcomes, health resource /services utilization, or training costs in healthcare settings (not restricted to studies in low-income settings).
Data collection and analysis
We independently selected studies for inclusion, abstracted data using a standardised form, and assessed study quality. Meta-analysis was not appropriate. Study results were summarised and appraised.
Main results
Two studies of varied designs were included. In one RCT of moderate quality, Newborn Resuscitation Training (NRT) was associated with a significant improvement in performance of adequate initial resuscitation steps (risk ratio 2.45, 95% confidence interval (CI) 1.75 to 3.42, P < 0.001, adjusted for clustering) and a reduction in the frequency of inappropriate and potentially harmful practices (mean difference 0.40, 95% CI 0.13 to 0.66, P = 0.004). In the second RCT, available limited data suggested that there was improvement in assessment of breathing and newborn care practices in the delivery room following implementation of Essential Newborn Care (ENC) training.
Authors' conclusions
There is limited evidence that in-service neonatal emergency care courses improve health-workers' practices when caring for a seriously ill newborn although there is some evidence of benefit. Rigorous trials evaluating the impact of refresher emergency care training on long-term professional practices are needed. To optimise appropriate policy decisions, studies should aim to collect data on resource use and costs of training implementation.
doi:10.1002/14651858.CD007071.pub2
PMCID: PMC2868967  PMID: 20393956
17.  An intervention to improve paediatric and newborn care in Kenyan district hospitals: Understanding the context 
Background
It is increasingly appreciated that the interpretation of health systems research studies is greatly facilitated by detailed descriptions of study context and the process of intervention. We have undertaken an 18-month hospital-based intervention study in Kenya aiming to improve care for admitted children and newborn infants. Here we describe the baseline characteristics of the eight hospitals as environments receiving the intervention, as well as the general and local health system context and its evolution over the 18 months.
Methods
Hospital characteristics were assessed using previously developed tools assessing the broad structure, process, and outcome of health service provision for children and newborns. Major health system or policy developments over the period of the intervention at a national level were documented prospectively by monitoring government policy announcements, the media, and through informal contacts with policy makers. At the hospital level, a structured, open questionnaire was used in face-to-face meetings with senior hospital staff every six months to identify major local developments that might influence implementation. These data provide an essential background for those seeking to understand the generalisability of reports describing the intervention's effects, and whether the intervention plausibly resulted in these effects.
Results
Hospitals had only modest capacity, in terms of infrastructure, equipment, supplies, and human resources available to provide high-quality care at baseline. For example, hospitals were lacking between 30 to 56% of items considered necessary for the provision of care to the seriously ill child or newborn. An increase in spending on hospital renovations, attempts to introduce performance contracts for health workers, and post-election violence were recorded as examples of national level factors that might influence implementation success generally. Examples of factors that might influence success locally included frequent and sometimes numerous staff changes, movements of senior departmental or administrative staff, and the presence of local 'donor' partners with alternative priorities.
Conclusion
The effectiveness of interventions delivered at hospital level over periods realistically required to achieve change may be influenced by a wide variety of factors at national and local levels. We have demonstrated how dynamic such contexts are, and therefore the need to consider context when interpreting an intervention's effectiveness.
doi:10.1186/1748-5908-4-42
PMCID: PMC2724481  PMID: 19627588
18.  Developing and Introducing Evidence Based Clinical Practice Guidelines for Serious Illness in Kenya 
Archives of disease in childhood  2008;93(9):799-804.
The under-5 mortality rate in most developing countries remains high yet many deaths could be averted if available knowledge was put into practice. For seriously ill children in hospital investigations in low-income countries commonly demonstrate incorrect diagnosis and treatment and frequent prescribing errors. To help improve hospital management of the major causes of inpatient childhood mortality we developed simple clinical guidelines for use in Kenya, a low-income setting. The participatory process we used to adapt existing WHO materials and further develop and build support for such guidelines is discussed. To facilitate use of the guidelines we also developed job-aides and a 5.5 days training programme for their dissemination and implementation. We attempted to base our training on modern theories around adult learning and deliberately attempted to train a ‘critical mass’ of health workers within each institution at low cost. Our experience suggests that with sustained effort it is possible to develop locally owned, appropriate clinical practice guidelines for emergency and initial hospital care for seriously ill children with involvement of pertinent stake holders throughout. Early experience suggests that the training developed to support the guidelines, despite the fact that it challenges many established practices, is well received, appropriate to the needs of front line health workers in Kenya and feasible. To our knowledge the process described in Kenya is among a handful of attempts globally to implement inpatient or referral care components of WHO / UNICEF’s Integrated Management of Childhood Illness approach. However, whether guideline dissemination and implementation result in improved quality of care in our environment remains to be seen.
doi:10.1136/adc.2007.126508
PMCID: PMC2654066  PMID: 18719161
19.  Effect of Newborn Resuscitation Training on Health Worker Practices in Pumwani Hospital, Kenya 
PLoS ONE  2008;3(2):e1599.
Background
Birth asphyxia kills 0.7 to 1.6 million newborns a year globally with 99% of deaths in developing countries. Effective newborn resuscitation could reduce this burden of disease but the training of health-care providers in low income settings is often outdated. Our aim was to determine if a simple one day newborn resuscitation training (NRT) alters health worker resuscitation practices in a public hospital setting in Kenya.
Methods/Principal Findings
We conducted a randomised, controlled trial with health workers receiving early training with NRT (n = 28) or late training (the control group, n = 55). The training was adapted locally from the approach of the UK Resuscitation Council. The primary outcome was the proportion of appropriate initial resuscitation steps with the frequency of inappropriate practices as a secondary outcome. Data were collected on 97 and 115 resuscitation episodes over 7 weeks after early training in the intervention and control groups respectively. Trained providers demonstrated a higher proportion of adequate initial resuscitation steps compared to the control group (trained 66% vs control 27%; risk ratio 2.45, [95% CI 1.75–3.42], p<0.001, adjusted for clustering). In addition, there was a statistically significant reduction in the frequency of inappropriate and potentially harmful practices per resuscitation in the trained group (trained 0.53 vs control 0.92; mean difference 0.40, [95% CI 0.13–0.66], p = 0.004).
Conclusions/Significance
Implementation of a simple, one day newborn resuscitation training can be followed immediately by significant improvement in health workers' practices. However, evidence of the effects on long term performance or clinical outcomes can only be established by larger cluster randomised trials.
Trial Registration
Controlled-Trials.com ISRCTN92218092
doi:10.1371/journal.pone.0001599
PMCID: PMC2229665  PMID: 18270586
20.  What clinical signs best identify severe illness in young infants aged 0–59 days in developing countries? A systematic review 
Archives of Disease in Childhood  2011;96(11):1052-1059.
Despite recent overall improvement in the survival of under-five children worldwide, mortality among young infants remains high, and accounts for an increasing proportion of child deaths in resource-poor settings. In such settings, clinical decisions for appropriate management of severely ill infants have to be made on the basis of presenting clinical signs, and with limited or no laboratory facilities. This review summarises the evidence from observational studies of clinical signs of severe illnesses in young infants aged 0–59 days, with a particular focus on defining a minimum set of best predictors of the need for hospital-level care. Available moderate to high quality evidence suggests that, among sick infants aged 0–59 days brought to a health facility, the following clinical signs—alone or in combination—are likely to be the most valuable in identifying infants at risk of severe illness warranting hospital-level care: history of feeding difficulty, history of convulsions, temperature (axillary) ≥37.5°C or <35.5°C, change in level of activity, fast breathing/respiratory rate ≥60 breaths per minute, severe chest indrawing, grunting and cyanosis.
doi:10.1136/adc.2010.186049
PMCID: PMC3081806  PMID: 21220263

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