Janine Dretzke

The clinical effectiveness of different parenting programmes for children with conduct problems: a systematic review of randomised controlled trials

BackgroundConduct problems are common, disabling and costly. The prognosis for children with conduct problems is poor, with outcomes in adulthood including criminal behaviour, alcoholism, drug abuse, domestic violence, child abuse and a range of psychiatric disorders.There has been a rapid expansion of group based parent-training programmes for the treatment of children with conduct problems in a number of countries over the past 10 years. Existing reviews of parent training have methodological limitations such as inclusion of non-randomised studies, the absence of investigation for heterogeneity prior to meta-analysis or failure to report confidence intervals.The objective of the current study was to systematically review randomised controlled trials of parenting programmes for the treatment of children with conduct problems.MethodsStandard systematic review methods were followed including duplicate inclusion decisions, data extraction and quality assessment. Twenty electronic databases from the fields of medicine, psychology, social science and education were comprehensively searched for RCTs and systematic reviews to February 2006.Inclusion criteria were: randomised controlled trial; of structured, repeatable parenting programmes; for parents/carers of children up to the age of 18 with a conduct problem; and at least one measure of child behaviour. Meta-analysis and qualitative synthesis were used to summarise included studies.Results57 RCTs were included. Studies were small with an average group size of 21. Meta-analyses using both parent (SMD -0.67; 95% CI: -0.91, -0.42) and independent (SMD -0.44; 95% CI: -0.66, -0.23) reports of outcome showed significant differences favouring the intervention group. There was insufficient evidence to determine the relative effectiveness of different approaches to delivering parenting programmes.ConclusionParenting programmes are an effective treatment for children with conduct problems. The relative effectiveness of different parenting programmes requires further research.

Subcutaneous and sublingual immunotherapy for seasonal allergic rhinitis: a systematic review and indirect comparison.

BACKGROUND Severe allergic rhinitis uncontrolled by pharmacotherapy can adversely affect quality of life. Both subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) have demonstrated effectiveness in this patient group; however, it remains uncertain which route of administration is more effective. OBJECTIVES We sought to update existing systematic reviews on the clinical effectiveness of SCIT and SLIT versus placebo, to undertake a systematic review of head-to-head trials, and to compare the relative effectiveness of SCIT and SLIT in an adjusted indirect comparison. METHODS Standard systematic review methods aimed at minimizing bias were used. Double-blind, randomized, placebo-controlled trials of SCIT or SLIT or trials of SCIT versus SLIT were included. Meta-analysis and indirect comparison meta-analysis with meta-regression were performed. RESULTS Updated meta-analyses confirmed statistically significant benefits for SCIT and SLIT compared with placebo in adults and, to a lesser extent, in children. Only 1 head-to-head trial met the inclusion criteria; both this and the indirect comparisons did not provide conclusive results in favor of either SCIT or SLIT based on symptom-medication or quality-of-life scores. There was a trend toward favoring SCIT for symptom and medication scores. CONCLUSIONS Although there is clear evidence of effectiveness of both SCIT and SLIT, superiority of one mode of administration over the other could not be consistently demonstrated through indirect comparison, and further research is needed to establish the comparative effectiveness of SCIT versus SLIT.

Do evidence-based interventions work when tested in the "real world?" A systematic review and meta-analysis of parent management training for the treatment of child disruptive behavior

Evidence-based interventions are often unavailable in everyday clinical settings. This may partly reflect practitioners’ assumptions that research evidence does not reflect “real-world” conditions. To examine this further, we systematically assessed the clinical effectiveness of parent management training (PMT) for the treatment of child disruptive behavior across different real-world practice contexts. We identified 28 relevant randomized controlled trials from a systematic search of electronic bibliographic databases and conducted a meta-analysis of child outcomes across trials. Planned subgroup analyses involved comparisons between studies grouped according to individual real-world practice criteria and total real-world practice criteria scores, reflecting the extent to which PMT was delivered by non-specialist therapists, to a clinic-referred population, in a routine setting, and as part of a routine service. Meta-analysis revealed a significant overall advantage for PMT compared with waitlist control conditions. Subgroup analyses did not demonstrate significant differences in effect size estimates according to the total number of real-world practice criteria met by studies. Moreover, no consistent relationships were found between specific practice criteria and effect size estimates. In conclusion, PMT appears to be an effective treatment for children with disruptive behavior problems. There was no clear evidence that conducting PMT in real-world practice contexts is a deterrent to achieving effective child behavior outcomes, although relative advantage to “usual care” was not directly examined and the power of the analysis was limited as a result of significant heterogeneity. More research is needed to investigate whether this finding is generalizable to other psychological interventions. Suggestions are also made for developing more differentiated criteria to assist with evaluating the specific applicability of research evidence to different care providers.

A systematic review and economic evaluation of subcutaneous and sublingual allergen immunotherapy in adults and children with seasonal allergic rhinitis

BACKGROUND Severe allergic rhinitis uncontrolled by conventional medication can substantially affect quality of life. Immunotherapy involves administering increasing doses of a specific allergen, with the aim of reducing sensitivity and symptomatic reactions. Recent meta-analyses have concluded that both subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) are more effective than placebo in reducing symptoms. It is uncertain which route of administration is more effective and whether or not treatment is cost-effective. OBJECTIVE To determine the comparative clinical effectiveness and cost-effectiveness of SCIT and SLIT for seasonal allergic rhinitis in adults and children. DATA SOURCES Electronic databases {MEDLINE, EMBASE, The Cochrane Library [Cochrane Central Register of Controlled Trials (CENTRAL)], NHS Economic Evaluation Database (NHS EED)} and trial registries (from inception up to April 2011). REVIEW METHODS Standard systematic review methods were used for study selection, data extraction and quality assessment. Double-blind randomised, placebo-controlled trials of SCIT or SLIT, or of SCIT compared with SLIT, and economic evaluations were included. Meta-analysis and indirect comparison meta-analysis and meta-regression were carried out. A new economic model was constructed to estimate cost-utility. RESULTS Meta-analyses found statistically significant effects for SCIT and SLIT compared with placebo across a number of outcome measures and for the vast majority of subgroup analyses (type and amount of allergen, duration of treatment). There was less evidence for children, but some results in favour of SLIT were statistically significant. Indirect comparisons did not provide conclusive results in favour of either SCIT or SLIT. Economic modelling suggested that, when compared with symptomatic treatment (ST), both SCIT and SLIT may become cost-effective at a threshold of £20,000-30,000 per quality-adjusted life-year (QALY) from around 6 years, or 5 years for SCIT compared with SLIT (NHS and patient perspective). LIMITATIONS It is uncertain to what extent changes in the outcome measures used in the trials translate into clinically meaningful benefits. Cost-effectiveness estimates are based on a simple model, limited data and a number of assumptions, and should be seen as indicative only. CONCLUSIONS A benefit from both SCIT and SLIT compared with placebo has been consistently demonstrated, but the extent of this effectiveness in terms of clinical benefit is unclear. Both SCIT and SLIT may be cost-effective compared with ST from around 6 years (threshold of £20,000-30,000 per QALY). Further research is needed to establish the comparative effectiveness of SCIT compared with SLIT and to provide more robust cost-effectiveness estimates. FUNDING The National Institute for Health Research Health Technology Assessment programme.

A systematic review of the clinical effectiveness of acupuncture for allergic rhinitis

BackgroundAllergies cause a considerable burden to both sufferers and the National Health Service. There is growing interest in acupuncture as a treatment for a range of conditions. Since acupuncture may modulate the immune system it could be a useful treatment for allergic rhinitis (AR) sufferers. We therefore assessed the evidence for the clinical effectiveness of acupuncture in patients with AR by performing a systematic review of the literature.MethodsSearches (to 2007) were conducted in all major databases for randomised controlled trials (RCTs) evaluating the clinical effectiveness of acupuncture in the treatment of AR. No limits were placed on language. Studies were included if they compared acupuncture to a sham or inactive acupuncture treatment (placebo) with or without standard care. Meta-analysis was performed where feasible.ResultsSeven relevant RCTs were included after screening and application of inclusion and exclusion criteria. The trials were generally of poor quality as assessed by a modified Jadad scale, with the exception of two studies which scored highly. A wide variety of outcomes was measured but most assessed symptom severity on a visual analogue scale. A meta-analysis failed to show any summary benefits of acupuncture treatment for symptom severity scores or serum IgE measures which could not have been accounted for by chance alone. Acupuncture was not associated with any additional adverse events in the trials.ConclusionThere is currently insufficient evidence to support or refute the use of acupuncture in patients with AR. A large well conducted RCT, which overcomes identified methodological problems in the existing RCTs, would be required to resolve this question.

Occipital Nerve Stimulation for Chronic Migraine—A Systematic Review and Meta-Analysis

Background Chronic migraine is a debilitating headache disorder that has significant impact on quality of life. Stimulation of peripheral nerves is increasingly being used to treat chronic refractory pain including headache disorders. This systematic review examines the effectiveness and adverse effects of occipital nerve stimulation (ONS) for chronic migraine. Methods Databases, including the Cochrane Library, MEDLINE, EMBASE, CINAHL and clinical trial registers were searched to September 2014. Randomized controlled trials (RCTs), other controlled and uncontrolled observational studies and case series (n≥ 10) were eligible. RCTs were assessed using the Cochrane risk of bias tool. Meta-analysis was carried out using a random-effects model. Findings are presented in summary tables and forest plots. Results Five RCTs (total n=402) and seven case series (total n=115) met the inclusion criteria. Pooled results from three multicenter RCTs show that ONS was associated with a mean reduction of 2.59 days (95% CI 0.91 to 4.27, I2=0%) of prolonged, moderate to severe headache per month at 3 months compared with a sham control. Results for other outcomes generally favour ONS over sham controls but quantitative analysis was hampered by incomplete publication and reporting of trial data. Lead migration and infections are common and often require revision surgery. Open-label follow-up of RCTs and case series suggest long-term effectiveness can be maintained in some patients but evidence is limited. Conclusions While the effectiveness of ONS compared to sham control has been shown in multiple RCTs, the average effect size is modest and may be exaggerated by bias as achieving effective blinding remains a methodological challenge. Further measures to reduce the risk of adverse events and revision surgery are needed. Systematic Review Registration this systematic review is an update and expanded work of part of a broader review registered with PROSPERO. Registration No. CRD42012002633.

Prehospital Blood Product Resuscitation for Trauma: A Systematic Review.

Introduction: Administration of high ratios of plasma to packed red blood cells is a routine practice for in-hospital trauma resuscitation. Military and civilian emergency teams are increasingly carrying prehospital blood products (PHBP) for trauma resuscitation. This study systematically reviewed the clinical literature to determine the extent to which the available evidence supports this practice. Methods: Bibliographic databases and other sources were searched to July 2015 using keywords and index terms related to the intervention, setting, and condition. Standard systematic review methodology aimed at minimizing bias was used for study selection, data extraction, and quality assessment (protocol registration PROSPERO: CRD42014013794). Synthesis was mainly narrative with random effects model meta-analysis limited to mortality outcomes. Results: No prospective comparative or randomized studies were identified. Sixteen case series and 11 comparative studies were included in the review. Seven studies included mixed populations of trauma and non-trauma patients. Twenty-five of 27 studies provided only very low quality evidence. No association between PHBP and survival was found (OR for mortality: 1.29, 95% CI: 0.84–1.96, P = 0.24). A single study showed improved survival in the first 24 h. No consistent physiological or biochemical benefit was identified, nor was there evidence of reduced in-hospital transfusion requirements. Transfusion reactions were rare, suggesting the short-term safety of PHBP administration. Conclusions: While PHBP resuscitation appears logical, the clinical literature is limited, provides only poor quality evidence, and does not demonstrate improved outcomes. No conclusions as to efficacy can be drawn. The results of randomized controlled trials are awaited.

A systematic review of objective burn scar measurements

BackgroundProblematic scarring remains a challenging aspect to address in the treatment of burns and can significantly affect the quality of life of the burn survivor. At present, there are few treatments available in the clinic to control adverse scarring, but experimental pharmacological anti-scarring strategies are now beginning to emerge. Their comparative success must be based on objective measurements of scarring, yet currently the clinical assessment of scars is not carried out systematically and is mostly based on subjective review of patients. However, several techniques and devices are being introduced that allow objective analysis of the burn scar. The aim of this article is to evaluate various objective measurement tools currently available and recommend a useful panel that is suitable for use in clinical trials of anti-scarring therapies.MethodsA systematic literature search was done using the Web of Science, PubMed and Cochrane databases. The identified devices were then classified and grouped according to the parameters they measured.The tools were then compared and assessed in terms of inter- and intra-rater reproducibility, ease of use and cost.ResultsAfter duplicates were removed, 5062 articles were obtained in the search. After further screening, 157 articles which utilised objective burn scar measurement systems or tools were obtained. The scar measurement devices can be broadly classified into those measuring colour, metric variables, texture, biomechanical properties and pathophysiological disturbances.ConclusionsObjective scar measurement tools allow the accurate and reproducible evaluation of scars, which is important for both clinical and scientific use. However, studies to evaluate their relative performance and merits of these tools are scarce, and there remain factors, such as itch and pain, which cannot be measured objectively. On reviewing the available evidence, a panel of devices for objective scar measurement is recommended consisting of the 3D cameras (Eykona/Lifeviz/Vectra H1) for surface area and volume, DSM II colorimeter for colour, Dermascan high-frequency ultrasound for scar thickness and Cutometer for skin elasticity and pliability.

Searching for the Optimal Fluid to Restore Microcirculatory Flow Dynamics After Haemorrhagic Shock: A Systematic Review of Preclinical Studies.

Background: Increased microcirculatory flow and perfusion has been reported to improve clinical outcomes following shock. The optimal resuscitation fluid to restore the flow dynamics of the microcirculation is unknown. This review summarizes the preclinical literature to inform the direction and most important hypotheses for future clinical interventional studies. Methods: Standard systematic review methodology was utilized, and registered with the Collaborative Approach to Meta Analysis and Review of Animal Data from Experimental Studies (CAMARADES). Medline and Embase (via OVID SP) and SCOPUS were searched for all preclinical studies of haemorrhagic shock that compared fluid resuscitation of any kind (e.g., blood products, crystalloids, colloids, or haemoglobin based oxygen carriers) to another fluid or haemorrhage only, and reported at least one microcirculatory physical endpoint (such as flow rate, velocity, vessel diameter, functional capillary density, or glycocalyx thickness). Risk of bias was assessed using the Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) tool. Translatability was also assessed for each study based on the most common recommendations. Results: There were 3,103 potential studies of interest, of which 71 studies fulfilled all eligibility criteria. There were 62 rodent, 5 canine, and 4 porcine studies. Flow rate, velocity, and vessel diameter were the most commonly reported endpoints. Studies reported the importance of the presence of haemoglobin, as well as osmotic potential and viscosity in providing optimal restoration of microcirculatory flow dynamics. Others reported the restoration of the endothelial glycocalyx and attenuation of inflammation as important properties for the choice of fluid. All studies were at potential risk of bias due to unclear randomization, concealment, and blinding. There were important threats to translatability for all studies. Conclusion: The ideal resuscitation fluid for restoration of the microcirculation following haemorrhagic shock is likely to contain a preparation of haemoglobin, favor higher oncotic potential, and viscosity, protect and reconstitute the endothelium, and attenuate inflammation. These hypotheses that are derived from preclinical research warrant further exploration in the clinical context.

Protocol for a systematic review of the clinical effectiveness of pre-hospital blood components compared to other resuscitative fluids in patients with major traumatic haemorrhage.

BackgroundThere is growing interest in the use of blood components for pre-hospital resuscitation of patients with major traumatic haemorrhage. It has been speculated that early resuscitation with blood components may have benefits in terms of treating trauma-induced coagulopathy, which in turn may influence survival. The proposed systematic review will evaluate the evidence on the clinical effectiveness of pre-hospital blood components (red blood cells and/or plasma or whole blood), in both civilian and military settings, compared with other resuscitation strategies in patients with major traumatic haemorrhage.Methods/designStandard systematic review methods aimed at minimising bias will be employed for study identification, selection and data extraction. General medical and specialist databases will be searched; the search strategy will combine terms for the population, intervention and setting. Studies will be selected for review if the population includes adult patients with major traumatic haemorrhage who receive blood components in a pre-hospital setting (civilian or military). Systematic reviews, randomised and non-randomised controlled trials and controlled observational studies will be included. Uncontrolled studies will be considered depending on the volume of controlled evidence. Quality assessment will be tailored to different study designs. Both patient related and surrogate outcomes will be considered. Synthesis is likely to be primarily narrative, but meta-analyses and subgroup analyses will be undertaken where clinical and methodological homogeneity exists.DiscussionGiven the increasing use by emergency services of blood components for pre-hospital resuscitation, this is a timely systematic review, which will attempt to clarify the evidence base for this practice. As far as the authors are aware, the proposed systematic review will be the first to address this topic.Systematic review registrationPROSPERO CRD42014013794