Interventions for the symptoms and signs resulting from jellyfish stings.

BACKGROUND: Jellyfish envenomation is common in many coastal regions and varies in severity depending upon the species. Stings cause a variety of symptoms and signs including pain, dermatological reactions, and, in some species, Irukandji syndrome (which may include abdominal/back/chest pain, tachycardia, hypertension, cardiac phenomena, and, rarely, death). Many treatments have been suggested for these symptoms, but their effectiveness is unclear. This is an update of a Cochrane Review last published in 2013. OBJECTIVES: To determine the benefits and harms associated with the use of any intervention, in both adults and children, for the treatment of jellyfish stings, as assessed by randomised and quasi-randomised trials. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and Web of Science up to 27 October 2022. We searched clinical trials registers and the grey literature, and conducted forward-citation searching of relevant articles.  SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs of any intervention given to treat stings from any species of jellyfish stings. Interventions were compared to another active intervention, placebo, or no treatment. If co-interventions were used, we included the study only if the co-intervention was used in each group.  DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane.  MAIN RESULTS: We included nine studies (six RCTs and three quasi-RCTs) involving a total of 574 participants. We found one ongoing study. Participants were either stung accidentally, or were healthy volunteers exposed to stings in a laboratory setting. Type of jellyfish could not be confirmed in beach settings and was determined by investigators using participant and local information. We categorised interventions into comparison groups: hot versus cold applications; topical applications. A third comparison of parenteral administration included no relevant outcome data: a single study (39 participants) evaluated intravenous magnesium sulfate after stings from jellyfish that cause Irukandji syndrome (Carukia). No studies assessed a fourth comparison group of pressure immobilisation bandages.  We downgraded the certainty of the evidence due to very serious risk of bias, serious and very serious imprecision, and serious inconsistency in some results.  Application of heat versus application of cold Four studies involved accidental stings treated on the beach or in hospital. Jellyfish were described as bluebottles (Physalia; location: Australia), and box jellyfish that do not cause Irukandji syndrome (Hawaiian box jellyfish (Carybdea alata) and major box jellyfish (Chironex fleckeri, location: Australia)). Treatments were applied with hot packs or hot water (showers, baths, buckets, or hoses), or ice packs or cold packs.  The evidence for all outcomes was of very low certainty, thus we are unsure whether heat compared to cold leads to at least a clinically significant reduction in pain within six hours of stings from Physalia (risk ratio (RR) 2.25, 95% confidence interval (CI) 1.42 to 3.56; 2 studies, 142 participants) or Carybdea alata and Chironex fleckeri (RR 1.66, 95% CI 0.56 to 4.94; 2 studies, 71 participants). We are unsure whether there is a difference in adverse events due to treatment (RR 0.50, 95% CI 0.05 to 5.19; 2 studies, 142 participants); these were minor adverse events reported for Physalia stings. We are also unsure whether either treatment leads to a clinically significant reduction in pain in the first hour (Physalia: RR 2.66, 95% CI 1.71 to 4.15; 1 study, 88 participants; Carybdea alata and Chironex fleckeri: RR 1.16, 95% CI 0.71 to 1.89; 1 study, 42 participants) or cessation of pain at the end of treatment (Physalia: RR 1.63, 95% CI 0.81 to 3.27; 1 study, 54 participants; Carybdea alata and Chironex fleckeri: RR 3.54, 95% CI 0.82 to 15.31; 1 study, 29 participants). Evidence for retreatment with the same intervention was only available for Physalia, with similar uncertain findings (RR 0.19, 95% CI 0.01 to 3.90; 1 study, 96 participants), as was the case for retreatment with the alternative hot or cold application after Physalia (RR 1.00, 95% CI 0.55 to 1.82; 1 study, 54 participants) and Chironex fleckeri stings (RR 0.48, 95% CI 0.02 to 11.17; 1 study, 42 participants). Evidence for dermatological signs (itchiness or rash) was available only at 24 hours for Physalia stings (RR 1.02, 95% CI 0.63 to 1.65; 2 studies, 98 participants).  Topical applications One study (62 participants) included accidental stings from Hawaiian box jellyfish (Carybdea alata) treated on the beach with fresh water, seawater, Sting Aid (a commercial product), or Adolph's (papain) meat tenderiser. In another study, healthy volunteers (97 participants) were stung with an Indonesian sea nettle (Chrysaora chinensis from Malaysia) in a laboratory setting and treated with isopropyl alcohol, ammonia, heated water, acetic acid, or sodium bicarbonate. Two other eligible studies (Carybdea alata and Physalia stings) did not measure the outcomes of this review.  The evidence for all outcomes was of very low certainty, thus we could not be certain whether or not topical applications provided at least a clinically significant reduction in pain (1 study, 62 participants with Carybdea alata stings, reported only as cessation of pain). For adverse events due to treatment, one study (Chrysaora chinensis stings) withdrew ammonia as a treatment following a first-degree burn in one participant. No studies evaluated clinically significant reduction in pain, retreatment with the same or the alternative treatment, or dermatological signs. AUTHORS' CONCLUSIONS: Few studies contributed data to this review, and those that did contribute varied in types of treatment, settings, and range of jellyfish species. We are unsure of the effectiveness of any of the treatments evaluated in this review given the very low certainty of all the evidence. This updated review includes two new studies (with 139 additional participants). The findings are consistent with the previous review.

Timing of submissions to The Journal of Paediatrics and Child Health: Associations with the COVID-19 pandemic and editorial decisions.

AIM: To determine if the timing of manuscript submissions to The Journal of Paediatrics and Child Health (JPCH) changed following the onset of the COVID-19 pandemic and to determine if the timing of manuscript submissions influenced editorial decisions. METHODS: A retrospective observational study of submissions to JPCH from 1 January 2015 to 1 August 2022 was performed. Regression models were used to explore the change over time. Editorial decisions were examined using a multinomial regression model with the three-category ordinal outcome of reject, revise and accept. All statistical models were fitted using a Bayesian approach and show 95% credible intervals (CI). RESULTS: The analyses included 11 499 manuscript submissions between 2015 and 2022. The mean number of manuscript submissions increased by 17 papers per month (CI 15-19), with a larger 4-month long increase after the COVID-19 pandemic was declared of 86 submissions per month (CI 67-103). There was no clear effect of the pandemic on weekend submissions, mean difference in probability 0.003 (CI -0.021 to 0.026). Throughout the study period, the peak submission time was later in the day and was shifted +37 min later post-March 2020 (CI +22 to +52 min). Throughout the study period, submissions out-of-hours and on weekends were less likely to get an editorial decision of 'accept' or 'revise': odds ratio weekend versus weekday 0.87 (CI 0.78-0.97). CONCLUSION: The COVID-19 pandemic had a limited effect on the timing of manuscript submissions to JPCH. However, the timing of manuscript submission impacted the likelihood of a more positive editorial decision. While the time of manuscript submission is only one part of the research process, it is postulated that it may be associated with research quality.

A systematic review of patient-reported outcome measures in paediatric endocrinology.

CONTEXT: Patient reported outcome measures (PROMs) are useful tools in paediatric endocrinology to gauge health status in children, especially since they are often unable to clearly communicate it themselves. We aimed to systematically search and appraise all available PROMs relevant to paediatric endocrinology and provide a curated resource for health professionals to utilise. EVIDENCE ACQUISITION: We identified PROMs in paediatric endocrinology by systematically searching the Cochrane Library, MEDLINE, World Health Organisation International Clinical Trials Registry Platform, and the Cumulative Index to Nursing and Allied Health Literature on May 20, 2022. Additional studies were located through hand searching and content area expert contributions. We assessed the quality of each PROM using the COSMIN risk of bias checklist. EVIDENCE SYNTHESIS: We identified 5003 papers in the initial search. After applying exclusion criteria we included seven PROMs in the review. Six PROMs were specific to Type I Diabetes and one to Hypothyroidism. We gave all studies an overall COSMIN score of 'inadequate' due to poorly detailed PROM development. CONCLUSION: The scope and quality of PROMs in paediatric endocrinology is limited. Further research and development of PROM tools are required in paediatric endocrinology to allow for improved patient care.

Fake news and fake research: Why meta-research matters more than ever.

Research is in a crisis of credibility, and this is to the peril of all paediatricians. Billions of dollars are being wasted each year because research is not planned, badly conducted or poorly reported, and this is on a background of rapidly reducing research budgets. How can paediatricians, families and patients make informed treatment choices if the evidence base is absent or not trustworthy? This article discusses why meta-research now matters more than ever, how it can help solve this crisis of credibility and how this should lead to more efficient and effective clinical care. The field of meta-research or research-on-research is the ultimate big picture approach to identifying and solving issues of bias, error, misconduct and waste in research. Meta-researchers value authenticity over aesthetics and quality over quantity. The utility of meta-research does not rely on accusations or critical assessments of individual research, but through highlighting where and how the scientific method and research standards across all fields can be improved. Meta-researchers study, analyse and critique the research pathway, focusing on elements such as methods (how to conduct), evaluation (how to test), reporting (how to communicate), reproducibility (how to verify) and incentives (how to reward). In the current climate it is now more critical than ever that we make use of meta-research and prioritise high-quality high-impact research, ultimately leading to improved patient outcomes.

How to Include Patient-Reported Outcome Measures in Clinical Trials.

PURPOSE OF REVIEW: Patient-reported outcome measures are increasingly important measures of patient experience, which can increase research robustness, maximise economic value and improve patient outcomes. This review outlines the benefits, challenges and practicalities of incorporating patient-reported outcome measures in clinical trials. RECENT FINDINGS: Patient-reported outcome measures are often the best way of measuring patient symptoms and quality of life. Patient-reported outcome measures can help reduce observer bias, engage patients in the research process, and inform health service resource planning. A range of tools exist to help facilitate clinicians and researchers in selecting and utilising patient reported outcome measures. Key issues to consider when selecting an appropriate tool include the development, format and psychometric properties of the patient-reported outcome measures. The use of patient-reported outcome measures allow us to better understand the patient experience and their values. A range of tools exist to help facilitate the use of patient-reported outcome measures. This article outlines how we can incorporate patient-reported outcome measures in clinical trials.

Assessing guideline adherence in the management of type 1 diabetes mellitus in Australian children: a population-based sample survey.

INTRODUCTION: To estimate adherence to clinical practice guidelines in selected settings at a population level for Australian children with type 1 diabetes mellitus. RESEARCH DESIGN AND METHODS: Medical records of children with type 1 diabetes mellitus aged 0-15 years in 2012-2013 were targeted for sampling across inpatient, emergency department and community visits with specialist pediatricians in regional and metropolitan areas and tertiary pediatric hospitals in three states where approximately 60% of Australian children reside. Clinical recommendations extracted from two clinical practice guidelines were used to audit adherence. Results were aggregated across types of care (diagnosis, routine care, emergency care). RESULTS: Surveyors conducted 6346 indicator assessments from an audit of 539 healthcare visits by 251 children. Average adherence across all indicators was estimated at 79.9% (95% CI 69.5 to 88.0). Children with type 1 diabetes mellitus have higher rates of behavioral and psychological disorders, but only a third of children (37.9%; 95% CI 11.7 to 70.7) with suboptimal glycemic control (eg, hemoglobin A1c >10% or 86 mmol/mol) were screened for psychological disorders using a validated tool; this was the only indicator with <50% estimated adherence. Adherence by care type was: 86.1% for diagnosis (95% CI 76.7 to 92.7); 78.8% for routine care (95% CI 65.4 to 88.9) and 83.9% for emergency care (95% CI 78.4 to 88.5). CONCLUSIONS: Most indicators for care of children with type 1 diabetes mellitus were adhered to. However, there remains room to improve adherence to guidelines for optimization of practice consistency and minimization of future disease burden.

Management for intussusception in children.

BACKGROUND: Intussusception is a common abdominal emergency in children with significant morbidity. Prompt diagnosis and management reduces associated risks and the need for surgical intervention. Despite widespread agreement on the use of contrast enema as opposed to surgery for initial management in most cases, debate persists on the appropriate contrast medium, imaging modality, pharmacological adjuvant, and protocol for delayed repeat enema, and on the best approach for surgical management for intussusception in children. OBJECTIVES: To assess the safety and effectiveness of non-surgical and surgical approaches in the management of intussusception in children. SEARCH METHODS: We searched the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 8) in the Cochrane Library; Ovid MEDLINE (1950 to September 2016); Ovid Embase (1974 to September 2016); Science Citation Index Expanded (via Web of Science) (1900 to September 2016); and BIOSIS Previews (1969 to September 2016).We examined the reference lists of all eligible trials to identify additional studies. To locate unpublished studies, we contacted content experts, searched the World Health Organization International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov (September 2016), and explored proceedings from meetings of the British Association of Paedatric Surgeons (BAPS), the American Soceity of Pediatric Surgery, and the World Congress of Pediatric Surgery. SELECTION CRITERIA: We included all randomised controlled trials comparing contrast media, imaging modalities, pharmacological adjuvants, protocols for delayed repeat enema, and/or surgical approaches for the management of intussusception in children. We applied no language, publication date, or publication status restrictions. DATA COLLECTION AND ANALYSIS: Two review authors independently conducted study selection and data extraction and assessed risk of bias using a standardised form. We resolved disagreements by consensus with a third review author when necessary. We reported dichotomous outcomes as risk ratios (RRs) with 95% confidence intervals (CIs). We analysed data on an intention-to-treat basis and evaluated the overall quality of evidence supporting the outcomes by using GRADE criteria. MAIN RESULTS: We included six randomised controlled trials (RCTs) with a total of 822 participants. Two trials compared liquid enema reduction plus glucagon versus liquid enema alone. One trial compared liquid enema plus dexamethasone versus liquid enema alone. Another trial compared air enema plus dexamethasone versus air enema alone, and two trials compared use of liquid enema versus air enema. We identified three ongoing trials.We judged all included trials to be at risk of bias owing to omissions in reported methods. We judged five of six trials as having high risk of bias in at least one domain. Therefore, the quality of the evidence (GRADE) for outcomes was low. Interventions and data presentation varied greatly across trials; therefore meta-analysis was not possible for most review outcomes. Enema plus glucagon versus enema alone It is uncertain whether use of glucagon improves the rate of successful reduction of intussusception when compared with enema alone (reported in two trials, 218 participants; RR 1.09, 95% CI 0.94 to 1.26;low quality of evidence). No trials in this comparison reported on the number of children with bowel perforation(s) nor on the number of children with recurrent intussusception. Enema plus dexamethasone versus enema alone Use of the adjunct, dexamethasone, may be beneficial in reducing intussusception recurrence with liquid or air enema (two trials, 299 participants; RR 0.14, 95% CI 0.03 to 0.60; low quality of evidence). This equates to a number needed to treat for an additional beneficial outcome of 13 (95% CI 8 to 37). It is uncertain whether use of the adjunct, dexamethasone, improves the rate of successful reduction of intussusception when compared with enema alone (reported in two trials, 356 participants; RR 1.01, 95% CI 0.92 to 1.10;low quality of evidence). Air enema versus liquid enema Air enema may be more successful than liquid enema for reducing intussusception (two trials, 199 participants; RR 1.28, 95% CI 1.10 to 1.49; low quality of evidence). This equates to a number needed to treat for an additional beneficial outcome of 6 (95% CI 4 to 19). No trials in this comparison reported on the number of children with bowel perforation(s) or on the number of children with recurrent intussusception nor any intraoperative complications, such as bowel perforation, or other adverse effects. Only one trial reported postoperative complications, but owing to the method of reporting used, a quantitative analysis was not possible. We identified no studies that exclusively evaluated surgical interventions for management of intussusception. AUTHORS' CONCLUSIONS: This review identified a small number of trials that assessed a variety of interventions. All included trials provided evidence of low quality and were subject to serious concerns about imprecision, high risk of bias, or both. Air enema may be superior to liquid enema for successfully reducing intussusception in children; however, this finding is based on a few studies including small numbers of participants. Dexamethasone as an adjuvant may be more effective in reducing intussusception recurrence rates following air enema or liquid enema, but these results are also based on a few studies of small numbers of participants. This review highlights several points that need to be addressed in future studies, including reducing the risk of bias and including relevant outcomes. Specifically, surgical trials are lacking, and future research is needed to address this evidence gap.

Probiotics for people with hepatic encephalopathy.

BACKGROUND: Hepatic encephalopathy is a disorder of brain function as a result of liver failure or portosystemic shunt or both. Both hepatic encephalopathy (clinically overt) and minimal hepatic encephalopathy (not clinically overt) significantly impair patient's quality of life and daily functioning, and represent a significant burden on healthcare resources. Probiotics are live micro-organisms, which when administered in adequate amounts, may confer a health benefit on the host. OBJECTIVES: To determine the beneficial and harmful effects of probiotics in any dosage, compared with placebo or no intervention, or with any other treatment for people with any grade of acute or chronic hepatic encephalopathy. This review did not consider the primary prophylaxis of hepatic encephalopathy. SEARCH METHODS: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, conference proceedings, reference lists of included trials, and the World Health Organization International Clinical Trials Registry Platform until June 2016. SELECTION CRITERIA: We included randomised clinical trials that compared probiotics in any dosage with placebo or no intervention, or with any other treatment in people with hepatic encephalopathy. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by The Cochrane Collaboration. We conducted random-effects model meta-analysis due to obvious heterogeneity of participants and interventions. We defined a P value of 0.05 or less as significant. We expressed dichotomous outcomes as risk ratio (RR) and continuous outcomes as mean difference (MD) with 95% confidence intervals (CI). MAIN RESULTS: We included 21 trials with 1420 participants, of these, 14 were new trials. Fourteen trials compared a probiotic with placebo or no treatment, and seven trials compared a probiotic with lactulose. The trials used a variety of probiotics; the most commonly used group of probiotic was VSL#3, a proprietary name for a group of eight probiotics. Duration of administration ranged from 10 days to 180 days. Eight trials declared their funding source, of which six were independently funded and two were industry funded. The remaining 13 trials did not disclose their funding source. We classified 19 of the 21 trials at high risk of bias.We found no effect on all-cause mortality when probiotics were compared with placebo or no treatment (7 trials; 404 participants; RR 0.58, 95% CI 0.23 to 1.44; low-quality evidence). No-recovery (as measured by incomplete resolution of symptoms) was lower for participants treated with probiotic (10 trials; 574 participants; RR 0.67, 95% CI 0.56 to 0.79; moderate-quality evidence). Adverse events were lower for participants treated with probiotic than with no intervention when considering the development of overt hepatic encephalopathy (10 trials; 585 participants; RR 0.29, 95% CI 0.16 to 0.51; low-quality evidence), but effects on hospitalisation and change of/or withdrawal from treatment were uncertain (hospitalisation: 3 trials, 163 participants; RR 0.67, 95% CI 0.11 to 4.00; very low-quality evidence; change of/or withdrawal from treatment: 9 trials, 551 participants; RR 0.70, 95% CI 0.46 to 1.07; very low-quality evidence). Probiotics may slightly improve quality of life compared with no intervention (3 trials; 115 participants; results not meta-analysed; low-quality evidence). Plasma ammonia concentration was lower for participants treated with probiotic (10 trials; 705 participants; MD -8.29 µmol/L, 95% CI -13.17 to -3.41; low-quality evidence). There were no reports of septicaemia attributable to probiotic in any trial.When probiotics were compared with lactulose, the effects on all-cause mortality were uncertain (2 trials; 200 participants; RR 5.00, 95% CI 0.25 to 102.00; very low-quality evidence); lack of recovery (7 trials; 430 participants; RR 1.01, 95% CI 0.85 to 1.21; very low-quality evidence); adverse events considering the development of overt hepatic encephalopathy (6 trials; 420 participants; RR 1.17, 95% CI 0.63 to 2.17; very low-quality evidence); hospitalisation (1 trial; 80 participants; RR 0.33, 95% CI 0.04 to 3.07; very low-quality evidence); intolerance leading to discontinuation (3 trials; 220 participants; RR 0.35, 95% CI 0.08 to 1.43; very low-quality evidence); change of/or withdrawal from treatment (7 trials; 490 participants; RR 1.27, 95% CI 0.88 to 1.82; very low-quality evidence); quality of life (results not meta-analysed; 1 trial; 69 participants); and plasma ammonia concentration overall (6 trials; 325 participants; MD -2.93 µmol/L, 95% CI -9.36 to 3.50; very low-quality evidence). There were no reports of septicaemia attributable to probiotic in any trial. AUTHORS' CONCLUSIONS: The majority of included trials suffered from a high risk of systematic error ('bias') and a high risk of random error ('play of chance'). Accordingly, we consider the evidence to be of low quality. Compared with placebo or no intervention, probiotics probably improve recovery and may lead to improvements in the development of overt hepatic encephalopathy, quality of life, and plasma ammonia concentrations, but probiotics may lead to little or no difference in mortality. Whether probiotics are better than lactulose for hepatic encephalopathy is uncertain because the quality of the available evidence is very low. High-quality randomised clinical trials with standardised outcome collection and data reporting are needed to further clarify the true efficacy of probiotics.

Pain from bluebottle jellyfish stings.

An 11-year-old girl presented to the emergency department with severe pain after a jellyfish sting at a New South Wales beach. Bluebottle (Physalia) jellyfish was deemed the most likely cause considering her geographical location. The Australian Resuscitation Council Guideline (2010) suggests immersing in water as hot as can be tolerated for 20 min for treating pain from jellyfish stings. This guideline was written based on past case reports, books and randomised controlled trials (RCTs). We performed a search to assess the most current evidence for relief of pain from Bluebottle jellyfish stings, which yielded two systematic reviews and seven RCTs. Both systematic reviews had similar conclusions, with one of the RCTs used in both reviews showing the most relevance to our presenting patient in terms of demographics, location and jellyfish type. This journal club article is an appraisal of this RCT by Loten et al. and the validity of its conclusion that hot water immersion is most effective for the relief of pain from Bluebottle stings.

Interventions for the symptoms and signs resulting from jellyfish stings.

BACKGROUND: Jellyfish envenomations are common amongst temperate coastal regions and vary in severity depending on the species. Stings result in a variety of symptoms and signs, including pain, dermatological reactions and, in some species, Irukandji syndrome (including abdominal/back/chest pain, tachycardia, hypertension, sweating, piloerection, agitation and sometimes cardiac complications). Many treatments have been suggested for the symptoms and signs of jellyfish stings. However, it is unclear which interventions are most effective. OBJECTIVES: To determine the benefits and harms associated with the use of any intervention, in both adults and children, for the treatment of jellyfish stings, as assessed from randomised trials. SEARCH METHODS: We searched the following electronic databases in October 2012 and again in October 2013: the Cochrane Central Register of Controlled Trials (CENTRAL;The Cochrane Library, Issue 9, 2013); MEDLINE via Ovid SP (1948 to 22 October 2013); EMBASE via Ovid SP (1980 to 21 October 2013); and Web of Science (all databases; 1899 to 21 October 2013). We also searched reference lists from eligible studies and guidelines, conference proceedings and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and contacted content experts to identify trials. SELECTION CRITERIA: We included randomised controlled trials that compared any intervention(s) to active and/or non-active controls for the treatment of symptoms and signs of jellyfish sting envenomation. No language, publication date or publication status restrictions were applied. DATA COLLECTION AND ANALYSIS: Two review authors independently conducted study selection and data extraction and assessed risk of bias using a standardised form. Disagreements were resolved by consensus with a third review author when necessary. MAIN RESULTS: We included seven trials with a total of 435 participants. Three trials focused on Physalia (Bluebottle) jellyfish, one trial on Carukia jellyfish and three on Carybdea alata (Hawaiian box) jellyfish. Two ongoing trials were identified.Six of the seven trials were judged as having high risk of bias. Blinding was not feasible in four of the included trials because of the nature of the interventions. A wide range of interventions were assessed across trials, and a wide range of outcomes were measured. We reported results from the two trials for which data were available and reported the effects of interventions according to our definition of primary or secondary outcomes.Hot water immersion was superior to ice packs in achieving clinically significant (at least 50%) pain relief at 10 minutes (one trial, 96 participants, risk ratio (RR) 1.66, 95% confidence interval (CI) 1.01 to 2.72; low-quality evidence) and 20 minutes (one trial, 88 participants, RR 2.66, 95% CI 1.71 to 4.15; low-quality evidence). No statistically significant differences between hot water immersion and ice packs were demonstrated for dermatological outcomes.Treatment with vinegar or Adolph's meat tenderizer compared with hot water made skin appear worse (one trial, 25 participants, RR 0.31, 95% CI 0.14 to 0.72; low-quality evidence).Adverse events due to treatment were not reported in any trial. AUTHORS' CONCLUSIONS: This review located a small number of trials that assessed a variety of different interventions applied in different ways and in different settings. Although heat appears to be an effective treatment for Physalia (Bluebottle) stings, this evidence is based on a single trial of low-quality evidence. It is still unclear what type of application, temperature, duration of treatment and type of water (salt or fresh) constitute the most effective treatment. In addition, these results may not apply to other species of jellyfish with different envenomation characteristics. Future research should further assess the most effective interventions using standardised research methodology.

Systematic reviews of surgical procedures in children: quantity, coverage and quality.

AIM: Systematic reviews have the potential to map those areas where children are under-represented in surgical research. We aimed to describe and evaluate the quantity, coverage and the quality of conduct and reporting of systematic reviews of surgical procedures in children. METHODS: We searched four biomedical databases, a systematic review register, reference lists and conducted hand searching to identify relevant reviews. Two reviewers worked independently to critically appraise included studies and abstract data. We assessed reporting quality using the preferred reporting items for systematic reviews and meta-analysis statement and methodological quality using the Assessment of Multiple SysTemAtic Reviews tool. RESULTS: Fifteen systematic reviews were identified, representing 0.01% of all paediatric surgical citations in MEDLINE and Embase. Thirteen of the reviews were Cochrane reviews, and most reviews (12/15) addressed subspecialty interests such as otorhinolaryngology. The median number of included trials per systematic review was four (interquartile range 1 to 9.5), the median number of primary outcomes was 5.5 (interquartile range 3.5 to 7.5). In general, reporting and methodological quality was good although there were several omissions, particularly around completeness of reporting of statistical methods used, and utilisation of quality assessments in analyses. Outcomes were often not clearly defined and descriptions of procedures lacked sufficient detail to determine the similarities and differences among surgical procedures within the contributing trials. CONCLUSION: Systematic reviews of surgical procedures in children are rarely published. To improve the evidence base and guide research agendas, more systematic reviews should be conducted, using standard guidelines for conduct and reporting.

Exercise training in solid organ transplant recipients: a systematic review and meta-analysis.

BACKGROUND: Exercise training is effective in improving the cardiovascular risk profiles of nontransplanted patients, but the health benefits and potential harms of routine exercise training after solid organ transplantation are unclear. This study aims to assess the health benefits and harms of supervised exercise training programs in solid organ recipients. METHODS: We systematically reviewed all randomized controlled trials (RCTs) comparing the outcomes of exercise training programs in solid organ recipients against standard care. MEDLINE, EMBASE, the Transplant Library from the Centre for Evidence in Transplantation, and the Cochrane Central Register of Controlled Trials were searched to June 2012. RESULTS: In total, 15 eligible RCTs involving 643 patients (9 cardiac transplants [n=250 patients], 2 kidney transplants [n=164 patients], 3 lung transplants [n=110 patients], and 1 liver transplant [n=119 patients]) were included. Cardiac transplant recipients who engaged in an exercise program after transplantation showed significant improvement in maximal oxygen uptake (standardized mean difference, 0.77; 95% confidence interval, 0.10-1.45) but no improvement in the overall serum lipid profile, blood pressure, and glycemic control compared with standard care. Among other solid organ transplant recipients, no significant improvements in exercise capacity or cardiovascular risk factors such as incidence of new-onset diabetes after transplantation were observed, but all effect estimates were very imprecise. CONCLUSIONS: Exercise training is a promising but unproven intervention for improving the cardiovascular outcomes of solid organ transplant recipients. Existing trials are small, of relatively short duration, and focused on surrogate outcomes. Large-scale RCTs are urgently required if resources are to be directed toward exercise programs.

Medical device regulation in Australia: safe and effective?

OBJECTIVE: To describe the frequency, characteristics and outcomes of reports of possible harms related to medical devices submitted to the Australian Therapeutic Goods Administration (TGA) using data made publicly available on the TGA website. DESIGN AND SETTING: A retrospective analysis, conducted in January 2012, of data made publicly available on the TGA website from January 2000 to December 2011. MAIN OUTCOME MEASURES: The number and nature of reports of medical device incidents, recalls and alerts. RESULTS: Up to December 2011, 6812 incidents involving medical devices were reported to the TGA, although there were several periods where data were unavailable. Incidents were reported more frequently in later years, most often by device sponsors, and were often attributed to mechanical problems. 295 deaths and 2357 serious injuries have been related to incidents, with serious injury (597) highest in 2009. Most incidents involving medical devices were not investigated (47.5%), or, after investigation, no further action was taken (25.0%). During the same time period, there were 35 medical device recalls and 34 medical device alerts issued by the TGA, with no consistent increase over time. CONCLUSIONS: Despite TGA reform proposals, greater transparency is still needed. Issues that have not been addressed include patchy and conflicting data in the public domain and lack of explanations for the large proportion of uninvestigated reports. To maintain public confidence in the national regulatory system these problems need to be resolved.

Probiotics for patients with hepatic encephalopathy.

BACKGROUND: Hepatic encephalopathy is a disorder of brain function as a result of liver failure and/or portosystemic shunt. Both hepatic encephalopathy (clinically overt) and minimal hepatic encephalopathy (not clinically overt) significantly impair patient's quality of life and daily functioning and represent a significant burden on health care resources. Probiotics are live microorganisms, which when administered in adequate amounts may confer a health benefit on the host. OBJECTIVES: To quantify the beneficial and harmful effects of any probiotic in any dosage, compared with placebo or no intervention, or with any other treatment for patients with any grade of acute or chronic hepatic encephalopathy as assessed from randomised trials. SEARCH METHODS: We searched the The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, conference proceedings, reference lists of included trials and the WHO international clinical trials registry until April 2011 registry platform to identify new and ongoing trials. SELECTION CRITERIA: We included randomised trials that compared probiotics in any dosage with placebo or no intervention, or with any other treatment in patients with hepatic encephalopathy. DATA COLLECTION AND ANALYSIS: Three authors independently assessed the risk of bias of the included trials and extracted data on relevant outcomes, with differences resolved by consensus. We conducted random-effects model meta-analysis due to obvious heterogeneity of patients and interventions. A P value of 0.05 or less was defined as significant. Dichotomous outcomes are expressed as risk ratio (RR) and continuous outcomes as mean difference (MD) with 95% confidence intervals (CI). MAIN RESULTS: We included seven trials of which 550 participants were randomised. Four of the seven trials compared a probiotic with placebo or no treatment in 245 participants, another trial compared a probiotic with lactulose in 40 participants , and the remaining two trials compared a probiotic with both placebo and lactulose in 265 participants. Each trial used different types of probiotics. Duration of administration of the experimental intervention varied from 10 days to 180 days. Two trials were industry funded, and five were unclear about origin of funding. All trials had high risk of bias. When probiotics were compared with no treatment, there was no significant difference in all-cause mortality (2 trials, 105 participants; 1/57 (2%) versus 1/48 (2%): RR 0.72; 95% CI 0.08 to 6.60), lack of recovery (4 trials, 206 participants; 54/107 (50%) versus 68/99 (69%): RR 0.72; 95% CI 0.49 to 1.05), adverse events (3 trials, 145 participants; 2/77 (3%) versus 6/68 (9%): RR 0.34; 95% CI 0.08 to 1.42), quality of life (1 trial, 20 participants contributed to the physical quality of life measurement, 20 participants contributed to the mental quality of life: MD Physical 0.00; 95% CI -5.47 to 5.47; MD Mental 4.00; 95% CI -1.82 to 9.82), or change of/or withdrawal from treatment (3 trials, 175 participants; 11/92 (12%) versus 7/83 (8%): RR 1.28; 95% CI 0.52 to 3.19). No trial reported sepsis or duration of hospital stay as an outcome. Plasma ammonia concentration was significantly lower for participants treated with probiotic at one month (3 trials, 226 participants: MD -2.99 µmol/L; 95% CI -5.70 to -0.29) but not at two months (3 trials, 181 participants: MD -1.82 µmol/L; 95% CI -14.04 to 10.41). Plasma ammonia decreased the most in the participants treated with probiotic at three months (1 trial, 73 participants: MD -6.79 µmol/L; 95% CI -10.39 to -3.19). When probiotics were compared with lactulose no trial reported all-cause mortality, quality of life, duration of hospital stay, or septicaemia. There were no significant differences in lack of recovery (3 trials, 173 participants; 47/87 (54%) versus 44/86 (51%): RR 1.05; 95% CI 0.75 to 1.47), adverse events (2 trials, 111 participants; 3/56 (5%) versus 6/55 (11%): RR 0.57; 95% CI 0.06 to 5.74), change of/or withdrawal from treatment at one month (3 trials, 190 participants; 8/95 (8%) versus 7/95 (7%): RR 1.10; 95% CI 0.40 to 3.03), plasma ammonia concentration (2 trials, 93 participants: MD -6.61 µmol/L; 95% CI -30.05 to 16.84), or change in plasma ammonia concentration (1 trial, 77 participants: MD 1.16 µmol/L; 95% CI -1.96 to 4.28). AUTHORS' CONCLUSIONS: The trials we located suffered from a high risk of systematic errors ('bias') and high risk of random errors ('play of chance'). While probiotics appear to reduce plasma ammonia concentration when compared with placebo or no intervention, we are unable to conclude that probiotics are efficacious in altering clinically relevant outcomes. Demonstration of unequivocal efficacy is needed before probiotics can be endorsed as effective therapy for hepatic encephalopathy. Further randomised clinical trials are needed.

Trial registration and declaration of registration by authors of randomized controlled trials.

BACKGROUND: Trial registration was introduced to reduce research bias by promoting trial transparency and accountability. We aimed to evaluate the frequency of, and factors associated with, trial registration and declaration of trial registration. METHODS: We selected all randomized controlled trials in kidney transplantation published between October 2005 and December 2010 and determined whether a trial was registered and whether a trial declared their registration in subsequent trial reports. RESULTS: Of 307 eligible trials identified, 24% (74/307) were registered, and of those, 59% (44/74) contained trial registration details within at least one trial report. Trial registration was more likely for trials published more than once, in later years or reported in journals that followed the International Committee of Medical Journal Editors guidelines. Trial registration was less likely for trials that did not declare their funding sources. Registered trials were more likely to declare registration details in related reports if published in later years or in a journal that followed International Committee of Medical Journal Editors guidelines. Trials that did not declare their funding sources were less likely to declare registration details. CONCLUSIONS: Although still suboptimal, the situation is improving over time, with both trial registration and declaration of registration details more likely in later years.