Argumentation Analysis of Risk Assessments: The Case of Perfluorooctanoic Acid.

Risk assessment of chemicals can be based on toxicology and/or epidemiology. The choice of toxicological or epidemiological data can result in different health-based guidance values (HBGVs). Communicating the underlying argumentation is important to explain these differences to the public and policymakers. In this article, we explore the argumentation used to justify the use of toxicological or epidemiological data in the derivation of HBGVs in four different risk assessments for the chemical Perfluorooctanoic acid (PFOA). The pragma-dialectical argumentation theory (PDAT) is hereby applied. The argumentations to select relevant health endpoints or certain studies to infer causality appeared mainly based on "symptomatic relations," that is, study results are used as characteristic of what was claimed to be a causal relation without delving into the actual causal argumentation that preceded it. Starting points that are at the basis of the chain of arguments remained implicit. Argumentation to use epidemiological and/or toxicological data was only briefly mentioned and the underlying argumentative foundation that led to the conclusion was seldom found or not addressed at all. The decision to include/exclude information was made based on the availability of data, or the motives for the choice remained largely unclear. We conclude that more depth in argumentation and a subordinative chain of arguments is needed to better disclose the underlying reasoning leading to a certain health-based guidance value (HBGV). More explicit identification and discussion of starting points could be a valuable addition to general risk assessment frameworks for maximum use of toxicological and epidemiological data and shared conclusions of the assessment.

A systematic review and trial sequential analysis of intravenous vs. oral peri-operative paracetamol.

Postoperative pain might be different after intravenous vs. oral paracetamol. We systematically reviewed randomised controlled trials in patients >15 years that compared intravenous with oral paracetamol for postoperative pain. We identified 14 trials with 1695 participants. There was inconclusive evidence for an effect of route of paracetamol administration on postoperative pain at 0-2 h (734 participants), 2-6 h (766 participants), 6-24 h (1115 participants) and >24 h (248 participants), with differences in standardised mean (95%CI) pain scores for intravenous vs. oral of -0.17 (-0.45 to 0.10), -0.09 (-0.24 to 0.06), 0.06 (-0.12 to 0.23) and 0.03 (-0.22 to 0.28), respectively. Trial sequential analyses suggested that a total of 3948 participants would be needed to demonstrate a meaningful difference in pain or its absence at 0-2 h. There were no differences in secondary outcomes. Intravenous paracetamol is more expensive than oral paracetamol. Substitution of oral paracetamol in half the patients given intravenous paracetamol in our hospital would save around £ 38,711 (€ 43,960 or US$ 47,498) per annum.

A systematic review of phenylephrine vs. noradrenaline for the management of hypotension associated with neuraxial anaesthesia in women undergoing caesarean section.

Phenylephrine is recommended for the management of hypotension after spinal anaesthesia in women undergoing caesarean section. Noradrenaline, an adrenergic agonist with weak ß-adrenergic activity, has been reported to have a more favourable haemodynamic profile than phenylephrine. However, there are concerns that noradrenaline may be associated with a higher risk of fetal acidosis, defined as an umbilical artery pH < 7.20. We performed a systematic review of trials comparing noradrenaline with phenylephrine, concentrating on primary outcomes of fetal acidosis and maternal hypotension. We identified 13 randomised controlled trials including 2002 patients. Heterogeneity among the studies was high, and there were too few data to calculate a pooled effect estimate. Fetal acidosis was assessed in four studies that had a low risk of bias and a low risk of confounding, that is, studies which used a prophylactic vasopressor and where women received the allocated vasopressor only. There were no significant differences between these studies. No significant differences were observed for hypotension. Two trials found a significantly lower incidence of bradycardia when using noradrenaline. Cardiac output was significantly higher after noradrenaline in two of three studies. For other secondary outcomes including nausea, vomiting and Apgar scores at 1 and 5 min, no studies found significant differences. The evidence so far is too limited to support an advantage of noradrenaline over phenylephrine. Concerns of a deleterious effect of noradrenaline on fetal blood gas status cannot currently be assuaged by the available data from randomised controlled studies.

Intrathecal catheterisation after observed accidental dural puncture in labouring women: update of a meta-analysis and a trial-sequential analysis.

BACKGROUND: Our meta-analysis from 2013 showed that inserting a catheter intrathecally after an observed accidental dural puncture can reduce the need for epidural blood patch in labouring women requesting epidural analgesia. We updated our conventional meta-analysis and added a trial-sequential analysis (TSA). METHODS: A systematic literature search was conducted to identify studies that compared inserting the catheter intrathecally with an epidural catheter re-site or with no intervention. The extracted data were pooled and the risk ratio (RR) and 95% confidence interval (95%CI) for the incidence of post-dural puncture headache (PDPH) was calculated, using the random effects model. A contour-enhanced funnel plot was constructed. A TSA was performed and the cumulative Z score, monitoring and futility boundaries were constructed. RESULTS: Our search identified 13 studies, reporting on 1653 patients, with a low risk of bias. The RR for the incidence of PDPH was 0.82 (95%CI 0.71 to 0.95) and the RR for the need for epidural blood patch was 0.62 (95%CI 0.49 to 0.79); heterogeneity of both analyses was high. The TSA showed that the monitoring or futility boundaries were not crossed, indicating insufficient data to exclude a type I error of statistical analysis. Contour-enhanced funnel plots were symmetric, suggesting no publication bias. CONCLUSIONS: Conventional meta-analyses showed for the first time that intrathecal catheterisation can reduce the incidence of PDPH. However, TSA did not corroborate this finding. Despite increasing use in clinical practice there is no firm evidence on which to base a definite conclusion.

Dural puncture epidural versus conventional epidural block for labor analgesia: a systematic review of randomized controlled trials.

INTRODUCTION: Dural puncture epidural (DPE) analgesia is a modification of conventional epidural analgesia that involves the intentional puncture of the dura with a spinal needle through the needle placed in the epidural space, without a medication being injected intrathecally. There have been contradictory findings regarding better analgesia and better block quality. METHODS: A systematic literature search was done to identify randomized controlled trials (RCT) comparing DPE with epidural analgesia. The risk of bias was assessed with the Cochrane tool. Risk ratio and 95% confidence intervals were calculated. RESULTS: Five RCTs including 581 patients were identified. One RCT on caesarean section was excluded. Single studies suggested slightly better analgesia by finding a median time to achieve sufficient analgesia of two minutes less in the DPE group, a higher number of women having a pain score <10/100 at 20 min, a reduction in the number of epidural top-ups and better sacral spread. The studies did not show a difference between DPE and epidural analgesia for catheter replacement or manipulation rates, the incidence of intravascular placement or unilateral block. CONCLUSION: There is a lack of clear evidence on either the benefits or therisks of the DPE technique, such that a recommendation for or against its routine use is premature. Two of the three studies showing a beneficial effect of DPE came from the same institution and replication of the findings by other groups is warranted.

Effect of intravenous dexamethasone on postoperative pain after spinal anaesthesia - a systematic review with meta-analysis and trial sequential analysis.

There are data suggesting that intravenous dexamethasone has an effect on postoperative analgesia when given during single-shot spinal anaesthesia. However, the research literature is equivocal. We performed a systematic literature search followed by conventional meta-analysis (random effects model). We used trial sequential analysis to control for type-1 and -2 statistical errors. We also performed a leave-one-out meta-analysis for our primary outcome, the consumption of intravenous morphine in the first 24 postoperative hours. We applied the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to rate the level of evidence. We obtained data from 1133 patients, reported in 17 trials. Reporting quality was high, with low risk of bias. Dexamethasone use was associated with a significant reduction in 24-h morphine consumption, the mean difference (95%CI) being -4.01 (-5.01 to -3.01) mg, 6 trials, 326 participants, I2 = 0%. Trial sequential analysis showed that there was firm evidence for the primary outcome, and leave-one-out meta-analysis showed that our result was not driven by one single trial. The GRADE evaluation showed a high level of evidence, suggesting that further studies are unlikely to alter the result. The time to first analgesic request (95%CI) was significantly prolonged by 86.62 (10.62-162.62) min, I2 = 93%, in the dexamethasone group. For other secondary outcomes including number of patients requiring rescue analgesia, or visual analogue scale pain scores, we found no evidence of a significant difference between the treatment arms. We report a high level of evidence that intravenous dexamethasone improves postoperative analgesia after spinal anaesthesia.

Ephedrine versus phenylephrine as a vasopressor for spinal anaesthesia-induced hypotension in parturients undergoing high-risk caesarean section: meta-analysis, meta-regression and trial sequential analysis.

BACKGROUND: Phenylephrine is the preferred vasopressor for the prevention and treatment of spinal anaesthesia-induced hypotension during caesarean section, because studies on low-risk elective patients found it to have a less detrimental effect on umbilical artery pH compared with ephedrine. However, limited data exist from high-risk parturients and parturients with uteroplacental insufficiency. METHODS: We systematically searched for randomised, controlled, double-blinded trials of these two vasopressors in high-risk caesarean sections. We applied conventional meta-analysis, trial sequential analysis, computing the required information size that would exclude type I and II errors, contour-enhanced funnel plot testing for publication bias, meta-regression to assess the dose-response relationship, and the Grading of Recommendations Assessment, Development, and Evaluation system (GRADE). The incidence of fetal acidosis (umbilical arterial pH <7.2) was the primary outcome. RESULTS: Eight trials (712 patients) with low risk of bias were identified. Pooling six studies of patients with preeclampsia and other reasons for fetal compromise, as well as subgroup analysis of the preeclampsia studies, revealed no significant differences in the incidence of fetal acidosis. Trial sequential analysis showed that the required information size was not reached. The funnel plot was not suggestive of publication bias. Meta-regression showed no dose-response relationship. The GRADE score was moderate quality. CONCLUSIONS: Despite several studies and a large number of patients there was insufficient evidence to make a recommendation for choice of vasopressor in high-risk caesarean section. Trials with adequate power to detect differences in the incidence of fetal acidosis between ephedrine and phenylephrine are required to provide evidence-based guidance.

Pediatric out-of-hospital cardiopulmonary resuscitation by helicopter emergency medical service, does it has added value compared to regular emergency medical service?

PURPOSE: To determine the outcome of out-of-hospital (OOH) cardiopulmonary resuscitation (CPR) and the advanced life support (ALS) procedures provided in pediatrics by the Rotterdam Helicopter Emergency Medical Service (HEMS) METHODS: Retrospective evaluation of all pediatric (0-17 years) OOH cardiopulmonary arrests within a 6-year period and attended by the Rotterdam HEMS team. RESULTS: There were 201 OOH CPRs from October 2008 until October 2014. Endotracheal intubation was performed in 164 cases and done by HEMS in 104 patients (63%), intraosseous/intravenous cannulation 43/27 times, and additional medication given by HEMS in 70 patients (35%). The overall survival rate for OOH CPR was 15%, but in trauma was low. Twenty-seven of the 29 pediatric patients who survived until discharge are neurological well. Although the Dutch nationwide ambulance protocol states intubation, intravenous, or intraosseal excess and medication, in many patients, only HEMS provided additional ALS care. CONCLUSION: The HEMS brings essential medical expertise in the field not provided by regular emergency medical service. HEMS provide a significant quantity of procedures, obviously needed by the OOH CPR of a pediatric patient.