Authors’ reply to Grundtvig Gram et al.

European Journal of Epidemiology -     

Collaborative working in health and social care: Lessons learned from post-hoc preliminary findings of a young families’ pregnancy to age 2 project in South Wales,United Kingdom

Children of young and socially disadvantaged parents are more likely to experience adverse outcomes. In response to this, a unique young families’ project in Swansea, UK, was created, which drew together a team of multi-agency professionals, to support people aged 16–24 from 17 weeks of pregnancy throughout 1,001 days of the child's life. The aim of the JIGSO (the Welsh word for Jigsaw) project is for young people to reach their potential as parents and to break the cycle of health and social inequality. This evaluation analysed routinely collected data held by the project from January 2017 to December 2018 exploring health and social outcomes, including smoking and alcohol use in pregnancy, breastfeeding, maternal diet and social services outcomes. Outcomes were compared to local and national averages, where available. Data relating to parenting knowledge and skills were available via records of 10-point Likert scales, one collected at the start of the JIGSO involvement and one around 4–6 months later. Findings showed higher than average levels of breastfeeding initiation and lower smoking and alcohol use in pregnancy. Parents also reported enhanced knowledge and confidence in their child care skills, as well as improved family relationships. Parents with high levels of engagement with JIGSO also appeared to have positive outcomes with Social Services (their child's name was removed from child protection register or their case was closed to social services). This was a post-hoc evaluation, not an intervention study or trial, and thus findings must be interpreted with caution. Despite this, the findings are promising and more prospective research exploring similar services is required.     

Thio TEPA pharmacokinetics during intravesical chemotherapy and the influence of Tween 80

Summary A pharmacokinetic study of randomised crossover design was carried out in which eight patients with recurrent stage pTa or pT1 transitional cell carcinoma of the bladder were given thio TEPA (30 mg) in distilled water or in 10% (v/v) Tween 80 (30 ml) intravesically for 2 h, followed 3 months later by the alternative treatment. Thio TEPA and its primary metabolite, TEPA, were measured in plasma and urine using a sensitive and specific chromatographic assay. Large differences between patients were observed in the proportion of thio TEPA absorbed, ranging from 20%–78%. Peak plasma levels of thio TEPA were observed within 1 h of intravesical administration. By 2 h after administration the plasma levels of TEPA were similar to those of thio TEPA and, in contrast to those of the parent compound, remained at a similar level over the next 4 h. The rate of absorption of thio TEPA was not influenced by Tween 80, but it did cause statistically significant increases in mean peak plasma levels (from 101 to 154 ng/ml) and mean AUC values (from 0.376 to 0.496 g h per ml) and a decrease in the mean half-life (from 1.83 to 1.25 h). To obtain plasma levels similar to those achieved after instillation with thio TEPA alone, the dose should be reduced with Tween 80.     

Reversible tonsillar prolapse in vein of Galen aneurysmal malformations: report of eight cases and pathophysiological hypothesis

We report eight cases of vein of Galen aneurysmal malformation (VGAM) assoicated with a Chiari type I malformation. In four cases magnetic resonance imaging (MRI) or computed tomography performed in the neonatal period did not demonstrate the posterior fossa anomaly, which appeared on later scans. In the other cases the MRI was performed in infancy and the anomaly was already present. We compared the venous phases of the posterior fossa angiograms and the MRI in these patients. In all eight cases, the angiograms showed a reflux in the cerebellar veins, via the petrous vein, associated with a uni-or bilateral stenosis or thrombosis of the distal posterior dural sinuses. Furthermore, in two cases the posterior fossa returned to normal on MRI following endovascular treatment, while in three cases the herniation of the cerebellar tonsils decreased after the embolization. Tonsillar prolapse becomes irreversible when the venous outlet is incapable of taking the flow even when the VGAM has been treated adequately. In eight additional cases of VGAM for which MRI and angiogram studies were available and in which stenosis or thrombosis of posterior dural sinuses was present without tonsillar prolapse, no reflux into the cerebellar veins was shown. We suggest that the posterior fossa hydrovenous congestion is a result of inadequate venous drainage and that the tonsillar descent is reversible if adequate venous drainage is reconstituted following therapeutic embolization of the fistula. Tonsillar prolapse is not a consequence of mass or raised intraventricular pressure. Our observation suggests that in some other conditions, the Chiari I malformations may be secondary to early hydrovenous dysfunction of the posterior fossa.     

Can parturients distinguish between intravenous and epidural fentanyl?

We tested the hypothesis that the sedative, euphoric, and analgesic effects of intravenous fentanyl would distinguish intravenous from epidural administration. One hundred ASA I and II labouring parturients received 100 μg fentanyl either iv or via an epidural catheter in a double-blind, randomized, crossover fashion. Nineteen anaesthetists (8 staff and 11 residents) participated and correctly guessed the route of administration of the fentanyl in 61/66 intravenous doses and in 69/75 epidural doses yielding a sensitivity of 92.4%, a specificity of 92.0%, a positive predictive value of 91.0%, and a negative predictive value of 93.2%. Of the 41 patients that were crossed over, 38 (92.7%) were able to detect a difference between the routes of administration. Most patients experienced prompt, short-lived symptoms with iv fentanyl but no important differences in fetal heart rate pattern or in maternal desaturation were seen between the groups. This study suggests that subjective symptoms will accurately distinguish intravenous from epidural fentanyl administration in labouring parturients (P < 0.001), and should serve as a safe and reliable intravenous test dose for epidural anaesthesia in the obstetric population.     

15th Scientific Congress of the European Society for Pediatric Hematology and Immunology (ESPHI) Bingen,Germany, 23–26 August 1995

Abstracts

15th Scientific Congress of the European Society for Pediatric Hematology and Immunology (ESPHI) Bingen, Germany, 23–26 August 1995     

Oligogenic determination of morphine analgesic magnitude: A genetic analysis of selectively bred mouse lines

Two ongoing selective breeding projects have produced mice that display divergent analgesic responses to morphine. These two projects have selected for similar phenotypes: high and low levorphanol analgesia (HAR/LAR lines; Portland, OR) and high and low swim stress-induced analgesia (HA/LA lines; Jastrzebiec, Poland). Evidence suggests genetic commonalities between mice of the two projects. Using a Mendelian breeding protocol, we have recently found that one or two genetic loci predominantly determine the high morphine analgesia exhibited by HA mice. In the present study we demonstrate that the differential morphine analgesia (5 mg/kg. i.p.) displayed by HAR and LAR mice is similarly oligogenic, predominantly determined by two unlinked loci. A complementation analysis, in which the analgesic responses to morphine of the recessive homozygotes of each project (HAR and HA) were compared to those of their hybrid offspring (HAR x HA), revealed that different genetic loci have been fixed in each project. An intriguing bimodal distribution was observed in the HAR x HA population: Some HAR x HA hybrids displayed greater morphine analgesia than either HAR or HA mice, whereas others displayed minimal analgesia. LAR x LA hybrids displayed less analgesia than either LAR or LA mice. The analgesic responses of HAR x LA and LAR x HA mice were comparable to those of their low-line parents. These findings indicate not only that different loci were responsible for producing high morphine responders in each selection project but that these distinct loci can interact synergistically to produce superhigh and superlow responders.     

Bupivacaine 0.1% does not improve postoperative epidural fentanyl analgesia after abdominal or thoracic surgery

Epidural infusions of fentanyl, in a 10 micrograms.ml-1 concentration, combined with bupivacaine 0.1% were compared with epidural infusions of fentanyl alone for postoperative analgesia following abdominal or thoracic surgery. There were no detectable differences between the two groups in analgesia (mean visual analogue scale pain scores ranging between 15-35 mm), average infusion rates of 7-9 ml.hr-1, and serum fentanyl concentrations which reached 1-2 ng.ml-1. There was no difference in postoperative pulmonary function (pH, PaCO2, SaO2), or bowel function (time to flatus or po fluids). The incidence of side-effects including somnolence, nausea and vomiting, pruritus and postural hypotension was also similar. Of the patients receiving fentanyl and bupivacaine 0.1%, three developed a transient unilateral sensory loss to pinprick and ice, and two of these patients had unilateral leg weakness equal to a Bromage 1 score. The addition of bupivacaine 0.1% does not improve epidural infusions of fentanyl using a 10 micrograms.ml-1 concentration following abdominal or thoracic surgery.