Massive intraventricular haemorrhage from aneurysmal rupture: patient proportions and eligibility for intraventricular fibrinolysis

Massive intraventricular haemorrhage (IVH) complicating aneurysmal subarachnoid haemorrhage (SAH) is associated with a poor prognosis. Small observational studies suggest favourable results from fibrinolysis of the intraventricular blood. We performed an observational study on IVH in a large series of patients with SAH to assess the proportion of patients that may benefit from fibrinolytic treatment. From our prospective database we retrieved patients with aneurysmal SAH admitted between January 2000 and January 2005. We calculated the proportion of patients with massive IVH and the proportion of patients that are eligible for fibrinolysis on basis of clinical and CT-scan characteristics and assessed neurological outcome in a treatment strategy without fibrinolysis. Poor neurological condition was defined as World Federation of Neurological Surgeons scale 4 and 5, poor outcome as death or dependence 3 months after SAH. Of the 573 patients admitted with aneurysmal SAH, 59 (10%; 95% confidence interval CI 8–13%) had massive IVH, of which 55 were in poor clinical condition. For these 55 patients, the case-fatality rate was 78% (95% CI 66–88%) and the proportion with poor outcome 91% (95% CI 81–97%). Of the 55 patients, 31 (56%, and 5% of all patients SAH within the study period) fulfilled our eligibility criteria and were considered suitable for intraventricular fibrinolysis. At 3 months, 30 of these 31 eligible patients (97%; 95% CI 85–100%) had a poor outcome. Massive IVH occurs in 10% of patients with aneurysmal SAH. Half of these patients may benefit from intraventricular fibrinolysis. Without fibrinolysis outcome is almost invariably poor in these patients

The association of genetic predisposition to depressive symptoms with non-suicidal and suicidal self-Injuries

Non-suicidal and suicidal self-injury are very destructive, yet surprisingly common behaviours. Depressed mood is a major risk factor for non-suicidal self-injury (NSSI), suicidal ideation and suicide attempts. We conducted a genetic risk prediction study to examine the polygenic overlap of depressive symptoms with lifetime NSSI, suicidal ideation, and suicide attempts in a sample of 6237 Australian adult twins and their family members (3740 females, mean age\ua0=\ua042.4\ua0years). Polygenic risk scores for depressive symptoms significantly predicted suicidal ideation, and some predictive ability was found for suicide attempts; the polygenic risk scores explained a significant amount of variance in suicidal ideation (lowest p\ua0=\ua00.008, explained variance ranging from 0.10 to 0.16\ua0%) and, less consistently, in suicide attempts (lowest p\ua0=\ua00.04, explained variance ranging from 0.12 to 0.23\ua0%). Polygenic risk scores did not significantly predict NSSI. Results highlight that individuals genetically predisposed to depression are also more likely to experience suicidal ideation/behaviour, whereas we found no evidence that this is also the case for NSSI

Dutch guidelines on care for extremely premature infants:Navigating between personalisation and standardization

OBJECTIVE: There is no international consensus on what type of guideline is preferred for care at the limit of viability. We aimed to conceptualize what type of guideline is preferred by Dutch healthcare professionals: 1) none; 2) gestational-age-based; 3) gestational-age-based-plus; or 4) prognosis-based via a survey instrument. Additional questions were asked to explore the grey zone and attitudes towards treatment variation. FINDING: 769 surveys were received. Most of the respondents (72.8%) preferred a gestational-age-based-plus guideline. Around 50% preferred 24+0/7 weeks gestational age as the lower limit of the grey zone, whereas 26+0/7 weeks was the most preferred upper limit. Professionals considered treatment variation acceptable when it is based upon parental values, but unacceptable when it is based upon the hospital's policy or the physician's opinion. CONCLUSION: In contrast to the current Dutch guideline, our results suggest that there is a preference to take into account individual factors besides gestational age

Viability, abortion and extreme prematurity:a critique

This article examines the ethical validity of using viability as the cutoff point for abortion in the Netherlands, in view of potential changes to the Dutch perinatal care guideline. According to the Dutch Penal Code, abortion is permitted until viability: the point at which a fetus can survive outside the womb with technological assistance. Since the law was enacted in 1984, viability has been set at 24 weeks gestational age. Currently, in the Netherlands, the treatment limit for extreme prematurity is also set at 24 weeks. The potential revision of the guideline could lower this threshold. Such a change could have implications for abortion in the Netherlands. We critically evaluate the use of viability within the Dutch context and offer recommendations for modifying the legal framework concerning abortion. We conclude that relying on any interpretation of viability is morally problematic for abortion regulation, as it is too indeterminate a concept to establish a threshold in a morally relevant way.</p

Viability, abortion and extreme prematurity:a critique

This article examines the ethical validity of using viability as the cutoff point for abortion in the Netherlands, in view of potential changes to the Dutch perinatal care guideline. According to the Dutch Penal Code, abortion is permitted until viability: the point at which a fetus can survive outside the womb with technological assistance. Since the law was enacted in 1984, viability has been set at 24 weeks gestational age. Currently, in the Netherlands, the treatment limit for extreme prematurity is also set at 24 weeks. The potential revision of the guideline could lower this threshold. Such a change could have implications for abortion in the Netherlands. We critically evaluate the use of viability within the Dutch context and offer recommendations for modifying the legal framework concerning abortion. We conclude that relying on any interpretation of viability is morally problematic for abortion regulation, as it is too indeterminate a concept to establish a threshold in a morally relevant way.</p

Viability, abortion and extreme prematurity:a critique

This article examines the ethical validity of using viability as the cutoff point for abortion in the Netherlands, in view of potential changes to the Dutch perinatal care guideline. According to the Dutch Penal Code, abortion is permitted until viability: the point at which a fetus can survive outside the womb with technological assistance. Since the law was enacted in 1984, viability has been set at 24 weeks gestational age. Currently, in the Netherlands, the treatment limit for extreme prematurity is also set at 24 weeks. The potential revision of the guideline could lower this threshold. Such a change could have implications for abortion in the Netherlands. We critically evaluate the use of viability within the Dutch context and offer recommendations for modifying the legal framework concerning abortion. We conclude that relying on any interpretation of viability is morally problematic for abortion regulation, as it is too indeterminate a concept to establish a threshold in a morally relevant way.</p

Viability, abortion and extreme prematurity:a critique

This article examines the ethical validity of using viability as the cutoff point for abortion in the Netherlands, in view of potential changes to the Dutch perinatal care guideline. According to the Dutch Penal Code, abortion is permitted until viability: the point at which a fetus can survive outside the womb with technological assistance. Since the law was enacted in 1984, viability has been set at 24 weeks gestational age. Currently, in the Netherlands, the treatment limit for extreme prematurity is also set at 24 weeks. The potential revision of the guideline could lower this threshold. Such a change could have implications for abortion in the Netherlands. We critically evaluate the use of viability within the Dutch context and offer recommendations for modifying the legal framework concerning abortion. We conclude that relying on any interpretation of viability is morally problematic for abortion regulation, as it is too indeterminate a concept to establish a threshold in a morally relevant way.</p

In-host microevolution of Aspergillus fumigatus : a phenotypic and genotypic analysis

Acknowledgments We are thankful to Kenny Ntwari Nindorera for performing the G. mellonella survival studies. EB, AB and AW are supported by the Wellcome Trust Strategic Award (grant 097377), the MRC Centre for Medical Mycology (grant MR/N006364/1) at the University of Aberdeen. AB was also supported by the Biotechnology and Biological Research Council (BB/K017365/1) and the Medical Research Council (MR/M026663/1). The work in this paper is funded by a BBSRC EASTBIO grant. The funders had no role in study design, data interpretation, or the decision to submit the work for publication.Peer reviewedPublisher PD

A prolonged methoxymorpholino doxorubicin (PNU-152243 or MMRDX) infusion schedule in patients with solid tumours: a phase 1 and pharmacokinetic study

The aim of this phase I study was to assess feasibility, pharmacokinetics and toxicity of methoxymorpholino doxorubicin (MMRDX or PNU-152243) administered as a 3 h intravenous infusion once every 4 weeks. Fourteen patients with intrinsically anthracycline-resistant tumours received 37 cycles of MMRDX. The first cohort of patients was treated with 1 mg m−2of MMRDX. The next cohorts received 1.25 mg m−2and 1.5 mg m−2respectively. Common toxicity criteria (CTC) grade III/IV nausea and vomiting were observed in 1/18 cycles at 1.25 mg m−2and in 2/11 cycles at 1.5 mg m−2. Transient elevation in transaminases up to CTC grade III was observed in 2/16 cycles at 1.25 mg m−2and 4/11 cycles at 1.5 mg m−2. No cardiotoxicity was observed. At 1.25 mg m−2CTC grade IV neutropenia occurred in 1/17 cycles. At 1.5 mg m−2CTC grade III neutropenia was seen in 2/7 and grade IV in 3/7 evaluable cycles. Thrombocytopenia grade III was observed in 2/9 and grade IV in 1/9 evaluable cycles. One patient treated at 1.5 mg m−2died with neutropenic fever. Therefore, dose-limiting toxicity was reached and 1.25 mg m−2was considered the maximum tolerated dose for MMRDX as 3 h infusion. No tumour responses were observed. Pharmacokinetic parameters showed a rapid clearance of MMRDX from the circulation by an extensive tissue distribution. Renal excretion of the drug and its metabolite was negligible. In conclusion, prolongation of MMRDX infusion to 3 h does not improve the toxicity profile as compared with bolus administration. © 2000 Cancer Research Campaig