Quantitative CT Evaluation of Bone Mineral Density in the Thoracic Spine on 18F-Fluorocholine PET/CT Imaging in Patients With Primary Hyperparathyroidism.

INTRODUCTION: Measurement of bone mineral density (BMD) with quantitative CT (QCT) carries several advantages over other densitometric techniques, including superior assessment of the spine. As most QCT studies evaluated the lumbar spine, measurements of the thoracic spine are limited. We performed QCT analysis of the thoracic spine in a cohort of patients with primary hyperparathyroidism. MATERIALS AND METHODS: This study was a retrospective QCT analysis of the thoracic spine on 18F-fluorocholine PET/CT scans in patients with primary hyperparathyroidism patients between March 2018 and December 2022. Correlations between QCT-derived BMD or Hounsfield units (HU) and demographic data, laboratory parameters, results from histopathological examination after parathyroidectomy and results of DXA imaging were analyzed, when available. RESULTS: In 189 patients, mean QCT-derived BMD at the thoracic spine was 85.6 mg/cm3. Results from recent DXA were available in 122 patients. Mean thoracic QCT-derived BMD and HU were significantly correlated with DXA-derived BMD in lumbar spine, total hip and femoral neck and with the lowest T-score at DXA imaging. Only weak correlations were found with BMI or 18F-fluorocholine uptake, while no significant correlations were found with adenoma weight, PTH or calcium levels. CONCLUSION: Our study confirms correlation between QCT-derived BMD in the thoracic spine with age and DXA-derived BMD measurements within a population of patients with primary hyperparathyroidism. Establishment of reference BMD values for individual thoracic vertebrae, may allow direct osteoporosis classification on thoracic CT imaging.

Correction to: The value of postmortem computed tomography in paediatric natural cause of death: a Dutch observational study.

When first published, this article inadvertently listed the Dutch NODO group individually within the author list without specifying the names of the collaborators. The collaborators have been listed within the Acknowledgements section only. The corrected author list is presented in this Correction.

Nifedipine versus atosiban for threatened preterm birth (APOSTEL III): a multicentre, randomised controlled trial.

BACKGROUND: In women with threatened preterm birth, delay of delivery by 48 h allows antenatal corticosteroids to improve neonatal outcomes. For this reason, tocolytics are often administered for 48 h; however, there is no consensus about which drug results in the best maternal and neonatal outcomes. In the APOSTEL III trial we aimed to compare the effectiveness and safety of the calcium-channel blocker nifedipine and the oxytocin inhibitor atosiban in women with threatened preterm birth. METHODS: We did this multicentre, randomised controlled trial in ten tertiary and nine teaching hospitals in the Netherlands and Belgium. Women with threatened preterm birth (gestational age 25-34 weeks) were randomly assigned (1:1) to either oral nifedipine or intravenous atosiban for 48 h. An independent data manager used a web-based computerised programme to randomly assign women in permuted block sizes of four, with groups stratified by centre. Clinicians, outcome assessors, and women were not masked to treatment group. The primary outcome was a composite of adverse perinatal outcomes, which included perinatal mortality, bronchopulmonary dysplasia, sepsis, intraventricular haemorrhage, periventricular leukomalacia, and necrotising enterocolitis. Analysis was done in all women and babies with follow-up data. The study is registered at the Dutch Clinical Trial Registry, number NTR2947. FINDINGS: Between July 6, 2011, and July 7, 2014, we randomly assigned 254 women to nifedipine and 256 to atosiban. Primary outcome data were available for 248 women and 297 babies in the nifedipine group and 255 women and 294 babies in the atosiban group. The primary outcome occurred in 42 babies (14%) in the nifedipine group and in 45 (15%) in the atosiban group (relative risk [RR] 0·91, 95% CI 0·61-1·37). 16 (5%) babies died in the nifedipine group and seven (2%) died in the atosiban group (RR 2·20, 95% CI 0·91-5·33); all deaths were deemed unlikely to be related to the study drug. Maternal adverse events did not differ between groups. INTERPRETATION: In women with threatened preterm birth, 48 h of tocolysis with nifedipine or atosiban results in similar perinatal outcomes. Future clinical research should focus on large placebo-controlled trials, powered for perinatal outcomes. FUNDING: ZonMw (the Netherlands Organisation for Health Research and Development).

Induction of labour at term with oral misoprostol versus a Foley catheter (PROBAAT-II): a multicentre randomised controlled non-inferiority trial.

BACKGROUND: Labour is induced in 20-30% of all pregnancies. In women with an unfavourable cervix, both oral misoprostol and Foley catheter are equally effective compared with dinoprostone in establishing vaginal birth, but each has a better safety profile. We did a trial to directly compare oral misoprostol with Foley catheter alone. METHODS: We did an open-label randomised non-inferiority trial in 29 hospitals in the Netherlands. Women with a term singleton pregnancy in cephalic presentation, an unfavourable cervix, intact membranes, and without a previous caesarean section who were scheduled for induction of labour were randomly allocated to cervical ripening with 50 µg oral misoprostol once every 4 h or to a 30 mL transcervical Foley catheter. The primary outcome was a composite of asphyxia (pH ≤7·05 or 5-min Apgar score <7) or post-partum haemorrhage (≥1000 mL). The non-inferiority margin was 5%. The trial is registered with the Netherlands Trial Register, NTR3466. FINDINGS: Between July, 2012, and October, 2013, we randomly assigned 932 women to oral misoprostol and 927 women to Foley catheter. The composite primary outcome occurred in 113 (12·2%) of 924 participants in the misoprostol group versus 106 (11·5%) of 921 in the Foley catheter group (adjusted relative risk 1·06, 90% CI 0·86-1·31). Caesarean section occurred in 155 (16·8%) women versus 185 (20·1%; relative risk 0·84, 95% CI 0·69-1·02, p=0·067). 27 adverse events were reported in the misoprostol group versus 25 in the Foley catheter group. None were directly related to the study procedure. INTERPRETATION: In women with an unfavourable cervix at term, induction of labour with oral misoprostol and Foley catheter has similar safety and effectiveness. FUNDING: FondsNutsOhra.

Pessary or Progesterone to Prevent Preterm delivery in women with short cervical length: the Quadruple P randomised controlled trial.

BACKGROUND: Preterm birth is in quantity and in severity the most important topic in obstetric care in the developed world. Progestogens and cervical pessaries have been studied as potential preventive treatments with conflicting results. So far, no study has compared both treatments. METHODS/DESIGN: The Quadruple P study aims to compare the efficacy of vaginal progesterone and cervical pessary in the prevention of adverse perinatal outcome associated with preterm birth in asymptomatic women with a short cervix, in singleton and multiple pregnancies separately. It is a nationwide open-label multicentre randomized clinical trial (RCT) with a superiority design and will be accompanied by an economic analysis. Pregnant women undergoing the routine anomaly scan will be offered cervical length measurement between 18 and 22 weeks in a singleton and at 16-22 weeks in a multiple pregnancy. Women with a short cervix, defined as less than, or equal to 35 mm in a singleton and less than 38 mm in a multiple pregnancy, will be invited to participate in the study. Eligible women will be randomly allocated to receive either progesterone or a cervical pessary. Following randomization, the silicone cervical pessary will be placed during vaginal examination or 200 mg progesterone capsules will be daily self-administered vaginally. Both interventions will be continued until 36 weeks gestation or until delivery, whichever comes first. Primary outcome will be composite adverse perinatal outcome of perinatal mortality and perinatal morbidity including bronchopulmonary dysplasia, intraventricular haemorrhage grade III and IV, periventricular leukomalacia higher than grade I, necrotizing enterocolitis higher than stage I, Retinopathy of prematurity (ROP) or culture proven sepsis. These outcomes will be measured up until 10 weeks after the expected due date. Secondary outcomes will be, among others, time to delivery, preterm birth rate before 28, 32, 34 and 37 weeks, admission to neonatal intensive care unit, maternal morbidity, maternal admission days for threatened preterm labour and costs. DISCUSSION: This trial will provide evidence on whether vaginal progesterone or a cervical pessary is more effective in decreasing adverse perinatal outcome in both singletons and multiples. TRIAL REGISTRATION: Trial registration number: NTR 4414 . Date of registration January 29th 2014.

The value of postmortem computed tomography in paediatric natural cause of death: a Dutch observational study.

BACKGROUND: Postmortem CT is a relatively new field of interest within paediatric radiology. This paper focusses on its value in cases of unexpected natural death. OBJECTIVE: We report on an observational Dutch study regarding the value of postmortem CT in children with an assumed natural unexpected death because postmortem CT is part of the Dutch NODO (additional investigations of cause of death) procedure. MATERIALS AND METHODS: We included consecutive children who fulfilled criteria for the NODO procedure and were therefore referred to one of the centres for the procedure. Postmortem CT was performed in all cases and skeletal survey was performed in all children ages <5 years. The cause of death was defined in a consensus meeting. RESULTS: We included a total of 54 children (30 boys, median age 1.1 years, and 24 girls, median age 0.8 years). A definitive cause of death was established in 38 cases. In 7 cases the cause of death could be identified on postmortem CT. In 7 cases imaging findings were clinically relevant but did not lead to a cause of death. In the remaining 40 cases postmortem CT did not add to the diagnostic workup. CONCLUSION: Our study shows that in a group of children who unexpectedly died of an assumed natural cause of death and in whom a cause of death was found at autopsy, postmortem CT detected the cause of death in a minority of cases (12.9%). In the majority of cases (74.1%) postmortem CT did not add value in diagnosing the cause of death.

tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia.

Pontocerebellar hypoplasias (PCH) represent a group of neurodegenerative autosomal recessive disorders with prenatal onset, atrophy or hypoplasia of the cerebellum, hypoplasia of the ventral pons, microcephaly, variable neocortical atrophy and severe mental and motor impairments. In two subtypes, PCH2 and PCH4, we identified mutations in three of the four different subunits of the tRNA-splicing endonuclease complex. Our findings point to RNA processing as a new basic cellular impairment in neurological disorders.

Evaluation of strategies regarding management of imminent preterm delivery before 32 weeks of gestation: a regional cohort study among 1375 women in the Netherlands.

OBJECTIVE: To evaluate the management of imminent preterm delivery with respect to prescription of antenatal corticosteroids (ACS) and referral to a tertiary center. STUDY DESIGN: A retrospective cohort study existing of 1 perinatal center and 9 referring hospitals. All women who received their first dose of ACS in 1 of the 10 hospitals between 24+0 and 32+0 weeks of gestation and/or delivered before 32 weeks of gestation from 2005 until 2010. Patients were identified using the electronic database of hospital pharmacies. Main outcome measures were time interval from administration to delivery for different indications and number of women who were not referred in time to a tertiary center. RESULTS: In total, 1375 women received ACS. Main indications were suspected preterm labor (44.7%), preterm prelabor rupture of membranes (15.9%), maternal indication (12.8%), fetal indication (9.2%) and vaginal blood loss (8.4%). Overall, 467 (34.0%) women delivered ≤7 days after ACS administration; 8.7% of women with vaginal blood loss and 54.5% of women with maternal indication. Among the 931 women who received ACS in the secondary hospitals, 452 (48.5%) women were referred to a tertiary hospital and 89 (6.5%) women delivered in a secondary hospital with a gestational age of less than 32 weeks. CONCLUSION: One-third of all women receiving ACS delivered within 7 days and half of the women who received ACS in a secondary hospital were referred to a tertiary center. There seems to be room for improvement regarding the timing of ACS administration and subsequently referral to a tertiary center.

Nifedipine versus atosiban in the treatment of threatened preterm labour (Assessment of Perinatal Outcome after Specific Tocolysis in Early Labour: APOSTEL III-Trial).

BACKGROUND: Preterm birth is the most common cause of neonatal morbidity and mortality. Postponing delivery for 48 hours with tocolytics to allow for maternal steroid administration and antenatal transportation to a centre with neonatal intensive care unit facilities is the standard treatment for women with threatening preterm delivery in most centres. However, there is controversy as to which tocolytic agent is the drug of first choice. Previous trials have focused on tocolytic efficacy and side effects, and are probably underpowered to detect clinically meaningfull differences in neonatal outcome. Thus, the current evidence is inconclusive to support a balanced recommendation for clinical practice. This multicenter randomised clinical trial aims to compare nifedipine and atosiban in terms of neonatal outcome, duration of pregnancy and maternal side effects. METHODS/DESIGN: The Apostel III trial is a nationwide multicenter randomised controlled study. Women with threatened preterm labour (gestational age 25 - 34 weeks) defined as at least 3 contractions per 30 minutes, and 1) a cervical length of ≤ 10 mm or 2) a cervical length of 11-30 mm and a positive Fibronectin test or 3) ruptured membranes will be randomly allocated to treatment with nifedipine or atosiban. Primary outcome is a composite measure of severe neonatal morbidity and mortality. Secondary outcomes will be time to delivery, gestational age at delivery, days on ventilation support, neonatal intensive care (NICU) admittance, length admission in neonatal intensive care, total days in hospital until 3 months corrected age, convulsions, apnoea, asphyxia, proven meningitis, pneumothorax, maternal side effects and costs. Furthermore, an economic evaluation of the treatment will be performed. Analysis will be by intention to treat principle. The power calculation is based on an expected 10% difference in the prevalence of adverse neonatal outcome. This implies that 500 women have to be randomised (two sided test, ß 0.2 at alpha 0.05). DISCUSSION: This trial will provide evidence on the optimal drug of choice in acute tocolysis in threatening preterm labour. CLINICAL TRIAL REGISTRATION: NTR2947, date of registration: June 20th 2011.

The Impact of Baseline PSMA PET/CT Versus CT on Outcomes of 223Ra Therapy in Metastatic Castration-Resistant Prostate Cancer Patients.

Imaging before 223Ra-dichloride (223Ra) therapy is crucial for selecting metastatic castration-resistant prostate cancer (mCRPC) patients with bone-only disease. The purpose of this study was to evaluate if baseline prostate-specific membrane antigen (PSMA) PET/CT (bPSMA) versus CT is associated with outcomes of 223Ra therapy. Methods: A secondary analysis of the data of a prospective observational study (NCT04995614) was performed. Patients received a maximum of 6 223Ra cycles and were retrospectively divided into the bPSMA or baseline CT (bCT) groups. All patients received baseline bone scintigraphy. Primary endpoints were alkaline phosphatase and prostate-specific antigen response. Secondary endpoints were overall survival (OS) and radiologic response. Results: Between 2017 and 2020, 122 mCRPC patients were included: 18 (14.8%) in the bPSMA group and 104 (85.2%) in the bCT group. All baseline characteristics were comparable. No significant differences in alkaline phosphatase or prostate-specific antigen response were found. The bCT group showed an OS significantly shorter than that of the bPSMA group (12.4 vs. 19.9 mo, P = 0.038). In 31 of 76 patients (40.1%) in the bCT group who also received posttherapy CT, lymph node or visceral metastases (soft-tissue involvement [STI]) were detected after 223Ra therapy, compared with 0 of 15 patients in the bPSMA group who received posttherapy PSMA PET/CT or CT. No significant difference in OS was found between patients in the bCT or posttherapy CT subgroup without STI (46/76) and the bPSMA group. Conclusion: bPSMA versus CT does not seem to impact biochemical response during 223Ra therapy in mCRPC patients. Nevertheless, patients in the bCT group had a significantly shorter OS, most likely due to underdetection of STI in this group. Therefore, replacing bCT with PSMA PET/CT appears to be a valuable screening method for identifying patients who will benefit most from 223Ra therapy.

Pharmacokinetics and central nervous system effects of the novel dual NK1 /NK3 receptor antagonist GSK1144814 in alcohol-intoxicated volunteers.

AIMS: Antagonism of both NK1 and NK3 receptors may be an effective strategy in the pharmacotherapy of schizophrenia, drug addiction or depression. GSK1144814 is a novel selective dual NK1 /NK3 receptor antagonist. The potential influence of GSK1144814 on the effects of alcohol was investigated. METHODS: In a blinded, randomized, placebo-controlled, two period crossover study, the pharmacokinetics and central nervous system (CNS) effects of single oral doses of 200 mg GSK1144814 were evaluated in 20 healthy volunteers, using a controlled alcohol infusion paradigm to maintain stable alcohol concentrations with subsequent analysis of eye movements, adaptive tracking, body sway, visual analogue scales, Epworth sleepiness scale and the verbal visual learning test. RESULTS: Frequent adverse effects were mild somnolence, fatigue and headache. Plasma concentration of GSK1144814 in the presence of alcohol was maximal 1.5 h after dose administration. GSK1144814 did not affect alcohol pharmacokinetics. Co-administration of GSK1144814 and alcohol impaired saccadic reaction time and peak velocity, adaptive tracking, alertness, sleepiness, word recognition and recognition reaction time compared with administration of alcohol alone, but the size of the interaction was small. CONCLUSIONS: Administration of GSK1144814 in the presence of alcohol was generally well tolerated and not likely to produce clinically relevant additional impairments after alcohol consumption.

Induction of labour with a Foley catheter or oral misoprostol at term: the PROBAAT-II study, a multicentre randomised controlled trial.

BACKGROUND: Induction of labour is a common obstetric procedure. At present, different methods are used for induction of labour in women with an unfavourable cervix. Recently, we showed that in term women with an unfavorable cervix the use of a Foley catheter in comparison with vaginal Prostaglandin E2 gel, results in a comparable vaginal delivery rate. A meta-analysis on the subject indicated lower rates of hyperstimulation, and probably as a sequel fewer cases of postpartum haemorrhage. Misoprostol (PgE1) is another type of prostaglandin frequently used for labour induction, recommended by the international federation of gynaecology and obstetrics (FIGO). Misoprostol can be administered by vaginal, rectal and oral route. There is evidence that oral administration results in less asphyxia and hyperstimulation than vaginal administration. At present, valid comparisons between oral misoprostol and Foley catheter are lacking. Therefore, we propose a randomised controlled trial comparing Foley catheter to oral misoprostol in order to assess safety and cost-effectiveness. METHODS/DESIGN: We plan a multicentre, randomised, controlled, open-label clinical trial among term pregnant women with a vital singleton in cephalic presentation, unfavorable cervix, intact membranes and an indication for induction of labour. After informed consent, women will be randomly allocated by a webbased randomisation system to transcervical Foley catheter or oral misoprostol (50 mcg every 4 hours). The primary outcome will be a composite of complications of uterine hyperstimulation, i.e. post partum haemorrhage and asphyxia. Secondary outcomes are mode of delivery, maternal and neonatal morbidity, costs and women's preference. Serious adverse events such as severe maternal or neonatal morbitity or mortality will be monitored and reported to an independent data safety monitory board. With a sample size of 1860 women we will be able to demonstrate a 5% non-inferiority of the Foley catheter as compared to misoprostol for the composite outcome. DISCUSSION: Worldwide, various methods are being used for labour induction. Results of the proposed trial will contribute to the answer which method of induction of labour is most safe, cost-effective, and patient friendly and will help to construct evidence based guidelines. TRIAL REGISTRATION: The Netherlands Trial Register NTR3466.

Clinical Pharmacology of Radiotheranostics in Oncology.

The combined use of diagnostic and therapeutic radioligands with the same molecular target, also known as theranostics, enables accurate patient selection, targeted therapy, and prediction of treatment response. Radioiodine, bone-seeking radioligands and norepinephrine analogs have been used for many years for diagnostic imaging and radioligand therapy of thyroid carcinoma, bone metastases, pheochromocytoma, paraganglioma, and neuroblastoma, respectively. In recent years, radiolabeled somatostatin analogs and prostate-specific membrane antigen ligands have shown clinical efficacy in the treatment of neuroendocrine tumors and prostate cancer, respectively. Several candidate compounds are targeting novel theranostic targets such as fibroblast activation protein, C-X-C chemokine receptor 4, and gastrin-releasing peptide receptor. In addition, several strategies to improve efficacy of radioligand therapy are being evaluated, including dosimetry-based dose optimization, multireceptor targeting, upregulation of target receptors, radiosensitization, pharmacogenomics, and radiation genomics. Design and evaluation of novel radioligands and optimization of dose and dose schedules, within the complex context of individualized multimodal cancer treatment, requires a multidisciplinary approach that includes clinical pharmacology. Significant increases in the use of these radiopharmaceuticals in routine oncological practice can be expected, which will have major impact on patient care as well as (radio)pharmacy utilization.

Gamma camera-specific reference standards for radioactive iodine uptake measurements.

BACKGROUND: Current guidelines of the radioiodine uptake (RAIU) test allow the use of different equipment, isotopes, activity and region-of-interest (ROI). We evaluated presence and extent of these differences in clinical practice and evaluated the effect of some of these variations on RAIU outcomes. Also, gamma camera-specific reference standards were calculated and retrospectively compared with measurements obtained during clinical RAIU tests. MATERIALS AND METHODS: First, questionnaires were sent to Dutch nuclear medicine departments requesting information about equipment usage, isotope, isotope formulation, activity and measurement techniques. Secondly, a neck phantom containing a range of activities in capsule or water-dissolved formulation was scanned. Counts were measured using automatic ROI, square box ROI or all counts in the image. Thirdly, clinical RAIU data were collected during 2015-2018 using three different gamma cameras. Reference standards for each scanner were calculated using regression analysis between reference activity and measured counts. Uptake measurements using this gamma camera-specific reference standard were compared with original measurements. RESULTS: The survey demonstrated significant differences in isotope, isotope formulation, activity, use of neck phantoms, frequency and duration of reference measurements, distance to collimator, use of background measurements and ROI delineation. The phantom study demonstrated higher counts for the water-dissolved formulation than capsules using both automatic and square box ROI. Also, higher counts were found using a square box ROI than an automatic ROI. The retrospective study showed feasibility of RAIU calculations using camera-specific reference standards and good correlation with the original RAIU measurements. CONCLUSIONS: This study demonstrated considerable technical variation in RAIU measurement in clinical practice. The phantom study demonstrated that these differences could result in differences in count measurements, potentially resulting in different dose calculations for radioactive iodine therapy. Retrospective data suggest that camera-specific reference standards may be used instead of individual reference measurements using separate activity sources, which may thus eliminate some sources of variation.

Feasibility of Left Ventricle Ejection Fraction Calculation Using Electrocardiographically Gated SPECT Acquisition of 99m Tc-HDP Bone Scintigraphy in Cardiac Amyloidosis.

ABSTRACT: We performed bone scintigraphy in 6 patients with suspected cardiac amyloidosis. To evaluate feasibility of left ventricle function analysis, we additionally performed electrocardiographically gated SPECT acquisition. The cardiac-gated SPECT data confirmed adequate tracer uptake for automatic myocardial contour determination. LVEF estimations ranged between 24% and 54%. Comparison with LVEF estimations from prior echocardiography generally showed only small differences. In one patient, the LVEF measurements from both methods seemed discordant, probably reflecting actual LVEF worsening, which was confirmed at follow-up echocardiography. Therefore, our results may suggest that cardiac-gated SPECT acquisition at bone scintigraphy can provide meaningful estimates of LVEF.

Manipulating brain connectivity with δ9-tetrahydrocannabinol: a pharmacological resting state FMRI study.

Resting state-functional magnetic resonance imaging (RS-FMRI) is a neuroimaging technique that allows repeated assessments of functional connectivity in resting state. While task-related FMRI is limited to indirectly measured drug effects in areas affected by the task, resting state can show direct CNS effects across all brain networks. Hence, RS-FMRI could be an objective measure for compounds affecting the CNS. Several studies on the effects of cannabinoid receptor type 1 (CB(1))-receptor agonist δ(9)-tetrahydrocannabinol (THC) on task-dependent FMRI have been performed. However, no studies on the effects of cannabinoids on resting state networks using RS-FMRI have been published. Therefore, we investigated the effects of THC on functional brain connectivity using RS-FMRI. Twelve healthy volunteers (9 male, 3 female) inhaled 2, 6 and 6 mg THC or placebo with 90-minute intervals in a randomized, double blind, cross-over trial. Eight RS-FMRI scans of 8 min were obtained per occasion. Subjects rated subjective psychedelic effects on a visual analog scale after each scan, as pharmacodynamic effect measures. Drug-induced effects on functional connectivity were examined using dual regression with FSL software (FMRIB Analysis Group, Oxford). Eight maps of voxel-wise connectivity throughout the entire brain were provided per RS-FMRI series with eight predefined resting-state networks of interest. These maps were used in a mixed effects model group analysis to determine brain regions with a statistically significant drug-by-time interaction. Statistical images were cluster-corrected, and results were Bonferroni-corrected across multiple contrasts. THC administration increased functional connectivity in the sensorimotor network, and was associated with dissociable lateralized connectivity changes in the right and left dorsal visual stream networks. The brain regions showing connectivity changes included the cerebellum and dorsal frontal cortical regions. Clear increases were found for feeling high, external perception, heart rate and cortisol, whereas prolactin decreased. This study shows that THC induces both increases and (to a lesser extent) decreases in functional brain connectivity, mainly in brain regions with high densities of CB(1)-receptors. Some of the involved regions could be functionally related to robust THC-induced CNS-effects that have been found in previous studies (Zuurman et al., 2008), such as postural stability, feeling high and altered time perception.

Foley catheter versus vaginal prostaglandin E2 gel for induction of labour at term (PROBAAT trial): an open-label, randomised controlled trial.

BACKGROUND: Induction of labour is a common obstetric procedure. Both mechanical (eg, Foley catheters) and pharmacological methods (eg, prostaglandins) are used for induction of labour in women with an unfavourable cervix. We aimed to compare the effectiveness and safety of induction of labour with a Foley catheter with induction with vaginal prostaglandin E2 gel. METHODS: We did an open-label, randomised controlled trial in 12 hospitals in the Netherlands between Feb 10, 2009, and May 17, 2010. We enrolled women with a term singleton pregnancy in cephalic presentation, intact membranes, an unfavourable cervix, an indication for induction of labour, and no prior caesarean section. Participants were randomly allocated by an online randomisation system to induction of labour with a 30 mL Foley catheter or vaginal prostaglandin E2 gel (1:1 ratio). Because of the nature of the intervention this study was not blinded. The primary outcome was caesarean section rate. Secondary outcomes were maternal and neonatal morbidity and time from intervention to birth. All analyses were done on an intention-to-treat basis. We also did a meta-analysis that included our trial. The trial was registered with the Dutch trial registry, number NTR 1646. FINDINGS: 824 women were allocated to induction of labour with a Foley catheter (n=412) or vaginal prostaglandin E2 gel (n=412). Caesarean section rates were much the same between the two groups (23%vs 20%, risk ratio [RR] 1·13, 95% CI 0·87-1·47). A meta-analysis including our trial data confirmed that a Foley catheter did not reduce caesarean section rates. We recorded two serious maternal adverse events, both in the prostaglandin group: one uterine perforation and one uterine rupture. INTERPRETATION: In women with an unfavourable cervix at term, induction of labour with a Foley catheter is similar to induction of labour with prostaglandin E2 gel, with fewer maternal and neonatal side-effects. FUNDING: None.

Safety of MF59-adjuvanted A/H1N1 influenza vaccine in pregnancy: a comparative cohort study.

OBJECTIVE: The 2009-2010 A/H1N1 pandemic provided a unique setting to study the safety of MF59-adjuvanted vaccination in pregnancy. STUDY DESIGN: This was an observational cohort study of the safety of an MF59-adjuvanted A/H1N1 vaccine (Focetria) conducted among 4508 pregnant women (2295 vaccinated vs 2213 unvaccinated), with 3 month follow-up of neonates. RESULTS: No maternal deaths or abortions occurred among the vaccinated women. No differences between the vaccinated and unvaccinated cohorts were observed for gestational diabetes, preeclampsia, stillbirth, low birthweight, neonatal deaths, or congenital malformations. The risk of premature birth was significantly decreased among the vaccinated women (adjusted proportional hazard, 0.69; 95% confidence interval, 0.51-0.92). No differences were observed in rates of congenital malformations after vaccination in the first (2.1%), second (2.7%), or third (2.1%) trimesters. CONCLUSION: There was no evidence of a safety risk for MF59-adjuvanted A/H1N1 vaccination in pregnant women; protection was observed against premature birth.

Predictive value of the baseline T-QRS ratio of the fetal electrocardiogram in intrapartum fetal monitoring: a prospective cohort study.

OBJECTIVE: To evaluate the added value of the baseline T/QRS ratio to other known risk factors in predicting adverse outcome and interventions for suspected fetal distress. DESIGN: Prospective cohort study. SETTING: Three academic and six non-academic teaching hospitals in the Netherlands. POPULATION: Laboring women with a high-risk cephalic singleton pregnancy beyond 36 weeks of gestation. METHODS: We obtained STAN(®) recordings (ST-analysis, Neoventa, Sweden) from two previous studies. Three patient groups were defined: cases with adverse outcome, cases with emergency delivery because of suspected fetal distress without adverse outcome, and a reference group of uncomplicated cases. Baseline T/QRS ratios among the adverse outcome and intervention for suspected fetal distress cases were compared to those of the uncomplicated cases. The ability of baseline T/QRS to predict adverse outcome and suspected fetal distress was determined using a multivariable logistic model. MAIN OUTCOME MEASURES: The added value of the baseline T/QRS to other known risk factors in the prediction of adverse outcome and interventions for suspected fetal distress. RESULTS: From 3462 recordings, 2459 were available for analysis. Median baseline T/QRS for uncomplicated cases, adverse outcome and interventions for suspected fetal distress were 0.12 (range 0.00-0.52), 0.12 (0.00-0.42) and 0.13 (0.00-0.39), respectively. There was no statistical difference between these groups. Multivariable analysis showed no added value of baseline T/QRS in the prediction of either adverse outcome or interventions for suspected fetal distress. CONCLUSION: Baseline T/QRS has no added value in the prediction of adverse neonatal outcome or interventions for suspected fetal distress.