The Prodromal Questionnaire: a case for IRT‐based adaptive testing of psychotic experiences?

Computerized adaptive tests (CATs) for positive and negative psychotic experiences were developed and tested in N = 5705 help‐seeking, non‐psychotic young individuals. Instead of presenting all items, CATs choose a varying number of different items during test administration depending on respondents' previous answers, reducing the average number of items while still obtaining accurate person estimates. We assessed the appropriateness of two‐parameter logistic models to positive and negative symptoms of the Prodromal Questionnaire (PQ), computed measurement precision of all items and resulting adaptive tests along psychotic dimensions by Real Data Simulations (RDS), and computed indices for criterion and predictive validities of the CATs. For all items, mean absolute differences between observed and expected response probabilities were smaller than 0.02. CAT‐POS predicted transition to psychosis and duration of hospitalization in individuals at‐risk for psychosis, and CAT‐NEG was suggestively related to later functioning. Regarding psychosis risk classifications of help‐seeking individuals, CAT‐POS performed less than the PQ‐16. Adaptive testing based on self‐reported positive and negative symptoms in individuals at‐risk for psychosis is a feasible method to select patients for further risk classification. These promising findings need to be replicated prospectively in a non‐selective sample that also includes non‐at‐risk individuals. Copyright © 2016 John Wiley & Sons, Ltd.     

Validation of the acenocoumarol EU-PACT algorithms: similar performance in the Rotterdam Study cohort as in the original study

Aim: To evaluate the performance of the European Pharmacogenetics of Anticoagulant Therapy (EU-PACT) acenocoumarol dose algorithms in an independent data set. The EU-PACT trial investigates the added value of pretreatment genotyping for use of warfarin, phenprocoumon and acenocoumarol. Patients & methods: External validation was performed in the Rotterdam Study cohort using information about 707 acenocoumarol users. R(2), which measures the strength of correlation between the predicted and observed acenocoumarol dose, mean absolute error and mean squared error were calculated to evaluate the performance of the original algorithm. Results: Validation resulted in a R(2) of 52.7 and 12.9% compared with an R(2) of 52.6 and 17.8% in the original study for the genotype-guided and nongenotype-guided dose algorithm, respectively. For the genotype-guided dose algorithm, the mean absolute error was 0.48 mg/day and the mean squared error was 0.38 (mg/day)(2). For the nongenotype-guided dose algorithm, the mean absolute error was 0.62 mg/day and the mean squared error was 0.63 (mg/day)(2). Conclusion: The EU-PACT acenocoumarol algorithm performs just as accurately in this study as in the original study, which implies applicability in various populations. Original submitted 4 April 2012; Revision submitted 31 May 2012.     

Cost-effectiveness of pharmacogenetics in anticoagulation: international differences in healthcare systems and costs

Genotyping patients for CYP2C9 and VKORC1 polymorphisms can improve the accuracy of dosing during the initiation of anticoagulation with vitamin K antagonists (coumarin derivatives). The anticipated degree of improvement in the safety of anticoagulation with coumarins through genotyping may vary depending on the quality of patient care, which varies both with and among countries. The management and the cost of anticoagulant care can therefore influence the cost-effectiveness of genotyping within any given country. In this article, we provide an overview of the cost-effectiveness of pharmacogenetics-guided dosing of coumarin derivatives. We describe the organization of anticoagulant care in the UK, Sweden, The Netherlands, Greece, Germany and Austria, where a genotype-guided dosing algorithm is currently being investigated as part of the EU-PACT trial. We also explore the costs of anticoagulant care for the treatment of atrial fibrillation in these countries.     

Cognitive functioning in compulsive hoarding

The aim of this study is to determine whether neurocognitive performance distinguishes individuals with compulsive hoarding (CH) from those with obsessive-compulsive disorder (OCD). Compared to control subjects, OCD patients and CHs scored significantly worse on the Serial Reaction Time Task suggesting disturbed implicit memory in both patient groups. On the Iowa Gambling Task, an overall learning progression difference over time was found between the CHs, OCD group, and control subjects, suggesting differences in decision-making between the groups. The groups did not differ in performance on the Stop Signal Reaction Time Task (motor inhibition). This study found evidence for impaired implicit memory in CHs, but also in OCD patients, albeit less severe. There was evidence that OCD patients learned more slowly on a decision-making task than CHs and control subjects. This latter finding provides some evidence to suggest that CH and OCD have, at least on this one measure, differing cognitive substrates.     

Synaptic plasticity in the substantia gelatinosa in a model of chronic neuropathic pain

Chronic neuropathic pain (CNP) is common after peripheral nerve injuries (PNI), but is rather refractory to available anti-pain medication. Advances in neuropathic pain research have identified cellular and molecular cues triggering the onset of neuropathic pain, but the mechanisms responsible for maintenance of chronic pain states are largely unknown. Structural changes such as sprouting of injured A-fibres into the substantia gelatinosa of the dorsal horn in the spinal cord have been proposed to relate to neuropathic pain in partial PNI models. Structural changes in central pain networks may also underlie the more persistent CNP following complete sectioning of a peripheral nerve, because this type of injury results in continuous and spontaneous afferent input to the spinal cord, which can trigger central sensitization. In the present study, the left sciatic nerve was completely sectioned and a 1-cm segment was removed to maintain a chronic pathology, whereas the right sciatic nerve was left intact. Mechanical allodynia was measured up to 84 days after injury, after which synaptic changes were studied in the lumbar substantia gelatinosa. The numbers of larger sized synaptophysin-immunoreactive presynaptic boutons were found to be increased in the substantia gelatinosa ipsilateral to the nerve injury. From these data we conclude that structural synaptic changes within the substantia gelatinosa are present months after complete nerve injury and that this plasticity may be involved in maintaining neuropathic pain states.     

Differences in cognitive performance during pregnancy and early motherhood

BACKGROUND: Pregnancy has often been associated with cognitive deficits, but results are equivocal and little is known about how these deficits progress with time. METHOD: In the present study, the cognitive performance of 57 pregnant women was compared with that of 50 non-pregnant women matched for age and education, using a well-validated neurocognitive test battery at weeks 14, 17, 29, and 36 of pregnancy, and 32 weeks postpartum in the pregnant group and at comparable times in the non-pregnant group. RESULTS: Memory encoding and retrieval, as assessed with a word learning task, were significantly lower in the pregnant group than in the control group. This difference was still present at 32 weeks after delivery. The two groups did not differ in complex speed of information processing at any of the test moments; however, general speed of information processing was significantly compromised during early motherhood (week 32 postpartum). CONCLUSION: Thus, memory performance is poorer during pregnancy and early motherhood, and general speed of information processing is slower during early motherhood.     

Effects of retro-nasal aroma release on satiation

It is suggested that the brain response of a food odour sensed retro-nasally is related to satiation. The extent of retro-nasal aroma release during consumption depends on the physical structure of a food, i.e. solid foods generate a longer, more pronounced retro-nasal aroma release than liquid foods. The aim of this study was to investigate if a beverage becomes more satiating when the retro-nasal aroma release profile coincides with the profile of a (soft) solid food. In a double-blind placebo-controlled randomised cross-over full factorial design, twenty-seven healthy subjects (fourteen males and thirteen females; aged 16-65 years; BMI 19-37 kg/m(2) were administered aroma profiles by a computer-controlled stimulator based on air dilution olfactometry. Profile A consisted of a profile that is obtained during consumption of normal beverages. Profile B is normally observed during consumption of (soft) solids. The two profiles were produced with strawberry aroma and administered in a retro-nasal fashion, while the subjects consumed a sweetened milk drink. Before, during and after the sensory stimulation, appetite profile measurements were performed. Subjects felt significantly more satiated if they were aroma stimulated with profile B (P = 0.04). After stimulation with sweet strawberry aroma, there was a significant decrease in desire to eat sweet products (P = 0.0001). In conclusion, perceived satiation was increased by altering the extent of retro-nasal aroma release.     

Computer-assisted detection of pulmonary embolism: evaluation of pulmonary CT angiograms performed in an on-call setting

Purpose

The purpose of the study was to assess the stand-alone performance of computer-assisted detection (CAD) for evaluation of pulmonary CT angiograms (CTPA) performed in an on-call setting.

Methods

In this institutional review board-approved study, we retrospectively included 292 consecutive CTPA performed during night shifts and weekends over a period of 16 months. Original reports were compared with a dedicated CAD system for pulmonary emboli (PE). A reference standard for the presence of PE was established using independent evaluation by two readers and consultation of a third experienced radiologist in discordant cases.

Results

Original reports had described 225 negative studies and 67 positive studies for PE. CAD found PE in seven patients originally reported as negative but identified by independent evaluation: emboli were located in segmental (n?=?2) and subsegmental arteries (n?=?5). The negative predictive value (NPV) of the CAD algorithm was 92% (44/48). On average there were 4.7 false positives (FP) per examination (median 2, range 0–42). In 72% of studies ≤5 FP were found, 13% of studies had ≥10 FP.

Conclusion

CAD identified small emboli originally missed under clinical conditions and found 93% of the isolated subsegmental emboli. On average there were 4.7 FP per examination.     

Developments in intravesical therapy for non-muscle-invasive bladder cancer

Non-muscle-invasive bladder cancer is a frequent and heterogeneous disease with varying oncologic outcomes. The main goal in treating is to prevent recurrences and progression to muscle-invasive disease. Developments to improve the quality of transurethral resection of the bladder tumor and new chemotherapeutic options, including two device-assisted therapies, are being discussed. A problem is failure of intravesical therapy, especially failure after bacillus Calmette-Guérin treatment. Cystectomy is currently the treatment of choice for these patients. However, not all patients are willing to undergo cystectomy or are unsuitable for surgery. New therapies are needed for these patients. Therefore, the role of intravesical chemotherapy, immunotherapy and device-assisted therapy after bacillus Calmette-Guérin failure is also reviewed.     

A 22-year follow-up reveals a variable disease severity in early-onset facioscapulohumeral dystrophy

Aim

To assess the long-term natural course of early-onset facioscapulohumeral dystrophy (FSHD), which is important for patient management and trial-readiness, and is currently lacking.