Validation of the Innsbruck REM sleep behavior disorder inventory

A diagnosis of definite REM sleep behavior disorder requires both a positive history for REM sleep behavior disorder and polysomnographic demonstration of REM sleep without atonia. To improve and facilitate screening for REM sleep behavior disorder, there is a need for simple clinical tools with sufficient sensitivity and specificity for the identification of subjects with probable REM sleep behavior disorder. We developed a short REM sleep behavior disorder screening questionnaire with 7 REM sleep behavior disorder– and 2 non‐REM sleep behavior disorder–specific control items and performed a validation study in 70 REM sleep behavior disorder subjects and 140 sleep disorder controls. Response patterns to all 7 REM sleep behavior disorder–specific items differed between REM sleep behavior disorder and non‐REM sleep behavior disorder patients (all P < 0.05), whereas the 2 non‐REM sleep behavior disorder–specific control items did not differentiate between REM sleep behavior disorder and non‐REM sleep behavior disorder (all P > .05). In 5 of the 7 REM sleep behavior disorder–specific items, AUC was greater than 0.700. These 5 items were included in the Innsbruck REM sleep behavior disorder inventory. In this questionnaire, a cutoff of 0.25 (number of positive symptoms divided by number of answered questions) had a sensitivity of 0.914 and a specificity of 0.857 for both idiopathic and Parkinson's‐related REM sleep behavior disorder (AUC, 0.886). The Innsbruck REM sleep behavior disorder inventory is a promising, easy‐to‐use, short screening tool for REM sleep behavior disorder with excellent sensitivity and specificity for both idiopathic and Parkinson's‐related REM sleep behavior disorder. © 2012 Movement Disorder Society     

Objective assessment of nonadherence and unknown co-medication in hospitalized patients

Purpose

The intake of medications (drugs) without the knowledge of the treating physician (unknown co-medication) and nonadherence strongly influence drug safety. The aim of our study was to objectively assess unknown co-medication and nonadherence in hospitalized patients by screening urine for a large number of drugs using highly sensitive full scan gas chromatograpy/mass spectrometry (GC/MS). Secondary objectives were to determine the relationship of co-medication and nonadherence to the number of drugs prescribed and to compare history-taking by a pharmacist versus a physician.

Methods

In 152 patients, the drug histories taken by physicians, patients’ self-reported adherence, and information compiled during as many as three structured interviews conducted by a trained pharmacist on days 1–2, 3–4, and 7–11 of the hospital stay were compared with the GC/MS results from urine samples collected after each interview.

Results

In the interviews performed by the pharmacist, 235 additional drugs were identified that were not documented in the chart. Of all the drugs indicated in any interview, 16.9% were identified only by the physician, 24.1% only by the pharmacist, and 59% by both. Overall, in 78% of the patients at least one additional drug was identified by urine screening. The findings suggest overall nonadherence to at least one drug in 13.0% of patients on admission and in 23.3% of patients at any time during hospitalization. Nonadherence was less frequent for critical dose drugs and correlated with the number of prescribed drugs.

Conclusions

The drug history among hospitalized patients is often incomplete, and nonadherence and unknown co-medication are alarmingly frequent. This lack of knowledge might impact the overall success of drug therapies in the hospital setting.     

Frequency and characterization of known and novel RHD variant alleles in 37 782 Dutch D‐negative pregnant women

To guide anti‐D prophylaxis, Dutch D‐ pregnant women are offered a quantitative fetal‐RHD‐genotyping assay to determine the RHD status of their fetus. This allowed us to determine the frequency of different maternal RHD variants in 37 782 serologically D‐ pregnant women. A variant allele is present in at least 0·96% of Dutch D‐ pregnant women The D‐ serology could be confirmed after further serological testing in only 54% of these women, which emphasizes the potential relevance of genotyping of blood donors. 43 different RHD variant alleles were detected, including 15 novel alleles (11 null‐, 2 partial D‐ and 2 DEL‐alleles). Of those novel null alleles, one allele contained a single missense mutation (RHD*443C>G) and one allele had a single amino acid deletion (RHD*424_426del). The D‐ phenotype was confirmed by transduction of human D‐ erythroblasts, consolidating that, for the first time, a single amino acid change or deletion causes the D‐ phenotype. Transduction also confirmed the phenotypes for the two new variant DEL‐alleles (RHD*721A>C and RHD*884T>C) and the novel partial RHD*492C>A allele. Notably, in three additional cases the DEL phenotype was observed but sequencing of the coding sequence, flanking introns and promoter region revealed an apparently wild‐type RHD allele without mutations.     

Suicide prevention by limiting access to methods: A review of theory and practice

This review discusses the limitation of access to suicide methods as a way to prevent suicide, an approach which forms a major component of many national suicide prevention strategies. An important distinction is made between efforts that attempt to limit physical access to suicide methods and those that attempt to reduce the cognitive availability of suicide. Physical imitations will be reviewed with reference to restricting access to domestic gas, catalytic converters, firearms, pesticides, jumping, paracetamol and methods used in prisons. Impacts of cognitive availability will be discussed mainly with regard to the media in terms of providing access to technical information and sensational or inaccurate portrayals of suicide. Drawing on psychological models of suicidal ideation and behaviour, this review explores how processes leading to suicidal behaviour and issues around method choice may relate to the effectiveness of limiting access to methods. Potential problems surrounding method limitations are explored, in particular the factors contributing to substitution, the risk that alternative methods of suicide may be used if one is restricted. It is concluded that in appropriate contexts, where substitution is less likely to occur, and in conjunction with psychosocial prevention efforts, limitation of both physical and cognitive access to suicide can be an effective suicide prevention strategy.     

Inhibition of Calcium-Dependent Protein Kinase 1 (CDPK1) In Vitro by Pyrazolopyrimidine Derivatives Does Not Correlate with Sensitivity of Cryptosporidium parvum Growth in Cell Culture

Cryptosporidiosis is a serious diarrheal disease in immunocompromised patients and malnourished children, and treatment is complicated by a lack of adequate drugs. Recent studies suggest that the natural occurrence of a small gatekeeper residue in serine threonine calcium-dependent protein kinase 1 (CDPK1) of Cryptosporidium parvum might be exploited to target this enzyme and block parasite growth. Here were explored the potency with which a series of pyrazolopyrimidine analogs, which are selective for small gatekeeper kinases, inhibit C. parvum CDPK1 and block C. parvum growth in tissue culture in vitro. Although these compounds potently inhibited kinase activity in vitro, most had no effect on parasite growth. Moreover, among those that were active against parasite growth, there was a very poor correlation with their 50% inhibitory concentrations against the enzyme. Active compounds also had no effect on cell invasion, unlike the situation in Toxoplasma gondii, where these compounds block CDPK1, prevent microneme secretion, and disrupt cell invasion. These findings suggest that CPDK1 is not essential for C. parvum host cell invasion or growth and therefore that it is not the optimal target for therapeutic intervention. Nonetheless, several inhibitors with low micromolar 50% effective concentrations were identified, and these may affect other essential targets in C. parvum that are worthy of further exploration.