[Long-term follow-up of psychogenic pseudosyncope]. / Het beloop van psychogene pseudosyncope na meedelen van de diagnose.

BACKGROUND: Patients with psychogenic pseudosyncope (PPS) are frequently seen by neurologists and psychiatrists. As of yet, there has been no follow-up study of patients with PPS after communicating the diagnosis. AIM: To determine the outcome of patients with psychogenic pseudosyncope (PPS) after communicatingthe diagnosis. METHOD: A retrospective cohort study of patients with PPS referred to a tertiary referral center for syncope from 2007 to 2015. We reviewed patient records, studying attack frequency, factors possibly affecting attack frequency, health care use and quality of life using questionnaires. We explored influences on absence of attack and attack frequency in the six months before follow-up for age, sex, level of education, duration until a diagnosis was made, probability of diagnosis, additional syncope and acceptance of diagnosis. RESULTS: 47 out 57 PPS cases could be traced, of these 35 (74%) participated. Twelve (34%) were attack free for at least six months. The median time from diagnosis to follow-up was 50 months (range 6-103 months). Communication and explanation of the diagnosis resulted in immediate reduction of attack frequency (p=0.007) from the month before diagnosis (median one attack, range 0-156) to the month afterwards (median one attack, range 0-16). In the six months before follow-up the number of admissions decreased from 19/35 to 0/35 (p = 0.002). Furthermore, the demand for somatic health care shifted to psychiatric care (p < 0.0001). Quality of life at follow-up (Short Form Health Survey 36; SF-36) showed lower scores for seven of the eight domains compared to matched Dutch control values. The quality of life was not significantly influenced by absence of attack. CONCLUSION: After communicating the diagnosis of PPS, attack frequency decreased and health care use shifted toward mental care. Low quality of life underlines the fact that PPS is a serious condition. Improvement of quality of life probably requires both a longer treatment and longer follow-up.

Long-term follow-up of psychogenic pseudosyncope.

OBJECTIVE: To determine the outcome of patients with psychogenic pseudosyncope (PPS) after communication of the diagnosis. METHODS: This was a retrospective cohort study of patients with PPS referred in 2007 to 2015 to a tertiary referral center for syncope. We reviewed patient records and studied attack frequency, factors affecting attack frequency, health care use, and quality of life using a questionnaire. We explored influences on attack freedom and attack frequency in the 6 months before follow-up for age, sex, education level, duration until diagnosis, probability of diagnosis, additional syncope, and acceptance of diagnosis. RESULTS: Forty-seven of 57 patients with PPS could be traced, of whom 35 (74%) participated. Twelve (34%) were attack-free for at least 6 months. The median time from diagnosis to follow-up was 50 months (range 6-103 months). Communicating and explaining the diagnosis resulted in immediate reduction of attack frequency (p = 0.007) from the month before diagnosis (median one attack, range 0-156) to the month after (median one attack, range 0-16). In the 6 months before follow-up, the number of admissions decreased from 19 of 35 to 0 of 35 (p = 0.002). The use of somatic and mental health care shifted toward the latter (p < 0.0001). Quality of life at follow-up (Short Form Health Survey 36) showed lower scores for 7 of 8 domains compared to matched Dutch control values; quality of life was not influenced by attack freedom. CONCLUSIONS: After communication of the diagnosis in PPS, attack frequency decreased and health care use shifted toward mental care. Low quality of life underlines that PPS is a serious condition.

[Unexplained loss of consciousness: the diagnosis is never based on one symptom]. / Onverklaarde wegrakingen: de diagnose berust nooit op één symptoom.

Patients with transient loss of consciousness are often seen by a variety of specialists. Even if typical signs occur, it can be difficult to identify specific causes. We discuss two patients with complex presentations. The first patient was diagnosed with sleep syncope, a relatively unknown type of reflex syncope. The prodromal symptoms of discomfort and the subsequent loss of consciousness occurred while the patient was in bed or got up to go to the toilet due to abdominal symptoms. The onset in supine position was misleading, since this is a well-known alarm symptom of a possible cardiac cause. The second patient had vasovagal syncope followed by a psychogenic pseudosyncope. This resulted in frequent loss of consciousness of long duration with typical and atypical triggers and uncommon syncopal signs, including eye closure. These conflicting symptoms can be a pitfall and clinical expertise is required to identify the type of syncope.

Finger snapping during seizures.

We describe two patients who showed snapping of the right hand fingers during invasive intracranial EEG evaluation for epilepsy surgery. We correlated the EEG changes with the finger-snapping movements in both patients to determine the underlying pathophysiology of this phenomenon. At the time of finger snapping, EEG spread from the supplementary motor area towards the temporal region was seen, suggesting involvement of these sites.

[Development of a fidelity scale for function assertive community treatment (FACT)]. / Ontwikkeling van een modelgetrouwheidsschaal voor functie-assertive community treatment (FACT).

BACKGROUND: Assertive community treatment (ACT) is one of the most important models for the care and treatment, in the community, of people with severe mental illness (SMI). ACT is concerned primarily with smi-patients who have the most complex problems and it provides care by means of intensive assertive outreach. Function act (FACT) provides care for the entire group of SMI - patients and combines the principles of case management and ACT. For a long time it has been possible to measure the degree of ACT model reliability using the facts reliability scale. Throughout this time, however, a reliability scale for FACT was not available. AIM: To develop a reliability scale for fact teams. METHOD: Using the knowledge of experts and feedback from fact teams it has been possible to develop a reliability scale for fact teams. The scale was tested and subsequently adapted as a result of 10 pilot trials performed by 10 fact teams. RESULTS: The definitive version of the scale was confirmed in 2008 and is currently used in the field. CONCLUSION: With the ACT and FACT reliability scales the research field now have two instruments with which teams working with SMI - patients can measure model reliability. The DACTS and FACTS provide opportunities for quality improvement and transparency.

Susceptibility to paratuberculosis infection in cattle is associated with single nucleotide polymorphisms in Toll-like receptor 2 which modulate immune responses against Mycobacterium avium subspecies paratuberculosis.

Paratuberculosis is a chronic intestinal infection in ruminants, caused by Mycobacterium avium subspecies paratuberculosis (Map). To study the role of host genetics in disease susceptibility, the Toll-like receptor 2 (TLR2) gene, selected based on its potential role in immunity to mycobacterial infections, was analyzed for single nucleotide polymorphisms (SNP) and their potential association with disease. For SNP discovery and to study SNP association with disease, a case-control study including 24 cows from farms with paratuberculosis was conducted. Sequence analysis of the TLR2 genes from 12 paratuberculosis-infected animals and 12 age-matched healthy herd mates revealed 21 different SNP. The TLR2-1903 T/C SNP was significantly associated with resistance to Map. This and four additional TLR2 SNP were studied in a subsequent observational field study with 553 cows from farms with paratuberculosis. The allelic distribution of the TLR2-1903 T/C SNP was confirmed to be significantly different between the infected and non-infected animals. For the TLR2-1903 T/C SNP the odds ratio was calculated, and similar to the dominance model in the association study, the CT and CC genotypes were compared to the TT genotype. Cows with the TLR2-1903 T/C mutation (i.e., the CT and CC genotypes) were at 1.7 (95% CI: 1.2, 2.8) times the odds of being Map-infected compared to cows with the TT genotype. In in vitro functional assays, monocyte-derived macrophages from animals with a TLR2-1903 TT genotype produced more IL12p40 and IL1beta when stimulated with Map compared to cells derived from TLR2-1903 CT and CC genotypes. Also, T cell proliferative responses to mycobacterial antigens were higher in animals with a TLR2-1903 TT genotype. In conclusion, we have found a significant association between SNP TLR2-1903 T/C in the bovine TLR2 gene and bovine paratuberculosis infection. This SNP and other genetic markers could be useful in marker-assisted breeding strategies as an additional tool in paratuberculosis control strategies. In addition, the functional studies suggest that genetic polymorphisms in bovine TLR2 which result in higher macrophage activity may contribute to enhanced T cell activation and a lower susceptibility to paratuberculosis in cattle.

Evaluation of different nucleic acid amplification techniques for the detection of M. pneumoniae, C. pneumoniae and Legionella spp. in respiratory specimens from patients with community-acquired pneumonia.

The number of pathogens involved in community-acquired pneumonia, with varying susceptibilities to antimicrobials, is numerous constituting an enormous challenge for diagnostic microbiology. Differentiation of infections due to Streptococcus pneumoniae and those due to Mycoplasma pneumoniae, Chlamydophila pneumoniae, or L. pneumophila as well as those due to viruses is essential to allow correct decisions concerning the antibiotics to be administered. The sensitivity and specificity of real-time simplex and multiplex nucleic acid sequence-based amplification (NASBA), and simplex PCR were compared for the detection of M. pneumoniae, C. pneumoniae and Legionella spp. in respiratory specimens from hospitalized and outpatients with community-acquired pneumonia (CAP). Two hundred fifty one respiratory specimens were collected from 147 patients with CAP. NASBA was done using the NucliSens Basic Kit (bioMérieux). PCR for M. pneumoniae and C. pneumoniae was done as described earlier [Ieven, M., Ursi, D., Van Bever, H., Quint, W., Niesters, H. G. M., and Goossens, H. 1996. Detection of Mycoplasma pneumoniae by two polymerase chain reactions and role of M. pneumoniae in acute respiratory tract infections in pediatric patients. J. Infect. Dis. 173, 1445-14452.; Ursi, D., Ieven, M., Van Bever, H. P., and Goossens, H. 1998. Construction of an internal control for the detection of Chlamydia pneumoniae by PCR. Mol. Cellul. Probes. 12, 235-238.]. A real-time PCR was developed to detect L. pneumophila whereas a real-time NASBA was designed to detect Legionella spp. All samples with discordant results were re-analysed. Compared to an expanded gold standard the sensitivities of the different techniques, were 77.8%, 100%, and 100% for detection of M. pneumoniae; and 50%, 100%, and 50% for detection of L. pneumophila by PCR, real-time simplex NASBA, and real-time multiplex NASBA, respectively. C. pneumoniae was detected in two samples only. Simplex real-time NASBA proved to be more sensitive than simplex PCR and was also more sensitive than real-time multiplex NASBA, as previously found with spiked clinical specimens. It's practical attractiveness pleads for further optimalisation of the multiplex approach.

Development of real-time multiplex nucleic acid sequence-based amplification for detection of Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Legionella spp. in respiratory specimens.

Real-time multiplex isothermal nucleic acid sequence-based amplification (NASBA) was developed to detect Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Legionella spp. in respiratory specimens using the NucliSens Basic Kit (bioMérieux, Boxtel, The Netherlands). Oligonucleotide primers were derived from the M. pneumoniae, C. pneumoniae, and Legionella pneumophila 16S rRNA. For real-time detection, molecular beacons were used. Specificity was established on a panel of bacterial strains. The analytical sensitivity of the assay was determined by testing dilutions of wild-type in vitro-generated RNA in water and dilutions of reference strains in lysis buffer or added to pools of respiratory specimens. Subsequently, a limited number of M. pneumoniae-, C. pneumoniae-, and L. pneumophila-positive and -negative clinical specimens were analyzed. Specific detection of the 16S rRNA of the three organisms was achieved. The analytical sensitivity of the multiplex NASBA on spiked respiratory specimens was slightly diminished compared to the results obtained with the single-target (mono) real-time assays. We conclude that the proposed real-time multiplex NASBA assay, although less sensitive than the real-time mono NASBA assay, is a promising tool for the detection of M. pneumoniae, C. pneumoniae, and Legionella spp. in respiratory specimens, regarding handling, speed, and number of samples that can be analyzed in a single run.

Development of conventional and real-time NASBA for the detection of Legionella species in respiratory specimens.

Isothermal nucleic acid sequence-based amplification (NASBA) was applied to detect Legionella 16S rRNA. The assay was originally developed as a Legionella pneumophila conventional NASBA assay with electrochemiluminescence (ECL) detection and was subsequently adapted to a L. pneumophila real-time NASBA format and a Legionella spp. real-time NASBA using molecular beacons. L. pneumophila RNA prepared from a plasmid construct was used to assess the analytical sensitivity of the assay. The sensitivity of the NASBA assay was 10 molecules of in vitro wild type L. pneumophila RNA and 0.1-1 colony-forming units (CFU) of L. pneumophila. In spiked respiratory specimens, the sensitivity of the NASBA assays was 1-10000 CFU of L. pneumophila serotype 1 depending on the background. After dilution of the nucleic acid extract prior to amplification, 1-10 CFU of L. pneumophila serotype 1 could be detected with both detection methods. Finally, 27 respiratory specimens, well characterized by culture and PCR, collected during a L. pneumophila outbreak, were tested by conventional and real-time NASBAs. All 11 PCR positive samples were positive by conventional NASBA, 9/11 and 10/11 were positive by L. pneumophila real-time NASBA and Legionella spp. real-time NASBA, respectively.

Development of conventional and real-time nucleic acid sequence-based amplification assays for detection of Chlamydophila pneumoniae in respiratory specimens.

Isothermal nucleic acid sequence-based amplification (NASBA) was applied to the detection of Chlamydophila pneumoniae 16S rRNA by using the NucliSens basic kit (bioMérieux, Boxtel, The Netherlands). The assay was originally developed as a conventional NASBA assay with electrochemiluminescence detection and was subsequently adapted to a real-time NASBA format by using a molecular beacon. C. pneumoniae RNA prepared from a plasmid construct was used to assess the analytical sensitivity of the assay. The sensitivity of the NASBA assay was 10 molecules of in vitro wild-type C. pneumoniae RNA and 0.1 inclusion-forming unit (IFU) of C. pneumoniae. In spiked respiratory specimens, the sensitivity of the C. pneumoniae NASBA assay varied between 0.1 and 1 IFU/100 mul sample, depending on the type of specimen. Finally, conventional and real-time NASBA were applied to respiratory specimens previously tested by PCR. A 100% concordance between the test results was obtained.

Detection of Mycoplasma pneumoniae by real-time nucleic acid sequence-based amplification.

Real-time isothermal nucleic acid sequence-based amplification (RT-NASBA) was applied to the detection of Mycoplasma pneumoniae. In vitro-generated M. pneumoniae RNA was used to assess the sensitivity of the assay. The 95% hit rate was 148 molecules of M. pneumoniae RNA in the amplification and 10(4) molecules of in vitro-generated RNA after nucleic acid extraction. The sensitivity of the RT-NASBA and the conventional NASBA assays corresponded to 5 color-changing units (CCU) of M. pneumoniae. In spiked throat swabs, nasopharyngeal aspirates, bronchoalveolar lavages, and sputum, the sensitivity of both NASBA assays corresponded to 5 to 50 CCU of M. pneumoniae. A total of 17 clinical specimens positive for M. pneumoniae by PCR were also positive by conventional NASBA, but one specimen was negative by RT-NASBA. These results indicate that the sensitivity of detection of M. pneumoniae by RT-NASBA in respiratory samples might be slightly reduced compared to that by conventional NASBA. However, the real-time assay is superior in speed and ease of handling.

Incidence of and risk factors for asymptomatic peripheral arterial occlusive disease: a longitudinal study.

The current study describes the age- and sex-specific incidence rates and risk factors for asymptomatic and symptomatic peripheral arterial occlusive disease (PAOD) among 2,327 subjects and the incidence of intermittent claudication in asymptomatic PAOD subjects. The study population was selected from 18 general practice centers in the Netherlands. PAOD was assessed with the ankle-brachial blood pressure index, and intermittent claudication was assessed with a modified version of the Rose questionnaire. After 7.2 years, the overall incidence rate for asymptomatic PAOD, using the person-years method, was 9.9 (95% confidence interval (CI): 7.3, 18.8) per 1,000 person-years at risk. The rate was 7.8 (95% CI: 4.9, 20.3) for men and 12.4 (95% CI: 7.7, 24.8) for women. For symptomatic PAOD, the incidence rate was 1.0 (95% CI: 0.7, 7.5) overall, 0.4 (95% CI: 0.3, 10.0) for men, and 1.8 (95% CI: 1.0, 10.3) for women. Multivariate analyses showed that increasing age, smoking, hypertension, and diabetes mellitus were the most important risk factors. The overall incidence rate for intermittent claudication among PAOD subjects who were asymptomatic at baseline was 90.5 per 1,000 person-years at risk (95% CI: 36.4, 378.3). The incidence of asymptomatic PAOD was higher than the incidence of symptomatic PAOD, with women developing PAOD more often than men. In the development of preventive strategies, modification of atherosclerotic risk factors, such as smoking, hypertension, and diabetes, should be the main goals.