Once Nocturia, Always Nocturia? Natural History of Nocturia in Older Men Based on Frequency-Volume Charts:The Krimpen Study

Purpose: Nocturia is a highly prevalent and bothersome symptom that might (spontaneously) resolve. However, longitudinal data are not available on the incidence and resolution of nocturia assessed with frequency-volume charts. In this study we determined the prevalence, incidence and resolution rates of nocturia assessed by frequency-volume charts, and compared nocturnal voiding frequency over time as assessed by frequency-volume charts and questionnaires. Materials and Methods: A longitudinal, population based study was conducted among 1,688 men 50 to 78 years old with followup rounds at 2.1, 4.2 and 6.5 years. Nocturnal voiding frequency was determined with frequency-volume charts and, for comparison purposes, with a question from the International Prostate Symptom Score. Nocturia was defined as nocturnal voiding frequency 2 or greater. Prevalence, incidence and resolution rates were also determined. Results: At the 2.1-year followup the incidence rate was 23.9% and the resolution rate was 36.7%. The incidence rate was highest in the oldest group (70 to 78 years) and lowest in the youngest (50 to 54 years), whereas the resolution rate was highest in the group 55 to 59 years old and lowest in the oldest group. Because of the high resolution rate, no reliable incidence rates can be calculated. Despite fluctuation, the prevalence of nocturia increased with age and over time (from 34.4% to 44.7% for the total group, p <0.05). Men who had a frequency-volume chart-nocturnal voiding frequency less than International Prostate Symptom Score-nocturnal voiding frequency (6% of the population) more often had this later on. Conclusions: In this population frequency-volume chart assessed nocturia shows considerable fluctuation. Nevertheless, prevalence increases over time and with increasing age. Men who once had frequency-volume chart-nocturnal voiding frequency less than International Prostate Symptom Score-nocturnal voiding frequency are more likely to have this again. Therefore, frequency-volume charts as well as the International Prostate Symptom Score should be used when evaluating nocturia

Validation of New Gene Variant Classification Methods:a Field-Test in Diagnostic Cardiogenetics

Background: In the molecular genetic diagnostics of Mendelian disorders, solutions are needed for the major challenge of dealing with the large number of variants of uncertain significance (VUSs) identified using next-generation sequencing (NGS). Recently, promising approaches using constraint metrics to calculate case excess scores (CE), etiological fractions (EF), and gnomAD-derived constraint scores have been reported that estimate the likelihood of rare variants in specific genes or regions that are pathogenic. Our objective is to study the usability of these constraint data into variant interpretation in a diagnostic setting, using our cardiomyopathy cohort. Methods and Results: Patients (N = 2002) referred for clinical genetic diagnostics underwent NGS testing of 55–61 genes associated with cardiomyopathies. Previously classified likely pathogenic (LP) and pathogenic (P) variants were used to validate the use of data from CE, EF, and gnomAD constraint analyses for (re)classification of associated variant types in specific cardiomyopathy subtype-related genes. The classifications corroborated in 94% (354/378) of cases. Next, we reclassified 23 unique VUSs to LP, increasing the diagnostic yield by 1.2%. In addition, 106 unique VUSs (5.3% of patients) were prioritized for co-segregation or functional analyses. Conclusions: Our analysis confirms that the use of constraint metrics data can improve variant interpretation, and we, therefore, recommend using constraint scores on other cohorts and disorders and its inclusion in variant interpretation protocols

An Exploratory Practice-Oriented Pilot Study into Matched Treatments in Patients with Non-Specific Neck Pain

Background: Even though physiotherapists attempt to match care to the patient’s needs, there is little knowledge about which treatments are applied in daily practice and which treatments have the most potential to improve ROM in patients with non-specific neck pain with a limited ROM. The objective of this study was 1) to establish the measurement error of the Sensamove cervical training accelerometer (SCT); 2) to describe the applied treatments for patients with non-specific neck pain with an identified restriction in cervical Range of Motion (ROM) in primary care physiotherapy clinics; 3) to explore if the cervical ROM, pain, (perceived) disability and motor control improved after one manual therapy treatment. Methods: The standard error of measurement (SEM) and the smallest detectable difference (SDD) were calculated based on a test-retest study. Second, an explorative, longitudinal study design (follow-up one week) was performed. Inclusion criterion: nonspecific neck pain with an identified restriction in cervical ROM. Measurements: pre- (T0) and post-treatment (T1), and one-week post-treatment (T2). Outcomes: ROM, motor control movement task, Numerical Pain Rating Scale (NPRS), and Patient Specific Function Scale (PSFS). Results: The SEM varied from 1.62° (lateral flexion right) to 3.46° (extension). The SDD varied from 4.49° (lateral flexion right) to 9.58° (extension). Four physiotherapists included 24 patients and used eight different treatments. The T0-T2 improvement in cervical ROM ranged from 2.95° (SD 6.09) (right lateral flexion) to 11.00° (SD11.87) (left rotation). The movement task was performed 3.96 (SD 4.24) seconds faster. The NPRS decreased by 3.08 (SD 1.82) points, and PSFS improved by 7.71 (SD 5.34) points. Conclusion: The measurement error has been established. Moreover, this study illustrates that matched treatments, as applied in daily practice, have the potential to induce short-term improvements

Diagnostic yield of targeted next generation sequencing in 2002 Dutch cardiomyopathy patients

BACKGROUND: Next-generation sequencing (NGS) is increasingly used for clinical evaluation of cardiomyopathy patients as it allows for simultaneous screening of multiple cardiomyopathy-associated genes. Adding copy number variant (CNV) analysis of NGS data is not routine yet and may contribute to the diagnostic yield. OBJECTIVES: Determine the diagnostic yield of our targeted NGS gene panel in routine clinical diagnostics of Dutch cardiomyopathy patients and explore the impact of exon CNVs on diagnostic yield. METHODS: Patients (N = 2002) referred for clinical genetic analysis underwent diagnostic testing of 55-61 genes associated with cardiomyopathies. Samples were analyzed and evaluated for single nucleotide variants (SNVs), indels and CNVs. CNVs identified in the NGS data and suspected of being pathogenic based on type, size and location were confirmed by additional molecular tests. RESULTS: A (likely) pathogenic (L)P variant was detected in 22.7% of patients, including 3 with CNVs and 25 where a variant was identified in a gene currently not associated with the patient's cardiomyopathy subtype. Only 15 out of 2002 patients (0.8%) were found to carry two (L)P variants. CONCLUSION: The yield of routine clinical diagnostics of cardiomyopathies was relatively low when compared to literature. This is likely due to the fact that our study reports the outcome of patients in daily routine diagnostics, therefore also including patients not fully fulfilling (subtype specific) cardiomyopathy criteria. This may also explain why (L)P variants were identified in genes not associated with the reported subtype. The added value of CNV analysis was shown to be limited but not negligible

Multidetector CT imaging of mechanical prosthetic heart valves: quantification of artifacts with a pulsatile in-vitro model

Item does not contain fulltextOBJECTIVES: Multidetector computed tomography (MDCT) can detect the cause of prosthetic heart valve (PHV) dysfunction but is hampered by valve-induced artifacts. We quantified artifacts of four PHV using a pulsatile in-vitro model and assessed the relation to leaflet motion and valve design. METHODS: A Medtronic Hall tilting disc (MH), and Carbomedics (CM), St Jude (SJM), and ON-X bileaflet valves underwent CT in an in-vitro model using retrospective gating with a 64 detector CT system in stationary and pulsatile conditions. Artifacts and radiopaque component volumes were quantified with thresholds based on surrounding structures and valvular components. RESULTS: Hypodense artifacts volumes (mm(3)) were 1,029 +/- 147, 535 +/- 53, 371 +/- 16, and 366 +/- 18 for the SJM, MH, CM and ON-X valves (p < 0.001 except for the latter two valves p = 0.43). Hyperdense artifact volumes were 3,546 +/- 141, 2,387 +/- 103, 2,003 +/- 102, and 3,033 +/- 31 for the SJM, MH, CM and ON-X valve, respectively (all differences p < 0.001). Leaflet motion affected hypodense (F = 41.5, p < 0.001) and hyperdense artifacts (F = 53.7, p < 0.001). Closed and moving leaflets were associated with the least and the most artifacts respectively (p < 0.001, both artifact types). CONCLUSION: Both valve design and leaflet motion affect PHV-induced artifacts. Best imaging results may be expected for the CM valve during phases in which the leaflets are closed

Prospective ECG triggering reduces prosthetic heart valve-induced artefacts compared with retrospective ECG gating on 256-slice CT

Item does not contain fulltextOBJECTIVES: Multidetector computed tomography (MDCT) has diagnostic value for the evaluation of prosthetic heart valve (PHV) dysfunction but it is hampered by artefacts. We hypothesised that image acquisition using prospective triggering instead of retrospective gating would reduce artefacts related to pulsating PHV. METHODS: In a pulsatile in vitro model, a mono- and bileaflet PHV were imaged using 256 MDCT at 60, 75 and 90 beats per minute (BPM) with either retrospective gating (120 kV, 600 mAs, pitch 0.2, CTDI(vol) 39.8 mGy) or prospective triggering (120 kV, 200 mAs, CTDI(vol) 13.3 mGy). Two thresholds (>175 and <-45HU), derived from the density of surrounding structures, were used for quantification of hyper- and hypodense artefacts. Image noise and artefacts were compared between protocols. RESULTS: Prospective triggering reduced hyperdense artefacts for both valves at every BPM (P = 0.001 all comparisons). Hypodense artefacts were reduced for the monoleaflet valve at 60 (P = 0.009), 75 (P = 0.016) and 90 BPM (P = 0.001), and for the bileaflet valves at 60 (P = 0.001), 90 (P = 0.001) but not at 75 BPM (P = 0.6). Prospective triggering reduced image noise at 60 (P = 0.001) and 75 (P < 0.03) but not at 90 BPM. CONCLUSIONS: Compared with retrospective gating, prospective triggering reduced most artefacts related to pulsating PHV in vitro. KEY POINTS: * Computed tomographic images are often degraded by prosthetic heart valve-induced artefacts * Prospective triggering reduces prosthetic heart valve-induced artefacts in vitro * Artefact reduction at 90 beats per minute occurs without image noise reduction * Prospective triggering may improve CT image quality of moving hyperdense structures.1 juni 201

Differential item functioning in multiple choice items

In multiple-choice items the response probability on an item may be viewed as the result of two distinct latent processes--a cognitive process to solve the problem, and another random process that leads to the choice of a certain alternative (the process of giving the actual response). An incomplete latent class model is formulated that describes the first process by a Rasch model and the second process by a guessing model. Alternative models are specified that contain additional parameters describing differential item functioning (DIF) in the two processes. DIF with respect to either known or unknown subgroups can be tested by a likelihood ratio test that is asymptotically distributed as chi-square. As an example of the model, four five-choice items from the Second International Mathematics Study (1987) with a sample of 3,002 secondary students were considered

Examining differential item functioning due to item difficulty and alternative attractiveness

differential item functioning, multiple choice items, Rasch model, guessing model, incomplete latent class model, goodness-of-fit testing,

2-iminobiotin, a selective inhibitor of nitric oxide synthase, improves memory and learning in a rat model after four vessel occlusion, mimicking cardiac arrest.

Survivors of out-of-hospital cardiac arrest (OHCA) experience between 30% and 50% cognitive deficits several years post-discharge. Especially spatial memory is affected due to ischemia-induced neuronal damage in the hippocampus. Aim of this study was to investigate the potential neuroprotective effect of 2-iminobiotin (2-IB), a biotin analogue, on memory and learning in a four-vessel occlusion model of global ischemia using the Water Maze test. Sprague-Dawley rats were randomly assigned to either sham operation (n = 6), vehicle treatment (n = 20), 1.1 (n = 15), 3.3 (n = 14), 10 (n = 14), or 30 mg/kg/dose 2-IB treatment (n = 15). Treatment was subcutaneously (s.c.) administered immediately upon reperfusion, at 12h, and at 24h after reperfusion. Memory function on day 32 was significantly preserved in all doses of 2-IB rats compared to vehicle, as was the learning curve in the 1.1, 3.3 and 30 mg/kg dose group. Adult rats treated s.c. with 3 gifts of 2-IB every 12 h in a dose range of 1.1-30 mg/kg/dose directly upon reperfusion showed significant improved memory and learning after four vessel occlusion compared to vehicle-treated rats. Since 2-IB has already shown to be safe in a phase 1 clinical trial in adult human volunteers, it is a suitable candidate for translation to a human phase 2 study after OHCA