Tolerability of 2 doses of pandemic influenza vaccine (Focetria®) and of a prior dose of seasonal 2009-2010 influenza vaccination in the Netherlands.

In the Netherlands, people indicated for seasonal influenza vaccination are divided in 3 risk groups, i.e. those less than 60 y (y) with comorbidity and those 60 y and over with and without comorbidity. Those risk groups were also eligible for pandemic vaccination during the 2009 influenza A(H1N1) pandemic. We assessed tolerability of seasonal influenza vaccination and 2 doses of pandemic influenza A(H1N1) vaccine, adjuvanted with MF-59, administered 2 and 5 weeks after seasonal 2009-2010 vaccination among adults. Vaccinees were asked to return questionnaires on local and systemic adverse events (AEs) after each of 3 consecutive vaccinations given at the office of their General Practitioner. Sex- and risk group-specific AE-frequencies were calculated. Generalized Linear Mixed Model with seasonal vaccination as reference was used to calculate odds ratios (ORs) for AEs of the 2 pandemic doses. 5553 questionnaires (3251 vaccinees) were returned. Vaccinees reported any local AE after seasonal vaccination and both pandemic doses in 34%, 23%, and 18%, respectively. These percentages were 29%, 25%, and 16% for any systemic AE. Men reported fewer local and systemic AEs then women (p<0.0001). The risk of local (OR range 0.34-0.63) and systemic (OR range 0.39-0.99) AEs (overall, stratified by risk group and by sex) was lower after both pandemic doses compared to seasonal vaccination. This decreased risk was more pronounced after the second pandemic dose than after the first. Therefore, we conclude that MF59-adjuvanted pandemic vaccine given after seasonal vaccination was well tolerated.

[Possible exposure to rabies in anamnesis: rabies advice in the Netherlands]. / Mogelijke blootstelling aan rabiës in de anamnese: rabiesadvisering in Nederland.

Anamnestic incidences of four patients have highlighted the potential risk ofexposure to rabies. The first patient was a 30-year-old woman who rescued a bat from the mouth of her dog; it bit her on the right wrist. In the Netherlands, bats may be infected with the Lyssa virus. The Preparedness and Response Unit (PRU) of the Centre for Infectious Disease Control (CIDC) advised human rabies immunoglobulin (HRIG) and a full vaccination programme. The second patient was a 37-year-old woman, who caught a 'sick' squirrel and was subsequently bitten on her left hand. The advice was not to use post exposure prophylaxis since rabies is not prevalent amongst squirrels in the Netherlands. The third patient, a 55-year-old man, was bitten on his right calf by a dog in Sri Lanka. He was treated with HRIG and given the full vaccination course. The fourth patient was a 14-month-old boy who was scratched on the face by a cat in Turkey. He immediately received the first vaccination and upon return to the Netherlands was treated with HRIG and the other vaccinations. All patients remained without symptoms. A structured approach for risk assessment of each potential rabies incident is possible. It requires balancing a number of criteria: the species of animal, the endemicity of rabies in a country, the observed health or vaccination status of an animal, whether the animal can be tested for rabies, if the exposure was provoked or unprovoked, the type of injury and its location on the body of the injured, and the time interval between administration of HRIG and vaccine. In the Netherlands all health care providers are expected to perform a proper risk assessment. They may seek advice from regional health departments (Municipal Health Services), who, in turn, can be assisted by the PRU. HRIG and vaccine are only provided by the National Vaccine Institute in Bilthoven.

Poststress left ventricular ejection fraction is an independent predictor of major cardiac events in patients with coronary artery disease and impaired left ventricular function.

AIM: The aim of this study was to investigate the prognostic value of myocardial perfusion and function SPECT imaging in patients with coronary artery disease (CAD) and poor left ventricular (LV) function. METHODS: We studied 261 patients (231 men, age 66+/-10 years) with CAD and a resting LV ejection fraction (LVEF)

[Safety surveillance in the National Vaccination Programme; fewer adverse events with the DTP-IPV-Hib vaccine after the transition to an acellular pertussis component in 2005]. / Veiligheidsbewaking van Rijksvaccinatieprogramma; minder bijwerkingen van DKTP-Hib-combinatievaccin sinds overgang in 2005 naar vaccin met acellulaire kinkhoestcomponent.

OBJECTIVE: To determine the adverse reactions to the combined vaccine against diptheria, acellular pertussis, tetanus, poliomyelitis and Haemophilus Infuenzae type B (DTP-IPV-Hib) before and after the introduction of an acellular pertussis component. DESIGN: Descriptive. METHOD: Safety surveillance of the Dutch National Vaccination Programme is performed by the National Institute for Public Health and Environment (RIVM). It is based on an enhanced passive reporting system and complemented by targeted survey-based studies. The data obtained were analysed. RESULTS: The passive surveillance system showed a large increase in reports in 2004, probably linked to increased media attention on the efficacy and safety of the whole-cell DTP-IPV-Hib vaccine. The Health Council recommended transitioning to the use of a DTP-IPV-Hib vaccine with an acellular pertussis component, which was implemented in January 2005. The number of reports dropped sharply in 2005 to a level below that of 2002-2003. Results of a survey study on adverse events following DTP-IPV-Hib vaccination that began in late 2003 and continued in 2005 confirmed the wide coverage ofthe enhanced passive surveillance system and revealed low rates of underreporting of rare adverse events, such as collapse and convulsions. CONCLUSION: This study confirms the data from the passive surveillance system, which show that the newly introduced acellular DTP-IPV-Hib vaccine is associated with fewer adverse events than the whole-cell vaccine that was used previously.

[Increase in the number of invasive Haemophilus influenzae type b infections]. / Toename van het aantal invasieve infecties door Haemophilus influenzae type b.

OBJECTIVE: To describe the increase of invasive Haemophilus influenzae type b (Hib) infections in The Netherlands before and after the introduction of Hib vaccination in 1993, and to hypothesise about possible explanations. DESIGN: Descriptive. METHOD: Data on the prevalence of invasive Hib infections, such as meningitis and epiglottitis, during 1990-2004 were obtained from The Netherlands Reference Laboratory for Bacterial Meningitis, which collects Hib isolates from spinal fluid and blood from across the country. RESULTS: The incidence of invasive Hib infections decreased substantially for a few years after 1993. The total number of isolates was at a minimum in 1999 (n = 12) and increased to 49 in 2004. The annual number of patients with vaccine failure was 5 or less during 1995-2001, but was between 10 and 15 from 2002 onwards. A definite explanation for the increase in the incidence of invasive Hib infections cannot be given. Improbable causes are a surveillance artefact, an impaired response to the vaccine due to vaccination-scheme changes or interaction with other vaccines, or selection of Hib variants that are less sensitive to the vaccine-induced immunity. It most likely involves secondary vaccine failure: Hib carriership is decreased by mass vaccination, whereupon natural boosting occurs less frequently later in life. Subsequently, immunity decreases and susceptibility to invasive infection increases. Careful surveillance of invasive Hib infections in The Netherlands remains important.

Combining SPECT medical imaging and computational fluid dynamics for analyzing blood and dialysate flow in hemodialyzers.

For a better insight in dialyzer efficiency with respect to local mass transport in a low flux dialyzer (Fresenius F6HPS), blood and dialysate flow distributions were visualized with computational fluid dynamic (CFD) simulations, which were validated with single photon emission computed tomography (SPECT) imaging. To visualize blood-side flow while avoiding transport through the fiber membrane, a bolus of 99m-Technetium labeled MAA (Macro Aggregated Albumin) was injected in the flow using an electronic valve. Water was used to simulate blood, but flow rate was adjusted according to laws of dynamic similarity to account for the viscosity difference (factor 2.75). For the visualization of dialysate flow, a bolus of 99m-Technetium labeled DMSA (Dimercaptosuccinic Acid) was injected, while pressurized air in the blood compartment avoided transmembrane flow. For each test series, 3D acquisitions were made on a two respectively three-headed SPECT camera. By evaluating the images at different time steps, dynamic 3D intensity plots were obtained, which were further used to derive local flow velocities. Additionally, three-dimensional CFD models were developed for simulating the overall blood and dialysate flow, respectively. In both models,the whole fiber compartment was defined as a porous medium with overall axial and radial permeability derived theoretically and from in vitro tests. With the imaging as well as with the computational technique, a homogeneous blood flow distribution was found, while vortices and fluid stagnation were observed in the dialyzer inlet manifold. The non-homogeneous dialysate distribution, as found with SPECT imaging, implies the occurrence of non-efficient sites with respect to mass transfer. The discrepancy between the dialysate results of both techniques indicated that the assumption of a constant fiber bundle permeability in the CFD model was too optimistic. In conclusion, medical imaging techniques like SPECT are very helpful to validate CFD models, which can be further applied for dialyzer design and optimization.

[Protection of children born to hepatitis-B-infected mothers]. / Bescherming van kinderen geboren uit met hepatitis-B-virus geïnfecteerde moeders.

The vaccination schedule implemented on 1 March 2003 for the approximately 1000 Dutch children per year born to hepatitis-B-virus-infected mothers is under discussion. The Health Council of The Netherlands and TNO have both published reports which reveal that the current schedule does not fulfil its objectives, as too many children are completely missed and many of the vaccinated children do not receive their scheduled vaccinations on time. Furthermore, doubts have been expressed about the effectiveness of the present vaccination schedule. In line with one of the schedules proposed by the Health Council we suggest the introduction of a 4-dose vaccination, in which the first vaccination is given immediately after the birth of the child. The subsequent vaccinations can then take place after 2, 4 and 11 months. These are the ages at which other children are also vaccinated against hepatitis B in accordance with the Dutch national vaccination programme. Furthermore, we advise an improved surveillance to ensure compliance with the individual vaccination schedules for these children. If data from the hepatitis-B screening of pregnant women, the regional vaccination registers, and the vaccinations actually administered are linked, then it will be possible to take swift action if a child is late for a hepatitis-B vaccination. In our opinion, this can best be achieved if a single national organisation is made responsible for the entire process, starting from the collection of the hepatitis-B data of pregnant women up to concluding the scheme, whether or not the serologic response is checked.

[Increased risk of hepatitis B due to incomplete or untimely immunisation in one-quarter of infants of hepatitis-B-virus carriers]. / Verhoogd risico op hepatitis B door onvolledige of ontijdige immunisatie bij een kwart van de zuigelingen van hepatitis-B-virusdraagsters.

OBJECTIVE: To determine the frequency of an increased risk of infection in children of hepatitis-B-virus carriers due to incomplete or untimely hepatitis-B immunisation. DESIGN: Descriptive. METHOD: Dates of birth and hepatitis-B immunisations were collected for all documented children of hepatitis-B-virus carriers in the vaccination registers, born in 2000 in The Netherlands. To assess the possible increased risk of infection, criteria were drawn up for the completeness and timeliness of the immunisations and on the basis of these the number of children who possibly had an increased risk of infection was determined. RESULTS: In total, 731 of the 769 children (95%) had received hepatitis-B immunoglobulins and at least 3 vaccinations. For 200 children (26%) the deviation from the immunisation schedule was so great that the child was possibly (temporarily) inadequately protected. CONCLUSION: A quarter of the children of hepatitis-B-virus carriers were immunised incompletely or at the wrong time. This calls for an adjustment of the immunisation schedule and national guidelines in which the responsibilities and tasks are clearly defined.

Validation of planar and tomographic radionuclide ventriculography by a dynamic ventricular phantom.

Although there is increasing interest in the automatic processing of tomographic radionuclide ventriculography (TRV) studies, validation is mainly limited to a comparison of TRV results with data from planar radionuclide ventriculography (PRV) or gated perfusion single photon emission computed tomography (SPECT). The aim of this study was to use a dynamic physical cardiac phantom to validate the ejection fraction (EF) and volumes from PRV and TRV studies. A new dynamic left ventricular phantom was constructed and used to obtain 21 acquisitions in the planar and tomographic mode. The directly measured volumes and EFs of the phantom during the acquisitions were considered as the gold standard for comparison with TRV and PRV. EFs were calculated from PRV by background-corrected end-diastolic and end-systolic frames. Volumes and EFs were calculated from TRV by region growing with different lower thresholds to search for the optimal threshold. EF from PRV correlated significantly with the real EF (r=0.94, P=0.00). The optimal threshold value for volume calculation from TRV in 336 cases was 50% (r=0.98, P=0.00) yielding the best slope after linear regression. When considering these calculated end-diastolic and end-systolic volumes, EF correlated well (r=0.99, P=0.00) with the real EF, and this correlation was significantly (P=0.04) higher than that of the EF from PRV. Our experiments prove that EF measured by TRV yields more accurate results compared with PRV in dynamic cardiac phantom studies.

The clinical value of nuclear medicine in the assessment of irradiation-induced and anthracycline-associated cardiac damage.

Two groups of patients, those treated for Hodgkin's disease and breast cancer, are particularly at risk of developing late myocardial damage, since radiotherapy (RT) techniques for both patient groups may include (large) parts of the heart, and adjuvant systemic therapy is frequently administered to these patients, in particular anthracycline-containing chemotherapy. Available literature on the monitoring and prediction of RT-induced and anthracycline-associated cardiac damage using nuclear medicine techniques is presented. Based on relevant studies, the risk of overall cardiac disease post-RT and overt congestive heart failure during anthracycline-containing chemotherapy is probably low. Conventional nuclear medicine imaging, i.e. myocardial perfusion scintigraphy, may be of complementary use to echocardiographical evaluation for routine follow-up after RT with modern techniques, in a subgroup of patients with known cardiovascular risk factors. Left ventricle ejection fraction (LVEF) measurements, as assessed by radionuclide angiography for the monitoring of anthracycline-associated cardiac injury, are not very sensitive and early detection will probably be enhanced by combining LVEF measurements with other cardiac function parameters. Also, it may be expected that nuclear medicine techniques using molecular radioligands will constitute an essential future step in the evaluation of subclinical cardiac injury afforded by the combined effect of RT and cardiotoxic chemotherapy.

Age- and gender-specific differences in left ventricular cardiac function and volumes determined by gated SPET.

The aim of this study was to determine normative volumetric data and ejection fraction values derived from gated myocardial single-photon emission tomography (SPET) using the commercially available software algorithm QGS (quantitative gated SPET). From a prospective database of 876 consecutive patients who were referred for a 2-day stress-rest technetium-99m tetrofosmin (925 MBq) gated SPET study, 102 patients (43 men, 59 women) with a low (<10%) pre-test likelihood of coronary disease were included (mean age 57.6 years). For stress imaging, a bicycle protocol was used in 79 of the patients and a dipyridamole protocol in 23. Left ventricular ejection fraction (LVEF) and end-diastolic and -systolic volumes (EDV and ESV) were calculated by QGS. EDV and ESV were corrected for body surface area, indicated by EDVi and ESVi. To allow comparison with previous reports using other imaging modalities, men and women were divided into three age groups (<45 years, > or =45 years but <65 years and > or =65 years). Men showed significantly higher EDVi and ESVi values throughout and lower LVEF values when compared with women in the subgroup > or =65 years (P<0.05, ANOVA). Significant negative and positive correlations were found between age and EDVi and ESVi values for both women and men and between LVEF and age in women (Pearson P< or =0.01). LVEF values at bicycle stress were significantly higher than at rest (P=0.000, paired t test), which was the result of a significant decrease in ESV (P=0.003), a phenomenon which did not occur following dipyridamole stress (P=0.409). The data presented suggest that LVEF and EDVi and ESVi as assessed by QGS are strongly gender-specific. Although the physiological significance of these results is uncertain and needs further study, these findings demonstrate that the evaluation of cardiac function and volumes of patients by means of QGS should consider age- and gender-matched normative values.

Coincidence camera FDG imaging for the diagnosis of chronic orthopedic infections: a feasibility study.

PURPOSE: Results of dedicated [(18)F]fluoro-2-deoxy-d-glucose (FDG) PET imaging in patients with suspected orthopedic infections are promising. This study evaluates the feasibility of dual-head gamma-camera coincidence (DHC) imaging in this population. METHOD: Twenty-four patients, referred for the confirmation or exclusion of orthopedic infection, were prospectively studied with consecutive FDG-dedicated PET and FDG DHC imaging. Images were read by two blinded readers experienced with FDG PET and compared with the final diagnosis, obtained by microbiologic proof in 11 patients and clinical follow-up of at least 9 months in 13 patients. RESULTS: Nine patients had osseous infection on final diagnosis. Sensitivity, specificity, and accuracy in this limited series were (Reader 1/Reader 2), respectively, 100/100, 86/86, and 92/92% for FDG-dedicated PET and 89/89, 100/93, and 96/92% for FDG DHC imaging. CONCLUSION: Despite lower image quality for FDG DHC imaging, results in this limited series were comparable with the results of FDG-dedicated PET. Further studies are needed to confirm the utility of FDG DHC imaging in suspected chronic orthopedic infections in larger patient groups.

Regional brain perfusion in 10 normal dogs measured using Technetium-99m ethyl cysteinate dimer spect.

Single photon emission computed tomography (SPECT) of the brain using perfusion tracers allows estimation of regional brain perfusion. This allows in vivo examination of brain function in the setting of neuropsychologic and pathophysiologic changes. However functional imaging data on brain perfusion in dogs are limited. Hence, the aim of this study was to determine the scintigraphic regional perfusion pattern of the normal canine brain. Ten healthy shepherd type dogs were injected with 925 MBq Technetium-99m ethyl cysteinate (ECD) 20 minutes before the examination. Acquisition was performed using a triple head gamma camera equipped with fanbeam collimators. Uniform attenuation correction and triple energy window correction were applied. Computed tomographic images were obtained from the same dogs, reoriented along the orbito-meatal axis and SPECT perfusion data were coregistered to the CT-volume data. Based on morphological and suggested brain divisions, regions-of-interest (ROIs) were defined for the bilateral frontocerebral, temporocerebral, parietocerebral, occipitocerebral, cerebellar, thalamic, and striatal area. Regional count density was normalized on total counts. All dogs had the highest uptake in the thalamic/striatal area compared to a rather homogeneous cerebral uptake. No significant left/right count differences were found, but a rostro-caudal gradient (+12-13%) was present. In this group, age and gender did not influence the perfusion pattern.

Cardiac fluorine-18 fluorodeoxyglucose imaging using a dual-head gamma camera with coincidence detection: a clinical pilot study.

Dual-headed gamma cameras with coincidence detection (MCD) are increasingly used for imaging of positron-emitting tracers, such as fluorine-18 fluorodeoxyglucose (FDG). In this study, we examined differences between FDG MCD and FDG positron emission tomography (PET) as the gold standard to determine whether FDG MCD could be used for assessment of myocardial viability in daily practice. Nineteen patients with a previous myocardial infarction (17 men; mean left ventricular ejection fraction 44%+/-13%) underwent FDG MCD, FDG PET, resting echocardiography and technetium-99m tetrofosmin gated single-photon emission tomography (SPET). At the 50% threshold value for FDG PET, the area under the receiver operating characteristic curve for FDG MCD was 0.77+/-0.03. In 107 dyssynergic segments on echocardiography and 151 segments with hypoperfusion on 99mTc-tetrofosmin SPET, the specificity of FDG MCD for the detection of myocardial viability was 72% and 76% respectively, with a sensitivity of 69% and 72% respectively. Regional analysis showed a significantly lower agreement of FDG MCD and FDG PET in the inferior and septal regions (58% for dyssynergic segments and 65% for segments with hypoperfusion), as compared with the other regions (85% for dyssynergic regions, P<0.05, and 86% for segments with hypoperfusion, P<0.05). Five patients (26%), who all had a body mass index > or =25% kg/m2, showed more than 25% disagreement between FDG MCD and FDG PET. Because of the moderate overall agreement with FDG PET, the low sensitivity in akinetic or dyskinetic regions and the low agreement in the inferior and septal regions, further studies and implementations of technical developments are needed before FDG MCD can be introduced into clinical practice for the assessment of myocardial viability.

Automatic quantification of defect size using normal templates: a comparative clinical study of three commercially available algorithms.

Infarct size assessed by myocardial single-photon emission tomography (SPET) imaging is an important prognostic parameter after myocardial infarction (MI). We compared three commercially available automatic quantification algorithms that make use of normal templates for the evaluation of infarct extent and severity in a large population of patients with remote MI. We studied 100 consecutive patients (80 men, mean age 63 +/- 11 years, mean LVEF 47% +/- 15%) with a remote MI who underwent resting technetium-99m tetrofosmin gated SPET study for infarct extent and severity quantification. The quantification algorithms used for comparison were a short-axis algorithm (Cedars-Emory quantitative analysis software, CEqual), a vertical long-axis algorithm (VLAX) and a three-dimensional fitting algorithm (Perfit). Semiquantitative visual infarct extent and severity assessment using a 20-segment model with a 5-point score and the relation of infarct extent and severity with rest LVEF determined by quantitative gated SPET (QGS) were used as standards to compare the different algorithms. Mean infarct extent was similar for visual analysis (30% +/- 21%) and the VLAX algorithm (25% +/- 17%), but CEqual (15% +/- 11%) and Perfit (5% +/- 6%) mean infarct extents were significantly lower compared with visual analysis and the VLAX algorithm. Moreover, infarct extent determined by Perfit was significantly lower than infarct extent determined by CEqual. Correlations between automatic and visual infarct extent and severity evaluations were moderate (r = 0.47, P < 0.0001 to r = 0.62, P < 0.0001) but comparable for all three algorithms. Correlations between LVEF and visual evaluation of infarct extent (r = -0.80, P < 0.0001) and severity (r = -0.82, P < 0.0001) were good but correlations were significantly lower for all three algorithms (r = -0.48, P < 0.0001 to r = -0.65, P < 0.0001). Systematically lower correlations were found in non-anterior infarctions (n = 69) and obese patients (BMI > or = 30 kg/m2, n = 32) compared with anterior infarctions and non-obese patients for all three algorithms. In this large series of post-MI patients, results of infarct extent and severity determination by automatic quantification algorithms that make use of normal templates were not interchangeable and correlated only moderately with semiquantitative visual analysis and LVEF.

Prevalence of potential candidates for biventricular pacing among patients with known coronary artery disease: a prospective registry from a single center.

New forms of ventricular pacing are increasingly studied as an option in the management of patients with heart failure. Coronary artery disease (CAD) is the most frequent cause of heart failure, and patients with complete left or right bundle branch block (LBBB and RBBB) and a reduced left ventricular ejection fraction (LVEF) are the best candidates for this new therapy. However, the prevalence of this clinical presentation is uncertain. During a 1-year period, 433 patients with documented CAD (mean age 64 +/- 10 years, 79% men) who were referred for myocardial perfusion imaging were prospectively studied. All patients underwent a 2-day stress-rest gated 99mTc-Tetrofosmin SPECT study with evaluation of resting LV enddiastolic (LVEDV) and endsystolic (LVESV) volumes and LVEF. The resting ECG was examined in all patients for the presence of complete LBBB or RBBB. Of the 433 patients with CAD 36 patients (8.3%) had LBBB (n = 14) or RBBB (n = 22) and a QRS width > 120 ms. These 36 patients were in general older and more frequently had diabetes and atrial fibrillation. Patients with LBBB or RBBB had a significantly lower LVEF (41 +/- 16% vs 48 +/- 14%, P < 0.01) and significantly higher LV volumes compared to patients without LBBB or RBBB (177 +/- 79 mL vs 131 +/- 53 mL, P < 0.001 for LVEDV and 116 +/- 76 mL vs 73 +/- 49 mL, P < 0.001 for LVESV). In total, 112/433 (26%) had an LVEF < or = 40%; 16 had also a LBBB or RBBB (3.7% of the whole population, 14% of the patients with a LVEF < or = 40%). Within the group of patients with a LVEF > or = 40%, patients with BBB had comparable LVEF (26 +/- 9% vs 30 +/- 8%, P = NS) but significantly higher LVEDV and LVESV (230 +/- 70 mL vs 190 +/- 64 mL, P < 0.05 for LVEDV and 170 +/- 65 mL vs 135 +/- 56 mL, P < 0.05 for LVESV). In this prospective registry 3.7% of all patients with known CAD had LBBB or RBBB in combination with a LVEF < or = 40%. This represented 14% of all patients with a LVEF > or = 40%. These limited numbers should be kept in mind when considering biventricular pacing as a new therapeutic options in patients with heart failure.