CYP2C19 genotype-guided antithrombotic treatment versus conventional clopidogrel therapy in peripheral arterial disease: study design of a randomized controlled trial (GENPAD).

BACKGROUND: Clopidogrel is recommended in international guidelines to prevent arterial thrombotic events in patients with peripheral arterial disease (PAD). Clopidogrel itself is inactive and metabolism is dependent on the CYP2C19 enzyme. About 30% of Caucasian PAD patients receiving clopidogrel carry 1 or 2 CYP2C19 loss-of-function allele(s) and do not or to a limited extent convert the prodrug into its active metabolite. As a result, platelet inhibition may be inadequate which could lead to an increased risk of adverse clinical events related to arterial thrombosis. A CYP2C19 genotype-guided antithrombotic treatment might be beneficial for PAD patients. METHODS: GENPAD is a multicenter randomized controlled trial involving 2,276 PAD patients with an indication for clopidogrel monotherapy. Patients with a separate indication for dual antiplatelet therapy or stronger antithrombotic therapy are not eligible for study participation. Patients randomized to the control group will receive clopidogrel 75 mg once daily without pharmacogenetic guidance. Patients randomized to the intervention group will be tested for carriage of CYP2C19 *2 and *3 loss-of-function alleles, followed by a genotype-guided antithrombotic treatment with either clopidogrel 75 mg once daily for normal metabolizers, clopidogrel 150 mg once daily for intermediate metabolizers, or acetylsalicylic acid 80 mg once daily plus rivaroxaban 2.5 mg twice daily for poor metabolizers. The primary outcome is a composite of myocardial infarction, ischemic stroke, cardiovascular death, acute or chronic limb ischemia, peripheral vascular interventions, or death. The secondary outcomes are the individual elements of the primary composite outcome and clinically relevant bleeding complications. CONCLUSION: The aim of the GENPAD study is to evaluate the efficacy, safety, and cost-effectiveness of a genotype-guided antithrombotic treatment strategy compared to conventional clopidogrel treatment in PAD patients.

[RCT about mindfulness-based cognitive therapy for psychological distress in cancer patients]. / RCT naar mindfulness-based cognitieve therapie voor psychische klachten bij oncologische patiënten.

BACKGROUND: Cancer patients may experience psychological distress, like anxiety and depressive symptoms. Mindfulness-based cognitive therapy (MBCT) has been shown to alleviate this psychological distress. However, patients experience barriers in participating in face-to-face MBCT. Individual internet-based MBCT (eMBCT) could be an alternative.
AIM: To compare MBCT and eMBCT to treatment as usual (TAU) for psychological distress in cancer patients.
METHOD: 245 cancer patients with psychological distress were randomly allocated to MBCT (n = 77), eMBCT (n = 90) or TAU (n = 78). Patients completed baseline (T0) and post-intervention (T1) assessments. The primary outcome was psychological distress on the Hospital Anxiety and Depression Scale. Outcomes were analyzed using linear mixed modeling on the intention-to-treat sample. Since both interventions were compared to TAU, the type I error rate was set to p < 0.025.
RESULTS: Compared to TAU, patients reported significantly less psychological distress after both MBCT (Cohen's d = 0.43, p < 0.001) and eMBCT (Cohen's d = 0.63, p < 0.001).
CONCLUSION: Compared to TAU, MBCT and eMBCT were similarly effective in reducing psychological distress in a sample of distressed heterogeneous cancer patients.

Efficacy of web-based cognitive-behavioural therapy for chronic fatigue syndrome: randomised controlled trial.

BACKGROUND: Face-to-face cognitive-behavioural therapy (CBT) leads to a reduction of fatigue in chronic fatigue syndrome (CFS). Aims To test the efficacy of internet-based CBT (iCBT) for adults with CFS. METHOD: A total of 240 patients with CFS were randomised to either iCBT with protocol-driven therapist feedback or with therapist feedback on demand, or a waiting list. Primary outcome was fatigue severity assessed with the Checklist Individual Strength (Netherlands Trial Register: NTR4013). RESULTS: Compared with a waiting list, intention-to-treat (ITT) analysis showed a significant reduction of fatigue for both iCBT conditions (protocol-driven feedback: B = -8.3, 97.5% CI -12.7 to -3.9, P < 0.0001; feedback on demand: B = -7.2, 97.5% CI -11.3 to -3.1, P < 0.0001). No significant differences were found between both iCBT conditions on all outcome measures (P = 0.3-0.9). An exploratory analysis revealed that feedback-on-demand iCBT required less therapist time (mean 4 h 37 min) than iCBT with protocol-driven feedback (mean 6 h 9 min, P < 0.001) and also less than face-to-face CBT as reported in the literature. CONCLUSIONS: Both iCBT conditions are efficacious and time efficient. Declaration of interest None.

[Transient monocular vision loss]. / Tijdelijke stoornissen van het zien met één oog.

Transient monocular vision loss (TMVL) caused by temporary disturbance of blood flow to the retina is a harbinger of future vascular complications. The diagnosis may be difficult, not only because it is solely dependent on history taking, but also because the range of monocular visual symptoms a patient may experience is wide. The classic pattern of a sudden black or grey visual field, or a curtain that is drooping in front of one eye, easily fits in the diagnosis of TMVL; however, coloured vision or flashes should not always be considered as benign. The distinction between visual symptoms of one or both eyes should receive attention during history taking. It is the professional expertise of the neurologist and ophthalmologist which should make it possible to establish the correct diagnosis. A patient suspected of a retinal TIA should be evaluated and treated with the same urgency as someone with a cerebral TIA.

Prediction of cardiovascular risk in rheumatoid arthritis: performance of original and adapted SCORE algorithms.

OBJECTIVES: Predictive performance of cardiovascular disease (CVD) risk calculators appears suboptimal in rheumatoid arthritis (RA). A disease-specific CVD risk algorithm may improve CVD risk prediction in RA. The objectives of this study are to adapt the Systematic COronary Risk Evaluation (SCORE) algorithm with determinants of CVD risk in RA and to assess the accuracy of CVD risk prediction calculated with the adapted SCORE algorithm. METHODS: Data from the Nijmegen early RA inception cohort were used. The primary outcome was first CVD events. The SCORE algorithm was recalibrated by reweighing included traditional CVD risk factors and adapted by adding other potential predictors of CVD. Predictive performance of the recalibrated and adapted SCORE algorithms was assessed and the adapted SCORE was externally validated. RESULTS: Of the 1016 included patients with RA, 103 patients experienced a CVD event. Discriminatory ability was comparable across the original, recalibrated and adapted SCORE algorithms. The Hosmer-Lemeshow test results indicated that all three algorithms provided poor model fit (p<0.05) for the Nijmegen and external validation cohort. The adapted SCORE algorithm mainly improves CVD risk estimation in non-event cases and does not show a clear advantage in reclassifying patients with RA who develop CVD (event cases) into more appropriate risk groups. CONCLUSIONS: This study demonstrates for the first time that adaptations of the SCORE algorithm do not provide sufficient improvement in risk prediction of future CVD in RA to serve as an appropriate alternative to the original SCORE. Risk assessment using the original SCORE algorithm may underestimate CVD risk in patients with RA.

Remote Ischemic Preconditioning To Reduce Contrast-Induced Nephropathy: A Randomized Controlled Trial.

BACKGROUND: Despite the increasing use of pre- and post-hydration protocols and low osmolar instead of high osmolar iodine containing contrast media, the incidence of contrast induced nephropathy (CIN) is still significant. There is evidence that contrast media cause ischemia reperfusion injury of the renal medulla. Remote ischemic preconditioning (RIPC) is a non-invasive, safe, and low cost method to reduce ischemia reperfusion injury. The aim of this study is to investigate whether RIPC, as an adjunct to standard preventive measures, reduces contrast induced acute kidney injury in patients at risk of CIN. METHODS: The RIPCIN study is a multicenter, single blinded, randomized controlled trial in which 76 patients at risk of CIN received standard hydration combined with RIPC or hydration with sham preconditioning. RIPC was applied by four cycles of 5 min ischemia and 5 min reperfusion of the forearm. The primary outcome measure was the change in serum creatinine from baseline to 48 to 72 hours after contrast administration. RESULTS: With regard to the primary endpoint, no significant effect of RIPC was found. CIN occurred in four patients (2 sham and 2 RIPC). A pre-defined subgroup analysis of patients with a Mehran risk score ≥11, showed a significantly reduced change in serum creatinine from baseline to 48 to 72 hours in patients allocated to the RIPC group (Δ creatinine -3.3 ± 9.8 µmol/L) compared with the sham group (Δ creatinine +17.8 ± 20.1 µmol/L). CONCLUSION: RIPC, as an adjunct to standard preventive measures, does not improve serum creatinine levels after contrast administration in patients at risk of CIN according to the Dutch guideline. However, the present data indicate that RIPC might have beneficial effects in patients at a high or very high risk of CIN (Mehran score ≥ 11). The RIPCIN study is registered at: http://www.controlled-trials.com/ISRCTN76496973.

Recalibration of the delirium prediction model for ICU patients (PRE-DELIRIC): a multinational observational study.

PURPOSE: Recalibration and determining discriminative power, internationally, of the existing delirium prediction model (PRE-DELIRIC) for intensive care patients. METHODS: A prospective multicenter cohort study was performed in eight intensive care units (ICUs) in six countries. The ten predictors (age, APACHE-II, urgent and admission category, infection, coma, sedation, morphine use, urea level, metabolic acidosis) were collected within 24 h after ICU admission. The confusion assessment method for the intensive care unit (CAM-ICU) was used to identify ICU delirium. CAM-ICU screening compliance and inter-rater reliability measurements were used to secure the quality of the data. RESULTS: A total of 2,852 adult ICU patients were screened of which 1,824 (64%) were eligible for the study. Main reasons for exclusion were length of stay <1 day (19.1%) and sustained coma (4.1%). CAM-ICU compliance was mean (SD) 82 ± 16% and inter-rater reliability 0.87 ± 0.17. The median delirium incidence was 22.5% (IQR 12.8-36.6%). Although the incidence of all ten predictors differed significantly between centers, the area under the receiver operating characteristic (AUROC) curve of the eight participating centers remained good: 0.77 (95% CI 0.74-0.79). The linear predictor and intercept of the prediction rule were adjusted and resulted in improved re-calibration of the PRE-DELIRIC model. CONCLUSIONS: In this multinational study, we recalibrated the PRE-DELIRIC model. Despite differences in the incidence of predictors between the centers in the different countries, the performance of the PRE-DELIRIC-model remained good. Following validation of the PRE-DELIRIC model, it may facilitate implementation of strategies to prevent delirium and aid improvements in delirium management of ICU patients.

Development and validation of PRE-DELIRIC (PREdiction of DELIRium in ICu patients) delirium prediction model for intensive care patients: observational multicentre study.

OBJECTIVES: To develop and validate a delirium prediction model for adult intensive care patients and determine its additional value compared with prediction by caregivers. DESIGN: Observational multicentre study. SETTING: Five intensive care units in the Netherlands (two university hospitals and three university affiliated teaching hospitals). PARTICIPANTS: 3056 intensive care patients aged 18 years or over. MAIN OUTCOME MEASURE: Development of delirium (defined as at least one positive delirium screening) during patients' stay in intensive care. RESULTS: The model was developed using 1613 consecutive intensive care patients in one hospital and temporally validated using 549 patients from the same hospital. For external validation, data were collected from 894 patients in four other hospitals. The prediction (PRE-DELIRIC) model contains 10 risk factors-age, APACHE-II score, admission group, coma, infection, metabolic acidosis, use of sedatives and morphine, urea concentration, and urgent admission. The model had an area under the receiver operating characteristics curve of 0.87 (95% confidence interval 0.85 to 0.89) and 0.86 after bootstrapping. Temporal validation and external validation resulted in areas under the curve of 0.89 (0.86 to 0.92) and 0.84 (0.82 to 0.87). The pooled area under the receiver operating characteristics curve (n=3056) was 0.85 (0.84 to 0.87). The area under the curve for nurses' and physicians' predictions (n=124) was significantly lower at 0.59 (0.49 to 0.70) for both. CONCLUSION: The PRE-DELIRIC model for intensive care patients consists of 10 risk factors that are readily available within 24 hours after intensive care admission and has a high predictive value. Clinical prediction by nurses and physicians performed significantly worse. The model allows for early prediction of delirium and initiation of preventive measures. Trial registration Clinical trials NCT00604773 (development study) and NCT00961389 (validation study).

Increasingly strong reduction in breast cancer mortality due to screening.

BACKGROUND: Favourable outcomes of breast cancer screening trials in the 1970s and 1980s resulted in the launch of population-based service screening programmes in many Western countries. We investigated whether improvements in mammography and treatment modalities have had an influence on the effectiveness of breast cancer screening from 1975 to 2008. METHODS: In Nijmegen, the Netherlands, 55,529 women received an invitation for screening between 1975 and 2008. We designed a case-referent study to evaluate the impact of mammographic screening on breast cancer mortality over time from 1975 to 2008. A total number of 282 breast cancer deaths were identified, and 1410 referents aged 50-69 were sampled from the population invited for screening. We estimated the effectiveness by calculating the odds ratio (OR) indicating the breast cancer death rate for screened vs unscreened women. RESULTS: The breast cancer death rate in the screened group over the complete period was 35% lower than in the unscreened group (OR=0.65; 95% CI=0.49-0.87). Analysis by calendar year showed an increasing effectiveness from a 28% reduction in breast cancer mortality in the period 1975-1991 (OR=0.72; 95% CI=0.47-1.09) to 65% in the period 1992-2008 (OR=0.35; 95% CI=0.19-0.64). CONCLUSION: Our results show an increasingly strong reduction in breast cancer mortality over time because of mammographic screening.

Ultrastructural and immunocytochemical analysis of multilineage differentiated human dental pulp- and umbilical cord-derived mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are one of the most promising stem cell types due to their availability and relatively simple requirements for in vitro expansion and genetic manipulation. Besides the well-characterized MSCs derived from bone marrow, there is growing evidence suggesting that dental pulp and the umbilical cord matrix both contain a substantial amount of cells having properties similar to those of MSCs. In order to assess the potential of dental pulp-derived MSCs (DPSC) and umbilical cord-derived MSCs (UCSC) in future clinical applications, it is essential to gain more insight into their differentiation capacity and to evaluate the tissues formed by these cells. In the present study, the morphological and ultrastructural characteristics of DPSC and UCSC induced towards osteogenic, adipogenic, and chondrogenic lineages were investigated. Cultured DPSC and UCSC showed a similar expression pattern of antigens characteristic of MSCs including CD105, CD29, CD44, CD146, and STRO-1. Under appropriate culture conditions, both DPSC and UCSC showed chondrogenic and osteogenic potential. Adipogenesis could be only partially induced in DPSC resulting in the de novo expression of fatty acid binding protein (FABP), whereas UCSC expressed FABP combined with a very high accumulation of lipid droplets in the cytoplasm. Our results demonstrate, at the biochemical and ultrastructural level, that DPSC display at least bilineage potential, whereas UCSC, which are developmentally more primitive cells, show trilineage potential. We emphasize that transmission electron microscopical analysis is useful to elucidate detailed structural information and provides indisputable evidence of differentiation. These findings highlight their potential therapeutic value for cell-based tissue engineering.

Transient monocular blindness.

An attack of abrupt loss of vision in one eye that recovers completely after a short period is called "transient monocular blindness" (TMB) or amaurosis fugax. The most common cause of TMB is atherothromboembolism from the origin of the internal carotid artery (ICA), whereas atrial fibrillation is quite uncommon. TMB also can be caused by anterior optic nerve ischemia, that is usually caused by thrombosis in the posterior ciliary artery. Thrombosis in the central retinal vein may be another cause. Dissection of the ICA, vascular malformations, or fibromuscular dysplasia are other potential etiologies. Blurring of vision as compared with blackened vision or positive phenomena such as flashing is probably associated with a higher risk of future cardiovascular events, whereas involvement of the partial monocular field is associated with a relative benign prognosis. In patients with atherosclerosis, antiplatelet therapy is indicated and treatment of vascular risk factors should have high priority. Carotid endarterectomy should be performed only in case of an ICA stenosis of more than 70% in the presence of at least one other risk factor for stroke.

Risk factors for voice problems in teachers.

In order to identify factors that are associated with voice problems and voice-related absenteeism in teachers, 1,878 questionnaires were analysed. The questionnaires inquired about personal data, voice complaints, voice-related absenteeism from work and conditions that may lead to voice complaints and absenteeism. Different factors play a role in the development and consolidation of voice problems. Physical and psycho-emotional factors appear to be the most important risk factors. Remarkably, voice load and environment seem to be less important as risk factors in the development and consolidation of voice complaints. Teachers who experienced voice problems during their training reported more voice problems during their career. The results of this study stress the importance of a multifactorial approach in the diagnosis and treatment of voice problems, whereby physical and psycho-emotional aspects should be considered as sensitive to the risk of developing voice problems. Moreover, this study shows the crucial importance of adequate voice training during the teacher training programme.

Type of stroke after transient monocular blindness or retinal infarction of presumed arterial origin.

BACKGROUND: Retinal infarction and transient monocular blindness (TMB) are associated with an increased risk of future ischaemic stroke. Little information is available on the type of subsequent ischaemic strokes that may occur (anterior or posterior circulation and small vessel or large vessel). AIM: To analyse the type of stroke after TMB. METHODS: Patients with transient or permanent retinal ischaemia were selected from three prospective studies: the Dutch TIA Trial, the Dutch Amaurosis Fugax Study and the European/Australian Stroke Prevention in Reversible Ischaemia Trial. On follow-up the type of stroke was classified according to the supply territory and the type of vessel involved. RESULTS: 654 patients were included. During a mean follow-up of 5.2 years, 42 patients were found to have had a cerebral or retinal infarct, of which 27 occurred in the carotid territory ipsilateral to the symptomatic eye, 9 in the territory of the contralateral carotid artery and 6 were infratentorial strokes. Thirty patients had a large-vessel infarct, four had a small-vessel infarct and eight had a retinal infarct. Characteristics associated with a notable increased risk for subsequent stroke or retinal infarction were age > or = 65 years, a history of stroke, a history of intermittent claudication, diabetes mellitus, Rankin score > or = 3, more than three attacks of retinal ischaemia and any degree of ipsilateral carotid stenosis on duplex ultrasonography observation. CONCLUSION: Ischaemic strokes after TMB or retinal infarction were found to be mainly large-vessel infarcts in the territory of the ipsilateral carotid artery. TMB and retinal infarction are probably manifestations of large-vessel disease.

Clinical features of transient monocular blindness and the likelihood of atherosclerotic lesions of the internal carotid artery.

To assess which features of transient monocular blindness (TMB) are associated with atherosclerotic changes in the ipsilateral internal carotid artery (ICA), 337 patients with sudden, transient monocular loss of vision were prospectively studied. History characteristics of the attack were compared with the presence of atherosclerotic lesions of the ipsilateral ICA. All patients were directly interviewed by a single investigator. Of all patients, 159 had a normal ICA on the relevant side, 33 had a stenosis between 0%-69%, 100 had a stenosis of 70%-99%, and 45 had an ICA occlusion. An altitudinal onset or disappearance of symptoms was associated with atherosclerotic lesions of the ipsilateral ICA. A severe (70%-99%) stenosis was also associated with a duration between 1 and 10 minutes, and with a speed of onset in seconds. An ICA occlusion was associated with attacks being provoked by bright light, an altitudinal onset, and the occurrence of more than 10 attacks. Patients who could not remember details about the mode of onset, disappearance, or duration of the attack were likely to have a normal ICA. Our findings may facilitate the clinical decision whether or not to perform ancillary investigations in these patients.

Persistent increase in plasma thrombomodulin in patients with a history of lupus nephritis: endothelial cell activation markers.

OBJECTIVE: To investigate the presence of continuing endothelial cell activation in patients with systemic lupus erythematosus (SLE) and its relationship with lupus nephritis. METHODS: We measured plasma concentrations of soluble thrombomodulin (sTM), vascular cellular adhesion molecule-1 (sVCAM-1), von Willebrand factor (vWf), sP-selectin, and ED1-fibronectin in 75 SLE patients with a median SLE disease activity index (SLEDAI) of 4. Forty patients with a history of lupus nephritis, confirmed by renal biopsy in 33, were compared with 35 patients without lupus nephritis and 25 controls. For subgroup analysis in patients with clinically stable remission we excluded patients with a SLEDAI > 6 or with evidence of renal disease activity. RESULTS: In the total SLE patient group sTM, sVCAM-1, vWf, and sP-selectin were significantly elevated compared with controls. In patients with a history of lupus nephritis plasma levels of sTM and vWf were significantly increased compared with SLE patients without nephritis. After adjustment for significantly associated variables, especially creatinine clearance and age, in a multivariate linear regression analysis, sTM remained significantly elevated in patients with a history of lupus nephritis (difference 28.9 ng/ml, 95% CI 11.5-46.4). In the subgroup analysis of 57 patients, the results remained unchanged. CONCLUSION: The increase of sVCAM-1, sP-selectin, sTM, and vWf reflects a state of persistent endothelial cell activation. Multivariate regression analysis shows that the elevated sTM levels are strongly associated with a history of lupus nephritis, independent of creatinine clearance or disease activity, suggesting endothelial cell activation specifically localized in the kidneys.

A comparison of cerebral hemodynamic parameters between transient monocular blindness patients, transient ischemic attack patients and control subjects.

PURPOSE: To assess whether patients with transient monocular blindness (TMB) and patients with hemispheric transient ischemic attacks (hTIA) differ from each other with respect to cerebral hemodynamic parameters. METHODS: Seventeen TMB patients and 23 hTIA patients with a moderate to severe stenosis or an occlusion of the internal carotid artery (ICA) underwent magnetic resonance (MR) angiography, (1)H MR spectroscopy and transcranial Doppler sonography. Thirty-one control subjects were investigated to obtain reference values for the MR investigations. Quantitative flow was measured in the ICAs, the basilar artery and the middle cerebral arteries (MCA). Metabolic changes in the MCA territory were studied by assessing N-acetyl-aspartate (NAA)/choline ratios and prevalences of lactate. The prevalence of collateral flow was assessed in the circle of Willis and the ophthalmic arteries. The vasomotor reactivity was studied by measuring the CO(2) reactivity of the MCA territories. RESULTS: Quantitative flow in the cerebropetal arteries and the MCAs did not differ between TMB patients and hTIA patients. Also patterns of collateral flow, prevalence of lactate and CO(2) reactivity were similar. The mean ipsilateral NAA/choline ratio was lower in hTIA patients compared with TMB patients (p < 0.01), and was predominantly correlated with symptomatology (p < 0.01), i.e. whether patients had TMB or hTIA, and not with ipsilateral MCA flow (p = 0.2) or ipsilateral CO(2) reactivity (p = 0.7). CONCLUSION: The results of this study indicate that there are no cerebral hemodynamic differences between TMB patients and hTIA patients. It is therefore unlikely that hemodynamic factors account for differences in clinical characteristics between the two patient groups.

Evidence of a chronic systemic cause of instability of atherosclerotic plaques.

BACKGROUND: Major thrombotic and embolic complications of atherosclerosis are closely associated with irregularity and rupture of atheromatous plaques in both the carotid and coronary arteries. Plaque instability is partly determined by local factors, but systemic factors, such as infection, autoimmunity, or genes, may also be important. If plaque stability is influenced by systemic factors that are present in only a proportion of patients, some individuals should be more prone to rupture of plaques than others--ie, irregular plaques should occur in multiple vascular beds in some individuals more frequently than would be expected by chance alone. METHODS: We studied 5393 carotid bifurcation angiograms from 3007 patients with a recently symptomatic carotid stenosis. We assessed the extent to which plaque-surface irregularity at the symptomatic carotid artery was associated with irregularity at a distant site, the contralateral carotid artery, and the extent to which plaque irregularity at these sites was associated with previous myocardial infarction or subsequent non-stroke vascular death (due mainly to coronary-artery disease). FINDINGS: Patients with plaque-surface irregularity (n=1897) in the symptomatic carotid artery were more likely than those with smooth plaque (n=110) to have irregularity in the contralateral carotid artery (odds ratio 2.21 [95% CI 1.62-3.01], p<0.001). Patients with irregular plaques in both arteries were more likely to have had a previous myocardial infarction than patients with smooth plaques (hazard ratio 1.82 [1.23-2.64], p<0.001), and were more likely to have a non-stroke vascular death on follow-up (hazard ratio 1.67 [1.15-2.44], p=0.007). However, there was no difference in the risk of non-vascular death (hazard ratio 0.92 [0.57-1.45], p=0.5). These associations were not explicable on the basis of differences in traditional vascular risk factors. INTERPRETATION: These data suggest that some individuals have a systemic predisposition to irregularity and rupture of atherosclerotic plaques that is independent of traditional vascular risk factors. This finding supports the hypothesis that other systemic factors are important in the cause of plaque instability.

How do general practitioners diagnose and manage patients with transient monocular loss of vision of sudden onset?

Symptoms of transient loss of vision in one eye differ widely. They may have different causes and therefore carry a different prognosis. We studied the influence of differences between characteristics of transient monocular blindness on the diagnosis and management by general practitioners (GPs). A postal questionnaire, was sent to 1600 GPs in The Netherlands along with four case vignettes describing a case history of a 56-year-old man with transient monocular disturbances of vision of sudden onset. We introduced random permutations in the following four elements of the history: partial or complete visual field involved, blurring or blacking out of vision, attacks lasting minutes or hours, and patients having covered either eye during the attack or not. Respondents were asked about the probable diagnosis and the preferred management. For each of the 16 permutations about 50 responses were obtained (overall response rate 54%). Ischemic transient monocular blindness (ITMB) was chosen as the most likely diagnosis in 49%. In 12% primary ocular disease was suspected. Involvement of the complete visual field, blacking out of vision, and short attacks were identified as independent predictors of a diagnosis of ITMB. A diagnosis of ITMB would have resulted in referral to a specialist in 72% of patients. Antithrombotic treatment would have been initiated in only 36% of ITMB patients. GPs consider brief attacks with complete blacking out of vision most typical for retinal ischemia. They refer only three-quarters of patients with probable ITMB to a specialist and start antithrombotic medication in only one-third of these patients. Therefore further education with regard to transient monocular blindness is needed.