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Biomedical subjects

M Limburg

Publications and source records attributed to M Limburg.

At least 19 recordsLinked to original sources

Sudden unexpected death in epilepsy patients: Risk factors. A systematic review.

INTRODUCTION: Several risk factors for sudden unexplained death in epilepsy patients (SUDEP) have been proposed, but subsequent work has yielded conflicting data. The relative importance of various risk factors for SUDEP was never explored. The aim of this study is to review systematically risk factors for SUDEP and also to determine their relevance for SUDEP by calculating relative risk factor ratios. METHODS AND MATERIALS: Authors performed a literature-search on "SUDEP" in Medline, the Cochrane Library and EMBASE. Studies with unknown number of SUDEP cases or with less than five SUDEP cases and reviews were excluded from further analysis. The value of each paper was assessed, based on the quality of the study and the reliability of the diagnosis of SUDEP. This value ranged from 1 (low quality) to 10 (high quality). Papers with a value below 7 were eliminated for further analysis. For each analysed factor, a risk factor ratio was determined, with a higher ratio for a stronger risk factor. RESULTS: A number of strong risk factors for SUDEP: young age, early onset of seizures, the presence of generalized tonic clonic seizures, male sex and being in bed. Weak risk factors for SUDEP: prone position, one or more subtherapeutic bloodlevels, being in the bedroom, a strucural brain lesion and sleeping. CONCLUSIONS: In this study, authors have designed a quality scale to select papers. The relative importance of risk factors for SUDEP is demonstrated.

Age Factors↗

Evidence-based re-engineering: re-engineering the evidence--a systematic review of the literature on business process redesign (BPR) in hospital care.

PURPOSE: Business process redesign (BPR) is used to implement organizational transformations towards more customer-focused and cost-effective care. Ideally, these innovations should be carefully described and evaluated so that "best practices" can be re-applied. To investigate this, available evidence was collected on patient care redesign projects. DESIGN/METHODOLOGY/APPROACH: The Ebsco Business Source Premier, Embase and Medline databases were searched. Studies on innovations related to re-engineering patient care that used before-after design as minimum prerequisites were selected. General characteristics, logistic parameters and other outcome measures to determine the objectives and results and interventions used were looked at. FINDINGS: A total of 86 studies that conformed to the criteria were found: a minority mentioned measurable parameters in their objectives. In the majority of studies, multiple interventions were combined within single studies, making it impossible to compare the effects of individual interventions. Only three randomized controlled trials were found. Furthermore, inconsistencies were noted between the study objectives and the reported results. Many more issues were reported in the results than were mentioned in the study aims. It would appear that publications were hard to find owing to a lack of specific MeSH headings. Nearly 7,500 abstracts were scanned and from these it was concluded that clear and univocal research methods, terms and reporting guidelines are advisable and must be developed in order to learn and benefit from BPR innovations in health care organizations. ORIGINALITY/VALUE: This appears to be the first time available evidence about redesign projects in hospitals has been systematically collected and assessed.

Evidence-Based Medicine↗

Genome-wide linkage in a large Dutch consanguineous family maps a locus for intracranial aneurysms to chromosome 2p13.

BACKGROUND AND PURPOSE: Familial occurrence of intracranial aneurysms suggests a genetic factor in the development of these aneurysms. In this study, we present the identification of a susceptibility locus for the development of intracranial aneurysms detected by a genome-wide linkage approach in a large consanguineous pedigree. METHODS: Patients with clinical signs and symptoms of intracranial aneurysms, confirmed by radiological, surgical, or postmortem investigations, were included in the study. Magnetic resonance angiography was used to detect asymptomatic aneurysms in relatives. RESULTS: Seven out of 20 siblings had an intracranial aneurysm. Genome-wide multipoint linkage analysis showed a significant logarithm of the odds score of 3.55. CONCLUSIONS: In a large consanguineous pedigree intracranial aneurysms are linked to chromosome 2p13 in a region between markers D2S2206 and D2S2977.

Chromosome Mapping↗

International Master Classes in health informatics.

Master Classes arose within the performing arts and are now being offered in system sciences. The IPhiE group of faculty from six universities in Europe and the United States has offered Master Classes in health informatics to provide an integrative forum for honors students. Featured are international views of health systems, varied opportunities for student interaction and promotion of informatics professionalism. Five years of experience indicate the success of this concept and suggest changes that will be considered for the future.

Curriculum↗

[The waiting time for heart interventions: trends for percutaneous coronary interventions and cardiothoracic interventions].

OBJECTIVE: (a) To describe trends in the number of heart interventions performed over time, (b) to determine the length of waiting lists for elective heart interventions in the Netherlands according to the monthly survey of the Supervisory Committee for Heart Interventions in the Netherlands [Begeleidingscommissie Hartinterventies Nederland (BHN)], (c) to compare the length of the waiting lists with existing standards, and (d) to determine the reliability of the waiting list survey. DESIGN: Prospective. METHOD: Data were obtained from the monthly waiting list survey of the 13 heart centres in the Netherlands (1 January 1999-30 November 2002) and from the intervention registry (1 January 1999-30 June 2001), which was complete for 10 centres. Both the survey and the maintenance of the registry are carried out by the Supervisory Committee for Heart Interventions in the Netherlands. RESULTS: (a) The number of percutaneous coronary interventions performed in the Netherlands has increased. The number of cardiothoracic interventions remained stable. (b) The number of patients waiting for a percutaneous coronary intervention is increasing by 16% per annum. In November 2002 there were 751 patients on the waiting list. The number of patients waiting for a cardiothoracic intervention increased by 20% per annum until August 2001 and since then there has been a decrease of 21% per annum. In November 2002, 1557 patients were on the waiting list. (c) The percentage of patients treated within existing standards has fallen to 78% for percutaneous coronary interventions and to 53% for cardiothoracic interventions. (d) The length of the waiting list and the waiting times obtained in the survey concurred with the data taken from the intervention registry. CONCLUSIONS: The length of the waiting list for heart interventions has increased and complies increasingly less with existing standards. The monthly waiting-list survey was a reliable method of determining the length of waiting lists for elective heart interventions.

Angioplasty, Balloon, Coronary↗

Anticipation in familial intracranial aneurysms in consecutive generations.

Intracranial aneurysms (IA) are the major cause of subarachnoid haemorrhages (SAH). A positive family history for SAH is reported in 5-10% of the patients. The mode of inheritance is not unambiguously established; both autosomal dominant and recessive modes have been reported. In sporadic as well as in familial SAH, approximately 60% of the SAH patients are female. Recently, anticipation has been described in familial SAH. Since up to 15% of the SAHs are not caused by an IA, we have analysed anticipation, sex ratio and mode of inheritance only in families with patients with a proven IA in two consecutive generations. A total of 10 families were studied in which at least two persons in consecutive generations were affected by SAH, a symptomatic IA (SIA) or a presymptomatic IA (PIA). We also analysed published data from families with a proven IA in two consecutive generations on age of SIA onset and sex ratios among affected family members (both SIA and PIA). The age of SIA onset in the parental generation (mean 55.5 years) differed significantly from the age of onset in their children (mean 32.4 years). In the parental generation 11 men and 37 women were affected (both SIA and PIA), in the consecutive generation these numbers were 28 men and 32 women. There is a significant difference in sex ratio of affected family members when the generations are compared (P<0.02). No family could be found in which three consecutive generations were affected by an IA (SIA or PIA).

Adult↗

The medical information sciences program of Amsterdam.

The medical information sciences program of Amsterdam has been in existence for 15 years now. Starting in 1987, the program has been modified several times. Now a full-fledged 4 years master program exists. Students are taught skills to adequately and systematically apply information and communication technologies in order to optimize health care information processing. The program is offered within the Faculty of Medicine of the University of Amsterdam. The structure and contents of the current program will be described.

Curriculum↗

Breath holding test in preeclampsia: lack of evidence for altered cerebral vascular reactivity.

Twenty-five healthy and thirty-one preeclamptic pregnant women were assessed by means of transcranial Doppler sonography. Resting cerebral blood flow velocities in the middle cerebral arteries were measured followed by a repeat measurement 30 s after breath holding. Absolute blood flow velocities and per cent changes after breath holding procedure were compared between the groups. Absolute blood flow velocities were higher in preeclamptic pregnant women both at rest and after breath holding. The percent increase in cerebral blood flow velocity after breath holding (cerebral vascular reactivity) was similar in the two groups. Our data suggest that cerebral vascular reactivity is preserved in pregnant women with preeclampsia.

Journal Article↗

Lack of gender difference in acetazolamide-induced cerebral vasomotor reactivity in patients suffering from type-1 diabetes mellitus.

The aim of the present work was to investigate the impact of gender on resting cerebral blood flow velocity and cerebrovascular reserve capacity among diabetic patients. Middle cerebral artery mean blood flow velocity (MCAV) was measured in 72 patients suffering from type 1 diabetes mellitus at rest and 5, 10, 15 and 20 min after intravenous administration of 1 g acetazolamide. Cerebrovascular reserve was calculated as the maximal percent increase in MCAV after acetazolamide. Resting MCAV and cerebrovascular reserve capacity were compared between males and females. Resting cerebral blood flow velocity was higher in diabetic females than in males (men, 55.0+/-17.0 cm/s; women, 64.4+/-12.6 cm/s, p=0.0094). Cerebrovascular reserve capacity was similar in diabetic women and men (men, 44.0%+/-18.6%; women, 52.6%+/-32.9%, p=0.17). Comparing MCAV and cerebrovascular reserve capacity among the diabetic subgroups with disease duration < or = 10 years and >10 years, we did not detect any differences between women and men. Duration of diabetes was an important factor in determining cerebrovascular reserve capacity in both sexes: long-term diabetic women and men showed lower CRC values than diabetics with < or = 10 years disease duration. Cerebrovascular reserve capacity is similar in diabetic women and men. Taking into consideration that cerebrovascular reserve is normally higher among women, our finding indicates a relatively more serious worsening of cerebral vasodilatory responses in women suffering from type 1 diabetes.

Acetazolamide↗

Assessment of cerebral hemodynamics during roll over test in healthy pregnant women and those with pre-eclampsia.

OBJECTIVE: To compare cerebral autoregulatory responses obtained during roll over tests in healthy pregnant women and those with pre-eclampsia in order to assess the middle cerebral artery velocity changes in relation to the roll over test in normotensive and pre-eclamptic women. PARTICIPANTS: Twenty-two healthy pregnant women and 26 with pre-eclampsia underwent transcranial Doppler measurements of the middle cerebral artery. METHODS: Systolic, mean and diastolic blood flow velocities and mean arterial blood pressures were recorded in the left lateral position and five minutes after turning to the supine position. Absolute values of mean blood flow velocities, mean arterial blood pressure values and calculated cerebral blood flow indices as well as cerebrovascular resistance area products were compared at different positions among the groups. RESULTS: Mean arterial blood pressure increased in both groups while turning from the left lateral to the supine position. In women with pre-eclampsia both mean arterial blood pressure and absolute values of mean blood flow velocity values were higher in both positions, compared with healthy pregnant women. In both groups, changing the position resulted in a decrease of absolute values of mean blood flow velocities. Calculated cerebral blood flow indices did not change, while cerebrovascular resistance area products increased significantly in the groups during roll over testing. In women with pre-eclampsia, the increase of cerebrovascular resistance area products was more pronounced as compared with healthy pregnant women. CONCLUSIONS: In women with pre-eclampsia roll over test results in an increase of the mean arterial blood pressure, which is accompanied by a decreased mean blood flow velocity in the middle cerebral artery. Further studies are needed to clarify the pathophysiological background of cerebral haemodynamic changes in pre-eclampsia.

Adult↗

Type III collagen deficiency in a family with intracranial aneurysms.

We present a family with 2 female cousins with intracranial aneurysms and type III collagen deficiency. DNA analysis revealed no mutations in the COL3A1 gene, encoding type III collagen, and including the segment encoding the C-propeptide of type III collagen. The 2 patients with low type III collagen production and intracranial aneurysms had inherited different type III collagen alleles. The type III collagen deficiency in this family may results from defects during posttranslational modification or from an altered collagen metabolism.

Adult↗

Impact of stroke type on survival and functional health.

In a cohort 760 consecutive stroke patients (23 hospitals in the Netherlands), we studied prognosis in relation to stroke type and focused on (a) short-term and long-term mortality, and (b) long-term functional health. Based on clinical and CT data, we distinguished infratentorial strokes from supratentorial strokes (lacunar infarctions, (sub)cortical infarctions and intracerebral hemorrhages). Cumulative mortality for all stroke patients was 34% at 6 months, 51% at 3 years, and 62% at 5 years. Short-term mortality could be explained by stroke type, whereas long-term mortality could not. Of all survivors, 55% were in poor functional health at 6 months, 49% at 3 years and 42% at 5 years. Long-term functional health outcomes were associated with stroke type. We conclude that the impact of stroke type on mortality is limited to the first 6 months, whereas the type of stroke influences the long-term functional health.

Aged↗

Very Early Nimodipine Use in Stroke (VENUS): a randomized, double-blind, placebo-controlled trial.

BACKGROUND AND PURPOSE: The Very Early Nimodipine Use in Stroke (VENUS) trial was designed to test the hypothesis that early treatment with nimodipine has a positive effect on survival and functional outcome after stroke. This was suggested in a previous meta-analysis on the use of nimodipine in stroke. However, in a recent Cochrane review we were unable to reproduce these positive results. This led to the early termination of VENUS after an interim analysis. METHODS: In this randomized, double-blind, placebo-controlled trial, treatment was started by general practitioners or neurologists within 6 hours after stroke onset (oral nimodipine 30 mg QID or identical placebo, for 10 days). Main analyses included comparisons of the primary end point (poor outcome, defined as death or dependency after 3 months) and secondary end points (neurological status and blood pressure 24 hours after inclusion, mortality after 10 days, and adverse events) between treatment groups. Subgroup analyses (on final diagnosis and based on the per-protocol data set) were performed. RESULTS: At trial termination, after inclusion of 454 patients (225 nimodipine, 229 placebo), no effect of nimodipine was found. After 3 months of follow-up, 32% (n=71) of patients in the nimodipine group had a poor outcome compared with 27% (n=62) in the placebo group (relative risk, 1.2; 95% CI, 0.9 to 1.6). A treatment effect was not found for secondary outcomes and in the subgroup analyses. CONCLUSIONS: The results of VENUS do not support the hypothesis of a beneficial effect of early nimodipine in stroke patients.

Acute Disease↗

Calcium antagonists for ischemic stroke: a systematic review.

BACKGROUND AND PURPOSE: Stroke is a common disease, and many trials with calcium antagonists as possible neuroprotective agents have been conducted. The aim of this review is to determine whether calcium antagonists reduce the risk of death or dependency after acute ischemic stroke. METHODS: Acute stroke trials were identified with help of the Cochrane Collaboration Stroke Group and personal contacts. All randomized trials (published and unpublished) investigating a calcium antagonist (acting on voltage-sensitive calcium channels) were included. Poor outcome, defined as death or dependency in activities of daily living, was used as main outcome. Analyses were, if possible, "intention-to-treat"; pooled relative risks with 95% CIs were calculated. RESULTS: Forty-seven trials were identified, of which 29 were included (7665 patients). No effect of calcium antagonists on poor outcome at the end of follow-up (relative risk, 1.04; 95% CI, 0.98 to 1.09) or on death at end of follow-up (relative risk, 1.07; 95% CI, 0.98 to 1.17) was found. Sensitivity analyses on route of administration and time interval between stroke and start of treatment showed no effect on outcome. In subgroups of unpublished and methodologically sound trials, a statistically significant negative effect for calcium antagonists was found. This contrasts with results of published trials and trials of moderate or poor methodological quality. CONCLUSIONS: The presented evidence rules out a clinically important effect of calcium antagonists after ischemic stroke. The large amount of data leads to narrow CIs with no significant heterogeneity, and the overall results are therefore likely to be statistically robust.

Brain Ischemia↗

Nimodipine in animal model experiments of focal cerebral ischemia: a systematic review.

BACKGROUND AND PURPOSE: Based on the results of animal experiments, clinical trials were performed with nimodipine, which did not demonstrate a beneficial effect on outcome after stroke. The aim of this study was to determine whether the evidence from animal experiments with nimodipine supported the use of nimodipine in clinical trials. METHODS: - We performed a systematic review of animal experiments with nimodipine in focal cerebral ischemia. Studies were identified by searching Medline and Embase. We assessed whether these studies showed a beneficial effect of active treatment. In-depth analyses were performed on infarct size and amount of edema, and subgroup analyses were performed on the length of the time window to the initiation of treatment and the methodological quality of the studies. RESULTS: - Of 225 identified articles, 20 studies were included. The methodological quality of the studies was poor. Of the included studies, 50% were in favor of nimodipine. In-depth analyses showed statistically significant effects in favor of treatment (10 studies). No influence of the length of time to the initiation of treatment or of the methodological quality on the results was found. CONCLUSIONS: - We conclude that the results of this review did not show convincing evidence to substantiate the decision to perform trials with nimodipine in large numbers of patients. There were no differences between the results of the animal experiments and clinical studies. Surprisingly, we found that animal experiments and clinical studies ran simultaneously.

Animals↗

[Calculation of costs of stroke, cost effectiveness of stroke units and secondary prevention in patients after a stroke, as recommended by revised CBO practice guideline 'Stroke'].

OBJECTIVE: Economic analyses have been part of the revision of the Dutch multi-disciplinary stroke guidelines. We evaluated the recommendations on stroke units and prevention of stroke recurrencies in terms of medical costs and health effects among stroke patients. DESIGN: Cost calculation. METHOD: Mathematical modelling of medical costs per patient and costs per life year gained without severe stroke (Rankin score (> 3)), by age and sex for each guideline. RESULTS: Lifetime costs of stroke depended on age and sex and vary between 84,000 and 292,000 Dutch guilders (HFL). The cost-effectiveness of stroke units decreases with age and varies between HFL 37,000 and HFL 60,200 with a large uncertainty range. Four of seven options in secondary prevention were cost-effective by previously established criteria (< HFL 40,000 per year gained without severe disease). Acetylsalicylic acid remained the drug of choice for monotherapy with dipyridamol as a second choice in patients without atrial fibrillation. Clopidogrel was not cost-effective at the current cost level. Anticoagulation after stroke in case of atrial fibrillation was cost-effective. CONCLUSIONS: Given a short hospital stay stroke units can be as affective as other hospital interventions. Acetylsalicylic acid is the most cost effective monotherapy for secondary prevention.

Age Factors↗

[CBO guideline 'Stroke' (revision) Dutch Institute for Healthcare Improvement].

The stroke consensus dating from 1991 had to be revised, because of the introduction of new developments in the treatment of patients with stroke. More than 50 representatives from 25 professions and institutions participated. Under methodological assistance of the Dutch Institute for Healthcare Improvement CBO separate working groups (diagnosis, treatment, organization of care, rehabilitation/education, implementation and cost-effectiveness) studied the literature and translated the results into recommendations with explanatory text. The strength of scientific evidence was classified. During a national public meeting the results were discussed. In the field of guideline development cost-effectiveness analyses and specific attention for implementation are new. Care on a stroke unit decreases the risk of mortality, life-long disabilities, and dependence on permanent care with about 20%. Regional stroke services should be instituted, in which continuity and efficient care can be guaranteed. Very early thrombolysis with recombinant tissue plasminogen activator strongly decreases the number of patients dying, or remaining care-dependent in a selected group of appropriate patients. Secondary prevention (lifestyle measures, acetylsalicyclic acid, treatment of hypertension and hypercholesterolaemia, and surgery of the carotids) may decrease the number of residual strokes and myocardial infarctions. In the occurrence of cerebral ischaemia and atrial fibrillation oral anticoagulants are indicated. Early intensive rehabilitation increases the chance of recovery. Silent cognitive defects may hinder rehabilitation. The extensive guideline summarises the scientific literature about treatment of patients with stroke and should serve as a basis for local protocols and appointments.

Acute Disease↗