M. Vermeulen

Complications and outcome in patients with aneurysmal subarachnoid haemorrhage: a prospective hospital based cohort study in the Netherlands

OBJECTIVE The aim of this study was to investigate prospectively in an unselected series of patients with an aneurysmal subarachnoid haemorrhage what at present the complications are, what the outcome is, how many of these patients have “modern treatment”—that is, early obliteration of the aneurysm and treatment with calcium antagonists—what factors cause a delay in surgical or endovascular treatment, and what the estimated effect on outcome will be of improved treatment. METHODS A prospective, observational cohort study of all patients with aneurysmal subarachnoid haemorrhage in the hospitals of a specified region in The Netherlands. The condition on admission, diagnostic procedures, and treatments were recorded. If a patient had a clinical deterioration, the change in Glasgow coma score (GCS), the presence of focal neurological signs, the results of additional investigations, and the final diagnosed cause of the deterioration were recorded. Clinical outcome was assessed with the Glasgow outcome scale (GOS) at 3 month follow up. In patients with poor outcome at follow up, the cause was diagnosed. RESULTS Of the 110 patients, 47 (43%) had a poor outcome. Cerebral ischaemia, 31 patients (28%), was the most often occurring complication. Major causes of poor outcome were the effects of the initial haemorrhage and rebleeding in 34% and 30% of the patients with poor outcome respectively. Of all patients 102 (93%) were treated with calcium antagonists and 45 (41%) patients had early treatment to obliterate the aneurysm. The major causes of delay of treatment were a poor condition on admission or deterioration shortly after admission, in 31% and 23% respectively. CONCLUSIONS In two thirds of the patients with poor outcome the causes of poor outcome are the effects of the initial bleeding and rebleeding. Improved treatment of delayed or postoperative ischaemia will have only minor effects on the outcome of patients with subarachnoid haemorrhage.

Prognostic factors for ambulation and activities of daily living in the subacute phase after stroke. A systematic review of the literature

Objective: To identify evidence-based prognostic factors in the subacute phase after stroke for activities of daily living (ADL) and ambulation at six months to one year after stroke. Design: Systematic literature search designed in accordance with the Cochrane Collaboration criteria with the following data sources: (1) MEDLINE, EMBASE, CINAHL, Current Contents, Cochrane Database of Systematic Reviews, Psyclit, and Sociological Abstracts. (2) Reference lists, personal archives, and consultation of experts. (3) Guidelines. Methods: Inclusion criteria were: (1) cohort studies of patients with an ischaemic or haemorrhagic stroke; (2) inception cohort with assessment of prognostic factors within the first two weeks after stroke; (3) outcome measures for ADL and ambulation; and (4) a follow-up of six months to one year. Internal, statistical and external validity of the studies were assessed using a checklist with 11 methodological criteria in accordance with the recommendations of the Cochrane Collaboration. Results: From 1027 potentially relevant studies 26 studies involving a total of 7850 patients met the inclusion criteria. Incontinence for urine is the only prognostic factor identified in three studies with a level A (i.e., a good level of scientific evidence according to the methodological score). The following factors were found in one level A study: initial ADL disability and ambulation, high age, severe paresis or paralysis, impaired swallowing, ideomotor apraxia, ideational apraxia, and visuospatial construction problems; as well as factors relating to complications of an ischaemic stroke, such as extraparenchymal bleeding, cerebral oedema and size of intraparenchymal haemorrhage. Conclusions: The present evidence concerning possible predictors in the subacute stage of stroke has insufficient quality to make an evidence-based prediction of ADL and ambulation after stroke because only one prognostic factor was demonstrated in at least two level A studies, our cut-off for sufficient scientific evidence.

Direct Costs of Modern Treatment of Aneurysmal Subarachnoid Hemorrhage in the First Year After Diagnosis

Background and Purpose— The purpose of this study was to investigate the current direct costs of modern management of patients with aneurysmal subarachnoid hemorrhage in the first year after diagnosis. Methods— During a 1-year period, we studied all admitted patients with subarachnoid hemorrhage from a population of 2 million people. We calculated the direct costs of treatment, which included the costs of medical and nursing care and the related travel expenses of patients. We calculated true costs for all major healthcare resources. National census data, if available, and standard charges were used to determine healthcare resource expenses. Results— Hospital admissions and diagnostic and therapeutic interventions in 110 patients accounted for 85% of all costs; 64% of the total direct medical costs during admission were the medical, nursing, and overhead costs alone. Patients discharged directly to home generated 4% of the total budget, whereas admission to a nursing home accounted for the remaining 11% of the total costs. Of the diagnostic and therapeutic costs, 45% was caused by imaging and 42% by surgery or coiling. Angiography alone accounted for 52% of the total imaging costs and 24% of the total diagnostic and therapeutic costs. Prescribed medication accounted for only 3% of the total budget of diagnostic and therapeutic costs. Conclusions— Most direct costs during the first year after aneurysmal subarachnoid hemorrhage are caused by the hospital inpatient days, accounting for two thirds of the total costs generated during the first year after the initial bleeding. If new costly treatments succeed in reducing the average length of inpatient hospital stays, then progress in therapy may prove cost effective and might even be cost saving.

Activities of daily living instruments:optimizing scales for neurologic assessments

The ability to perform activities of daily living (ADL) is an important part of assessment in neurologic patients. A literature search was carried out to identify multi-item ADL scales developed for the assessment of neurologic patients, comparing item content, range, and detail of ADL scales. Of the 113 ADL scales identified, 27 (24%) were designed for use in neurology. In the basic ADL (BADL) domains (basic mobility and self-care), individual items were present in 44% to 81% of instruments. In the extended ADL (EADL) domains (e.g., outdoor mobility, housekeeping), items were present in up to 67% of the instruments identified. A typical trade-off was observed between the range, the detail (number of items), and hence the practicality of a scale. In general, scales focus on either BADL or EADL domains or, on occasion, some of both, rather than measuring the full range of functioning. There are many ADL scales in neurology, with much overlap in item content, leading to redundancy. New scales developed with the traditional methods will not solve the existing difficulties associated with range and detail, ordinal scale scores, and cross-instrument comparability. The possibilities of a modern psychometric method known as item response theory that was designed to solve these problems are discussed.

Perioperative arginine-supplemented nutrition in malnourished patients with head and neck cancer improves long-term survival

BACKGROUND Plasma arginine concentrations are lower in patients with cancer, which indicates that arginine metabolism may be disturbed in these patients. Arginine supplementation has been associated with positive effects on antitumor mechanisms and has been shown to reduce tumor growth and to prolong survival. Furthermore, the prognosis of patients with head and neck cancer remains disappointing. Insufficient intake frequently leads to malnutrition, which contributes to high morbidity and mortality rates. OBJECTIVE The aim of this study was to assess the long-term effects of perioperative arginine supplementation in severely malnourished patients with head and neck cancer. DESIGN In this double-blind, randomized, controlled trial, we randomly assigned 32 severely malnourished patients with head and neck cancer to receive 1) standard perioperative enteral nutrition (n = 15) or 2) arginine-supplemented perioperative enteral nutrition (n = 17). The primary outcome was long-term (≥10 y) survival. Secondary outcomes included the long-term appearance of locoregional recurrence, distant metastases, and second primary tumors. RESULTS No significant differences in baseline characteristics were observed between groups. The group receiving arginine-enriched nutrition had a significantly better overall survival (P = 0.019) and better disease-specific survival (P = 0.022). Furthermore, the arginine-supplemented group had a significantly better locoregional recurrence-free survival (P = 0.027). No significant difference in the occurrence of distant metastases or occurrence of a second primary tumor was observed between the groups. CONCLUSION Perioperative arginine-enriched enteral nutrition significantly improved the long-term overall survival and long-term disease-specific survival in malnourished patients with head and neck cancer.

Specific amino acids in the critically ill patient--exogenous glutamine/arginine: a common denominator?

Objective:Glutamine and arginine are both used as nutritional supplements in critically ill patients. Although glutamine has been shown to be beneficial for the metabolically stressed patient, considerations about arginine supplementation are not unanimously determined. Our aim is to review the current knowledge on the possible interplay between glutamine and arginine generation in the stressed patient and to elaborate on whether these amino acids may function as a common denominator. Because glutamine can be given by the parenteral and enteral routes, possible different actions on the metabolic fate (e.g., generation of citrulline) with both routes are analyzed. Data Source:A summary of data on the clinical effect of glutamine and arginine metabolism is given, incorporating data on glutamine and arginine supplementation. Differences between the route of administration, parenteral or enteral, and the molecular form of supplied glutamine, free or as dipeptide, on citrulline generation by the gut and production of arginine are discussed. Results:Glutamine and arginine influence similar organ systems; however, they differ in their targets. For example, glutamine serves as fuel for the immune cells, increases human leukocyte antigen-DR expression on monocytes, enhances neutrophil phagocytosis, and increases heat shock protein expression. Arginine affects the immune system by stimulating direct or indirect proliferation of immune cells. This indirect effect is possibly mediated by nitric oxide, which also enhances macrophage cytotoxicity. Furthermore, glutamine serves as a precursor for the de novo production of arginine through the citrulline-arginine pathway. Glutamine has shown to be beneficial in the surgical and critically ill patient, whereas arginine supplementation is still under debate. The route of glutamine administration (parenteral or enteral) determines the effect on citrulline and on the de novo arginine generation. There is a marked difference between the administration of free glutamine and dipeptide enterally or parenterally. Splanchnic extraction of the hydrolyzed glutamine in mice when administering the dipeptide enterally is higher compared with administering free glutamine from the enteral site. In patients, splanchnic extraction of the dipeptide given enterally is 100% when comparing supplementation of the dipeptide intravenously. Conclusions:The beneficial effects of free glutamine or dipeptide may depend on the route of administration but also on the metabolic fate of amino acids generated (e.g., citrulline, arginine). Glutamine serves as a substrate for de novo citrulline and arginine synthesis. More research needs to be done to establish the direct clinical relevance of the different metabolic pathways. Future perspectives might include combining enteral and parenteral routes of administrating free glutamine or dipeptide.

Long-term remission of CIDP after pulsed dexamethasone or short-term prednisolone treatment

Objective: Achieving long-term remission after a limited more intense treatment period would prevent prolonged use of corticosteroids or IV immunoglobulin (IVIg) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). In this prospective cohort study we present long-term follow-up data on patients included in a multicenter randomized controlled trial comparing 6 monthly pulses of dexamethasone with 8 months of daily prednisolone. Methods: Treatment effect was assessed with the Inflammatory Neuropathy Cause and Treatment disability scale and the Rivermead Mobility Index and was categorized using the CIDP Disease Activity Status (CDAS) scale. Results: By March 2011, 39 out of 40 patients were included with a median follow-up of 4.5 years. Cure (>5 years off treatment) or remission according to the CDAS criteria after 1 or 2 courses of pulsed dexamethasone or daily prednisolone was achieved in 10 out of 39 patients (26%). Half of the patients who were in remission after initial treatment experienced a relapse (median treatment-free interval: 17.5 months for dexamethasone, 11 months for prednisolone). Alternative diagnosis was made in 7 out of 12 (58%) who did not respond to any therapy and in none of the treatment-responsive patients. Conclusions: Cure or long-term remission can be achieved in about one-quarter of patients with CIDP after 1 or 2 courses of pulsed dexamethasone or 8-month daily prednisolone. In treatment-nonresponsive patients, the diagnosis CIDP should be reconsidered. Classification of Evidence: This study provides Class IV evidence that pulsed dexamethasone or 8-month daily prednisolone can lead to long-term remission in CIDP.

Nimodipine increases fibrinolytic activity in patients with aneurysmal subarachnoid hemorrhage

Background and Purpose— The purpose of this study was first, to investigate which factor in the fibrinolytic cascade is responsible for the recently observed increase of fibrinolytic activity in patients with aneurysmal subarachnoid hemorrhage (SAH), and second, the cause of this increase. Methods— Fibrinolytic activity and the main regulators of endogenous fibrinolytic activity, tissue plasminogen activator, and plasminogen activator inhibitor 1 (PAI-1) were measured in patients treated with and without nimodipine. Results— In patients with aneurysmal SAH, fibrinolytic activity significantly increases from 2.7 IU/mL on admission to 4.2 IU/mL in week 3 (P <0.01, paired-sample t test), caused by a 1.6-fold decrease in plasma levels of PAI-1. The results also show that increased fibrinolytic activity is seen only in patients treated with nimodipine and that plasminogen activity and PAI-1 returned to baseline levels after treatment with nimodipine had been discontinued. Conclusions— The mechanism of increased fibrinolytic activity in patients with aneurysmal SAH is a decrease in the level of PAI-1, which is most likely caused by treatment with nimodipine.

Prognostic factors in the subacute phase after stroke for the future residence after six months to one year. A systematic review of the literature

Objective: To identify evidence-based prognostic factors in the subacute phase after a stroke for future residence at six months to one year post stroke. Design: Systematic literature search designed in accordance with the Cochrane Collaboration criteria with the following data sources: (1) MEDLINE, EMBASE, CINAHL, Current Contents, Cochrane Database of Systematic Reviews, PsycLIT and Sociological Abstracts. (2) Reference lists, personal archives and consultation of experts in the field. (3) Guidelines. Methods: Inclusion criteria were: (1) cohort studies of patients with an ischaemic or haemorrhagic stroke; (2) inception cohort with assessment of prognostic factors within the first two weeks after stroke; (3) outcome measures for future residence; and (4) a follow-up of six months to one year. Internal, statistical and external validity of the studies were assessed using a checklist with 11 methodological criteria in accordance with the recommendations of the Cochrane Collaboration. Results: From 1027 potentially relevant studies 10 studies involving a total of 3564 patients met the inclusion criteria. No prognostic factor was identified in at least two level A (i.e., a good level of scientific evidence according to the methodological score) studies, our standard for scientific proof. The following factors were found in at least one level A study: low initial ADL functioning, high age, cognitive disturbance, paresis of arm and leg, not alert as initial level of consciousness, old hemiplegia, homonymous hemianopia, visual extinction, constructional apraxia, no transfer to the stroke unit, nonlacunar stroke type, visuospatial construction problems, urinary incontinence and female gender. Conclusions: At present there is insufficient evidence concerning possible predictors in the subacute stage of stroke to make an evidence-based prediction of the future residence. In the scientific research until now social factors and their contribution to the possibility of living independently have not been investigated, or at least less well. None of the studies in this review described a conceptual framework as basis for the choice of the examined prognostic factors.

Impact of neurologic signs and symptoms on functional status in peripheral neuropathies

Objective: To determine whether the Neurologic Disability Score (NDS), the Neuropathic Symptom Score (NSS), and the Medical Research Council (MRC) “sumscore” are reliable, and to determine whether they provide information regarding the functional status of patients with peripheral neuropathies. Methods: The authors analyzed homogeneity of the frequently used outcome measures in 97 patients using Cronbach’s alpha coefficient and corrected item–total correlations. Their association with functional status (sickness impact profile and modified Rankin score) was analyzed univariately with Pearson’s and Spearman’s correlation coefficients, and multivariately with linear regression analysis. Results: The NDS and MRC scales were homogeneous (range of Cronbach’s alpha, 0.81 to 0.97) compared with the NSS scales (range, 0.20 to 0.63). The correlation patterns between neurologic signs and symptoms and functional status ranged from 0.13 to 0.65. Multivariate linear regression analyses showed that 40% or less of patients’ functional status could be explained by the three tested outcome measures. Conclusion: The NDS and MRC are reliable measures, but these measures do not correlate with measures of functional status.