Protocol of a randomized open label multicentre trial comparing continuous intrajejunal levodopa infusion with deep brain stimulation in Parkinson's disease - the INfusion VErsus STimulation (INVEST) study.

BACKGROUND: Both Deep Brain Stimulation (DBS) and Continuous intrajejunal Levodopa Infusion (CLI) are effective therapies for the treatment of Parkinson's disease (PD). To our knowledge, no direct head-to-head comparison of DBS and CLI has been performed, whilst the costs probably differ significantly. In the INfusion VErsus STimulation (INVEST) study, costs and effectiveness of DBS and CLI are compared in a randomized controlled trial (RCT) in patients with PD, to study whether higher costs of one of the therapies are justified by superiority of that treatment. METHODS: A prospective open label multicentre RCT is being performed, with ancillary patient preference observational arms. Patients with PD who, despite optimal pharmacological treatment, have severe response fluctuations, bradykinesia, dyskinesias, or painful dystonia are eligible for inclusion. A total of 66 patients will be randomized. There is no minimal inclusion in the patient preference arms. The primary health economic outcomes are costs per unit on the Parkinson's Disease Questionnaire-39 (PDQ-39) and costs per unit Quality-Adjusted Life Year (QALY) at 12 months. The main clinical outcome is patient-reported quality of life measured with the PDQ-39 at 12 months. Patients will additionally be followed during 36 months after initiation of the study treatment. DISCUSSION: The INVEST trial directly compares the costs and effectiveness of the advanced therapies DBS and CLI. TRIAL REGISTRATION: Dutch Trial Register identifier 4753, registered November 3rd, 2014; EudraCT number 2014-001501-32, Clinicaltrials.gov: NCT02480803.

Screening and patient-tailored care for emotional and cognitive problems compared to care as usual in patients discharged home after ischemic stroke (ECO-stroke): a protocol for a multicenter, patient-blinded, cluster randomized controlled trial.

BACKGROUND: Ischemic stroke patients with a good outcome in terms of motor functioning and communication are likely to be discharged home without further rehabilitation. A significant number of these patients experience cognitive and emotional problems resulting in lower quality of life and decreased participation in society. This paper presents the protocol of a study examining the clinical effectiveness, cost-effectiveness and implementation of an intervention focused on screening and patient-tailored care for cognitive and emotional problems as compared to usual care in patients discharged home after ischemic stroke. METHODS / DESIGN: A multicenter, patient-blinded, cluster randomized controlled trial will be performed. Centers will be randomized (1:1) to the intervention group or the usual care group. Patients (> 18 years old) with a neurological confirmed diagnosis of ischemic stroke who can be discharged home without follow-up treatment at an outpatient rehabilitation clinic will be included. In the intervention group, patients will receive a short, individualized, semi-structured consultation by specialized nurses in addition to usual care. This consultation includes 1) screening for cognitive and emotional problems, 2) screening for restrictions in participation, 3) promotion of self-management strategies and 4) a decision tool for referral to rehabilitation services. The intervention will be performed approximately 6 weeks after the stroke at the neurology outpatient clinics and will take approximately 60 min. The control group will receive care as usual. Both groups will be followed-up at 6 weeks, 3 months and 12 months after stroke. The primary outcome will be the level of participation measured with the Restriction subscale of the Utrecht Scale for Evaluation of Rehabilitation on the level of Participation (USER-Participation-R) at 12 months. A cost-effectiveness analysis and process evaluation will be performed alongside. DISCUSSION: This trial is the first to evaluate clinical effectiveness, cost-effectiveness and implementation of screening and patient-tailored care for cognitive and emotional problems compared to care as usual in patients discharged home after ischemic stroke. Potentially, this will improve the outcomes for patients with frequently occurring cognitive and emotional problems after stroke. TRIAL REGISTRATION: Netherlands Trial Register: NL7295 , registered 25 September 2018.

Clinimetric evaluation and clinical outcomes of the Dutch version of the Chronic Ear Survey.

BACKGROUND: To validate and evaluate the reliability of the Dutch version of the Chronic Ear Survey (CES) in patients suffering from Chronic Suppurative Otitis Media (CSOM) and to evaluate clinical outcomes of surgery using this questionnaire. METHODS: We developed the Dutch version of the CES (D-CES) using forward-backward translation of the original CES into the Dutch language. Next, patients with CSOM and controls completed the D-CES pre- and postoperatively. Internal consistency, test-retest reliability, known-group validity and convergent validity were evaluated. In addition to the D-CES, the Short Form 36 (SF-36) was administered to all participants to correlate D-CES data to quality of life. RESULTS: A total of 29 patients with CSOM scheduled for ear surgery were included. Our control group consisted of 26 patients scheduled for eye surgery, all without signs and symptoms of CSOM. Cronbachs' α of the complete questionnaire was 0.69. The Intraclass Correlation Coefficients (ICCs), reflecting test-retest reliability, ranged between 0.69 and 0.82. Scores differed significantly between CSOM patients and controls with substantial lower (more impaired) D-CES scores in the CSOM group. Duration of complaints preoperatively and the presence of a dry ear and/or improvement of hearing postoperatively all had a significant impact on D-CES improvement scores. Small to moderate correlations were found between D-CES subscales and matching subscales of the SF-36. CONCLUSION: The D-CES is an appropriate disease specific questionnaire to assess a patient's perceived functional health in CSOM.

Clinimetric Evaluation of the Vascular Quality of Life Questionnaire in Patients with Lower Limb Ischaemia.

OBJECTIVES: Although commonly used to measure health related quality of life in patients with lower limb ischaemia, the measurement properties of the VascuQol and its assumed underlying health dimensions have not been studied in depth. The objective of this study was therefore to evaluate aspects of reliability and validity of the Dutch version of the VascuQol in patients with intermittent claudication (IC) and critical limb ischaemia (CLI). METHODS: Two datasets containing 195 patients with IC and 150 patients with CLI were used. Face validity of the VascuQol was examined in interviews with patients and a survey among health professionals. Homogeneity and structural validity of the VascuQol were assessed using Cronbach's α coefficients and explanatory factor analysis. Furthermore, convergent validity and known group validity were assessed. RESULTS: During the face validity interviews, three items were indicated as less relevant. Homogeneity analysis showed that the α coefficient of the VascuQol was .93, while the symptoms and social domains had α coefficients below the threshold of .70. The original five domains of the VascuQol could not be reproduced. Instead, factor analysis yielded a three factor solution. Moderate correlations were found for the activities, social and emotional VascuQol domains and matching health domains of other patient reported outcome measures (PROMs). Lower convergent correlations were observed for the pain domain and the sumscore of the VascuQol. The VascuQol was able to distinguish between patients' level of HRQL in relation to their disease severity (IC versus CLI patients). CONCLUSIONS: There is room for improvement of the VascuQol questionnaire. Further clinimetric studies should be performed to strengthen clinically relevant findings based on this instrument.

Protocol of a randomised delayed-start double-blind placebo-controlled multi-centre trial for Levodopa in EArly Parkinson's disease: the LEAP-study.

BACKGROUND: The aim of this study is to investigate if early treatment with levodopa has a beneficial disease modifying effect on Parkinson's disease (PD) symptoms and functional health, improves the ability to (maintain) work, and reduces the use of (informal) care, caregiver burden, and costs. Additionally, cost-effectiveness and cost-utility of early levodopa treatment will be assessed. METHODS: To differentiate between the direct symptomatic effects and possible disease modifying effects of levodopa, we use a randomised delayed-start double-blind placebo-controlled multi-centre trial design. Patients with early stage PD whose functional health does not yet necessitate initiation of PD-medication will be randomised to either 40 weeks of treatment with levodopa/carbidopa 100/25 mg TID including 2 weeks of dose escalation or to 40 weeks placebo TID. Subsequently, all patients receive levodopa/carbidopa 100/25 mg TID for 40 weeks. There are 8 assessments: at baseline and at 4, 22, 40, 44, 56, 68, and 80 weeks. The primary outcome measure is the difference in the mean total Unified Parkinson's Disease Rating Scale scores between the early- and delayed-start groups at 80 weeks. Secondary outcome measures are rate of progression, the AMC Linear Disability Score, side effects, perceived quality of life with the Parkinson's Disease Questionnaire-39, the European Quality of Life-5 Dimensions (EQ-5D), ability to (maintain) work, the use of (informal) care, caregiver burden, and costs. 446 newly diagnosed PD patients without impaired functional health need to be recruited in order to detect a minimal clinical relevant difference of 4 points on the total UPDRS at 80 weeks. DISCUSSION: The LEAP-study will provide insights into the possible disease modifying effects of early levodopa. TRIAL REGISTRATION: ISRCTN30518857, EudraCT number 2011-000678-72.

Evaluation of a multi-center randomised clinical trial on prophylactic transfusion of fresh frozen plasma: implications for future trials.

BACKGROUND: Prophylactic use of fresh frozen plasma (FFP) in critically ill patients with a coagulopathy is common. However, a lack of evidence of efficacy has resulted in a call for trials on the benefit of FFP in these patients. To date, conducting a trial on this subject has not been successful. Recently, a multi-center randomised trial was stopped prematurely due to slow inclusion. OBJECTIVE: To assess clinicians' opinions regarding a trial on prophylactic administration of FFP in coagulopathic critically ill patients who need to undergo an intervention. METHODS: A survey among 55 intensivists who all participated in a randomised trial on the risks and benefits of FFP in critically ill patients. RESULTS: Response rate was 84%. Majority of respondents indicated that international normalised ratio (INR) should be assessed before insertion of a central venous catheter (CVC) (61%), chest tube (89%) or tracheostomy (91%). Reasons to withhold transfusion of FFP to non-bleeding critically ill patients are risk of transfusion-related acute lung injury (TRALI) (46%), fluid overload (39%) and allergic reaction (24%). Although, the majority of respondents expressed the opinion that the trial was clinically relevant, 56% indicated that ≥1 patient subgroups should have been excluded from participation. CONCLUSION: Intensivists express the need for more evidence on the prophylactic use of FFP in coagulopathic critically ill patients. However, lack of knowledge about FFP and personal beliefs about the preferable transfusion strategy among clinicians, resulted in premature termination of a clinical trial on this topic.

Intravenous immunoglobulin and intravenous methylprednisolone as optimal induction treatment in chronic inflammatory demyelinating polyradiculoneuropathy: protocol of an international, randomised, double-blind, placebo-controlled trial (OPTIC).

BACKGROUND: International guidelines recommend either intravenous immunoglobulin (IVIg) or corticosteroids as first-line treatment for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). IVIg treatment usually leads to rapid improvement and is generally safe, but does not seem to lead to long-term remissions. Corticosteroids act more slowly and are associated with more side effects, but may induce long-term remissions. The hypothesis of this study is that combined IVIg and corticosteroid induction treatment will lead to more frequent long-term remissions than IVIg treatment alone. METHODS: An international, randomised, double-blind, placebo-controlled trial, in adults with 'probable' or 'definite' CIDP according to the EFNS/PNS 2010 criteria. Three groups of patients are included: (1) treatment naïve, (2) known CIDP patients with a relapse after > 1 year without treatment, and (3) patients with CIDP who improved within 3 months after a single course of IVIg, who subsequently deteriorate at any interval without having received additional treatment. Patients are randomised to receive 7 courses of IVIg and 1000 mg intravenous methylprednisolone (IVMP) (in sodium chloride 0.9%) or IVIg and placebo (sodium chloride 0.9%), every 3 weeks for 18 weeks. IVIg treatment consists of a loading dose of 2 g/kg (over 3-5 days) followed by 6 courses of IVIg 1/g/kg (over 1-2 days). The primary outcome is remission at 1 year, defined as improvement in disability from baseline, sustained between week 18 and week 52 without further treatment. Secondary outcomes include changes in disability, impairment, pain, fatigue, quality of life, care use and costs and (long-term) safety. DISCUSSION: In case of superiority of the combined treatment, patients will experience the advantages of two proven efficacious treatments, namely rapid improvement due to IVIg and long-term remission due to corticosteroids. Long-term remission would reduce the need for maintenance IVIg treatment and may decrease health care costs. Additionally, we expect that the combined treatment leads to a higher proportion of patients with improvement as some patients who do not respond to IVIg will respond to corticosteroids. Risks of short and long-term additional adverse events of the combined treatment need to be assessed. TRIAL REGISTRATION: ISRCTN registry ISRCTN15893334 . Prospectively registered on 12 February 2018.

Antiplatelet therapy in combination with rt-PA thrombolysis in ischemic stroke (ARTIS): rationale and design of a randomized controlled trial.

BACKGROUND: Thrombolysis with recombinant tissue plasminogen activator (rt-PA) is currently the only approved acute therapy for ischemic stroke. After rt-PA-induced recanalization, reocclusion is observed in 20-34%, probably caused by platelet activation. In acute myocardial infarction, the combination of thrombolytic and antiplatelet therapy leads to a better outcome compared to thrombolytic treatment alone. In patients with acute ischemic stroke, several studies showed that those on antiplatelet treatment prior to rt-PA had an equal or even better outcome compared to patients without prior use of antiplatelet therapy, despite an increased risk of bleeding. METHODS: We present the protocol of a multicenter randomized clinical trial (n = 800) investigating the effects of immediate addition of aspirin to rt-PA on poor outcome (modified Rankin score >2) in ischemic stroke patients. CONCLUSION: This study will answer the question whether the combination of rt-PA and antiplatelet therapy improves the functional outcome in ischemic stroke patients.

Presence and persistence of nutrition-related symptoms during the first year following esophagectomy with gastric tube reconstruction in clinically disease-free patients.

BACKGROUND: Esophagectomy with gastric tube reconstruction results in a variety of postoperative nutrition-related symptoms that may influence the patient's nutritional status. METHODS: We developed a 15-item questionnaire, focusing on the nutrition-related complaints the first year after an esophagectomy. The questionnaire was filled out the first week after discharge and 3, 6, and 12 months after surgery. The use of enteral nutrition, meal size and frequency, social aspects related to eating, defecation pattern, and body weight were recorded at the same time points. We analyzed the relationship between the baseline characteristics and the number of nutrition-related symptoms, as well as the relationship between those symptoms and body weight with linear mixed models. RESULTS: We found no significant within-patient change for the total number of nutrition-related symptoms (P = 0.67). None of the baseline factors were identified as predictors of the complaint scores. The most frequently experienced complaints were early satiety, postprandial dumping syndrome, inhibited passage due to high viscosity, reflux, and absence of hunger. One year after surgery, meal sizes were still smaller, the social aspects of eating were influenced negatively, and patients experienced an altered stool frequency. Directly after the surgical procedure 78% of the patients lost weight, and the entire postoperative year the mean body weight remained lower (P = 0.47). We observed no association between the complaint scores and body weight (P = 0.15). CONCLUSIONS: After an esophagectomy, most patients struggle with nutrition-related symptoms, are confronted with nutrition-related adjustments and a reduced body weight.

What should be defined as good outcome in stroke trials; a modified Rankin score of 0-1 or 0-2?

BACKGROUND AND PURPOSE: Good outcome in stroke trials has been defined as a modified Rankin scale (mRs) score of 0-1 or 0-2. The aim of this study was to investigate the clinical meaning of these two dichotomies. METHODS: We studied 152 patients six months post stroke using the mRs and a new disability measure the AMC Linear Disability Scale (ALDS) item bank. Descriptive statistics were used to show the ALDS scores by the levels of the mRs. To investigate the clinical meaning of the different definitions of good outcome, the mean probability to perform activities of daily life (ADL) of all mRs grades and these two dichotomies was calculated. RESULTS: The ability to perform difficult ALDS items declined gradually with increasing mRs grade. When favourable outcome is defined as mRs 0-1, 15 % of the cohort has a good outcome; of these patients 84 % were likely to perform outdoor activities. If good outcome is defined as mRs 0-2, the percentage of patients with good outcome increased to 37 %, whereas 66 % of these patients were likely to perform outdoor activities. CONCLUSION: If good outcome is defined as the ability to perform outdoor activities mRs 0-1 should be chosen. If complex ADL are considered as good outcome mRs 0-2 is the outcome measure of choice. Independent of which outcome measure is chosen, the treatment effect in clinical trials must be large before good outcome is achieved. Therefore, it is likely that clinically important treatment effects can be missed in clinical trials with both these mRs endpoints.

Botulinum toxin for writer's cramp: a randomised, placebo-controlled trial and 1-year follow-up.

BACKGROUND: Botulinum toxin type A (BoNT-A) has become the treatment of choice for most types of focal dystonia. OBJECTIVE: To investigate the efficacy of BoNT-A injections in patients with writer's cramp in a double-blind, randomised, placebo-controlled trial and to evaluate the follow-up results. METHODS: Forty participants were randomised to treatment with either BoNT-A or placebo injections in two sessions. Trial duration was 12 weeks. The primary outcome measure was the patients' choice to continue with the treatment, despite its possible disadvantages. Secondary outcome measures included several clinical rating scales on the levels of impairment and disability. Assessments were made at baseline and 2 months (secondary outcomes) and 3 months (primary outcome). Duration of follow-up was 1 year. RESULTS: 39 patients completed the trial. Fourteen of 20 patients (70%) receiving BoNT-A reported a beneficial effect and chose to continue treatment, versus 6 of 19 patients (31.6%) in the placebo group (p = 0.03). The changes on most of the clinical rating scales were significantly in favour of BoNT-A. Side effects reported were hand weakness, which was mostly mild and always transient, and pain at the injection site. After 1 year, 20 of 39 patients were still under treatment with a positive effect. CONCLUSION: Treatment with BoNT-A injections led to a significantly greater improvement compared with placebo, according to patients' opinion and clinical assessment scales. Weakness in the hand is an important side effect of BoNT-A injections, but despite this disadvantage, most patients preferred to continue treatment. About 50% of our patients were still under treatment after 1 year.

Interobserver variation in the interpretation of SSEPs in anoxic-ischaemic coma.

OBJECTIVE: To study interobserver variation in the interpretation of median nerve SSEPs in patients with anoxic-ischaemic coma. METHODS: SSEPs of 56 consecutive patients with anoxic-ischaemic coma were interpreted independently by 5 experienced clinical neurophysiologists using guidelines derived from a pilot study. Interobserver agreement was expressed as kappa coefficients. RESULTS: Kappa ranged from 0.20 to 0.65 (mean 0.52, SD 0.14). Disagreement was related with noise level and failure to adhere strictly to the guidelines in 15 cases. The presence or absence of N13 and cortical peaks caused disagreement in 5 cases each. For recordings with a noise level of 0.25 microV or more, mean kappa was 0.34; for recordings with a noise level below 0.25 microV mean kappa was 0.74. CONCLUSIONS: Interobserver agreement for SSEPs in anoxic-ischaemic coma was only moderate. Since the noise level strongly influenced interobserver variation, utmost attention should be given to its reduction. If an artefact level over 0.25 microV remains, absence of N20 cannot be judged with sufficient certainty and the SSEP should be repeated at a later stage. SIGNIFICANCE: Because of its moderate interobserver agreement, great care has to be given to accurate recording and interpretation of SSEPs before using the recordings for non-treatment decisions.

Palliative chemotherapy or watchful waiting? A vignettes study among oncologists.

PURPOSE: To determine the preferences of oncologists for palliative chemotherapy or watchful waiting and the factors considered important to that preference. METHODS: Sixteen vignettes (paper case descriptions), varying on eight patient and treatment characteristics, were designed to assess the oncologists' preferences. Their strength of preference was rated on a 7-point scale. An orthogonal main effects design provided a subset of all possible combinations of the characteristics, allowing estimations of the relative weights of the presented characteristics. A written questionnaire was sent to a random sample of oncologists (N = 1,235). RESULTS: The response rate was 67%, and 697 questionnaires were available for analysis. Eighty-one percent of the respondents were male. The mean age was 46 years. We found considerable variation among the oncologists. No major associations between physician characteristics and preferences were found. Of the patient and treatment characteristics affecting treatment preference, age was the strongest predictor, followed by the patient's wish to be treated and the expected survival gain. Other patient and treatment characteristics had a limited effect on preferences, except for psychologic distress, which had no independent impact. CONCLUSION: Patients will encounter different decisions depending on their oncologists' preferences and their own personal background. Therefore, to ensure adequate information for decision-making processes, decision aids are proposed.

Quality of survival after cardiopulmonary resuscitation.

BACKGROUND: Outcome of cardiopulmonary resuscitation (CPR) can be poor, in terms of life expectancy and quality of life. OBJECTIVES: To determine the impact of patient characteristics before, during, and after CPR on these outcomes, and to compare results of the quality-of-life assessment with published studies. METHODS: In a cohort study, we assessed by formal instruments the quality of life, cognitive functioning, depression, and level of dependence of survivors after inhospital CPR. Follow-up was at least 3 months after discharge from the hospital (tertiary care center). RESULTS: Of 827 resuscitated patients, 12% (n = 101) survived to follow-up. Of the survivors, 89% participated in the study. Most survivors were independent in daily life (75%), 17% were cognitively impaired, and 16% had depressive symptoms. Multivariate regression analysis showed that quality of life and cognitive function were determined by 2 factors known before CPR-the reason for admission and age. Factors during and after resuscitation, such as prolonged cardiac arrest and coma, did not significantly determine the quality of life or cognitive functioning of survivors. The quality of life of our CPR survivors was worse compared with a reference group of elderly individuals, but better than that of a reference group of patients with stroke. The quality of life did not importantly differ between the compared studies of CPR survivors. CONCLUSIONS: Cardiopulmonary resuscitation is frequently unsuccessful, but if survival is achieved, a relatively good quality of life can be expected. Quality of life after CPR is mostly determined by factors known before CPR. These findings may be helpful in informing patients about the outcomes of CPR.

In-hospital cardiopulmonary resuscitation: prearrest morbidity and outcome.

BACKGROUND: Considerations about the application of cardiopulmonary resuscitation (CPR) should include the expected probability of survival. The survival probability after CPR may be more accurately estimated by the occurrence in time of the prearrest morbidity of patients. OBJECTIVE: To identify risk factors for poor survival after CPR in relation to the dynamics of prearrest morbidity. METHODS: Medical records of CPR patients were reviewed. Prearrest morbidity was established by categorizing the medical diagnoses according to 3 functional time frames: before hospital admission, on hospital admission, and during hospital admission. Indicators of poor survival after CPR were identified through a logistic regression model. RESULTS: Included in the study were 553 CPR patients with a median age of 68 years (age range, 18-98 years); 21.7% survived to hospital discharge. Independent indicators of poor outcome were an age of 70 years or older (odds ratio [OR]=0.6, 95% confidence interval [CI]=0.4-0.9), stroke (OR=0.3, 95% CI=0.1-0.7) or renal failure (OR=0.3, 95% CI=0.1-0.8) before hospital admission, and congestive heart failure during hospital admission (OR=0.4, 95% CI=0.2-0.9). Indicators of good survival were angina pectoris before hospital admission (OR=2.1, 95% CI=1.3-.3.3) or ventricular dysrhythmia as the diagnosis on hospital admission (OR=11.0, 95% CI=4.1-33.7). Based on a logistic regression model, 17.4% of our CPR patients (n= 96) were identified as having a high risk for a poor outcome (< 10% survival). CONCLUSIONS: Time of prearrest morbidity has a prognostic value for survival after CPR. Patients at risk for poor survival can be identified on or during hospital admission, but the reliability and validity of the model needs further research. Although decisions will not be made by the model, its information can be useful for physicians in discussions about patient prognoses and to make decisions about CPR with more confidence.

[A modified informed-consent procedure in which the complete information is given retrospectively: no objection from participating patients]. / Een aangepaste 'informed consent'-procedure waarbij de volledige informatie pas achteraf wordt gegeven: geen bezwaar bij deelnemende patiënten.

OBJECTIVE: To determine whether a modified informed-consent procedure, in which permission is requested to send a questionnaire and to provide all the information about the study only after it is completed, would raise objections from patients who were asked to participate in a study on satisfaction with the follow-up care after a cerebrovascular accident. DESIGN: Descriptive cohort study. METHOD: 123 patients were approached for the randomised study. The patients who were included were interviewed by telephone two weeks after they had been sent the postponed information. RESULTS: During recruitment, 5 patients refused to participate but this was not because of the modified procedure. Of the 112 survivors, 102 (91%) could be interviewed and 79 had read the letter. Nobody (0%; 95% CI: 0-5) said that their trust in doctors had decreased; one patient (1%; 95% CI: 0-7) indicated decreased willingness to participate in future studies; two patients (3%; 95% CI: 0-9) were dissatisfied about the procedure followed. CONCLUSION: The participants in the trial had no major objections to the modified informed-consent procedure in which full information was given only after their participation had ended. Furthermore, patients did not refuse participation because of the modified procedure.

Bioelectrical impedance analysis to estimate body composition in surgical and oncological patients: a systematic review.

OBJECTIVE: Bioelectrical impedance analysis (BIA) is a commonly used method for the evaluation of body composition. However, BIA estimations are subject to uncertainties.The aim of this systematic review was to explore the variability of empirical prediction equations used in BIA estimations and to evaluate the validity of BIA estimations in adult surgical and oncological patients. SUBJECTS: Studies developing new empirical prediction equations and studies evaluating the validity of BIA estimations compared with a reference method were included. Only studies using BIA devices measuring the entire body were included. Studies that included patients with altered body composition or a disturbed fluid balance and studies written in languages other than English were excluded.To illustrate variability between equations, fixed normal reference values of resistance values were entered into the existing empirical prediction equations of the included studies and the results were plotted in figures. The validity was expressed by the difference in means between BIA estimates and the reference method, and relative difference in %. RESULTS: Substantial variability between equations for groups (including men and women) was found for total body water (TBW) and fat free mass (FFM). The gender-specific existing general equations assume less variability for TBW and FFM. BIA mainly underestimated TBW (range relative difference -18.8% to +7.2%) and FFM (range relative differences -15.2% to +3.8%). Estimates of the fat mass (FM) demonstrated large variability (range relative difference -15.7 to +43.1%). CONCLUSIONS: Application of equations validated in healthy subjects to predict body composition performs less well in oncologic and surgical patients. We suggest that BIA estimations, irrespective of the device, can only be useful when performed longitudinally and under the same standard conditions.

Clinical meaning of the Stroke-Adapted Sickness Impact Profile-30 and the Sickness Impact Profile-136.

BACKGROUND AND PURPOSE: Handicap or health-related quality of life (HRQL) measures are seldom used in stroke trials, although the importance of these measures has been stressed frequently. We studied the clinical meaning of the Stroke-Adapted Sickness Impact Profile-30 (SA-SIP30) and the original SIP136 for use in stroke research. METHODS: We included 418 patients who had had a stroke 6 months earlier. We studied the associations between the SA-SIP30 and SIP136 scores versus other frequently used outcome measures from the International Classification of Impairments, Disabilities, and Handicaps (ICIDH) (Barthel Index, Rankin Scale) and the HRQL model (health perception items, Euroqol). To interpret the continuous SA-SIP30 and SIP136 scores, we used receiver operating characteristic curve analysis with the aforementioned measures as external criteria. RESULTS: The psychosocial dimension scores of both SIP versions remained largely unexplained. The physical dimension and total scores of both SIP versions were mainly associated with the disability measures derived from the ICIDH model, as well as with the physical HRQL domains. Most patients with an SA-SIP30 total score >33 or an SIP136 total score >22 had poor health profiles. There were no major differences between the SA-SIP30 and the SIP136, although the SA-SIP30 scores were less skewed toward the healthier outcomes than the SIP136. CONCLUSIONS: Our study showed that (1) both SIP total scores primarily represent aspects of physical functioning and not HRQL; (2) both SIP versions provide more clinical information than the frequently used disability measures; and (3) the SA-SIP30 should be preferred over the SIP136.

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.

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.