Applying generalizability theory to examine assessments of subjective cognitive complaints: whose reports should we rely on - participant versus informant?

OBJECTIVES: This study aimed to apply the generalizability theory (G-theory) to investigate dynamic and enduring patterns of subjective cognitive complaints (SCC), and reliability of two widely used SCC assessment tools. DESIGN: G-theory was applied to assessment scales using longitudinal measurement design with five assessments spanning 10 years of follow-up. SETTING: Community-dwelling older adults aged 70-90 years and their informants, living in Sydney, Australia, participated in the longitudinal Sydney Memory and Ageing Study. PARTICIPANTS: The sample included 232 participants aged 70 years and older, and 232 associated informants. Participants were predominantly White Europeans (97.8%). The sample of informants included 76 males (32.8%), 153 females (65.9%), and their age ranged from 27 to 86 years, with a mean age of 61.3 years (SD = 14.38). MEASUREMENTS: The Memory Complaint Questionnaire (MAC-Q) and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). RESULTS: The IQCODE demonstrated strong reliability in measuring enduring patterns of SCC with G = 0.86. Marginally acceptable reliability of the 6-item MAC-Q (G = 0.77-0.80) was optimized by removing one item resulting in G = 0.80-0.81. Most items of both assessments were measuring enduring SCC with exception of one dynamic MAC-Q item. The IQCODE significantly predicted global cognition scores and risk of dementia incident across all occasions, while MAC-Q scores were only significant predictors on some occasions. CONCLUSIONS: While both informants' (IQCODE) and self-reported (MAC-Q) SCC scores were generalizable across sample population and occasions, self-reported (MAC-Q) scores may be less accurate in predicting cognitive ability and diagnosis of each individual.

MLC901 (NeuroAiD II™) for cognition after traumatic brain injury: a pilot randomized clinical trial.

BACKGROUND AND PURPOSE: Treatments to facilitate recovery after traumatic brain injury (TBI) are urgently needed. We conducted a 9-month pilot, randomized placebo-controlled clinical trial to examine the safety and potential effects of the herbal supplement MLC901 (NeuroAiD II™) on cognitive functioning following TBI. METHODS: Adults aged 18-65 years at 1-12 months after mild or moderate TBI were randomized to receive MLC901 (0.8 g capsules 3 times daily) or placebo for 6 months. The primary outcome was cognitive functioning as assessed by the CNS Vital Signs online neuropsychological test. Secondary outcomes included the Cognitive Failures Questionnaire, the Rivermead Post-concussion Symptom Questionnaire (neurobehavioral sequelae), Quality of Life after Brain Injury, Hospital Anxiety and Depression Scale, Modified Fatigue Impact Scale and extended Glasgow Outcome Scale (physical disability). Assessments were completed at baseline and at 3-, 6- and 9-month follow-up. Linear mixed-effects models were conducted, with the primary outcome time-point of 6 months. RESULTS: A total of 78 participants [mean age 37.5 ± 14.8 years, 39 (50%) female] were included in the analysis. Baseline variables were similar between groups (treatment group, n = 36; control group, n = 42). Linear mixed-effects models controlling for time, group allocation, repeated measurements, adherence and baseline assessment scores revealed significant improvements in complex attention (P = 0.04, d = 0.6) and executive functioning (P = 0.04, d = 0.4) at 6 months in the MLC901 group compared with controls. There were no significant differences between the groups for neurobehavioral sequelae, mood, fatigue, physical disability or overall quality of life at 6 months. No serious adverse events were reported. CONCLUSIONS: MLC901 was safe and well tolerated post-TBI. This study provided Class I/II evidence that, for patients with mild to moderate TBI, 6 months of MLC901 improved cognitive functioning.

Prevalence, natural course and predictors of depression 1 year following traumatic brain injury from a population-based study in New Zealand.

OBJECTIVE: Depression is common post-TBI, yet has not been studied longitudinally, nor at a population level. This study examined prevalence of depression in a population-based sample across the first year post-TBI. DESIGN AND METHODS: Prospective follow-up of 315 adults (>16 years) with assessments (Hospital Anxiety Depression Scale, DSM-IV criteria) at 1-, 6- and 12-months post-TBI. Demographic and injury-related predictors of depression at 1-year post-TBI were also explored. RESULTS: The number of individuals identified as depressed reduced significantly between baseline and 12-months post-TBI from 21-12.4% using the HADS and 49-34% using DSM-IV criteria; with only 10 of the 28 individuals initially meeting criteria on the HADS continuing to do so at 12-month follow-up. Meeting HADS depression criteria was linked to pre-morbid depression and/or anxiety; while those meeting DSM-IV criteria were older, but not significantly so. CONCLUSIONS: The findings suggest depression is common post-TBI and that clinicians/researchers use caution in its diagnosis, as existing criteria have significant overlap with common TBI sequels.

Enzogenol for cognitive functioning in traumatic brain injury: a pilot placebo-controlled RCT.

BACKGROUND AND PURPOSE: Enzogenol, a flavonoid-rich extract from Pinus radiata bark with antioxidant and anti-inflammatory properties has been shown to improve working memory in healthy adults. In traumatic brain injury (TBI), oxidation and inflammation have been linked to poorer cognitive outcomes. Hence, this phase II, randomized controlled trial investigated safety, compliance and efficacy of Enzogenol for improving cognitive functioning in people following mild TBI. METHODS: Sixty adults, who sustained a mild TBI, 3-12 months prior to recruitment, and who were experiencing persistent cognitive difficulties [Cognitive Failures Questionnaire (CFQ) score > 38], were randomized to receive Enzogenol (1000 mg/day) or matching placebo for 6 weeks. Subsequently, all participants received Enzogenol for a further 6 weeks, followed by placebo for 4 weeks. Compliance, side-effects, cognitive failures, working and episodic memory, post-concussive symptoms and mood were assessed at baseline, 6, 12 and 16 weeks. Simultaneous estimation of treatment effect and breakpoint was effected, with confidence intervals (CIs) obtained through a treatment-placebo balance-preserving bootstrap procedure. RESULTS: Enzogenol was found to be safe and well tolerated. Trend and breakpoint analyses showed a significant reduction in cognitive failures after 6 weeks [mean CFQ score, 95% CI, Enzogenol versus placebo -6.9 (-10.8 to -4.1)]. Improvements in the frequency of self-reported cognitive failures were estimated to continue until week 11 before stabilizing. Other outcome measures showed some positive trends but no significant treatment effects. CONCLUSIONS: Enzogenol supplementation is safe and well tolerated in people after mild TBI, and may improve cognitive functioning in this patient population. This study provides Class IIB evidence that Enzogenol is well tolerated and may reduce self-perceived cognitive failures in patients 3-12 months post-mild TBI.

The spectrum captured: a methodological approach to studying incidence and outcomes of traumatic brain injury on a population level.

OBJECTIVE: Drawing on the experience of conducting the Brain Injury Incidence and Outcomes New Zealand in the Community study, this article aims to identify the issues arising from the implementation of proposed guidelines for population-based studies of incidence and outcomes in traumatic brain injury (TBI). STUDY DESIGN AND SETTING: All new cases of TBI (all ages and severities) were ascertained over a 1-year period, using overlapping prospective and retrospective sources of case ascertainment in New Zealand. All eligible TBI cases were invited to participate in a comprehensive assessment at baseline and at 1-month follow-up. RESULTS: Our experience to date has revealed the feasibility of case ascertainment methods. Consultation with community health services and professionals resulted in feasible referral pathways to support the identification of TBI cases. 'Hot pursuit' methods of recruitment were essential to ensure complete case ascertainment for this population with few additional cases of TBI identified through cross-checks. CONCLUSION: This review of proposed guidelines in relation to practical study methodology provides a framework for future comparable population-based epidemiological studies of TBI incidence and outcomes in developed countries.

Calcium antagonists for aneurysmal subarachnoid haemorrhage.

BACKGROUND: Secondary ischaemia is a frequent cause of poor outcome in patients with subarachnoid haemorrhage (SAH). Its pathogenesis has been incompletely elucidated, but vasospasm probably is a contributing factor. Experimental studies have suggested that calcium antagonists can prevent or reverse vasospasm and have neuroprotective properties. OBJECTIVES: To determine whether calcium antagonists improve outcome in patients with aneurysmal SAH. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched April 2006), MEDLINE (1966 to March 2006) and EMBASE (1980 to March 2006). We handsearched two Russian journals (1990 to 2003), and contacted trialists and pharmaceutical companies in 1995 and 1996. SELECTION CRITERIA: Randomised controlled trials comparing calcium antagonists with control, or a second calcium antagonist (magnesium sulphate) versus control in addition to another calcium antagonist (nimodipine) in both the intervention and control groups. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted the data and assessed trial quality. Trialists were contacted to obtain missing information. MAIN RESULTS: Sixteen trials, involving 3361 patients, were included in the review; three of the studies were of magnesium sulphate in addition to nimodipine. Overall, calcium antagonists reduced the risk of poor outcome: the relative risk (RR) was 0.81 (95% confidence interval (CI) 0.72 to 0.92); the corresponding number of patients needed to treat was 19 (95% CI 1 to 51). For oral nimodipine alone the RR was 0.67 (95% CI 0.55 to 0.81), for other calcium antagonists or intravenous administration of nimodipine the results were not statistically significant. Calcium antagonists reduced the occurrence of secondary ischaemia and showed a favourable trend for case fatality. For magnesium in addition to standard treatment with nimodipine, the RR was 0.75 (95% CI 0.57 to 1.00) for a poor outcome and 0.66 (95% CI 0.45 to 0.96) for clinical signs of secondary ischaemia. AUTHORS' CONCLUSIONS: Calcium antagonists reduce the risk of poor outcome and secondary ischaemia after aneurysmal SAH. The results for 'poor outcome' depend largely on a single large trial of oral nimodipine; the evidence for other calcium antagonists is inconclusive. The evidence for nimodipine is not beyond all doubt, but given the potential benefits and modest risks of this treatment, oral nimodipine is currently indicated in patients with aneurysmal SAH. Intravenous administration of calcium antagonists cannot be recommended for routine practice on the basis of the present evidence. Magnesium sulphate is a promising agent but more evidence is needed before definite conclusions can be drawn.

Risk factors for Alzheimer's disease in Russia: a case-control study.

No reliable data on risk factors of Alzheimer's disease (AD) are available in Russia. We aimed to evaluate the relative importance of various putative environmental and medical risk factors of AD in a Russian population. We conducted a hospital-based case-control study. Two hundred and sixty consecutive AD patients and an equal number of cognitive impairment-free control subjects matched for sex, age, level of education and place of birth selected from nursing homes and other long-term healthcare facilities in the Novosibirsk region for the period from 1998 to 2002 were examined. A conditional logistic regression analysis was employed to calculate odds ratios (OR) and corresponding 95% confidence intervals (CI) for various putative risk factors. Of the 260 patients with AD, 187 (72%) were females. Patients' age varied from 40 to 89 years (mean +/- SD: 69.2 +/- 7.7 years). The majority of the patients (77%) had secondary education and 12% had university education. Risk factors independently associated with AD were family history of parkinsonism among first-degree relatives (OR = 4.2; 95% CI 1.2-15.1), hypothyroidism (OR = 2.7; 95% CI 1.1-6.7), and history of head trauma with loss of consciousness (OR = 1.7; 95% CI 1.0-2.8). The most important risk factors for AD in the Russian community are family history of parkinsonism, hypothyroidism and a history of head trauma with loss of consciousness. These findings have implications for developing preventive strategies of AD.

Calcium antagonists for aneurysmal subarachnoid haemorrhage.

BACKGROUND: Secondary ischaemia is a frequent cause of poor outcome in patients with subarachnoid haemorrhage (SAH). Its pathogenesis has not been elucidated yet, but may be related to vasospasm. Experimental studies have indicated that calcium antagonists can prevent or reverse vasospasm and have neuroprotective properties. Several types of calcium antagonists have been studied in several clinical trials. OBJECTIVES: To determine whether calcium antagonists improve outcome in patients with aneurysmal SAH. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (September 2003). In addition, we searched MEDLINE (1966 to October 2003) and EMBASE (1980 to October 2003), handsearched two Russian journals (1990 to 2003) and contacted trialists and pharmaceutical companies (in 1995 and 1996) to identify further studies. SELECTION CRITERIA: All unconfounded, truly randomised controlled trials comparing any calcium antagonist with control. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted the data and assessed trial quality. Trialists were contacted to obtain missing information. MAIN RESULTS: We analysed 12 trials totalling 2844 patients with SAH (1396 in the treatment group and 1448 in the control group). The drugs analysed were: nimodipine (eight trials, 1574 patients), nicardipine (two trials, 954 patients), AT877 (one trial, 276 patients) and magnesium (one trial, 40 patients). Overall, calcium antagonists reduced the risk of poor outcome: relative risk (RR) 0.82 (95% confidence interval (CI) 0.72 to 0.93); the absolute risk reduction was 5.1%, the corresponding number of patients needed to treat to prevent a single poor outcome event was 20. For oral nimodipine alone the RR was 0.70 (0.58 to 0.84). The RR of death on treatment with calcium antagonists was 0.90 (95% CI 0.76 to 1.07), that of clinical signs of secondary ischaemia 0.67 (95% CI 0.60 to 0.76), and that of CT or MR confirmed infarction 0.80 (95% CI 0.71 to 0.89). AUTHORS' CONCLUSIONS: Calcium antagonists reduce the risk of poor outcome and secondary ischaemia after aneurysmal SAH. The results for 'poor outcome' depend largely on a single large trial with oral nimodipine; the evidence for nicardipine, AT877 and magnesium is inconclusive. The evidence for nimodipine is not beyond every doubt, but given the potential benefits and modest risks of this treatment, against the background of a devastating natural history, oral nimodipine (60 mg every 4 hours) is currently indicated in patients with aneurysmal SAH. Intravenous administration of calcium antagonists cannot be recommended for routine practice on the basis of the present evidence.

Corticosteroids for aneurysmal subarachnoid haemorrhage and primary intracerebral haemorrhage.

BACKGROUND: Corticosteroids, particularly dexamethasone, are commonly used for treatments in patients with subarachnoid haemorrhage (SAH) and primary intracerebral haemorrhage (PICH) despite the lack of evidence. OBJECTIVES: This review aimed: (1) to determine whether corticosteroid therapy reduces the proportion of patients who die or have a poor outcome at one to six months after the onset of SAH or PICH; (2) to determine whether corticosteroid therapy reduces the frequency of delayed cerebral ischaemia (DCI) in patients with SAH; (3) to determine the frequency of adverse effects of corticosteroid therapy in patients with SAH or PICH within six months of the onset of the event. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched November 2003). In addition, we searched MEDLINE (1966 to March 2004) and EMBASE (1980 to March 2004), and searched reference lists of relevant studies identified. We also made an attempt to identify any relevant ongoing and published or unpublished studies by contacting trialists and pharmaceutical companies. SELECTION CRITERIA: We sought to identify all randomised or quasi-randomised clinical trials of corticosteroid therapy, in patients with SAH or PICH, that have a placebo or standard strategy arm as control. Patients of any age and either gender with clinically (bed-side) diagnosed PICH and cerebrospinal fluid documented SAH were included in the analysis. The data were analysed both separately and combined for computed tomography (CT)/magnetic resonance imaging (MRI)/autopsy/angiography verified patients. DATA COLLECTION AND ANALYSIS: Data extracted from eligible clinical trials included: (1) death and poor outcome (death, severe disability, or vegetative state) within the first one to six months of the event onset (primary outcomes); (2) development of delayed cerebral ischaemia (as defined by the trialists) in patients with SAH; and (3) adverse effects of the treatment during the scheduled treatment or follow-up period (secondary outcomes). A pooled estimate of the effect size was computed, and the test for heterogeneity between trial results was carried out using The Cochrane Collaboration's Review Manager software, RevMan 4.2. Intention-to-treat analysis was carried out whenever possible. MAIN RESULTS: Eight trials that fulfilled the eligibility criteria were identified, with a total of 256 randomised patients in three SAH trials, and 206 patients in five PICH trials. The studies differed substantially with regard to the study populations and drugs, and methodological quality. The number of patients allocated to either hydrocortisone or fludrocortisone acetate treatment in patients with SAH, or to dexamethasone treatment in patients with PICH, was too small to make any definitive conclusions (confidence intervals were wide for any of the outcome estimates). AUTHORS' CONCLUSIONS: Overall, there is no evidence of a beneficial or adverse effect of corticosteroids in patients with either SAH or PICH. Confidence intervals are wide and include clinically significant effects in both directions.

Is there a temporal pattern in the occurrence of subarachnoid hemorrhage in the southern hemisphere? Pooled data from 3 large, population-based incidence studies in Australasia, 1981 to 1997.

BACKGROUND AND PURPOSE: Publications on the temporal pattern of the occurrence of subarachnoid hemorrhage (SAH) have produced conflicting results. Variations between studies may relate to the relatively small numbers of SAH cases analyzed, including those in meta-analyses. METHODS: We identified all cases of SAH from 3 well-designed population-based studies in Australia (Adelaide, Hobart, and Perth) and New Zealand (Auckland) during 3 periods between 1981 and 1997. The diagnosis of SAH was confirmed with CT, cerebral angiography, cerebrospinal fluid analysis, or autopsy in all cases. Information on the time of occurrence of each event was obtained. Risk ratios (RRs) and 95% CIs were calculated using Poisson regression, with age, sex, smoking status, and history of hypertension entered in the model as covariates. RESULTS: A total of 783 cases of SAH were registered. Age- and sex-adjusted RRs of SAH occurrence were highest in the period between 6 AM and 12 MIDNIGHT (RR 3.2, 95% CI 2.4-4.3) and in winter and spring (RR 1.3, 95% CI 1.1-1.5; RR 1.3, 95% CI 1.1-1.5; respectively). No particular pattern of SAH occurrence was observed according to the day of the week. Restriction of the analyses to proved aneurysmal SAH did not substantially change the point estimates. CONCLUSIONS: Circadian and circaseptan (weekly) fluctuations of SAH occurrence in the southern hemisphere are similar to those in the northern hemisphere, but the occurrence of SAH in Australasia exhibits clear seasonal (winter and spring) peaks.

Calcium antagonists in patients with aneurysmal subarachnoid hemorrhage: a systematic review.

BACKGROUND AND PURPOSE: It has been reported that nimodipine reduces the frequency of secondary ischemia and improves outcome after aneurysmal SAH, but definitive evidence concerning all available calcium antagonists is lacking. METHODS: Systematic overview of randomized trials that were completed by January 1996 compared calcium antagonists with control and started treatment within 10 days after onset of subarachnoid hemorrhage (SAH) was performed. All calcium antagonists studied thus far (nimodipine, nicardipine, and AT877) were included. RESULTS: We analyzed 10 trials totaling 2756 patients. The relative risk (RR) reduction of poor outcome (death or dependency) was 16% (95% CI, 6 to 27%) and that of case fatality was 10% (95% CI, -6 to 25%). To prevent one poor outcome, 19 (12 to 59) patients need to be treated. Calcium antagonists give a 33% (95%, CI 25 to 41) RR reduction in the frequency of ischemic neurologic deficit and a 20% (95% CI, 11 to 28) RR reduction in the frequency of CT-scan documented cerebral infarction. Eight (6 to 11) patients need to be treated to prevent one ischemic neurologic deficit. In the analyses for nimodipine only, treatment was associated with a 24% RR reduction of poor outcome (95% CI, 12 to 38). To prevent one poor outcome, 13 (8 to 30) patients need to be treated with nimodipine. The RR reduction of angiographically detected cerebral vasospasm was statistically significant for AT877 (38%; 95% CI, 17 to 54%) and nicardipine (21%; 95% CI, 6 to 34%) but not for nimodipine (9%; 95% CI, -2 to 19%). CONCLUSION: Calcium antagonists reduce the proportion of ischemic neurologic deficits and nimodipine improves overall outcome within 3 months of aneurysmal SAH; evidence for a reduction of poor outcome from all causes by nicardipine and AT877 is inconclusive. The intermediate factors by which nimodipine exerts its beneficial effect remain uncertain.

Stroke epidemiology in Novosibirsk, Russia: a population-based study.

OBJECTIVE: To determine first-ever stroke incidence, 30-day case-fatality rates, and frequency of various risk factors among patients with stroke in Novosibirsk, Russia, during 1992. DESIGN: A population-based study of an administratively defined district of Novosibirsk was conducted to identify residents with a first-ever stroke that occurred between Jan. 1, 1992, and Dec. 31, 1992. MATERIAL AND METHODS: For case ascertainment, mortality statistics, death certificates, hospital registrations, outpatient clinical data, and all ambulance calls for the study area were reviewed. Patients with stroke or suspected stroke were examined and interviewed by a cerebrovascular neurologist, and the type of stroke was determined. RESULTS: During the 12-month study period, 366 patients with first-ever stroke were registered. A diagnosis of cerebral infarction or intracerebral hemorrhage was confirmed by computed tomography or autopsy in 42% of cases. The diagnosis of subarachnoid hemorrhage was established by cerebrospinal fluid examination in all 14 cases. The age- and sex-adjusted annual incidence rate for stroke was 232 per 100,000. The distribution of incidence cases by diagnostic category was as follows: cerebral infarction, 87.7%; intracerebral hemorrhage, 8.5%; and subarachnoid hemorrhage, 3.8%. The overall 30-day case-fatality rate for stroke was 22.4%. Hypertension, angina pectoris, and cigarette smoking were the most frequent risk factors in patients with stroke in Novosibirsk. CONCLUSION: The incidence rate of first-ever stroke in Novosibirsk, Russia, is one of the highest in the world, but the 30-day case-fatality rates are similar to those in other populations.

Circulatory volume expansion for aneurysmal subarachnoid hemorrhage.

BACKGROUND: Patients with subarachnoid haemorrhage who develop spasm of the cerebral arteries may suffer from delayed cerebral ischaemia. This may be exacerbated by reduced circulatory volume. Intravenous fluid therapy to expand the circulating volume might reduce the risk of delayed cerebral ischaemia and so reduce the risk of neurological disability. OBJECTIVES: The object of this review was to determine whether there is evidence that volume expansion therapy improves outcome in patients with aneurysmal subarachnoid haemorrhage. SEARCH STRATEGY: The Cochrane Stroke Group's Specialised Register was searched for trials relevant to this review (last searched: March 1999). Trialists were also contacted. SELECTION CRITERIA: All randomized controlled trials of volume expansion therapy in patients with aneurysmal subarachnoid haemorrhage. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted the data and assessed trial quality. Trialists were contacted to obtain missing information. MAIN RESULTS: Two trials were identified. For one trial the decision about inclusion is pending because clinical data on follow up have not been provided yet. In the other trial, outcome assessment was done at the day of operation (7 to 10 days after subarachnoid haemorrhage); data on longer follow up have not been collected. REVIEWER'S CONCLUSIONS: The effects of volume expansion therapy have not been studied properly in patients with aneurysmal subarachnoid haemorrhage. At present, there is no sound evidence for or against the use of volume expansion therapy in patients with aneurysmal subarachnoid haemorrhage.

Calcium antagonists for aneurysmal subarachnoid haemorrhage.

BACKGROUND: Rupture of an intracranial aneurysm causes bleeding into the subarachnoid space, which may lead to spasm of the cerebral arteries and ischaemic damage to the brain. Prophylactic use of calcium antagonists in patients with ruptured intracranial aneurysms might reduce the risk of ischaemic damage. OBJECTIVES: This review aimed to determine whether calcium antagonists improve outcome in patients with aneurysmal subarachnoid haemorrhage (SAH). SEARCH STRATEGY: The Cochrane Stroke Group trials register (last searched: March 1999) plus hand searching and personal contacts with trialists and pharmaceutical companies marketing calcium antagonists. SELECTION CRITERIA: All completed, unconfounded, truly randomised controlled trials comparing any calcium antagonist with control, within ten days of SAH onset. Eleven trials that met the inclusion criteria were included in the overview. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. Trialists were contacted to obtain missing information. MAIN RESULTS: We analysed 11 trials totalling 2804 randomized patients with subarachnoid haemorrhage (1376 in the treatment and 1428 in the control group). The drugs analyzed were: nimodipine (eight trials, 1574 patients), nicardipine (two trials, 954 patients), and AT877 (one trial, 276 patients). In 92% of the patients aneurysms were confirmed by angiography or autopsy. Overall, calcium antagonists significantly reduce the risk of poor outcome after subarachnoid haemorrhage: relative risk (RR) 0.82 (95% CI 0. 72-0.93); the absolute risk reduction was 5.1%, the corresponding number of patients needed to treat to prevent a single poor outcome event is 20. For oral nimodipine alone the RR was 0.69 (0.58-0.84). The RR of death on treatment with calcium antagonists was 0.94 (95% CI 0.80-1.10), that of ischaemic neurological deficits 0.67 (95% CI 0.59-0.76), and that of CT-scan documented cerebral infarction 0.80 (95% CI 0.71-0.89). REVIEWER'S CONCLUSIONS: Calcium antagonists reduce the proportion of patients with poor outcome and ischemic neurological deficits after aneurysmal SAH; the risk reduction for case fatality alone is not statistically significant. The results for 'poor outcome' are statistically robust, but depend mainly on trials with oral nimodipine; the evidence for nicardipine and AT877 is inconclusive. The intermediate factors through which nimodipine exerts its beneficial effect after aneurysmal SAH remain uncertain.

Circulatory volume expansion therapy for aneurysmal subarachnoid haemorrhage.

BACKGROUND: Secondary ischaemia is a frequent complication after aneurysmal subarachnoid haemorrhage (SAH), and responsible for a substantial proportion of patients with poor outcome after SAH. The cause of secondary ischaemia is unknown, but hypovolaemia and fluid restriction are important risk factors. Therefore, volume expansion therapy (hypervolaemia) is frequently used in patients with SAH to prevent or treat secondary ischaemia. OBJECTIVES: To determine the effectiveness of volume expansion therapy for improving outcome in patients with aneurysmal SAH. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched September 2003). In addition we searched MEDLINE (1966 to January 2004) and EMBASE (1980 to January 2004) and contacted trialists to identify further published and unpublished studies. SELECTION CRITERIA: All randomised controlled trials of volume expansion therapy in patients with aneurysmal SAH. We also sought controlled trials based on consecutive groups of patients quasi-randomly allocated to treatment or control group and included these in the analysis if the two groups were well comparable with regard to major prognostic factors. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted the data and assessed trial quality. Trialists were contacted to obtain missing information. MAIN RESULTS: We identified three trials. One truly randomised trial and one quasi-randomised trial with comparable baseline characteristics for both groups were included in the analyses. Volume expansion therapy did not improve outcome (Relative Risk (RR) 1.0; 95% Confidence Interval (CI) 0.5 to 2.2), nor the occurrence of secondary ischaemia (RR 1.1; 95% CI 0.5 to 2.2). Hypervolaemia tended to increase the rate of complications (RR 1.8; 95% CI 0.9 to 3.7) In another quasi-randomised trial, outcome assessment was done only at the day of operation (7 to 10 days after SAH). In the period before operation, treatment resulted in a reduction of secondary ischaemia (RR 0.33; 95% CI 0.11 to 0.99) and case fatality (RR 0.20; 95% CI 0.07 to 1.2). REVIEWERS' CONCLUSIONS: The effects of volume expansion therapy have been studied properly in only two trials of patients with aneurysmal SAH, with very small numbers. At present, there is no sound evidence for the use of volume expansion therapy in patients with aneurysmal SAH.

Calcium antagonists for aneurysmal subarachnoid haemorrhage.

BACKGROUND: Secondary ischaemia is a frequent cause of poor outcome in patients with subarachnoid haemorrhage. Its pathogenesis has not been elucidated yet, but may be related to vasospasm. Experimental studies have indicated that calcium antagonists can prevent or reverse vasospasm. Calcium antagonists have been studied in several trials, but data are conflicting. There is no overview concerning all available calcium antagonists. OBJECTIVES: To determine whether calcium antagonists improve outcome in patients with aneurysmal subarachnoid haemorrhage (SAH). SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched November 2001). In addition, we handsearched two Russian journals (1990-1995) and contacted trialists and pharmaceutical companies to identify further studies SELECTION CRITERIA: All completed, unconfounded, truly randomised controlled trials comparing any calcium antagonist with control, within ten days of SAH onset. Eleven trials that met the inclusion criteria were included in the overview. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted the data and assessed trial quality. Trialists were contacted to obtain missing information MAIN RESULTS: We analysed 11 trials totaling 2804 randomised patients with subarachnoid haemorrhage (1376 in the treatment and 1428 in the control group). The drugs analysed were: nimodipine (eight trials, 1574 patients), nicardipine (two trials, 954 patients), and AT877 (one trial, 276 patients). In 92% of the patients aneurysms were confirmed by angiography or autopsy. Overall, calcium antagonists significantly reduced the risk of poor outcome after subarachnoid haemorrhage: relative risk (RR) 0.82 (95% CI 0.72 to 0.93); the absolute risk reduction was 5.1%, the corresponding number of patients needed to treat to prevent a single poor outcome event is 20. For oral nimodipine alone the RR was 0.69 (0.58 to 0.84). The RR of death on treatment with calcium antagonists was 0.94 (95% CI 0.80 to 1.10), that of ischaemic neurological deficits 0.67 (95% CI 0.59 to 0.76), and that of CT-scan documented cerebral infarction 0.80 (95% CI 0.71 to 0.89). REVIEWER'S CONCLUSIONS: Calcium antagonists reduce the proportion of patients with poor outcome and ischaemic neurological deficits after aneurysmal SAH. The results for 'poor outcome' are statistically robust, but depend largely on one large trial with oral nimodipine; the evidence for nicardipine and AT877 is inconclusive. The evidence for nimodipine is not beyond every doubt, but given the potential benefits and modest risks associated with this treatment, against the background of a devastating natural history, oral nimodipine (60 mg every 4 hours) is indicated in patients with aneurysmal SAH. Intravenous administration of calcium antagonists cannot be recommended on the basis of the present evidence. For oral nimodipine uncertainty remains regarding the (dis)advantages in patients in poor clinical condition on admission or in patients with established cerebral ischaemia, the optimal dose and time window, the question whether other types of calcium antagonists offer better protection and the intermediate factors through which nimodipine exerts its beneficial effect after aneurysmal SAH.

[Epidemiologic characteristics of minor strokes in Novosibirsk]. / Epidemiologicheskaia kharakteristika malogo insul'ta v Novosibirske.

The article presents data on the frequency, clinical picture, causes, and prognosis of minor strokes observed in a large population. The annual incidence of minor strokes was 0.55 per 1,000 people. There are no significant differences in the rate of minor strokes between males and females. It has been found that with age the proportion of minor strokes among all patients with stroke shows a considerable reduction. The author compares some factors of risk for minor stroke and for complete cerebral infarct.

[Epidemiology stroke in a large city in Western Siberia according to registry statistics (morbidity and mortality)]. / Epidemiologiia mozgovogo insul'ta v usloviiakh krupnogo goroda Zapadnoi Sibiri po dannym registra (zabolevaemost' i smertnost').

A study of the cerebral stroke morbidity and mortality was first carried out using the method of registering cerebral stroke under specific conditions of such a large city of Western Siberia as Novosibirsk. The annual incidence of cerebral stroke constituted 3.37 and that of mortality 1.2 per 1000 population. The study was specific in that it took into account minor (reversible) episodes of cerebral stroke, whose annual incidence was 0.52 per 1000 population. The characteristics of the morbidity and mortality are described for different age groups with the varying nature of stroke. It was noted that the morbidity and mortality associated with cerebral infarction were higher as compared with cerebral hemorrhage.

[Experience of prognosis and the risk factors of stroke in Novosibirsk]. / Opyt prognozirovaniia i faktory riska mozgovogo insul'ta v Novosibirske.

On the basis of the data from the registry of cerebral stroke (CS) cases in Novosibirsk (covering 937 patients and 314 healthy control subjects) the authors have made a mathematical analysis of 19 factors of the risk of disease development. Nine factors have been isolated whose varying combinations were most contributory to the risk of the development of CS in the studied population: cardiac diseases, transient disorder of the cerebral circulation, arterial hypertension, atherosclerosis, aggravated heredity for cardiovascular diseases, intermittent claudication, diabetes mellitus, systematic alcohol abuse, and hypodynamia. The authors have developed a practicable and reliable system for predicting the development of cerebral stroke in apparently healthy subjects (the accuracy of prediction is 86%).