Peer reviewers' willingness to review, their recommendations and quality of reviews after the Finnish Medical Journal switched from single-blind to double-blind peer review.

BACKGROUND: There is a power imbalance between authors and reviewers in single-blind peer review. We explored how switching from single-blind to double-blind peer review affected 1) the willingness of experts to review, 2) their publication recommendations, and 3) the quality of review reports. METHODS: The Finnish Medical Journal switched from single-blind to double-blind peer review in September 2017. The proportion of review invitations that resulted in a received review report was counted. The reviewers' recommendations of "accept as is", "minor revision", "major revision" or "reject" were explored. The content of the reviews was assessed by two experienced reviewers using the Review Quality Instrument modified to apply to both original research and review manuscripts. The study material comprised reviews submitted from September 2017 to February 2018. The controls were the reviews submitted between September 2015 and February 2016 and between September 2016 and February 2017. The reviewers' recommendations and the scorings of quality assessments were tested with the Chi square test, and the means of quality assessments with the independent-samples t test. RESULTS: A total of 118 double-blind first-round reviews of 59 manuscripts were compared with 232 single-blind first-round reviews of 116 manuscripts. The proportion of successful review invitations when reviewing single-blinded was 67%, and when reviewing double-blinded, 66%. When reviewing double-blinded, the reviewers recommended accept as is or minor revision less often than during the control period (59% vs. 73%), and major revision or rejection more often (41% vs 27%, P = 0.010). For the quality assessment, 116 reviews from the double-blind period were compared with 104 reviews conducted between September 2016 and February 2017. On a 1-5 scale (1 poor, 5 excellent), double-blind reviews received higher overall proportion of ratings of 4 and 5 than single-blind reviews (56% vs. 49%, P < 0.001). Means for the overall quality of double-blind reviews were 3.38 (IQR, 3.33-3.44) vs. 3.22 (3.17-3.28; P < 0.001) for single-blind reviews. CONCLUSIONS: The quality of the reviews conducted double-blind was better than of those conducted single-blind. Switching to double-blind review did not alter the reviewers' willingness to review. The reviewers became slightly more critical.

Poststroke epilepsy in long-term survivors of primary intracerebral hemorrhage.

OBJECTIVE: To identify the incidence and predisposing factors for development of poststroke epilepsy (PSE) after primary intracerebral hemorrhage (PICH) during a long-term follow-up. METHODS: We performed a retrospective study of patients who had had their first-ever PICH between January 1993 and January 2008 in Northern Ostrobothnia, Finland, and who survived for at least 3 months. These patients were followed up for PSE. The associations between PSE occurrence and sex, age, Glasgow Coma Scale (GCS) score on admission, hematoma location and volume, early seizures, and other possible risk factors for PSE were assessed using the Cox proportional hazards regression model. RESULTS: Of the 615 PICH patients who survived for longer than 3 months, 83 (13.5%) developed PSE. The risk of new-onset PSE was highest during the first year after PICH with cumulative incidence of 6.8%. In univariable analysis, the risk factors for PSE were early seizures, subcortical hematoma location, larger hematoma volume, hematoma evacuation, and a lower GCS score on admission, whereas patients with infratentorial hematoma location or hypertension were less likely to develop PSE (all variables p < 0.05). In multivariable analysis, we found subcortical location (hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.35-3.81, p < 0.01) and early seizures (HR 3.63, 95% CI 1.99-6.64, p < 0.01) to be independent risk factors, but patients with hypertension had a lower risk of PSE (HR 0.54, 0.35-0.84, p < 0.01). CONCLUSIONS: Subcortical hematoma location and early seizures increased the risk of PSE after PICH in long-term survivors, while hypertension seemed to reduce the risk.

Improved survival of patients with warfarin-associated intracerebral haemorrhage: a retrospective longitudinal population-based study.

BACKGROUND: Warfarin-associated intracerebral haemorrhage carries poor outcome due to rapid haemorrhage growth. Reversal of warfarin anticoagulation with prothrombin complex concentrate has been implemented as an acute treatment option for these subjects. AIM: We investigated whether survival of subjects with warfarin-associated intracerebral haemorrhage had improved after implementation of reversal of warfarin anticoagulation with prothrombin complex concentrate. METHODS: We identified all subjects with warfarin-associated intracerebral haemorrhage during 1993-2008 among the population of Northern Ostrobothnia, Finland. From 2004 onwards, prothrombin complex concentrate was used in Oulu University Hospital, the only hospital treating intracerebral haemorrhage subjects in the region, to counteract the effect of warfarin in subjects with warfarin-associated intracerebral haemorrhage. We compared the outcomes of subjects admitted during 1993-2003 and 2004-2008 and those treated and not treated with prothrombin complex concentrate. We also explored the predictors for one-year survival of the warfarin-associated intracerebral haemorrhage subjects. RESULTS: We identified altogether 181 subjects who had intracerebral haemorrhage while on warfarin. One-year survival was significantly (P = 0·031) higher for the 60 subjects admitted during 2004-2008 (43·3%) than for the 121 admitted before 2004 (30·6%). In multivariable analysis, prothrombin complex concentrate treatment reduced one-year case fatality (hazard ratio 0·52, 95% confidence interval 0·29-0·93). Thromboembolic complications did not occur more frequently among those treated with prothrombin complex concentrate. CONCLUSION: The survival of warfarin-associated intracerebral haemorrhage subjects among the population of Northern Ostrobothnia has improved likely because of introduction of prothrombin complex concentrate.

Association between warfarin combined with serotonin-modulating antidepressants and increased case fatality in primary intracerebral hemorrhage: a population-based study.

OBJECT: Patients receiving oral anticoagulants run a higher risk of cerebral hemorrhage with a poor outcome. Serotonin-modulating antidepressants (selective serotonin reuptake inhibitors [SSRIs], serotonin-norepinephrine reuptake inhibitors [SNRIs]) are frequently used in combination with warfarin, but it is unclear whether this combination of drugs influences outcome after primary intracerebral hemorrhage (PICH). The authors investigated case fatality in PICH among patients from a defined population who were receiving warfarin alone, with aspirin, or with serotonin-modulating antidepressants. METHODS: Nine hundred eighty-two subjects with PICH were derived from the population of Northern Ostrobothnia, Finland, for the years 1993-2008, and those with warfarin-associated PICH were eligible for analysis. Their hospital records were reviewed, and medication data were obtained from the national register of prescribed medicines. Kaplan-Meier survival curves were drawn to illustrate cumulative case fatality, and a Cox proportional-hazards analysis was performed to demonstrate predictors of death. RESULTS: Of the 176 patients eligible for analysis, 17 had been taking aspirin and 19 had been taking SSRI/SNRI together with warfarin. The 30-day case fatality rates were 50.7%, 58.8%, and 78.9%, respectively, for those taking warfarin alone, with aspirin, or with SSRI/SNRI (p = 0.033, warfarin plus SSRI/SNRI compared with warfarin alone). Warfarin combined with SSRI/SNRI was a significant independent predictor of case fatality (adjusted HR 2.10, 95% CI 1.13-3.92, p = 0.019). CONCLUSIONS: Concurrent use of warfarin and a serotonin-modulating antidepressant, relative to warfarin alone, seemed to increase the case fatality rate for PICH. This finding should be taken into account if hematoma evacuation is planned.

Diagnosis and management of Marchiafava-Bignami disease: a review of CT/MRI confirmed cases.

OBJECTIVE: Marchiafava-Bignami disease (MBD) is a rare condition mainly associated with alcoholism, although it may be mimicked by several other disorders that cause corpus callosum lesions. Our objective was to identify helpful features for differential diagnosis and assess whether any treatment can be recommended. METHODS: We reviewed 122 reports containing data on 153 subjects with confirmed MBD that was associated with either alcoholism or malnutrition, and 20 reports with data on 53 subjects with conditions mimicking MBD. All the cases had been verified antemortem by brain imaging. Unconditional logistic regression was used to demonstrate factors that were associated with the outcome of MBD. RESULTS: The mimicking conditions were differentiated from MBD by the occurrence of solitary and rapidly disappearing splenial lesions; fewer signs and symptoms with exception of seizures, hemiparesis and tetraparesis; nystagmus; and rapid and complete recovery. MBD occurred most frequently among alcoholics, but it was also reported in 11 non-alcoholics (7.2% of all the MBD cases). A better outcome was observed among those who were treated within 2 weeks after onset of symptoms with parenteral thiamine (p=0.033). CONCLUSIONS: As thiamine deficiency is frequently associated with alcoholism, malnutrition and prolonged vomiting; we recommend prompt treatment of MBD with parenteral thiamine in such subjects. Recovery should be followed by repeated neuropsychological and MRI examinations, preferably using diffusion tensor imaging.

A population based study of outcomes after evacuation of primary supratentorial intracerebral hemorrhage.

BACKGROUND AND PURPOSE: The role of surgery after primary intracerebral hemorrhage (ICH) is controversial. To explore whether hematoma evacuation after ICH had improved short-term survival or functional outcome we conducted a retrospective observational population-based study. METHODS: We identified all subjects with primary ICH between 1993 and 2008 among the population of Northern Ostrobothnia, Finland. Hematoma evacuation was carried out by using standard craniotomy or through a burr hole. We compared mortality rates and functional outcomes of patients with hematoma evacuation with those treated conservatively. RESULTS: Of 982 patients with verified ICH during the study period, 127 (13%) underwent hematoma evacuation. Surgically treated patients were significantly younger (mean±SD, 63±11 vs. 70±12 years; p<0.001), had larger hematomas (66±36 vs. 28±40 ml; p<0.001), lower Glasgow Coma Scale scores (median, 11 vs. 14; p<0.001) and more frequently subcortical hematomas (68% vs. 24%; p<0.001) than those treated conservatively. In multivariable analysis, hematoma evacuation independently lowered 3-month mortality (adjusted hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.43-0.88; p<0.03), particularly among patients aged≤70 years with ≥30 ml supratentorial hematomas (adjusted HR, 0.26; 95% CI, 0.14-0.49; p<0.001). However, poor outcome was not improved by surgery (adjusted odds ratio 0.71; 95% CI 0.29-1.70). CONCLUSIONS: Improved 3-month survival was observed in patients who had undergone hematoma evacuation relative to patients not undergoing evacuation particularly in the subgroup of patients aged≤70 years with ≥30 ml supratentorial hematomas. Surgery might improve outcome if cases could be selected more precisely and if performed before deterioration.

Predictors for recurrent primary intracerebral hemorrhage: a retrospective population-based study.

BACKGROUND AND PURPOSE: Underlying comorbidities, previous strokes, and medication may increase the risk for primary intracerebral hemorrhage (PICH) and its recurrence. The aim of this study was to determine the independent predictors for recurrent PICH. METHODS: We identified 961 subjects with first-ever PICH from 1993 to 2008 among the population of Northern Ostrobothnia, Finland. Hospital and death records were reviewed and data on drug use were obtained from the national register of prescribed medicines. Kaplan-Meier survival curves and Cox proportional hazards models were used to demonstrate predictors for recurrence of PICH. RESULTS: Total follow-up time of the 961 patients was 3481 person-years. During the follow-up time, 58 subjects had altogether 68 recurrent PICHs. The annual average incidence of first recurrence was 1.67%. Cumulative 5- and 10-year incidence rates were 9.6% and 14.2%, respectively. In univariable analysis, history of ischemic stroke, diabetes mellitus, and aspirin use were associated with a higher recurrence rate. In multivariable analysis, only previous ischemic stroke (adjusted hazard ratio, 2.22; 95% confidence interval, 1.22-4.05; P=0.009) independently predicted PICH recurrence. Diabetes mellitus tended to increase (adjusted hazard ratio, 2.38; 95% confidence interval, 0.98-5.80; P=0.056), whereas treated hypertension tended to decrease (0.45, 0.20-1.01; P=0.054) the risk for fatal recurrent PICH. CONCLUSIONS: Previous ischemic stroke independent of confounding factors may increase the risk for PICH recurrence.

Effect of increased warfarin use on warfarin-related cerebral hemorrhage: a longitudinal population-based study.

BACKGROUND AND PURPOSE: Warfarin use has rapidly increased with the aging of the population. We investigated the temporal trends in the incidence and outcome of warfarin-related intracerebral hemorrhages (ICHs) in a defined population. METHODS: We identified all subjects with first-ever primary ICH during 1993 to 2008 among the population of Northern Ostrobothnia, Finland. The number of warfarin users was obtained from the national register of prescribed medicines kept by the Social Insurance Institution of Finland. We calculated the annual incidence of warfarin-related ICHs, 28-day case fatality, and deaths from the primary bleed. RESULTS: The proportion of warfarin users among the population increased 3.6-fold from 0.68% in 1993 to 2.28% in 2008. Of a total of 982 patients with ICH, 182 (18.5%) had warfarin-related ICH. One-year survival rate after onset of stroke was 35.2% among warfarin users and 67.9% among nonusers. The annual incidence (P=0.062) and 28-day case fatality of warfarin-related ICHs (P=0.002) decreased during the observation period. Warfarin users were older (mean difference 6.6; 95% CI, 5.0 to 8.1; P<0.001) than nonusers. Admission international normalized ratio values above the therapeutic range (2.0 to 3.0) decreased through the observation period, suggesting improved control of anticoagulant therapy over time. CONCLUSIONS: The annual incidence and case fatality of warfarin-related ICHs decreased, although the proportion of warfarin users almost quadrupled in our population.

Alcohol consumption, blood pressure, and the risk of stroke.

A synergistic effect of alcohol and hypertension has been suggested to increase the risk for stroke. However, the contribution of alcohol-induced hypertension to stroke morbidity and mortality may be greater than observed, because the effects of different drinking patterns have not been separately investigated. Alcohol-induced transient peaks in systolic blood pressure may predispose to stroke. Recent studies have measured time trends of blood pressure elevations in relation to alcohol consumption. They found a significant morning surge in blood pressure, which was related to alcohol intake in a dose-dependent manner and was independent of smoking. Men with a severe form of hypertension showed a 12-fold increased risk for cardiovascular disease mortality associated with heavy binge drinking. Binge drinking is a significant risk factor for stroke. Hypertensive patients should be warned about the risks of alcohol and urged to avoid binge drinking because of an increased risk for all subtypes of stroke.

Hypertension and diabetes as predictors of early death after spontaneous intracerebral hemorrhage.

OBJECT: Previous investigators have suggested that a high mean arterial blood pressure (MABP) and an elevated plasma glucose level at admission are associated with a poor outcome after hemorrhagic stroke. It remains unclear, however, whether hypertension and diabetes are responsible for this effect. High admission MABP and plasma glucose levels may also be markers of other factors such as stroke severity. METHODS: The authors retrospectively investigated the role of a high admission MABP and plasma glucose level together with other predictors of early death among 379 nonsurgical patients with spontaneous intracerebral hemorrhages (ICHs) who were admitted to the stroke unit of Oulu University Hospital. RESULTS: The 3-month mortality rate was 28%. The patients who died within 3 months of ICH had significantly higher plasma glucose levels and MABPs at admission (p < 0.001). After adjustments for patient sex, age, size and location of hematoma, Glasgow Coma Scale score at admission, presence of intraventricular hemorrhage, history of cardiac disease, and previous use of warfarin, history of diabetes (relative risk 1.61, 95% CI 1.03-2.53, p < 0.05) and high MABP at admission (relative risk 1.01 per mm Hg, 95% CI 1.00-1.02, p < 0.05) remained independent predictors of death 3 months after ICH. A high admission plasma glucose level and history of hypertension were not independent predictors of death. CONCLUSIONS: A high MABP at admission was found to be an independent predictor of early death in patients with ICH. History of hypertension was not responsible for the effect. Admission hyperglycemia appeared to be a stress response to the severity of the bleeding, whereas diabetes predicted early death.

Impact of ischemic heart disease and atrial fibrillation on survival after spontaneous intracerebral hemorrhage.

OBJECT: The well-known predictors for increased early deaths after spontaneous intracerebral hemorrhage (ICH) include the clinical and radiological severity of bleeding as well as being on a warfarin regimen at the onset of stroke. Ischemic heart disease and atrial fibrillation may also increase early deaths. In the present study the authors aimed to elucidate the role of the last 2 factors. METHODS: The authors assessed the 3-month mortality rate in patients with spontaneous ICH (453 individuals) who were admitted to the stroke unit of Oulu University Hospital within a period of 11 years (1993-2004). RESULTS: The 3-month mortality rate for the 453 patients was 28%. The corresponding mortality rates were 42% for the patients who had ischemic heart disease and 61% for those with atrial fibrillation on admission. The following independent predictors of death emerged after adjustment for sex and the use of warfarin or aspirin at the onset of ICH: 1) ischemic heart disease (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.12-2.48, p < 0.02); 2) atrial fibrillation on admission (HR 1.79, 95% CI 1.12-2.86, p < 0.02); 3) the Glasgow Coma Scale score on admission (HR 0.82 per unit, 95% CI 0.79-0.87, p < 0.01); 4) size of hematoma (HR 1.11 per 10 ml, 95% CI 1.07-1.16, p < 0.01); 5) intraventricular hemorrhage (HR 2.62, 95% CI 1.71-4.02, p < 0.01); 6) age (HR 1.04 per year, 95% CI 1.02-1.06, p < 0.01); and 7) infratentorial location of the hematoma (HR 1.93, 95% CI 1.26-2.97, p < 0.01). CONCLUSIONS: Both ischemic heart disease and atrial fibrillation independently and significantly impaired the 3-month survival of patients with ICH.

Safety of low-dose subcutaneous enoxaparin for the prevention of venous thromboembolism after primary intracerebral haemorrhage.

BACKGROUND: The risks and benefits of low molecular weight heparins (LMWH) for the prevention of deep-vein thrombosis (DVT) and pulmonary embolism (PE) after intracerebral haemorrhage (ICH) have not been assessed. The few studies on this subject have revealed conflicting results. METHODS: We retrospectively evaluated whether subcutaneous enoxaparin (20 mg daily) reduced symptomatic venous complications or caused increased 3-month death rate. We included 407 patients who were admitted to a stroke unit and survived the first two days after onset of ICH. There were 232 patients who received anticoagulant treatment for the prevention of DVT and PE and 175 who did not. RESULTS: Despite the fact that the treated patients were in worse clinical condition at the start of the treatment, 3-month death rate was 19% among them compared to 21% among those not receiving anticoagulant therapy. Low-dose subcutaneous enoxaparin (20 mg once daily) induced a significant plasma anti-factor Xa activity 2-3 hours after administration (p=0.018). Haematoma enlargements (33%) occurred in 9% and 7% of the treated and untreated patients, whereas symptomatic venous thromboembolic complications were observed in 3% and 2%, respectively. CONCLUSIONS: We did not observe any increased mortality among ICH patients who survived the first 2 days after the onset of ICH and were thereafter treated with enoxaparin 20 mg daily relative to patients remaining untreated. A randomized trial of the effect of LMWH with a higher dose in prevention of venous thromboembolic complications would be indicated.

The impact of functional status at three months on long-term survival after spontaneous intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Few studies have assessed long-term prognosis and risk factors for death after spontaneous intracerebral hemorrhage (ICH). Patients who survive the acute phase may run different prognoses, depending on their disability, treatment, and lifestyle. The present study was performed to find out the predictors for long-term mortality after ICH. METHODS: We assessed 7-year prognosis in a population-based cohort of patients who had survived the first 3 months after ICH (n=140). Controls (n=206) living in the same geographical area were randomly drawn from the population register and followed up for the same time. RESULTS: Seven-year mortality was significantly higher in ICH patients than in controls (32.9 and 19.4%, respectively; P=0.0034). The annual risk for death in ICH patients was 5.6%, and the annual risk for fatal recurrent ICH was 1.3%. The ICH patients with good recovery at 3 months showed similar risk for death as controls. Recurrent ICH and pneumonia were the most common causes of death in ICH patients. Cigarette smoking, age, and diabetes seemed to increase the risk for death in patients and controls. CONCLUSIONS: Survivors of ICH run a higher long-term risk for death than age- and sex-matched controls. However, those who show good recovery at 3 months run a similar outcome as controls.

Regular aspirin-use preceding the onset of primary intracerebral hemorrhage is an independent predictor for death.

BACKGROUND AND PURPOSE: Hematoma volume and impaired level of consciousness are the most potent predictors of outcome after spontaneous intracerebral hemorrhage (ICH). The effect of preceding aspirin-use on outcome after ICH is poorly investigated. We investigated short-term mortality and hematoma enlargement in subjects with ICH to find the predictors for these outcomes. METHODS: This population-based study included all subjects with ICH during a period of 33 months in the population of Northern Ostrobothnia, Finland. The subjects were identified, and their clinical characteristics and outcomes were checked from hospital records or death records. RESULTS: Three-month mortality of the 208 identified subjects with ICH was 33%. The independent risk factors for death were regular aspirin-use at the onset of ICH (relative risks [RR], 2.5; 95% CI, 1.3 to 4.6; P=0.004), warfarin-use at the onset of ICH (RR, 3.2; 95% CI, 1.6 to 6.1; P=0.001), and ICH score higher than 2 on admission (RR, 13.8; 95% CI, 6.0 to 31.4; P<0.001). Regular aspirin-use preceding the onset of ICH associated significantly with hematoma enlargement during the first week after ICH (P=0.006). CONCLUSIONS: We observed poor short-term outcomes and increased mortality, probably attributable to rapid enlargement of hematomas, in the subjects with ICH who had been taking regularly moderate doses of aspirin (median 250 mg) immediately before the onset of the stroke.

Thromboxane and prostacyclin biosynthesis in patients with acute spontaneous intracerebral hemorrhage.

OBJECTIVE: Elevated levels of 11-dehydrothromboxane B2 (11-dehydro-TXB2) excreted in urine have been observed in acute ischemic stroke. This marker of platelet activation has not been investigated in patients with acute spontaneous intracerebral hemorrhage (ICH). METHODS: We examined 43 patients with spontaneous ICH and 23 controls. Urinary excretion rates of 11-dehydro-TXB2, 2,3-dinor-thromboxane B2 (2,3 dinor-TXB2) and 2,3-dinor-6-ketoprostaglandin F(1alpha) (2,3-dinor-PGF(1alpha)) during the first week and at 3 months after ICH were compared between patients who had or had not used aspirin and controls. RESULTS: On admission, ICH patients without aspirin use had significantly higher urinary levels of 11-dehydro-TXB2 (p<0.001), 2,3-dinor-TXB2 (p<0.001) and 2,3-dinor-PGF(1alpha) (p=0.019) than controls. Aspirin users had significantly lower urinary levels of these metabolites than nonusers. The metabolite levels of aspirin users on admission did not significantly differ from those of controls. The differences between aspirin users and nonusers leveled off during the following 3-5 days, however, as the blocking effect of aspirin on the production of TXA2 and PGI2 ceased. Three months after ICH, the metabolite excretion levels in all the patients were similar to those in nonusers of aspirin on admission. On admission, aspirin users had longer bleeding times (p=0.032) than nonusers, but aspirin use did not associate with impaired recovery or hematoma enlargement. CONCLUSIONS: Urinary excretion levels of 11-dehydro-TXB2, 2,3-dinor-TXB2 and 2,3-dinor-PGF1alpha were higher in patients with acute ICH than in controls. The levels in aspirin users were equally low as in controls but rose to the levels of the other patients within a few days. The metabolite levels remained high 3 months after ICH in all patients. Prior use of aspirin did not seem to cause hematoma enlargement.