Early vs. late enoxaparin for the prevention of venous thromboembolism in patients with ICH: A double blind placebo controlled multicenter study.

BACKROUND: Venous thromboembolism (VTE) after primary intracerebral hemorrhage (ICH) worsens patient prognosis. Administering low-molecular weight heparins (LMWH) to prevent VTE early (24 h) may increase the risk of hematoma enlargement, whereas administering late (72 h) after onset may decrease its effect on VTE prevention. The authors investigated when it is safe and effective to start LMWH in ICH patients. METHODS: In the setting of double blinded, placebo controlled randomization, patients >18 years of age with paretic lower extremity, and admitted to the emergency room within 12 h of the onset of ICH, were randomized into two groups. Patients in the enoxaparin group received 20 mg twice a day 24 h (early) after the onset of ICH and in the placebo group 72 h (late) after onset respectively. Both groups immediately received intermittent pneumatic compression stockings at the ER. Patients were prospectively and routinely screened for VTE and hemorrhagic complications 1 day after entering the study and again before discharge. RESULTS: 139 patients were included for randomization in this study. Only 3 patients developed VTE, 2 in the early enoxaparin group and one in the late enoxaparin group. No patients developed PE. Thromboembolic events (p = 0.901), risk of hematoma enlargement (p = 0.927) and overall outcome (P = 0.904) did not differ significantly between the groups. CONCLUSION: Administering 40 mg/d LMWH for prevention of VTE to a spontaneous ICH patient is safe regardless of whether it is started 24 h (early) or 72 h (late) after the hemorrhage. Risk of hemorrhage enlargement is not associated with early LMWH treatment. Administering LMWH late did not increase VTEs.

Mortality of subjects with alcohol-related seizures increased after alcohol cheapening.

OBJECTIVE: To investigate whether the reduction of alcohol prices in Finland (March 1, 2004) associated with an increase in mortality of subjects with alcohol-related seizures. PATIENTS AND METHODS: All subjects with head trauma in Oulu University Hospital during 1999 (n = 827) were identified and thereafter followed up until death or the end of 2009. We used National Hospital Discharge Register, hospital charts, and death records from Official Cause-of-Death Statistics to identify seizure visits and alcohol-related deaths. Kaplan-Meier survival curves were used to characterize the effect of alcohol price reduction on risk of death. Cox proportional hazards model was used to identify independent predictors of death. RESULTS: Twenty-five subjects had alcohol-related seizures before the alcohol price reduction. Their cumulative mortality rate was significantly higher (P = 0.015) than that of other head trauma subjects during the follow-up and it clearly increased after the price reduction. Age (HR 1.06 per year, 95% CI 1.05-1.07, P < 0.001), moderate-to-severe traumatic brain injury (HR 2.04 95% CI 1.37-3.04, P < 0.001), and alcohol-related seizure (HR 3.02, 95% CI 1.48-6.16, P = 0.002) were independent predictors of death after adjustment for confounding factors. CONCLUSION: We conclude that the political decision to lower alcohol price associated with a significant increase in the mortality rate of subjects with alcohol-related seizures.

Head trauma sustained under the influence of alcohol is a predictor for future traumatic brain injury: a long-term follow-up study.

BACKGROUND AND PURPOSE: Hazardous drinking may result in recurrent head trauma. It was investigated whether head trauma sustained under the influence of alcohol is a predictor of future traumatic brain injury (TBI). METHODS: All subjects with head trauma (n = 827) brought to the emergency room at Oulu University Hospital during 1999 were identified and followed up until death or the end of 2009. The National Hospital Discharge Register and hospital charts were used to identify TBIs during the follow-up and Kaplan-Meier curves and the Cox proportional hazards model were used to characterize predictors of TBI. RESULTS: During the total follow-up of 7386 person-years, 52/827 subjects sustained a new head trauma with TBI and the risk of TBI was significantly (P = 0.005) higher amongst subjects who had been under the influence of alcohol at the time of the index trauma in 1999. New TBI occurred under the influence of alcohol in 30/52 cases (57.7%). An alcohol-related index trauma [adjusted hazard ratio (HR) 2.51, 95% confidence interval (CI) 1.38-4.56, P < 0.01] and history of TBI (HR 3.39, 95% CI 1.32-8.72, P < 0.05) were independent risk factors for subsequent TBI after adjustment for sex and age. A history of harmful drinking was also a significant risk factor (adjusted HR 10.37, 95% CI 5.53-19.43, P < 0.001). In the subset of 396 patients having an index head trauma without TBI, this being alcohol related was also a significant risk factor for subsequent TBI after adjustment for sex, age and history of TBI (HR 3.54, 95% CI 1.36-9.18, P = 0.009). CONCLUSIONS: Even head trauma without TBI under the influence of alcohol implies an elevated risk of subsequent TBI. A brief intervention to reduce hazardous drinking is needed to prevent TBI.

Better than expected survival after primary intracerebral hemorrhage in patients with untreated hypertension despite high admission blood pressures.

BACKGROUND: Hypertension is the most important modifiable risk factor for primary intracerebral hemorrhage (ICH), but little is known of the effect of preceding hypertension on outcome. Because high mean arterial blood pressure (MABP) at admission is an independent predictor of early death in patients with ICH, we explored its role on survival and poor outcome separately in normotensive subjects and subjects with treated and untreated hypertension. METHODS: We assessed clinical data and the 3-month outcome of patients with spontaneous ICH (n = 453) admitted to the stroke unit of Oulu University Hospital between 1993 and 2004. Standard medical treatment was used to lower MABP from levels >127 mmHg to <120 mmHg. RESULTS: Overall mortality within 3 months was 28%. Patients with untreated hypertension had significantly lower mortality (6%) than those with treated hypertension (36%, P < 0.001) or those without hypertension (25%, P < 0.01). High admission MABP associated with early death in normotensive subjects (P < 0.05) and those on medication for hypertension (P < 0.01) but not in those with untreated hypertension. Patients with untreated hypertension were younger and had less frequently cardiac disease, diabetes, and/or warfarin or aspirin medications, but they showed the highest blood pressures (BPs) at admission. Amongst patients with high admission MABP, favorable outcome was seen most frequently in those who had untreated hypertension. Hematoma growth did not associate with high MABP amongst them. CONCLUSION: Despite their higher BP values at admission, subjects with untreated hypertension showed better survival and more frequently favorable outcome after BP-lowering therapy than other patients.

Penetration of Ullevaal hip screw into the pelvis.

The fracture of the femoral neck is usually treated operatively with screw osteosynthesis or prosthesis. There have been reported a rare complication both with screws and lag screws used in hip fractures, both can penetrate into the pelvis postoperatively. We present two cases with this similar rare complication when using Ullevaal screws. Both patients were reoperated on with a total hip arthroplasty (THA). We think that the exact anatomical reposition and good operation technique should make this complication even more rare. The canal should always be drilled only to the line of the fracture, so that there is no canal for the screw to squeeze further. To prevent penetration some kind of cap fixed the lateral end of the screw could also be worth while.

Modulation of murine phenobarbital-inducible CYP2A5, CYP2B10 and CYP1A enzymes by inhibitors of protein kinases and phosphatases.

Phenobarbital causes a multitude of effects in hepatocytes, including increased cell proliferation, inhibition of apoptosis and upregulation of xenobiotic and endobiotic metabolizing enzymes. In this study, the involvement of several protein kinase and phosphatase pathways on constitutive and phenobarbital-induced activities of CYP2A5, CYP2B10 and CYP1A1/2 in primary mouse hepatocytes was determined using well-defined chemical modulators of intracellular protein phosphorylation and desphosphorylation events. A 48-h treatment of the hepatocytes with 2-aminopurine, a nonspecific serine/threonine kinase inhibitor, elicited dose-dependent increases in both basal and phenobarbital-induced CYP2A5 catalytic activity (assayed as coumarin 7-hydroxylation), the maximal induction being 60-fold greater than the control value upon cotreatment with 1.5 mM phenobarbital and 10 mM 2-aminopurine. In contrast, phenobarbital induction of CYP2B10 (pentoxyresorufin O-deethylase) and CYP1A1/2 (ethoxyresorufin O-deethylase) activities were blocked by 2-aminopurine. Increases in CYP2A5 activity were also observed after exposure of the hepatocytes to other protein kinase inhibitors affecting the cell cycle, i.e. roscovitine, K-252a and rapamycin. Inhibitors of protein kinases A and C, as well as tyrosine kinases, did not appreciably affect CYP2A5 activity levels. The serine/threonine phosphatase inhibitors tautomycin, calyculin A and okadaic acid all reduced both basal and phenobarbital-induced CYP2A5, CYP2B10 and CYP1A1/2 activities. These results further strengthen the concept that hepatic CYP2A5 is regulated in a unique way compared with CYP2B10 and CYP1A.