Tero Vahlberg

Mortality and cause of death in hip fracture patients aged 65 or older - a population-based study

BackgroundThe high mortality of hip fracture patients is well documented, but sex- and cause-specific mortality after hip fracture has not been extensively studied. The purpose of the present study was to evaluate mortality and cause of death in patients after hip fracture surgery and to compare their mortality and cause of death to those in the general population.MethodsRecords of 428 consecutive hip fracture patients were collected on a population-basis and data on the general population comprising all Finns 65 years of age or older were collected on a cohort-basis. Cause of death was classified as follows: malignant neoplasms, dementia, circulatory disease, respiratory disease, digestive system disease, and other.ResultsMean follow-up was 3.7 years (range 0-9 years). Overall 1-year postoperative mortality was 27.3% and mortality after hip fracture at the end of the follow-up was 79.0%. During the follow-up, age-adjusted mortality after hip fracture surgery was higher in men than in women with hazard ratio (HR) 1.55 and 95% confidence interval (95% CI) 1.21-2.00. Among hip surgery patients, the most common causes of death were circulatory diseases, followed by dementia and Alzheimers disease. After hip fracture, men were more likely than women to die from respiratory disease, malignant neoplasm, and circulatory disease. During the follow-up, all-cause age- and sex-standardized mortality after hip fracture was 3-fold higher than that of the general population and included every cause-of-death category.ConclusionDuring the study period, the risk of mortality in hip fracture patients was 3-fold higher than that in the general population and included every major cause of death.

Hippocampal and prefrontal atrophy in patients with early non-demented Parkinson’s disease is related to cognitive impairment

Background: Early stage patients with Parkinson’s disease (PD) show cognitive impairment in frontal lobe functions and memory tests. Hippocampal atrophy is seen in medicated patients with advanced PD. Objectives: To examine whether prefrontal or hippocampal atrophy are already present in early stage PD, and whether such atrophy is associated with cognitive impairment. Methods: Twenty non-medicated, non-demented patients with early stage PD and 22 neurologically healthy age matched controls were studied. All subjects underwent magnetic resonance imaging to study hippocampal and prefrontal atrophy. Atrophy was evaluated by a neuroradiologist using a five point scale. In addition, the patients underwent a neuropsychological test battery sensitive to frontal lobe functions and memory. Results: Patients with PD had atrophy in the right and the left prefrontal cortex. In the right hippocampus, the mean atrophy score was 1.15 in PD and 0.45 in controls. Corresponding figures for the left hippocampus were 1.05 for PD and 0.64 for controls. In PD, the left hippocampus atrophy correlated with verbal memory and prefrontal atrophy correlated with impaired performance in a test measuring vigilance. Conclusions: Non-medicated, non-demented patients with early stage PD show hippocampal and prefrontal atrophy. Impaired memory is related to hippocampal atrophy, whereas sustained attention is related to prefrontal atrophy.

Amyloid PET imaging in patients with mild cognitive impairment: A 2-year follow-up study

Background: Patients with amnestic mild cognitive impairment (MCI) have greater risk of conversion to Alzheimer disease (AD). Increased brain amyloid burden in AD and MCI has been demonstrated with PET using [11C] Pittsburgh compound B (PiB) as a tracer. Objective: To evaluate change in β-amyloid deposition in with MCI during 2-year follow-up. Methods: Patients with MCI and controls were studied with [11C] PiB PET, MRI, and neuropsychometry at baseline and these investigations were repeated in patients with MCI after follow-up. Results: Those patients with MCI converting to AD during follow-up had greater [11C] PiB retention in the posterior cingulate (p = 0.020), in the lateral frontal cortex (p = 0.006), in the temporal cortex (p = 0.022), in the putamen (p = 0.041), and in the caudate nucleus (p = 0.025) as compared to nonconverters. In converters, there was no significant change in [11C] PiB uptake, whereas an increase was seen as compared to baseline in nonconverters in the anterior and posterior cingulate, temporal and parietal cortices, and putamen. Hippocampal atrophy was greater in converters at baseline than in nonconverters, but increased significantly in both groups during follow-up. Conclusions: Hippocampal atrophy and amyloid deposition seem to dissociate during the evolution of MCI, the atrophy increasing clearly and [11C] PiB retention changing modestly when conversion to AD occurs. Longer follow-up is needed to determine whether nonconverters would convert to AD later, which would suggest accelerated [11C] PiB retention preceding clinical conversion.

Early Oseltamivir Treatment of Influenza in Children 1–3 Years of Age: A Randomized Controlled Trial

BACKGROUND Oseltamivir provides modest clinical benefits to children with influenza when started within 48 hours of symptom onset. The effectiveness of oseltamivir could be substantially greater if the treatment were started earlier during the course of the illness. METHODS We carried out a randomized, double-blind, placebo-controlled trial of the efficacy of oseltamivir started within 24 hours of symptom onset in children 1-3 years of age with laboratory-confirmed influenza during the seasons of 2007-2008 and 2008-2009. Eligible children received either orally administered oseltamivir suspension or a matching placebo twice daily for 5 days. The children received clinical examinations, and the parents filled out detailed symptom diaries for 21 days. RESULTS Of 408 randomized children who received the study drug (oseltamivir, 203, and placebo, 205), 98 had laboratory-confirmed influenza (influenza A, 79, and influenza B, 19). When started within 12 hours of the onset of symptoms, oseltamivir decreased the incidence of acute otitis media by 85% (95% confidence interval, 25%-97%), but no significant reduction was observed with treatment started within 24 hours. Among children with influenza A, oseltamivir treatment started within 24 hours shortened the median time to resolution of illness by 3.5 days (3.0 vs 6.5 days; P = .006) in all children and by 4.0 days (3.4 vs 7.3; P = .006) in unvaccinated children and reduced parental work absenteeism by 3.0 days. No efficacy was demonstrated against influenza B infections. CONCLUSIONS Oseltamivir treatment started within 24 hours of symptom onset provides substantial benefits to children with influenza A infection. Clinical trials registration. ClinicalTrials.gov identifier: NCT00593502.

Estimation of glomerular filtration rate in the elderly: a comparison of creatinine-based formulae with serum cystatin C

Objectives.  To estimate the prevalence of decreased kidney function in an elderly population and to evaluate the impact of using alternative markers of glomerular filtration rate (GFR), focusing on serum cystatin C (Cys C) and the Modification of Diet in Renal Disease (MDRD) Study prediction equation.

Hippocampal dopamine D2 receptors correlate with memory functions in Alzheimer's disease

Post mortem studies have revealed a loss of dopamine D2 receptors in the temporal lobes in Alzheimers disease (AD). Moreover, the role of hippocampal D2 receptors on memory performance has been suggested in experimental studies. However, there are no previous in vivo studies on extrastriatal D2 receptors in AD. Our aim was to examine in vivo whether hippocampal or temporal cortical dopamine D2 receptors are affected in AD and whether D2 receptor availability is associated with the memory dysfunction seen in AD. Fourteen patients with probable AD and 11 age‐ and sex‐matched controls were studied with positron emission tomography using a dopamine D2/D3 receptor antagonist [11C]FLB 457. The D2 receptor binding potentials (BPs) were measured in extrastriatal brain regions and a neuropsychological investigation was performed on the patients with AD. In AD, the D2 receptor availability was reduced in the hippocampus: by 34% (P = 0.03) in the right hippocampus and by 14% (P = 0.78) in the left hippocampus as compared with controls. Multiple linear regression analysis showed that the BP in the right hippocampus had a significant positive association with verbal memory performance (Wechsler Memory Scale – Revised) (P = 0.001) and picture naming (the Boston Naming Test) (P = 0.002). Our findings suggest a role for temporal lobe D2 receptors in the memory and naming performance in AD, and suggest that studies to evaluate the efficiency of dopaminergic medication on patients with early AD might be warranted.

Investigating minimal clinically important difference for Constant score in patients undergoing rotator cuff surgery.

BACKGROUND The minimal clinically important difference (MCID) is increasingly used to evaluate treatment effectiveness. The MCID for the Constant score has not been previously reported. MATERIALS AND METHODS A prospectively collected cohort of 802 consecutive shoulders with arthroscopically treated partial- or full-thickness rotator cuff tears was analyzed. The Constant score was measured preoperatively and at 3 months and 1 year postoperatively. At follow-up visits, the patients were asked a simple 2-stage question: Is the shoulder better or worse after the operation compared with the preoperative state? This single 2-level question was used as an indicator of patient satisfaction and as an anchor to calculate the MCID for the Constant score. RESULTS At 1 year, 781 (97.4%) patients (474 men, 307 women) were available for follow-up. The preoperative Constant score was 53.1 (SD 17.2) in all patients, 56.2 (SD 17.4) in male patients, and 48.2 (SD 15.6) in female patients. Postoperatively at 3 months, the scores were 61.7 (SD 16.4) in all patients, 65.1 (SD 16.1) in male patients, and 56.8 (SD 15.5) in female patients. At 1 year, the scores were 75.9 (SD 15.2) in all patients, 79.0 (SD 14.9) in male patients, and 71.0 (SD 14.3) in female patients. At 3 months postoperatively, 92.2% of male patients and 87.2% of female patients were satisfied with the outcome (P = .027); at 1 year, the satisfaction was 93.2% and 89.5%, respectively (P = .067). Five different statistical approaches yielded 5 different MCID estimates (range, 2-16). The 3-month mean change estimate of MCID was 10.4 points. CONCLUSION Our study demonstrates an MCID estimate of 10.4 points as the threshold for the Constant score in patients with rotator cuff tear. LEVEL OF EVIDENCE Basic science study, validation of outcomes instruments/classification systems.

Safety of percutaneous coronary intervention during uninterrupted oral anticoagulant treatment

AIMS Uninterrupted anticoagulation (UAC) is assumed to increase bleeding and access-site complications. A common consensus is to postpone percutaneous coronary interventions (PCI) to reach international normalized ratio (INR) levels < 1.5-1.8. METHODS AND RESULTS To assess the safety and feasibility of UAC, we analysed retrospectively all consecutive patients (n = 523) on warfarin therapy referred for PCI in four centres with a policy to interrupt anticoagulation (IAC) before PCI and in three centres with a long experience on UAC during PCI. Major bleeding, access-site complications, and major adverse cardiac events (death, myocardial infarction, target vessel revascularization, and stent thrombosis) were recorded during hospitalization. In the IAC group, warfarin was withdrawn for a mean of 3 days prior to PCI (mean INR 1.7). In the UAC group, mean INR value was 2.2. Glycoprotein IIb/IIIa (GP) inhibitors (P < 0.001) and low-molecular-weight heparins (P < 0.001) were more often used in the IAC group. Major bleeding and access-site complications were more common in the IAC group (5.0% vs. 1.2%, P = 0.02 and 11.3% vs. 5.0%, P = 0.01, respectively) than in the UAC group. After adjusting for propensity score, the group difference in access-site complications remained significant [OR (odds ratio) 2.8, 95% CI (confidence interval) 1.3-6.1, P = 0.008], but did not remain significant in major bleeding (OR 3.9, 95% CI 1.0-15.3, P = 0.05). In multivariable analysis, femoral access (OR 9.9, 95% CI 1.3-75.2), use of access-site closure devices (OR 2.1, 95% CI 1.1-4.0), low-molecular-weight heparin (OR 2.7, 95% CI 1.1-6.7) and old age predicted access-site complications, and the use of GP inhibitors (OR 3.0, 95% CI 1.0-9.1) remained as a predictor of major bleeding. CONCLUSION Our study shows that PCI is a safe procedure during UAC with no excess bleeding complications.

C957T polymorphism of the human dopamine D2 receptor gene predicts extrastriatal dopamine receptor availability in vivo

The C957T (rs6277) single nucleotide polymorphism (SNP) of the human dopamine D2 receptor (DRD2) gene (DRD2) affects DRD2 mRNA stability and has been shown to predict striatal DRD2 availability (B(max)/K(D)) in vivo in man. Specifically, the C/C genotype is associated with low striatal DRD2 availability (C/C<C/T<T/T). It is not known, however, whether this pattern of genetic regulation of DRD2 expression also applies to low density DRD2 populations in extrastriatal regions. We analyzed extrastriatal DRD2 availability (indexed by binding potential, BP(ND)) measured in 38 healthy male volunteers with 3D-PET and the high-affinity DRD2 radioligand [(11)C]FLB457. The subjects were genotyped for the C957T as well as for two other widely studied DRD2 SNPs, the TaqIA (rs1800497) and the -141C Ins/Del (rs1799732). Statistical analyses showed that the C957T C/C genotype was associated with high extrastriatal DRD2 BP(ND) throughout the cortex and the thalamus (C/C>C/T>T/T). Also the TaqIA A1 allele carriers (p=0.101) tended to have higher extrastriatal DRD2 BP(ND) compared to non-carriers whereas the -141C Ins/Del genotype did not influence extrastriatal DRD2 BP(ND). Our findings indicate that the DRD2 SNPs regulate DRD2 availability in the human cortex and in the thalamus in vivo. However, the regulation pattern is different from that observed previously for striatal DRD2 availability in vivo, which may reflect distinct functional roles of dopamine and DRD2 in the cortex versus the striatum. The results provide useful information for the interpretation of genetic studies exploring the role of the DRD2 in normal physiology as well as in psychiatric and neurological diseases.

Seroprevalence, incidence of prenatal infections and reliability of maternal history of varicella zoster virus, cytomegalovirus, herpes simplex virus and parvovirus B19 infection in South-Western Finland

Objective  To study seroprevalence and incidence and fetal transmission of varicella zoster virus (VZV), cytomegalovirus (CMV), herpes simplex virus (HSV) types 1 and 2 and parvovirus B19 infections during pregnancy and to evaluate the reliability of maternal past history of VZV, HSV and parvovirus infections.