Varsinais-Suomen Sairaanhoitopiiri

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.

IMPORTANCE: An increasing amount of evidence supports the use of antibiotics instead of surgery for treating patients with uncomplicated acute appendicitis. OBJECTIVE: To compare antibiotic therapy with appendectomy in the treatment of uncomplicated acute appendicitis confirmed by computed tomography (CT). DESIGN, SETTING, AND PARTICIPANTS: The Appendicitis Acuta (APPAC) multicenter, open-label, noninferiority randomized clinical trial was conducted from November 2009 until June 2012 in Finland. The trial enrolled 530 patients aged 18 to 60 years with uncomplicated acute appendicitis confirmed by a CT scan. Patients were randomly assigned to early appendectomy or antibiotic treatment with a 1-year follow-up period. INTERVENTIONS: Patients randomized to antibiotic therapy received intravenous ertapenem (1 g/d) for 3 days followed by 7 days of oral levofloxacin (500 mg once daily) and metronidazole (500 mg 3 times per day). Patients randomized to the surgical treatment group were assigned to undergo standard open appendectomy. MAIN OUTCOMES AND MEASURES: The primary end point for the surgical intervention was the successful completion of an appendectomy. The primary end point for antibiotic-treated patients was discharge from the hospital without the need for surgery and no recurrent appendicitis during a 1-year follow-up period. RESULTS: There were 273 patients in the surgical group and 257 in the antibiotic group. Of 273 patients in the surgical group, all but 1 underwent successful appendectomy, resulting in a success rate of 99.6% (95% CI, 98.0% to 100.0%). In the antibiotic group, 70 patients (27.3%; 95% CI, 22.0% to 33.2%) underwent appendectomy within 1 year of initial presentation for appendicitis. Of the 256 patients available for follow-up in the antibiotic group, 186 (72.7%; 95% CI, 66.8% to 78.0%) did not require surgery. The intention-to-treat analysis yielded a difference in treatment efficacy between groups of -27.0% (95% CI, -31.6% to ∞) (P = .89). Given the prespecified noninferiority margin of 24%, we were unable to demonstrate noninferiority of antibiotic treatment relative to surgery. Of the 70 patients randomized to antibiotic treatment who subsequently underwent appendectomy, 58 (82.9%; 95% CI, 72.0% to 90.8%) had uncomplicated appendicitis, 7 (10.0%; 95% CI, 4.1% to 19.5%) had complicated acute appendicitis, and 5 (7.1%; 95% CI, 2.4% to 15.9%) did not have appendicitis but received appendectomy for suspected recurrence. There were no intra-abdominal abscesses or other major complications associated with delayed appendectomy in patients randomized to antibiotic treatment. CONCLUSIONS AND RELEVANCE: Among patients with CT-proven, uncomplicated appendicitis, antibiotic treatment did not meet the prespecified criterion for noninferiority compared with appendectomy. Most patients randomized to antibiotic treatment for uncomplicated appendicitis did not require appendectomy during the 1-year follow-up period, and those who required appendectomy did not experience significant complications. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01022567.

Primary open-angle glaucoma (POAG), is a heritable common cause of blindness world-wide. To identify risk loci, we conduct a large multi-ethnic meta-analysis of genome-wide association studies on a total of 34,179 cases and 349,321 controls, identifying 44 previously unreported risk loci and confirming 83 loci that were previously known. The majority of loci have broadly consistent effects across European, Asian and African ancestries. Cross-ancestry data improve fine-mapping of causal variants for several loci. Integration of multiple lines of genetic evidence support the functional relevance of the identified POAG risk loci and highlight potential contributions of several genes to POAG pathogenesis, including SVEP1, RERE, VCAM1, ZNF638, CLIC5, SLC2A12, YAP1, MXRA5, and SMAD6. Several drug compounds targeting POAG risk genes may be potential glaucoma therapeutic candidates.

Importance: Short-term results support antibiotics as an alternative to surgery for treating uncomplicated acute appendicitis, but long-term outcomes are not known. Objective: To determine the late recurrence rate of appendicitis after antibiotic therapy for the treatment of uncomplicated acute appendicitis. Design, Setting, and Participants: Five-year observational follow-up of patients in the Appendicitis Acuta (APPAC) multicenter randomized clinical trial comparing appendectomy with antibiotic therapy, in which 530 patients aged 18 to 60 years with computed tomography-confirmed uncomplicated acute appendicitis were randomized to undergo an appendectomy (n = 273) or receive antibiotic therapy (n = 257). The initial trial was conducted from November 2009 to June 2012 in Finland; last follow-up was September 6, 2017. This current analysis focused on assessing the 5-year outcomes for the group of patients treated with antibiotics alone. Interventions: Open appendectomy vs antibiotic therapy with intravenous ertapenem for 3 days followed by 7 days of oral levofloxacin and metronidazole. Main Outcomes and Measures: In this analysis, prespecified secondary end points reported at 5-year follow-up included late (after 1 year) appendicitis recurrence after antibiotic treatment, complications, length of hospital stay, and sick leave. Results: Of the 530 patients (201 women; 329 men) enrolled in the trial, 273 patients (median age, 35 years [IQR, 27-46]) were randomized to undergo appendectomy, and 257 (median age, 33 years, [IQR, 26-47]) were randomized to receive antibiotic therapy. In addition to 70 patients who initially received antibiotics but underwent appendectomy within the first year (27.3% [95% CI, 22.0%-33.2%]; 70/256), 30 additional antibiotic-treated patients (16.1% [95% CI, 11.2%-22.2%]; 30/186) underwent appendectomy between 1 and 5 years. The cumulative incidence of appendicitis recurrence was 34.0% (95% CI, 28.2%-40.1%; 87/256) at 2 years, 35.2% (95% CI, 29.3%-41.4%; 90/256) at 3 years, 37.1% (95% CI, 31.2%-43.3%; 95/256) at 4 years, and 39.1% (95% CI, 33.1%-45.3%; 100/256) at 5 years. Of the 85 patients in the antibiotic group who subsequently underwent appendectomy for recurrent appendicitis, 76 had uncomplicated appendicitis, 2 had complicated appendicitis, and 7 did not have appendicitis. At 5 years, the overall complication rate (surgical site infections, incisional hernias, abdominal pain, and obstructive symptoms) was 24.4% (95% CI, 19.2%-30.3%) (n = 60/246) in the appendectomy group and 6.5% (95% CI, 3.8%-10.4%) (n = 16/246) in antibiotic group (P < .001), which calculates to 17.9 percentage points (95% CI, 11.7-24.1) higher after surgery. There was no difference between groups for length of hospital stay, but there was a significant difference in sick leave (11 days more for the appendectomy group). Conclusions and Relevance: Among patients who were initially treated with antibiotics for uncomplicated acute appendicitis, the likelihood of late recurrence within 5 years was 39.1%. This long-term follow-up supports the feasibility of antibiotic treatment alone as an alternative to surgery for uncomplicated acute appendicitis. Trial Registration: ClinicalTrials.gov Identifier: NCT01022567.

Objective Intestinal microbiota is implicated in the pathogenesis of autoimmune type 1 diabetes in humans and in non-obese diabetic (NOD) mice, but evidence on its causality and on the role of individual microbiota members is limited. We investigated if different diabetes incidence in two NOD colonies was due to microbiota differences and aimed to identify individual microbiota members with potential significance. Design We profiled intestinal microbiota between two NOD mouse colonies showing high or low diabetes incidence by 16S ribosomal RNA gene sequencing and colonised the high-incidence colony with the microbiota of the low-incidence colony. Based on unaltered incidence, we identified a few taxa which were not effectively transferred and thereafter, transferred experimentally one of these to test its potential significance. Results Although the high-incidence colony adopted most microbial taxa present in the low-incidence colony, diabetes incidence remained unaltered. Among the few taxa which were not transferred, Akkermansia muciniphila was identified. As A. muciniphila abundancy is inversely correlated to the risk of developing type 1 diabetes-related autoantibodies, we transferred A. muciniphila experimentally to the high-incidence colony. A. muciniphila transfer promoted mucus production and increased expression of antimicrobial peptide Reg3γ , outcompeted Ruminococcus torques from the microbiota, lowered serum endotoxin levels and islet toll-like receptor expression, promoted regulatory immunity and delayed diabetes development. Conclusion Transfer of the whole microbiota may not reduce diabetes incidence despite a major change in gut microbiota, but single symbionts such as A. muciniphila with beneficial metabolic and immune signalling effects may reduce diabetes incidence when administered as a probiotic.

In Brief Objective: To prospectively compare the accuracy of combined positron emission tomography/computed tomography using 18F-fluorodeoxyglucose (FDG-PET/CT), multidetector row computed tomography (MDCT), and magnetic resonance imaging (MRI) in the evaluation of patients with suspected pancreatic malignancy. Summary Background Data: FDG-PET/CT imaging is increasingly used for staging of pancreatic cancer. Preliminary data suggest a significant influence of FDG-PET/CT on treatment planning, although its role is still evolving. Methods: Thirty-eight consecutive patients with suspicion of pancreatic malignancy were enrolled. Patients underwent a protocol including FDG-PET/CT, MDCT, and MRI combined with magnetic resonance cholangiopancreatography, all of which were blindly evaluated. The findings were confirmed macroscopically at operation and/or by histopathologic analysis (n = 29) or follow-up (n = 9). Results of TNM classification of different imaging methods were compared with clinical TNM classification. Results: Pancreatic adenocarcinoma was diagnosed in 17 patients, neuroendocrine tumor in 3, mass-forming pancreatitis in 4, cystic lesion in 6, and fibrosis in 2. Six patients had a finding of a normal pancreas. The diagnostic accuracy of FDG-PET/CT for pancreatic malignancy was 89%, compared with 76% and 79% for MDCT and MRI, respectively. In the differential diagnosis of suspected malignant biliary stricture at endoscopic retrograde cholangiopancreaticography (n = 21), FDG-PET/CT had a positive predictive value of 92%. In 17 patients with advanced pancreatic adenocarcinoma, FDG-PET/CT had a sensitivity of 30% for N- and 88% for M-staging. Both MDCT and MRI had sensitivities of 30% for N- and 38% for M-staging. Furthermore, the clinical management of 10 patients (26%) was altered after FDG-PET/CT. Conclusion: FDG-PET/CT was more sensitive than conventional imaging in the diagnosis of both primary pancreatic adenocarcinoma and associated distant metastases. In contrast, the sensitivity of FDG-PET/CT was poor in detecting local lymph node metastasis, which would have been important for an assessment of resectability. We recommend the use of FDG-PET/CT in the evaluation of diagnostically challenging cases, especially in patients with biliary strictures without evidence of malignancy in conventional imaging. The aim of the study was to prospectively compare 18F-fluorodeoxyglucose positron emission tomography or computed tomography, multidetector row computed tomography, and magnetic resonance imaging in the diagnosis of pancreatic cancer. In group of 38 patients, 18F-fluorodeoxyglucose positron emission tomography or computed tomography was more sensitive than conventional imaging in the diagnosis of both primary pancreatic adenocarcinoma and associated distant metastases.

Abstract Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P &lt;5 ×10 −8 ), 10 of which associate with CVD risk including five new loci- COL5A1 , GLTPD2 , SPTLC3 , MBOAT7 and GALNT16 (false discovery rate&lt;0.05). We identify loci for lipid species that are shown to predict CVD e.g., SPTLC3 for CER(d18:1/24:1). We show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacylglycerides (TAGs) than others. Polyunsaturated lipids have highest heritability and genetic correlations, suggesting considerable genetic regulation at fatty acids levels. We find low genetic correlations between traditional lipids and lipid species. Our results show that lipidomic profiles capture information beyond traditional lipids and identify genetic variants modifying lipid levels and risk of CVD.

Abstract We systematically surveyed period variations of superhumps in SU UMa-type dwarf novae based on newly obtained data and past publications. In many systems, the evolution of the superhump period is found to be composed of three distinct stages: an early evolutionary stage with a longer superhump period, a middle stage with systematically varying periods, and a final stage with a shorter, stable superhump period. During the middle stage, many systems with superhump periods of less than 0.08 d show positive period derivatives. We present observational characteristics of these stages and give greatly improved statistics. Contrary to an earlier claim, we found no clear evidence for a variation of period derivatives among different superoutbursts of the same object. We present an interpretation that the lengthening of the superhump period is a result of the outward propagation of an eccentricity wave, which is limited by the radius near the tidal truncation. We interpret that late-stage superhumps are rejuvenated excitation of a 3:1 resonance when superhumps in the outer disk are effectively quenched. The general behavior of the period variation, particularly in systems with short orbital periods, appears to follow a scenario proposed in Kato, Maehara, and Monard (2008, PASJ, 60, L23). We also present an observational summary of WZ Sge-type dwarf novae. Many of them have shown long-enduring superhumps during a post-superoutburst stage having longer periods than those during the main superoutburst. The period derivatives in WZ Sge-type dwarf novae are found to be strongly correlated with the fractional superhump excess, or consequently with the mass ratio. WZ Sge-type dwarf novae with a long-lasting rebrightening or with multiple rebrightenings tend to have smaller period derivatives, and are excellent candidates for those systems around or after the period minimum of evolution of cataclysmic variables.

AIMS: We compared metformin with insulin as treatment of gestational diabetes mellitus (GDM). Furthermore, we aimed to characterize metformin-treated patients needing additional insulin to achieve prespecified glucose targets. METHODS: We conducted a single centre randomized controlled study with non-inferiority design comparing metformin and insulin in the treatment of 217 GDM patients having birth weight as primary outcome variable. RESULTS: There were no significant differences in mean birth weight expressed in grams [+15 (90% confidence interval (CI): -121 to 89)] or SD units [+0.04 (90% CI: -0.27 to 0.18)] between the metformin and insulin groups. There were no significant differences in neonatal or maternal data between the groups. Only 23 (20.9%) of the 110 patients in the metformin group needed additional insulin. Compared with the patients on metformin only, those needing additional insulin were older (p = 0.04), their oral glucose tolerance test had been performed earlier and diabetes therapy started earlier in gestation (p = 0.01 and p = 0.004, respectively). The risk for additional insulin was 4.6-fold in women with baseline serum fructosamine concentration above median compared with those below median. CONCLUSIONS: Metformin is an effective alternative to insulin in the treatment of GDM patients. Serum fructosamine may help in predicting the adequacy of metformin treatment alone.

Abstract Polygenic risk scores (PRS) for breast cancer have potential to improve risk prediction, but there is limited information on their utility in various clinical situations. Here we show that among 122,978 women in the FinnGen study with 8401 breast cancer cases, the PRS modifies the breast cancer risk of two high-impact frameshift risk variants. Similarly, we show that after the breast cancer diagnosis, individuals with elevated PRS have an elevated risk of developing contralateral breast cancer, and that the PRS can considerably improve risk assessment among their female first-degree relatives. In more detail, women with the c.1592delT variant in PALB2 (242-fold enrichment in Finland, 336 carriers) and an average PRS (10–90 th percentile) have a lifetime risk of breast cancer at 55% (95% CI 49–61%), which increases to 84% (71–97%) with a high PRS ( &gt; 90 th percentile), and decreases to 49% (30–68%) with a low PRS ( &lt; 10 th percentile). Similarly, for c.1100delC in CHEK2 (3.7–fold enrichment; 1648 carriers), the respective lifetime risks are 29% (27–32%), 59% (52–66%), and 9% (5–14%). The PRS also refines the risk assessment of women with first-degree relatives diagnosed with breast cancer, particularly among women with positive family history of early-onset breast cancer. Here we demonstrate the opportunities for a comprehensive way of assessing genetic risk in the general population, in breast cancer patients, and in unaffected family members.

Purpose – The purpose of this paper is to review an evidence-based tool for training child forensic interviewers called the National Institute of Child Health and Human Development Protocol (NICHD Protocol), with a specific focus on how the Protocol is being adapted in various countries. Design/methodology/approach – The authors include international contributions from experienced trainers, practitioners, and scientists, who are already using the Protocol or whose national or regional procedures have been directly influenced by the NICHD Protocol research (Canada, Finland, Israel, Japan, Korea, Norway, Portugal, Scotland, and USA). Throughout the review, these experts comment on: how and when the Protocol was adopted in their country; who uses it; training procedures; challenges to implementation and translation; and other pertinent aspects. The authors aim to further promote good interviewing practice by sharing the experiences of these international experts. Findings – The NICHD Protocol can be easily incorporated into existing training programs worldwide and is available for free. It was originally developed in English and Hebrew and is available in several other languages. Originality/value – This paper reviews an evidence-based tool for training child forensic interviewers called the NICHD Protocol. It has been extensively studied and reviewed over the past 20 years. This paper is unique in that it brings together practitioners who are actually responsible for training forensic interviewers and conducting forensic interviews from all around the world.

BACKGROUND: Anterior cruciate ligament rupture is a common knee injury. Surgical treatment, usually involving reconstruction of the ligament, is widely used especially in active individuals. OBJECTIVES: Evaluation of the effect of surgical treatment compared with conservative treatment of anterior cruciate ligament (ACL) rupture. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Injuries Group Specialised Register (January 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2005), MEDLINE (1966 to January Week 3 2005), EMBASE (1988 to 2005 Week 05), MEDIC (1978 to January 1999), Current Contents (9.2.1998 to 1.2.1999), BIOSIS (1970 to December 1998), reference lists of articles and consulted trialists and experts. SELECTION CRITERIA: All randomised and quasi-randomised trials that compared surgical with conservative treatment of ACL rupture in adults. DATA COLLECTION AND ANALYSIS: Two authors independently performed study selection, data extraction and quality assessment. MAIN RESULTS: Two poor quality randomised trials conducted in the early 1980s were included in the review. The two trials differed considerably and no data pooling was done for the few shared outcome measures. One quasi-randomised trial of 167 people with a complete ACL rupture treated with repair or augmented repair versus conservative treatment found no difference in the return to sports activities between people treated surgically and those treated conservatively. Measures of knee stability and functional (Lysholm) knee scores were higher in surgically-treated participants. By the end of the follow-up period (average 55 months), three people treated with repair only and 16 treated conservatively had had ACL reconstruction. The other trial included 157 people with ACL injury. This found that conservatively-treated participants recovered from their injury more rapidly but, at the last follow up (minimum 13 months), the functional outcome was similar in both treatment groups. A large proportion of participants experienced some temporary discomfort after surgery and there were some more serious postoperative complications. There was less knee instability in surgically-treated participants and a tendency to fewer subsequent operations in the longer term. AUTHORS' CONCLUSIONS: There is insufficient evidence from randomised trials to determine whether surgery or conservative management was best for ACL injury in the 1980s, and no evidence to inform current practice. Good quality randomised trials are required to remedy this situation.

In a time of global nursing shortages an alarming number of young registered nurses have expressed a willingness to leave the profession. In this qualitative case study we investigate in depth why young nurses leave nursing profession and reeducate themselves for a new career. The study is based on longitudinal interviews of three young registered nurses in Finland. These nurses were first interviewed between December 2006 and May 2007, when they were 29-32 years old and having an intention to leave the profession. The second interview took place four years later, from January 2011 to March 2011 when all of them had made the transition to a new career. Data were analyzed in two stages. In the first stage, comprehensive career story narratives were formed on the basis of the interviews. In the second stage, emerging themes in these stories were compared, contrasted, and interpreted in the context of the overall career histories. Nursing as a second career choice and demanding work content as well as poor practice environment and the inability to identify with the stereotypical images of nurses were main themes that emerged from these career stories. The results of this interpretative qualitative study reflect a shift toward insights into understanding professional turnover as a complex and long-lasting process.

BACKGROUND: Tendon disorders are common problems in sports and are known to be difficult to treat. Only limited information is available concerning treatment of proximal hamstring tendinopathy. To the authors' knowledge, no histopathologic findings of proximal hamstring tendinosis have been published. HYPOTHESIS: Surgery (semimembranosus tenotomy and exploration of the sciatic nerve) is an effective treatment for proximal hamstring tendinopathy. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A total of 103 cases of proximal hamstring tendinopathy in athletes (58 men, 32 women; 13 bilateral operations) with surgical treatment were included. The cases were retrospectively analyzed, and a 4-category rating system was used to evaluate the overall result. At the follow-up, the patients were asked about possible symptoms and their return to sports. Biopsy samples from 15 of the operated tendons were taken and analyzed by a pathologist. RESULTS: The average follow-up was 49 months (range, 12-156 months). The result was evaluated to be excellent in 62 cases, good in 30, fair in 5, and poor in 6. After surgery, 80 of the 90 patients were able to return to the same level of sporting activity as before the onset of the symptoms. This took a mean of 5 months (range, 2-12 months). Typical morphologic findings of tendinosis were found in all biopsy specimens. CONCLUSION: Given the good functional outcome and low complication rate, the authors present surgical treatment as a valuable option in proximal hamstring tendinopathy if conservative treatment fails.

Both low back pain (LBP) and obesity are common public health problems, yet their relation remains controversial. The aim of this study was to investigate the associations between weight-related factors and the prevalence of LBP in young adults in Finland. Participants in the ongoing Cardiovascular Risk in Young Finns Study aged 24-39 years were included (N = 2,575). In 2001, 31.2% of men and 39.5% of women reported LBP with recovery within a month or recurrent or continuous pain during the preceding 12 months. For women only, those with higher body mass index, waist circumference, hip circumference, waist-to-hip ratio, serum leptin level, and C-reactive protein level showed an increased prevalence of LBP. With all weight-related factors in the model, only waist circumference was related to LBP in women. For women, the odds ratios of LBP were 1.2 (95% confidence interval: 0.8, 1.8) for a waist circumference of 80-87.9 cm and 1.8 (95% confidence interval: 1.0, 3.2) for a waist circumference of > or =88 cm compared with a waist circumference of <80 cm. This association was independent of C-reactive protein, leptin, and adiponectin levels. The authors' findings in a relatively young population suggest that abdominal obesity may increase the risk of LBP in women.

BACKGROUND: The burden of recurrent respiratory infections is unclear. We identified young children with recurrent respiratory infections in order to characterize the clinical manifestations, risk factors and short-term consequences. METHODS: In this prospective cohort study, 1089 children were followed from birth to 2 years of age for respiratory infections by a daily symptom diary. Nasal swabs taken during respiratory infections were analyzed for viruses from 714 children. Nasopharyngeal swabs collected at 2 months of age were cultured for bacteria. The 10% of children with the highest number of annual respiratory illness days were defined to have recurrent respiratory tract infections. RESULTS: The 90th percentile in the number of annual respiratory illness days was 98. Children above this limit (n = 109) had a median of 9.6 acute respiratory infections per year. Rhinovirus was detected in 58% of their infections. Of the children with recurrent infections, 60% were diagnosed with at least 3 episodes of acute otitis media, 73% received at least 3 antibiotic treatments and 21% were hospitalized for an acute respiratory infection. Tympanostomy was performed for 35% and adenoidectomy for 13% of the children. Asthma was diagnosed in 12% by 24 months of age. Older siblings increased the risk of recurrent respiratory infections. Early nasopharyngeal colonization with Streptococcus pneumoniae was common in children who later developed recurrent infections. CONCLUSIONS: Children with recurrent respiratory infections frequently use health care services and antibiotics, undergo surgical procedures and are at risk for asthma in early life. Having older siblings increases the risk of recurrent infections.

BACKGROUND: Health care policies in many countries aim to enable people with dementia to live in their own homes as long as possible. However, at some point during the disease the needs of a significant number of people with dementia cannot be appropriately met at home and institutional care is required. Evidence as to best practice strategies enabling people with dementia to live at home as long as possible and also identifying the right time to trigger admission to a long-term nursing care facility is therefore urgently required. The current paper presents the rationale and methods of a study generating primary data for best-practice development in the transition from home towards institutional nursing care for people with dementia and their informal caregivers. The study has two main objectives: 1) investigate country-specific factors influencing institutionalization and 2) investigate the circumstances of people with dementia and their informal caregivers in eight European countries. Additionally, data for economic evaluation purposes are being collected. METHODS/DESIGN: This paper describes a prospective study, conducted in eight European countries (Estonia, Finland, France, Germany, Netherlands, Sweden, Spain, United Kingdom). A baseline assessment and follow-up measurement after 3 months will be performed. Two groups of people with dementia and their informal caregivers will be included: 1) newly admitted to institutional long-term nursing care facilities; and 2) receiving professional long-term home care, and being at risk for institutionalization. Data will be collected on outcomes for people with dementia (e.g. quality of life, quality of care), informal caregivers (e.g. caregiver burden, quality of life) and costs (e.g. resource utilization). Statistical analyses consist of descriptive and multivariate regression techniques and cross-country comparisons. DISCUSSION: The current study, which is part of a large European project 'RightTimePlaceCare', generates primary data on outcomes and costs of long-term nursing care for people with dementia and their informal caregivers, specifically focusing on the transition from home towards institutional care. Together with data collected in three other work packages, knowledge gathered in this study will be used to inform and empower patients, professionals, policy and related decision makers to manage and improve health and social dementia care services.

BACKGROUND: vitamin B12 deficiency is common in the aged, but it is controversial whether only some risk groups should be investigated instead of screening the entire aged population. OBJECTIVES: to describe the prevalence of vitamin B12 deficiency in the Finnish aged, and to find out if the subjects especially prone to vitamin B12 deficiency could be identified by the risk factors or clinical correlates. DESIGN: a cross-sectional, population-based study of 1048 aged subjects (age 65-100 years) was carried out. Data on lifestyle factors and clinical conditions were collected, physical examinations were conducted and laboratory variables related to vitamin B12 were measured. RESULTS: vitamin B12 deficiency had been previously diagnosed in 27 (2.6%) subjects, and a laboratory diagnosis (total vitamin B12 <150 pmol/l, or total vitamin B12 150-250 pmol/l and holotranscobalamin < or =37 pmol/l and homocysteine > or =15 micromol/l) was made for 97 (9.5%) subjects. Low serum total vitamin B12 (<150 pmol/l) was observed in 6.1% and borderline total vitamin B12 (150-250 pmol/l) in 32% of the subjects. Male gender (OR 1.9, 95% CI 1.2-2.9), age > or =75 (OR 2.2, 95% CI 1.4-3.4) and refraining from milk products (OR 2.3, 95% CI 1.2-4.4) increased the probability for vitamin B12 deficiency. Anaemia (OR 1.3, 95% CI 0.7-2.3) or macrocytosis (OR 1.2, 95% CI 0.6-2.7) did not predict vitamin B12 deficiency. CONCLUSION: undiagnosed vitamin B12 deficiency is remarkably common in the aged, but no specific risk group for screening can be identified. Thus, biochemical screening of unselected aged population is justified. General practitioners play a key role in diagnosing early vitamin B12 deficiency.

Accessible summary Simulation has become a valuable educational tool with a variety of devices available for use. Examples of simulation scenarios developed especially for use with psychiatric and mental health nursing students are scarce. A simulation technique with considerable potential for the teaching and learning of essential mental health nursing skills is the narrative virtual patient. Wider use of virtual patient tools would help establish if it is a viable educational device. Abstract This paper discusses the use of simulation in nursing education and training, including potential benefits and barriers associated with its use. In particular, it addresses the hitherto scant application of diverse simulation devices and dedicated simulation scenarios in psychiatric and mental health nursing. It goes on to describe a low‐cost, narrative‐based virtual patient simulation technique which has the potential for wide application within health and social care education. An example of the implementation of this technology in a web‐based pilot course for acute mental health nurses is given. This particular virtual patient technique is a simulation type ideally suited to promoting essential mental health nursing skills such as critical thinking, communication and decision making. Furthermore, it is argued that it is particularly amenable to e‐learning and blended learning environments, as well as being an apt tool where multilingual simulations are required. The continued development, implementation and evaluation of narrative virtual patient simulations across a variety of health and social care programmes would help ascertain their success as an educational tool.

Between 2002 and 2008, 130 consecutive ankles were replaced with an hydroxyapatite (HA) and titanium-HA-coated Ankle Evolutive System total ankle prosthesis. Plain radiographs were analysed by two independent observers. Osteolytic lesions were classified by their size and location, with cavities > 10 mm in diameter considered to be 'marked'. CT scanning was undertaken in all patients with marked osteolysis seen on the plain radiographs. Osteolytic lesions were seen on the plain films in 48 (37%) and marked lesions in 27 (21%) ankles. The risk for osteolysis was found to be 3.1 (95% confidence interval 1.6 to 5.9) times higher with implants with Ti-HA porous coating. Care should be taken with ankle arthroplasty until more is known about the reasons for these severe osteolyses.