Necropsy-based study on dairy cow mortality-Underlying causes of death.

The worldwide problem of increasing dairy cow mortality is widespread in modern production systems, it causes economic losses, and indicates problems with herd health and welfare. Most studies on causes of dairy cow mortality are limited as they are based on secondary register data, or questionnaires for producers or veterinarians, and neither necropsies nor histopathologic analyses are usually performed. For this reason, no definite causes for dairy cow deaths have been determined making it difficult or impossible to implement effective preventive measures. The objectives of this study were to (1) determine the causes of on-farm mortality of Finnish dairy cows, (2) determine the usefulness of routine histopathologic analysis in bovine necropsies, and (3) assess how reliable producers' perception about the cause of death is. Underlying diagnoses of on-farm deaths were determined through necropsy of 319 dairy cows at an incineration plant. The necropsy data were combined with background information obtained from online questionnaires covering cow and herd records. Mastitis was the most common underlying diagnosis of death (26.6%), followed by digestive disorders (15.4%), other known disorders (13.8%), calving-associated disorders (12.2%), and locomotion disorders (11.9%). The underlying diagnoses of death varied during different stages of lactation and with parity. A large proportion of the study cows (46.7%) died during the first 30 d after calving, and of those, 63.6% died during the first 5 d. A routine histopathologic analysis was performed in every necropsy, and it changed the preliminary gross diagnosis in 18.2% of the cases. Producers' perception about the cause of death agreed with the necropsy-based underlying diagnosis of death in 42.8% of the cases. It was most consistent for mastitis, calving disorders, locomotion diseases, and accidents. In cases where producers had no insights about the cause of death, necropsy revealed the final underlying diagnosis in 88.2% of cases, demonstrating the usefulness of necropsy. Based on our findings, necropsies provide useful and reliable information to develop control programs for cow mortality. Including routine histopathologic analysis in necropsies, more accurate information may be obtained. Furthermore, targeting preventive measures on transitional cows may be most effective, as the number of deaths was highest at this time.

Risk factors for suicide in depression in Finland: first-hospitalized patients followed up to 24 years.

OBJECTIVE: To examine longitudinally risk factors for suicide in depression, and gender differences in risk factors and suicide methods. METHOD: We linked data from (i) The Finnish Hospital Discharge Register, (ii) the Census Register of Statistics Finland, and (iii) Statistics Finland's register on causes of deaths. All 56 826 first-hospitalized patients (25 188 men, 31 638 women) in Finland in 1991-2011 with a principal diagnosis of depressive disorder were followed up until death (2587 suicides) or end of the year 2014 (maximum 24 years). RESULTS: Clinical characteristics (severe depression adjusted hazard ratio [AHR] 1.19 [95% CI 1.08-1.30]; psychotic depression AHR 1.45 [1.30-1.62]; and comorbid alcohol dependence AHR 1.26 [1.13-1.41]), male gender (AHR 2.07 [1.91-2.24]), higher socioeconomic status and living alone at first hospitalization were long-term predictors of suicide deaths. Highest risk was associated with previous suicide attempts (cumulative probability 15.4% [13.7-17.3%] in men, 8.5% [7.3-9.7%] in women). Gender differences in risk factors were modest, but in lethal methods prominent. CONCLUSION: Sociodemographic and clinical characteristics at first hospitalization predict suicide in the long term. Inpatients with previous suicide attempts constitute a high-risk group. Despite some gender differences in risk factors, those in lethal methods may better explain gender disparity in risk.

Biological treatment in ankylosing spondylitis in the Nordic countries during 2010-2016: a collaboration between five biological registries.

OBJECTIVES: Large-scale observational cohorts may be used to study the effectiveness and rare side effects of biological disease-modifying anti-rheumatic drugs (bDMARDs) in ankylosing spondylitis (AS), but may be hampered by differences in baseline characteristics and disease activity across countries. We aimed to explore the research infrastructure in the five Nordic countries regarding bDMARD treatment in AS. METHOD: This observational cohort study was based on data from biological registries in Denmark (DANBIO), Sweden (SRQ/ARTIS), Finland (ROB-FIN), Norway (NOR-DMARD), and Iceland (ICEBIO). Data were collected for the years 2010-2016. Registry coverage, registry inventory (patient characteristics, disease activity measures), and national guidelines for bDMARD prescription in AS were described per country. Incident (first line) and prevalent bDMARD use per capita, country, and year were calculated. In AS patients who started first line bDMARDs during 2010-2016 (n = 4392), baseline characteristics and disease activity measures were retrieved. RESULTS: Registry coverage of bDMARD-treated patients ranged from 60% to 95%. All registries included extensive prospectively collected data at patient level. Guidelines regarding choice of first line drug and prescription patterns varied across countries. During the period 2010-2016 prevalent bDMARD use increased (p < 0.001), whereas incident use tended to decrease (p for trend < 0.004), with large national variations (e.g. 2016 incidence: Iceland 10.7/100 000, Finland 1.7/100 000). Baseline characteristics were similar regarding C-reactive protein, but differed for other variables, including the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (range 3.5-6.3) and Ankylosing Spondylitis Disease Activity Score (ASDAS) (2.7-3.8) (both p < 0.0001). CONCLUSION: Collaboration across the five Nordic biological registries regarding bDMARD use in AS is feasible but national differences in coverage, prescription patterns, and patient characteristics must be taken into account depending on the scientific question.

Drug survival on tumour necrosis factor inhibitors in patients with rheumatoid arthritis in Finland.

OBJECTIVE: A systematic review found that an average of 27% of rheumatoid arthritis (RA) patients using tumour necrosis factor (TNF) inhibitors discontinue their treatment within 1 year. The aim of this study was to assess drug survival on TNF inhibitors among patients with RA. METHODS: Patients were identified from the National Register for Biologic Treatment in Finland (ROB-FIN), which is a longitudinal cohort study established to monitor the effectiveness and safety of biologic drugs in rheumatic diseases. Inclusion was limited to TNF-inhibitor treatments started as the patient's first, second, or third biologic treatment between 2004 and 2014. Follow-up was truncated at 36 months. The results of a time-dependent Cox proportional hazards model were reported as adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: Of the 4200 TNF-inhibitor treatment periods identified from ROB-FIN, 3443 periods from 2687 patients met the inclusion criteria. Twenty-seven per cent of the patients discontinued their treatment within 12 months. Infliximab (HR 1.8, 95% CI 1.3-2.5) and certolizumab pegol (HR 1.7, 95% CI 1.2-2.3) had lower drug survival compared to golimumab. A similar trend was seen with adalimumab (HR 1.2, 95% CI 0.90-1.7) and etanercept (HR 1.2, 95% CI 0.87-1.6). Concomitant use of methotrexate (MTX) was associated with improved drug survival (HR 0.76, 95% CI 0.64-0.90) in comparison with TNF-inhibitor monotherapy. CONCLUSIONS: Golimumab was better in terms of drug survival than infliximab or certolizumab pegol and at least as good as adalimumab and etanercept. Concomitant use of MTX improved drug survival on TNF inhibitors.

Three out of four disease-modifying anti-rheumatic drug-naïve rheumatoid arthritis patients meet 28-joint Disease Activity Score remission at 12 months: results from the FIN-ERA cohort.

OBJECTIVE: To assess what proportion of patients with disease-modifying anti-rheumatic drug (DMARD)-naïve early rheumatoid arthritis (ERA) reach 28-joint Disease Activity Score (DAS28) remission over 1 year, and remission variability across clinics in Finland. METHOD: Patients with DMARD-naïve newly diagnosed inflammatory arthritis were recruited. The proportion of patients in 28-joint Disease Activity Score with three variables (DAS28-3) remission was compared across sites. Repeated measures were analysed using a mixed models approach with appropriate distribution and link function. RESULTS: In total, 611 patients were recruited at five sites: 67% were female; the mean (sd) age was 57 (16) years; 71% and 68% were positive for rheumatoid factor and anti-cyclic citrullinated peptides, respectively; and 23% had radiographic erosions. A total of 506 (83%) fulfilled the American College of Rheumatology/European League Against Rheumatism 2010 classification criteria for rheumatoid arthritis for further analyses. DAS28-3 remission was met by 68% and 75% at 3 and 12 months, respectively. The clinical site had no effect on remission when adjusted for confounders. At baseline, 68% used methotrexate-based combination therapy, and 31% used triple therapy with methotrexate, hydroxychloroquine, and sulphasalazine (the Fin-RACo regimen). In multivariate analysis, the only independent predictors of DAS28-3 remission at 12 months were lower baseline DAS28-3 and triple therapy as the initial treatment. CONCLUSION: Three out of four DMARD-naïve ERA patients in Finland are in remission during the first year from the diagnosis. High remission rates were achieved for most patients with the use of conventional synthetic DMARDs in combination. Treatment of DMARD-naïve ERA patients with the FIN-RACo regimen is a predictor of DAS28-3 remission in real-life rheumatology settings.

Aleutian mink disease virus in free-ranging mustelids in Finland - a cross-sectional epidemiological and phylogenetic study.

Aleutian mink disease virus (AMDV) can cause severe immune-complex-mediated disease in American mink. AMDV has also been detected in several other mustelid species with potential negative impact on their health and population. A molecular and cross-sectional epidemiological study was conducted to obtain data on the prevalence, distribution, transmission and diversity of AMDV strains in Finnish free-ranging mustelids and risk factors associated with infection. The presence of anti-AMDV antibodies and/or AMDV DNA was tested from 308 samples representing eight mustelid species and 17 administrative regions. Positive samples were detected across Finland, and in 54 % (31/57) of feral American mink, 27 % (7/26) of European badgers and 7 % (1/14) of European polecats. Samples from Eurasian otters, European pine martens, least weasels, stoat and wolverine were negative. Major risk factors for infection were the species American mink with 335 and badger with 74 times higher odds than other species, and the years 2006-2009 with five times higher odds than the years 2010-2014. No clustering according to species, geographical origin or year was evident in phylogeny, except for four divergent sequences from Estonian badgers that formed a separate phylogroup distinct from other AMDV strains. This study showed that AMDV was prevalent in certain species of Finnish free-ranging mustelids and widely distributed across Finland. Furthermore, the free-ranging mustelids carried both strains similar to those found in farmed mink, but also distinct strains that may represent novel amdoparvoviruses.

Molecular detection of Bartonella spp. in deer ked pupae, adult keds and moose blood in Finland.

The deer ked (Lipoptena cervi) is a haematophagous ectoparasite of cervids that harbours haemotrophic Bartonella. A prerequisite for the vector competence of the deer ked is the vertical transmission of the pathogen from the mother to its progeny and transstadial transmission from pupa to winged adult. We screened 1154 pupae and 59 pools of winged adult deer keds from different areas in Finland for Bartonella DNA using PCR. Altogether 13 pupa samples and one winged adult deer ked were positive for the presence of Bartonella DNA. The amplified sequences were closely related to either B. schoenbuchensis or B. bovis. The same lineages were identified in eight blood samples collected from free-ranging moose. This is the first demonstration of Bartonella spp. DNA in a winged adult deer ked and, thus, evidence for potential transstadial transmission of Bartonella spp. in the species.

A nationwide cross-sectional overview of patients with rheumatoid arthritis followed in outpatient specialty clinics in Finland.

OBJECTIVES: We aimed to conduct a cross-sectional overview of patients with rheumatoid arthritis (RA) in outpatient specialized clinics in Finland. METHOD: Consecutive patients were enrolled in the study. The data collected comprised demographic, disease- and treatment-related variables. RESULTS: Between November 2011 and May 2012, 890 patients with RA (77% female) were enrolled from 14 sites. The median age was 59.8 years and the time from diagnosis 7.2 years. Values for the Disease Activity Score using 28 joint counts (DAS28) ranged from 0.28 to 6.61 (median 2.55) with 52% and 70% of patients reaching remission and low disease activity, respectively. Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies were evident in 70% and 63% of patients, respectively. Median Health Assessment Questionnaire (HAQ) scores with and without aids and devices were 0.75 [interquartile range (IQR) 0.13-1.38] and 0.63 (IQR 0.13-1.13), respectively. Conventional disease-modifying anti-rheumatic drugs (DMARDs) were used by 91% of patients. A triple therapy of methotrexate (MTX), hydroxychloroquine (HCQ), and sulfasalazine (SSZ) was used by 15%, other MTX-based combination by 30%, MTX alone by 20%, and other DMARDs alone or in combination by 26% of patients. In addition, glucocorticoids and biologics were taken by 58% and 21% of patients, respectively. Of the 184 biologics users, 18% were not using DMARDs concomitantly. CONCLUSIONS: Our cross-sectional review of patients with RA revealed that > 50% of patients were in remission according to DAS28. Comparison with previous studies revealed a reduction in disease activity of prevalent RA cases, possibly resulting from increased use of aggressive anti-rheumatic treatments.

Mechanisms behind the varying severity of Aleutian mink disease virus: Comparison of three farms with a different disease status.

Aleutian mink disease virus (AMDV) is distributed widely among mink farms and wild mustelids despite ongoing attempts to stop the spread. The severity of Aleutian disease (AD) varies from subclinical to fatal but the reasons for its varying severity are complex and unclear. Recently, breeding of tolerant mink has drawn attention as the possible solution to reduce the effects of AD in farms. The aim of this study was to gather information on the effects of breeding based on overall health, production traits, and antibody titer on AD severity by comparing a positive farm (farm 1) that has been breeding for tolerance in mink to an infected farm without tolerance selection, and an AMDV-free farm. During the 2.5-year follow-up, the mink in farm 1 remained mostly free of clinical AD, had normal pelt quality and litter size, and had low virus copy numbers in tissues and low antibody titers in ELISA. In histopathological studies, most of the farm 1 mink had no/mild lesions in their kidneys. 29-43% of the mink were ELISA negative but PCR positive throughout the follow-up and frequent changes in virus strains and coinfections were observed. Several differences in gene expression between animals from different farms were also detected. These results indicate that the disease burden of AMDV can be reduced, with seemingly normal health and production rates, despite continual circulation of ADMV in cases where eradication attempts are unsuccessful.

High cyclin B1 expression is associated with poor survival in breast cancer.

Cyclin B1 regulates the G(2)-M transition of the cell cycle. Cyclin B1 expression is higher in premalignant and malignant than normal breast lesions. Correlation of cyclin B1 expression with other histopathological variables and prognostic role in breast cancer are not fully understood. Traditionally used prognostic criteria identify large subset of patients to receive adjuvant chemotherapy and to be exposed to adverse effects. A reliable and simple method helping prognostic evaluation in breast cancer is needed. We analysed cyclin B1 expression on 1348 invasive breast cancers and studied correlations with other histopathological variables and survival. High cyclin B1 correlated with high tumour grade, large tumour size and positive nodal status, oestrogen and progesterone receptor negativity, positive HER2 and p53 status, young age at diagnosis, and high cyclin E, cyclin A and Ki67 expression. Among patients not given adjuvant chemotherapy high cyclin B1 was a strong predictor of shorter overall and metastasis-free survival (RR 3.74, P<0.0005 and RR 3.51, P<0.0005, respectively), and remained as an independent prognostic factor also in multivariate analysis (RR 1.80, P=0.04 and RR 2.31, P=0.02, respectively). This study suggests high cyclin B1 associates with aggressive phenotype and is an independent prognostic factor in breast cancer.

Self-reported psychosis-like experiences in patients with mood disorders.

BACKGROUND: Self-reported psychosis-like experiences (PEs) may be common in patients with mood disorders, but their clinical correlates are not well known. We investigated their prevalence and relationships with self-reported symptoms of depression, mania, anxiety, borderline (BPD) and schizotypal (SPD) personality disorders among psychiatric patients with mood disorders. METHODS: The Community Assessment of Psychic Experiences (CAPE-42), Mood Disorder Questionnaire (MDQ), McLean Screening Instrument (MSI), The Beck Depressive Inventory (BDI), Overall Anxiety Severity and Impairment Scale (OASIS) and Schizotypal Personality Questionnaire-Brief form (SPQ-B) were filled in by patients with mood disorders (n=282) from specialized care. Correlation coefficients between total scores and individual items of CAPE-42 and BDI, SPQ-B, MSI and MDQ were estimated. Hierarchical multivariate regression analysis was conducted to examine factors influencing the frequency of self-reported PE. RESULTS: PEs are common in patients with mood disorders. The "frequency of positive symptoms" score of CAPE-42 correlated strongly with total score of SPQ-B (rho=0.63; P<0.001) and moderately with total scores of BDI, MDQ, OASIS and MSI (rho varied from 0.37 to 0.56; P<0.001). Individual items of CAPE-42 correlated moderately with specific items of BDI, MDQ, SPQ-B and MSI (rφ varied from 0.2 to 0.5; P<0.001). Symptoms of anxiety, mania or hypomania and BPD were significant predictors of the "frequency of positive symptoms" score of CAPE-42. CONCLUSIONS: Several, state- and trait-related factors may underlie self-reported PEs among mood disorder patients. These include cognitive-perceptual distortions of SPD; distrustfulness, identity disturbance, dissociative and affective symptoms of BPD; and cognitive biases related to depressive or manic symptoms.

Mediating role of borderline personality disorder traits in the effects of childhood maltreatment on suicidal behaviour among mood disorder patients.

BACKGROUND: Substantial evidence supports an association between childhood maltreatment and suicidal behaviour. However, few studies have examined factors mediating this relationship among patients with unipolar or bipolar mood disorders. METHODS: Depressive disorder and bipolar disorder (ICD-10-DCR) patients (n=287) from the Helsinki University Psychiatric Consortium (HUPC) Study were surveyed on self-reported childhood experiences, current depressive symptoms, borderline personality disorder traits, and lifetime suicidal behaviour. Psychiatric records served to complement the information on suicide attempts. We examined by formal mediation analyses whether (1) the effect of childhood maltreatment on suicidal behaviour is mediated through borderline personality disorder traits and (2) the mediation effect differs between lifetime suicidal ideation and lifetime suicide attempts. RESULTS: The impact of childhood maltreatment in multivariate models on either lifetime suicidal ideation or lifetime suicide attempts showed comparable total effects. In formal mediation analyses, borderline personality disorder traits mediated all of the total effect of childhood maltreatment on lifetime suicide attempts, but only one fifth of the total effect on lifetime suicidal ideation. The mediation effect was stronger for lifetime suicide attempts than for lifetime suicidal ideation (P=0.002) and independent of current depressive symptoms. CONCLUSIONS: The mechanisms of the effect of childhood maltreatment on suicidal ideation versus suicide attempts may diverge among psychiatric patients with mood disorders. Borderline personality disorder traits may contribute to these mechanisms, although the influence appears considerably stronger for suicide attempts than for suicidal ideation.

Level of functioning, perceived work ability, and work status among psychiatric patients with major mental disorders.

BACKGROUND: Major mental disorders are highly disabling conditions that result in substantial socioeconomic burden. Subjective and objective measures of functioning or ability to work, their concordance, or risk factors for them may differ between disorders. METHODS: Self-reported level of functioning, perceived work ability, and current work status were evaluated among psychiatric care patients with schizophrenia or schizoaffective disorder (SSA, n=113), bipolar disorder (BD, n=99), or depressive disorder (DD, n=188) within the Helsinki University Psychiatric Consortium Study. Correlates of functional impairment, subjective work disability, and occupational status were investigated using regression analysis. RESULTS: DD patients reported the highest and SSA patients the lowest perceived functional impairment. Depressive symptoms in all diagnostic groups and anxiety in SSA and BD groups were significantly associated with disability. Only 5.3% of SSA patients versus 29.3% or 33.0% of BD or DD patients, respectively, were currently working. About half of all patients reported subjective work disability. Objective work status and perceived disability correlated strongly among BD and DD patients, but not among SSA patients. Work status was associated with number of hospitalizations, and perceived work disability with current depressive symptoms. CONCLUSIONS: Psychiatric care patients commonly end up outside the labour force. However, while among patients with mood disorders objective and subjective indicators of ability to work are largely concordant, among those with schizophrenia or schizoaffective disorder they are commonly contradictory. Among all groups, perceived functional impairment and work disability are coloured by current depressive symptoms, but objective work status reflects illness course, particularly preceding psychiatric hospitalizations.

Self-reported symptoms of schizotypal and borderline personality disorder in patients with mood disorders.

BACKGROUND: Distinguishing between symptoms of schizotypal (SPD) and borderline personality disorders (BPD) is often difficult due to their partial overlap and frequent co-occurrence. We investigated correlations in self-reported symptoms of SPD and BPD in questionnaires at the levels of both total scores and individual items, examining overlapping dimensions. METHODS: Two questionnaires, the McLean Screening Instrument (MSI) for BPD and the Schizotypal Personality Questionnaire Brief (SPQ-B) for SPD, were filled in by patients with mood disorders (n=282) from specialized psychiatric care in a study of the Helsinki University Psychiatric Consortium. Correlation coefficients between total scores and individual items of the MSI and SPQ-B were estimated. Multivariate regression analysis (MRA) was conducted to examine the relationships between SPQ-B and MSI. RESULTS: The Spearman's correlation between total scores of the MSI and SPQ-B was strong (rho=0.616, P<0.005). Items of MSI reflecting disrupted relatedness and affective dysregulation correlated moderately (rφ varied between 0.2 and 0.4, P<0.005) with items of SPQ. Items of MSI reflecting behavioural dysregulation correlated only weakly with items of SPQ. In MRA, depressive symptoms, sex and MSI were significant predictors of SPQ-B score, whereas symptoms of anxiety, age and SPQ-B were significant predictors of MSI score. CONCLUSIONS: Items reflecting cognitive-perceptual distortions and affective symptoms of BPD appear to overlap with disorganized and cognitive-perceptual symptoms of SPD. Symptoms of depression may aggravate self-reported features of SPQ-B, and symptoms of anxiety features of MSI. Symptoms of behavioural dysregulation of BPD and interpersonal deficits of SPQ appear to be non-overlapping.

Anxiety symptoms in a major mood and schizophrenia spectrum disorders.

BACKGROUND: Comorbid anxiety symptoms and disorders are present in many psychiatric disorders, but methodological variations render comparisons of their frequency and intensity difficult. Furthermore, whether risk factors for comorbid anxiety symptoms are similar in patients with mood disorders and schizophrenia spectrum disorders remains unclear. METHODS: The Overall Anxiety Severity and Impairment Scale (OASIS) was used to measure anxiety symptoms in psychiatric care patients with schizophrenia or schizoaffective disorder (SSA, n=113), bipolar disorder (BD, n=99), or depressive disorder (DD, n=188) in the Helsinki University Psychiatric Consortium Study. Bivariate correlations and multivariate linear regression models were used to examine associations of depressive symptoms, neuroticism, early psychological trauma and distress, self-efficacy, symptoms of borderline personality disorder, and attachment style with anxiety symptoms in the three diagnostic groups. RESULTS: Frequent or constant anxiety was reported by 40.2% of SSA, 51.5% of BD, and 55.6% of DD patients; it was described as severe or extreme by 43.8%, 41.4%, and 41.2% of these patients, respectively. SSA patients were significantly less anxious (P=0.010) and less often avoided anxiety-provoking situations (P=0.009) than the other patients. In regression analyses, OASIS was associated with high neuroticism, symptoms of depression and borderline personality disorder and low self-efficacy in all patients, and with early trauma in patients with mood disorders. CONCLUSIONS: Comorbid anxiety symptoms are ubiquitous among psychiatric patients with mood or schizophrenia spectrum disorders, and in almost half of them, reportedly severe. Anxiety symptoms appear to be strongly related to both concurrent depressive symptoms and personality characteristics, regardless of principal diagnosis.

Differences and overlap in self-reported symptoms of bipolar disorder and borderline personality disorder.

BACKGROUND: Differential diagnosis between bipolar disorder (BD) and borderline personality disorder (BPD) is often challenging due to some overlap in symptoms and comorbidity of disorders. We investigated correlations in self-reported symptoms of BD and BPD in screening questionnaires at the levels of both total scores and individual items and explored overlapping dimensions. METHODS: The McLean Screening Instrument (MSI) for BPD and the Mood Disorder Questionnaire (MDQ) for BD were filled in by patients with unipolar and bipolar mood disorders (n=313) from specialized psychiatric care within a pilot study of the Helsinki University Psychiatric Consortium. Pearson's correlation coefficients between total scores and individual items of the MSI and the MDQ were estimated. Relationships between MDQ and MSI were evaluated by exploratory factor analysis (EFA). RESULTS: The correlation between total scores of the MDQ and MSI was moderate (r=0.431, P<0.001). Significant correlations were found between the MSI items of "impulsivity" and "mood instability" and all MDQ items (P<0.01). In the EFA, the MSI "impulsivity" and "mood instability" items had significant cross-loadings (0.348 and 0.298, respectively) with the MDQ factor. The MDQ items of "irritability", "flight of thoughts" and "distractibility" (0.280, 0.210 and 0.386, respectively) cross-loaded on the MSI factor. CONCLUSIONS: The MDQ and MSI items of "affective instability", "impulsivity", "irritability", "flight of thoughts" and "distractibility" appear to overlap in content. The other scale items are more disorder-specific, and thus, may help to distinguish BD and BPD.

Ki67 and cyclin A as prognostic factors in early breast cancer. What are the optimal cut-off values?

AIMS: To find the optimal cut-off values for cyclin A and Ki67 in early breast cancer tumours and to evaluate their prognostic values. METHODS AND RESULTS: Tissue microarray (TMA) slides were constructed from 570 T1-4 N0-1 M0 breast cancer tumours. The TMA slides were stained for cyclin A and Ki67 using immunohistochemistry with commercial antibodies. To investigate the optimal cut-off values for cyclin A, Ki67 average and maximum values the material was split into two parts at cut-offs defined by dividing it into deciles. For each cut-off value the relative risk (RR) for metastasis-free survival (MFS) and overall survival (OS) was calculated comparing patients with high versus low cyclin A or Ki67 expression. When using a cut-off value around the seventh decile, cyclin A and Ki67 score correlated with the highest RR ratio for MFS in the chemotherapy-naïve subgroup. Among patients having received adjuvant chemotherapy, no statistically significant differences in MFS or OS were found. CONCLUSIONS: The optimal cut-off value for cyclin A average is 8% and for cyclin A maximum value 11%; for Ki67 the corresponding values are 15% and 22%. Additional studies are needed to verify these results.

Reliability of cyclin A assessment on tissue microarrays in breast cancer compared to conventional histological slides.

Cyclin A has in some studies been associated with poor breast cancer survival, although all studies have not confirmed this. Its prognostic significance in breast cancer needs evaluation in larger studies. Tissue microarray (TMA) technique allows a simultaneous analysis of large amount of tumours on a single microscopic slide. This makes a rapid screening of molecular markers in large amount of tumours possible. Because only a small tissue sample of each tumour is punched on an array, the question has arisen about the representativeness of TMA when studying markers that are expressed in only a small proportion of cells. For this reason, we wanted to compare cyclin A expression on TMA and on traditional large sections. Two breast cancer TMAs were constructed of 200 breast tumours diagnosed between 1997-1998. TMA slides and traditional large section slides of these 200 tumours were stained with cyclin A antibody and analysed by two independent readers. The reproducibility of the two readers' results was good or even very good, with kappa values 0.71-0.87. The agreement of TMA and large section results was good with kappa value 0.62-0.75. Cyclin A overexpression was significantly (P<0.001) associated with oestrogen receptor and progesterone receptor negativity and high grade both on TMA and large sections. Cyclin A overexpression was significantly associated with poor metastasis-free survival both on TMA and large sections. The relative risks for metastasis were similar on TMA and large sections. This study suggests that TMA technique could be useful to study histological correlations and prognostic significance of cyclin A on breast cancer on a large scale.

Migraine attacks and sleep in children.

Falling asleep as a means of ending migraine attack was studied in 133 4-16-year-old children in out-patient settings. Children registered 999 migraine attacks in headache diaries using a visual analogue scale (VAS) in 409 attacks and a five-face scale in 590 attacks. The distribution of maximal pain intensity was similar on both scales; on VAS 88% assigned grades between 63 and 100, and on the face scale 93% assigned grades of 4 or 5. Children fell asleep during 33% of the attacks (n = 329), in 64% of these within the first hour (n = 209). Of the children, 68% (n = 91) had fallen asleep at least once during an attack. Falling asleep was more common in children under 8 years of age than in older children. In those under 8 years, 62% (95% confidence interval (CI) 49-75%) of attacks were resolved by sleep, in those aged 8-12 years 34% (26-41%), and in children >12 years 24% (15-33%) (ANOVA, P<0.0001). Pain was relieved without sleep in 43% (n = 431) of attacks, in 38% of these (n = 383) within the first 4 h. The data on migraine resolution were missing for 24% (n = 239) of the attacks, most often because the attack exceeded the 5-h observation period. This study confirms that migraine attacks in children are extremely painful and often resolve during an interval of sleep in children under 8 years of age.