Liver Fat, Adipose Tissue, and Body Composition Changes After Switching from a Protease Inhibitor or Efavirenz to Raltegravir.

Integrase inhibitors appear to increase body weight, but paradoxically some data indicate that raltegravir (RAL) may decrease liver fat. Our objective was to study the effects of switching from a protease inhibitor (PI) or efavirenz (EFV) to RAL on liver fat, body composition, and metabolic parameters among people living with HIV (PLWH) with high risk for nonalcoholic fatty liver disease (NAFLD). We randomized overweight PLWH with signs of metabolic syndrome to switch a PI or EFV to RAL (n = 19) or to continue unchanged antiretroviral therapy (control, n = 24) for 24 weeks. Liver fat was measured by magnetic resonance spectroscopy (MRS), body composition by magnetic resonance imaging, and bioimpedance analysis; subcutaneous fat biopsies were obtained. Median (interquartile range) liver fat content was normal in RAL 2.3% (1.1-6.0) and control 3.1% (1.6-7.3) group at baseline. Liver fat and visceral adipose tissue remained unchanged during the study. Body weight [from 85.9 kg (76.1-97.7) to 89.3 (78.7-98.7), p = 0.019], body fat mass [from 20.3 kg (14.6-29.7) to 22.7 (17.0-29.7), p = 0.015], and subcutaneous adipose tissue (SAT) volume [from 3979 mL (2068-6468) to 4043 (2206-6433), p = 0.048] increased, yet, adipocyte size [from 564 pL (437-733) to 478 (423-587), p = 0.019] decreased in RAL but remained unchanged in control group. Circulating lipids and inflammatory markers improved in RAL compared to control group. The median liver fat measured by MRS was unexpectedly within normal range in this relatively small study population with presumably high risk for NAFLD contradicting high prevalence of NAFLD reported with other methods. Despite weight gain, increase in SAT together with decreased adipocyte size and reduced inflammation may reflect improved adipose tissue function. Clinical Trial Registration number: NCT03374358.

Dominant TOM1 mutation associated with combined immunodeficiency and autoimmune disease.

Mutations in several proteins functioning as endolysosomal components cause monogenic autoimmune diseases, of which pathogenesis is linked to increased endoplasmic reticulum stress, inefficient autophagy, and defective recycling of immune receptors. We report here a heterozygous TOM1 p.G307D missense mutation, detected by whole-exome sequencing, in two related patients presenting with early-onset autoimmunity, antibody deficiency, and features of combined immunodeficiency. The index patient suffered from recurrent respiratory tract infections and oligoarthritis since early teens, and later developed persistent low-copy EBV-viremia, as well as an antibody deficiency. Her infant son developed hypogammaglobulinemia, autoimmune enteropathy, interstitial lung disease, profound growth failure, and treatment-resistant psoriasis vulgaris. Consistent with previous knowledge on TOM1 protein function, we detected impaired autophagy and enhanced susceptibility to apoptosis in patient-derived cells. In addition, we noted diminished STAT and ERK1/2 signaling in patient fibroblasts, as well as poor IFN-γ and IL-17 secretion in T cells. The mutant TOM1 failed to interact with TOLLIP, a protein required for IL-1 recycling, PAMP signaling and autophagosome maturation, further strengthening the link between the candidate mutation and patient pathophysiology. In sum, we report here an identification of a novel gene, TOM1, associating with early-onset autoimmunity, antibody deficiency, and features of combined immunodeficiency. Other patient cases from unrelated families are needed to firmly establish a causal relationship between the genotype and the phenotype.

Weak sense of coherence predicts depression: 1-year and 9-year follow-ups of the Finnish Outcomes of Depression International Network (ODIN) sample.

BACKGROUND: Previous studies show conflicting results on the role of weak sense of coherence (SOC) as a risk factor for depression. AIMS: The aim of this work was to study whether a weak SOC predicts depressive symptoms in a non-depressive population sample in the short or long perspective. METHOD: Participants without depressive symptoms (n = 1645) in the Finnish sample of the Outcomes of Depression International Network (ODIN) study were assessed at 1-year and 9-year follow-up. Depressive symptoms were assessed by the Beck Depression Inventory (BDI), and SOC by the 13-item Orientation to Life Questionnaire (SOC-13). Logistic regression analysis was used to test the association between baseline SOC and depressive symptoms measured at the follow-ups. RESULTS: In univariate analysis, there was a significant inverse association between baseline SOC and depressive symptoms at 1 year (p = 0.000) and at 9 years (p = 0.000). In multivariate analysis, weak SOC continued to predict depressive symptoms at 1 year (p = 0.022) and 9 years (p = 0.015). CONCLUSIONS: Weak SOC predicted depressive symptoms in the short and long perspective. It seems likely that a strong SOC represents a protective function, not only absence of current depression.

Usefulness of the Beck Depression Inventory as a screening method for depression among the general population of Finland.

BACKGROUND: The present paper studies the effectiveness of the Beck Depression Inventory (BDI) as a screening measure for depression in a general population sample from Finland. METHODS: The study analysed the Finnish sample of the ODIN study, a multicentre epidemiology study of depression in Europe. From this general population sample, 311 subjects were selected according to their score on the BDI within a larger assessment that included a structured diagnostic interview. Of these, 31.2% were diagnosed with major depression. RESULTS: A cut-off score of 17/18 simultaneously maximized both sensitivity and specificity in the Receiver Operating Characteristic (ROC) curve analysis, with an Area Under the Curve (AUC) of 0.806. Similar results were found across gender, and the AUCs were not significantly different between men and women. LIMITATIONS: The results cannot be directly generalized to institutionalized persons, people in clinical settings, or those with range of ages not included in the present study. CONCLUSIONS: The Beck Depression Inventory is a valid instrument for the diagnosis of depression among the general population of Finland. As a screening measure, the optimal cut-off score would be 17 or higher.

Cross-cultural equivalence of the Beck Depression Inventory: a five-country analysis from the ODIN study.

BACKGROUND: The Beck Depression Inventory (BDI) has demonstrated excellent psychometric properties and good performance as a screening measure in different contexts and languages. However, comparison of its structure across countries and languages remains understudied. Measurement invariance is a prerequisite for considering the BDI equivalent across versions, and for using it to make valid and interpretable comparisons of the severity of depression among different groups. METHODS: As part of a five-country (UK, Ireland, Spain, Norway, and Finland), two-stage epidemiological study of depressive disorder, 7934 persons were screened using the BDI. The item equivalence and measurement invariance of the BDI across the samples of the five countries was tested using Item Response Theory (IRT) and Multiple Indicators Multiple Causes (MIMIC) models. RESULTS: Overall results support the factorial validity of the BDI, with a unidimensional structure. Item 19 (weight loss) presented a clear misfit in the five countries. IRT models, as well as MIMIC models, suggest that complete measurement invariance cannot be assumed across the five countries. The Spanish sample accounted for the majority of the differences, with a moderate to low Differential Item Functioning for the other countries on the different items. CONCLUSIONS: The BDI could be used cross-culturally in Europe, with particular cautions regarding the Spanish sample, and with the constraints and limits pointed out for the present results. The methodology used for the present work is suggested as a soundness approach for testing the cross-cultural validity of severity rating scales.

Japanese encephalitis in a Finnish traveler on a two-week holiday in Thailand.

Japanese encephalitis (JE) virus is a mosquito-borne flavivirus, and one of the leading causes of epidemic encephalitis in Southeast Asia. Reports of symptomatic JEV encephalitis in tourists have been rare. We describe a case of symptomatic JE transmitted in 2004 during a short two-week trip to common tourist attractions in Thailand.

The prevalence of suicidal ideation in the general population: results from the Outcome of Depression International Network (ODIN) study.

BACKGROUND: Suicidal ideation is believed to be part of a constellation of suicidal behaviours that culminates in suicide. There is little information on the cross-national prevalence of all suicidal ideation or of serious suicidal ideation in spite of its likely public health importance. METHODS: A two-stage screening approach of over 12,000 adults from the general population were evaluated by face to face interview to identify those meeting ICD-10 criteria for depressive disorders at eight sites in five European countries. This study is a cross-sectional analysis of item 9 (suicidal ideation) of the Beck depression inventory from the total screened sample. RESULTS: The standardised period prevalence for all suicidal ideation varied from 1.1 to 19.8% while for serious suicidal ideation there was much less variation. Examining the inter-relationships between all suicide ideation, serious suicide ideation, depressive disorders and suicide failed to support a seamless transition from suicide ideation through depression and serious ideation to suicide. CONCLUSIONS: Strategies to prevent suicide should be tailored to take account of site specific differences in its aetiology and understanding the path from suicidal ideation through depression to suicide is crucial to this.

Factors associated with suicidal ideation in the general population: five-centre analysis from the ODIN study.

BACKGROUND: Very few studies have examined the cross-national prevalence of suicidal ideation in the general population or variables associated with it. AIMS: To examine the risk factors for suicidal ideas in the general population. METHOD: As part of a five-country two stage epidemiological study of depressive disorder (the ODIN study) a random sample of over 12 000 people were screened using the Beck Depression Inventory (BDI). There followed detailed analysis of item 9 of the BDI, which measured the severity of suicidal ideation. RESULTS: Age, marriage, concern by others and severity of depressed mood independently increased or decreased the odds of suicidal ideation overall. An interaction between life events and social supports was identified, although this differed between men and women. Only concern by others and severity of depression were independently associated with serious suicidal ideation. The study does not allow for interpretation of the direction of the association. CONCLUSIONS: A number of social, clinical and demographic variables were independently associated with all suicidal ideation and with serious suicidal ideation. Longitudinal studies are required to confirm whether these are risk factors for or the result of suicidal ideation or have some other relationship.

Predicting medication-free treatment response in acute psychosis: cross-validation from the Finnish Need-Adapted Project.

This study tested predictors of 2-year antipsychotic-free response from the Soteria study (older, better social functioning, fewer cardinal symptoms) using data from the Finnish Acute Psychosis Integrated treatment study. The quasi-experimental study compared need-adapted family-oriented psychosocial intervention within a 3-week antipsychotic-free trial to psychosocial intervention plus antipsychotic medications. Forty-six percent of experimental completers (37% of intent-to-treat subjects) were successfully treated without antipsychotic medications for the entire 2-year study. The DSM-III-R diagnoses of schizophrenia and schizophreniform disorder and Soteria-suggested predictors were not related to antipsychotic-free response. Different variables within the same domains of good prognosis and fewer schizophrenia symptoms predicted antipsychotic-free response or nonresponse with 74% accuracy. The 6-month duration of symptom criterion distinguishing schizophrenia from schizophreniform disorder does not separate medication-free treatment responders from those requiring medications. Prognosis appears related to antipsychotic-free response and may be helpful in distinguishing schizophrenia from schizophreniform disorder in early episodes.

Health service use by adults with depression: community survey in five European countries. Evidence from the ODIN study.

BACKGROUND: Little is known about patterns of healthcare use by people with depression in Europe. AIMS: To examine the use and cost of services by adults with depressive or adjustment disorders in five European countries, and predictive factors. METHOD: People aged 18-65 years with depressive or adjustment disorders (n=427) in Ireland, Finland, Norway, Spain and the UK provided information on predisposition (demographics, social support), enablement (country, urban/rural, social function) and need (symptom severity, perceived health status) for services. Outcome measures were self-reported use Client Services Receipt Interview and costs of general practice, generic, psychiatric or social services in the past 6 months. RESULTS: Less frequent use was made of generic services in Norway and psychiatric services in the UK. Severity of depression, perceived health status, social functioning and level of social support were significant predictors of use; the number of people able to provide support was positively associated with greater health service use. CONCLUSIONS: Individual participant factors provided greater explanatory power than national differences in healthcare delivery. The association between social support and service use suggests that interventions may be needed for those who lack social support.

Negative life events, social support and gender difference in depression: a multinational community survey with data from the ODIN study.

OBJECTIVE: To explore if differences in negative life events, vulnerability and social support may explain the gender difference in depression. METHODS: Cross-sectional, multinational, community survey from five European countries (n = 8,787). Depression is measured by Beck Depression Inventory, whereas negative life events and social support are measured by various questionnaires. RESULTS: Women report slightly more negative life events than men do, mainly related to the social network, but more social support in general and in connection with reported life events. This trend is the same in all participating countries except Spain, where there is no gender difference in the reported support. In general, women are not more vulnerable to negative life events than men are. However, women with no social support, who are exposed to life events, are more vulnerable than men without support. CONCLUSION: The higher rate of depression in women is not explained by gender differences in negative life events, social support or vulnerability.

Can adjustment disorder and depressive episode be distinguished? Results from ODIN.

BACKGROUND: No large-scale epidemiological study has included adjustment disorders (AD) for consideration yet it is considered to be a common psychiatric diagnosis. METHODS: Using a two stage screening method, those above a threshold score for possible caseness on the Beck Depression Inventory (BDI), were interviewed using SCAN to identify those with depressive episode and AD. Variables that might distinguish AD from depressive episode were examined. RESULTS: The prevalence of AD was extremely low with one centre having no cases. Finland, the country with the highest prevalence, only achieved a frequency of 0.8% and 1%, respectively, for urban and rural sites. Logistic regression failed to identify any variables that independently differentiated AD from depressive episode. Findings relating to severity of symptoms using BDI were robust. LIMITATIONS: The small sample size might have contributed to a failure to identify distinguishing features between AD and other disorders. CONCLUSIONS: Reasons for the failure of even robust results, such as BDI severity, to distinguish AD from depressive episode are considered of which problems in conceptualising AD are the most likely. Further studies are required.

Schizophrenia, neuroleptic medication and mortality.

BACKGROUND: There is an excess of death from natural causes among people with schizophrenia. AIMS: Schizophrenia and its treatment with neuroleptics were studied for their prediction of mortality in a representative population sample of 7217 Finns aged >/= 30 years. METHOD: A comprehensive health examination was carried out at baseline. Schizophrenia was determined using the Present State Examination and previous medical records. RESULTS: During a 17-year follow-up, 39 of the 99 people with schizophrenia died. Adjusted for age and gender, the relative mortality risk between those with schizophrenia and others was 2.84 (95% CI 2.06-3.90), and was 2.25 (95% CI1.61-3.15) after further adjusting for somatic diseases, bloodpressure, cholesterol, body mass index, smoking, exercise, alcohol intake and education. The number of neuroleptics used at the time of the baseline survey showed a graded relation to mortality. Adjusted for age, gender, somatic diseases and other potential risk factors for premature death, the relative risk was 2.50 (95% CI1.46-4.30) per increment of one neuroleptic. CONCLUSIONS: There is an urgent need to ascertain whether the high mortality in schizophrenia is attributable to the disorder itself or the antipsychotic medication.

Territorial waters of the Baltic Sea as a source of infections caused by Vibrio cholerae non-O1, non-O139: report of 3 hospitalized cases.

A fatal infection with temporal relation to 2 other febrile infections caused by Vibrio cholerae non-O1, non-O139 (NCV) occurred in Finland in 2003. All infections were associated with contact with seawater. The patient who died had also eaten home-salted whitefish, tested positive for NCV, preceding his symptoms. All patients had compromising factors, and all strains were distinguishable by pulsed-field gel electrophoresis and negative for the ctx gene. These 3 cases illustrate that, despite being uncommon in Finland, NCVs can cause clinically significant and even fatal infections.

The estimated incidence of depressive disorder and its determinants in the Finnish ODIN sample.

BACKGROUND: In contrast to the huge number of prevalence studies, there are relatively few incidence studies of depressive disorders. Furthermore, estimates of incidence vary remarkably between existing studies. The aim of this paper is to add knowledge about the incidence and determinants of depressive disorder, based on the Finnish sub-sample of the European Outcomes of Depression International Network study. METHOD: The random population sample in the Finnish sub-study consisted of 2,999 subjects, aged 18-64, selected from one urban and one rural area. In the baseline survey, potential cases of depressive disorder were identified using the Beck Depression Inventory. SCAN-2 interview was used to assign caseness against ICD-10 criteria. Findings from the 1-year follow-up survey with those who responded in the baseline survey (N=1,939), using the same case-finding instruments, were used to estimate the incidence rate of depressive disorder. RESULTS: The estimated annual incidence rate for all depressive disorders, including both first-time and recurrent episodes, was 28.5 per 1,000; for first-time episodes it was 20.5 per 1,000. Significant predictors for experiencing a depressive episode were: suffering from self-perceived long-term illness or handicap, experiencing little or no concern from friends, low sense of coherence, low self-confidence, uncertainty about one's future and reporting two or more threatening life events during the preceding 6 months. CONCLUSIONS: About 3% of the working-age population experience an episode of depressive disorder each year. Due to recall problems, the estimate of first-time incidence may be too high.

Level of positive mental health in the European Union: results from the Eurobarometer 2002 survey.

BACKGROUND: Few epidemiological studies have focused on the occurrence of positive mental health, and those comparing several countries practically non-existent. This study presents comparative findings of positive mental health in 11 EU countries or regions, based on the Eurobarometer 2002 (autumn) survey. METHOD: The sample (n = 10,878) represents the general population, aged 15 or over, of 11 European countries or regions (all old EU Member States except Denmark, Greece, Ireland, Finland and Great Britain which had to be excluded because of poor response rate, less than 45%). The method of opinion survey was applied using face-to-face interviews. The Energy and Vitality Index (EVI) from the SF-36 questionnaire was use as measure of positive mental health. RESULTS: Overall, there were between-country differences in the gender- and age-adjusted EVI mean scores. In general, poorer mental health was found in women, older age groups, those in poor economic position and those experiencing weak social support. CONCLUSION: Methodological biases cannot be fully excluded, and thus, one has to take the presented results with certain caution, especially when comparing the results from the different countries. On the other hand, the results on the determinants of positive mental health are in concordance with most previous studies.

Blood culture Gram stain and clinical categorization based empirical antimicrobial therapy of bloodstream infection.

Early antimicrobial treatment has a great influence on the outcome of patients with blood stream infections (BSI). The study was designed to see if the simple practice of patient categorization (community acquired, nosocomial or infection in haematological unit) combined with Gram stain data could be used to guide empirical treatment of BSI in 1901 consecutive positive blood culture findings. There were considerable differences in the occurrence of common pathogens and their antimicrobial susceptibilities between patient categories especially for Gram-positive cocci. For example, second generation cephalosporins covered more than 70% cocci in clusters and over 80% of cocci in chains in community acquired infections whereas in hospital acquired infections the corresponding figures were only 47 and 44%. We conclude that Gram stain results of positive blood cultures along with the knowledge of where the infection was acquired, would allow early accurate targeting of antimicrobial therapy for BSI.