Opportunistic treatment of hepatitis C virus infection (OPPORTUNI-C): study protocol for a pragmatic stepped wedge cluster randomized trial of immediate versus outpatient treatment initiation among hospitalized people who inject drugs.

BACKGROUND: Scaled-up direct-acting antiviral (DAA) treatment of hepatitis C virus (HCV) infection among people who inject drugs (PWID) is crucial to reach the World Health Organization HCV elimination targets within 2030. One of the critical obstacles to HCV care in this population is the lack of treatment models within specialist healthcare adapted to marginalized individuals. METHODS: OPPORTUNI-C is a pragmatic stepped wedge cluster randomized trial comparing the efficacy of immediate initiation of HCV treatment with the current standard of care among PWID admitted for inpatient care. Screening for HCV RNA will be performed as soon as possible after admission. The intervention includes immediate non-invasive liver disease assessment, counseling, and initiation of pan-genotypic DAA treatment with individualized follow-up. Standard of care is a referral to outpatient care at discharge. To mimic usual clinical practice as closely as possible, we will use a pragmatic clinical trial approach utilizing clinical infrastructure, broad eligibility criteria, flexible intervention delivery, clinically relevant outcomes, and collection of data readily available from the electronic patient files. The stepped wedge design involves a sequential rollout of the intervention over 16 months, in which seven participating clusters will be randomized from standard of care to intervention in a stepwise manner. Randomization will be stratified according to cluster size to keep high prevalence clusters separated. The trial will include approximately 220 HCV RNA positive individuals recruited from departments of internal medicine, addiction medicine, and psychiatry at Akershus University Hospital, Oslo University Hospital, and Lovisenberg Diaconal Hospital, Oslo, Norway. Individuals not able or willing to give informed consent and those with ongoing HCV assessment or treatment will be excluded. The primary outcome is treatment completion, defined as dispensing of the final prescribed DAA package from the pharmacy within 6 months after inclusion. Secondary outcomes include treatment uptake, virologic response, reinfection incidence, and resistance-associated substitutions. DISCUSSION: Representing a novel model of care suited to reach and engage marginalized PWID in HCV care, this study will inform HCV elimination efforts locally and internationally. If the model proves efficacious and feasible, it should be considered for broader implementation, replacing the current standard of care. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04220645. Registered on 7 January 2020.

Feasibility of reaching world health organization targets for hepatitis C and the cost-effectiveness of alternative strategies.

New drugs for treating hepatitis C have considerably increased the probability of being cured. Treatment uptake, however, is still low. The objectives of this study were to analyse the impact of initiatives that may increase the proportion of infected people on treatment and interventions aimed at reducing the incidence of new infection among people who inject drugs. A compartmental model for Norway was used to simulate hepatitis C and related complications. We analysed 2 different screening initiatives aimed to increase the proportion of infected people on treatment. Interventions aiming at reducing the hepatitis C incidence analysed were opioid substitution therapy (OST), a clean needle and syringe programme and a combination of both. The most cost-effective strategy for increasing hepatitis C treatment uptake was screening by general practitioners while simultaneously allowing for all infected people to be treated. We estimated that this intervention reduces the incidence of hepatitis C by 2030 by 63% compared with the current incidence. The 2 harm reduction strategies both reduced the incidence of hepatitis C by about 70%. Combining an increase in the current clean needles and syringe programme with OST was clearly the most cost-effective option. This strategy would reduce the incidence of hepatitis C by 80% compared with the current incidence by 2030. Thus, interventions to reduce the burden and spread of hepatitis C are cost-effective. Reaching the WHO target of a 90% reduction in hepatitis C incidence by 2030 may be difficult without combining different initiatives.

Historical epidemiology of hepatitis C virus (HCV) in select countries - volume 2.

Chronic hepatitis C virus (HCV) infection is a leading cause of liver related morbidity and mortality. In many countries, there is a lack of comprehensive epidemiological data that are crucial in implementing disease control measures as new treatment options become available. Published literature, unpublished data and expert consensus were used to determine key parameters, including prevalence, viremia, genotype and the number of patients diagnosed and treated. In this study of 15 countries, viremic prevalence ranged from 0.13% in the Netherlands to 2.91% in Russia. The largest viremic populations were in India (8 666 000 cases) and Russia (4 162 000 cases). In most countries, males had a higher rate of infections, likely due to higher rates of injection drug use (IDU). Estimates characterizing the infected population are critical to focus screening and treatment efforts as new therapeutic options become available.

Strategies to manage hepatitis C virus (HCV) infection disease burden - volume 2.

The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 15 countries, and the relative impact of two scenarios was considered: (i) increased treatment efficacy while holding the treated population constant and (ii) increased treatment efficacy and increased annual treated population. Increasing levels of diagnosis and treatment, in combination with improved treatment efficacy, were critical for achieving substantial reductions in disease burden. In most countries, the annual treated population had to increase several fold to achieve the largest reductions in HCV-related morbidity and mortality. This suggests that increased capacity for screening and treatment will be critical in many countries. Birth cohort screening is a helpful tool for maximizing resources. In most of the studied countries, the majority of patients were born between 1945 and 1985.

The present and future disease burden of hepatitis C virus (HCV) infections with today's treatment paradigm - volume 2.

Morbidity and mortality attributable to chronic hepatitis C virus (HCV) infection are increasing in many countries as the infected population ages. Models were developed for 15 countries to quantify and characterize the viremic population, as well as estimate the number of new infections and HCV related deaths from 2013 to 2030. Expert consensus was used to determine current treatment levels and outcomes in each country. In most countries, viremic prevalence has already peaked. In every country studied, prevalence begins to decline before 2030, when current treatment levels were held constant. In contrast, cases of advanced liver disease and liver related deaths will continue to increase through 2030 in most countries. The current treatment paradigm is inadequate if large reductions in HCV related morbidity and mortality are to be achieved.

Predicting long-term recovery from depression in community settings in Western Europe: evidence from ODIN.

OBJECTIVE: To test the impact of socio-economic and psychological adversity and healthcare on long-term recovery from depression. METHOD: A community sample of 347 people with depressive disorders was followed up after 9 years. Baseline socio-economic adversity, social support, healthcare use, and psychiatric history were identified. Respondents completed self-report instruments on current depressive status (Beck depression inventory) and longstanding psychosocial adversity (sexual, physical or emotional abuse). Univariate analyses tested for association between recovery and respondent characteristics. RESULTS: Follow-up was achieved for 182 (52%) of the sample, of whom 75 (41%) indicated recovery from depression. Psychological adversity definitely and socio-economic adversity probably were associated with lack of recovery. Baseline healthcare had no apparent impact on outcome. Rurality and support after life events were associated with recovery. History of depression was associated with non-recovery. CONCLUSION: Psychological adversity is, and socio-economic adversity may be, associated with long-term non-recovery from depression in community settings.

Ribavirin dosage in patients with HCV genotypes 2 and 3 who completed short therapy with peg-interferon alpha-2b and ribavirin.

BACKGROUND: The optimal dose of ribavirin to be used in combination with Peg-IFN in patients with HCV genotypes 2 and 3 undergoing short treatment has not been established. AIM: To explore the relationship between starting ribavirin doses, expressed as mg/kg body weight and both rapid viral response at treatment week 4 (RVR) and sustained virological response (SVR) in patients treated for 12-14 weeks with peg-interferon alpha-2b and ribavirin. METHODS: A post hoc analysis of data collected from two multicenter clinical trials was performed. Multiple regression analyses were employed to identify independent baseline and on-treatment predictors of RVR and SVR. For each dose of ribavirin, the empirical estimated probability of response was computed and the continuous exposure index was dichotomized by using a recursive partitioning and amalgamation method. RESULTS: A nonlinear relationship was ascertained between ribavirin dose and RVR, but not SVR. A dose of 15.2 mg/kg was selected as the best splitting value for discriminating RVR vs. non-RVR. Regression analysis identified low baseline viraemia, genotype 2 and high ribavirin dose as independent prognostic factors for RVR. The likelihood of an SVR was not correlated with baseline ribavirin dose, but was independently predicted by adherence to the full dose throughout treatment and normal platelet counts. CONCLUSIONS: Starting high ribavirin doses appears capable of increasing the rate of RVR in patients with HCV genotypes 2 and 3 undergoing short treatment. Maintenance of the full planned dose throughout treatment is essential for achieving optimal SVR rates.

Impact of severity and type of depression on quality of life in cases identified in the community.

BACKGROUND: The impact of different levels of depression severity on quality of life (QoL) is not well studied, particularly regarding ICD-10 criteria. The ICD classification of depressive episodes in three levels of severity is also controversial and the less severe category, mild, has been considered as unnecessary and not clearly distinguishable from non-clinical states. The present work aimed to test the relationship between depression severity according to ICD-10 criteria and several dimensions of functioning as assessed by Medical Outcome Study (MOS) 36-item Short Form general health survey (SF-36) at the population level. METHOD: A sample of 551 participants from the second phase of the Outcome of Depression International Network (ODIN) study (228 controls without depression and 313 persons fulfilling ICD criteria for depressive episode) was selected for a further assessment of several variables, including QoL related to physical and mental health as measured with the SF-36. RESULTS: Statistically significant differences between controls and the depression group were found in both physical and mental markers of health, regardless of the level of depression severity; however, there were very few differences in QoL between levels of depression as defined by ICD-10. Regardless of the presence of depression, disability, widowed status, being a woman and older age were associated with worse QoL in a structural equation analysis with covariates. Likewise, there were no differences according to the type of depression (single-episode versus recurrent). CONCLUSIONS: These results cast doubt on the adequacy of the current ICD classification of depression in three levels of severity.

Predictors of compliance with psychological interventions offered in the community.

BACKGROUND: This study sought to evaluate the acceptance of two brief psychological interventions for depressed individuals, contacted through a community survey, and to look for predictors of adherence at the patient level. METHOD: The authors used data from the Outcomes of Depression International Network (ODIN) study, which included a randomized controlled trial in which depressed individuals from five European countries, and nine geographical areas were assigned to one of three groups: individual problem-solving treatment, group psychoeducation, or control group. In this analysis, we included all of the individuals who had been assigned to one of the psychological interventions. Compliance with intervention was defined in two different ways. Multiple logistic regression was used to see which variables might predict an individual's compliance with psychological treatment. RESULTS: Psychological intervention was offered to 236 subjects. Treatment was completed by 128 subjects and not by 108 (compliance definition A). Three variables were found to have an effect on compliance A: the presence of a confidant, the use of antidepressant medication during the previous 6 months, and the previous use of any social or health services. On the other hand, 164 subjects had agreed to at least start the treatment, and 72 had not (compliance definition B). The three factors associated with compliance B were presence of a confidant, previous use of services, and the 'desire for change' score. CONCLUSIONS: Social support and previous use of services are the main predictors of compliance with a psychological treatment in depressed individuals from the community. Implications for clinical practice and community programs are discussed.

Short-term treatment duration for HCV-2 and HCV-3 infected patients.

BACKGROUND: We have shown that 12-14 weeks treatment is effective in HCV-2 or -3 patients with undetectable HCV-RNA after 4 weeks of therapy (rapid virologic response). PATIENTS: To identify predictors of sustained virologic response, rapid virologic response and relapse following short treatment, we pooled data from the original Italian and Norwegian studies. Four hundreds and three patients were treated with PegIFN alpha-2b (1.0, n=281 or 1.5 microg/kg, n=122) and ribavirin (800-1200 mg) for 12-14 or 24 weeks, depending on negative or positive HCV-RNA at week 4. RESULTS: Sustained virologic response differed between cases with and without rapid virologic response (85% versus 62%, P<0.0001), mild and severe fibrosis (83% versus 67%, P=0.004), and HCV-2 and -3 (81% versus 73%, P=0.05). In a regression model, RVR (odds ratio 3.49, confidence interval 1.73-5.36) and mild fibrosis (odds ratio 2.91, confidence interval 1.57-5.38) independently predicted sustained virologic response. Rapid virologic response was obtained in 274 (68%) patients, 163/242 (67%) HCV-2, and 111/161 (69%) HCV-3. Patients with RVR had more frequently mild fibrosis (70% versus 54%, P=0.03), and high PegIFN dose (78% versus 64%, P=0.005). In a regression model, mild fibrosis independently predicted rapid virologic response (odds ratio 1.87, confidence interval 1.10-3.16). In rapid virologic response patients, sustained virologic response was achieved in 85% of both HCV-2 and -3. Virologic relapse was observed in 10.6% rapid virologic response patients and was more frequent among those with low ALT (14% versus 2%, P=0.04). CONCLUSION: In HCV-2 or -3, the HCV-RNA status after 4 weeks of therapy may guide treatment duration. HCV-2 and HCV-3 patients with severe fibrosis are less likely to experience both rapid virologic response and sustained virologic response, and more frequently relapse after a 12 or 14 weeks duration of antiviral therapy.

A rapid real-time PCR assay for determination of hepatitis C virus genotypes 1, 2 and 3a.

The genotypes of hepatitis C virus (HCV) in serum of patients have been described as independent predictors of success of antiviral therapy. Therefore, different antiviral regimens have been proposed depending on the infecting HCV genotype. HCV strain is usually determined by polymerase chain reaction (PCR) amplification of genome followed by sequencing or by line-probe assays. We report a new one step real-time PCR assay for genotyping of HCV strains that are prevalent in patients in Norway. HCV types 1, 2 and 3a were genotyped unambiguously in 37 patient serum samples with 100% correlation to genotyping by nucleotide sequence analysis and line-probe assays. Genotyping could also be confirmed against an HCV genotype panel from the National Institute for Biological Standards and Control. This assay does not require manipulation of amplified PCR products, it involves very little hands on and analysis time. This assay can be used for rapid genotyping of HCV-RNA in infected patients to aid physicians decide suitability of patients for treatment and subsequent length of treatment.

Self-reported skin morbidity and mental health. A population survey among adults in a Norwegian city.

BACKGROUND: Several studies among dermatological patients have shown a link between various chronic dermatological diseases and mental morbidity. OBJECTIVES: To explore the association between self-reported skin morbidity and psychosocial factors in the general population. METHODS: This population-based cross-sectional study is part of the Oslo Health Study conducted during 2000-2001. All individuals in Oslo County, Norway, born in 1924/25, 1940/41, 1955, 1960 and 1970 received a postal questionnaire, which 18,770 men and women answered. The questionnaire provided information on sociodemographic factors and self-reported health and psychosocial factors. Dichotomous variables for 10 self-reported skin complaints were used. These were previously validated and refer to the most common chronic skin diseases. Mental distress was measured with a validated 10-item instrument, the Hopkins Symptom Check List-10; social support with the number of confidants; and negative life events with a 12-item validated instrument. RESULTS: The odds ratio (OR) for mental distress was 1.70 [95% confidence interval (CI) 1.21-2.38] for having itch, 1.64 (95% CI 1.15-2.34) for pimples and 1.72 (95% CI 1.06-2.80) for face rash in an adjusted model. In an adjusted model the OR for skin disease was 1.60 (95% CI 1.39-1.84) when the individual had experienced more than two negative life events; and 2.52 (95% CI 2.12-3.00) for mental distress. Skin morbidity increased for both genders, with poor social support network. There was a significant interaction between social support network and negative life events in the logistic regression model for skin disease when adjusted for sociodemographic factors. CONCLUSIONS: The study quantifies the association between dermatological problems and psychosocial factors at a population level. It underlines the need to focus on these issues in research and needs assessment in dermatology.

Estimating psychological treatment effects from a randomised controlled trial with both non-compliance and loss to follow-up.

BACKGROUND: The Outcomes of Depression International Network (ODIN) trial evaluated the effect of two psychological interventions for the treatment of depression in primary care. Only about half of the patients in the treatment arm complied with the offer of treatment, prompting the question:'what was the effect of treatment in those patients who actually received it?' AIMS: To illustrate the estimation of the effect of receipt of treatment in a randomised controlled trial subject to non-compliance and loss to follow-up. METHOD: We estimated the complier average causal effect (CACE) of treatment. RESULTS: In the ODIN trial the effect of receipt of psychological intervention (an average of about 4 points on the Beck Depression Inventory) is about twice that of offering it. CONCLUSIONS: The statistical analysis of the results of a clinical trial subject to non-compliance to allocated treatment is now reasonably straightforward through estimation of a CACE and investigators should be encouraged to present the results of analyses of this type as a routine component of a trial report.

Hepatitis C in the general adult population of Oslo: prevalence and clinical spectrum.

BACKGROUND: The prevalence of hepatitis C (HCV) in Northern Europe has not been well described. This study aimed to estimate the prevalence and spectrum of hepatitis C infection in the general adult population of Oslo, Norway. METHODS: The study was part of the Oslo Health Study 2000-2001 and included a random selection of individuals older than 30 years living in Oslo County. Sera from 11,456 participants were screened for anti-HCV (EIA-3), positive samples were confirmed (RIBA-3) and examined for HCV RNA (PCR). All anti-HCV positive patients were offered clinical evaluation. Routine biochemical liver tests were performed. Candidates for HCV treatment were asked to undergo a percutanous liver biopsy. RESULTS: Among 11,456 participants HCV RNA was detected in 62 (0.5%) and HCV RNA with raised serum alanine aminotransferase (ALT) in 46 (0.4%). Anti-HCV was detected in 78 (0.7%) with a peak prevalence of 1.5% among subjects 40 and 45 years old. Being anti-HCV positive was associated with being unmarried, unemployed and having low education. Anti-HCV prevalence was higher among subjects with alcohol-related problems compared to those without (4.4% versus 0.6%, P < 0.001). It was also higher among smokers compared to non-smokers (2.0% versus 0.2%, P < 0.001). In 33 liver biopsies, bridging fibrosis was seen in 8 (24%) and cirrhosis in 1 (3%). The route of transmission was injecting drug use in 67%, transfusion in 6% and unknown in 27%. CONCLUSION: In this population-based survey the prevalence of chronic hepatitis C was 0.5% and ALT was raised in 80% of those with chronic infection.

Thyroid dysfunction during treatment of chronic hepatitis C with interferon alpha: no association with either interferon dosage or efficacy of therapy.

OBJECTIVES: Treatment of chronic hepatitis C with interferon-alpha (IFN-alpha) may induce thyroid disorders. We evaluated whether this risk is related to the dosage of IFN-alpha or the virological treatment response. Other possible risk factors as well as the evolution of the thyroid abnormalities were also studied. METHODS: In this prospective trial (n=254), thyroid-stimulating hormone (TSH), free thyroxin (fT4) and thyroid peroxidase autoantibodies were measured before, during and after treatment for hepatitis C virus (HCV). The patients were randomized to either induction therapy [IFN-alpha 6 million units (MIU) daily for 4 weeks and 3 MIU 3/7 days for 22 weeks] or conventional therapy [IFN-alpha 3 MIU 3/7 days for 26 weeks]. In addition, all patients received ribavirin (1000 or 1200 mg) daily. Sustained virological response was defined as loss of detectable HCV RNA at 6 months follow-up. Thyroid dysfunction was defined as TSH level below or above the normal range (0.2-4.5 MIU L-1). RESULTS: Biochemical thyroid dysfunction developed in 30 (11.8%) of 254 patients. Hypothyroidism (TSH > 4.5 MIU L-1) was seen in 20 and hyperthyroidism (TSH < 0.2 MIU L-1) in 10 patients. Nine of the 30 patients developed symptomatic thyroid disease and HCV treatment was discontinued because of thyroid dysfunction in three of these patients. Thyroid dysfunction occurred in 15 (11.7%) of 128 patients who received high-dose IFN-alpha induction therapy as compared with 15 (11.9%) of 126 patients who received conventional IFN-alpha therapy (P=0.96). Amongst 231 patients who completed all 6 months of HCV treatment, a sustained virological response was obtained in 19 (66%) of 29 with thyroid dysfunction and 109 (54%) of 202 without (P=0.24). By multivariate analysis female gender and Asian origin were independent predictors of developing biochemical thyroid dysfunction (P < 0.01). CONCLUSION: Thyroid dysfunction occurred in 11.8% of patients treated for chronic hepatitis C with IFN-alpha and ribavirin. Neither the IFN-alpha dosage nor the virological response to treatment were related to the incidence of thyroid dysfunction.

Treatment of chronic hepatitis C in injecting drug users: 5 years' follow-up.

AIM OF THE STUDY: To assess the long-term hepatitis C (HCV) treatment outcome in former injecting drug users (IDUs). MATERIALS AND METHODS: A long-term follow-up of 27 former IDUs who had been successfully treated for chronic hepatitis C was performed. These patients represented all IDUs who had obtained a sustained virological response in a Norwegian HCV treatment trial. The patients had been treated with interferon-alpha alone or in combination with ribavirin. At 5 years' follow-up the 27 IDUs were retested for HCV RNA and risk behaviour for HCV transmission after treatment was assessed. In the control group all 18 non-IDUs who had obtained a sustained virological response in the same treatment trial were included. RESULTS: At follow-up 13-82 months (median 64) after the end of treatment only one case of probable reinfection was seen among the 27 IUDs. No reoccurrence of HCV was observed in the control group. The IDU who was HCV RNA positive at follow-up had continued injecting drugs and reported frequent needle sharing. At follow-up HCV of genotype 1a was detected in contrast to genotype 1b before treatment indicating that this patient was reinfected with HCV. A return to injecting drug use occurred in 9 (33%) of 27 IDUs. CONCLUSION: The long-term outcome of HCV treatment in former IDUs was excellent. Despite frequent reinitiation of drug injection all but 1 remained HCV RNA negative.

Depressive disorders in Europe: prevalence figures from the ODIN study.

BACKGROUND: This is the first report on the epidemiology of depressive disorders from the European Outcome of Depression International Network (ODIN) study. AIMS: To assess the prevalence of depressive disorders in randomly selected samples of the general population in five European countries. METHOD: The study was designed as a cross-sectional two-phase community study using the Beck Depression inventory during Phase 1, and the Schedule for Clinical Assessment in Neuropsychiatry during Phase 2. RESULTS: An analysis of the combined sample (n=8.764) gave an overall prevalence of depressive disorders of 8.56% (95% CI 7.05-10.37). The figures were 10.05% (95% CI 7.80-12.85) for women and 6.61% (95% CI 4.92-8.83) for men. The centres fall into three categories: high prevalence (urban Ireland and urban UK), low prevalence (urban Spain) and medium prevalence (the remaining sites). CONCLUSIONS: Depressive disorder is a highly prevalent condition in Europe. The major finding is the wide difference in the prevalence of depressive disorders found across the study sites.

Problem solving treatment and group psychoeducation for depression: multicentre randomised controlled trial. Outcomes of Depression International Network (ODIN) Group.

OBJECTIVES: To determine the acceptability of two psychological interventions for depressed adults in the community and their effect on caseness, symptoms, and subjective function. DESIGN: A pragmatic multicentre randomised controlled trial, stratified by centre. SETTING: Nine urban and rural communities in Finland, Republic of Ireland, Norway, Spain, and the United Kingdom. PARTICIPANTS: 452 participants aged 18 to 65, identified through a community survey with depressive or adjustment disorders according to the international classification of diseases, 10th revision or Diagnostic and Statistical Manual of Mental Disorders, fourth edition. INTERVENTIONS: Six individual sessions of problem solving treatment (n=128), eight group sessions of the course on prevention of depression (n=108), and controls (n=189). MAIN OUTCOME MEASURES: Completion rates for each intervention, diagnosis of depression, and depressive symptoms and subjective function. RESULTS: 63% of participants assigned to problem solving and 44% assigned to prevention of depression completed their intervention. The proportion of problem solving participants depressed at six months was 17% less than that for controls, giving a number needed to treat of 6; the mean difference in Beck depression inventory score was -2. 63 (95% confidence interval -4.95 to -0.32), and there were significant improvements in SF-36 scores. For depression prevention, the difference in proportions of depressed participants was 14% (number needed to treat of 7); the mean difference in Beck depression inventory score was -1.50 (-4.16 to 1.17), and there were significant improvements in SF-36 scores. Such differences were not observed at 12 months. Neither specific diagnosis nor treatment with antidepressants affected outcome. CONCLUSIONS: When offered to adults with depressive disorders in the community, problem solving treatment was more acceptable than the course on prevention of depression. Both interventions reduced caseness and improved subjective function.

Symptoms of anxiety and depression among mothers of pre-school children: effect of chronic strain related to children and child care-taking.

BACKGROUND: Factors that affect maternal mental health were studied when the children were 30 and 50 months old, and changes in the importance of these factors over time were analyzed. A specific aim was to elucidate the role of chronic strain related to children and child care-taking. This study follows up previous work on the influence of social class, strain and social support on maternal mental distress when the children were 18 months old. METHODS: The sample is population based, and 1,081 parents were invited to fill out questionnaires. Maternal mental distress was measured by the Hopkins Symptom Checklist (SCL-25). Multiple regression analyses were conducted at each time point and chi-square tests were used to analyze the changes between the estimated regression coefficients over time. RESULTS: Chronic strain related to children and child care-taking consistently predicted maternal mental distress. Among the specific child related strains, problems with child care-taking were significantly associated with maternal symptom levels at all time points. The importance of two specific child problem behaviors (activity level and the child being a worrier) on maternal mental health changed over time. LIMITATIONS: Conclusions about causality can not be drawn based on cross-sectional analyses. The self-report measures used here may be biased by the current mood state. CONCLUSIONS: Problems with child care arrangements and combining work and child care-taking are predictive of maternal mental health when the children are 18, 30 and 50 months old. The risk and protective factors found here may have implications for prevention and intervention.

Organizing ODIN: a case study in European academic co-operation. The ODIN Group.

The European Commission is an increasingly important source of funding for international research projects and is due to announce its Framework 5 program early in 1999. The Outcomes of Depression International Network (ODIN), funded from the current EC Biomed 2 program, is a case study in European academic co-operation. Its organization has three key elements. First, engaging the principal investigators: this has involved identifying potential partners, ensuring reciprocity of interests, effective co-ordination, 'dividing the spoils' in advance, and setting up good personal and electronic communication systems. Second, an esprit de corps has been created amongst the researchers, maintaining contact and consistency, and promoting higher degrees. Third, ongoing problems including difficulties in negotiations with the EC, divergence of detailed study methods, and isolation and demoralization amongst researchers, have been addressed. ODIN may provide a useful model for researchers wishing to set up international collaborative groups.