The DANIsh VASculitis cohort study: protocol for a national multicenter prospective study including incident and prevalent patients with giant cell arteritis and polymyalgia rheumatica.

The DANIsh VASculitis cohort study, DANIVAS, is an observational national multicenter study with the overall aim to prospectively collect protocolized clinical data and biobank material from patients with polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) diagnosed and/or followed at Danish rheumatology departments. A long-term key objective is to investigate whether the use of new clinically implemented diagnostic imaging modalities facilitates disease stratification in the GCA-PMR disease spectrum. In particular, we aim to evaluate treatment requirements in GCA patients with and without large-vessel involvement, treatment needs in PMR patients with and without subclinical giant cell arteritis, and the prognostic role of imaging with respect to aneurysm development. Hence, in GCA and PMR, imaging stratification is hypothesized to be able to guide management strategies. With an established infrastructure within rheumatology for clinical studies in Denmark, the infrastructure of the Danish Rheumatologic Biobank, and the possibility to cross-link data with valid nationwide registries, the DANIVAS project holds an exceptional possibility to collect comprehensive real-world data on diagnosis, disease severity, disease duration, treatment effect, complications, and adverse events. In this paper, we present the research protocol for the DANIVAS study. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT05935709.

Cognitive impairment in long-COVID and its association with persistent dysregulation in inflammatory markers.

Objective: To analyze the potential impact of sociodemographic, clinical and biological factors on the long-term cognitive outcome of patients who survived moderate and severe forms of COVID-19. Methods: We assessed 710 adult participants (Mean age = 55 ± 14; 48.3% were female) 6 to 11 months after hospital discharge with a complete cognitive battery, as well as a psychiatric, clinical and laboratory evaluation. A large set of inferential statistical methods was used to predict potential variables associated with any long-term cognitive impairment, with a focus on a panel of 28 cytokines and other blood inflammatory and disease severity markers. Results: Concerning the subjective assessment of cognitive performance, 36.1% reported a slightly poorer overall cognitive performance, and 14.6% reported being severely impacted, compared to their pre-COVID-19 status. Multivariate analysis found sex, age, ethnicity, education, comorbidity, frailty and physical activity associated with general cognition. A bivariate analysis found that G-CSF, IFN-alfa2, IL13, IL15, IL1.RA, EL1.alfa, IL45, IL5, IL6, IL7, TNF-Beta, VEGF, Follow-up C-Reactive Protein, and Follow-up D-Dimer were significantly (p<.05) associated with general cognition. However, a LASSO regression that included all follow-up variables, inflammatory markers and cytokines did not support these findings. Conclusion: Though we identified several sociodemographic characteristics that might protect against cognitive impairment following SARS-CoV-2 infection, our data do not support a prominent role for clinical status (both during acute and long-stage of COVID-19) or inflammatory background (also during acute and long-stage of COVID-19) to explain the cognitive deficits that can follow COVID-19 infection.

The association between vitamin D deficiency and risk of renal event: Results from the Korean cohort study for outcomes in patients with chronic kidney disease (KNOW-CKD).

Backgrounds: Some observational studies have suggested a possible association between vitamin D deficiency and CKD. However, in most studies, the causality between low levels of vitamin D and risk of renal events could not be explained. We investigated the relationship between vitamin D deficiency and risk of severe CKD stage and renal event in a large-scale prospective cohort study. Methods: We used data from a prospective cohort of 2,144 patients with available information on serum 25-hydroxyvitamin D (25(OH)D) levels at baseline from KNOW-CKD, 2011-2015 were included. Vitamin D deficiency was defined as serum 25(OH)D levels < 15 ng/mL. We performed a cross-sectional analysis to elucidate the relationship between 25(OH)D and CKD stage using baseline CKD patient data. We further examined a cohort analysis to clarify the association between 25(OH)D and risk of renal event. Renal event was a composite of the first occurrence of a 50% decline in eGFR from the baseline value or the onset of CKD stage 5 (initiation of dialysis or kidney transplantation) across the follow-up period. We also investigated the associations of vitamin D deficiency with risk of renal event according to diabetes and overweight status. Results: Vitamin D deficiency were significantly associated with an increased risk of severe CKD stage - 1.30-fold (95% CI: 1.10-1.69) for 25(OH)D. Deficiency of 25(OH)D with 1.64-fold (95% CI: 1.32-2.65) was related to renal event compared with the reference. Furthermore, vitamin D deficiency patients with presence of DM and overweight status also displayed higher risk than non-deficient patients for risk of renal event. Conclusion: Vitamin D deficiency is associated with significantly increased risk of severe CKD stage and renal event.

Association between use of psychotropic medications prior to SARS-COV-2 infection and trajectories of COVID-19 recovery: Findings from the prospective Predi-COVID cohort study.

Psychological disturbances are frequent following COVID-19. However, there is not much information about whether pre-existing psychological disorders are associated with the severity and evolution of COVID-19. We aimed to explore the associations between regular psychotropic medication use (PM) before infection as a proxy for mood or anxiety disorders with COVID-19 recovery trajectories. We used data from the Predi-COVID study. We followed adults, tested positive for SARS-CoV-2 and collected demographics, clinical characteristics, comorbidities and daily symptoms 14 days after inclusion. We calculated a score based on 16 symptoms and modeled latent class trajectories. We performed polynomial logistic regression with PM as primary exposure and the different trajectories as outcome. We included 791 participants, 51% were men, and 5.3% reported regular PM before infection. We identified four trajectories characterizing recovery dynamics: "Almost asymptomatic," "Quick recovery," "Slow recovery," and "Persisting symptoms". With a fully adjusted model for age, sex, socioeconomic, lifestyle and comorbidity, we observed associations between PM with the risks of being in more severe trajectories than "Almost Asymptomatic": "Quick recovery" (relative risk (95% confidence intervals) 3.1 (2.7, 3.4), "Slow recovery" 5.2 (3.0, 9.2), and "Persisting symptoms"11.7 (6.9, 19.6) trajectories. We observed a gradient of risk between PM before the infection and the risk of slow or no recovery in the first 14 days. These results suggest that a pre-existing psychological condition increases the risk of a poorer evolution of COVID-19 and may increase the risk of Long COVID. Our findings can help to personalize the care of people with COVID-19.

Depressive symptoms increase the risk of falls and injurious falls in Chinese adults aged ≥ 45 years: A 3-year cohort study.

Background: Falls and depressive symptoms are both public health concerns in China, but the effects of depressive symptoms on falls and injurious falls have not been thoroughly investigated. Methods: This population-based prospective cohort study used data derived from adults aged ≥45 years acquired from the 2015 and 2018 China Health and Retirement Longitudinal Study. Data were analyzed from August 2021 to December 2021. Self-reported depressive symptoms were determined using a 10-item Center for Epidemiologic Studies Depression scale (CESD-10) with a total score range of 0-30. Item responses of 3-4 or 5-7 days were deemed indicative of specific depressive symptoms. The outcome variables were self-reported accidental falls and injurious falls. Results: Of the 12,392 participants included in the study, 3,671 (29.6%) had high baseline depressive symptoms (CESD-10 scores ≥ 10), 1,892 (15.3%) experienced falls, and 805 (6.5%) experienced injurious falls during 2015-2018 follow-up. High depressive symptoms increased the risk of falls [odds ratio (OR) 1.34, 95% confidence interval (CI) 1.19-1.50] and injurious falls (OR 1.28, 95% CI 1.09-1.51) in a multivariable logistic regression model adjusted for major demographic, health-related, and anthropometric covariates. All of the 10 specific depressive symptoms except "felt hopeless" were associated with falls, and four specific symptoms significantly increased the risk of injurious falls; "had trouble concentrating" (OR 1.32, 95% CI 1.13-1.55); "felt depressed" (OR 1.32, 95% CI 1.12-1.55); "everything was an effort" (OR 1.23, 95% CI 1.04-1.45); and "restless sleep" (OR 1.18, 95% CI 1.02-1.40). Conclusion: High depressive symptoms are significantly related to risk of falls and injurious falls. Four specific symptoms (had trouble concentrating, felt depressed, everything was an effort, and restless sleep) increase the risk of injurious falls in Chinese adults aged ≥ 45 years.

Longitudinal transition of body mass index status and its associated factors among Chinese middle-aged and older adults in Markov model.

Introduction: Body mass index (BMI) has a strong correlation with chronic diseases and all-cause mortality. However, few studies have previously reported the longitudinal transition of BMI status and its influential factors, especially among Chinese middle-aged and older adults. Methods: This population-based cohort study involved 6,507 participants derived from the China Health and Retirement Longitudinal Study from 2011 to 2015, including objectively measured BMI recorded in 26,028 person-year of all observations followed up. Multistate Markov model was performed to estimate the BMI state transition intensity and hazard ratios of each potential exposure risk. Results: The mean intensity of the population that shifted from normal to overweight was more than twice than shifted to underweight. Besides, a predicted probability was up to 16.16% that the population with overweight would suffer from obesity and more than half of the population with underweight would return to normal weight over a 6-year interval. The study also implied significant effects of baseline age, gender, marital status, education level, alcohol consumption, smoking, depression symptoms, and activities of daily living impairment on BMI status transition to varying degrees. Conclusions: Findings of this study indicated that the mean transition probability between different BMI statuses varied, specific exposure factors serving as barriers or motivators to future transitions based on current BMI status was clarified for the health promotion strategies.

Parental pre-pregnancy body mass index and risk of low birth weight in offspring: A prospective cohort study in central China.

Background: Low birth weight (LBW) is one of the most common adverse pregnancy outcomes. Previous studies have consistently shown that maternal body mass index (BMI) status before and during pregnancy is associated with LBW. However, previous studies lacked an association between paternal BMI and the conjunction effect of a couple's BMI and LBW in the offspring. Therefore, we established a cohort of pre-pregnancy couples to prospectively assess the relationship between maternal and paternal pre-pregnancy BMI and offspring LBW, very low birth weight (VLBW), and extremely low birth weight (ELBW). Methods: A prospective cohort study was established in Central China. A total of 34,104 pregnant women with singleton pregnancies at 8-14 gestational weeks and their husbands were finally enrolled and followed to 3 months postpartum. The multivariate logistic regression and restrictive cubic spline model were used to explore the relationship between parental pre-pregnancy BMI and the risk of LBW, VLBW, and ELBW in offspring. Results: Of the 34,104 participants, maternal pre-pregnancy overweight and obesity were associated with a higher risk of LBW (overweight: OR = 1.720, 95% CI = 1.533 ~ 1.930; obesity: OR = 1.710, 95% CI = 1.360 ~ 2.151), VLBW (overweight: OR = 2.283, 95% CI = 1.839 ~ 2.834; obesity: OR = 4.023, 95% CI = 2.855 ~ 5.670), and ELBW (overweight: OR = 3.292, 95% CI = 2.151 ~ 5.036; obesity: OR = 3.467, 95% CI = 1.481 ~ 8.115), while underweight was associated with a higher risk of LBW (OR = 1.438, 95% CI = 1.294 ~ 1.599) and a lower risk of ELBW (OR = 0.473, 95% CI = 0.236 ~ 0.946). Paternal pre-pregnancy overweight and obesity were associated with a higher risk of LBW (overweight: OR = 1.637, 95% CI = 1.501 ~ 1.784; obesity: OR = 1.454, 95% CI = 1.289 ~ 1.641) and VLBW (overweight: OR = 1.310, 95% CI = 1.097 ~ 1.564; obesity: OR = 1.320, 95% CI = 1.037 ~ 1.681), while underweight was associated with a lower risk of LBW (OR = 0.660, 95% CI = 0.519 ~ 0.839). Parents who were both excessive-weights in pre-pregnancy BMI, as well as overweight mothers and normal-weight fathers before pre-pregnancy, were more likely to have offspring with LBW, VLBW, and ELBW. Dose-response relationship existed between parental pre-pregnancy and LBW, VLBW, and ELBW, except for paternal BMI and ELBW. Conclusions: Parental pre-pregnancy BMI was associated with the risk of LBW in offspring. Management of weight before pregnancy for couples might help reduce their adverse pregnancy outcomes in future intervention studies.

Effects of oily fish and its fatty acid intake on non-alcoholic fatty liver disease development among South Korean adults.

Background: The benefits of fish fatty acid intake for non-alcoholic fatty liver disease (NAFLD) are rarely reported, although a previous study assessed the relationship between oily fish consumption and the prevalence of NAFLD. Aims: We investigated whether oily fish and fish-based monounsaturated fatty acids, polyunsaturated fatty acids, and omega-3 fatty acids affect the development of NAFLD in South Korean adults. Methods: In this large-scale cohort study, 44,139 participants of the Health Examinees study were selected for analysis after 5 years of follow-up. NAFLD is diagnosed with a non-invasive index, the fatty liver index. Using multivariable Cox proportional hazards models, adjusted for age, body mass index, total energy intake, education, physical activity, smoking status, and drinking (alcohol) status, we calculated the hazard ratios and 95% confidence intervals. Results: For men, NAFLD had no statistically significant associations with quartiles of total oily fish or its fatty acid intake. However, among women, an inverse association was observed (all p for trend <0.05). Regarding the standard deviation (SD) increment of total oily fish or its fatty acid intake by one, all fatty acids from oily fish showed inverse associations for NAFLD in both men and women. After stratified analyses, we found that drinking status and menopause status were independent risk factors for NAFLD. Oily fish or its fatty acid intake has the same benefit pattern on metabolic dysfunction-associated fatty liver disease as NAFLD. Conclusion: Oily fish and its fatty acid intake showed a preventative benefit for NAFLD and metabolic dysfunction-associated fatty liver disease, especially in South Korean women.

Gender-specific association between the regular use of statins and the risk of irritable bowel syndrome: A population-based prospective cohort study.

Introduction: In addition to lipid-lowering effects, statins might modulate the gut microbiome and alleviate systematic inflammation, which in turn, may have a protective effect against irritable bowel syndrome (IBS). The aim of our study was to evaluate the gender-specific association between statin exposure and the risk of IBS. Method: We undertook a prospective analysis based on the United Kingdom Biobank, a large ongoing cohort including 477,293 participants aged 37-73 years. We included participants based on information on their personal statin use and also those free of IBS and cancer at the baseline. We evaluated the gender-specific hazard ratio (HR) and 95% confidence interval (CI) with Cox proportional hazards regression, adjusting for demographic factors, lifestyle factors, comorbidities, and statin indications. Result: A total of 438,805 participants (206,499 males and 232,306 females) were included in the analysis. Among male participants, the regular use of statins was associated with a decreased risk of IBS (HR: 0.77; 95% CI: 0.61-0.97). This association persists across multiple sensitivity and subgroup analyses and did not show clear evidence of variance among the major types of statins. We did not find sufficient evidence of the association between the statin use and IBS risk in females (HR: 0.98; 95% CI: 0.82-1.16). Conclusion: Our study found that the regular use of statins was associated with a decreased risk of IBS in male participants. Further studies are required to confirm the beneficial effect of statins.

Use of Tri-Ponderal Mass Index in Predicting Late Adolescent Overweight and Obesity in Children Aged 7-18.

Background: Current reference systems using body mass index (BMI) or BMI z-scores to estimate overweight and obesity risk in adolescents are complex to use. An easy and effective measure and cutoffs such as the tri-ponderal mass index (TMI) are in need for parents and grassroots health workers. Objective: The aim of this study was to test whether cohort-derived TMI could be efficient for obesity prediction and to find out whether simplified TMI cutoffs could be used in the prediction. Methods: Data were obtained from a 12-year retrospective growth cohort generated in Guangdong, China. A total of 17,815 children (53.9% were boys) with 151,879 follow-ups conducted annually between 2005 and 2016 were involved. Late adolescent overweight and obesity were defined based on the BMI z-score (WHO 2007 growth reference) of the last measurement, which happened at the mean age of 17.2 (SD: 0.7) for both sexes. Analysis of the area under the curve (AUC) of the receiver operating characteristic curves was used to find the most appropriate cutoff. Results: In total, 9,604 boys and 8,211 girls were included in the final analysis. TMI cutoffs performed better than WHO BMI cutoffs in the prediction of late adolescent overweight and obesity, with all corresponding AUCs <0.7. The simplified TMI cutoffs used to predict late adolescent overweight and obesity were 13.1 and 14.1 kg/m3 for children aged 7 to 15 years, respectively, with the corresponding AUCs ranging from 0.7315 (standard error, SE: 0.0132) to 0.9367 (SE: 0.0052). The cutoffs for predicting late adolescent overweight and obesity for children aged 16 to 18 years were 14.0 and 15.8 kg/m3, respectively, with the corresponding AUCs ranging from 0.9189 (SE: 0.0048) to 0.9841 (95% CI: 0.0027). Conclusion: Tri-ponderal mass index with the ease of administration in practice could be a promising alternative screening tool to BMI for the prediction of late adolescent overweight and obesity.

Design of the Arizona CoVHORT: A Population-Based COVID-19 Cohort.

This study is a prospective, population-based cohort of individuals with a history of SARS-CoV-2 infection and those without past infection through multiple recruitment sources. The main study goal is to track health status over time, within the diverse populations of Arizona and to identify the long-term consequences of COVID-19 on health and well-being. A total of 2,881 study participants (16.2% with a confirmed SARS-CoV-2 infection) have been enrolled as of December 22, 2020, with a target enrollment of 10,000 participants and a planned follow-up of at least 2 years. This manuscript describes a scalable study design that utilizes a wide range of recruitment sources, leveraging electronic data collection to capture and link longitudinal participant data on the current and emerging issues associated with the COVID-19 pandemic. The cohort is built within a collaborative infrastructure that includes new and established partnerships with multiple stakeholders, including the state's public universities, local health departments, tribes, and tribal organizations. Challenges remain for ensuring recruitment of diverse participants and participant retention, although the electronic data management system and timing of participant contact can help to mitigate these problems.

Analysis of Granulomatous Lymphocytic Interstitial Lung Disease Using Two Scoring Systems for Computed Tomography Scans-A Retrospective Cohort Study.

Background: Granulomatous lymphocytic interstitial lung disease (GLILD) is present in about 20% of patients with common variable immunodeficiency disorders (CVID). GLILD is characterized by nodules, reticulation, and ground-glass opacities on CT scans. To date, large cohort studies that include sensitive CT outcome measures are lacking, and severity of structural lung disease remains unknown. The aim of this study was to introduce and compare two scoring methods to phenotype CT scans of GLILD patients. Methods: Patients were enrolled in the "Study of Interstitial Lung Disease in Primary Antibody Deficiency" (STILPAD) international cohort. Inclusion criteria were diagnosis of both CVID and GLILD, as defined by the treating immunologist and radiologist. Retrospectively collected CT scans were scored systematically with the Baumann and Hartmann methods. Results: In total, 356 CT scans from 138 patients were included. Cross-sectionally, 95% of patients met a radiological definition of GLILD using both methods. Bronchiectasis was present in 82% of patients. Inter-observer reproducibility (intraclass correlation coefficients) of GLILD and airway disease were 0.84 and 0.69 for the Hartmann method and 0.74 and 0.42 for the Baumann method. Conclusions: In both the Hartmann and Baumann scoring method, the composite score GLILD was reproducible and therefore might be a valuable outcome measure in future studies. Overall, the reproducibility of the Hartmann method appears to be slightly better than that of the Baumann method. With a systematic analysis, we showed that GLILD patients suffer from extensive lung disease, including airway disease. Further validation of these scoring methods should be performed in a prospective cohort study involving routine collection of standardized CT scans. Clinical Trial Registration: https://www.drks.de, identifier DRKS00000799.

Lifetime Pesticide Use and Antinuclear Antibodies in Male Farmers From the Agricultural Health Study.

Farming and pesticide use have been associated with systemic autoimmune diseases, and while certain organochlorine insecticides and other pesticides are suspected to influence risk, the role of specific pesticides in the development of systemic autoimmunity is not known. We measured serum antinuclear autoantibodies (ANA) by immunofluorescence on Hep-2 cells in 668 male farmers in the study of Biomarkers of Exposure and Effect in Agriculture (BEEA; 2010-2013), an Agricultural Health Study (AHS) subcohort. We examined ANA in relation to lifetime use of 46 pesticides first reported at AHS enrollment (1993-1997) and updated at intervals through BEEA enrollment. Odds ratios (OR) and 95% confidence intervals (CI) were estimated after adjusting for age, state, education, season of blood draw, current pesticide use, and correlated pesticides. Having ANA antibodies (3 or 4+ intensity at a 1:80 dilution, 21% of study participants) was associated with a reported history of seeking medical care due to exposure to pesticides (OR 2.15; 95%CI 1.17, 3.95), use of the fumigant methyl bromide (OR 3.16; 95%CI 1.05, 9.5), and use of petroleum oil/distillates (OR 1.50; 95%CI 1.00, 2.25). Using a higher threshold (3 or 4+ at a 1:160 dilution, 9%) ANA positivity was associated with the carbamate insecticide aldicarb (OR 4.82; 95%CI 1.33, 17.5) and greater combined use of four cyclodiene organochlorine insecticides (top tertile of intensity-weighted lifetime days vs. no use; OR T3 3.20; 95%CI 1.10, 9.27). By contrast, greater use of non-cyclodiene organochlorine insecticides was inversely associated with ANA (1:80 dilution 3 or 4+, OR T3 0.24; 95%CI 0.08, 0.72). Specific autoantibodies (to extractable nuclear antigens and anti-dsDNA), measured on those with ANA detected at the 1:80 dilution 3 or 4+, were seen in 15 individuals (2%), and were associated with use of two or more cyclodiene organochlorine insecticides and several other pesticides (e.g., carbofuran, ethylene dibromide). These findings suggest that specific pesticide exposures may have long-term effects on ANA prevalence and support the hypothesis that certain organochlorine insecticides may increase the risk of developing systemic autoimmunity.

Longitudinal Associations of Modifiable Lifestyle Factors With Positive Depression-Screen Over 2.5-Years in an International Cohort of People Living With Multiple Sclerosis.

Background: Depression is common and has a significant impact on quality of life for many people with multiple sclerosis (MS). A preventive management approach via modification of lifestyle risk factors holds potential benefits. We examined the relationship between modifiable lifestyle factors and depression risk and the change in depression over 2.5 years. Methods: Sample recruited using online platforms. 2,224 (88.9%) at baseline and 1,309 (93.4%) at 2.5 years follow up completed the necessary survey data. Depression risk was measured by the Patient Health Questionnaire-2 (PHQ-2) at baseline and Patient Health Questionniare-9 (PHQ-9) at 2.5-years follow-up. Multivariable regression models assessed the relationships between lifestyle factors and depression risk, adjusted for sex, age, fatigue, disability, antidepressant medication use, and baseline depression score, as appropriate. Results: The prevalence of depression risk at 2.5-years follow-up in this cohort was 14.5% using the PHQ-2 and 21.7% using the PHQ-9. Moderate alcohol intake, being a non-smoker, diet quality, no meat or dairy intake, vitamin D supplementation, omega 3 supplement use, regular exercise, and meditation at baseline were associated with lower frequencies of positive depression-screen 2.5 years later. Moderate alcohol intake was associated with greater likelihood of becoming depression-free and a lower likelihood of becoming depressed at 2.5-years follow-up. Meditating at least once a week was associated with a decreased frequency of losing depression risk, against our expectation. After adjusting for potential confounders, smoking, diet, physical activity, and vitamin D and omega-3 supplementation were not associated with a change in risk for depression. Conclusion: In a large prospective cohort study of people with MS and depression, in line with the emerging treatment paradigm of early intervention, these results suggest a role for some lifestyle factors in depression risk. Further studies should endeavor to explore the impact of positive lifestyle change and improving depression in people living with MS.

Combination of self-harm methods and fatal and non-fatal repetition: A cohort study.

BACKGROUND: Assessment and aftercare for people who self-harm needs to be related to an understanding of risks of adverse outcomes. We aimed to determine whether self-harm by a combination of methods and its early repetition are associated with adverse outcomes - especially non-fatal repetition and suicide. METHOD: 10,829 consecutive general hospital attendances due to self-harm in one large English city were monitored, through scrutiny of Emergency Department attendances, over three years and followed up to determine the incidence of non-fatal repetition. Subsequent deaths, by any cause and by suicide, were determined from national statistical records. RESULTS: 6155 patients accounted for the 10,829 episodes: 72% by self-poisoning, 21% self-injury, and 746 episodes (7%) due to a combination of methods. After a combined-methods index episode, non-fatal repetition (P=0.001) and suicide (P=0.002) occurred sooner and more frequently than it did among those who had self-poisoned. Further hospital attendance due to self-harm within a month was associated with a 3.7-fold (95% CI 2.1-6.4) risk of subsequent suicide. LIMITATIONS: The data exclude self-harm episodes that do not result in a hospital attendance. Index episodes in the study are not generally life-time first episodes so follow-up data are based on an arbitrary start-point. Both of these limitations are common to all studies of this kind. CONCLUSIONS: At psychosocial assessment and the making of aftercare arrangements, combined methods of self-harm or another recent episode should be considered 'red-flag' indicators for attention to care.