Factors associated with suicide risk among Chinese adults: A prospective cohort study of 0.5 million individuals

BackgroundSuicide is a leading cause of death in China and accounts for about one-sixth of all suicides worldwide. The objective of this study was to examine the recent distribution of suicide and risk factors for death by suicide. Identifying underlying risk factors could benefit development of evidence-based prevention and intervention programs.Methods and findingsWe conducted a prospective study, the China Kadoorie Biobank, of 512,715 individuals (41% men, mean age 52 years) from 10 (5 urban, 5 rural) areas which are diverse across China in geographic locations, social economic developmental stages, and prevalence of disease patterns. After the baseline measurements of risk factors during 2004 to 2008, participants were followed up for suicide outcomes including suicide and possible suicide deaths. Risk factors, such as sociodemographic factors and physical and mental health status, were assessed by semistructured interviews and self-report questionnaires. Suicide and possible suicide deaths were identified through linkage to the local death registries using ICD-10 codes. We conducted Cox regression to calculate hazard ratios (HRs) for suicide and for possible suicide in sensitivity analyses.During an average follow-up period of 9.9 years, 520 (101 per 100,000) people died from suicide (51.3% male), and 79.8% of them lived in rural areas. Sociodemographic factors associated with increased suicide risk were male gender (adjusted hazard ratios [aHR] = 1.6 [95% CI 1.4 to 2.0], p < 0.001), older age (1.3 [1.2 to 1.5] by each 10-yr increase, p < 0.001), rural residence (2.6 [2.1 to 3.3], p < 0.001), and single status (1.7 [1.4 to 2.2], p < 0.001). Increased hazards were found for family-related stressful life events (aHR = 1.8 [1.2 to 1.9], p < 0.001) and for major physical illnesses (1.5 [1.3 to 1.9], p < 0.001). There were strong associations of suicide with a history of lifetime mental disorders (aHR = 9.6 [5.9 to 15.6], p < 0.001) and lifetime schizophrenia-spectrum disorders (11.0 [7.1 to 17.0], p < 0.001). Links between suicide risk and depressive disorders (aHR = 2.6 [1.4 to 4.8], p = 0.002) and generalized anxiety disorders (2.6 [1.0 to 7.1], p = 0.056) in the last 12 months, and sleep disorders (1.4 [1.2 to 1.7], p < 0.001) in the past month were also found. All HRs were adjusted for sociodemographic factors including gender, age, residence, single status, education, and income. The associations with possible suicide deaths were mostly similar to those with suicide deaths, although there was no clear link between possible suicide deaths and psychiatric factors such as depression and generalized anxiety disorders. A limitation of the study is that there is likely underreporting of mental disorders due to the use of self-report information for some diagnostic categories.ConclusionsIn this study, we observed that a range of sociodemographic, lifestyle, stressful life events, physical, and mental health factors were associated with suicide in China. High-risk groups identified were elderly men in rural settings and individuals with mental disorders. These findings could form the basis of targeted approaches to reduce suicide mortality in China.

In a prospective cohort study, Rongqin Yu, Yiping Chen and colleagues investigate factors related to death by suicide among Chinese adults.     

Genome-wide methylation profiling reveals Zinc finger protein 516 (ZNF516) and FK-506-binding protein 6 (FKBP6) promoters frequently methylated in cervical neoplasia,associated with HPV status and ethnicity in a Chilean population

Cervical cancer is a major health concern among women in Latin America due to its high incidence and mortality. Therefore, the discovery of molecular markers for cervical cancer screening and triage is imperative. The aim of this study was to use a genome wide DNA methylation approach to identify novel methylation biomarkers in cervical cancer. DNA from normal cervical mucosa and cervical cancer tissue samples from Chile was enriched with Methylated DNA Immunoprecipitation (MeDIP), hybridized to oligonucleotide methylation microarrays and analyzed with a stringent bioinformatics pipeline to identify differentially methylated regions (DMRs) as candidate biomarkers. Quantitative Methylation Specific PCR (qMSP) was used to study promoter methylation of candidate DMRs in clinical samples from two independent cohorts. HPV detection and genotyping were performed by Reverse Line Blot analysis. Bioinformatics analysis revealed GGTLA4, FKBP6, ZNF516, SAP130, and INTS1 to be differentially methylated in cancer and normal tissues in the Discovery cohort. In the Validation cohort FKBP6 promoter methylation had 73% sensitivity and 80% specificity (AUC = 0.80). ZNF516 promoter methylation was the best biomarker, with both sensitivity and specificity of 90% (AUC = 0.92), results subsequently corroborated in a Prevalence cohort. Together, ZNF516 and FKBP6 exhibited a sensitivity of 84% and specificity of 81%, when considering both cohorts. Our genome wide DNA methylation assessment approach (MeDIP-chip) successfully identified novel biomarkers that differentiate between cervical cancer and normal samples, after adjusting for age and HPV status. These biomarkers need to be further explored in case-control and prospective cohorts to validate them as cervical cancer biomarkers.     

Robust prediction of mortality of COVID-19 patients based on quantitative,operator-independent,lung CT densitometry

PurposeTo train and validate a predictive model of mortality for hospitalized COVID-19 patients based on lung densitometry.MethodsTwo-hundred-fifty-one patients with respiratory symptoms underwent CT few days after hospitalization. “Aerated” (AV), “consolidated” (CV) and “intermediate” (IV) lung sub-volumes were quantified by an operator-independent method based on individual HU maximum gradient recognition. AV, CV, IV, CV/AV, IV/AV, and HU of the first peak position were extracted. Relevant clinical parameters were prospectively collected. The population was composed by training (n = 166) and validation (n = 85) consecutive cohorts, and backward multi-variate logistic regression was applied on the training group to build a CT_model. Similarly, models including only clinical parameters (CLIN_model) and both CT/clinical parameters (COMB_model) were developed. Model’s performances were assessed by goodness-of-fit (H&L-test), calibration and discrimination. Model’s performances were tested in the validation group.ResultsForty-three patients died (25/18 in training/validation). CT_model included AVmax (i.e. maximum AV between lungs), CV and CV/AE, while CLIN_model included random glycemia, C-reactive protein and biological drugs (protective). Goodness-of-fit and discrimination were similar (H&L:0.70 vs 0.80; AUC:0.80 vs 0.80). COMB_model including AVmax, CV, CV/AE, random glycemia, biological drugs and active cancer, outperformed both models (H&L:0.91; AUC:0.89, 95%CI:0.82–0.93). All models showed good calibration (R²:0.77–0.97). Despite several patient's characteristics were different between training and validation cohorts, performances in the validation cohort confirmed good calibration (R²:0–70-0.81) and discrimination for CT_model/COMB_model (AUC:0.72/0.76), while CLIN_model performed worse (AUC:0.64).ConclusionsFew automatically extracted densitometry parameters with clear functional meaning predicted mortality of COVID-19 patients. Combined with clinical features, the resulting predictive model showed higher discrimination/calibration.     

Relationship between the Bolsa Família national cash transfer programme and suicide incidence in Brazil: A quasi-experimental study

BackgroundSocioeconomic factors have been consistently associated with suicide, and economic recessions are linked to rising suicide rates. However, evidence on the impact of socioeconomic interventions to reduce suicide rates is limited. This study investigates the association of the world’s largest conditional cash transfer programme with suicide rates in a cohort of half of the Brazilian population.Methods and findingsWe used data from the 100 Million Brazilian Cohort, covering a 12-year period (2004 to 2015). It comprises socioeconomic and demographic information on 114,008,317 individuals, linked to the “Bolsa Família” programme (BFP) payroll database, and nationwide death registration data. BFP was implemented by the Brazilian government in 2004. We estimated the association of BFP using inverse probability of treatment weighting, estimating the weights for BFP beneficiaries (weight = 1) and nonbeneficiaries by the inverse probability of receiving treatment (weight = E(ps)/(1-E(ps))). We used an average treatment effect on the treated (ATT) estimator and fitted Poisson models to estimate the incidence rate ratios (IRRs) for suicide associated with BFP experience. At the cohort baseline, BFP beneficiaries were younger (median age 27.4 versus 35.4), had higher unemployment rates (56% versus 32%), a lower level of education, resided in rural areas, and experienced worse household conditions. There were 36,742 suicide cases among the 76,532,158 individuals aged 10 years, or older, followed for 489,500,000 person-years at risk. Suicide rates among beneficiaries and nonbeneficiaries were 5.4 (95% CI = 5.32, 5.47, p < 0.001) and 10.7 (95% CI = 10.51, 10.87, p < 0.001) per 100,000 individuals, respectively. BFP beneficiaries had a lower suicide rate than nonbeneficiaries (IRR = 0.44, 95% CI = 0.42, 0.45, p < 0.001). This association was stronger among women (IRR = 0.36, 95% CI = 0.33, 0.38, p < 0.001), and individuals aged between 25 and 59 (IRR = 0.41, 95% CI = 0.40, 0.43, p < 0.001). Study limitations include a lack of control for previous mental disorders and access to means of suicide, and the possible under-registration of suicide cases due to stigma.ConclusionsWe observed that BFP was associated with lower suicide rates, with similar results in all sensitivity analyses. These findings should help to inform policymakers and health authorities to better design suicide prevention strategies. Targeting social determinants using cash transfer programmes could be important in limiting suicide, which is predicted to rise with the economic recession, consequent to the Coronavirus Disease 2019 (COVID-19) pandemic.

In a quasi-experimental study, Daiane Borges Machado and colleagues investigate the association between rates of suicide and the Bolsa Familia cash transfer program in the 100 Million Brazilian Cohort.     

Prevalence of Suicide Attempts among College Students in China: A Meta-Analysis

BackgroundSuicide is the leading cause of death among 15–34 year olds in China, but no national data are available on the suicide and suicide attempts rates of college students, a sub-group of youth with 23 million. Several studies have reported the prevalence of suicide attempts among college students, however, no meta-analysis pooling the prevalence of suicide attempts is found.ResultsA total of 29 eligible studies, with 88,225 college students, were finally included. The maximum and minimum reported prevalences of suicide attempts among college students in China were 0.4% and 10.5%, respectively. The pooled prevalence of suicide attempts was 2.8% (95%CI: 2.3%–3.3%). Subgroup analyses showed that the pooled estimate of prevalence of life time suicide attempts was 2.7% (95%CI: 2.1%–3.3%), and 12-month suicide attempts was 2.9% (95%CI: 2.0%–3.8%). The prevalence for males was 2.4% (95%CI: 1.8%–3.0%), and for females was 2.7% (95%CI: 1.9%–3.7%). The prevalences among college students in grade 1 through 4 were 2.8% (95%CI: 1.7%–3.8%), 1.8% (95%CI: 1.2%–2.3%), 2.0% (95%CI: 0.8%–3.1%), and 2.9% (95%CI: 0.1%–6.7%), respectively. The prevalences among college students from rural and urban areas were 5.1% (95%CI: 2.8%–7.5%) and 3.7% (95%CI: 1.4%–5.9%), respectively.Conclusions2.8% prevalence of suicide attempts and more than 600,000 suicide attempters among college students indicate that suicide attempt among college students is an important public health problem in China. More attention should be paid to the current situation.     

All-cause and cause-specific mortality during and following incarceration in Brazil: A retrospective cohort study

BackgroundMortality during and after incarceration is poorly understood in low- and middle-income countries (LMICs). The need to address this knowledge gap is especially urgent in South America, which has the fastest growing prison population in the world. In Brazil, insufficient data have precluded our understanding of all-cause and cause-specific mortality during and after incarceration.Methods and findingsWe linked incarceration and mortality databases for the Brazilian state of Mato Grosso do Sul to obtain a retrospective cohort of 114,751 individuals with recent incarceration. Between January 1, 2009 and December 31, 2018, we identified 3,127 deaths of individuals with recent incarceration (705 in detention and 2,422 following release). We analyzed age-standardized, all-cause, and cause-specific mortality rates among individuals detained in different facility types and following release, compared to non-incarcerated residents. We additionally modeled mortality rates over time during and after incarceration for all causes of death, violence, or suicide. Deaths in custody were 2.2 times the number reported by the national prison administration (n = 317). Incarcerated men and boys experienced elevated mortality, compared with the non-incarcerated population, due to increased risk of death from violence, suicide, and communicable diseases, with the highest standardized incidence rate ratio (IRR) in semi-open prisons (2.4; 95% confidence interval [CI]: 2.0 to 2.8), police stations (3.1; 95% CI: 2.5 to 3.9), and youth detention (8.1; 95% CI: 5.9 to 10.8). Incarcerated women experienced increased mortality from suicide (IRR = 6.0, 95% CI: 1.2 to 17.7) and communicable diseases (IRR = 2.5, 95% CI: 1.1 to 5.0). Following release from prison, mortality was markedly elevated for men (IRR = 3.0; 95% CI: 2.8 to 3.1) and women (IRR = 2.4; 95% CI: 2.1 to 2.9). The risk of violent death and suicide was highest immediately post-release and declined over time; however, all-cause mortality remained elevated 8 years post-release. The limitations of this study include inability to establish causality, uncertain reliability of data during incarceration, and underestimation of mortality rates due to imperfect database linkage.ConclusionsIncarcerated individuals in Brazil experienced increased mortality from violence, suicide, and communicable diseases. Mortality was heightened following release for all leading causes of death, with particularly high risk of early violent death and elevated all-cause mortality up to 8 years post-release. These disparities may have been underrecognized in Brazil due to underreporting and insufficient data.

In a retrospective cohort study, Yiran E Liu and colleagues investigate all-cause and cause-specific mortality during and following incarceration in Brazil.     

Socioeconomic predictors of suicide risk among cancer patients in the United States: A population-based study

ObjectiveTo assess the socioeconomic predictors of suicide risk among cancer patients in the United States.MethodsCancer patients available within Surveillance, Epidemiology and End Results (SEER) database who were diagnosed between 2000–2010 have been reviewed. Linkage analysis to Census 2000 SF files was conducted to determine area-based socioeconomic attributes. Observed/ Expected ratios were calculated for the overall cohort as well as for clinically and socioeconomically defined subgroups. “Observed” is the number of observed completed suicide cases in the studied cohort; while “Expected” is the number of completed suicide cases in a demographically similar cohort within the United States and within the same period of time.ResultsThe current study reviews a total of 3,149,235 cancer patients (diagnosed 2000–2010) within the SEER database. Regarding socioeconomic county attributes, higher risk of suicide seems to be associated with lower educational attainment (O/E for counties with > 20% individuals with less than high school education: 1.41; 95% CI: 1.35–1.47), poverty rates (O/E for counties with > 5% individuals below poverty line: 1.39; 95% CI: 1.34–1.43), unemployment rates (O/E for counties with >5% families below poverty line: 1.36; 95% CI: 1.31–1.41) and less people living in urban areas (O/E for counties with < 50% individuals living in urban areas: 1.63; 95% CI: 1.50–1.77). On the other hand, risk of suicide seems to be inversely related to a higher representation of foreign-born individuals (O/E for counties with < 5% foreign-born individuals: 1.56; 95% CI: 1.47–1.65); and inversely related to a higher representation with recent immigrants to the US (O/E for counties with < 5% recent immigrants: 1.33; 95% CI: 1.29–1.38).ConclusionsCancer patients living in a socioeconomically vulnerable environment (lower educational status, poverty, and unemployment) seem to have higher suicide risk compared to other cancer patients.     

Genome-wide methylation profiling reveals Zinc finger protein 516 (ZNF516) and FK-506-binding protein 6 (FKBP6) promoters frequently methylated in cervical neoplasia,associated with HPV status and ethnicity in a Chilean population

Cervical cancer is a major health concern among women in Latin America due to its high incidence and mortality. Therefore, the discovery of molecular markers for cervical cancer screening and triage is imperative. The aim of this study was to use a genome wide DNA methylation approach to identify novel methylation biomarkers in cervical cancer. DNA from normal cervical mucosa and cervical cancer tissue samples from Chile was enriched with Methylated DNA Immunoprecipitation (MeDIP), hybridized to oligonucleotide methylation microarrays and analyzed with a stringent bioinformatics pipeline to identify differentially methylated regions (DMRs) as candidate biomarkers. Quantitative Methylation Specific PCR (qMSP) was used to study promoter methylation of candidate DMRs in clinical samples from two independent cohorts. HPV detection and genotyping were performed by Reverse Line Blot analysis. Bioinformatics analysis revealed GGTLA4, FKBP6, ZNF516, SAP130, and INTS1 to be differentially methylated in cancer and normal tissues in the Discovery cohort. In the Validation cohort FKBP6 promoter methylation had 73% sensitivity and 80% specificity (AUC = 0.80). ZNF516 promoter methylation was the best biomarker, with both sensitivity and specificity of 90% (AUC = 0.92), results subsequently corroborated in a Prevalence cohort. Together, ZNF516 and FKBP6 exhibited a sensitivity of 84% and specificity of 81%, when considering both cohorts. Our genome wide DNA methylation assessment approach (MeDIP-chip) successfully identified novel biomarkers that differentiate between cervical cancer and normal samples, after adjusting for age and HPV status. These biomarkers need to be further explored in case-control and prospective cohorts to validate them as cervical cancer biomarkers.     

Predictive Validity of the Suicide Trigger Scale (STS-3) for Post-Discharge Suicide Attempt in High-Risk Psychiatric Inpatients

Background

The greatly increased risk of suicide after psychiatric hospitalization is a critical problem, yet we are unable to identify individuals who would attempt suicide upon discharge. The Suicide Trigger Scale v.3 (STS-3), was designed to measure the construct of an affective ‘suicide trigger state’ hypothesized to precede a suicide attempt (SA). This study aims to test the predictive validity of the STS-3 for post-discharge SA on a high-risk psychiatric-inpatient sample.

Methods

The STS-3, and a psychological test battery measuring suicidality, mood, impulsivity, trauma history, and attachment style were administered to 161 adult psychiatric patients hospitalized following suicidal ideation (SI) or SA. Receiver Operator Characteristic and logistic regression analyses were used to assess prediction of SA in the 6-month period following discharge from hospitalization.

Results

STS-3 scores for the patients who made post-discharge SA followed a bimodal distribution skewed to high and low scores, thus a distance from median transform was applied to the scores. The transformed score was a significant predictor of post-discharge SA (AUC 0.731), and a subset of six STS-3 scale items was identified that produced improved prediction of post-discharge SA (AUC 0.814). Scores on C-SSRS and BSS were not predictive. Patients with ultra-high (90^th percentile) STS-3 scores differed significantly from ultra-low (10^th percentile) scorers on measures of affective intensity, depression, impulsiveness, abuse history, and attachment security.

Conclusion

STS-3 transformed scores at admission to the psychiatric hospital predict suicide attempts following discharge among the high-risk group of suicidal inpatients. Patients with high transformed scores appear to comprise two clinically distinct groups; an impulsive, affectively intense, fearfully attached group with high raw STS-3 scores and a low-impulsivity, low affect and low trauma-reporting group with low raw STS-3 scores. These groups may correspond to low-plan and planned suicide attempts, respectively, but this remains to be established by future research.     

Suicide attempts in the Epidemiologic Catchment Area Study

This study examines risk factors for attempted suicide in the general community. Data from the five-site NIMH Epidemiologic Catchment Area (ECA) Study were used to estimate lifetime prevalence and identify risk factors for suicide attempts. Occurrence of suicide attempts and lifetime diagnosis of psychiatric disorder were ascertained, using the NIMH Diagnostic Interview Schedule (DIS). Of 18,571 adult respondents aged 18 and over, 2.9 percent reported that they had attempted suicide at some time in their lives. A weighted logistic regression model was constructed to ascertain significant (p less than .0028 with Bonferroni correction) risk factors for attempted suicide. Persons who had a lifetime diagnosis of a psychiatric disorder had the highest risk of attempted suicide (odds ratio [OR] = 8.4). Females (OR = 3.3), separated or divorced persons (OR = 2.5), Whites (OR = 1.7), persons in the two lowest socioeconomic quartiles (ORs = 2.2, 2.3), and respondents from the Los Angeles ECA (OR = 1.8) were also more likely to have attempted suicide. These findings contribute to an understanding of suicide and suicidal behavior in general populations, outside the clinical setting.     

Perinatal photoperiod and childhood cancer: pooled results from 182,856 individuals in the international childhood cancer cohort consortium (I4C)

ABSTRACT

Experimental evidence suggests that perinatal light imprinting of circadian clocks and systems may affect downstream physiology and cancer risk in later life. For humans, the predominant circadian stimulus is the daily light-dark cycle. Herein, we explore associations between perinatal photoperiod characteristics (photoperiod: duration of daylight as determined by time-of-year and location) and childhood cancer risk. We use pooled data on 182,856 mothers and babies from prospective birth cohorts in six countries (Australia, Denmark, Israel, Norway, UK, USA) within the International Childhood Cancer Cohort Consortium (I4C). Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). In line with predicted differential dose–responses, restricted cubic splines indicate a potential non-linear, non-monotonic relationship between perinatal mean daily photoperiod (0–24 h) and childhood cancer risk. In a restricted analysis of 154,121 individuals who experienced third trimester photoperiods exclusively within the 8–16-h range, the relative risk of developing childhood cancer decreased by 9% with every hour increase in third trimester mean daily photoperiod [HR: 0.91 (95%CIs: 0.84–0.99)]. In conclusion, in this first study of perinatal photoperiod and childhood cancer, we detected an inverse [“protective”] linear association between third trimester mean daily photoperiod and childhood cancer risk in the 8–16-h set of the total study population. Limited statistical power impeded the investigation of risks with individuals exposed to more extreme photoperiods. Future studies are needed to confirm differential photoperiod-associated risks and further investigations into the hypothesized circadian imprinting mechanism are warranted.     

Deep radiomic model based on the sphere–shell partition for predicting treatment response to chemotherapy in lung cancer

BackgroundThe prognosis of chemotherapy is important in clinical decision-making for non-small cell lung cancer (NSCLC) patients.ObjectivesTo develop a model for predicting treatment response to chemotherapy in NSCLC patients from pre-chemotherapy CT images.Materials and MethodsThis retrospective multicenter study enrolled 485 patients with NSCLC who received chemotherapy alone as a first-line treatment. Two integrated models were developed using radiomic and deep-learning-based features. First, we partitioned pre-chemotherapy CT images into spheres and shells with different radii around the tumor (0–3, 3–6, 6–9, 9–12, 12–15 mm) containing intratumoral and peritumoral regions. Second, we extracted radiomic and deep-learning-based features from each partition. Third, using radiomic features, five sphere–shell models, one feature fusion model, and one image fusion model were developed. Finally, the model with the best performance was validated in two cohorts.ResultsAmong the five partitions, the model of 9–12 mm achieved the highest area under the curve (AUC) of 0.87 (95% confidence interval: 0.77–0.94). The AUC was 0.94 (0.85–0.98) for the feature fusion model and 0.91 (0.82–0.97) for the image fusion model. For the model integrating radiomic and deep-learning-based features, the AUC was 0.96 (0.88–0.99) for the feature fusion method and 0.94 (0.85–0.98) for the image fusion method. The best-performing model had an AUC of 0.91 (0.81–0.97) and 0.89 (0.79–0.93) in two validation sets, respectively.ConclusionsThis integrated model can predict the response to chemotherapy in NSCLC patients and assist physicians in clinical decision-making.     

CT radiomics combined with clinical variables for predicting the overall survival of hepatocellular carcinoma patients after hepatectomy

PurposeTo establish a model for assessing the overall survival (OS) of the hepatocellular carcinoma (HCC) patients after hepatectomy based on the clinical and radiomics features.MethodsThis study recruited a total of 267 patients with HCC, which were randomly divided into the training (N = 188) and validation (N = 79) cohorts. In the training cohort, radiomic features were selected with the intra-reader and inter-reader correlation coefficient (ICC), Spearman's correlation coefficient, and the least absolute shrinkage and selection operator (LASSO). The radiomics signatures were built by COX regression analysis and compared the predictive potential in the different phases (arterial, portal, and double-phase) and regions of interest (tumor, peritumor 3 mm, peritumor 5 mm). A clinical-radiomics model (CR model) was established by combining the radiomics signatures and clinical risk factors. The validation cohort was used to validate the proposed models.ResultsA total of 267 patients 86 (45.74%) and 37 (46.84%) patients died in the training and validation cohorts, respectively. Among all the radiomics signatures, those based on the tumor and peritumor (5 mm) (AP-TP5-Signature) showed the best prognostic potential (training cohort 1–3 years AUC:0.774–0.837; validation cohort 1–3 years AUC:0.754–0.810). The CR model showed better discrimination, calibration, and clinical applicability as compared to the clinical model and radiomics features. In addition, the CR model could perform risk-stratification and also allowed for significant discrimination between the Kaplan-Meier curves in most of the subgroups.ConclusionsThe CR model could predict the OS of the HCC patients after hepatectomy.     

Non–Laboratory-Based Self-Assessment Screening Score for Non-Alcoholic Fatty Liver Disease: Development,Validation and Comparison with Other Scores

Background

Non-alcoholic fatty liver disease (NAFLD) is a prevalent and rapidly increasing disease worldwide; however, no widely accepted screening models to assess the risk of NAFLD are available. Therefore, we aimed to develop and validate a self-assessment score for NAFLD in the general population using two independent cohorts.

Methods

The development cohort comprised 15676 subjects (8313 males and 7363 females) who visited the National Health Insurance Service Ilsan Hospital in Korea in 2008–2010. Anthropometric, clinical, and laboratory data were examined during regular health check-ups and fatty liver diagnosed by abdominal ultrasound. Logistic regression analysis was conducted to determine predictors of prevalent NAFLD and to derive risk scores/models. We validated our models and compared them with other existing methods using an external cohort (N = 66868).

Results

The simple self-assessment score consists of age, sex, waist circumference, body mass index, history of diabetes and dyslipidemia, alcohol intake, physical activity and menopause status, which are independently associated with NAFLD, and has a value of 0–15. A cut-off point of ≥8 defined 58% of males and 36% of females as being at high-risk of NAFLD, and yielded a sensitivity of 80% in men (77% in women), a specificity of 67% (81%), a positive predictive value of 72% (63%), a negative predictive value of 76% (89%) and an AUC of 0.82 (0.88). Comparable results were obtained using the validation dataset. The comprehensive NAFLD score, which includes additional laboratory parameters, has enhanced discrimination ability, with an AUC of 0.86 for males and 0.91 for females. Both simple and comprehensive NAFLD scores were significantly increased in subjects with higher fatty liver grades or severity of liver conditions (e.g., simple steatosis, steatohepatitis).

Conclusions

The new non–laboratory-based self-assessment score may be useful for identifying individuals at high-risk of NAFLD. Further studies are warranted to evaluate the utility and feasibility of the scores in various settings.     

Alcohol-Related Risk of Suicidal Ideation,Suicide Attempt,and Completed Suicide: A Meta-Analysis

BackgroundSeveral original studies have investigated the effect of alcohol use disorder (AUD) on suicidal thought and behavior, but there are serious discrepancies across the studies. Thus, a systematic assessment of the association between AUD and suicide is required.MethodsWe searched PubMed, Web of Science, and Scopus until February 2015. We also searched the Psycinfo web site and journals and contacted authors. We included observational (cohort, case-control, and cross-sectional) studies addressing the association between AUD and suicide. The exposure of interest was AUD. The primary outcomes were suicidal ideation, suicide attempt, and completed suicide. We assessed heterogeneity using Q-test and I² statistic. We explored publication bias using the Egger''s and Begg''s tests and funnel plot. We meta-analyzed the data with the random-effects models. For each outcome we calculated the overall odds ratio (OR) or risk ratio (RR) with 95% confidence intervals (CI).ResultsWe included 31 out of 8548 retrieved studies, with 420,732 participants. There was a significant association between AUD and suicidal ideation (OR=1.86; 95% CI: 1.38, 2.35), suicide attempt (OR=3.13; 95% CI: 2.45, 3.81); and completed suicide (OR=2.59; 95% CI: 1.95, 3.23 and RR=1.74; 95% CI: 1.26, 2.21). There was a significant heterogeneity among the studies, but little concern to the presence of publication bias.ConclusionsThere is sufficient evidence that AUD significantly increases the risk of suicidal ideation, suicide attempt, and completed suicide. Therefore, AUD can be considered an important predictor of suicide and a great source of premature death.     

Trajectories of Work-Related Functional Impairment prior to Suicide

BackgroundWork-related functional impairment in terms of sickness absence and disability pension (SA/DP) has been reported to be associated with subsequent suicide. However, there is only limited knowledge on SA/DP patterns prior to suicide. The aim was to identify trajectories of work-related functional impairment prior to suicide and to describe associations of socio-demographic and medical factors with such trajectories.MethodsThis is a population-based retrospective cohort study of the 4 209 individuals aged 22–65 years who committed suicide during 2007–2010 in Sweden. Work-related functional impairment was measured as mean annual number of months of SA/DP. We analyzed trajectories of SA/DP during five years prior to suicide (i.e., 2002–2009) by a group-based trajectory method. Associations between socio-demographic and medical factors with different groups of trajectories were estimated by chi²-test and multinomial logistic regression.ResultsFive different functional impairment trajectory groups were identified prior to suicide. One group had constant low levels of SA/DP (46%), while 30% had constant high levels of SA/DP. Two groups (16%) showed increasing number of SA/DP months. The remaining 7% showed decreasing number of SA/DP months before the suicide. Sex, age, educational level, family situation, and diagnosis-specific healthcare were significantly associated with different trajectory groups (Likelihood ratio X² tests <0.05). A larger proportion of higher educated and younger men with a lower proportion of previous suicide attempts were found in the group with constant low levels. Opposite characteristics were displayed in the group with constant high levels.ConclusionsThis study identified five different groups of work-related functional impairment trajectories before suicide. These differences might be partly explained by the variations in socio-demographic profiles and health care consumptions five years before suicide.     

The Delayed Risk Stratification System in the Risk of Differentiated Thyroid Cancer Recurrence

ContextThere has been a marked increase in the detection of differentiated thyroid carcinoma (DTC) over the past few years, which has improved the prognosis. However, it is necessary to adjust treatment and monitoring strategies relative to the risk of an unfavourable disease course.ResultsThe PPV and NPV for the ATA (24.59% and 95.42%, respectively) and ETA (24.28% and 95.68%, respectively) were significantly lower than those for the DRS (56.76% and 98.5%, respectively) (p<0.0001). The proportion of variance for predicting the final outcome was 15.8% for ATA, 16.1% for ETA and 56.7% for the DRS. Recurrent disease was rare (1% of patients), and was nearly always identified in patients at intermediate/high risk according to the initial stratification (9/10 cases).ConclusionsThe DRS showed a better correlation with the risk of persistent disease than the early stratification systems and allows personalisation of follow-up. If clinicians plan to alter the intensity of surveillance, patients at intermediate/high risk according to the early stratification systems should remain within the specialized centers; however, low risk patients can be referred to endocrinologists or other appropriate practitioners for long-term follow-up, as these patients remained at low risk after risk re-stratification.     

A Novel Brief Therapy for Patients Who Attempt Suicide: A 24-months Follow-Up Randomized Controlled Study of the Attempted Suicide Short Intervention Program (ASSIP)

Background

Attempted suicide is the main risk factor for suicide and repeated suicide attempts. However, the evidence for follow-up treatments reducing suicidal behavior in these patients is limited. The objective of the present study was to evaluate the efficacy of the Attempted Suicide Short Intervention Program (ASSIP) in reducing suicidal behavior. ASSIP is a novel brief therapy based on a patient-centered model of suicidal behavior, with an emphasis on early therapeutic alliance.

Methods and Findings

Patients who had recently attempted suicide were randomly allocated to treatment as usual (n = 60) or treatment as usual plus ASSIP (n = 60). ASSIP participants received three therapy sessions followed by regular contact through personalized letters over 24 months. Participants considered to be at high risk of suicide were included, 63% were diagnosed with an affective disorder, and 50% had a history of prior suicide attempts. Clinical exclusion criteria were habitual self-harm, serious cognitive impairment, and psychotic disorder. Study participants completed a set of psychosocial and clinical questionnaires every 6 months over a 24-month follow-up period.The study represents a real-world clinical setting at an outpatient clinic of a university hospital of psychiatry. The primary outcome measure was repeat suicide attempts during the 24-month follow-up period. Secondary outcome measures were suicidal ideation, depression, and health-care utilization. Furthermore, effects of prior suicide attempts, depression at baseline, diagnosis, and therapeutic alliance on outcome were investigated.During the 24-month follow-up period, five repeat suicide attempts were recorded in the ASSIP group and 41 attempts in the control group. The rates of participants reattempting suicide at least once were 8.3% (n = 5) and 26.7% (n = 16). ASSIP was associated with an approximately 80% reduced risk of participants making at least one repeat suicide attempt (Wald χ² ₁ = 13.1, 95% CI 12.4–13.7, p < 0.001). ASSIP participants spent 72% fewer days in the hospital during follow-up (ASSIP: 29 d; control group: 105 d; W = 94.5, p = 0.038). Higher scores of patient-rated therapeutic alliance in the ASSIP group were associated with a lower rate of repeat suicide attempts. Prior suicide attempts, depression, and a diagnosis of personality disorder at baseline did not significantly affect outcome. Participants with a diagnosis of borderline personality disorder (n = 20) had more previous suicide attempts and a higher number of reattempts.Key study limitations were missing data and dropout rates. Although both were generally low, they increased during follow-up. At 24 months, the group difference in dropout rate was significant: ASSIP, 7% (n = 4); control, 22% (n = 13). A further limitation is that we do not have detailed information of the co-active follow-up treatment apart from participant self-reports every 6 months on the setting and the duration of the co-active treatment.

Conclusions

ASSIP, a manual-based brief therapy for patients who have recently attempted suicide, administered in addition to the usual clinical treatment, was efficacious in reducing suicidal behavior in a real-world clinical setting. ASSIP fulfills the need for an easy-to-administer low-cost intervention. Large pragmatic trials will be needed to conclusively establish the efficacy of ASSIP and replicate our findings in other clinical settings.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02505373","term_id":"NCT02505373"}}NCT02505373     

Accurate and Robust Genomic Prediction of Celiac Disease Using Statistical Learning

Practical application of genomic-based risk stratification to clinical diagnosis is appealing yet performance varies widely depending on the disease and genomic risk score (GRS) method. Celiac disease (CD), a common immune-mediated illness, is strongly genetically determined and requires specific HLA haplotypes. HLA testing can exclude diagnosis but has low specificity, providing little information suitable for clinical risk stratification. Using six European cohorts, we provide a proof-of-concept that statistical learning approaches which simultaneously model all SNPs can generate robust and highly accurate predictive models of CD based on genome-wide SNP profiles. The high predictive capacity replicated both in cross-validation within each cohort (AUC of 0.87–0.89) and in independent replication across cohorts (AUC of 0.86–0.9), despite differences in ethnicity. The models explained 30–35% of disease variance and up to ∼43% of heritability. The GRS''s utility was assessed in different clinically relevant settings. Comparable to HLA typing, the GRS can be used to identify individuals without CD with ≥99.6% negative predictive value however, unlike HLA typing, fine-scale stratification of individuals into categories of higher-risk for CD can identify those that would benefit from more invasive and costly definitive testing. The GRS is flexible and its performance can be adapted to the clinical situation by adjusting the threshold cut-off. Despite explaining a minority of disease heritability, our findings indicate a genomic risk score provides clinically relevant information to improve upon current diagnostic pathways for CD and support further studies evaluating the clinical utility of this approach in CD and other complex diseases.