Depression among Parents Two to Six Years Following the Loss of a Child by Suicide: A Novel Prediction Model.

BACKGROUND: Parents who lose a child by suicide have elevated risks of depression. No clinical prediction tools exist to identify which suicide-bereaved parents will be particularly vulnerable; we aimed to create a prediction model for long-term depression for this purpose. METHOD: During 2009 and 2010 we collected data using a nationwide study-specific questionnaire among parents in Sweden who had lost a child aged 15-30 by suicide in years 2004-2007. Current depression was assessed with the Patient Health Questionnaire (PHQ-9) and a single question on antidepressant use. We considered 26 potential predictors assumed clinically assessable at the time of loss, including socio-economics, relationship status, history of psychological stress and morbidity, and suicide-related circumstances. We developed a novel prediction model using logistic regression with all subsets selection and stratified cross-validation. The model was assessed for classification performance and calibration, overall and stratified by time since loss. RESULTS: In total 666/915 (73%) participated. The model showed acceptable classification performance (adjusted area under the curve [AUC] = 0.720, 95% confidence interval [CI] 0.673-0.766), but performed classification best for those at shortest time since loss. Agreement between model-predicted and observed risks was fair, but with a tendency for underestimation and overestimation for individuals with shortest and longest time since loss, respectively. The identified predictors include female sex (odds ratio [OR] = 1.84); sick-leave (OR = 2.81) or unemployment (OR = 1.64); psychological premorbidity debuting during the last 10 years, before loss (OR = 3.64), or more than 10 years ago (OR = 4.96); suicide in biological relatives (OR = 1.54); with non-legal guardianship during the child's upbringing (OR = 0.48); and non-biological parenthood (OR = 0.22) found as protective. CONCLUSIONS: Our prediction model shows promising internal validity, but should be externally validated before application. Psychological premorbidity seems to be a prominent predictor of long-term depression among suicide-bereaved parents, and thus important for healthcare providers to assess

Acute central nervous system toxicity during treatment of pediatric acute lymphoblastic leukemia : phenotypes, risk factors and genotypes

Publisher Copyright: © 2022 Ferrata Storti Foundation Published under a CC BY-NC license.Central nervous system (CNS) toxicity is common at diagnosis and during treatment of pediatric acute lymphoblastic leukemia (ALL). We studied CNS toxicity in 1, 464 children aged 1.0-17.9 years, diagnosed with ALL and treated according to the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol. Genome-wide association studies, and a candidate single-nucleotide polymorphism (SNP; n=19) study were performed in 1, 166 patients. Findings were validated in an independent Australian cohort of children with ALL (n=797) in whom two phenotypes were evaluated: diverse CNS toxicities (n=103) and methotrexate-related CNS toxicity (n=48). In total, 135/1, 464 (9.2%) patients experienced CNS toxicity for a cumulative incidence of 8.7% (95% confidence interval: 7.31-10.20) at 12 months from diagnosis. Patients aged ≥10 years had a higher risk of CNS toxicity than had younger patients (16.3% vs. 7.4%; P<0.001). The most common CNS toxicities were posterior reversible encephalopathy syndrome (n=52, 43 with seizures), sinus venous thrombosis (n=28, 9 with seizures), and isolated seizures (n=16). The most significant SNP identified by the genome-wide association studies did not reach genomic significance (lowest P-value: 1.11x10-6), but several were annotated in genes regulating neuronal functions. In candidate SNP analysis, ATXN1 rs68082256, related to epilepsy, was associated with seizures in patients <10 years (P=0.01). ATXN1 rs68082256 was validated in the Australian cohort with diverse CNS toxicities (P=0.04). The role of ATXN1 as well as the novel SNP in neurotoxicity in pediatric ALL should be further explored.Peer reviewe

Optical Coherence Tomography Identifies Visual Pathway Involvement Earlier than Visual Function Tests in Children with MRI-Verified Optic Pathway Gliomas

This study investigates whether optical coherence tomography (OCT) could add useful information in the examination of children with optic pathway glioma (OPG) at high risk of developing vision loss. For this purpose, the relationship between ganglion cell-inner plexiform layer (GC-IPL) thickness and visual function, evaluated with tests of visual acuity (VA) and visual field (VF), as well as tumor site according to magnetic resonance imaging (MRI), were examined in a geographically defined group of children with OPG. Methods: Children aged &lt;18 years with OPG underwent ophthalmic examination including VA, VF (Zeiss HFA perimetry) and OCT imaging (Zeiss Cirrus HD-OCT). Results: Out of 51 patients included, 45 provided 77 eyes with MRI-verified OPG, and 19 patients provided 25 eyes without OPG. Significant correlations were found between GC-IPL, VF and VA (p &lt; 0.001). The GC-IPL pattern loss corresponded in 95% to VF defects and in 92% to MRI findings. Conclusions: Our study indicates that GC-IPL measures could serve as an early marker of vision-threatening changes related to OPG and as a valuable link between MRI and visual function tests. Thinning of GC-IPL and differences in topography between eyes are strong indicators of and predictive of vision loss related to OPG

Calibration.

<p>Calibration plots between model-predicted and observed (LOESS smoothed) probabilities, for (a) entire cohort, and (b) in each time-frame. The histograms at top and bottom show the distribution of model-predicted probabilities among depressed and non-depressed respectively.</p

Odds ratios from the multivariable prediction model for long-term depression.

<p>Odds ratios from the multivariable prediction model for long-term depression.</p

Classification performance.

<p>Receiver operating characteristic (ROC) curves, and corresponding areas under the curves (AUC) with 95% confidence intervals (CI), for (a) entire cohort, unadjusted and for 100 repetitions of ten-fold stratified cross-validation (SCV), and (b) for each of the four time-frames after cross-validation against a model derived from data in the other three time-frames. The ten-fold SCV adjusted values of AUC and CI limits are the corresponding mean values among the 100 repetitions, and the solid black line is a LOESS smoothed curve for the 100 SCV adjusted ROC curves outlined in gray.</p

Treatment-related mortality in relapsed childhood acute lymphoblastic leukemia

To access publisher's full text version of this article click on the hyperlink belowBACKGROUND: Treatment of relapsed childhood acute lymphoblastic leukemia (ALL) is particularly challenging due to the high treatment intensity needed to induce and sustain a second remission. To improve results, it is important to understand how treatment-related toxicity impacts survival. PROCEDURE: In this retrospective population-based study, we described the causes of death and estimated the risk for treatment-related mortality in patients with first relapse of childhood ALL in the Nordic Society of Paediatric Haematology and Oncology ALL-92 and ALL-2000 trials. RESULTS: Among the 483 patients who received relapse treatment with curative intent, we identified 52 patients (10.8%) who died of treatment-related causes. Twelve of these died before achieving second remission and 40 died in second remission. Infections were the cause of death in 38 patients (73.1%), predominantly bacterial infections during the chemotherapy phases of the relapse treatment. Viral infections were more common following hematopoietic stem cell transplantation (HSCT) in second remission. Independent risk factors for treatment-related mortality were as follows: high-risk stratification at relapse (hazard ratio [HR] 2.2; 95% confidence interval [CI] 1.3-3.9; P < 0.01), unfavorable cytogenetic aberrations (HR 3.4; 95% CI 1.3-9.2; P = 0.01), and HSCT (HR 4.64; 95% CI 2.17-9.92; P < 0.001). In contrast to previous findings, we did not observe any statistically significant sex or age differences. Interestingly, none of the 17 patients with Down syndrome died of treatment-related causes. CONCLUSIONS: Fatal treatment complications contribute significantly to the poor overall survival after relapse. Implementation of novel therapies with reduced toxicity and aggressive supportive care management are important to improve survival in relapsed childhood ALL

Autoimmune and Metabolic Diseases and the Risk of Early-Onset Colorectal Cancer, a Nationwide Nested Case-Control Study

Simple Summary Early onset of colorectal cancer (EOCRC) is increasing in developed countries. The aim was to investigate autoimmune and metabolic conditions as risk factors for EOCRC. We investigated preexisting autoimmune and metabolic diagnoses of 2626 EOCRC patients in Sweden, diagnosed in 2007-2016, together with 15,756 controls matched for birth year, sex, and county. Comorbid diagnoses were collected from the National Patient Register. A history of metabolic disease nearly doubled the incidence of EOCRC, and presence of inflammatory bowel disease (IBD) was associated with a sixfold increased incidence of EOCRC. Patients with both IBD and metabolic disease had a lower incidence of EOCRC compared with IBD patients without metabolic condition. Non-IBD autoimmune disease was not associated with an increased incidence of EOCRC. IBD and metabolic disease are risk factors for EOCRC and should be considered in screening guidelines. Incidence of early-onset (&amp;lt;50 years) colorectal cancer (EOCRC) is increasing in developed countries. The aim was to investigate autoimmune and metabolic conditions as risk factors for EOCRC. In a nationwide nested case-control study, we included all EOCRC cases in Sweden diagnosed during 2007-2016, together with controls, matched for birth year, sex, and county. Information on exposure of autoimmune or metabolic disease was collected from the National Patient Register and Prescribed Drugs Registry. Hazard ratios (HR) as measures of the association between EOCRC and the exposures were estimated using conditional logistic regression. In total, 2626 EOCRC patients and 15,756 controls were included. A history of metabolic disease nearly doubled the incidence hazard of EOCRC (HR 1.82, 95% CI 1.66-1.99). A sixfold increased incidence hazard of EOCRC (HR 5.98, 95% CI 4.78-7.48) was seen in those with inflammatory bowel disease (IBD), but the risk increment decreased in presence of concomitant metabolic disease (HR 3.65, 95% CI 2.57-5.19). Non-IBD autoimmune disease was not statistically significantly associated with EOCRC. IBD and metabolic disease are risk factors for EOCRC and should be considered in screening guidelines.Funding Agencies|Swedish Research Council; Swedish Cancer Society; Stockholm Cancer Society; Medical Research Council of Southeast Sweden; Region Stockholm (ALF project); Bengt Ihre Foundation; Mag-Tarmfonden</p

Seizures during treatment of childhood acute lymphoblastic leukemia: A population-based cohort study

Background Seizures are common in children with acute lymphoblastic leukemia (ALL). As ALL survival rates are improving, the challenge to minimize treatment related side effects and late sequelae rises. Here, we studied the frequency, timing, etiology and risk factors of seizures in ALL patients. Methods The study included children aged 1–17.9 years at diagnosis of B-cell-precursor and T cell ALL who were treated according to the Nordic Society of Pediatric Haematology and Oncology (NOPHO) ALL2008 protocol between 2008 and 2015. Detailed patient data were acquired from the NOPHO ALL2008 registry and by review of medical records. Results Seizures occurred in 81/1464 (5.5%) patients. The cumulative incidence of seizures at one months was 1.7% (95% CI: 1.2–2.5) and at one year 5.3% (95% CI 4.2–6.5%). Patients aged 10–17.9 years, those with T cell immunophenotype, CNS involvement, or high-risk induction with dexamethasone had higher risk for seizures in univariable analyses. Only age remained a risk factor in multivariable analyses (the cumulative incidence of seizures for patients 10–17.9 years old at one year was 9.0% (95% CI: 6.2–12.9)). Of the 81 patients with seizures, 43 had posterior reversible encephalopathy syndrome (PRES), 15 had isolated seizures, nine had sinus venous thrombosis (SVT), three had stroke-like syndrome, and 11 had other neurotoxicities. Epilepsy diagnosis was reported in totally 11 ALL survivors at last follow up. Conclusion Seizures are relatively common in ALL patients and occur most often in patients with PRES, SVT, or as an isolated symptom. Older children have higher risk of seizures.Peer reviewe