Influence of familial forms of inflammatory bowel disease on the use of immunosuppressants, biological agents, and surgery in the era of biological therapies. Results from the ENEIDA project.

BACKGROUND AND AIMS: Familial inflammatory bowel disease (IBD) history is a controversial prognostic factor in IBD. We aimed to evaluate the impact of a familial history of IBD on the use of medical and surgical treatments in the biological era. METHODS: Patients included in the prospectively maintained ENEIDA database and diagnosed with IBD after 2005 were included. Familial forms were defined as those cases with at least one first-degree relative diagnosed with IBD. Disease phenotype, the use of biological agents, or surgical treatments were the main outcomes. RESULTS: A total of 5263 patients [2627 Crohn's disease (CD); 2636 ulcerative colitis (UC)] were included, with a median follow-up of 31 months. Of these, 507 (10%) corresponded to familial forms. No clinical differences were observed between familial and sporadic IBD forms except a lower age at IBD diagnosis and a higher rate of males in familial forms of UC. In CD, the proportions of patients treated with thiopurines (54.4% vs 46.7%; P = .015) and survival time free of thiopurines (P = .009) were lower in familial forms. No differences were found regarding the use of biological agents. Concerning surgery, a higher rate of intestinal resections was observed in sporadic CD (14.8% vs 9.9%, P = .027). No differences were observed in UC. CONCLUSIONS: In the era of biological therapies, familial and sporadic forms of IBD show similar phenotypes and are managed medically in a similar way; whether these is due to lack of phenotypical differences or an effect of biological therapies is uncertain. What is already known on this topic: IBD's etiopathogenesis points to an interaction between environmental and genetic factors, being familial history a controversial prognostic factor. Biological agents use and need for surgery regarding familial or sporadic forms of IBDs present conflicting results. What this study adds: Familial and sporadic forms of IBD have similar phenotypes and are managed medically and surgically in a similar way. How this study might affect research, practice or policy: Familial aggregation should not be considered a factor associated with more aggressive disease.

Positive renal familial history in IgA nephropathy is associated with worse renal outcomes: a single-center longitudinal study.

BACKGROUND: IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Although most IgAN cases are sporadic, few show a familial aggregation. However, the prevalence and prognosis of IgAN individuals with positive familial history (FH) of renal disorders remains uncertain. To address these issues, we conducted a longitudinal observational study on a single-institution cohort of patients with biopsy-proven IgAN. METHODS: A total of 467 IgAN patients who underwent renal biopsy during 1994 to 2019 were ascertained to have positive- or negative-FH by history taking and were followed for an average of 8.9 years. We compared the clinical and pathological features of the two subgroups. The primary outcome, a composite of a hard endpoint (end-stage renal disease [ESRD]) and surrogate endpoint (a 50% or more reduction in the estimated glomerular filtration rate [eGFR] from baseline), was evaluated. To estimate the risk for progression to ESRD, a Cox proportional hazards analysis was performed for a subset of patients who underwent follow-up for > 2 years and had an eGFR > 30 mL/min/1.73 m2 at baseline (n = 389; observation, 8.7 years). RESULTS: Positive-FH subtype accounted for 11.6% (n = 54) of all IgAN patients. At baseline, there were no significant differences between the positive- and negative-FH subgroups regarding age, sex, comorbid disease, MEST-C score, observation period, and therapeutic interventions. However, the eGFR value at baselines was significantly lower in the positive-FH subgroup than in the negative-FH subgroup (P < 0.01). On multivariate analysis, positive-FH emerged an independent determinant of poorer renal outcomes (odds ratio, 2.31; 95% confidence interval, 1.10-4.85; P = 0.03), after adjusting for confounding factors. eGFR at follow-up was significantly lower in the positive-FH subgroup than in the negative-FH subgroup after adjustment for age and observation period. CONCLUSIONS: Positive-FH was found in 11.6% of all IgAN patients, consistent with the incidence seen in previous literature. A significantly lower eGFR at baseline and last follow-up and unfavorable renal outcomes in the positive-FH subgroup suggest that certain genetic risk factors predisposing to renal failure may exist in a fraction of our IgAN cohort. (331 words).

Prognosis and Clinical Characteristics of Dilated Cardiomyopathy With Family History via Pedigree Analysis.

BACKGROUND: The clinical characteristics and prognostic outcomes of dilated cardiomyopathy (DCM) with a familial history (FHx) via pedigree analysis are unclear.Methods and Results:We conducted a prospective observational study of 514 consecutive Japanese patients with DCM. FHx was defined as the presence of DCM in ≥1 family member within 2-degrees relative based on pedigree analysis. The primary endpoint was a composite of major cardiac events (sudden cardiac death and pump failure death). The prevalence of FHx was 7.4% (n=38). During a median follow-up of 3.6 years, 77 (15%) patients experienced a major cardiac event. Multivariable Cox regression analysis identified FHx as independently associated with major cardiac events (hazard ratio [HR] 4.32; 95% confidence interval [CI], 2.04-9.19; P<0.001) compared with conventional risk factors such as age, QRS duration, and left ventricular volume. In the propensity score-matched cohort (n=38 each), the FHx group had a significantly higher incidence of major cardiac events (HR, 4.48; 95% CI, 1.25-16.13; P=0.022). In addition, the FHx group had a higher prevalence of a diffuse late gadolinium enhancement (LGE) pattern than the no-FHx group (32% vs. 17%, P=0.022). CONCLUSIONS: DCM patients with FHx had a worse prognosis, which was associated with a higher prevalence of a diffuse LGE pattern, than patients without FHx.

Adolescent Endometriosis: Report of a Series of 55 Cases With a Focus on Clinical Presentation and Long-Term Issues.

STUDY OBJECTIVE: To report the clinical presentation and long-term issues of adolescent endometriosis. DESIGN: Retrospective cohort study. SETTING: Single private clinical center, Bordeaux, France. PATIENTS: Adolescents with a confirmed diagnosis of endometriosis. INTERVENTIONS: Surgical excision or ablation or lesions performed at laparoscopy. MEASUREMENTS AND MAIN RESULTS: Fifty-five adolescents, ages from 12 to 19 years (mean age 17.8), who were diagnosed with endometriosis from March 1998 to April 2013 were included in the study. Pain of various types was the leading symptom in all patients, except 2. Twenty-three patients had an adnexal mass identified preoperatively, and 5 had an associated infertility issue at the time of diagnostic laparoscopy. Four patients had an associated genital malformation. Fifty-one percent of the patients had a history of appendectomy. A familial history of endometriosis was reported by 19 patients (34.5%), with a first-degree relative affected in 14 cases (25.45%), and 47.3% of patients were smoking at least 5 cigarettes a day. Superficial implants was encountered in 31 cases (56.4%), endometriomas in 18 cases (32.72%), and deep infiltrating endometriosis (DIE) in 6 cases (10.90%). Sixty percent of patients were scored as stages I to II and 40% as stages III to IV. Five patients were lost to follow-up, and 37 had a follow-up ranging from 36 to 315 months (mean follow-up 125.5 months). Among the 50 patients not lost to follow-up, 13 (26%) had either no pain, or improved and had acceptable pain with medical treatment. Seventeen patients of the 50 adolescents not lost to follow-up (34%) underwent a repeat laparoscopy. A subsequent laparoscopic and/or magnetic resonance imaging scan was performed in 35 patients because of persistent pain. Among these, there was 12 endometriomas (7 recurrences) and 12 DIEs (3 recurrences), giving recurrence rates for endometriomas and DIEs of 36.84% and 50%, respectively. During the study, 18 patients wished to have a child. Thirteen had a delivery (72.2%), and 9 pregnancies occurred in patients who initially presented with stage I to II endometriosis. Of the 11 patients who had subfertility, 6 successfully conceived (54.5%). CONCLUSIONS: Adolescent endometriosis is not a rare condition. In our study a familial history was reported in more than one-third of patients. Among those patients treated for DIE, there was a trend for higher rates of recurrences (symptoms or lesions) that required repeat laparoscopy. However, the impact on subsequent fertility appeared to have been limited.

Facial palsy in Melkersson-Rosenthal syndrome and Bell's palsy: familial history and recurrence tendency.

OBJECTIVE: The aim of this study was to compare genetic predilection and recurrence tendency between facial palsy in Melkersson-Rosenthal syndrome (MRS) and Bell's palsy METHODS: We carried out an investigation on patients with facial palsy in MRS and those with Bell's palsy who visited the outpatient department in our hospital between February 2009 and February 2013. They were asked about familial history and whether it was the first episode, with the results recorded and compared. RESULTS: There were 16 patients with facial palsy in MRS and 860 patients with Bell's palsy involved in the study. Familial history was positive in 5 of 16 patients (31.3%) with facial palsy in MRS and 56 of 860 patients (6.5%) with Bell's palsy (P < .01). Twelve of 16 cases (75%) with facial palsy in MRS and 88 of 860 cases (10.2%) with Bell's palsy had a history of facial palsy in the past (P < .01). CONCLUSION: Compared to Bell's palsy, facial palsy in MRS has an obvious genetic predilection and recurrence tendency.

Family studies: A useful tool to better understand spondyloarthritis.

Spondyloarthritis (SpA) is an immune-mediated disease characterized by a high heritability, reflected by strong familial aggregation. Therefore, family studies are a powerful tool for elucidating the genetic basis of SpA. First, they helped to assess the relative importance of genetic and environmental factors and established the polygenic character of the disease. Family-based designs were also historically used to identify genetic factors of susceptibility through linkage analyses. In SpA, three whole-genome linkage studies were published in the 1990's, unfortunately with few consistent results. After having been put aside for several years in favour of case-control GWAS, there is a renewed interest in family-based designs in particular to detect rare variant associations. This review aims at summarizing what family studies have brought to the field of SpA genetics, from genetic epidemiology studies to the most recent rare variant analyses. It also highlights the potential interest of family history of SpA to help diagnosis and detection of patients at high risk to develop the disease.

Identifying childhood leukemia with an excess of hematological malignancies in first-degree relatives in Brazil.

Background: Familial aggregation in childhood leukemia is associated with epidemiological and genomic factors. Albeit epidemiological studies on the familial history of hematological malignancies (FHHMs) are scarce, genome-wide studies have identified inherited gene variants associated with leukemia risk. We revisited a dataset of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) patients to explore the familial aggregation of malignancies among their relatives. Methods: A series of 5,878 childhood leukemia (≤21 years of age) from the EMiLI study (2000-2019) were assessed. Lack of well-documented familial history of cancer (FHC) and 670 cases associated with genetic phenotypic syndromes were excluded. Leukemia subtypes were established according to World Health Organization recommendations. Logistic regression-derived odds ratios (ORs) and 95% confidence intervals (CIs) were performed and adjusted by age as a continuous variable, where ALL was the reference group for AML and conversely. The pedigree of 18 families with excess hematological malignancy was constructed. Results: FHC was identified in 472 of 3,618 eligible cases (13%). Ninety-six of the 472 patients (20.3%) had an occurrence of FHHMs among relatives. Overall, FHC was significantly associated with AML (OR, 1.36; 95% CI, 1.01-1.82; p = 0.040). Regarding the first-degree relatives, the OR, 2.92 95% CI,1.57-5.42 and the adjOR, 1.16 (1.03-1.30; p0.001) were found for FHC and FHHM, respectively. Conclusion: Our findings confirmed that AML subtypes presented a significant association with hematological malignancies in first-degree relatives. Genomic studies are needed to identify germline mutations that significantly increase the risk of developing myeloid malignancies in Brazil.

Predictors of future suicide attempts in individuals with high suicide risk admitted to an acute psychiatry suicide intervention unit in India. A survival analysis study.

OBJECTIVE: Determination of suicide vulnerability remains challenging in mental illness. Variability in risk factors identified compound its poor predictability. Longitudinal studies, offering more reliable indices of risk, from developing countries are conspicuously limited. Furthermore, research advances allude to inherent vulnerability. This study, the first of its kind from India, consequently aimed to delineate factors influencing subsequent attempts in mental illness and acute suicidality. METHOD: Baseline and follow-up information (up to five years) was obtained from medical records of individuals (n = 130) with acute suicidality [recent attempt (first attempt/ reattempt) and high-risk ideators]. Variables were compared between individuals with, and without subsequent suicide attempts. Time to attempt and factors influencing the same was determined using survival analysis, and Cox proportional hazard for estimating the likelihood of a subsequent suicide attempt. RESULTS: Median duration of follow up of the sample (n = 130) was 23 months. The sample comprised of individuals with a recent attempt (first-time attempt), recent reattempt and recent high-risk ideators. Subsequent suicide attempts were noted in 30 (23.1 %) patients. Baseline sociodemographic and clinical variables, including suicidality, could not differentiate individuals with a subsequent suicide attempt. Survival analysis indicated that 65 % of subsequent attempts occurred within 9 months of discharge. Family history of suicide and the presence of impulsive-aggressive traits were associated with both, reduced survival time and overall increased risk of a subsequent suicide attempt. CONCLUSION: This study delineates both, the time frame associated with greatest risk, as well as individuals most likely to reattempt suicide. It thereby offers insights into potential windows of opportunity to mitigate prospective suicide risk. Strategies such as enhanced after-care and integrating specific interventions to attenuate impulsive-aggressive behaviors could be a focus to prevent future attempts, thereby decreasing rates of suicide amongst those with mental illness. Furthermore, the findings of this study reaffirm the role of factors that independently confer vulnerability to suicide. Traversing noted regional variations, the findings importantly reinforce the distinct pathophysiological underpinnings of suicide in mental illness.

Clinical characteristics of familial schizophrenia.

INTRODUCTION: A family history of psychiatric disorders is one of the strongest risk factors for schizophrenia. The characteristics of patients with a family history of psychiatric disorders have not been systematically evaluated. METHODS: This multicenter study (26 centers, 2425 cases) was performed in a Chinese population to examine the sociodemographic and clinical characteristics of schizophrenia patients with a family history of psychotic disorders in comparison with those of patients with sporadic schizophrenia. RESULTS: Nineteen percent of patients had a family history of mental disease. Multiple logistic regression analysis revealed that ≥4 hospitalizations (OR = 1.78, P = .004), tobacco dependence (OR = 1.48, P = .006), alcohol dependence (OR = 1.74, P = .013), and physical illness (OR = 1.89, P = .001) were independently and significantly associated with a family history of mental disease. CONCLUSION: Patients with a family history of mental disorders present different demographics and clinical features than patients without a family history of psychiatric disorders.

Feasibility and cost of FH cascade screening in Belgium (BEL-CASCADE) including a novel rapid rule-out strategy.

BACKGROUND: Familial hypercholesterolaemia (FH) is underdiagnosed in most countries. We report our first experience from a national pilot project of cascade screening in relatives of FH patients. METHODOLOGY: Participating specialists recruited consecutive index patients (IP) with Dutch Lipid Clinic Network (DLCN) score ≥6. After informed consent, the relatives were visited by the nurses to collect relevant clinical data and perform blood sampling for lipid profile measurement. FH diagnosis in the relatives was based on the DLCN and/or MEDPED FH (Make-Early-Diagnosis-to-Prevent-Early-Deaths-in-FH) criteria. RESULTS: In a period of 18 months, a total of 127 IP (90 with definite FH and 37 with probable FH) were enrolled in 15 centres. Out of the 270 relatives visited by the nurses, 105 were suspected of having FH: 31 with DCLN score >8, 33 with DLCN score 5-8 and 41 with MEDPED FH criteria. In a post-hoc analysis, another set of MEDPED FH criteria established in the Netherlands and adapted to Belgium allowed to detect FH in 51 additional relatives. CONCLUSION: In a country with no national FH screening program, our pilot project demonstrated that implementing a simple phenotypical FH cascade screening strategy using the collaboration of motivated specialists and two nurses, allowed to diagnose FH in 127 index patients and an additional 105 of their relatives over the two-year period. Newly developed MEDPED FH cut-offs, easily applicable by a nurse with a single blood sample, might further improve the sensitivity of detecting FH within families.

Cost-effectiveness analysis of alternative colorectal cancer screening strategies in high-risk individuals.

BACKGROUND AND AIMS: Current guidelines recommend colonoscopy every 3-5 years for colorectal cancer (CRC) screening of individuals with a familial history of CRC. The objective of this study was to compare the cost effectiveness of screening alternatives in this population. METHODS: Eight screening strategies were compared with no screening: fecal immunochemical test (FIT), Stool DNA and blood-based screening every 2 years, colonoscopy, computed tomography colonography, colon capsules, and sigmoidoscopy every 5 years, and colonoscopy at 45 years followed, if negative, by FIT every 2 years. Screening test and procedures performance were obtained from the literature. A microsimulation model reproducing the natural history of CRC was used to estimate the cost (€2018) and effectiveness [quality-adjusted life-years (QALYs)] of each strategy. A lifetime horizon was used. Costs and effectiveness were discounted at 3.5% annually. RESULTS: Compared with no screening, colonoscopy and sigmoidoscopy at a 30% uptake were the most effective strategy (46.3 and 43.9 QALY/1000). FIT at a 30 µg/g threshold with 30% uptake was only half as effective (25.7 QALY). Colonoscopy was associated with a cost of €484,000 per 1000 individuals whereas sigmoidoscopy and FIT were associated with much lower costs (€123,610 and €66,860). Incremental cost-effectiveness rate for FIT and sigmoidoscopy were €2600/QALY (versus no screening) and €3100/QALY (versus FIT), respectively, whereas it was €150,000/QALY for colonoscopy (versus sigmoidoscopy). With a lower threshold (10 µg/g) and a higher uptake of 45%, FIT was more effective and less costly than colonoscopy at a 30% uptake and was associated with an incremental cost-effectiveness ratio (ICER) of €4240/QALY versus no screening. CONCLUSION: At 30% uptake, current screening is the most effective screening strategy for high-risk individuals but is associated with a high ICER. Sigmoidoscopy and FIT at lower thresholds (10 µg/g) and a higher uptake should be given consideration as cost-effective alternatives. PLAIN LANGUAGE SUMMARY: Cost-effectiveness analysis of colorectal cancer screening strategies in high-risk individuals Fecal occult blood testing with an immunochemical test (FIT) is generally considered as the most cost-effective alternative in colorectal cancer screening programs for average risk individuals without family history.Current screening guidelines for high-risk individuals with familial history recommend colonoscopy every 3-5 years.Colonoscopy every 3-5 years for individuals with familial history is the most effective strategy but is associated with a high incremental cost-effectiveness ratio.Compared with colonoscopy, if screening based on FIT is associated with a higher participation rate, it can achieve a similar effectiveness at a lower cost.

Tracking Familial History of Reading and Math Difficulties in Children's Academic Outcomes.

The current study aimed to investigate the extent to which familial history of reading and math difficulties have an impact on children's academic outcomes within a 3-year longitudinal study, which evaluated their core reading and math skills after first (N = 198; 53% girls) and second grades (N = 166), as well as performance on complex academic tasks after second and third grades (N = 148). At baseline, parents were asked to complete the Adult Reading History Questionnaire (ARHQ) and its adaption, Adult Math History Questionnaire (AMHQ), to index familial history of reading and math difficulties, respectively. Preliminary findings established the psychometric properties of the AMHQ, suggesting that it is a reliable and valid scale. Correlation analyses indicated that the ARHQ was negatively associated with children's reading skills, whereas the AMHQ was negatively related to math outcomes. Path results revealed that the ARHQ predicted children's performance on complex reading tasks indirectly via their core reading skills, and the AMHQ was linked to complex math outcomes indirectly via core math abilities. The ARHQ was also found to be negatively correlated with measures of children's math performance, with path findings suggesting that these relations were indirectly explained by differences in their core reading skills. These results suggest that assessing familial risk for academic difficulties may be crucial to understanding comorbid etiological and developmental associations between reading and math differences.

Generalization of memory-related brain function in asymptomatic older women with a family history of late onset Alzheimer's Disease: Results from the PREVENT-AD Cohort.

Late-onset Alzheimer's disease (AD) disproportionately affects women compared to men. Episodic memory decline is one of the earliest and most pronounced deficits observed in AD. However, it remains unclear whether sex influences episodic memory-related brain function in cognitively intact older adults at risk of developing AD. Here we used task-based multivariate partial least squares analysis to examine sex differences in episodic memory-related brain activity and brain activity-behavior correlations in a matched sample of cognitively intact older women and men with a family history of AD from the PREVENT-AD cohort study in Montreal, Canada (Mage=63.03±3.78; Meducation=15.41±3.40). We observed sex differences in task-related brain activity and brain activity-behavior correlations during the encoding of object-location associative memories and object-only item memory, and the retrieval of object only item memories. Our findings suggest a generalization of episodic memory-related brain activation and performance in women compared to men. Follow up analyses should test for sex differences in the relationship between brain activity patterns and performance longitudinally, in association with risk factors for AD development. This article is part of the Virtual Special Issue titled COGNITIVE NEUROSCIENCE OF HEALTHY AND PATHOLOGICAL AGING. The full issue can be found on ScienceDirect at https://www.sciencedirect.com/journal/neurobiology-of-aging/special-issue/105379XPWJP.

A case of lip squamous cell carcinoma with a familial history of Xeroderma pigmentosum.

Xeroderma pigmentosum is an orphan hereditary photosensitive human disorder that is recognized by the development of skin lesions in sun-exposed regions of the body due to severe photosensitivity. Patients with this condition have an abnormal DNA repair process due to a genetic mutation. Xeroderma pigmentosum is considered as a risk factor of cancer since the affected population may develop various cutaneous cancers including both melanoma and non-melanoma cutaneous malignancies even at a younger age than the general population. This risk concerns also asymptomatic heterozygote individuals. Here, we present a case of 46 years old man with a familial history of Xeroderma pigmentosum who developed a microscopically confirmed squamous cell carcinoma of the lip.

Hypertension in a mountainous province of Vietnam: prevalence and risk factors.

BACKGROUND: Hypertension (HTN) significantly contributes to global disease burden, and its prevalence varies amongst different countries and regions. This work is aimed to characterize the hypertensive prevalence and identify risk factors for HTN among the residents in five locations (four communes and one town) of Moc Chau district (Son La province, Vietnam). METHODS: A cross-sectional study with a cross-sectional methodology was done in selected places from August 2018 to December 2018. We interviewed 197 participants aged equal to or more than 18 years old and measured their blood pressure (BP). Univariate and multivariate logistic regression were applied. RESULTS: The overall HTN prevalence of 30.0% was recorded. The differences of HTN prevalence rates were seen by several characters including age groups (p <0.001), accompanying disease (p <0.001) and alcohol drinking (p <0.05). Factors independently associated with hypertension were age (ORs: 3.1 [1.1-9.1]; 6.1 [1.7-22.3]), much salty consumption (OR: 2.6 [1.1-6.6]), alcohol use (OR: 3.1 [1.2-8.1]), HTN familial history (OR: 4.2 [1.3-13.3]) and at least one suffering disease (OR: 5.2 [2.1-12.7]). CONCLUSIONS: Thus, this study highlighted the high overall HTN prevalence in the Vietnam Northwestern region. Significant differences of HTN rate were observed among several characteristics such as age groups, accompanying disease and alcohol drinking. Age group, much salty consumption, alcohol use, hypertension familial history and at least one suffering disease were risk factors for HTN in study group.

APOE4 Status is Related to Differences in Memory-Related Brain Function in Asymptomatic Older Adults with Family History of Alzheimer's Disease: Baseline Analysis of the PREVENT-AD Task Functional MRI Dataset.

BACKGROUND: Episodic memory decline is one of the earliest symptoms of late-onset Alzheimer's disease (AD). Older adults with the apolipoprotein E ɛ4 (+APOE4) genetic risk factor for AD may exhibit altered patterns of memory-related brain activity years prior to initial symptom onset. OBJECTIVE: Here we report the baseline episodic memory task functional MRI results from the PRe-symptomatic EValuation of Experimental or Novel Treatments for Alzheimer's Disease cohort in Montreal, Canada, in which 327 healthy older adults were scanned within 15 years of their parent's conversion to AD. METHODS: Volunteers were scanned as they encoded and retrieved object-location spatial source associations. The task was designed to discriminate between brain activity related to spatial source recollection and object-only (recognition) memory. We used multivariate partial least squares (PLS) to test the hypothesis that +APOE4 adults with family history of AD would exhibit altered patterns of brain activity in the recollection-related memory network, comprised of medial frontal, parietal, and medial temporal cortices, compared to APOE4 non-carriers (-APOE4). We also examined group differences in the correlation between event-related brain activity and memory performance. RESULTS: We found group similarities in memory performance and in task-related brain activity in the recollection network, but differences in brain activity-behavior correlations in ventral occipito-temporal, medial temporal, and medial prefrontal cortices during episodic encoding. CONCLUSION: These findings are consistent with previous literature on the influence of APOE4 on brain activity and provide new perspective on potential gene-based differences in brain-behavior relationships in people with first-degree family history of AD.

Pediatric multiple sclerosis and its familial recurrence: A population based study (1999-2017).

BACKGROUND: The Pediatric onset multiple sclerosis (POMS) prevalence is increasing worldwide accounting for around 3 to 10% of MS cases. The risk of POMS is supposed to reflect a complex interaction between environmental and genetic risk factors that may occur during the childhood, adolescent, or post-pubertal years. OBJECTIVE: The present study aimed at estimating the prevalence of POMS and assessing the epidemiology of familial recurrence of POMS in Tehran. METHOD: A retrospective population based cross-sectional study was designed from 1999 to 2017. The baseline characteristic information was collected from MS patient's ≤18 years old (y/o). Pearson's chi-square test and logistic regression were used to analyze the relationship among variables and estimate the odds ratio (OR) via SPSS software, version 23. RESULTS: A total of 1937 POMS patients (77.80% female and 22.20% male patients) participated in the study. The point prevalence of POMS was 16.20 per 100,000 populations in 2017. Mean age at disease onset was 15.96 ± 2.28 y/o. The female to male ratio was 2.02:1 in pre-pubertal cases (3-12 y/o), but it increased to 3.69:1 in 13-18 y/o age groups (P value = 0.001, OR = 1.82; 95% CI = 1.27-2.26). There were 288 (14.9%) cases with positive familial history of MS. The strongest association between MS risk and positive familial history was observed in second degree relatives who presented MS (P value = 0.046, OR = 1.74; 95%CI = 1.01-3.01). A significant association was observed among maternal second degree relatives with POMS (P value = 0.018, OR = 2.27; 95%CI = 1.15-4.47). CONCLUSION: In comparison to other large studies, the prevalence of POMS was high in the data collected from Tehran. POMS risk is higher among females and the sex ratio increases after puberty. We found a significant association between POMS risk and familial history in maternal second degree relatives. Further studies of POMS epidemiology might yield greater understanding of the natural history of this disease.

Familial history of reading difficulty is associated with diffused bilateral brain activation during reading and greater association with visual attention abilities.

Reading difficulty (RD; or dyslexia) is a heritable condition characterized by slow, inaccurate reading accompanied by executive dysfunction, specifically with respect to visual attention. The current study was designed to examine the effect of familial history of RD on the relationship between reading and visual attention abilities in children with RD using a functional MRI reading task. Seventy-one children with RD participated in the study. Based on parental reports of the existence of RD in one or both of each child's parents, children with RD were divided into two groups: (1) those with a familial history of RD and (2) those without a familial history of RD. Reading and visual attention measures were collected from all participants. Functional MRI data during word reading was acquired in 30 participants of the entire cohort. Children with or without a familial history of RD demonstrated below-average reading and visual attention scores, with greater interaction between these measures in the group with a familial history of RD. Greater bilateral and diffused activation during word reading also were found in this group. We suggest that a familial history of RD is related to greater association between lower reading abilities and visual attention abilities. Parental history of RD therefore may be an important preschool screener (before reading age) to prompt early intervention focused on executive functions and reading-related skills.

Influence of a Positive Family History on the Clinical Course of Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Previous studies on the difference in phenotypes and disease course between familial and sporadic inflammatory bowel disease (IBD) have been controversial, although family history is considered to increase the risk of developing IBD. METHODS: The influence of family history on phenotype and disease course of IBD was analysed in 2805 Korean patients with Crohn's disease (CD) and 3266 with ulcerative colitis (UC). Familial IBD was defined as the existence of one or more first-, second- and/or third-degree relatives affected with CD or UC. RESULTS: A positive family history of IBD was noted in 191 patients with CD (6.8%) and 212 patients with UC (6.5%). In the patients with CD, the probability of anti-TNF use was higher in the familial cases than in the sporadic cases (56.3 vs 43.4%, respectively, at 10 years, p = 0.019). When analysed after excluding patients who had undergone intestinal resection within 1 year of diagnosis, the cumulative probability of intestinal resection was higher in the familial cases than in the sporadic cases (55.0 vs 32.2%, respectively, at 10 years; p = 0.007). In multivariate analysis, family history was an independent risk factor for the time to first intestinal resection in patients with CD (hazard ratio: 1.61, 95% confidence interval: 1.13-2.29; p = 0.009). In patients with UC, younger age at diagnosis and more females were observed in the familial cases (p < 0.001). CONCLUSIONS: The present study suggests the possibility of a more aggressive clinical course of CD in familial compared with sporadic cases.

Seroepidemiology of hepatitis B virus infection and impact of vaccination.

AIM: To investigate hepatitis B virus (HBV) prevalence in the general population in China. METHODS: A total of 148931 individuals were investigated by multistage random sampling in Eastern China. Data were collected on demographics and hepatitis B vaccination history, and serum was tested for hepatitis B surface antigen (HBsAg) by ELISA. RESULTS: A total of 11469 participants (7.70%, 95%CI: 7.57%-7.84%) were positive for HBsAg. HBsAg prevalence was 0.77% among children < 5 years old but increased progressively from adolescents (1.40%-2.55%) to adults (5.69%-11.22%). A decrease in HBsAg prevalence was strongly associated with vaccination and familial history of HBV among both children and adult groups. Meanwhile, HBsAg risk in adults was associated with invasive testing and sharing needles. The HBV immunization rate among participants aged < 20 years was 93.30% (95%CI: 93.01%-93.58%). Significant difference in HBsAg prevalence appeared between vaccinated and unvaccinated participants (3.59% vs 10.22%). CONCLUSION: Although the national goal of HBsAg prevalence < 1% among children < 5 years old has been reached, immunization programs should be maintained to prevent resurgence.