Years For Siblings Research Articles

A nationwide population-based longitudinal study mapping psychiatric disorders during lifetime in siblings to patients with bipolar disorder.

The aim was to map rates and cumulative incidences of psychiatric disorders during lifetime for siblings to patients with a diagnosis of bipolar disorder compared with the general population. Danish nationwide population-based longitudinal register linkage study including 13,923 unaffected siblings to 19,955 patients with bipolar disorder and 278,460 unaffected control individuals from the general population matched according to year of birth and sex. Follow-up covered 22years from 1995 to 2017. Rates of 'any psychiatric disorder' among siblings compared with control individuals were constantly around twofold increased throughout lifespan whereas there was a bimodal age distribution of hazard ratios of bipolar disorder, unipolar disorder and use of alcohol or psychoactive drugs with the highest hazard ratios up to age 20 and above 60years of age. Cumulative incidences from age 15years of any psychiatric disorder were 44.2% at age 80years for siblings versus 27.6% for control individuals and the corresponding numbers for bipolar disorder was 8.7% for siblings compared with 1.6% for control individuals. Strategies to prevent onset of psychiatric illness in individuals with a first-generation family history of bipolar disorder should not be limited to adolescence and early adulthood but should be lifetime, likely with differentiated age-specific strategies.

Late effects in survivors of acute leukemia treated with hematopoietic cell transplantation: a report from the Bone Marrow Transplant Survivor Study

The Bone Marrow Transplant Survivor Study is a retrospective cohort study in which participants who received HCT between 1974–1998 and survived for ≥2 yr completed a 255 item questionnaire on late effects occurring after HCT. There were 281 survivors with AML and 120 with ALL. Siblings of participants (n=319) were recruited for comparison. Median age at interview was 36.5 yr for survivors and 44yr for siblings. Median follow-up after HCT was 8.4 yr. Conditioning included TBI in 86% of AML and 100% of ALL subjects. The frequencies of late effects did not differ between ALL and AML survivors. Compared to siblings, survivors had a higher frequency of diabetes, hypothyroidism, osteoporosis, exercise induced shortness of breath (EISB), neurosensory impairments, and problems with balance, tremor or weakness. In multivariable analysis, the risk of these outcomes did not differ by diagnosis. Survivors after allogeneic HCT had higher odds of diabetes (odds ratio [OR] 3.9, p=0.04), osteoporosis (OR 3.1, p=0.05), abnormal sense of touch (OR 2.6, p=0.02) and to report their overall health as fair or poor (OR 2.2, p=0.03). Ongoing surveillance for these late effects and appropriate interventions are required to improve the health status of ALL and AML survivors after HCT.

Cardiovascular risk factors in adult survivors of pediatric cancer--a report from the childhood cancer survivor study.

Childhood cancer survivors are at higher risk of morbidity and mortality from cardiovascular disease compared with the general population. Eight thousand five hundred ninety-nine survivors (52% male) and 2,936 siblings (46% male) from the Childhood Cancer Survivor Study, a retrospectively ascertained, prospectively followed study of persons who survived 5 years after childhood cancer diagnosed from 1970 to 1986, were evaluated for body mass index of > or =30 kg/m(2) based on self-reported heights and weights and self-reported use of medications for hypertension, dyslipidemia, and impaired glucose metabolism. The presence of three or more of the above constituted Cardiovascular Risk Factor Cluster (CVRFC), a surrogate for Metabolic Syndrome. Survivors were more likely than siblings to take medications for hypertension [odds ratio (OR), 1.9; 95% confidence interval (95% CI), 1.6-2.2], dyslipidemia (OR, 1.6; 95% CI, 1.3-2.0) or diabetes (OR, 1.7; 95% CI, 1.2-2.3). Among these young adults (mean age of 32 years for survivors and 33 years for siblings), survivors were not more likely than siblings to be obese or have CVRFC. In a multivariable logistic regression analysis, factors associated with having CVRFC included older age at interview [> or =40 versus <30 years of age (OR, 8.2; 95% CI, 3.5-19.9)], exposure to total body irradiation (OR, 5.5; 95% CI, 1.5-15.8) or radiation to the chest and abdomen (OR, 2.3; 95% CI, 1.2-2.4), and physical inactivity (OR, 1.7; 95% CI, 1.1-2.6). Among adult survivors of pediatric cancer, older attained age, exposure to total body irradiation or abdominal plus chest radiation, and a sedentary life-style are associated with CVRFC.

Influence of familial factors on radiologic disease progression over two years in siblings with osteoarthritis at multiple sites: A prospective longitudinal cohort study

The contribution of genetics to osteoarthritis (OA) progression is not known. To gain more insight into whether familial factors play a role in disease progression of OA, we analyzed familial aggregation of radiologic OA progression in a study of sibling pairs (the Genetics, Arthrosis, and Progression [GARP] study). A total of 105 white probands and their 105 siblings with OA at multiple joint sites were included in a prospective cohort study. Radiologic progression of OA was defined as a 1-point score increase in total scores for severity of joint space narrowing (JSN) or osteophytes on standardized radiographs of the hands, knees, and hips obtained at baseline and after 2 years. Odds ratios were calculated for siblings and probands sharing radiologic disease progression. A total of 100 probands and 93 siblings were followed for 2 years (median age 60 years, 80% women). In 92 sibling pairs both the proband and sibling had complete radiographic followup. Radiologic progression of JSN and osteophytes was present in 47% and 42% of the probands and 34% and 37% of the siblings, respectively. The odds ratios (95% confidence intervals), adjusted for age, sex, and body mass index, of a sibling having radiologic progression if the proband had progression were 3.0 (1.2-7.8) for JSN progression and 1.5 (0.6-3.6) for osteophyte progression. A dose-response relationship was found between the amount of increase in JSN total scores among probands and the progression of JSN in siblings. Familial factors played a role in the radiologic progression of JSN over 2 years in patients with OA at multiple sites.

Diabetes, hypertension, and cardiovascular events in survivors of hematopoietic cell transplantation: a report from the bone marrow transplantation survivor study

AbstractWe ascertained the prevalence of self-reported late occurrence of diabetes, hypertension, and cardiovascular (CV) disease in 1089 hematopoietic cell transplantation (HCT) survivors who underwent HCT between 1974 and 1998, survived at least 2 years, and were not currently taking immunosuppressant agents and compared them with 383 sibling controls. All subjects completed a 255-item health questionnaire. The mean age at survey completion was 39.3 years for survivors and 38.6 years for siblings; mean follow-up was 8.6 years. Adjusting for age, sex, race, and body mass index (BMI), survivors of allogeneic HCT were 3.65 times (95% confidence interval [CI], 1.82-7.32) more likely to report diabetes than siblings and 2.06 times (95% CI, 1.39-3.04) more likely to report hypertension compared with siblings but did not report other CV outcomes with any greater frequency. Recipients of autologous HCTs were no more likely than siblings to report any of the outcomes studied. Allogeneic HCT survivors were also more likely to develop hypertension (odds ratio [OR] = 2.31; 95% CI, 1.45-3.67) than autologous recipients. Total body irradiation (TBI) exposure was associated with an increased risk of diabetes (OR = 3.42; 95% CI, 1.55-7.52). Thus, HCT survivors have a higher age- and BMI-adjusted risk of diabetes and hypertension, potentially leading to a higher than expected risk of CV events with age.

Visual screening for malignant melanoma: a cost-effectiveness analysis.

To evaluate the cost-effectiveness of various melanoma screening strategies proposed in the United States. We developed a computer simulation Markov model to evaluate alternative melanoma screening strategies. Hypothetical cohort of the general population and siblings of patients with melanoma. Intervention We considered the following 4 strategies: background screening only, and screening 1 time, every 2 years, and annually, all beginning at age 50 years. Prevalence, incidence, and mortality data were taken from the Surveillance, Epidemiology, and End Results Program. Sibling risk, recurrence rates, and treatment costs were taken from the literature. Outcomes included life expectancy, quality-adjusted life expectancy, and lifetime costs. Cost-effectiveness ratios were in dollars per quality-adjusted life year (US dollars/QALY) gained. In the general population, screening 1 time, every 2 years, and annually saved 1.6, 4.4, and 5.2 QALYs per 1000 persons screened, with incremental cost-effectiveness ratios of US dollars 10,100/QALY, US dollars 80,700/QALY, and US dollars 586,800/QALY, respectively. In siblings of patients with melanoma (relative risk, 2.24 compared with the general population), 1-time, every-2-years, and annual screenings saved 3.6, 9.8, and 11.4 QALYs per 1000 persons screened, with incremental cost-effectiveness ratios of US dollars 4000/QALY, US dollars 35,500/QALY, and US dollars 257,800/QALY, respectively. In higher risk siblings of patients with melanoma (relative risk, 5.56), screening was more cost-effective. Results were most sensitive to screening cost, melanoma progression rate, and specificity of visual screening. One-time melanoma screening of the general population older than 50 years is very cost-effective compared with other cancer screening programs in the United States. Screening every 2 years in siblings of patients with melanoma is also cost-effective.

Antibodies to Glutamic Acid Decarboxylase in Syrian and Jordanian Type 1 Diabetes Patients and their Siblings

Attempts to identify the earliest events in the autoimmune process in type I diabetes mellitus suggests the glutamic acid decarboxylase (GAD) is one of the first and most important autoantigens. We conducted this study to determine the prevalence of antibodies to glutamic acid decarboxylase (anti-GAD) in both Syrian and Jordanian children with Type I diabetes and their siblings. sera were obtained from 85 Syrian patients with type I diabetes (mean age 13.6 + 5.9 years), from 45 of their siblings (mean age 11 + 6.1 years), from 78 randomly selected Syrian control subjects (mean age 9.9 + 43 years), and from 95 Jordanian patients with type I diabetes (mean age 13.9 + 65 years), from 78 of their siblings (mean age 12.3 + 7.1 years), and from 100 randomly selected Jordanian control subjects (mean age 7.8 + 4.5 years). Sera were analyzed from anti-GAD using the enzyme linked immunosorbent assay (ELISA) technique. Prevalence of anti-GAD was 34.1% (29/85) in Syrian type I diabetes patients, 20% (9/45) in their siblings, 1.3% (1/78) in Syrian control subjects, 49.5% (47/95) in Jordanian type I diabetes patients, 23% (18/78) in their siblings, and 2% (2/100) in Jordanian control subjects. Differences between the Syrian and Jordanian type I diabetes groups and their siblings and controls were statistically significant. In patients with less than two years of diabetes duration, the frequency was 88.8% (16/18) for both groups. There was no correlation between sex and anti-GAD levels in their Syrian and Jordanian type I diabetes patients and their siblings. The positivity of anti-GAD tended to be more frequent at the age range of 5 to 8 years in siblings. Anti-GAD titers >90 ng/ml were found in 58.8% of type I diabetes patients and in 38% of siblings who were anti-GAD positive. Syria and Jordan have prevalence rates of anti-GAD among type I diabetes patients and their siblings that are among the highest reported in the world. Therefore, anti-GAD may be valuable as an early predictive marker for type I diabetes.

Insulin-dependent diabetic sibling pairs are concordant for sodium-hydrogen antiport activity

Insulin-dependent diabetic sibling pairs are concordant for sodium-hydrogen antiport activity. Recent findings of enhanced Na+/H+ antiport activity in cultured fibroblasts and immortalized lymphoblasts from type 1 diabetic patients with nephropathy support the view that a phenotypic or genotypic factor(s) underlies nephropathy risk. This study evaluated the kinetic properties of Na+/H+ antiporter in cultured fibroblasts from families with two siblings affected by type 1 (insulin-dependent) diabetes. Seventeen diabetic sibling pairs were studied. The age was 38 +/- 10 years (mean +/- SD) in probands, the first to develop diabetes, and 39 +/- 7 in siblings; the duration of diabetes was, by definition, longer in probands (24 +/- 12 vs. 17 +/- 8 years in siblings). Na+/H+ antiport activity was determined using a microfluorometric technique with the pH sensitive dye 2', 7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein in skin fibroblasts cultured for at least six passages. There were no significant differences between probands and siblings for the following parameters: glycated hemoglobin, 8.3 +/- 0.8% in probands and 8.6 +/- 1.4% in siblings; creatinine clearance, 103 +/- 24 ml/min/1.73 m2 in probands and 103 +/- 25 in siblings; albumin excretion rate, 6.8 (1 to 860) microgram/min (median and range) in probands and 4.9 (2 to 1334) in siblings. Intracellular pH and buffering capacity were superimposable in the sibling pairs. The Vmax for the antiport was 39.2 +/- 14.7 mmol/liter cell/min in probands and 40.3 +/- 17.6 in siblings. The internal pH for half-maximal activation (Km) and Hill coefficient was also similar in probands and siblings. There were correlations between probands and siblings in values for intracellular pH (r = 0.51, P < 0.04), Vmax (r = 0.84, P < 0.0001), and buffering capacity (r = 0.53, P < 0. 03). Glycated hemoglobin values over five years were not significantly correlated in the sibling pairs (r = 0.3, P > 0.1). Vmax was related with the albumin excretion rate (r = +0.49, P = 0. 005) and glycated hemoglobin (r = +0.41, P = 0.017) in the total cohort of sibling pairs. However, multiple regression analysis, using Vmax as the dependent variable, found no correlations between any of the subjects' clinical and demographic variables. Familial concordance for Na+/H+ antiport activity in long-term cultured skin fibroblasts from type 1 diabetic siblings suggests that at least some of the in vitro phenotypical characteristics of these cells are likely to be genetically determined and to be, at least in part, independent of in vivo metabolic control.

Sexual interactions among siblings and cousins: Experimentation or exploitation?

Incest by cousins has not been well documented compared with sibling incest. The purpose of this study was to describe the features of incest by cousins and siblings presenting to a sexual assault center and to differentiate cases of abusive behavior from normal sexual exploration. Four criteria were considered indicative of abusive behavior (1) age difference of ≥ 5 years between victim and perpetrator, (2) use of force, threat, or authority by abuser; (3) attempted penile penetration; and (4) documented injury in victim. Of 831 sexually abused children < 14 years of age evaluated for sexual assault complaints, 49 cases of cousin incest (5.9%) and 35 cases of sibling incest (4.2%) were identified. A total of 54 male cousins abused 8 boys and 41 girls; brothers abused 3 boys and 32 girls. The victims' median age was 5 years for cousins and 7 years for siblings. The perpetrators' mean age was 16.2 years for cousins and 15.5 years for siblings, with only 16 (19%) of all perpetrators being > 16 years old. Of the perpetrators, 66(79%) were ≥ 5 years older than their victims. All 18 victims with age differences of < 5 years met one or more of the other abusive criteria. A similar pattern of adolescent perpetrators having abusive sexual contact with young children was demonstrated by analysis of cousin incest and sibling incest in this study. Appropriate case management requires understanding of normal sexual experimentation and recognition of the abusive nature of these cases.