Impact of Prosigna test on adjuvant treatment decision in lymph node-negative early breast cancer-a prospective national multicentre study (EMIT-1).

BACKGROUND: EMIT-1 is a national, observational, single-arm trial designed to assess the value of the Prosigna, Prediction Analysis of Microarray using the 50 gene classifier (PAM50)/Risk of Recurrence (ROR), test as a routine diagnostic tool, examining its impact on adjuvant treatment decisions, clinical outcomes, side-effects and cost-effectiveness. Here we present the impact on treatment decisions. PATIENTS AND METHODS: Patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative pT1-pT2 lymph node-negative early breast cancer (EBC) were included. The Prosigna test and standard histopathology assessments were carried out. Clinicians' treatment decisions were recorded before (pre-Prosigna) and after (post-Prosigna) the Prosigna test results were disclosed. RESULTS: Of 2217 patients included, 2178 had conclusive Prosigna results. The pre-Prosigna treatment decisions were: no systemic treatment (NT) in 27% of patients, endocrine treatment alone (ET) in 38% and chemotherapy (CT) followed by ET (CT + ET) in 35%. Post-Prosigna treatment decisions were 25% NT, 51% ET and 24% CT + ET, respectively. Adjuvant treatment changed in 28% of patients, including 21% change in CT use. Among patients assigned to CT + ET pre-Prosigna, 45% were de-escalated to ET post-Prosigna. Of patients assigned to ET, 12% were escalated to CT + ET and 8% were de-escalated to NT; of those assigned to NT, 18% were escalated to ET/CT + ET. CT was more frequently recommended for patients aged ≤50 years. In the subgroup with pT1c-pT2 G2 and intermediate Ki67 (0.5-1.5× local laboratory median Ki67 score), the pre-Prosigna CT treatment decision varied widely across hospitals (3%-51%). Post-Prosigna, the variability of CT use was markedly reduced (8%-24%). The correlation between Ki67 and ROR score within this subgroup was poor (r = 0.25-0.39). The median ROR score increased by increasing histological grade, but the ROR score ranges were wide (for G1 0-79, G2 0-90, G3 16-94). CONCLUSION: The Prosigna test result changed adjuvant treatment decisions in all EBC clinical risk groups, markedly decreased the CT use for patients categorized as higher clinical risk pre-Prosigna and reduced treatment decision discrepancies between hospitals.

Personality and risk of hospital diagnosed mental disorder: a 35 years' prospective study.

PURPOSE: The present study examined the prospective association of neuroticism, extraversion and psychoticism with risk of hospital diagnosed mental disorder, examining intelligence as a potential confounder of this association. METHODS: A total of 1118 Danish men and women completed the Eysenck personality questionnaire at the mean age of 27 years. Information on psychiatric diagnoses was obtained by linking the study population to the national Danish psychiatric registers, and risk of diagnoses associated with each personality trait was examined using multiple Cox regression in models including the three personality traits unadjusted and adjusted for intelligence. Participants with diagnosis from a psychiatric department prior to the personality assessment were excluded. RESULTS: In total, 122 participants were diagnosed with a mental disorder during follow-up. Neuroticism significantly predicted risk of anxiety-, adjustment-, personality- and alcohol and substance abuse diagnoses. Extraversion did not significantly predict any diagnosis type, while psychoticism predicted a combined category of mood and anxiety diagnoses. Despite intelligence being a significant predictor of the majority of the included diagnoses, adjusting for intelligence did not substantially influence any trait-disorder associations. CONCLUSION: The results confirm high neuroticism as a prospective vulnerability factor for mental disorder and indicate high psychoticism to be a potential risk factor for mood and anxiety disorders. These associations are not confounded by intelligence.

Traumatic brain injury and risk of dementia at different levels of cognitive ability and education.

BACKGROUND AND PURPOSE: The effect of cognitive resources on the risk of dementia following traumatic brain injury (TBI) has hardly been investigated. The aim of this study was to examine the influence of cognitive ability and education in young adulthood on the association between TBI and dementia in men. METHOD: A cohort of 658 447 Danish men, born between 1939 and 1959, who had been cognitively assessed at conscription were followed in the Danish National Patient Registry and the National Prescription Registry from 1977 through 2016 for incident TBI and dementia. The association between TBI and dementia was analysed using Cox proportional regression. RESULTS: During follow-up, 29 781(4.5%) men experienced TBI and 10 971(1.7%) developed dementia. TBI was associated with a higher risk of subsequent dementia after adjustment for cognitive ability, education and psychiatric comorbidity. The risk estimate was higher for early-onset dementia (hazard ratio 5.49, 95% confidence interval 4.97-6.06) than for dementia diagnosed after age 60 years (hazard ratio 2.85, 95% confidence interval 2.63-3.10). The association was slightly stronger in men with the highest cognitive scores or education than amongst those at lower levels. CONCLUSION: Young adult cognitive ability did not explain a relatively strong association between TBI and dementia, and no evidence was found that cognitive ability or education was protective.

Grip Work Measurement with the Jamar Dynamometer: Validation of a Simple Equation for Clinical Use.

OBJECTIVES: Previously, we developed and validated an easy test to measure muscle fatigability during sustained maximal handgrip contraction in older persons using a Martin Vigorimeter device. This study aimed at validating the equation to estimate grip work (GW) during sustained maximal handgrip contraction, by monitoring continuously the grip strength (GS) decay using a Jamar Dynamometer-like (JD) device. DESIGN: Cross sectional, explorative study. SETTING: Data collection took place at The National Research Centre for the Working Environment in Copenhagen, Denmark. PARTICIPANTS: 962 subjects, belonging to a subgroup of the Copenhagen Aging and Midlife Biobank, were enrolled. METHODS: GS was recorded continuously during sustained maximal contraction until it dropped to 50% of its maximum and fatigue resistance (FR, time to fatigue) was noted. GW, area under the force-time curve, was compared to its estimate which was calculated as GWestimated=GSmax*0.75*FR. RESULTS: Excellent correlation was found between GWestimated and GWmeasured (R²=0.98 p<0.001). The equation slightly overestimated GW by 6.04 kg*s (95% CI[-0.08, 12.15]) with a coefficient of variation method error of 6%. CONCLUSION: GW estimation is a valid parameter reflecting muscle work output during a sustained maximal grip effort in healthy middle-aged community-dwelling persons when using a JD. GW estimation is a promising outcome parameter in comprehensive geriatric assessment and its validation for commonly used instruments in geriatric practice will increase its clinical implementation.

Alcohol and delirium tremens: effects of average number of drinks per day and beverage type.

OBJECTIVE: Associations of amount of alcohol intake and beverage type with the risk of delirium tremens (DT) have not been studied. This longitudinal study investigated if the average number of drinks per day and beverage type predict DT. METHODS: A cohort of 3 582 alcohol-dependent men and women aged 19-82 without previous DT were interviewed about alcohol intake and beverage type at baseline in 1994-2005 and followed through record linkage in Danish nationwide registers to identify incident DT. Data were analyzed by means of Cox regression models. RESULTS: An average number of drinks per day of 20-30 or >30 was associated with hazard ratios (HRs) of 1.38 (95% CI 1.03-1.84) and 1.64 (95% CI 1.19-2.27) relative to the reference category (1-9 drinks). Independently of amount consumed and covariates (age, gender, civil status and work status), beverage type (spirits vs. mixed alcohol) was associated with a HR of 1.63 (95% CI 1.08-2.46). Male gender was robustly associated with increased risk (HR = 1.62 (95% CI 1.25-2.08). CONCLUSIONS: In alcohol-dependent men and women, daily alcohol intake above a threshold of 20 beverages or 240 g alcohol and a preference for spirits increase the risk of developing DT.

Association studies of genetic scores of serum vitamin B12 and folate levels with symptoms of depression and anxiety in two danish population studies.

BACKGROUND/OBJECTIVES: Observational studies have suggested low serum levels of vitamin B12 or folate to be risk factors of depression and anxiety. However, these results may be biased by confounding and reverse causation. Mendelian randomization studies are not subject to these limitations. The aim was to examine the association of genetic scores of vitamin B12 and folate-associated alleles with depression and anxiety. SUBJECTS/METHODS: The study included 4126 participants from two Danish population-based studies. Serum vitamin B12 and folate were measured. Weighed allele scores were calculated as the sum of weights (genetic effect sizes) for 12 and two variants increasing circulating levels of vitamin B12 and folate, respectively. Symptoms of depression and anxiety were assessed by the Symptom Check List (SCL)-90-R, and self-reported doctor-diagnosed depression and anxiety. RESULTS: An increased weighed allele score for serum vitamin B12 was associated with decreased odds of a SCL-90-R score above the 90th percentile (OR 0.540 (95%CI 0.302-0.967)) in Health2006 but not in Inter99, in the pooled analysis (OR 0.817 (95%CI 0.331-2.018)) or with other outcomes. The weighed allele score for serum folate was not associated with any of the measured outcome variables: SCL-90-R scores of depression (pooled OR 0.603 (95%CI 0.101-3.602)), anxiety (pooled OR 0.619 (95%CI 0.110-3.495)), combined score or history of doctor-diagnosed depression or anxiety. CONCLUSION: Our results do not provide evidence for a causal effect of circulating folate or vitamin B12 on the risk of depression or anxiety. However, we cannot rule out small to moderate effects, and thus large scale studies are needed.

Structure and clinical correlates of obsessive-compulsive symptoms in a large sample of children and adolescents: a factor analytic study across five nations.

The underlying structure of obsessive-compulsive disorder (OCD) remains to be confirmed in child and adolescent populations. In this paper we report the first factor analytic study of individual OCD items from Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS). OCD symptoms were assessed using the CY-BOCS symptom checklist in a sample of 854 patients with OCD (7-18 years of age) recruited from clinics in five countries. Pooled data were subjected to exploratory and confirmatory factor analysis (CFA) to identify the optimal factor structure. Various models were tested for age and gender subgroups. Also, the invariance of the solution across age and gender was tested and associations with demographic and clinical factors were explored. A three-factor model provided the best-fit solution. It consisted of the following factors: (1) harm/sexual, (2) symmetry/hoarding, (3) contamination/cleaning. The factor structure was invariant for age and gender across subgroups. Factor one was significantly correlated with anxiety, and factor two with depression and anxiety. Factor three was negatively correlated with tic disorder and attention-deficit/hyperactivity disorder (ADHD). Females had higher scores on factor two than males. The OCD symptom structure in children and adolescents is consistent across age and gender and similar to results from recent child and adolescents although hoarding may not be a separate factor. Our three-factor structure is almost identical to that seen in early studies on adults. Common mental disorders had specific patterns of associations with the different factors.

Exploring social cognition in schizophrenia.

The aim of the study was to compare social cognition between groups of patients diagnosed with schizophrenia and healthy controls and to replicate two previous studies using tests of social cognition that may be particularly sensitive to social cognitive deficits in schizophrenia. Thirty-eight first-admitted patients with schizophrenia and 38 healthy controls solved 11 "imaginary conversation (i.e., theory of mind)" items, 10 "psychological understanding" items, and 10 "practical understanding" items. Statistical tests were made of unadjusted and adjusted group differences in models adjusting for intelligence and neuropsychological test performance. Healthy controls performed better than patients on all types of social cognitive tests, particularly on "psychological understanding." However, after adjusting for intelligence and neuropsychological test performance, all group differences became nonsignificant. When intelligence and global cognitive functioning is taken into account, schizophrenia patients and healthy controls perform similarly on social cognitive tests.

Tracking of body mass index from 7 to 69 years of age.

BACKGROUND: Heavy children have an increased risk of being overweight young adults. Whether this risk remains in late adulthood is not well-understood. We investigated body mass index (BMI; kg m(-2)) tracking from childhood to late adulthood. METHODS: From the Copenhagen School Health Records Register, 72 959 men and 25 252 women born between 1930 and 1989 with BMI values at 7 and/or 13 years and as adults were included. Using a meta-regression approach, age- and sex-specific partial correlation analyses and logistic regressions were performed. RESULTS: Correlations between BMI at 7 years and young adult ages (18-19 years) were r=0.55 for men and r=0.55 for women. At late ages (60-69 years) these were r=0.28 for men and r=0.26 for women. The correlations did not differ by birth years. Compared with normal-weight 7-year-olds, overweight children had a higher odds of overweight at 18-19 years; odds ratio (OR)=14.02 (95% confidence interval (CI): 12.14-16.19) for men and 10.46 (95% CI: 4.82-22.70) for women. At ages 60-69 years ORs were 5.46 (95% CI: 0.95-31.36) for men and 1.61 (95% CI: 0.83-3.15) for women. Correlations and ORs were stronger at age 13 years than age 7 years as expected, but the overall patterns were similar. CONCLUSIONS: BMI tracking was weaker at late adult ages than at young adult ages. Although BMI tracks across the life course, childhood BMI is relatively poor at identifying later adult overweight or obesity at ages when chronic diseases generally emerge.

Childhood body mass index and risk of schizophrenia in relation to childhood age, sex and age of first contact with schizophrenia.

UNLABELLED: Childhood leanness is associated with an increased risk of schizophrenia, but the effects of gender, age at anthropometric measurements and age at first diagnosis on this relationship are unclear. The present study aimed at elucidating these associations. METHODS: Population-based cohort study with childhood anthropometric measures obtained annually from the age of 7 to 13 years in 253,353 Danes born 1930-1976 and followed to 31 December 2010. During this period, 4936 were registered with schizophrenia. The associations of childhood BMI with risk of schizophrenia were estimated with Cox regression models. RESULTS: Childhood BMI was significantly inversely associated with risk of schizophrenia, however with different patterns among boys and girls. In boys, childhood BMI had an inverse non-linear association with schizophrenia risk dependent on age at diagnosis; in particular, a surprisingly strong association was found between leanness and later onset of schizophrenia. In girls, the risk of schizophrenia decreased linearly with increasing BMI z-score (HR: 0.93; 95% CI: 0.88-0.98). In both boys and girls, birth weight was inversely associated with later risk. In girls, but not in boys, birth weight appeared to significantly modify the associations; there was a somewhat stronger inverse association in the lowest birth weight category. CONCLUSION: Birth weight as well as childhood BMI at ages 7 through 13 years is associated with risk of schizophrenia in both genders, but with a particular high risk of late-onset in lean boys irrespective of birth weight, and in lean girls with low birth weight. If replicated, these observations may inform preventive efforts build on schizophrenia trajectories rooted in early life.

Pre-diagnostic high-sensitive C-reactive protein and breast cancer risk, recurrence, and survival.

Inflammation may initiate and promote breast cancer development, and be associated with elevated circulating levels of inflammation markers. A total of eight 130 initially healthy women, participated in the population-based Tromsø study (1994-2008). Pre-diagnostic high-sensitivity C-reactive protein (hs-CRP) was assessed. During 14.6 years of follow-up, a total of 192 women developed invasive breast cancer. These cases were followed for additional 7.2 years. Detailed medical records were obtained. We observed an overall positive dose-response relationship between pre-diagnostic hs-CRP and breast cancer risk (hazard ratio (HR) = 1.06, 95 % CI 1.01-1.11). Postmenopausal women with above median levels of hs-CRP (>1.2 mg/l) had a 1.42 (95 % CI 1.01-2.00) higher breast cancer risk compared to postmenopausal women with hs-CRP below median. Postmenopausal women, who were hormone replacement therapy non-users, and were in the middle tertile (0.8-1.9 mg/l), or highest tertile of hs-CRP (>1.9 mg/l), had a 2.31 (95 % CI 1.31-4.03) and 2.08 (95 % CI 1.16-3.76) higher breast cancer risk, respectively, compared with women in the lowest tertile. For each unit increase in pre-diagnostic hs-CRP levels (mg/l), we observed an 18 % increase in disease-free interval (95 % CI 0.70-0.97), and a 22 % reduction in overall mortality (95 % CI 0.62-0.98). Our study supports a positive association between pre-diagnostic hs-CRP and breast cancer risk. In contrast, increased pre-diagnostic hs-CRP was associated with improved overall mortality, but our findings are based on a small sample size, and should be interpreted with caution.

Tuberculosis and other opportunistic infections in tofacitinib-treated patients with rheumatoid arthritis.

OBJECTIVES: To evaluate the risk of opportunistic infections (OIs) in patients with rheumatoid arthritis (RA) treated with tofacitinib. METHODS: Phase II, III and long-term extension clinical trial data (April 2013 data-cut) from the tofacitinib RA programme were reviewed. OIs defined a priori included mycobacterial and fungal infections, multidermatomal herpes zoster and other viral infections associated with immunosuppression. For OIs, we calculated crude incidence rates (IRs; per 100 patient-years (95% CI)); for tuberculosis (TB) specifically, we calculated rates stratified by patient enrolment region according to background TB IR (per 100 patient-years): low (≤0.01), medium (>0.01 to ≤0.05) and high (>0.05). RESULTS: We identified 60 OIs among 5671 subjects; all occurred among tofacitinib-treated patients. TB (crude IR 0.21, 95% CI of (0.14 to 0.30)) was the most common OI (n=26); median time between drug start and diagnosis was 64 weeks (range 15-161 weeks). Twenty-one cases (81%) occurred in countries with high background TB IR, and the rate varied with regional background TB IR: low 0.02 (0.003 to 0.15), medium 0.08 (0.03 to 0.21) and high 0.75 (0.49 to 1.15). In Phase III studies, 263 patients diagnosed with latent TB infection were treated with isoniazid and tofacitinib concurrently; none developed TB. For OIs other than TB, 34 events were reported (crude IR 0.25 (95% CI 0.18 to 0.36)). CONCLUSIONS: Within the global tofacitinib RA development programme, TB was the most common OI reported but was rare in regions of low and medium TB incidence. Patients who screen positive for latent TB can be treated with isoniazid during tofacitinib therapy.

Increased post-operative cardiopulmonary fitness in gastric bypass patients is explained by weight loss.

Roux-en-Y gastric bypass (RYGB) leads to a major weight loss in obese patients. However, given that most patients remain obese after the weight loss, regular exercise should be part of a healthier lifestyle. The primary aim of this study was to investigate the cardiopulmonary fitness in obese patients before and after RYGB. Thirty-four patients had body composition and cardiopulmonary fitness (VO2max ) assessed and completed questionnaires regarding physical activity and function twice before RYGB (time points A and B) and 4 and 18 months after surgery (time points C and D). Weight loss was 37 ± 2 kg during the study period. VO2max increased (A: 21 ± 1 vs D: 29 mL/min/kg, P < 0.001), but absolute VO2max decreased (A: 2713 ± 126 vs 2609 ± 187 mL/min, P = 0.02) and VO2max per kilogram fat free mass did not change. Self-perceived limitations to perform exercise decreased and self-perceived physical fitness increased after RYGB. Self-reported low- and high-intensity physical activity did not change. With weight loss, self-rated fitness level increased and the limitations to perform exercise decreased in RYGB patients. Nevertheless, as shown by the lower absolute VO2max , RYGB patients do not adopt new exercise habits following surgery.

Serum 25-hydroxyvitamin D and self-reported mental health status in adult Danes.

BACKGROUND/OBJECTIVES: Vitamin D receptors and vitamin D-metabolising enzymes are present in the brain and in the central nervous system at sites responsible for the regulation of emotions and behaviour. This raises the hypothesis that low vitamin D is related to poor mental health. Our aim was to examine the association between serum 25-hydroxyvitamin D (25(OH)D) and the self-reported symptoms and diagnosis of depression and anxiety in the adult general population. SUBJECTS/METHODS: Serum 25(OH)D was measured in three Danish population-based studies, including 5308 adults aged 18-64 years. After 5 years, 2004 participants were re-examined. Symptoms of depression and anxiety were assessed by the Symptom Check List (SCL)-90-R, and self-reported doctor-diagnosed depression and anxiety was recorded by using a questionnaire. RESULTS: Serum 25(OH)D was not associated with SCL average scores for depression and anxiety when analysed by quantile median regression adjusted for sex, age and other potential confounders. The ß-coefficient and 95% confidence interval (CI) per 10 nmol/l serum 25(OH)D were 0.00 (-0.00 to 0.01) and P=0.23 for depression and -0.00 (-0.01 to 0.00) and P=0.19 for anxiety. Furthermore, no evidence of an association was observed with longitudinal changes (combining depression and anxiety score: ß (95% CI)=0.00 (-0.00 to 0.00), P=0.90), with scores >90 percentiles (odds ratio (OR) (95% CI)=1.02 (0.98-1.07), P=0.32), or with self-reported history (OR (95% CI)=1.02 (0.97-1.07), P=0.47) or incidence (OR (95% CI)=1.02 (0.92-1.12), P=0.77) of doctor-diagnosed depression and/or anxiety. CONCLUSIONS: Our results suggest that low serum 25(OH)D is not associated with self-reported symptoms/diagnosis of depression and anxiety.

The association of pre-pregnancy alcohol drinking with child neuropsychological functioning.

OBJECTIVE: To examine the effects of pre-pregnancy alcohol drinking on child neuropsychological functioning. DESIGN: Prospective follow-up study. SETTING AND POPULATION: 154 women and their children sampled from the Danish National Birth Cohort. METHODS: Participants were sampled based on maternal alcohol consumption before pregnancy. At 5 years of age, the children were tested with the Wechsler Preschool and Primary Scale of Intelligence-Revised, the Test of Everyday Attention for Children at Five (TEACh-5), and the Movement Assessment Battery for Children (MABC). The Behaviour Rating Inventory of Executive Function (BRIEF) was completed by the mothers and a preschool teacher. Parental education, maternal IQ, prenatal maternal smoking, child's age at testing, child's sex, and maternal alcohol intake during pregnancy were considered potential confounders. MAIN OUTCOME MEASURES: Performance on the Wechsler Preschool and Primary Scale of Intelligence-Revised, the TEACh-5, the MABC, and the BRIEF. RESULTS: Intake of 15-21 drinks/week on average prior to pregnancy was not associated with any of the outcomes, but intake of ≥22 drinks/week on average was associated with a significantly lower adjusted mean full scale IQ and lower adjusted means in overall attention and sustained attention score, but not in selective attention score or any of the BRIEF index scores or MABC scores. CONCLUSIONS: Intake of ≥22 drinks/week before pregnancy was associated with lower mean full scale IQ, overall attention and sustained attention. Assessment of pre-pregnancy drinking provides additional information regarding potential prenatal alcohol exposure and its implications for child neurodevelopment.

Impact of empiric weight-based vancomycin dosing on nephrotoxicity and mortality in geriatric patients with methicillin-resistant Staphylococcus aureus bacteraemia.

WHAT IS KNOWN AND OBJECTIVE: Few studies have evaluated the effect of vancomycin dosing on the health outcomes in geriatric patients. Data are needed to determine whether higher vancomycin dosing strategies are more effective in geriatric patients and/or lead to excessive rates of adverse events. METHODS: This study used a subset of patients aged ≥65 years from a multicentre, retrospective, cohort study of methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia. Patients received ≥ 48 h of empiric vancomycin between 1 July 2002 and 30 June 2008. We compared the incidence of nephrotoxicity and in-hospital mortality in patients who received guideline-recommended dosing (at least 15 mg/kg/dose) to patients who received lower dosing. Multivariable generalized mixed-effect models were constructed to determine independent risk factors for nephrotoxicity and in-hospital mortality. RESULTS AND DISCUSSION: Half of the cohort (46% of 92 patients) received guideline-recommended dosing. Empiric use of weight-based dosing did increase the percentage of patients achieving a vancomycin trough ≥ 15 mg/L (57% vs. 42%). Nephrotoxicity occurred in 32% of patients and 26% died during their hospitalization. Guideline-recommended dosing was not associated with significant changes in nephrotoxicity (OR 1·13; 95% CI 0·40-3·19) or in-hospital mortality (OR 1·14; 95% CI 0·41-3·18) in the multivariable analysis. WHAT IS NEW AND CONCLUSION: In this study of geriatric patients, guideline-recommended dosing was not associated with significant changes in nephrotoxicity or mortality. As 40% of the patients who received guideline-recommended dosing failed to achieve a target vancomycin trough of ≥ 15 mg/L, future studies should focus on dosing strategies to increase target attainment rate.

Effects of body size and change in body size from infancy through childhood on body mass index in adulthood.

BACKGROUND: Weight and weight gain throughout infancy are related to later obesity, but whether the strength of the associations varies during the infancy period is uncertain. AIMS: Our aims were to identify the period of infancy when change in body weight has the strongest association with adult body mass index (BMI) and also the extent to which these associations during infancy are mediated through childhood BMI. METHODS: The Copenhagen Perinatal Cohort, in which participants were followed from birth through 42 years of age, provided information on weight at 12 months and BMI at 42 years for 1633 individuals. Information on weight at birth, 2 weeks, 1, 2, 3, 4 and 6 months was retrieved from health visitors' records and information on BMI at ages 7 and 13 years from school health records. The associations of infant weight and weight gain standard deviation scores (SDS) with adult BMI-SDS were analyzed using multiple linear regression and path analysis. RESULTS: Higher-weight-SDS at all ages from birth to an age 12 months were associated with higher-BMI-SDS at 42 years (regression coefficients 0.08-0.12). Infant weight gain-SDS was associated with greater BMI-SDS at 42 years only between birth and 3 months (0.09, 95% confidence intervals (CI) 0.04, 0.15) driven by an association between 2 and 3 months (0.12, 95% CI: 0.04, 0.20). The latter was partly mediated through later BMI in the path analysis. Infant weight gain-SDS between 3 and 12 months was not associated with greater BMI-SDS at 42 years. CONCLUSIONS: Faster weight gain during only the first 3 months of infancy was associated with increased adult BMI, although not in a consistent monthly pattern. Adult BMI is more sensitive to high weight gain during early infancy than late infancy, but not specifically to the first month of life.

Fertility treatment and child intelligence, attention, and executive functions in 5-year-old singletons: a cohort study.

OBJECTIVE: To assess the association of fertility treatment and subfertility with offspring intelligence, attention, and executive functions in 5-year-old singletons. DESIGN: Follow-up study. SETTING: Denmark 2003-2008. POPULATION: A cohort of 1782 children sampled from the Danish National Birth Cohort. METHODS: The children were tested with a neuropsychological battery at age five. In addition to tests of intelligence, attention and executive functions, the follow up included extensive information on important covariates. The analyses were conducted using multiple linear regression and adjusted for parental educational level, maternal intelligence, age, parity, body mass index, smoking in pregnancy, alcohol consumption in pregnancy and child gender, child age, and examiner. MAIN OUTCOME MEASURES: Wechsler Preschool and Primary Scale of Intelligence-Revised, the Test of Everyday Attention for Children at Five, and the Behavior Rating Inventory of Executive Functions scores. RESULTS: A consistent pattern of nonsignificantly lower scores were only observed for intelligence and executive functions in children born after fertility treatment or by subfertile parents when the results were unadjusted for maternal intelligence and parental educational level. When adjusted for these and other covariates, there were no significant mean differences in intelligence (mean difference -2.8, 95% CI -7.8, 2.2), overall attention (-0.1, 95% CI -0.6, 0.3), or parent-rated executive functions (-0.1, 95% CI -3.0, 2.9) between children born after spontaneous conception and children born to parents conceiving after fertility treatment. Similarly, there were no significant mean differences in intelligence (mean difference 0.6, 95% CI -2.2, 3.4), overall attention (0.1, 95% CI -0.2, 0.4), or parent-rated executive functions (1.0, 95% CI -1.8, 3.7) between children born after spontaneous conception and children born to subfertile parents waiting more than 12 months before conceiving naturally. CONCLUSIONS: This study suggests that parental subfertility and fertility treatment are unrelated to offspring intelligence, attention and executive functions.

Does Harm Avoidance mediate effects of recollected parental bonding on mental distress in adulthood?

BACKGROUND: Adverse early life conditions such as perceived low quality of parental bonding increase vulnerability to stress and psychopathology in adulthood. However, the mechanisms by which perceptions of parental bonding translate into vulnerability are unclear and remain sparsely investigated in healthy populations. We proposed a model, in which the personality trait Harm Avoidance would mediate effects of recollected parental bonding during the first sixteen years of life on measures of perceived stress and mental distress severity in adulthood. METHOD: Five-hundred-eighteen adults (65.1 % women), aged 18-53years, completed questionnaires of parental bonding, perceived stress, trait Harm Avoidance, and severity of mental distress. Direct and indirect effects mediated through trait Harm Avoidance were examined in a structural equation model. RESULTS: Under the causal assumptions of our proposed model, indirect effects of trait Harm Avoidance mediated the relationship between parental overprotection and severity of mental distress, while significantly attenuating the direct effects of parental care on severity of mental distress. Moreover, indirect effects of trait Harm Avoidance significantly attenuated the direct effects of parental overprotection and care on perceived stress. CONCLUSION: In this large sample of mentally healthy adults, recollected parental bonding was significantly associated with levels of perceived stress and severity of mental distress. The results from our proposed model further suggest that trait Harm Avoidance may be a developmental link, by which the quality of recollected parental bonding in childhood translates into adult vulnerability to stress and mental distress.

Three cases of donor-derived pulmonary tuberculosis in lung transplant recipients and review of 12 previously reported cases: opportunities for early diagnosis and prevention.

INTRODUCTION: Solid organ transplant recipients have a higher frequency of tuberculosis (TB) than the general population, with mortality rates of approximately 30%. Although donor-derived TB is reported to account for <5% of TB in solid organ transplants, the source of Mycobacterium tuberculosis infection is infrequently determined. METHODS: We report 3 new cases of pulmonary TB in lung transplant recipients attributed to donor infection, and review the 12 previously reported cases to assess whether cases could have been prevented and whether any cases that might occur in the future could be detected and investigated more quickly. Specifically, we evaluate whether opportunities existed to determine TB risk on the basis of routine donor history, to expedite diagnosis through routine mycobacterial smears and cultures of respiratory specimens early post transplant, and to utilize molecular tools to investigate infection sources epidemiologically. FINDINGS: On review, donor TB risk was present among 7 cases. Routine smears and cultures diagnosed 4 asymptomatic cases. Genotyping was used to support epidemiologic findings in 6 cases. CONCLUSION: Validated screening protocols, including microbiological testing and newer technologies (e.g., interferon-gamma release assays) to identify unrecognized M. tuberculosis infection in deceased donors, are warranted.