Systematic reviews of observational studies of Risk of Thrombosis and Bleeding in General and Gynecologic Surgery (ROTBIGGS): introduction and methodology.

BACKGROUND: Venous thromboembolism (VTE) and bleeding are serious and potentially fatal complications of surgical procedures. Pharmacological thromboprophylaxis decreases the risk of VTE but increases the risk of major post-operative bleeding. The decision to use pharmacologic prophylaxis therefore represents a trade-off that critically depends on the incidence of VTE and bleeding in the absence of prophylaxis. These baseline risks vary widely between procedures, but their magnitude is uncertain. Systematic reviews addressing baseline risks are scarce, needed, and require innovations in methodology. Indeed, systematic summaries of these baseline risk estimates exist neither in general nor gynecologic surgery. We will fill this knowledge gap by performing a series of systematic reviews and meta-analyses of the procedure-specific and patient risk factor stratified risk estimates in general and gynecologic surgeries. METHODS: We will perform comprehensive literature searches for observational studies in general and gynecologic surgery reporting symptomatic VTE or bleeding estimates. Pairs of methodologically trained reviewers will independently assess the studies for eligibility, evaluate the risk of bias by using an instrument developed for this review, and extract data. We will perform meta-analyses and modeling studies to adjust the reported risk estimates for the use of thromboprophylaxis and length of follow up. We will derive the estimates of risk from the median estimates of studies rated at the lowest risk of bias. The primary outcomes are the risk estimates of symptomatic VTE and major bleeding at 4 weeks post-operatively for each procedure stratified by patient risk factors. We will apply the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate evidence certainty. DISCUSSION: This series of systematic reviews, modeling studies, and meta-analyses will inform clinicians and patients regarding the trade-off between VTE prevention and bleeding in general and gynecologic surgeries. Our work advances the standards in systematic reviews of surgical complications, including assessment of risk of bias, criteria for arriving at the best estimates of risk (including modeling of the timing of events and dealing with suboptimal data reporting), dealing with subgroups at higher and lower risk of bias, and use of the GRADE approach. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021234119.

Executive Function Profiles at Home and at School in 11-Year-Old Very Low Birth Weight or Very Low Gestational Age Children.

OBJECTIVE: Executive function (EF) problems of children born at very low birth weight (VLBW; ≤1500 g) or very low gestational age (VLGA; <32 gestational weeks) may present differently at school compared to the home environment. Ecological assessment of EF including parent- and teacher-rated profiles and associated risk factors of 11-year-old children born at VLBW or VLGA was evaluated. METHODS: A total of 125 VLBW or VLGA children and 132 controls were assessed using the Behavior Rating Inventory of EF, which includes 8 subscales that form the Behavioral Regulation and Metacognition Indexes. For VLBW or VLGA children, full-scale intelligence quotient (IQ) was assessed using the Wechsler Intelligence scale for Children, Fourth Edition. Neonatal data were collected systematically. RESULTS: VLBW or VLGA children with full-scale IQ ≥ 70 had clinically significant problems in the Working Memory subscale at school. Although they had clinically significant problems at home in the Behavioral Regulation Index, the difference disappeared when adjusted for paternal education. Lower gestational age, lower birth weight z-score, surgical necrotizing enterocolitis, low paternal and maternal education, and lower full-scale IQ were identified to be risk factors for higher scores in ecological assessment of EF. CONCLUSION: VLBW or VLGA children in this cohort exhibit fewer EF problems in ecological assessment of EF compared to previous literature. EF problems of this study population vary by home and school setting and are emphasized in working memory at school. Screening for EF problems in school environment is recommended to target the support.

School performance is age appropriate with support services in very preterm children at 11 years of age.

AIM: This Finnish regional birth-cohort study compared the school performance of very preterm and full-term children when they reached 11 years of age. METHODS: Teachers rated the educational abilities of 123 preterm children and 133 full-term controls at the age of 11 years as well as the support services they received. The children were all born in the Turku University Hospital between 2001 and 2005. In the preterm group, neurosensory impairments were confirmed at two years of corrected age, and full-scale intelligence quotient (IQ) was assessed at 11 years of age using the Wechsler Intelligence Scale, Fourth Edition. RESULTS: Educational abilities, including academic skills and classroom functioning, did not differ between the two groups after excluding the children with a full-scale IQ < 70. However, 40% of the preterm group and 26% of the controls had received at least one support service (p <0.02). The 13 preterm children with a full-scale IQ <70 and the 10 with neurosensory impairment received more support services. Boys in both groups displayed more classroom-functioning problems than girls. CONCLUSION: A full-scale IQ ≥ 70 and age-appropriate educational abilities do not exclude a significant need for support services in very preterm children at the age of 11 years.

Working memory in very-low-birthweight children at the age of 11 years.

The aim of this study is to investigate the working memory (WM) of very-low-birthweight (VLBW, ≤ 1500 g) children at the age of 11 years using Baddeley's WM model. A regional cohort of 95 VLBW children was assessed for the domains of the WM model (central executive [CE], visuospatial sketchpad [VS], and phonological loop [PL]) using subtests from the Working Memory Test Battery for Children (WMTB-C) and the Wechsler Intelligence Scale for Children - Fourth Edition (WISC-IV). VLBW children were categorized into three groups according to their degree of brain pathology (normal, minor, or major) in neonatal brain magnetic resonance imaging at the term age, and the WM performance was compared between groups to test norms. The structure of the WM model was studied by analyzing correlations among domains. Even VLBW children with normal cognitive development (general ability index ≥ 85) performed worse compared to the test norms (M = 100, SD = 15) on CE (M = 87.64, SD = 20.54, p < .001) and VS (M = 91.65, SD = 11.03, p < .001), but their performance on PL was above the norm (M = 110.79, SD = 13.79, p < .001). VLBW children with major brain pathology performed significantly worse on VS and PL compared to the other groups. The correlations among the WM domains of the VLBW children differ from earlier findings in normative populations. To conclude, the WM of the VLBW children in the study differ-especially in the CE and VS subtest scores-from the normative population irrespective of the degree of brain pathology and level of cognitive development.

Factors affecting the cognitive profile of 11-year-old children born very preterm.

BackgroundPreterm birth is a risk for cognitive development. This study assessed the cognitive profile of children born very preterm at the age of 11 years as well as the associated risk factors.MethodsA total of 128 children born very preterm were included. Magnetic resonance imaging was performed at term age. Cognitive development was assessed using the full-scale intelligence quotient (IQ) and four domains of the Wechsler Intelligence Scale for Children, fourth edition (WISC-IV), Finnish translation. The results were compared with test norms.ResultsMost study children performed at average (51%) or low average (21%) levels in the full-scale IQ assessment. The correlation between 5- and 11-year full-scale IQ was 0.73 (P<0.001). Compared with the normative data, children born very preterm performed poorer in all domains of the cognitive profile. The only significant risk factor for poor general cognition was major brain pathology. When considering all four domains of WISC-IV, low paternal education, male gender, and low birth weight z score were also found to be significant risk factors.ConclusionsLess than one-third of the children born very preterm performed below the low average cognitive level at 11 years of age. Specific neonatal and sociodemographic risk factors were identified as affecting the cognitive profile.

A 13-year follow-up of Finnish patients with Salla disease.

BACKGROUND: Salla disease (SD) is a rare lysosomal storage disorder leading to severe intellectual disability. SD belongs to the Finnish disease heritage, and it is caused by mutations in the SLC17A5 gene. The aim of the study was to investigate the course of neurocognitive features of SD patients in a long-term follow-up. METHODS: Neuropsychological and neurological investigations were carried out on 24 SD patients, aged 16-65 years, 13 years after a similar examination. RESULTS: The survival analysis showed excess mortality among patients with SD after the age of 30 years. The course of the disease was progressive, but follow-up of SD patients revealed that motor skills improved till the age of 20 years, while mental abilities improved in most patients till 40 years of age. Verbal comprehension skills did not diminish during the follow-up, but productive speech deteriorated because of dyspraxia and dysarthria. Motor deficits were marked. Ataxia was prominent in childhood, but it was replaced by athetotic movements during the teens. Spasticity became more obvious with age especially in severely disabled SD patients. CONCLUSIONS: Younger SD patients performed better in almost every task measuring mental abilities that then seem to remain fairly constant till early sixties. Thus, the results indicate better prognosis in cognitive skills than earlier assumed. There is an apparent decline in motor skills after the age of 20 years. The early neurocognitive development predicts the later course of motor and cognitive development.

Neurocognitive disorders in sentenced male offenders: implications for rehabilitation.

BACKGROUND: Neurocognitive deficits are frequent among male offenders and tend to be associated with a more serious risk of anti-social activity, but they are not systematically allowed for in rehabilitation programmes. AIM: The aim of this study was to evaluate neurocognitive performance in a sample of sentenced Finnish male prisoners and consider the implications for prison programme entry. METHODS: Seventy-five sentenced male prisoners were examined using a neurocognitive test battery. RESULTS: Depending on the neurocognitive domain, from 5% to 49% of the men demonstrated marked neurocognitive deficits in tests of motor dexterity, visuospatial/construction skills, verbal comprehension, verbal and visual memory and attention shift. Verbal IQ was more impaired than performance IQ. There was no association between most serious offence type and neurocognitive performance, but correlations between attention deficit indices and number of previous convictions suggested that recidivists may have an attention disorder profile. Cluster analysis identified two subgroups of offenders, separated by very poor or merely poor cognitive performance. Motor dexterity, visuo-construction and verbal memory deficits were not wholly explained by lower IQ measures. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Our sample was small, but the nature and extent of the neurocognitive deficits found suggest that wider use of neurocognitive assessments, which the men generally tolerated well, could help select those most likely to need offender programmes and that the effectiveness of these may be enhanced by some specific cognitive remediation before progressing to more complex social tasks.

An Unusual Developmental Profile of Salla Disease in a Patient with the SallaFIN Mutation.

Salla disease (SD) is a disorder caused by defective storage of free sialic acid and results from mutations in the SLC17A5 gene. Early developmental delay of motor functions, and later cognitive skills, is typical. We describe a developmental profile of an unusual homozygous patient, who harboured the SallaFIN (p.R39C) mutation gene. The study involved neurological examination, neuropsychological investigation, and brain imaging. The neurocognitive findings were atypical in comparison with other patients with the SallaFIN mutation. Interestingly, there was no deterioration in the patient's neurological condition during adulthood. Her neurocognitive skills were remarkably higher than those of other patients with a conventional phenotype of SD. Our results suggest that the phenotype of SD is broad. Unidentified genetic or environmental variation might explain the unique SD type of this case.

Elements of working memory as predictors of goal-setting skills in children with attention-deficit/ hyperactivity disorder.

The aim of the study was to examine how goal-setting skills of children with attention-deficit/hyperactivity disorder (ADHD) can be predicted with elements of working memory. The study involved 30 children with an ADHD diagnosis and 30 healthy volunteers. The IQ of the participants was assessed, and ADHD symptoms were evaluated by parents. Each of the elements of working memory was assessed with two measures as well as goal-setting skills. In the tests of the central executive and in one of the tests of the visuospatial sketch pad, children with ADHD performed more poorly than did controls but not in the tests of the phonological loop. Children with ADHD performed more poorly than controls did on the mastery scores of the goal-setting measures but not on the Strategy scores. According to regression analysis, central executive functions are critical for the variance in goal-setting skills in children with ADHD.

From genetic risk awareness to overt type 1 diabetes: parental stress in a placebo-controlled prevention trial.

OBJECTIVE: To evaluate the psychological burden of parents facing increasing risk of type 1 diabetes in their children. RESEARCH DESIGN AND METHODS: In the population-based Type 1 Diabetes Prediction and Prevention (DIPP) Study, newborn infants with HLA-DQB1-conferred diabetes risk were enrolled in sequential analyses of diabetes-associated autoantibodies. Those persistently positive for at least two autoantibodies were recruited to a randomized double-blinded intervention trial. The experience of stress in parents of 664 children was measured using Parenting Stress Index self-report inventory. RESULTS: While diagnosis of diabetes increased parental stress, the appearance of autoantibodies or participation in the intervention trial did not. Mothers had higher stress levels than fathers. Single parenthood and chronically ill family members increased parental stress. CONCLUSIONS: Parental stress was not increased by notification of autoantibody positivity or by participation in an intervention trial. Other demanding family conditions contributed to the experience of stress.

Parental reactions to information about increased genetic risk of type 1 diabetes mellitus in infants.

OBJECTIVE: To assess the anxiety, emotions, thoughts, and coping behaviors of parents 1 week after they receive the results of screening of their infant's genetic risk of type 1 diabetes mellitus. DESIGN: Survey. SETTING: The population-based Type 1 Diabetes Prediction and Prevention project conducted in Turku. PARTICIPANTS: Parents of 443 consecutive high-risk infants and 506 next-born low-risk infants. INTERVENTIONS: An infant's genetic risk of type 1 diabetes mellitus was measured from cord blood. High-risk information was delivered by telephone and low-risk information by mail 4 weeks later. MAIN OUTCOME MEASURES: Anxiety measured using the state anxiety scale of the State-Trait Anxiety Inventory, and feelings, thoughts, and coping behaviors extracted from the questionnaire. RESULTS: One week after obtaining the results, 67% of mothers and 63% of fathers of high-risk children and 58% of mothers and 54% of fathers of low-risk children had returned the questionnaire. Anxiety levels of parents of high-risk infants were similar to those of parents of low-risk infants (P = .86). More than 90% of the parents thought that it was good to know about the risk. Fifty-five percent of mothers and 37% of fathers of high-risk infants expressed modest worry. Increased anxiety was connected with other stressful life events, catastrophizing thoughts of diabetes mellitus risk, and emotion-focused or avoiding coping attitudes. CONCLUSIONS: Learning about their infant's genetic diabetes mellitus risk induces only mild anxiety in most parents. Identifying the few parents with stronger anxiety helps focus intensified counseling.

Rapid serial naming: relations between different stimuli and neuropsychological factors.

We report two studies on rapid serial naming (RSN). Study 1 addressed the relations among RSN tasks comprising different stimuli. Separate components for RSN of alphanumeric and non-alphanumeric stimuli, as well as for tasks in which the stimuli alternated between categories were identified. In Study 2, phonological skills, processing speed, motor dexterity, and verbal fluency were found to explain RSN performance. The studies indicate: (1) that RSN tasks vary in their properties according to the stimuli used and according to the way the tasks are arranged, and (2) that RSN tasks are multi-componented.

Neurocognitive profiles in Salla disease.

Salla disease, a free sialic acid storage disorder, is one of the 36 currently known disorders in Finland that form the Finnish disease heritage. Salla disease leads to learning disability* with a wide clinical variation. Two main categories of the disease have been classified: a conventional subtype and a severe subtype with more severe defects. We present detailed neurocognitive profiles of 41 Finnish patients with Salla disease (19 females, 22 males; age range 11mo to 63y, median 19y). The neurocognitive development of patients with Salla disease was assessed by psychological and neuropsychological testing. All patients were also examined by a paediatric neurologist and a speech therapist. The characteristic cognitive profile consisted of a lower non-verbal performance (mean developmental age 13mo) compared with linguistic skills (mean developmental age 17mo). In particular, spatial and visual-constructive impairments were typical of these patients. Tactile and visual discrimination of forms was poor. Tasks demanding hand-eye coordination, maintenance of visual attention, and those requiring short-term visual memory and executive skills were performed better. Receptive language skills were notably better compared with expressive speech. The patients' interactive and non-verbal communication skills were quite strong. Another typical pattern with Salla disease was severe motor disability. After the second decade of life, the decline in these skills was more pronounced than patients' cognitive deterioration. Our results indicate that even though there is a considerable variation in the clinical findings of patients with Salla disease, the characteristic neurocognitive profile of the disease can be outlined.

Phenotypic spectrum of Salla disease, a free sialic acid storage disorder.

Salla disease (MIM 269920) represents the mildest phenotype among recessively inherited lysosomal-free sialic acid storage disorders. Although the vast majority of Salla disease patients in Finland share the same founder mutation, R39C in the SLC17A5 gene, there still is a wide clinical variation among mentally retarded, ataxic patients. We evaluated neurologic and neurocognitive findings of Salla disease in a cross-sectional study of 41 Finnish patients who were 11 months to 63 years of age (median = 19.5 years). The phenotype of Salla disease could be classified into two main categories. The majority of patients (90%) had so-called conventional phenotype, including a subgroup of seven patients with relatively mild symptoms. All but two patients with conventional phenotype were homozygous for the Finnish founder mutation. Four severely disabled, profoundly mentally retarded patients, 15-28 years of age, clearly could be clinically delineated as a separate group, likely reflecting the underlying compound heterozygous genotype. A typical developmental pattern could be outlined in the conventional type of the disease, emphasizing a strong motor handicap in Salla disease. The cognitive profile consisted of better verbal ability, especially speech comprehension, compared with nonverbal functioning in all patients. Our results indicate a partial genotype-phenotype correlation, although factors other than the molecular background are also involved in the phenotypic manifestation of Salla disease.

Academic achievement of small-for-gestational-age children at age 10 years.

OBJECTIVES: To provide current information on the academic achievement of small-for-gestational-age (SGA) children at age 10 years, to analyze predictors, and to evaluate the smallness of a newborn as a risk factor for school failure. DESIGN: Prospective, population-based birth cohort study with 10-year follow-up. PARTICIPANTS: The SGA group consisted of 106 children born in 1985 whose birth weight had been below the 2.5th percentile on the population-based fetal growth chart. The control group consisted of 105 appropriate-for-gestational-age (AGA) children born as closely as possible in time to SGA infants and matched for gestational age and mode of delivery. Both groups were evaluated at age 10 years. MAIN OUTCOME MEASURE: Academic achievement. RESULTS: Twenty-five percent of SGA children were school failures (vs 14% of AGA children; P =.05). There were significantly more SGA than AGA children with unfavorable backgrounds and deficient performances associated with poor academic achievement. Independent predictors of poor academic achievement in SGA and AGA children were inattention-passiveness as rated by their teachers (masked to grouping; corresponding to a 1-point increase in inattention-passiveness score: odds ratio, 5.1; 95% confidence interval, 2.1-12.1), a low verbal IQ score (psychologists masked; corresponding to a 10-point decrease in IQ score: odds ratio, 3.2; 95% confidence interval, 1.6-6.2), and restlessness at the follow-up visit (one examiner masked and the other not; odds ratio, 14.3; 95% confidence interval, 2.1-97.3). CONCLUSION: Being SGA at birth has a clinically significant impact on the academic achievement of a 10-year-old child.