Association of population mixing and acute lymphocytic leukemia in children and young adults.

BACKGROUND: The association of population mixing (PM1) with childhood acute lymphocytic leukemia (ALL2) has been reproduced in multiple studies. However, the mechanism underlying this association is unknown. METHODS: Ecological study of incidence of pediatric ALL among 253 counties in the State of Texas (USA) using surrogates of genetic and environmental PM. ALL incidence data were obtained from Texas Cancer Registry and county population statistics from the US Census Bureau. Poisson regression was used to compare ALL incidence and PM. RESULTS: There is substantial and variable genetic and environmental PM among counties in Texas. Indicators of genetic PM including proportion of multiracial households, ratio of Hispanics to non-Hispanics, and ratio of foreign to native-born residents were all significantly associated with a higher incidence of ALL (IRR3 1.81 (95CI 1.05-3.13), 1.67 (95CI 1.16-2.37), and 1.59 (95CI 1.03-2.48), respectively). Surrogates of environmental PM namely population density and persons per household were not associated with incidence of ALL; IRRs 1.29 (95CI 0.4-4.15) and 1.47 (95CI 0.89-2.43). CONCLUSIONS: These findings are consistent with prior patterns and magnitudes of PM association with ALL. Our findings suggest that the implicated mechanism of leukemogenesis in PM may be genetically transmitted rather than environmental.

Follow-up study of the early, randomised paracetamol trial to preterm infants, found no adverse reactions at the two-years corrected age.

AIM: We examined the long-term outcomes and safety of early intravenous paracetamol for ductus arteriosus closure at a corrected age of two years. METHODS: This was a follow-up of the 2013-2014 randomised, double-blind Preterm Infant's Paracetamol Study at Oulu University Hospital, Finland, which recruited 48 very preterm infants within 24 hours of birth. They received intravenous paracetamol or a placebo for four days. In 2015-2017, we followed up 44 infants (92%) at two years of corrected age. This included clinical and neurodevelopmental assessments and a parental medical history questionnaire. RESULTS: The 44 infants (55% boys) were born at 235 -316 weeks of gestation. No differences in the cardiac parameters, including blood pressures and ultrasound scan results, were found. Neurodevelopmental stages, as quantified by the Griffiths test, were similar. No signs of autism were reported. Asthma medication was more common in the control group, but the difference was not significant. Atopy scores, numbers of infections and the use of public health services were similar between the two groups. CONCLUSION: No long-term adverse reactions of early intravenous paracetamol were detected two years later. Larger trials are needed on the safety and efficacy of paracetamol prophylaxis for early ductal closure in very preterm infants.

The gap between behavioral risk status and willingness to change behavior among healthcare professionals.

AIMS:: This study explored behavioral health risk factors among healthcare professionals and investigated the at-risk persons' satisfaction with their health habits and ongoing change attempts. METHODS:: The study was based on a cross-sectional web-based survey directed at the nurses and physicians ( N = 1233) in Finnish healthcare. Obesity, low physical activity, smoking, and risky alcohol drinking were used as behavioral health risk factors. RESULTS:: In all, 70% of the participants had at least one behavioral risk factor, and a significant number of at-risk persons were satisfied with their health habits and had no ongoing change process. Good self-rated health and good self-rated work ability were significantly associated with whether a participant had a behavioral health risk factor. CONCLUSION:: Overall, unhealthy behaviors and a lack of ongoing change attempts were commonly observed among healthcare professionals. Work in healthcare is demanding, and healthy lifestyles can support coping. Thus, healthy lifestyle programs should also be targeted to healthcare professionals.

Intravenous paracetamol was associated with closure of the ductus arteriosus in extremely premature infants.

AIM: Symptomatic patent ductus arteriosus may lead to serious complications in extremely preterm and extremely low birthweight infants and is often resistant to medication. We evaluated early intravenous paracetamol for pain prevention during respiratory therapy, in an attempt to understand the ductal treatment of such infants. METHODS: Our cohort were 295 extremely preterm or extremely low birthweight infants, born at less than 28 weeks or 1000 g, respectively, who were treated in the neonatal intensive care unit of Oulu University Hospital from 2002 to 2015, before and after intravenous paracetamol was introduced in June 2009. Ductal closure dates, paracetamol medication details, morbidities and mortality data were evaluated. RESULTS: Intravenous paracetamol was given to 128 infants, starting at a median of 4.4 hours age (range: 0-169 hours), with a mean total dosage of 212 mg/kg (range: 7.5-1175 mg/kg). We also included 167 controls who were mainly treated before we used intravenous paracetamol. Ibuprofen (p < 0.001) and ligation (p = 0.002) were lower in the paracetamol group than controls. No adverse effects were detected. Paracetamol was not associated with other morbidities. CONCLUSION: We found that early use of intravenous paracetamol decreased the incidence of ductal therapies in extremely premature or extremely low birthweight infants.

A systematic review and meta-analysis of long-term studies (five or more years) assessing maxillary sinus floor augmentation.

The objective was to test the hypothesis of no difference in long-term (≥5 years) implant treatment outcomes after maxillary sinus floor augmentation (MSFA) with autogenous bone graft compared to a mixture of autogenous bone graft and bone substitutes or bone substitutes alone. A MEDLINE (PubMed), Embase, and Cochrane Library search in combination with a hand-search of relevant journals was conducted. Human studies published in English between January 1, 1990 and October 1, 2016 were included. Nine studies fulfilled the inclusion criteria. The survival of suprastructures has never been compared within the same study. The 5-year implant survival after MSFA with autogenous bone graft was 97%, compared to 95% for Bio-Oss; the reduction in vertical height of the augmented sinus was equivalent with the two treatment modalities. Non-comparative studies demonstrated high survival rates for suprastructures and implants regardless of the grafting material used. Meta-analysis revealed an overall estimated patient-based implant survival of 95% (confidence interval 0.92-0.96). High implant stability quotient values, high patient satisfaction, and limited peri-implant marginal bone loss were revealed in non-comparative studies. No long-term randomized controlled trial comparing the different treatment modalities was identified. Hence, the conclusions drawn from the results of this systematic review should be interpreted with caution.

Lateral ridge augmentation with Bio-Oss alone or Bio-Oss mixed with particulate autogenous bone graft: a systematic review.

The objective of this systematic review was to test the hypothesis of no difference in implant treatment outcomes when using Bio-Oss alone or Bio-Oss mixed with particulate autogenous bone grafts for lateral ridge augmentation. A search of the MEDLINE, Cochrane Library, and Embase databases in combination with a hand-search of relevant journals was conducted. Human studies published in English from 1 January 1990 to 1 May 2016 were included. The search provided 337 titles and six studies fulfilled the inclusion criteria. Considerable variation prevented a meta-analysis from being performed. The two treatment modalities have never been compared within the same study. Non-comparative studies demonstrated a 3-year implant survival of 96% with 50% Bio-Oss mixed with 50% autogenous bone graft. Moreover, Bio-Oss alone or Bio-Oss mixed with autogenous bone graft seems to increase the amount of newly formed bone as well as the width of the alveolar process. Within the limitations of this systematic review, lateral ridge augmentation with Bio-Oss alone or in combination with autogenous bone graft seems to induce newly formed bone and increase the width of the alveolar process, with high short-term implant survival. However, long-term studies comparing the two treatment modalities are needed before final conclusions can be drawn.

Randomized trial of early erythropoietin supplementation after preterm birth: Iron metabolism and outcome.

BACKGROUND: Excess of iron and oxidant injury shortly after birth may be associated with neonatal morbidities in preterm infants. AIMS: The aim was to determine whether administration of erythropoietin without iron supplementation decreases iron load and morbidity. STUDY DESIGN AND SUBJECTS: In a randomized trial, we administered erythropoietin (EPO 250IU/kg daily during the first 6days of life) or placebo to 39 preterm infants (BW 700-1500g, GA≤30.0weeks). OUTCOME MEASURES: The iron status, postnatal morbidities and follow-up at the age of two years were investigated. RESULTS: In all, 21 EPO- and 18 placebo-treated infants were recruited. A requirement of red blood cell transfusions during first 28days was similar between the study groups. EPO treatment decreased total serum iron concentration (p=0.035). EPO supplementation had no significant effect on serum transferrin receptors or reactive non-protein-bound iron. There were no differences in neonatal morbidity or in survival without major neurological abnormality at two years of age. CONCLUSIONS: A 6-day course of EPO decreased the iron load in preterm infants. There was no change in reactive, non-protein bound iron plasma levels and no influence on the outcomes during early childhood. Whether the neurocognitive effects of early EPO treatment can be detectable later in childhood remained to be verified.

Apolipoprotein E, brain injury and neurodevelopmental outcome of children.

Apolipoprotein E plays an important role in neurodegenerative processes in adulthood, whereas its neurodevelopmental role is uncertain. We aimed to study the effect of apolipoprotein E on neurodevelopment in a cohort liable to neurodevelopmental changes. The cohort consisted of very preterm (<32 gestational weeks) and/or very low birth weight (<1500 g) children, and the longitudinal follow-up protocol included sequential cranial ultrasounds during infancy, brain magnetic resonance imaging at term-equivalent age, neurological and cognitive assessment (Mental Developmental Index) at the corrected age of 2 years and cognitive and neuropsychological assessments (Wechsler Preschool and Primary Scale of Intelligence and Developmental NEuroPSYchological Assessment) at the chronological age of 5 years. Apolipoprotein E genotypes were determined from 322 children. Ultrasound and magnetic resonance imaging data were available for 321 (99.7%) and 151 (46.9%) children, respectively. Neurodevelopmental assessment data were available for 138 (42.9%) to 171 (53.1%) children. Abnormal findings in ultrasounds and magnetic resonance imaging were found in 163 (50.8%) and 64 (42.4%) children, respectively. Mild cognitive delay at the corrected age of 2 years and the chronological age of 5 years was suspected in 21 (12.3%) of 171 and 19 (13.8%) of 138 children, respectively. In the Developmental NEuroPSYchological Assessment, 47 (32.6%) of 144 children had significantly impaired performances in more than one study subtest. No associations between the apolipoprotein E genotypes and imaging findings or measured neurodevelopmental variables were found. Apolipoprotein E genotypes do not appear to have major impact on brain vulnerability or neurodevelopment in children.

The reliability of the disabled children's quality-of-life questionnaire in Swedish children with diabetes.

AIM: To determine the reliability of the disabled children's quality-of-life measure (DISABKIDS) chronic generic questionnaire and diabetes module in children. The questionnaire is being evaluated for repeated routine health-related quality-of-life (HrQoL) assessment and in association with the Swedish national paediatric diabetes registry (Swediabkids), which is a tool for regular clinical use. METHODS: Children and parents completed the questionnaire during a routine visit to the diabetes clinic. In total, 120 families completed the test and retest. Split-half reliability correlation and intraclass correlation (ICC) coefficients were calculated. Bland & Altman plots were calculated on the generic HRQoL domain. RESULTS: Both child and parent versions showed good internal consistency. Test-retest ICC coefficients for the generic HrQoL module were 0.913 for the children and 0.820 for the parent version. All generic domains independently showed good reliability. The diabetes module had a score of 0.855 for children and 0.823 for parents. Split-half correlation for generic and diabetes modules was 0.930 and 0.848 for children, 0.953 and 0.903 for parents. Bland and Altman plots showed substantial agreement between the two administrations for both children and parents. CONCLUSION: The DISABKIDS questionnaire is a reliable instrument for the repeated measurements of HrQoL in children with diabetes.

Intramembraneous bone tissue responses to calcium sulfate: an experimental study in the rabbit maxilla.

OBJECTIVES: The purpose of this study was to histologically examine the responses of intramembraneous bone to calcium sulfate (CaS) and evaluate the resorption and replacement process. MATERIAL AND METHODS: Fourteen rabbits were used in this study. Defect healing without any filling material was compared with CaS. Five millimetres wide and 4 mm deep defects were drilled with a trephine bur on both sides of the edentulous space between the incisors and the molars. Test vs. control sites were randomly selected and thereby compared in each animal. The animals were killed after 2, 4 and 8 weeks for histological examination. RESULTS: After 2 weeks, the specimens showed a great extent of degradation of CaS. No signs of the material could be seen after 4 and 8 weeks. There were no statistically significant differences in bone regeneration between the test and control sites within the 8 weeks group in this study. However, there was tendency of more blood vessels in the test sites after 4 weeks of healing. CONCLUSION: The present study showed that CaS does not interfere with intramembraneous bone healing. In this animal model, the CaS exhibited resorption/degradation early in the healing process while seemingly stimulating angiogenesis. However, there was no significant increase in bone regeneration in the sites treated with CaS during an 8 week period of healing and observation time, as compared with a control defect.

Health and the use of health care services in 5-year-old very-low-birth-weight infants.

AIM: We aimed to study the effect of prematurity, time of birth and level of birth hospital on morbidity and the use of health care services at age 5. METHODS: This national study included all very-low-birth-weight infants (VLBWI, <32 gestational weeks or birth weight < or =1500 g) born in Finnish level II or III hospitals in 2001-2002 (n = 918), and full-term controls (n = 381). Parental questionnaires and register data were used to compare morbidity, and the use of health care services between VLBWI and full-term controls, and within VLBWI according to the time of birth and birth hospital level. RESULTS: Cerebral palsy, retinopathy of prematurity, other ophthalmic problems, respiratory infections, asthma or chronic lung disease, and inguinal hernia were overrepresented in VLBWI compared with the controls. VLBWI had more outpatient and inpatient days than the controls. The time of birth and birth hospital level were not associated with the use of services or with prematurity-related morbidity. CONCLUSION: Although morbidity and the use of health care services were increased in the surviving VLBWI, the average use of services was relatively small at age 5. In surviving VLBWI, the time of birth and the birth hospital level did not affect morbidity or the use of services.

Two-year follow-up of a randomised trial with repeated antenatal betamethasone.

BACKGROUND: Weekly repeated antenatal corticosteroid treatment improves respiratory outcome but decreases fetal growth and may impair neurodevelopmental outcome. We have previously reported that a single repeat betamethasone (BM) dose neither decreased fetal growth nor improved the outcome of preterm infants during the first hospitalisation. OBJECTIVE: To study prospectively whether a single repeat dose of BM influences neurodevelopment and growth within 2 years. DESIGN: Women with imminent delivery before 34.0 gestational weeks were eligible if they remained undelivered for >7 days after a single course of antenatal BM. After stratification, a single repeat dose of BM (12 mg) or placebo was given. The children underwent neurological and psychometric examinations and a speech evaluation at a corrected age of 2 years. SETTING: Prospective, blinded evaluation following the randomised multicentre trial. PATIENTS: 259 (82%) surviving infants completed the 2-year follow-up, 120 in the BM group and 139 in the placebo group. RESULTS: The rate of survival without severe neurodevelopmental impairment was similar in both groups (BM 98%, placebo 99%). The risk of cerebral palsy (BM 2%, placebo 1%), growth or re-hospitalisation rates (BM 60%, placebo 50%) did not differ between the groups. CONCLUSIONS: A single repeat dose of antenatal BM tended not to influence physical growth or neurodevelopment at 2 years of age.

[EuroNeoStat: a European information system on the outcomes of care for very-low-birth-weight infants (< 1500 g)]. / EuroNeoStat: ein Europäisches Informationssystem zur erfassung der behandlungsergebnisse von sehr untergewichtigen Frühgeborenen mit einem Geburtsgewicht < 1500 g.

BACKGROUND: Prematurity rates are increasing throughout the world. Despite an overall rather small percentage of very low birth weight infants (VLBWI), which is approx. 1-2 % in most countries, these infants contribute significantly to morbidity and neonatal and infant mortality rates. METHODS: EuroNeoStat was initiated as an European information system on the outcomes of VLBWI to monitor and improve the care of these infants throughout Europe. EuroNeoStat includes an initiative, called EuroNeoSafe, to promote the safety of these high risk preterm infants. Perinatal and neonatal data from VLBWI is collected without using data that identify individuals or institutions. These data is analyzed at the coordination center in Bilbao. All institutions taking care on VLBWI in Europe can participate in this network and will be able to compare their own outcome data with other institutions from the network. Information on EuroNeoStat and the current data set is available on www.euroneostat.org. CONCLUSION: Successful initiatives aiming at improving outcomes in perinatal and neonatal care require collaborative networking, an attitude of constructive criticism and thorough comparative analysis of the outcomes and incidents in the health-care process.

Blood glucose level in preterm infants after antenatal exposure to glucocorticoid.

AIM: To determine the impact of antenatal glucocorticoid on neonatal glucose homeostasis. METHODS: This is a retrospective gestationally paired survey followed by a randomized study. On the basis of the interval between last antenatal dexamethasone and birth, 228 preterm infants born before 34 weeks were divided into Short (< 24 h), Intermediate (1-6 days), and Long (> or = 7 days) exposure groups and compared their gestationally paired controls. After a single course of betamethasone, the parturients remaining undelivered for one week were randomized to receive either one dose of betamethasone (n = 52) or placebo (n = 53). Glucose values were recorded at 11 time points in the first 3 days of life. Hypoglycaemic and hyperglycaemic values were counted. RESULTS: There were no overall differences in mean glucose levels between the antenatal glucocorticoid and the control groups. However, the long exposure time to antenatal glucocorticoid was associated with increased risk of hyperglycaemia (OR 4.1; 2.2-7.6). CONCLUSION: Antenatal glucocorticoid administration was associated with subtle disturbances of glucose homeostasis in preterm infants. These differences were dependent on the length of drug-delivery interval so that long exposition time seemed to increase the incidence of hyperglycaemia during the first days of life.

Bruton's tyrosine kinase together with PI 3-kinase are part of Toll-like receptor 2 multiprotein complex and mediate LTA induced Toll-like receptor 2 responses in macrophages.

Lipoteichoic acid (LTA) of Gram-positive bacteria initiates innate immune responses via Toll-like receptor-2 (TLR2), resulting in the activation of intracellular signaling and production of inflammatory cytokines in macrophages. Although Bruton's tyrosine kinase (Btk) is biologically important molecule implicated in immune regulation and recently in TLR signaling its importance for LTA-TLR2 mediated responses has not been evaluated. In this study, we detected Btk in the LTA signaling complex with TLR2 and PI 3-kinase (PI3K). The constitutive interaction of these proteins was mediated via PI3K Src homology (SH3) -domain. Both Btk and PI3K were activated by LTA stimulation and the LTA induced cytokine expression was differentially modulated by these kinases. LTA induced the activation of nuclear factor kappaB (NFkappaB), however, only Btk inhibition affected the LTA induced Ser536 phosphorylation and DNA-binding of NFkappaB. In conclusion, our results demonstrate that Btk and PI3K occupy important roles in TLR2-induced activation of macrophages, resulting in selective regulation of cytokines.

A 3-year prospective follow-up study of implant-supported fixed prostheses in patients subjected to maxillary sinus floor augmentation with a 80:20 mixture of deproteinized bovine bone and autogenous bone Clinical, radiographic and resonance frequency analysis.

The purpose of this prospective clinical study was to evaluate the 3-year outcome of 30 maxillary sinus floor augmentations with an autogenous bone-deproteinized bovine bone mixture (20:80). A total of 108 dental implants were placed after 6 months of graft healing. After another 6 months, the occlusion was restored with fixed prostheses and followed for 3 years of functional loading. Clinical and radiographic examinations of the sinuses and implants, including computerized tomography (CT) were performed. The stability of the implants was evaluated by means of resonance frequency analyses (RFA). After 3 years of functional loading with fixed bridges, 15 of 108 implants were lost giving a cumulative survival rate (CSR) of 86%. All followed patients, except one, had fixed bridges in function after 3 years of loading. The mean marginal bone loss was 1.3+/-1.1 mm after 3 years. RFA showed a mean implant stability quotient (ISQ) value of 66+/-4.1 after 3 years with no significant difference between implants in grafted and residual bone. Examination with CT showed that 67% of the maxillary sinuses were healthy prior to treatment and 71% after 3 years of loading. It was concluded that grafting of the maxillary sinus with a mixture of autogenous bone and deproteinized bovine bone is a reliable procedure.

Changing incidence and outcome of infants with respiratory distress syndrome in the 1990s: a population-based survey.

AIM: To evaluate the trends in the incidence, clinical course and outcome of respiratory distress syndrome (RDS) in the newborn in the Oulu University Hospital region in northern Finland. METHODS: In the population of 58 990 infants, the incidence rates of RDS specific to gestational age and birthweight in two consecutive periods, 1990-95 and 1996-99, were calculated. Clinical course and other neonatal morbidities were reported. All surviving infants were followed up until 1 y of corrected age. RESULTS: The overall incidence of RDS did not change significantly (8.7/1000 livebirths in 1990-95 vs 7.6 in 1996-99; p = 0.15), but the gestational age-adjusted incidence decreased between the two consecutive periods (p = 0.005). The frequency of infants with gestational age below 28 wk tended to increase towards the late 1990s, while their RDS incidence remained unchanged. RDS-related neonatal mortality decreased in parallel with neonatal mortality, accounting for 15% of all neonatal deaths. The duration of oxygen therapy shortened (8.0 vs 5.5 d) and the incidence of pneumothorax decreased (9.7 vs 4.1%), whereas the rate of chronic lung disease at 36 wk of postconceptional age (16.4 vs 16.7%) and at 1 y of corrected age (9.2 vs 8.2%) remained unchanged, as did also associated neurosensory morbidity (8.8 vs 9.5%). CONCLUSION: During the 1990s, the incidence of RDS shifted towards more immature infants and the gestational-age specific incidence decreased. The course of the disease shortened and acute complications decreased. The frequency of chronic pulmonary sequelae (and associated neurosensory morbidity) at the age of 1 y did not change significantly.