Perceived barriers and facilitators to infection prevention and control in Dutch residential care facilities for people with intellectual and developmental disabilities: a cross-sectional study.

BACKGROUND: Adequate implementation of infection prevention and control (IPC) in residential care facilities (RCFs) for people with intellectual and developmental disabilities (IDDs) is crucial to safeguarding this vulnerable population. Studies in this field are scarce. This study aimed to identify perceived barriers to and facilitators of IPC among professionals working in these settings, along with recommendations to improve IPC, to inform the development of targeted interventions. METHODS: We administered an online questionnaire to 319 professionals from 16 Dutch RCFs for people with IDDs (March 2021-March 2022). Perceived multilevel barriers and facilitators (guideline, client, interpersonal, organisational, care sector, and policy level) were measured on a 5-point Likert scale (totally disagree-totally agree). Recommendations were assessed using a 5-point Likert scale (not at all helpful-extremely helpful), supplemented by an open-ended question. Barriers, facilitators, and recommendations were analysed by descriptive statistics. Open answers to recommendations were analysed through thematic coding. RESULTS: Barriers to IPC implementation included the client group (e.g., lack of hygiene awareness) (63%), competing values between IPC and the home-like environment (42%), high work pressure (39%), and the overwhelming quantity of IPC guidelines/protocols (33%). Facilitators included perceived social support on IPC between professionals and from supervisors (90% and 80%, respectively), procedural clarity of IPC guidelines/protocols (83%), and the sense of urgency for IPC in the organisation (74%). Main recommendations included the implementation of clear IPC policies and regulations (86%), the development of a practical IPC guideline (84%), and the introduction of structural IPC education and training programmes (for new staff members) (85%). Professionals also emphasised the need for IPC improvement efforts to be tailored to the local care context, and to involve clients and their relatives. CONCLUSIONS: To improve IPC in disability care settings, multifaceted strategies should be adopted. Initial efforts should involve clients (and relatives), develop a practical and context-specific IPC guideline, encourage social support among colleagues through interprofessional coaching, reduce workload, and foster an IPC culture including shared responsibility within the organisation.

Early childhood development monitoring during the first thousand days: Investigating the relationship between the developmental surveillance instrument and standardized scales.

OBJECTIVE: This study aims to investigate the relationship between the Developmental Surveillance Instrument -Instrumento de Vigilância do Desenvolvimento (IVD), found in the Child's Booklet Caderneta da Crianca (CC), and standardized scales: Alberta Infant Motor Scale (AIMS) and Denver Developmental Screening Test (Denver-II). METHODS: Employing an exploratory observational approach, we adopted a prospective longitudinal design with a quantitative approach. The convenience sample included 83 Brazilian children born between May and August 2019 in a public hospital. Of the total, 45 (54.22 %) were male, and 38 (45.78 %) were female. Developmental screening utilized the IVD, AIMS and Denver-II tests. Comparative analysis between groups employed Mann-Whitney or Kruskal-Wallis tests for numerical variables and chi-square/Fisher tests for categorical variables, with a significance level of 5 % (p < 0.05). RESULTS: A significant correlation was observed between the IVD and the AIMS and Denver-II tests (p < 0.001) at months 1, 4, and 8. CONCLUSION: The presence of a robust correlation between the IVD and the AIMS and Denver-II tests at months 1, 4, and 8 implies that the IVD in the Child's Booklet serves as a reliable and effective indicator for screening infant development during this critical period. Detecting issues early through these methods is crucial to ensure the well-being of children, allowing for appropriate interventions as needed.

Child Neurodevelopment After Multidomain Interventions From Preconception Through Early Childhood: The WINGS Randomized Clinical Trial.

Importance: Multidomain interventions in pregnancy and early childhood have improved child neurodevelopment, but little is known about the effects of additional preconception interventions. Objective: To evaluate the effect of a multifaceted approach including health; nutrition; water, sanitation, and hygiene (WASH); and psychosocial support interventions delivered during the preconception period and/or during pregnancy and early childhood on child neurodevelopment. Design, Setting, and Participants: In this randomized trial involving low- and middle-income neighborhoods in Delhi, India, 13 500 participants were assigned to preconception interventions or routine care for the primary outcome of preterm births and childhood growth. Participants who became pregnant were randomized to pregnancy and early childhood interventions or routine care. Neurodevelopmental assessments, the trial's secondary outcome reported herein, were conducted in a subsample of children at age 24 months, including 509 with preconception, pregnancy, and early childhood interventions; 473 with preconception interventions alone; 380 with pregnancy and early childhood interventions alone; and 350 with routine care. This study was conducted from November 1, 2000, through February 25, 2022. Interventions: Health, nutrition, psychosocial care and support, and WASH interventions delivered during preconception, pregnancy, and early childhood periods. Main Outcomes and Measures: Cognitive, motor, language, and socioemotional performance at age 24 months, assessed using the Bayley Scales of Infant and Toddler Development 3 tool. Results: The mean age of participants at enrollment was 23.8 years (SD, 3.0 years). Compared with the controls at age 24 months, children in the preconception intervention groups had higher cognitive scores (mean difference [MD], 1.16; 98.3% CI, 0.18-2.13) but had similar language, motor, and socioemotional scores as controls. Those receiving pregnancy and early childhood interventions had higher cognitive (MD, 1.48; 98.3% CI, 0.49-2.46), language (MD, 2.29; 98.3% CI, 1.07-3.50), motor (MD, 1.53; 98.3% CI, 0.65-2.42), and socioemotional scores (MD, 4.15; 98.3% CI, 2.18-6.13) than did controls. The pregnancy and early childhood group also had lower incidence rate ratios (RRs) of moderate to severe delay in cognitive (incidence RR, 0.62; 98.3% CI, 0.40-0.96), language (incidence RR, 0.73; 98.3% CI, 0.57-0.93), and socioemotional (incidence RR, 0.49; 98.3% CI, 0.24-0.97) development than did those in the control group. Children in the preconception, pregnancy, and early childhood intervention group had higher cognitive (MD, 2.60; 98.3% CI, 1.08-4.12), language (MD, 3.46; 98.3% CI, 1.65-5.27), motor (MD, 2.31; 98.3% CI, 0.93-3.69), and socioemotional (MD, 5.55; 98.3% CI, 2.66-8.43) scores than did those in the control group. Conclusions and Relevance: Multidomain interventions during preconception, pregnancy and early childhood led to modest improvements in child neurodevelopment at 24 months. Such interventions for enhancing children's development warrant further evaluation. Trial Registration: Clinical Trials Registry-India CTRI/2017/06/008908.

Psychosocial determinants associated with healthcare workers' self-reported compliance with infection prevention and control during the COVID-19 pandemic: a cross-sectional study in Dutch residential care facilities for people with intellectual and developmental disabilities.

BACKGROUND: Healthcare workers' (HCWs) compliance with infection prevention and control (IPC) is crucial to reduce the infection transmission risk. However, HCWs' compliance with IPC in residential care facilities (RCFs) for people with intellectual and developmental disabilities (IDDs) is known to be suboptimal. Therefore, this study examined sociodemographic and psychosocial determinants associated with IPC non-compliance in this setting, to inform IPC policy and promotion programmes for adequate IPC behaviour. METHODS: An online questionnaire was administered to 285 HCWs from 16 RCFs between March 2021 and March 2022. Determinants associated with IPC non-compliance were assessed using logistic regression analyses. RESULTS: Being a woman (OR: 3.57; 1.73-7.37), and being a non-medical professional were associated with increased odds of non-compliance (social workers, OR: 2.83; 1.65-4.85; behavioural specialists, OR: 6.09; 1.98-18.72). Perceived inadequate education/training (aOR: 1.62; 1.15-2.27) and perceived time constraints/competing priorities (aOR: 1.43; 1.03-1.98) were also associated with increased odds of non-compliance, independent of sociodemographic variables. In contrast, the belief that the supervisor complies with IPC (descriptive norm supervisor) was associated with decreased odds of non-compliance (aOR: 0.60; 0.41-0.88). CONCLUSIONS: To improve IPC in disability care settings, the implementation of tailored and structural IPC education and training programmes (e.g., on-the-job training) is recommended to increase HCWs' capabilities and bridge the IPC compliance gap between medical and non-medical professionals. In addition, role models, particularly supervisors, are crucial for promoting IPC behaviour. Facilities should create a culture of IPC compliance by norm setting, acting on, and modelling IPC behaviours at all levels of the organisation (management, medical, and non-medical staff).

Early-childhood linear growth faltering in low- and middle-income countries.

Globally, 149 million children under 5 years of age are estimated to be stunted (length more than 2 standard deviations below international growth standards)1,2. Stunting, a form of linear growth faltering, increases the risk of illness, impaired cognitive development and mortality. Global stunting estimates rely on cross-sectional surveys, which cannot provide direct information about the timing of onset or persistence of growth faltering-a key consideration for defining critical windows to deliver preventive interventions. Here we completed a pooled analysis of longitudinal studies in low- and middle-income countries (n = 32 cohorts, 52,640 children, ages 0-24 months), allowing us to identify the typical age of onset of linear growth faltering and to investigate recurrent faltering in early life. The highest incidence of stunting onset occurred from birth to the age of 3 months, with substantially higher stunting at birth in South Asia. From 0 to 15 months, stunting reversal was rare; children who reversed their stunting status frequently relapsed, and relapse rates were substantially higher among children born stunted. Early onset and low reversal rates suggest that improving children's linear growth will require life course interventions for women of childbearing age and a greater emphasis on interventions for children under 6 months of age.

A call for obesity prevention interventions for young children with intellectual and developmental disabilities.

Health disparities among children with intellectual and developmental disabilities (IDD) are present in early childhood. Yet, this population is underrepresented in health behavior research. In this commentary the authors highlight the need for multi-level physical activity and nutrition research for obesity prevention with a specific focus on young children with Down syndrome, a population at greater risk of developing overweight and obesity compared to typically developing peers. This commentary describes the comorbidities and developmental challenges faced by many children with Down syndrome which may influence weight-related physical activity and nutrition behaviors. Additionally, the authors advocate for involving a multidisciplinary team of experts to inform the adaptation or development of multi-level, theory-driven behavioral interventions to prevent obesity among children with Down syndrome.

Evaluation of the Developmental Assessment for Intervention Manual (DAIM) for developmental screening in high-risk infants at 12 months of corrected age.

Early detection of developmental delay provides opportunities for early intervention. The Developmental Assessment for Intervention Manual (DAIM) is the simplified screening tool for detection of developmental delay in Thai young infants implemented country-wide by the Ministry of Public Health since 2015. Unlike standard assessment tool, DAIM can be obtained by lay staff or parents and takes less time. We aimed to evaluate the accuracy of the DAIM for detection of developmental delay among high-risk infants. This single center prospective study was conducted from May, 2017 to December, 2021. The infants with corrected aged of 12 months with history of birth asphyxia or low birth weight (<2500 g) who visited a tertiary hospital for developmental assessment were invited to participate the study. The four developmental domains (gross motor, fine motor, receptive language, and expressive language) were assessed by Bayley-III and followed by DAIM in the same visit. The 126 infants were enrolled, 50% were male. Using Bayley-III score < 7 as reference, the sensitivity for gross motor domain, fine motor domain, receptive language and expressive language were 83.3%, 57.1%, 55% and 19.2%, respectively. Specificity for each domain was 75.4%, 88.2%, 74.5% and 92%. Positive predictive value for each domain was 26.3%, 22.2%, 28.9% and 38.5%. Negative predictive value (NPV) for each domain was 97.7%, 97.2%, 89.8% and 81.4%. With high sensitivity and NPV of DAIM in motor domain, but low in expressive language domains, using DAIM alone in high-risk infants can detect motor delay well but will miss many infants with expressive language delaye.

GLUT1 Deficiency Syndrome-Early Treatment Maintains Cognitive Development? (Literature Review and Case Report).

Glucose transporter type 1 (GLUT1) is the most important energy carrier of the brain across the blood-brain barrier, and a genetic defect of GLUT1 is known as GLUT1 deficiency syndrome (GLUT1DS). It is characterized by early infantile seizures, developmental delay, microcephaly, ataxia, and various paroxysmal neurological phenomena. In most cases, GLUT1DS is caused by heterozygous single-nucleotide variants (SNVs) in the SLC2A1 gene that provoke complete or severe impairment of the functionality and/or expression of GLUT1 in the brain. Despite the rarity of these diseases, GLUT1DS is of high clinical interest since a very effective therapy, the ketogenic diet, can improve or reverse symptoms, especially if it is started as early as possible. We present a clinical phenotype, biochemical analysis, electroencephalographic and neuropsychological features of an 11-month-old boy with myoclonic seizures, hypogammaglobulinemia, and mildly impaired gross motor development. Using sequence analysis and deletion/duplication testing, deletion of an entire coding sequence in the SLC2A1 gene was detected. Early introduction of a modified Atkins diet maintained a seizure-free period without antiseizure medications and normal cognitive development in the follow-up period. Our report summarizes the clinical features of GLUT1 syndromes and discusses the importance of early identification and molecular confirmation of GLUT1DS as a treatable metabolic disorder.

Cost-effectiveness and economic returns of group-based parenting interventions to promote early childhood development: Results from a randomized controlled trial in rural Kenya.

BACKGROUND: Early childhood development (ECD) programs can help address disadvantages for the 43% of children under 5 in low- and middle-income countries (LMICs) experiencing compromised development. However, very few studies from LMIC settings include information on their program's cost-effectiveness or potential returns to investment. We estimated the cost-effectiveness, benefit-cost ratios (BCRs), and returns on investment (ROIs) for 2 effective group-based delivery models of an ECD parenting intervention that utilized Kenya's network of local community health volunteers (CHVs). METHODS AND FINDINGS: Between October 1 and November 12, 2018, 1,152 mothers with children aged 6 to 24 months were surveyed from 60 villages in rural western Kenya. After baseline, villages were randomly assigned to one of 3 intervention arms: a group-only delivery model with 16 fortnightly sessions, a mixed-delivery model combining 12 group sessions with 4 home visits, and a control group. At endline (August 5 to October 31, 2019), 1,070 children were retained and assessed for primary outcomes including cognitive and receptive language development (with the Bayley Scales of Infant Development, Third Edition) and socioemotional development (with the Wolke scale). Children in the 2 intervention arms showed better developmental outcomes than children in the control arm, although the group-only delivery model generally had larger effects on children. Total program costs included provider's implementation costs collected during the intervention period using financial reports from the local nongovernmental organization (NGO) implementer, as well as societal costs such as opportunity costs to mothers and delivery agents. We combined program impacts with these total costs to estimate incremental cost-effectiveness ratios (ICERs), as well as BCRs and the program's ROI for the government based on predictions of future lifetime wages and societal costs. Total costs per child were US$140 in the group-only arm and US$145 in the mixed-delivery arm. Because of higher intention-to-treat (ITT) impacts at marginally lower costs, the group-only model was the most cost-effective across all child outcomes. Focusing on child cognition in this arm, we estimated an ICER of a 0.37 standard deviation (SD) improvement in cognition per US$100 invested, a BCR of 15.5, and an ROI of 127%. A limitation of our study is that our estimated BCR and ROI necessarily make assumptions about the discount rate, income tax rates, and predictions of intervention impacts on future wages and schooling. We examine the sensitivity of our results to these assumptions. CONCLUSIONS: To the best of our knowledge, this study is the first economic evaluation of an effective ECD parenting intervention targeted to young children in sub-Saharan Africa (SSA) and the first to adopt a societal perspective in calculating cost-effectiveness that accounts for opportunity costs to delivery agents and program participants. Our cost-effectiveness and benefit-cost estimates are higher than most of the limited number of prior studies from LMIC settings providing information about costs. Our results represent a strong case for scaling similar interventions in impoverished rural settings, and, under reasonable assumptions about the future, demonstrate that the private and social returns of such investments are likely to largely outweigh their costs. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov, NCT03548558, June 7, 2018. American Economic Association RCT Registry trial AEARCTR-0002913.

Maternal nutrients and effects of gestational COVID-19 infection on fetal brain development.

BACKGROUND & AIMS: Maternal gestational infection is a well-characterized risk factor for offsprings' development of mental disorders including schizophrenia, autism, and attention deficit disorder. The inflammatory response elicited by the infection is partly directed against the placenta and fetus and is the putative pathogenic mechanism for fetal brain developmental abnormalities. Fetal brain abnormalities are generally irreversible after birth and increase risk for later mental disorders. Maternal immune activation in animals models this pathophysiology. SARS-CoV-2 produces maternal inflammatory responses during pregnancy similar to previously studied common respiratory viruses. METHOD: Choline, folic acid, Vitamin D, and n-3 polyunsaturated fatty acids are among the nutrients that have been studied as possible mitigating factors for effects of maternal infection and inflammation on fetal development. Clinical and animal studies relevant to their use in pregnant women who have been infected are reviewed. RESULTS: Higher maternal choline levels have positive effects on the development of brain function for infants of mothers who experienced viral infections in early pregnancy. No other nutrient has been studied in the context of viral inflammation. Vitamin D reduces pro-inflammatory cytokines in some, but not all, studies. Active folic acid metabolites decrease anti-inflammatory cytokines. N-3 polyunsaturated fatty acids have no effect. CONCLUSIONS: Vitamin D and folic acid are already supplemented in food additives and in prenatal vitamins. Despite recommendations by several public health agencies and medical societies, choline intake is often inadequate in early gestation when the brain is forming. A public health initiative for choline supplements during the pandemic could be helpful for women planning or already pregnant who also become exposed or infected with SARS-CoV-2.

Children Treated for Nonsyndromic Craniosynostosis Exhibit Average Adaptive Behavior Skills with Only Minor Shortcomings.

BACKGROUND: Adaptive behavior skills are important when assessing cognitive functions related to daily life; however, few studies have assessed these skills in patients treated for nonsyndromic craniosynostosis. In this study, the authors assessed the adaptive behavior skills of children treated for craniosynostosis and examined whether their outcomes are related to surgical technique. METHODS: The Adaptive Behavior Assessment System, 2nd Edition, parent report was used for children (age, 7 to 16 years) treated for sagittal (n = 41), metopic (n = 24), and other rare synostoses (n = 8). Background data, including intelligence quotient, were controlled for confounders. RESULTS: All evaluated children treated for craniosynostosis were estimated as lower in all aspects of adaptive behavior skills (full-scale, conceptual, social, and practical composites; effect size, 0.36 to 0.44) as compared with norms. The sagittal group showed shortcomings in social composite (effect size, 0.48) and subscales measuring self-care and self-direction, although no difference was observed between spring-assisted surgery and pi-plasty regarding outcomes of adaptive behavior skills. In addition, children treated for metopic synostosis showed results indicating shortcomings with adaptive behavior according to the full-scale, conceptual, and social composites (effect size, 0.53 to 0.61) relative to norms. Furthermore, attrition analysis revealed no significant differences between responders (rate, 80.2 percent) and nonresponders. CONCLUSION: These results found that children treated for craniosynostosis display average adaptive behavior skills, and that the two surgical techniques used to treat sagittal synostosis did not differ in their behavioral outcomes. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Prenatal cytomegalovirus, rubella, and Zika virus infections associated with developmental disabilities: past, present, and future.

Prenatal infections have long been recognized as important, preventable causes of developmental disabilities. The list of pathogens that are recognized to have deleterious effects on fetal brain development continues to grow, most recently with the association between Zika virus (ZIKV) and microcephaly. To answer clinical questions in real time about the impact of a novel infection on developmental disabilities, an historical framework is key. The lessons learned from three historically important pathogens: rubella, cytomegalovirus, and ZIKV, and how these lessons are useful to approach emerging congenital infections are discussed in this review. Congenital infections are preventable causes of developmental disabilities and several public health approaches may be used to prevent prenatal infection. When they cannot be prevented, the sequelae of prenatal infection may be treatable. WHAT THIS PAPER ADDS: The list of prenatal infections associated with developmental disabilities continues to increase. Lessons learned from rubella, cytomegalovirus, and Zika virus have implications for new pathogens. Severity of illness in the mother does not correlate with severity of sequelae in the infant.

Development of a Prediction Model to Identify Children at Risk of Future Developmental Delay at Age 4 in a Population-Based Setting.

Our aim was to develop a prediction model for infants from the general population, with easily obtainable predictors, that accurately predicts risk of future developmental delay at age 4 and then assess its performance. Longitudinal cohort data were used (N = 1983), including full-term and preterm children. Development at age 4 was assessed using the Ages and Stages Questionnaire. Candidate predictors included perinatal and parental factors as well as growth and developmental milestones during the first two years. We applied multiple logistic regression with backwards selection and internal validation, and we assessed calibration and discriminative performance (i.e., area under the curve (AUC)). The model was evaluated in terms of sensitivity and specificity at several cut-off values. The final model included sex, maternal educational level, pre-existing maternal obesity, several milestones (smiling, speaking 2-3 word sentences, standing) and weight for height z score at age 1. The fit was good, and the discriminative performance was high (AUC: 0.837). Sensitivity and specificity were 73% and 80% at a cut-off probability of 10%. Our model is promising for use as a prediction tool in community-based settings. It could aid to identify infants in early life (age 2) with increased risk of future developmental problems at age 4 that may benefit from early interventions.

Neurodevelopmental outcomes after neonatal caffeine therapy.

Improving the adverse neurodevelopmental outcomes associated with prematurity is a priority. In the large international Caffeine for Apnea of Prematurity trial, caffeine improved survival without neurodevelopmental disability at 18 months and demonstrated long term safety up to 11 years. Caffeine is an adenosine receptor antagonist with effects on the brain, lung and other systems. The benefits of caffeine may be primary neuroprotection or reduction of risk factors for impairment, especially bronchopulmonary dysplasia. The effects of caffeine vary with age and dose. Animal data show risks of loss of neuronal protection from hypoxia. Treatment with earlier and higher dose caffeine may be beneficial but concerns remain.

Effectiveness of a home-based early cognitive-motor intervention provided in daycare, home care, and foster care settings: Changes in motor development and context affordances.

BACKGROUND: Appropriate opportunities within the context are crucial to affect the motor trajectory positively. OBJECTIVE: To investigate the effectiveness of professional-parental/caregivers' early motor-cognitive intervention on infants' motor development in Daycare (DC), Home Care (HC), and Foster Care (FC). Secondary objectives were to examine if parents and caregivers modified the context to meet the infants' needs and if making modifications was positively associated with infants' development. METHODS: Participants were 176 infants (DC = 48; HC = 58, FC = 70). Infants' were randomly assigned to intervention (IG) or comparison (CG) groups within each context. The Alberta Infant Motor Scale and Affordances in the Daycare and Home Environment for Motor Development were used. A cognitive-motor intervention was provided for infants in the intervention groups; and, a home-based support protocol for all caregivers and parents. RESULTS: IGs showed higher motor scores at post-test than CGs (p values from 0.018 to 0.026) and positive changes were observed from the pre-to-post intervention for all IGs (p ≤ .0001), and for two CGs (DC p ≤ .0001; HC p = .028). Maternal daily care and home opportunities improved for all infants. CONCLUSIONS: Parents/caregivers' protocol combined with the cognitive-motor intervention lead to better motor outcomes and changes in the context for the IGs. Only the parent/caregivers' protocol was not strong to improve CGs motor outcomes, although changes in context were found. Intensive intervention is need for infants living in vulnerability.

Early intervention and its short-term effect on the temporal organization of fidgety movements.

BACKGROUND: The Prechtl General Movement Assessment (GMA) predicts various neurological and developmental disorders while also documenting therapeutic effects. AIMS: To describe the temporal organization of fidgety general movements in infants with mild to moderate postural asymmetries and/or tonus regulation problems, and to analyze to what extent the temporal organization of fidgety movements will change after physiotherapy. STUDY DESIGN: Repeated measure design. PARTICIPANTS: Twelve infants (five females) with mild to moderate postural asymmetries and/or tonus regulation problems were admitted for an early intervention program. The gestational age ranged from 27 to 40 weeks (Median, 36 weeks; nine infants born preterm) with birth weights ranging from 740 g to 3500 g (Median, 2590 g). MEASURES: Fidgety movements and their temporal organization were measured using the Prechtl GMA at 9 to 19 weeks post term age (Median, 14 weeks) before and after an early motor training procedure. The movements of one of the infants were analysed using a computer-based approach, measuring the mean and standard deviation of quantity of motion, height of motion and width of motion. RESULTS: Seven infants had sporadic fidgety movements, and five had intermittent fidgety movements. None had continual fidgety movements before the intervention was initiated. After intervention, the temporal organization of fidgety movements increased in all infants. The observations of these movements were supported by computer-based analysis. CONCLUSION: The study indicates that early intervention increases the temporal organization of fidgety movements in infants with postural asymmetries and/or tonus regulation problems. The clinical significance of this finding needs to be further evaluated.