In this nationwide study involving preterm infants in Sweden, Apgar scores at 5 and 10 minutes and the change in the Apgar score between 5 and 10 minutes provided prognostic information about ...neonatal survival across gestational-age strata.
ObjectiveHereditary hypophosphatemias (HH) are rare monogenic conditions characterized by decreased renal tubular phosphate reabsorption. The aim of this study was to explore the prevalence, ...genotypes, phenotypic spectrum, treatment response, and complications of treatment in the Norwegian population of children with HH.DesignRetrospective national cohort study.MethodsSanger sequencing and multiplex ligand-dependent probe amplification analysis of PHEX and Sanger sequencing of FGF23, DMP1, ENPP1KL, and FAM20C were performed to assess genotype in patients with HH with or without rickets in all pediatric hospital departments across Norway. Patients with hypercalcuria were screened for SLC34A3 mutations. In one family, exome sequencing was performed. Information from the patients' medical records was collected for the evaluation of phenotype.ResultsTwety-eight patients with HH (18 females and ten males) from 19 different families were identified. X-linked dominant hypophosphatemic rickets (XLHR) was confirmed in 21 children from 13 families. The total number of inhabitants in Norway aged 18 or below by 1st January 2010 was 1 109 156, giving an XLHR prevalence of ∼1 in 60 000 Norwegian children. FAM20C mutations were found in two brothers and SLC34A3 mutations in one patient. In XLHR, growth was compromised in spite of treatment with oral phosphate and active vitamin D compounds, with males tending to be more affected than females. Nephrocalcinosis tended to be slightly more common in patients starting treatment before 1 year of age, and was associated with higher average treatment doses of phosphate. However, none of these differences reached statistical significance.ConclusionsWe present the first national cohort of HH in children. The prevalence of XLHR seems to be lower in Norwegian children than reported earlier.
IMPORTANCE Preterm birth is a leading cause of infant mortality, morbidity, and long-term disability, and these risks increase with decreasing gestational age. Obesity increases the risk of preterm ...delivery, but the associations between overweight and obesity and subtypes of preterm delivery are not clear. OBJECTIVE To study the associations between early pregnancy body mass index (BMI) and risk of preterm delivery by gestational age and by precursors of preterm delivery. DESIGN, SETTING, AND PARTICIPANTS Population-based cohort study of women with live singleton births in Sweden from 1992 through 2010. Maternal and pregnancy characteristics were obtained from the nationwide Swedish Medical Birth Register. MAIN OUTCOMES AND MEASURES Risks of preterm deliveries (extremely, 22-27 weeks; very, 28-31 weeks; and moderately, 32-36 weeks). These outcomes were further characterized as spontaneous (related to preterm contractions or preterm premature rupture of membranes) and medically indicated preterm delivery (cesarean delivery before onset of labor or induced onset of labor). Risk estimates were adjusted for maternal age, parity, smoking, education, height, mother's country of birth, and year of delivery. RESULTS Among 1 599 551 deliveries with information on early pregnancy BMI, 3082 were extremely preterm, 6893 were very preterm, and 67 059 were moderately preterm. Risks of extremely, very, and moderately preterm deliveries increased with BMI and the overweight and obesity-related risks were highest for extremely preterm delivery. Among normal-weight women (BMI 18.5-<25), the rate of extremely preterm delivery was 0.17%. As compared with normal-weight women, rates (%) and adjusted odds ratios (ORs 95% CIs) of extremely preterm delivery were as follows: BMI 25 to less than 30 (0.21%; OR, 1.26; 95% CI, 1.15-1.37), BMI 30 to less than 35 (0.27%; OR, 1.58; 95% CI, 1.39-1.79), BMI 35 to less than 40 (0.35%; OR, 2.01; 95% CI, 1.66-2.45), and BMI of 40 or greater (0.52%; OR, 2.99; 95% CI, 2.28-3.92). Risk of spontaneous extremely preterm delivery increased with BMI among obese women (BMI≥30). Risks of medically indicated preterm deliveries increased with BMI among overweight and obese women. CONCLUSIONS AND RELEVANCE In Sweden, maternal overweight and obesity during pregnancy were associated with increased risks of preterm delivery, especially extremely preterm delivery. These associations should be assessed in other populations.
Sustainable and effective eHealth requires accessibility for everyone. Little is known about how accessibility of eHealth is perceived among people with various impairments. The aim of this study was ...to compare use and perceived difficulty in the use of eHealth among people with and without impairment, and how different types of impairment were associated with perceived difficulty in the use of eHealth.
This study used data collected in a nationwide survey in Sweden. Snowball sampling was used to recruit participants with self-reported impairment, from June to October 2019. In February 2020, the survey was posted to people in the general population who were matched to the participants with impairment by age, gender and county of residence. Multiple logistic regression was used to analyse the use of four eHealth services, and perceived difficulty in the use of six eHealth services.
In total, 1631 participants with, and 1084 participants without impairment responded to the survey. Participants with impairment reported less use and more difficulty in the use of all eHealth services as compared to participants without impairment. When comparing types of impairment, booking healthcare appointments online was least used and most avoided by participants with communication, language and calculation impairments (adjusted odds ratio (aOR) use 0.64, 95% confidence interval (95%CI) 0.49-0.83; aOR avoid 1.64, 95%CI 1.19-2.27), and intellectual impairments (aOR use 0.28, 95%CI 0.20-0.39; aOR avoid 2.88, 95%CI 1.86-4.45). The Swedish national web-portal for health information and services, 1177.se, was reported difficult to use the most among participants with communication, language and calculation impairments (aOR 2.24, 95%CI 1.50-3.36), deaf-blindness (aOR 11.24, 95%CI 3.49-36.23) and hearing impairment (aOR 2.50, 95%CI 1.17-5.35).
The results confirm the existence of an eHealth disability digital divide. People with impairment were not one homogeneous group, but differed in perceived difficulties in regard to eHealth. Based on a purposeful subgrouping of impairments, we showed that people with communication, language and calculation impairments, and intellectual impairments, reported least use and most difficulty in using eHealth. The findings can guide further research in creating eHealth that is accessible for all, including those with the most significant difficulties.
SNP arrays, short- and long-read genome sequencing are genome-wide high-throughput technologies that may be used to assay copy number variants (CNVs) in a personal genome. Each of these technologies ...comes with its own limitations and biases, many of which are well-known, but not all of them are thoroughly quantified. We assembled an ensemble of public datasets of published CNV calls and raw data for the well-studied Genome in a Bottle individual NA12878. This assembly represents a variety of methods and pipelines used for CNV calling from array, short- and long-read technologies. We then performed cross-technology comparisons regarding their ability to call CNVs. Different from other studies, we refrained from using the golden standard. Instead, we attempted to validate the CNV calls by the raw data of each technology. Our study confirms that long-read platforms enable recalling CNVs in genomic regions inaccessible to arrays or short reads. We also found that the reproducibility of a CNV by different pipelines within each technology is strongly linked to other CNV evidence measures. Importantly, the three technologies show distinct public database frequency profiles, which differ depending on what technology the database was built on.
Insights into the genetic basis of type 2 diabetes mellitus (T2DM) have been difficult to discern, despite substantial research. More is known about rare forms of diabetes mellitus, several of which ...share clinical and genetic features with the common form of T2DM. In this Review, we discuss the extent to which the study of rare and low-frequency mutations in large populations has begun to bridge the gap between rare and common forms of diabetes mellitus. We hypothesize that the perceived division between these diseases might be due, in part, to the historical ascertainment bias of genetic studies, rather than a clear distinction between disease pathophysiologies. We also discuss possible implications of a new model for the genetic basis of diabetes mellitus subtypes, where the boundary between subtypes becomes blurred.
Maternal overweight and obesity increase risks of pregnancy and delivery complications and neonatal mortality, but the mechanisms are unclear. The objective of the study was to investigate ...associations between maternal body mass index (BMI) in early pregnancy and severe asphyxia-related outcomes in infants delivered at term (≥37 weeks).
A nation-wide Swedish cohort study based on data from the Medical Birth Register included all live singleton term births in Sweden between 1992 and 2010. Logistic regression analyses were used to obtain odds ratios (ORs) with 95% CIs for Apgar scores between 0 and 3 at 5 and 10 minutes, meconium aspiration syndrome, and neonatal seizures, adjusted for maternal height, maternal age, parity, mother's smoking habits, education, country of birth, and year of infant birth. Among 1,764,403 term births, 86% had data on early pregnancy BMI and Apgar scores. There were 1,380 infants who had Apgar score 0-3 at 5 minutes (absolute risk = 0.8 per 1,000) and 894 had Apgar score 0-3 at 10 minutes (absolute risk = 0.5 per 1,000). Compared with infants of mothers with normal BMI (18.5-24.9), the adjusted ORs (95% CI) for Apgar scores 0-3 at 10 minutes were as follows: BMI 25-29.9: 1.32 (1.10-1.58); BMI 30-34.9: 1.57 (1.20-2.07); BMI 35-39.9: 1.80 (1.15-2.82); and BMI ≥40: 3.41 (1.91-6.09). The ORs for Apgar scores 0-3 at 5 minutes, meconium aspiration, and neonatal seizures increased similarly with maternal BMI. A study limitation was lack of data on effects of obstetric interventions and neonatal resuscitation efforts.
Risks of severe asphyxia-related outcomes in term infants increase with maternal overweight and obesity. Given the high prevalence of the exposure and the severity of the outcomes studied, the results are of potential public health relevance and should be confirmed in other populations. Prevention of overweight and obesity in women of reproductive age is important to improve perinatal health.
Carboxyl ester lipase is a digestive pancreatic enzyme encoded by the CEL gene. Mutations in CEL cause maturity-onset diabetes of the young as well as pancreatic exocrine dysfunction. Here we ...describe a hybrid allele (CEL-HYB) originating from a crossover between CEL and its neighboring pseudogene, CELP. In a discovery series of familial chronic pancreatitis cases, we observed CEL-HYB in 14.1% (10/71) of cases compared to 1.0% (5/478) of controls (odds ratio (OR) = 15.5; 95% confidence interval (CI) = 5.1-46.9; P = 1.3 × 10(-6) by two-tailed Fisher's exact test). In three replication studies of nonalcoholic chronic pancreatitis, we identified CEL-HYB in a total of 3.7% (42/1,122) cases and 0.7% (30/4,152) controls (OR = 5.2; 95% CI = 3.2-8.5; P = 1.2 × 10(-11); formal meta-analysis). The allele was also enriched in alcoholic chronic pancreatitis. Expression of CEL-HYB in cellular models showed reduced lipolytic activity, impaired secretion, prominent intracellular accumulation and induced autophagy. These findings implicate a new pathway distinct from the protease-antiprotease system of pancreatic acinar cells in chronic pancreatitis.
Aims/hypothesis
MODY can be wrongly diagnosed as type 1 diabetes in children. We aimed to find the prevalence of MODY in a nationwide population-based registry of childhood diabetes.
Methods
Using ...next-generation sequencing, we screened the
HNF1A
,
HNF4A
,
HNF1B
,
GCK
and
INS
genes in all 469 children (12.1%) negative for both GAD and IA-2 autoantibodies and 469 antibody-positive matched controls selected from the Norwegian Childhood Diabetes Registry (3882 children). Variants were classified using clinical diagnostic criteria for pathogenicity ranging from class 1 (neutral) to class 5 (pathogenic).
Results
We identified 58 rare exonic and splice variants in cases and controls. Among antibody-negative patients, 6.5% had genetic variants of classes 3–5 (vs 2.4% in controls;
p
= 0.002). For the stricter classification (classes 4 and 5), the corresponding number was 4.1% (vs 0.2% in controls;
p
= 1.6 × 10
−5
).
HNF1A
showed the strongest enrichment of class 3–5 variants, with 3.9% among antibody-negative patients (vs 0.4% in controls;
p
= 0.0002). Antibody-negative carriers of variants in class 3 had a similar phenotype to those carrying variants in classes 4 and 5.
Conclusions/interpretation
This is the first study screening for MODY in all antibody-negative children in a nationwide population-based registry. Our results suggest that the prevalence of MODY in antibody-negative childhood diabetes may reach 6.5%. One-third of these MODY cases had not been recognised by clinicians. Since a precise diagnosis is important for treatment and genetic counselling, molecular screening of all antibody-negative children should be considered in routine diagnostics.
Background
Accessibility is acknowledged as a key to inclusion in the Convention of Rights for People with Disabilities. An inaccessible design can result in exclusion from eHealth and cause ...disability among people who have impairments.
Objective
This scoping literature review aimed to investigate how eHealth services have been developed and evaluated regarding accessibility for people with impairments.
Methods
In line with Arksey and O’Malley’s framework for scoping studies and using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR), we conducted a search in 4 databases (PubMed, Scopus, IEEE, and Web of Science) in October 2020 and an update of the search in June 2022. The search strategy was structured according to the PICO model as follows: Population/Problem, digital accessibility for users with impairment; Intervention, health care delivered by any digital solution; Comparison, not applicable; Outcome, use of and adherence to (1) Web Content Accessibility Guidelines (WCAG), (2) other accessibility guidelines, and (3) other means, for designing or evaluating accessibility in eHealth services. A Boolean search was conducted by combining terms related to accessibility and eHealth. All authors participated in screening abstracts according to the eligibility criteria. Each publication, containing a potentially relevant abstract, was read (full text) and assessed for eligibility by 2 authors independently and pairwise. Publications deemed eligible were read by all authors and discussed for consensus.
Results
A total of 8643 publications were identified. After abstract screening, 131 publications remained for full-text reading. Of those, 116 publications were excluded as they did not meet the eligibility criteria. Fifteen publications involving studies of 12 eHealth services were included in the study. Of the 15 publications, 2 provided a definition of accessibility, 5 provided an explanation of accessibility, and 8 did not provide any explanation. Five publications used the WCAG to evaluate accessibility when developing eHealth services. One publication used International Organization for Standardization (ISO) 29138, ISO 2941, and ISO/International Electrotechnical Commission (IEC) 30071-1 standards together with the Spanish Association for Standardization (UNE) 139803 standard. Eleven publications used other means to address accessibility, including text-level grading; literature review about accessibility; user tests, focus groups, interviews, and design workshops with target groups of patients, relatives, and health care professionals; and comparative analysis of existing technical solutions to provide information about useful requirements.
Conclusions
Although a clear definition of accessibility can enhance operationalization and thus measurability when evaluating accessibility in eHealth services, accessibility was insufficiently defined in most of the included studies. Further, accessibility guidelines and standards were used to a very limited extent in the development and evaluation of eHealth services. Guidelines for developing complex interventions that include guidance for accessibility are motivated to ensure that accessibility will be considered systematically in eHealth services.
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