Genome sequencing is a sensitive first-line test to diagnose individuals with intellectual disability.

PURPOSE: Individuals with intellectual disability (ID) and/or neurodevelopment disorders (NDDs) are currently investigated with several different approaches in clinical genetic diagnostics. METHODS: We compared the results from 3 diagnostic pipelines in patients with ID/NDD: genome sequencing (GS) first (N = 100), GS as a secondary test (N = 129), or chromosomal microarray (CMA) with or without FMR1 analysis (N = 421). RESULTS: The diagnostic yield was 35% (GS-first), 26% (GS as a secondary test), and 11% (CMA/FMR1). Notably, the age of diagnosis was delayed by 1 year when GS was performed as a secondary test and the cost per diagnosed individual was 36% lower with GS first than with CMA/FMR1. Furthermore, 91% of those with a negative result after CMA/FMR1 analysis (338 individuals) have not yet been referred for additional genetic testing and remain undiagnosed. CONCLUSION: Our findings strongly suggest that genome analysis outperforms other testing strategies and should replace traditional CMA and FMR1 analysis as a first-line genetic test in individuals with ID/NDD. GS is a sensitive, time- and cost-effective method that results in a confirmed molecular diagnosis in 35% of all referred patients.

Inter-rater reliability of the assessment of learning powered mobility use, version 2.0, when applied with children and adults engaged in Driving to Learn in a powered wheelchair.

INTRODUCTION: The Assessment of Learning Powered mobility use (ALP) tool including the ALP instrument and facilitating strategies, was developed for Driving to Learn. This therapeutic intervention aims to provide children and adults who have profound cognitive disabilities with opportunities to learn tool use through powered mobility practise. To allow for longer intervention periods, a partnership was developed between professionals supervising Driving to Learn and persons accompanying children or adults to their practice sessions. Accompanying persons (relatives or assistants) gradually took on shared responsibility for applying the intervention and conducting assessments with the ALP-instrument. The aim of this study was to test the inter-rater reliability of the ALP-instrument version 2.0 as applied in this novel partnership in assessment and intervention. METHOD: A psychometric analysis compared pair-wise assessments with the ALP-instrument version 2.0, made independently by professional supervisors and accompanying persons following each Driving to Learn session. Weighted kappa statistic was used to compare the matched pair ordinal data. RESULTS: Eight professional supervisors and 22 accompanying persons independently completed assessments with the ALP-instrument after 55 sessions with six children and five adults, who each participated in five Driving to Learn sessions. When the scores from the 55 pairs of assessments were compared, a weighted kappa value of 0.85 was obtained, indicating very good inter-rater reliability between the two rater groups. CONCLUSION: The resulting inter-rater reliability suggests that it is reliable to implement the ALP-instrument as part of partnership in intervention between supervisors and accompanying persons. Provision of longer periods of Driving to Learn is possible when those who accompany the child or adult are able to gradually assume responsibility for practice and assessment under the supervision of a professional. This partnership approach enables children and adults with multiple and complex disabilities to practise and learn in accordance with their conditions and needs.

Influence of well-known risk factors for hearing loss in a longitudinal twin study.

OBJECTIVE: The aim was to investigate the influence of environmental exposures on hearing loss in a twin cohort. STUDY SAMPLE: Male twins born 1914-1958, representing an unscreened population, were tested for hearing loss at two occasions, 18 years apart. DESIGN: Clinical audiometry and a questionnaire were performed at both time points in this longitudinal study. Noise and solvent exposure were assessed using occupational work codes and a job exposure matrix. Hearing impairment was investigated using two different pure tone averages: PTA4 (0.5, 1, 2, and 4 kHz) and HPTA4 (3, 4, 6, and 8 kHz). RESULTS: Age affected all outcome measures. Noise exposure between time point one and two affected the threshold shifts of PTA4 and HPTA4 more in participants with a pre-existing hearing loss at time point one. Lifetime occupational noise exposure was a risk factor especially for the low-frequency hearing threshold PTA4. Firearm use was a statistically significant risk factor for all outcome measures. CONCLUSIONS: Pre-existing hearing loss can increase the risk of hearing impairment due to occupational noise exposure. An increased risk for NIHL was also seen in the group with exposures below 85 dB(A), a result that indicates awareness of NIHL should be raised even for those working in environments where sound levels are below 85 dB(A).

A comparison of occupational and nonoccupational noise exposures in Sweden.

This study was conducted to evaluate noise exposures and the contributions of occupational and nonoccupational activities among three groups of Swedish workers (office workers, day care workers, and military flight technicians), and to evaluate risk factors for elevated hearing threshold levels. Forty-five subjects were recruited across the three groups. Each subject completed a risk factor questionnaire along with Békésy audiometry at frequencies between 125 and 8000 Hz. Subjects also wore a noise dosimeter continuously for 1 week, and documented their occupational and nonoccupational activities using a time-activity log. Subjects in all groups completed >7400 h of dosimetry, and had weekly exposures between 76 and 81 dBA. Day care workers had the highest daily exposures, and flight technicians had the highest weekly exposures. Most daily and weekly exposures exceeded the 70 dBA exposure limit recommended for prevention of any hearing loss. Subjects' perceptions of their exposures generally agreed well with measured noise levels. Among office workers, exposures were predominately nonoccupational, while among flight technicians nonoccupational and occupational activities contributed roughly equally, and among day care workers occupational exposures were dominant. Extreme exposures and cumulative noise exposure were associated with an increased risk of hearing threshold levels >10 dB hearing level. Effective hearing loss prevention programs may be needed in occupations not historically considered to be at high risk of noise-induced hearing loss (e.g., day care workers). Prevention efforts need to address nonoccupational exposures as well as occupational exposures, as nonoccupational activities may present the dominant risk of noise-induced hearing loss for some workers.

Seizures in hospitalised paediatric patients with SARS-CoV-2 and comparison of severity with seizures in hospitalised paediatric patients with other respiratory viruses during the COVID-19 pandemic: a population-based cohort study.

OBJECTIVE: To study seizures in patients hospitalised due to SARS-CoV-2 infection, and compare their severity with seizures in patients hospitalised due to other viral respiratory tract infections (RTIs). DESIGN: Observational population-based cohort study. SETTING: Northern Stockholm. PATIENTS: Patients aged 1 month-18 years hospitalised due to SARS-CoV-2 with and without seizures, and patients of the same age hospitalised due to other viral RTIs with seizures, between 1 March 2020 and 30 June 2022. MAIN OUTCOME MEASURES: The prevalence of seizures in hospitalised patients due to SARS-CoV-2, the evaluation of assumed predictors of seizures and the comparison of severity markers in patients with SARS-CoV-2 versus other RTIs. RESULTS: 32 of 239 included patients (13.4%) admitted due to SARS-CoV-2 infection had seizures. Central nervous system (CNS) disease and the omicron period had significantly increased OR for seizures (OR: 5.12; CI: 2.06 to 12.72 and OR: 3.01; CI: 1.15 to 7.88, respectively). Seizures in patients with SARS-CoV-2 were more common in children older than 5 years (p=0.001), even in the absence of fever (p=0.007), as compared with other viral RTIs. The duration of hospitalisation was longer in patients with seizures due to other viral RTIs (p=0.023). There was no significant difference regarding severity markers of seizures between the two groups. CONCLUSIONS: CNS disease and the omicron period were risk factors for seizures in patients with SARS-CoV-2, who were older than patients with other RTIs. The severity of seizures was comparable between the two groups; hospitalisation was however longer in patients with other RTIs.

The clinical spectrum of ataxia telangiectasia in a cohort in Sweden.

Ataxia telangiectasia (A-T), caused by biallelic variants in the ATM gene, is a multisystemic and severe syndrome characterized by progressive ataxia, telangiectasia, hyperkinesia, immunodeficiency, increased risk of malignancy, and typically death before the age of 30. In this retrospective study we describe the phenotype of 14 pediatric and adult A-T patients evaluated at the Karolinska University Hospital in Sweden during the last 12 years. Most of the patients in this cohort were severely affected by ataxia and wheelchair use started at a median age of 9 years. One patient died before the age of 30 years, but five patients had survived beyond this age. Four patients received prophylactic immunoglobulin replacement therapy due to hypogammaglobulinemia and respiratory complications ranged from mild to moderate severity. Three patients developed type 2 diabetes in young adulthood and nine patients (64%) had a history of elevated liver function tests. Four patients were diagnosed with cancer at ages 7, 41, 47, and 49 years. All the ATM variants in these patients were previously reported as pathogenic except one, c.6040G > A, which results in a p.Glu2014Lys missense variant. With increased life expectancy, A-T complications such as diabetes type 2 and liver disease may become more common. Despite having severe neurological presentations, the A-T patients in this case series had relatively mild infectious and respiratory complications.

Participants' dynamic orientation to folder navigation when using a VOCA with a touch screen in talk-in-interaction.

This paper reports on a conversation-analysis case study of interaction between a child with cerebral palsy and an adult using a computer-based voice output communication aid (VOCA) device with a touch-sensitive screen-input system. Data was collected from video recordings of everyday activities at school. The public nature of the VOCA-mediated turn construction process (hand movements towards the screen, on-screen folder navigation, synthetic speech) displays the projection of the turn under way and its possible continuations. The adult interlocutor orients to such projections when contributing to the topic of the ongoing turn and when initiating repair on its topical development. Contributing may activate the AAC user's further involvement in the ongoing turn, while repair may restrict the AAC user's influence on the topical progression. The findings are relevant for clinical assessment and intervention.

Prospective Evaluation of Childhood Encephalitis: Predisposing Factors, Prevention and Outcome.

BACKGROUND: Acute encephalitis in childhood is a serious condition. The severity varies between studies, partly reflecting differences in study design where only severe cases from referral centers often are reported. The aim of this study was to prospectively study the clinical picture and etiology of acute encephalitis in childhood at a primary and tertiary pediatric hospital in Sweden. METHODS: All children with acute encephalitis were prospectively included from 2011 to 2016. Laboratory tests, investigations and follow-up were performed according to standardized study protocols. RESULTS: Eighty-nine children were included (46 female and 43 male) with a median age of 53 months. An etiology was established in 61/89. Tick-borne encephalitis virus, enterovirus and rotavirus dominated and 34% were caused by a virus preventable by vaccination. Immune-mediated encephalitis was seen in 7 children. An abnormal electroencephalography picture was seen in 77/86, pathologic findings on neuroimaging in 13/49, and 38/89 children had seizures. Sequelae were reported by 49%. A high prevalence of previous contact with child and adolescent psychiatry was seen and, although not statistically significant, the need for extra support at school before encephalitis and the presence of central nervous system disease in the family seemed to predispose for a longer hospital stay. CONCLUSION: Encephalitis is a condition with long-term consequences. Most children need admission to hospital, and many need surveillance in the intensive care unit. The etiology can be determined in a majority of cases, and 1/3 could have been prevented by vaccination. This study corroborates electroencephalography as a cornerstone in diagnosis.

Noise Exposure and Hearing Impairment in Air Force Pilots.

OBJECTIVE: The goal of this study was to estimate noise exposure and hearing impairments in Swedish military pilots. It also aimed to analyze possible relations between noise exposure and hearing impairments.METHODS: The study group was an open cohort of 337 male pilots. They were longitudinally followed with pure tone audiograms every fifth year from the beginning of flight service until discharge. Outcome measures were prevalence of thresholds >20 dB HL and >40 dB HL at different ages, and incidence of impairments >20 dB HL, 30 dB HL, and 40 dB HL. Exposure variables were individual flight data and noise dose measurements. The ISO 1999 Database A was used for reference data.RESULTS: At 50 yr of age, 41% of the pilots were exposed to an equivalent noise dose exceeding the EU action level of Leq 80 dB(A). We observed significant elevated prevalence values of thresholds >20 dB HL in all age classes compared to the ISO 1999 Database A. These elevations were most pronounced at ages 30 and 40 yr and at 4 and 6 kHz in the left ear. Significantly elevated prevalence values of thresholds >40 dB HL compared to the ISO 1999 Database A were observed at age 40 and 50 yr at 4 and 6 kHz. In a Cox analysis we observed elevated hazard ratios of deteriorating thresholds with longer flight time/year in fast jet pilots.DISCUSSION: Military pilots had elevated prevalence values of hearing impairment. Of the subjects, 41% had been exposed to noise exceeding the EU risk limit. Increased flight time/year and flying fast jets were associated with elevated risk of hearing deterioration.Muhr P, Johnson A-C, Selander J, Svensson E, Rosenhall U. Noise exposure and hearing impairment in air force pilots. Aerosp Med Hum Perform. 2019; 90(9):757-763.

Experiences of returning to work after acquired brain injury.

The purpose of this qualitative study was to explore experiences of returning to work after rehabilitation, from the viewpoint of people with acquired brain injury. A purposive sampling of eight informants was made, and data were collected through personal interviews with open questions. The data were then analysed through qualitative content analyses in five steps, resulting in four main categories of experiences: "A new person", "Stimulants and fellowship", "Understanding and support", and "To reach insight" with appurtenant sub-categories. The overarching theme was "Returning to work after acquired brain injury is a long process". The conclusion of this study is that returning to work after acquired brain injury requires motivated individuals, flexible work, accommodating labour management, and prolonged environmental support. This study also shows that the informants need support for a long period of time to reach a balance and to obtain a functional working role. In order to achieve this, client-centred rehabilitation, professional teamwork, and longer follow-up periods than those of today are required.

How to avoid glucose degradation products in peritoneal dialysis fluids.

OBJECTIVE: The formation of glucose degradation products (GDPs) during sterilization of peritoneal dialysis fluids (PDFs) is one of the most important aspects of biocompatibility of glucose-containing PDFs. Producers of PDFs are thus trying to minimize the level of GDPs in their products. 3,4-Dideoxyglucosone-3-ene (3,4-DGE) has been identified as the most bioreactive GDP in PDFs. It exists in a temperature-dependent equilibrium with a pool of 3-deoxyglucosone (3-DG) and is a precursor in the irreversible formation of 5-hydroxymethyl furaldehyde (5-HMF). The aim of the present study was to investigate how to minimize GDPs in PDFs and how different manufacturers have succeeded in doing so. DESIGN: Glucose solutions at different pHs and concentrations were heat sterilized and 3-DG, 3,4-DGE, 5-HMF, formaldehyde, and acetaldehyde were analyzed. Conventional as well as biocompatible fluids from different manufacturers were analyzed in parallel for GDP concentrations. RESULTS: The concentrations of 3-DG and 3,4-DGE produced during heat sterilization decreased when pH was reduced to about 2. Concentration of 5-HMF decreased when pH was reduced to 2.6. After further decrease to a pH of 2.0, concentration of 5-HMF increased slightly, and below a pH of 2.0 it increased considerably, together with formaldehyde; 3-DG continued to drop and 3,4-DGE remained constant. Inhibition of cell growth was paralleled by 3,4-DGE concentration at pH 2.0 - 6.0. A high glucose concentration lowered concentrations of 3,4-DGE and 3-DG at pH 5.5 and of 5-HMF at pH 1. At pH 2.2 and 3.2, glucose concentration had a minor effect on the formation of GDPs. All conventional PDFs contained high levels of 3,4-DGE and 3-DG. Concentrations were considerably lower in the biocompatible fluids. However, the concentration of 5-H M F was slightly higher in all the biocompatible fluids. CONCLUSION: The best way to avoid reactive GDPs is to have a pH between 2.0 and 2.6 during sterilization. If pHs outside this range are used, it becomes more important to have high glucose concentration during the sterilization process. There are large variations in GDPs, both within and between biocompatible and conventionally manufactured PDFs.

Audiological findings in workers exposed to styrene alone or in concert with noise.

Audiological testing, interviews and exposure measurements were used to collect data on the health effects of styrene exposures in 313 workers from fiberglass and metal-product manufacturing plants and a mail terminal. The audiological test battery included pure-tone audiometry, distortion product otoacoustic emissions (DPOAE), psychoacoustic modulation transfer function, interrupted speech, speech recognition in noise and cortical response audiometry (CRA). Workers exposed to noise and styrene had significantly poorer pure-tone thresholds in the high-frequency range (3 to 8 kHz) than the controls, noise-exposed workers and those listed in a Swedish age-specific database. Even though abnormalities were noted on DPOAE and CRA testing, the interrupted speech and speech recognition in noise tests were the more sensitive tests for styrene effects. Further research is needed on the underlying mechanisms to understand the effects of styrene and on audiological test batteries to detect changes in populations exposed to solvents.

Take care in how you store your PD fluids: actual temperature determines the balance between reactive and non-reactive GDPs.

OBJECTIVE: During heat sterilization and during prolonged storage, glucose in peritoneal dialysis fluids (PDF) degrades to carbonyl compounds commonly known as glucose degradation products (GDPs). Of these, 3,4-dideoxyglucosone-3-ene (3,4-DGE) is the most cytotoxic. It is an intermediate in degradation between 3-deoxyglucosone (3-DG) and 5-hydroxymethyl-2-furaldehyde (5-HMF). We have earlier reported that there seems to be equilibrium between these GDPs in PDF. The aim of the present study was to investigate details of this equilibrium. METHODS: Aqueous solutions of pure 3-DG, 3,4-DGE, and 5-HMF were incubated at 40 degrees C for 40 days. Conventional and low-GDP fluids were incubated at various temperatures for up to 3 weeks. Formaldehyde, acetaldehyde, glyoxal, methylglyoxal, 3-DG, 3,4-DGE, and 5-HMF were analyzed using high performance liquid chromatography. RESULTS: Incubation of 100 micromol/L 3,4-DGE resulted in the production of 36 micromol/L 3-DG, 4 micromol/L 5-HMF, and 40 micromol/L unidentified substances. With the same incubation, 200 micromol/L 3-DG was converted to 9 micromol/L 3,4-DGE, 6 micromol/L 5-HMF, and 14 micromol/L unidentified substances. By contrast, 100 micromol/L 5-HMF was uninfLuenced byincubation. In a conventional PDF incubated at 60 degrees C for 1 day, the 3,4-DGE concentration increased from 14 to a maximum of 49 micromol/L. When the fluids were returned to room temperature, the concentration decreased but did not reach original values until after 40 days. In a low GDP fluid, 3,4-DGE increased and decreased in the same manner as in the conventional fluid but reached a maximum of only 0.8 micromol/L. CONCLUSIONS: Considerable amounts of 3,4-DGE may be recruited by increases in temperature in conventional PDFs. Lowering the temperature will again reduce the concentration but much more time will be needed. Precursors for 3,4-DGE recruitment are most probably 3-DG and the enol 3-deoxyaldose-2-ene, but not 5-HMF. Considering the ease at which 3,4-DGE is recruited from its pool of precursors and the difficulty of getting rid of it again, one should be extremely careful with the temperatures conventional PDFs are exposed to.

Oscillometric casual blood pressure normative standards for Swedish children using ABPM to exclude casual hypertension.

BACKGROUND: Casual blood pressure (CBP) is considered a reliable proxy for cardiovascular health. Although the auscultatory technique is the reference standard method for measuring CBP, oscillometric devices are increasingly being used in children. We sought to establish oscillometric CBP normative standards for Swedish children. METHODS: Cross-sectional oscillometric CBP readings were obtained by the Welch Allyn Spot Vital Signs 420 monitor and measured according to the International Guidelines' recommendations. Participants with elevated oscillometric CBP levels underwent verification by the auscultatory method. Ambulatory blood pressure monitoring (ABPM) was used to exclude casual hypertension. Data on 1,470 (772 males) apparently healthy Swedish schoolchildren aged 6-16 years were analyzed and sex-specific reference charts normalized to age or height were constructed. RESULTS: Systolic and diastolic CBP values were significantly higher with age, height, height standard deviation score (SDS), body mass index (BMI), and BMI SDS. Gender differences for systolic CBP were present starting from age of 15 years and revealed significantly higher values in boys than in girls, whereas for diastolic CBP, the differences were apparent at the age of 12 years, with higher values in girls. Increased BMI and BMI SDS were positively associated with CBP levels. Positive parental history of hypertension turned out to be a risk factor for higher systolic and diastolic CBP across all ages. CONCLUSIONS: Our normative standard for CBP can be used for blood pressure screening and control programs in Swedish children. The use of ABPM should be considered to confirm the diagnosis of casual hypertension.

Audiometric findings in workers exposed to low levels of styrene and noise.

Audiometry and exposure measurements were conducted on workers from fiberglass and metal products manufacturing plants and a mail distribution terminal (N = 313). Workers exposed to noise and styrene had significantly worse pure-tone thresholds at 2, 3, 4, and 6 kHz when compared with noise-exposed or nonexposed workers. Age, noise exposure, and urinary mandelic acid (a biologic marker for styrene) were the variables that met the significance level criterion in the multiple logistic regression. The odds ratios for hearing loss were 1.19 for each increment of 1 year of age (95% confidence interval [CI], 1.11-1.28), 1.18 for every decibel >85 dB(A) of noise exposure (95% CI, 1.01-1.34), and 2.44 for each millimole of mandelic acid per gram of creatinine in urine (95% CI, 1.01-5.89). Our findings suggest that exposure to styrene even below recommended values had a toxic effect on the auditory system.

[Compulsory outpatient treatment can prevent involuntary commitment].

Compulsory outpatient treatment (co-pt) has been possible in Denmark since 2010. The aim is to secure necessary treatment, reduce involuntary commitment and improve quality of life for patients with a severe psychiatric illness. Co-pt has been brought into use in 33 cases. This case report describes a patient with paranoid schizophrenia who several times developed severe psychotic symptoms shortly after discharge due to lack of compliance with treatment. Within one year of co-pt the patient was not admitted to hospital and improved in overall functioning. After terminating co-pt the patient rapidly deteriorated into psychotic relapse.

Beliefs and attitudes among Swedish workers regarding the risk of hearing loss.

The beliefs and attitudes regarding the risk of hearing loss and their impact on hearing protector use were investigated among Swedish workers. A questionnaire, developed by the US National Institute for Occupational Safety and Health (NIOSH), was used. The study objective was to assess workers' attitudes towards using hearing protection devices (HPDs) and to enhance the ability of workers to protect themselves from occupational hearing loss. Ninety-five per cent of the respondents were aware that loud noise could damage their hearing, 90% considered that a hearing loss would be a serious problem, and 85% believed that HPDs could protect their hearing. However, lower percentages of workers always used the HPDs when they were noise-exposed. Fifty-five per cent of the workers indicated that they could not hear warning signals when using HPDs, and 45% of the workers indicated that they considered HPDs to be uncomfortable. These issues must be addressed to make HPD use more effective.

Survival factors regulating ovarian apoptosis -- dependence on follicle differentiation.

Only a minute fraction of the ovarian follicles present in a fetal ovary will complete the path to ovulation. Most of the follicles will undergo atresia, a hormonally controlled apoptotic process. Apoptosis occurs at each stage of follicular development and there is a marked reduction in the number of follicles present at birth. Stage-dependent mechanisms of follicle survival can be postulated to achieve co-ordinated development, leading to ovulation of a small fraction of follicles. Indeed, hormone and growth factor regulation of follicular atresia is stage-specific. This short review considers the factors that promote survival of ovarian follicles throughout development, including endocrine, locally produced and intracellular mediators, as exemplified mainly by follicular development in rodents. In primordial follicles, oocyte apoptosis is considered to be the cause of subsequent follicle degeneration. In slow-growing preantral follicles, FSH is not a survival factor, but some locally produced growth factors are. Progression to the antral follicle stage is probably the most critical stage of follicle development in vivo, and FSH is a major survival factor at this stage. In addition, insulin-like growth factor I and interleukin 1beta are potent survival factors for cultured rat follicles at the antral stage. Preovulatory follicles express receptors for LH, and both of the gonadotrophins are survival factors at this stage. Relatively little is known about the period between the LH surge and ovulation; however, it has been suggested that at this stage progesterone acts as a survival factor.