Self-reported shorter/longer sleep duration, insomnia, and evening preference are associated with hyperglycaemia in observational analyses, with similar observations in small studies using accelerometer-derived sleep traits. Mendelian randomization (MR) studies support an effect of self-reported insomnia, but not others, on glycated haemoglobin (HbA1c). To explore potential effects, we used MR methods to assess effects of accelerometer-derived sleep traits (duration, mid-point least active 5-h, mid-point most active 10-h, sleep fragmentation, and efficiency) on HbA1c/glucose in European adults from the UK Biobank (UKB) (n = 73,797) and the MAGIC consortium (n = 146,806). Cross-trait linkage disequilibrium score regression was applied to determine genetic correlations across accelerometer-derived, self-reported sleep traits, and HbA1c/glucose. We found no causal effect of any accelerometer-derived sleep trait on HbA1c or glucose. Similar MR results for self-reported sleep traits in the UKB sub-sample with accelerometer-derived measures suggested our results were not explained by selection bias. Phenotypic and genetic correlation analyses suggested complex relationships between self-reported and accelerometer-derived traits indicating that they may reflect different types of exposure. These findings suggested accelerometer-derived sleep traits do not affect HbA1c. Accelerometer-derived measures of sleep duration and quality might not simply be \'objective\' measures of self-reported sleep duration and insomnia, but rather captured different sleep characteristics.

BACKGROUND: Limited evidence exists regarding children receiving home healthcare devices (HHDs). This study aimed to describe the range and type of HHD use by children with chronic medical conditions in Japan and explore factors leading to increased use of these devices.
METHODS: This retrospective cohort study was conducted using data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan. Children receiving HHD aged ≤18 years between April 2011 and March 2019 were included. Children newly administered HHD between 2011 and 2013 were followed up for 5 years, and logistic regression analysis was performed to assess the relationship between increased HHD use and each selected risk factor (comorbidity or types of HHD). The models were adjusted for age category at home device introduction, sex and region.
RESULTS: Overall, 52 375 children receiving HHD were identified. The number (proportion) of children receiving HHD increased during the study period (11 556 [0.05%] in 2010 and 25 593 [0.13%] in 2018). The most commonly administered HHD was oxygen (51.0% in 2018). Among the 12 205 children receiving HHD followed up for 5 years, 70.4% and 68.3% who used oxygen or continuous positive airway pressure, respectively, were released from the devices, while only 25.8% who used mechanical ventilation were released from the device. The following diagnosis/comorbidities were associated with increased HHD use: other neurological diseases (OR): 2.85, 95% CI): 2.54-3.19), cerebral palsy (OR: 2.16, 95% CI: 1.87 to 2.49), congenital malformations of the nervous system (OR: 1.70, 95% CI: 1.34 to 2.13) and low birth weight (OR: 1.68, 95% CI: 1.41 to 2.00).
CONCLUSIONS: This study provides nationwide population-based empirical data to clarify the detailed information regarding children receiving HHD in Japan. This information could assist healthcare professionals in improving the quality of life of these children and their families and help health policymakers consider measures.

Pulmonary hypertension (PH), a syndrome characterized by elevated pulmonary pressures, commonly complicates connective tissue disease (CTD) and is associated with increased morbidity and mortality. The incidence of PH varies widely between CTDs; patients with systemic sclerosis are most likely to develop PH. Several different types of PH can present in CTD, including PH related to left heart disease and respiratory disease. Importantly, CTD patients are at risk for developing pulmonary arterial hypertension, a rare form of PH that is associated with high morbidity and mortality. Future therapies targeting pulmonary vascular remodeling may improve outcomes for patients with this devastating disease.

Chronic pain (CP) significantly impacts quality of life and increases non-communicable disease risk, with recent U.S. data showing a 6.3% incidence rate, surpassing diabetes, depression, and hypertension. International studies suggest higher mortality in CP populations, yet prior U.S. data is inconclusive. To investigate CP\'s mortality risk, we analyzed National Health Interview Survey (NHIS) and National Death Index (NDI) data. We hypothesized individuals with CP and high-impact CP (HICP, (≥1 activity limitation) would exhibit higher mortality rates. NHIS provided demographics, pain reporting, lifestyle, and psychosocial data, matched with NDI mortality records. Chi-Square analyses explored relationships between CP/HICP and demographics, lifestyle factors, psychosocial variables, and mortality. Cox proportional hazards models assessed mortality risk between groups. The weighted sample was 245,899,776; 20% reported CP and 8% HICP, both groups exhibiting higher mortality rates than pain-free individuals (CP: 5.55%, HICP: 8.79%, total: 2.82%). Hazard ratios indicated nearly double the mortality risk for CP and two-and-a-half times higher risk for HICP compared to those without these conditions. Adjusting for lifestyle and psychosocial factors reduced mortality risk but remained elevated compared to non-CP individuals. Heart disease, malignant neoplasms, and chronic lower respiratory diseases accounted for a higher percentage of deaths in CP cases. CP individuals showed higher rates of smoking, alcohol consumption, obesity, inactivity, depression, anxiety, emotional problems, and sleep disturbances. CP and HICP significantly influence mortality outcomes, leading to excess deaths compared to pain-free individuals. Given the relationship between pain, lifestyle, psychosocial variables, and mortality, further investigations are needed into CP causation and prevention strategies. PERSPECTIVE: This article presents evidence regarding the relationship between chronic pain, high impact chronic pain, and mortality. Additional findings are discussed regarding the impact of demographics, lifestyle, and psychosocial variables on mortality in those with versus without chronic pain and high impact chronic pain. These findings are crucial for informing future research, prevention, and healthcare management strategies.

BACKGROUND: Associations between magnetic resonance imaging (MRI)-detected lumbar intervertebral disc degeneration (LDD) and LBP are often of modest magnitude. This association may be larger in specific patient subgroups.
OBJECTIVE: To examine whether the association between LDD and LBP is modified by underlying genetic predispositions to pain.
METHODS: Cross-sectional study in UK Biobank (UKB) and TwinsUK.
METHODS: A genome-wide association study (GWAS) of the number of anatomical chronic pain locations was conducted in 347,538 UKB participants. The GWAS was used to develop a genome-wide polygenic risk score (PRS) in a holdout sample of 30,000 UKB participants. The PRS model was then used in analyses of 645 TwinsUK participants with standardized LDD MRI assessments.
METHODS: Ever having had LBP associated with disability lasting ≥1 month (LBP1).
METHODS: Using the PRS as a proxy for \"genetically-predicted propensity to pain\", we stratified TwinsUK participants into PRS quartiles. A \"basic\" model examined the association between an LDD summary score (LSUM) and LBP1, adjusting for covariates. A \"fully-adjusted\" model also adjusted for PRS quartile and LSUM x PRS quartile interaction terms.
RESULTS: In the basic model, the odds ratio (OR) of LBP1 was 1.8 per standard deviation of LSUM (95% confidence interval [CI] 1.4 -2.3). In the fully-adjusted model, there was a statistically significant LSUM-LBP1 association in quartile 4, the highest PRS quartile (OR = 2.5 [95% CI 1.7-3.7], p=2.6×10-6), and in quartile 3 (OR=2.0, [95% CI 1.3-3.0]; p=0.002), with small-magnitude and/or non-significant associations in the lowest two PRS quartiles. PRS quartile was a significant effect modifier of the LSUM-LBP1 association (interaction p≤0.05).
CONCLUSIONS: Genetically-predicted propensity to pain modifies the LDD-LBP association, with the strongest association present in people with the highest genetic propensity to pain. Lumbar MRI findings may have stronger connections to LBP in specific subgroups of people.

Enterococci are Gram-positive coccus bacteria that are normally present in the gastrointestinal tract and ordinarily function commensally with humans. Very few studies have investigated the characteristics of enterococcal infections. We aimed to characterize patients with urinary tract infections (UTIs) due to Enterococci and their outcomes. This was a retrospective cohort study between June 2012-November 2022. Patients who had clinically and microbiologically confirmed Enterococcal UTI based on a urine culture positive for E. faecalis or E. faecium with a count of ≥ 105 CFU/mL and having urinary tract symptoms were included. A total of 396 patients were eligible and included. The patients had a median age of 61 years and were mostly females (56.8%). The most common characteristics were hospitalization in a non-ICU ward, having a urinary catheter, and recent use of antibiotics within the last 3 months (66.4%, 59.3%, and 51.8%, respectively). Infection with E. faecalis was more common than E. faecium (77.3% vs. 22.7%). However, the latter exhibited higher rates of antibiotic resistance (P<0.001 to several antibiotics) and was associated with significantly higher median C-reactive protein level (26.7 vs. 13 mg/dL; P=0.025), mortality (23% vs. 10.1%; P=0.002), and median length of stay (25 vs. 11.5 days; P<0.001). We found that most patients with enterococcal UTIs had a history of having a urinary catheter and recent antibiotic use and were mostly females and hospitalized in non-ICU wards. E. faecium-infected patients experienced more severe episodes and poorer outcomes compared to patients infected with E. faecalis; thus, would need more aggressive therapy.

BACKGROUND: The incidence of sudden cardiac arrest (SCA) during acute coronary syndrome is somewhat unclear, since often subjects dying before the first healthcare contact are not included in the estimates. We aimed to investigate the complete incidence of SCA during ACS.
METHODS: The study population consists of two cohorts. The first cohort includes 472 ACS patients from Northern Ostrobothnia, Finland from year 2016 and the second cohort 162 autopsy-verified SCD subjects (extrapolated) from the same region and year, whose death was attributable to coronary artery disease (CAD) and ACS. An extrapolation of SCA incidence during ACS was done by utilizing autopsy data and data from prior autopsy study on this sample.
RESULTS: The overall incidence of SCA in the setting of ACS was 17.5%. The incidence of SCA was 20.6% in all ACS subjects without prior CAD diagnosis, and 25.4% in STEMI subjects without prior CAD diagnosis. In subjects with previously diagnosed CAD, the incidence of SCA was 10.9% in all ACS subjects and 16.1% in STEMI subjects. There was a statistically significant difference in the incidence of SCA between subjects with and without prior CAD diagnoses (p=0.0052).
CONCLUSIONS: The inclusion of ACS-SCA subjects dying before the first emergency medical service (EMS) contact results in a higher and likely more accurate estimation of SCA during ACS. The incidence of SCA was higher among subjects without prior CAD diagnosis. The high mortality rate highlights the importance of early ACS detection to reduce the burden of CAD-related premature deaths.

Early detection of melanoma is a major determinant in disease outcome and drives the number of (over)excised naevi in clinical practice. This study aimed to evaluate demographic features and melanoma risk of clinically suspicious, mainly flat naevus subtypes. Based on the methodology of ex vivo dermoscopy and derm dotting, the 12 most prevalent naevus subtypes were identified in a collection of over 7000 naevi excised for medical reason. Dermoscopical, histopathological and clinical features of these subtypes were described. In addition, the association with melanoma history, histopathological atypia and melanoma occurrence within naevi was compared. Nearly half of the naevi removed for medical reasons were of the hypermelanotic subtype with no or mild histopathological atypia and low melanoma association, suggesting overtreatment in daily practice. Contrarily, the subtypes atypical lentiginous naevus and orange pulverocytic flat naevus were associated with higher proportions of (severe) atypia and melanoma (history). We believe these subtypes may reflect different tumoural and/or (germline) genetic entities with different melanoma risk. The data from this study may direct further prospective research on specific naevus subtypes in order to obtain better insights in associated clinical/genetic factors and melanoma risk.

OBJECTIVE: Metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiometabolic conditions affect populations across economic strata. Nevertheless, there are limited epidemiological studies addressing these diseases in low (LICs) and lower-middle-income countries (lower MICs). Therefore, an analysis of the trend of MASLD and cardiometabolic conditions in these countries is necessary.
METHODS: From 2000 to 2019, jointpoint regression analysis was employed to calculate the prevalence, mortality, and disability-adjusted life years (DALYs) for cardiometabolic conditions including MASLD, type 2 diabetes mellitus (T2DM), dyslipidemia (DLP), hypertension (HTN), obesity, peripheral artery disease (PAD), atrial fibrillation and flutter (AF/AFL), ischemic heart disease (IHD), stroke, and chronic kidney disease from HTN and T2DM, in LICs and lower MICs (according to the World Bank Classification 2019) using the Global Burden of Disease 2019 data.
RESULTS: Among the eleven cardiometabolic conditions, MASLD (533.65 million), T2DM (162.96 million), and IHD (76.81 million) had the highest prevalence in LICs and Lower MICs in 2019. MASLD represented the largest proportion of global prevalence in these countries (43 %). From 2000 to 2019, mortality in LICs and lower MICs increased in all cardiometabolic conditions, with obesity-related mortality having the highest increase (+134 %). During this timeframe, there were increased age-standardized death rates (ASDR) from obesity, PAD, and AF/AFL. From all conditions, the DALYs-to-prevalence ratio was higher in LICs and lower MICs than the global average.
CONCLUSIONS: The burden of MASLD and cardiometabolic conditions is increasing worldwide, with LICs and lower MICs experiencing higher disability per prevalence. As these conditions are preventable, counteracting these trends requires not only the modification of ongoing actions but also the strategizing of immediate interventions.

BACKGROUND: The current Institute of Medicine pregnancy weight gain guidelines were developed using the best available evidence, but were limited by substantial knowledge gaps. Some have raised concern that the guidelines for individuals affected by overweight or obesity are too high and contribute to short- and long-term complications for the mother and child.
OBJECTIVE: To determine the association between pregnancy weight gain below the lower limit of the current Institute of Medicine (IOM) recommendations and risk of 10 adverse maternal and child health outcomes among individuals with overweight and obesity.
METHODS: We used data from a prospective cohort study of US nulliparae with prepregnancy overweight (n=955) or obesity (n=897) followed from the first trimester to 2-7 years postpartum. We used multivariable Poisson regression to relate pregnancy weight gain z-scores with a severity-weighted composite outcome consisting of ≥1 of 10 adverse outcomes (gestational diabetes, preeclampsia, unplanned cesarean delivery, maternal postpartum weight increase >10kg, maternal postpartum metabolic syndrome, infant death, stillbirth, preterm birth, small-for-gestational age birth, and childhood obesity).
RESULTS: Pregnancy weight gain z-scores below, within, and above the IOM-recommended ranges occurred in 5%, 13%, and 80% of pregnancies with overweight and 17%, 13%, and 70% of pregnancies with obesity. There was a positive association between pregnancy weight gain z-scores and all adverse maternal outcomes, childhood obesity, and the composite outcome. Pregnancy weight gain z-scores below the lower limit of the recommended ranges (<6.8 kg for overweight, <5 kg for obesity) were not associated with the severity-weighted composite outcome. For example, compared with the lower limit, adjusted rate ratios (95% confidence interval) for z-scores of -2 standard deviations in pregnancies with overweight (equivalent to 3.6kg at 40 weeks) and obesity (-2.8kg at 40 weeks) were 0.99 (0.91, 1.06) and 0.97 (0.87, 1.07).
CONCLUSIONS: These findings support arguments to decrease the lower limit of recommended weight gain ranges in these prepregnancy BMI groups.