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The school-based prospective cohort study showed that higher baseline tessellation density (TD) was associated with rapid AL elongation (>0.36 mm/year) and SE progression (>1.00 D/year) in children aged 7 to 9 years. TD is a potential indicator to identify children at a high risk of rapid progression, urging early follow-ups and interventions.

Chronic obstructive pulmonary disease (COPD) is a long-term, irreversible, and progressive respiratory disease that often leads to lung function decline. Pulmonary function tests (PFTs) provide valuable information for diagnosing COPD; however, they are underutilised in clinical practice, with only a subset of test values being used for decision making. The final clinical diagnosis requires combining PFT results with patient information, symptoms, and other tests, such as imaging and blood analysis. This study aims to comprehensively utilise all the testing information in PFTs to assist in the diagnosis of COPD. Various machine learning models, such as logistic regression, support vector machine (SVM), k-nearest neighbour (KNN), random forest, decision tree, and XGBoost, have been employed to establish COPD diagnosis assistance models. The XGBoost model, trained with features extracted by the group LASSO algorithm, achieved the best performance, with an area under the receiver operating characteristic curve (ROC) of 0.90, 88.6% accuracy, and 98.5% sensitivity. This model can assist doctors in the clinical diagnosis and early prediction of COPD.

PurposeTo compare mydriatic and eye-steering ultrawide field imaging (UWFI) with standard non-mydriatic UWFI examination in detecting peripheral retinal lesions in myopic patients.MethodsCross-sectional, observational study. 220 eyes of 110 myopic patients with known peripheral retinal lesions in at least one eye under Goldmann three mirror contact lens examination were recruited. Non-mydriatic standard and eye-steering UWFI images were taken centrally and with eye-steering technique in upper, lower, nasal and temporal gazes under Optomap UWFI (Daytona, Optos, UK). Mydriatic standard and eye-steering UWFI was captured in central gaze and four different peripheral gazes. Sensitivity of detecting peripheral retinal lesions under different UWFI settings was compared.Results141 (64.09%) eyes were with peripheral retinal lesions. The sensitivity for detecting peripheral lesions from low to high was 41.84% (95% CI 33.62% to 50.54%) under non-mydriatic standard UWFI setting, 52.48% (95% CI 44.08% to 60.75%) under mydriatic standard setting, 75.18% (95% CI 67.21% to 82.06%) under non-mydriatic eye-steering setting and 86.52% (95% CI 79.76% to 91.69%) under mydriatic eye-steering setting. Both mydriasis and eye-steering technique increased sensitivity of detecting peripheral lesions with statistical significance (p<0.001). By applying eye-steering technique, sensitivity of detecting lesions located in superior and inferior quadrants witnessed a greater increase compared with other two quadrants (p<0.05). Neither spherical equivalence (p>0.05) nor axial length (p>0.05) was an independent influence factor for detecting peripheral lesions.ConclusionsEye-steering technique and mydriasis could both efficiently improve the sensitivity of detecting peripheral retinal lesions in myopic patients. Lesions of superior and inferior quadrants benefited more from eye-steering technique.

Worldwide, hypertensive disorders of pregnancy (HDPs) affect up to 10% of pregnancies. It has been associated with adverse pregnancy and birth outcomes, as well as diseases in the offspring later in life, such as metabolic syndrome, and neurodevelopmental and psychiatric disorders. It has been proposed that maternal HDPs may increase the susceptibility of offspring to disease through multiple pathways, such as placental dysfunction, a hypoxic-ischemic environment in pregnancy, abnormal inflammatory levels, and epigenetic changes. However, there is a scarcity of evidence to support this association. The aim of this study was to examine the association between maternal HDPs with mortality in offspring from birth to young adulthood.This was a population-based cohort study based on data from Danish national health registries. Included were all live births in Denmark between 1978 and 2018. Excluded were those with a birth weight <500 g and gestational age at birth <22 weeks and those who died on the day of birth. Live-born individuals were followed from the date of birth until the date of death, emigration, or December 31, 2018, whichever came first. Maternal HDP was categorized as eclampsia, preeclampsia, or hypertension.Overall, 4.2% of 2,437,718 live-born offspring were exposed prenatally to maternal HDP, including 2.8% exposed to preeclampsia or eclampsia and 1.4% to hypertension. During follow-up of up to 41 years (median, 19.4 [interquartile range 9.7–28.7] years), there were 781 deaths (58.94 per 100,000 person years) among offspring exposed to preeclampsia, 17 deaths (133.73 per 100,000) among those exposed to eclampsia, 223 deaths (44.38 per 100,000) among those exposed to hypertension, and 19,119 deaths (41.99 per 100,000) among those not exposed to HDP. The HDP-exposed cohort had a higher cumulative incidence of all-cause mortality than the nonexposed cohort (2.06% [95% confidence interval {CI}, 1.82%–2.34%] vs 1.69% [95% CI, 1.65%–1.73%]), a 0.37% difference (95% CI, 0.11%–0.64%). The HDP-exposed cohort also had a 26% higher risk (hazard ratio, 1.26 [95% CI, 1.18–1.34]) of all-cause mortality than nonexposed offspring. The risks of all-cause mortality were 29% in those exposed to preeclampsia (1.29 [95% CI, 1.20–1.38]), 118% in those exposed to eclampsia (2.88 [95% CI, 1.79–4.63]), and 12% in those exposed to hypertension (1.12 [95% CI, 0.98–1.28]). There were increased risks for cause-specific mortality in the HDP-exposed cohort, including from digestive diseases (2.09 [95% CI, 1.27–3.43]); conditions originating in the perinatal period (2.04 [95% CI, 1.81–2.30]); endocrine, nutritional, and metabolic diseases (1.56 [95% CI, 1.08–2.27]); and cardiovascular diseases (1.52 [95% CI, 1.08–2.13]).In conclusion, maternal HDP was associated with increased risks of all-cause mortality, as well as cause-specific deaths, including digestive diseases; conditions originating in the perinatal period; endocrine, nutritional, and metabolic diseases; and cardiovascular disease.

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ObjectivesThe study aimed to investigate the association between maternal body mass index (BMI) in early pregnancy and children’s intellectual disability (ID) risk in the absence of chromosomal disorders, neurofibromatosis and tuberous sclerosis, taking adverse birth outcomes, maternal hypertension/diabetes and maternal socioeconomic status into consideration.MethodsWe conducted a cohort study of singletons without common genetic defects born in Sweden during 1992–2006, and followed them from birth until 31 December 2014 (n=1 186 836). Cox proportional hazards models were used to analyse the association between maternal BMI in early pregnancy and the risk of offspring’s ID.ResultsThe risk of ID was higher in children born to mothers who were underweight (HR=1.21, 95% CI=1.07 to 1.36), overweight (HR=1.28, 95% CI=1.21 to 1.34) or had obesity class I (HR=1.63, 95% CI=1.53 to 1.74), obesity class II (HR=2.08, 95% CI=1.88 to 2.30) and obesity class III (HR=2.31, 95% CI=1.46 to 3.65) than in children born to normal weight mothers. Results remained consistent after excluding children with adverse birth outcome or born to mothers with gestational hypertension/diabetes. Analysis stratified by maternal education and annual household income showed that the association between maternal underweight and children’s ID risk was attenuated among children of mothers with tertiary education or with high income.ConclusionsOur findings suggest that maternal underweight or overweight/obesity in early pregnancy was associated with the development of ID in their offspring. This association was independent of the effect of adverse birth outcomes and maternal hypertension/diabetes. High socioeconomic status may attenuate the risk of ID among children of underweight mothers. This study highlights the importance of improving health education before conception to reduce children’s ID risk.

(Abstracted from JAMA Network Open2021;4:e2114913)Gestational age (GA) is associated with brain growth and development. When the duration of gestation is not optimal, a range of adverse health outcomes in the offspring including neuropsychiatric morbidities may occur.

(Abstracted from BMJ2019;367:l6398)The primary cause of worldwide mortality and morbidity is cardiovascular disease (CVD). Recently, increases in CVD have disproportionately affected children and young adults, who have experienced the most drastic upticks in disease incidence.

IMPORTANCE: The death of a close relative is associated with an increased mortality risk among the bereaved, but much less is known about the potential association of the death of a sibling in childhood with mortality in this population. OBJECTIVE: To examine the association between sibling death in childhood and subsequent mortality risk. DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study of 5 005 029 participants evaluated linked national registers in Denmark (January 1, 1973, through December 31, 2009) and Sweden (January 1, 1973, through December 31, 2008). A total of 2 060 354 Danish and 2 944 675 Swedish children who survived the first 6 months of their life were included. We excluded 14 children who died of the same external cause as their siblings within 30 days. Data were analyzed from November 2, 2015, through October 14, 2016. EXPOSURES: Participants were classified as exposed if a sibling died in childhood (age &lt;18 years). MAIN OUTCOMES AND MEASURES: Poisson regression was used to estimate mortality rate ratio (MRR) with the exposure as a time-varying variable. RESULTS: Among the 55 818 participants who experienced sibling death in childhood (51.5% male and 48.5% female; median age at loss, 7.0 [interquartile range, 3.3-12.1] years), all-cause mortality risk was increased by 71% (MRR, 1.71; 95% CI, 1.57-1.87) during the follow-up of 37 years. The excess mortality risk was observed for groups with specific causes of death, and the higher MRRs were found when the sibling pairs died of the same cause (death due to disease [MRR, 2.16; 95% CI, 1.87-2.49]; death due to external cause [MRR, 1.91; 95% CI, 1.54-2.37]). The increased mortality risk after sibling death was seen across the follow-up period, regardless of the age at bereavement and the type of death among bereaved siblings, but the magnitude of association was stronger during the first year after sibling death (MRR, 2.51; 95% CI, 1.79-3.54). Higher MRRs were found among sibling pairs with the same sex (MRR, 1.92; 95% CI, 1.70-2.18) and close age (MRR, 1.94; 95% CI, 1.58-2.37). CONCLUSIONS AND RELEVANCE: Bereavement in childhood because of the death of a sibling was associated with an increased risk for mortality in the short and long term. Health care professionals should be aware of individuals’ vulnerability due to sibling death, especially for sibling pairs of close age or the same sex. Social and health care support may help to minimize the potential adverse effects on the bereaved sibling.

PURPOSE:To investigate objective optical quality and changes in light scatter after femtosecond laser small incision lenticule extraction (SMILE) for moderate to high myopia correction.METHODS:Prospective clinical study of 66 eyes of 66 patients (23 males, 43 females) with a mean age of 28.67 ± 6.62 years, mean spherical refraction of −6.06 ± 1.57 diopters, and mean cylindrical refraction of −0.68 ± 0.46 diopters. Every patient had a 3-month follow-up after a standard SMILE procedure. An optical quality analysis system was used to measure modulation transfer function cutoff frequency (MTFProspective clinical study of 66 eyes of 66 patients (23 males, 43 females) with a mean age of 28.67 ± 6.62 years, mean spherical refraction of −6.06 ± 1.57 diopters, and mean cylindrical refraction of −0.68 ± 0.46 diopters. Every patient had a 3-month follow-up after a standard SMILE procedure. An optical quality analysis system was used to measure modulation transfer function cutoff frequency (MTFcutoff), Strehl2D ratio, and objective scatter index (OSI).RESULTS:At 3 months postoperatively, mean spherical equivalent was 0.03 ± 0.24 diopters and corrected distance visual acuities of all patients were equal to or better than preoperative values, with a mean safety index of 1.12 ± 0.17 (range: 0.80 to 1.50) and mean efficacy index of 1.18 ± 0.21 (range: 0.80 to 1.50). Mean OSI increased from 0.75 preoperatively to 1.09 at 20 days postoperatively (At 3 months postoperatively, mean spherical equivalent was 0.03 ± 0.24 diopters and corrected distance visual acuities of all patients were equal to or better than preoperative values, with a mean safety index of 1.12 ± 0.17 (range: 0.80 to 1.50) and mean efficacy index of 1.18 ± 0.21 (range: 0.80 to 1.50). Mean OSI increased from 0.75 preoperatively to 1.09 at 20 days postoperatively (P< .05), and gradually declined to 0.94 at 40 days and 0.82 at 3 months postoperatively (P> .05). MTFcutoffand Strehl2D ratio did not change significantly compared with preoperative values (P> .05). Multiple linear regression analysis revealed that preoperative OSI was significantly correlated with optical quality at 3 months. Patients with less preoperative OSI tended to acquire higher MTFcutoff(b = −8.61) and lower OSI (b = 0.65) (P< .05).CONCLUSIONS:SMILE had little impact on retinal image quality after myopia correction. Postoperative OSI showed a temporary increase and then returned to normal.[[J Refract Surg.2014;30(5):296–302.]

The mutations in oncogenic genes, such as EGFR, ALK, BRAF, HER2, DDR2, RET, and AKT1, defined subsets of non-small cell lung cancers (NSCLCs) with potential sensitivity to targeted therapies. At present, the mutational spectrum, prevalence, and clinicopathologic characteristics in squamous cell carcinomas with minor (< 10%) glandular component (SQCC-mGCs) are not well established.

ObjectiveTo examine the association of maternal hypertensive disorder of pregnancy (HDP) with overall and cause specific mortality in offspring from birth to young adulthood.DesignNationwide population based cohort study.SettingDanish national health registers.ParticipantsAll 2 437 718 individuals live born in Denmark, 1978-2018, with follow-up from date of birth until date of death, emigration, or 31 December 2018, whichever came first.Main outcome measuresThe primary outcome was all cause mortality. Secondary outcomes were 13 specific causes of death in offspring from birth to young adulthood (age 41 years). Cox regression was used to assess the association, taking into consideration several potential confounders. The role of timing of onset and severity of pre-eclampsia, maternal history of diabetes, and maternal education were also studied.Results102 095 mothers had HDP: 67 683 with pre-eclampsia, 679 with eclampsia, and 33 733 with hypertension. During follow-up to 41 years (median 19.4 (interquartile range 9.7-28.7) years), deaths occurred in 781 (58.94 per 100 000 person years) offspring born to mothers with pre-eclampsia, 17 (133.73 per 100 000 person years) born to mothers with eclampsia, 223 (44.38 per 100 000 person years) born to mothers with hypertension, and 19 119 (41.99 per 100 000 person years) born to mothers with no HDP. The difference in cumulative incidence in overall mortality between cohorts exposed and unexposed to maternal HDP was 0.37% (95% confidence interval 0.11% to 0.64%), and the population attributable fraction for maternal HDP was estimated as 1.09% (95% confidence interval 0.77% to 1.41%). Maternal HDP was associated with a 26% (hazard ratio 1.26, 95% confidence interval 1.18 to 1.34) higher risk of all cause mortality in offspring. The corresponding estimates for maternal pre-eclampsia, eclampsia, and hypertension were 1.29 (1.20 to 1.38), 2.88 (1.79 to 4.63), and 1.12 (0.98 to 1.28). Increased risks were also observed for several cause specific mortalities, such as deaths from conditions originating in the perinatal period (2.04, 1.81 to 2.30), cardiovascular diseases (1.52, 1.08 to 2.13), digestive system diseases (2.09, 1.27 to 3.43), and endocrine, nutritional, and metabolic diseases (1.56, 1.08 to 2.27). The increased risks were more pronounced among offspring of mothers with early onset and severe pre-eclampsia (6.06, 5.35 to 6.86) or with both HDP and diabetes history (1.57, 1.16 to 2.14) or HDP and low education level (1.49, 1.34 to 1.66).ConclusionMaternal HDP, particularly eclampsia and severe pre-eclampsia, is associated with increased risks of overall mortality and various cause specific mortalities in offspring from birth to young adulthood.

IMPORTANCE: Nonoptimal gestational durations could be associated with neurodevelopmental disabilities, yet evidence regarding finer classification of gestational age and rates of multiple major neuropsychiatric disorders beyond childhood is limited. OBJECTIVE: To comprehensively evaluate associations between 6 gestational age groups and rates of 9 major types and 8 subtypes of childhood and adult-onset neuropsychiatric disorders. DESIGN, SETTING, AND PARTICIPANTS: This cohort study evaluated data from a nationwide register of singleton births in Denmark from January 1, 1978, to December 31, 2016. Data analyses were conducted from October 1, 2019, through November 15, 2020. EXPOSURES: Gestational age subgroups were classified according to data from the Danish Medical Birth Register: very preterm (20-31 completed weeks), moderately preterm (32-33 completed weeks), late preterm (34-36 completed weeks), early term (37-38 completed weeks), term (39-40 completed weeks, reference), and late or postterm (41-45 completed weeks). MAIN OUTCOMES AND MEASURES: Neuropsychiatric diagnostic records (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes F00-F99) were ascertained from the Danish Psychiatric Central Register up to August 10, 2017. Poisson regression was used to estimate the incidence rate ratio (IRR) and 95% CI for neuropsychiatric disorders, adjusting for selected sociodemographic factors. RESULTS: Of all 2?327?639 singleton births studied (1?194?925 male newborns [51.3%]), 22?647 (1.0%) were born very preterm, 19?801 (0.9%) were born moderately preterm, 99?488 (4.3%) were born late preterm, 388?416 (16.7%) were born early term, 1?198?605 (51.5%) were born at term, and 598?682 (25.7%) were born late or postterm. A gradient of decreasing IRRs was found from very preterm to late preterm for having any or each of the 9 neuropsychiatric disorders (eg, very preterm: IRR,?1.49 [95% CI, 1.43-1.55]; moderately preterm: IRR,?1.23 [95% CI, 1.18-1.28]; late preterm: IRR,?1.17 [95% CI, 1.14-1.19] for any disorders) compared with term births. Individuals born early term had 7% higher rates (IRR,?1.07 [95% CI, 1.06-1.08]) for any neuropsychiatric diagnosis and a 31% higher rate for intellectual disability (IRR,?1.31 [95% CI, 1.25-1.37]) compared with those born at term. The late or postterm group had lower IRRs for most disorders, except pervasive developmental disorders, for which the rate was higher for postterm births compared with term births (IRR,?1.06 [95% CI,?1.03-1.09]). CONCLUSIONS AND RELEVANCE: Higher incidences of all major neuropsychiatric disorders were observed across the spectrum of preterm births. Early term and late or postterm births might not share a homogeneous low risk with individuals born at term. These findings suggest that interventions that address perinatal factors associated with nonoptimal gestation might reduce long-term neuropsychiatric risks in the population.

Cardiovascular disease (CVD) is increasing in youths, but there is limited knowledge about the etiology of early-onset CVD. We aimed to examine the association between maternal education before childbirth and CVD risk in offspring during early adulthood (20-40 years old).

ObjectiveTo evaluate the associations between maternal diabetes diagnosed before or during pregnancy and early onset cardiovascular disease (CVD) in offspring during their first four decades of life.DesignPopulation based cohort study.SettingDanish national health registries.ParticipantsAll 2 432 000 liveborn children without congenital heart disease in Denmark during 1977-2016. Follow-up began at birth and continued until first time diagnosis of CVD, death, emigration, or 31 December 2016, whichever came first.Exposures for observational studiesPregestational diabetes, including type 1 diabetes (n=22 055) and type 2 diabetes (n=6537), and gestational diabetes (n=26 272).Main outcome measuresThe primary outcome was early onset CVD (excluding congenital heart diseases) defined by hospital diagnosis. Associations between maternal diabetes and risks of early onset CVD in offspring were studied. Cox regression was used to assess whether a maternal history of CVD or maternal diabetic complications affected these associations. Adjustments were made for calendar year, sex, singleton status, maternal factors (parity, age, smoking, education, cohabitation, residence at childbirth, history of CVD before childbirth), and paternal history of CVD before childbirth. The cumulative incidence was averaged across all individuals, and factors were adjusted while treating deaths from causes other than CVD as competing events.ResultsDuring up to 40 years of follow-up, 1153 offspring of mothers with diabetes and 91 311 offspring of mothers who did not have diabetes were diagnosed with CVD. Offspring of mothers with diabetes had a 29% increased overall rate of early onset CVD (hazard ratio 1.29 (95% confidence interval 1.21 to 1.37); cumulative incidence among offspring unexposed to maternal diabetes at 40 years of age 13.07% (12.92% to 13.21%), difference in cumulative incidence between exposed and unexposed offspring 4.72% (2.37% to 7.06%)). The sibship design yielded results similar to those of the unpaired design based on the whole cohort. Both pregestational diabetes (1.34 (1.25 to 1.43)) and gestational diabetes (1.19 (1.07 to 1.32)) were associated with increased rates of CVD in offspring. We also observed varied increased rates of specific early onset CVDs, particularly heart failure (1.45 (0.89 to 2.35)), hypertensive disease (1.78 (1.50 to 2.11)), deep vein thrombosis (1.82 (1.38 to 2.41)), and pulmonary embolism (1.91 (1.31 to 2.80)). Increased rates of CVD were seen in different age groups from childhood to early adulthood until age 40 years. The increased rates were more pronounced among offspring of mothers with diabetic complications (1.60 (1.25 to 2.05)). A higher incidence of early onset CVD in offspring of mothers with diabetes and comorbid CVD (1.73 (1.36 to 2.20)) was associated with the added influence of comorbid CVD but not due to the interaction between diabetes and CVD on the multiplicative scale (P value for interaction 0.94).ConclusionsChildren of mothers with diabetes, especially those mothers with a history of CVD or diabetic complications, have increased rates of early onset CVD from childhood to early adulthood. If maternal diabetes does have a causal association with increased CVD rate in offspring, the prevention, screening, and treatment of diabetes in women of childbearing age could help to reduce the risk of CVD in the next generation.