Specific Birth Defects Following Antiseizure Medications Used By Pregnant Women With Epilepsy.

Background and Objectives: Previous research has been limited in the comprehensive study of associations between the use of individual antiseizure medications (ASMs) in pregnancy and specific groups of birth defects, and systematic reviews and meta-analyses on the topic are limited by pooled samples and study designs. This study investigated birth defects related to ASM use in pregnancy in children born to women with epilepsy in Sweden over 20 years. Methods: We used data from Swedish national registers to follow a cohort of 17,996 children born to women diagnosed with epilepsy any time before conception in Sweden from 1996 to 2016, following them through 2017. We examined maternal-reported use of the 4 most commonly reported ASMs: lamotrigine (n = 2,148, 11.9%), carbamazepine (n = 1,940, 10.8%), valproic acid (n = 1,043, 5.80%), and levetiracetam (n = 587, 3.26%). We identified birth defects using diagnoses recorded at the time of discharge from the hospital and inpatient and outpatient diagnoses recorded in the first year of life. Models were estimated in a stepped fashion: unadjusted, adjusted for covariates, among a subcohort born to women diagnosed 10 years before conception (n = 14,586), and restricted to monotherapy. Results: Valproic acid use in pregnancy had the strongest and most widespread associations with birth defects in children, with carbamazepine also having links to several birth defects, including respiratory system and genital organ defects. Lamotrigine use in pregnancy was associated with cleft lip/palate and chromosomal abnormalities. Levetiracetam was most often used with other ASMs and preliminarily associated with many birth defects. Discussion: Our findings support avoidance of valproic acid use in pregnancy whenever possible. Lamotrigine and carbamazepine may be safer alternatives. However, these medications were also associated with certain birth defects, including some not reported previously. We are among the first to examine the possible effects of levetiracetam use in pregnancy, though more research is needed to investigate this further.

Digital device viewing behaviour in children.

INTRODUCTION: Habitual viewing behaviour is widely believed to be an important contributing factor to the onset and progression of myopia and may be task dependent. The purpose of this study was to quantify the habitual viewing distance of children performing five different tasks on a smartphone digital device. METHODS: The real-time viewing distance in 38 children with their habitual correction was measured using software (MyopiaApp) on a handheld (Google Pixel 3) device. Five tasks were performed in a randomised sequence: playing a game, watching video in a light (680 lux) and dark (5.5 lux) environment and reading small (8 pt) and large (16 pt) text. ANCOVA statistical analysis was used to evaluate the effect of task, group (myope vs. non-myope) and arm length on the median relative viewing distance. RESULTS: Arm length was not correlated with viewing distance in any of the tasks, and there was no significant difference in viewing distance between any of the tasks. Specifically, a two-way mixed ANCOVA indicated that task, refractive group (myopic vs. non-myopic), age and arm length, as well as all two-way interactions were not significantly associated with viewing distance. Overall, 60% of the total variance in viewing distance was accounted for by individual differences. CONCLUSIONS: The average handheld viewing distance was similar across a variety of everyday tasks in a representative sample of myopic and emmetropic children. Neither arm length, age nor refractive group were associated with viewing distance in any of the tasks. Importantly, myopic children of a given size did not hold the smartphone digital device at a different distance for any task than their equally sized non-myopic peers. However, both groups exhibited high inter-individual variability in mean viewing distance, indicating some subjects performed all tasks at further distances while other subjects used at nearer distances.

The association between participant-reported ratings of comfort, dryness and vision quality in soft contact lens wearers.

INTRODUCTION: Previous literature has indicated an association between participant-reported perceptions (e.g., ratings) of comfort, dryness and vision quality during soft contact lens wear. However, these reports do not account for participant- and lens-specific factors which may impact the interpretation of these results. The purpose of this project was to quantify the association between these participant-reported ratings while accounting for both participant- and lens-specific factors. METHODS: Participant-reported ratings (scale 0-100) of comfort, dryness and quality of vision for 675 soft contact lens wearers (1207 eyes) were aggregated across 31 studies completed at Indiana University. Linear mixed-effects regression modelling was performed on each outcome rating individually. Covariate-adjusted models incorporated both participant- (e.g., age, sex) and lens-related (e.g., lens material, edge and optics) factors. The models were statistically adjusted for the duration of lens wear in hours and cumulative days of exposure. RESULTS: Consistent with estimates from covariate-adjusted regression models, pairwise Spearman correlations [95% CI] between dryness and comfort (rs = 0.71, [0.69, 0.74]), vision quality and comfort (rs = 0.53, [0.49, 0.57]) and vision quality and dryness (rs = 0.49, [0.42, 0.54]) were all positive and had p < 0.001. Average participant-reported ratings of comfort, dryness and vision quality decreased by (bs [95% CI]) = -0.81 [-1.15, -0.46] -0.34 [-0.67, 0.0005] and -0.90 [-1.19, -0.60] rating units, respectively, for each hour of lens wear. CONCLUSIONS: Significant positive associations were found between participant-reported measures of comfort, dryness and vision quality during soft contact lens wear. The associations between these ratings and the participant- and lens-related factors that drive them should be considered by clinicians and manufacturers when fitting and designing soft contact lenses.

On-eye centration of soft contact lenses.

PURPOSE: To evaluate the relative positions of modern soft contact lenses (SCLs) relative to the limbus/cornea and the pupil. METHODS: Sixty images of the anterior eyes of 101 subjects were acquired over 10 s while participants fixated the centre of the camera lens located 33 cm in front of the eye in a well-lit (300 lux) clinic. Custom validated image analysis software was used to locate the boundaries of the contact lenses, pupils and corneas (limbus). Horizontal and vertical relative positions of the contact lens, pupil and limbus were calculated from the fitted boundaries. RESULTS: The mean (standard deviation) pupil and corneal diameters for all subjects were 3.84 mm, (0.83) and 11.97 mm (0.48), respectively. The mean [95% confidence interval] pupil centre was located 0.28 mm [0.26, 0.30] nasally and 0.07 mm [0.05, 0.10] superiorly to the corneal centre. Consistent with clinical observations, the contact lenses centred accurately relative to the corneal centre both nasally 0.04 mm [0.01, 0.07] and inferiorly -0.01 mm [-0.06, 0.03]. However, regardless of the eye, the contact lens was significantly (p < 0.001) decentred relative to the pupil centre both temporally -0.23 mm [-0.26, -0.20] and inferiorly -0.08 mm [-0.12, -0.04]. Decentration magnitudes were significantly correlated between the right and left eyes. CONCLUSIONS: Spherical SCLs centred well on the cornea but temporally and inferiorly from the primary line of sight (pupil centre), due to the differences in the location of the pupil and corneal centres. Contrary to some previous reports, there was no evidence that lens optics or material affected lens centration significantly.

Racial-Ethnic Differences in ADHD Diagnosis and Treatment During Adolescence and Early Adulthood.

OBJECTIVE: This study examined racial-ethnic differences in attention-deficit hyperactivity disorder (ADHD) diagnosis and treatment during adolescence and early adulthood. METHODS: A national health care claims database was used to identify a cohort of 4,216,757 commercially insured youths with at least 1 year of coverage during 2014-2019. Racial-ethnic differences in the prevalence of visits with a recorded ADHD diagnosis (identified through ICD-9-CM and ICD-10-CM codes) and of ADHD treatment (identified through medical claims for psychosocial treatments and pharmacy claims for ADHD medications) were examined. Period prevalence rates were determined within five age categories, stratified by race-ethnicity. Poisson regression with a natural log link was used within each age category to estimate prevalence ratios (PRs) comparing prevalence in each racially and ethnically minoritized group with prevalence in the White group. RESULTS: The overall prevalence of ADHD diagnosis was 9.1% at ages 12-14 and 5.3% at ages 24-25. In each age category, Asian, Black, and Hispanic youths had lower prevalence of ADHD diagnosis than did White youths (PR=0.29-0.77). Among youths with an ADHD diagnosis, relative racial-ethnic differences in treatment were small (PR=0.92-1.03). CONCLUSIONS: Throughout adolescence and early adulthood, racially and ethnically minoritized youths were less likely than White youths to have health care visits with recorded ADHD diagnoses and, among those with diagnoses, were also slightly less likely to receive treatment. More research is needed to understand the processes underlying these differences and their potential health consequences among racially and ethnically minoritized youths.

Clinical Comparison of High-resolution and Standard Refractions and Prescriptions.

SIGNIFICANCE: Recently, novel refraction technology allows subjective refractions to be performed with a higher-resolution. It is unclear, however, if these benefits are noticed and appreciated by the patient during the examination and after dispensing. PURPOSE: This study investigated benefits and drawbacks of high-resolution refraction technology over standard, specifically in terms of the refraction, glasses prescription, and participant's perceptions of the technology. METHODS: Sixty progressive-addition-lens wearers (aged 35 to 70 years) and 60 single-vision wearers (18 years or older) were randomized to a high-resolution refraction (Vision-R 800; Essilor Instruments, Dallas, TX; essilorinstrumentsusa.com ) and standard refraction in a 2-week crossover dispensing design. Refractive results were converted to M, J0, and J45 and analyzed using multivariate t tests. Bayesian estimation was used to analyze differences between refraction type and age group for subjective outcomes. RESULTS: Differences in refractive error between the two refractions were small, and none differed statistically ( P > .05) or clinically (e.g., <0.25 D) in either subgroup. Visual acuities at distance and near were better than 0.00 logMAR; none of the mean differences between the refractions reached statistical or clinical (e.g., <0.10 D) significance. Participants significantly preferred the high-resolution refraction for its quickness and efficiency, improved comfort, and less stress. Bayesian analysis indicated a 76% probability that participants had higher confidence in the high-resolution refraction, 93% probability that they would seek it out for their care, and 94% probability that they would recommend an optometrist using this technology. CONCLUSIONS: Refractive and acuity endpoints were similar with the high-resolution and standard refraction. Participants, however, perceived several key benefits of the high-resolution refraction and prescription for their care, the care of their friends/family, and the practice itself.

Impact of zone geometry on the introduction of myopic defocus in young adult eyes wearing multi-zone lenses.

PURPOSE: Multizone contact lenses control myopia progression by proposed introduction of myopic defocus. This project investigated how much of the pupil area and how many dioptres of myopic defocus are introduced by different lens zone geometries with near- and off-axis viewing. METHODS: Ten young myopic adults (18-25 years) binocularly wore four soft contact lenses including a single vision (SV), concentric-ring dual-focus (DF), centre-distance multifocal (MF) and a RingBoost™ (RB) multi-zone design containing a combination of coaxial and non-coaxial zones. A modified aberrometer captured aberrations and pupil sizes at four target vergences between -0.25 and -4.00 D (on-axis) and across the central ±30° of the horizontal retina (off-axis). Defocus was quantified as the difference between the measured refractive state and the target vergence within each zone of a multi-zone design within the pupil and compared with that of equivalent zone areas of the SV lens. The percentage of the pupil containing myopic defocused light for each lens was calculated. RESULTS: Defocus within the distance correction zones of multi-zone lenses was similar to that of the SV lens. When viewing on-axis at -0.25 D target vergence, on average 11% of the pupil was myopic with SV, whereas 62%, 84% and 50% of the pupil was myopic for the DF, MF and RB designs, respectively. At -4.00 D target vergence, all lenses exhibited a systematic decrease in the percentage of pupil area having myopic defocus (SV: 3%; DF: 18%; MF: 5% and RB: 26%). The off-axis proportions were similar across multi-zone lenses; however, multi-zone lenses retained approximately 1.25-3.0× more myopic defocus than the SV lens. CONCLUSIONS: Subjects accommodated using the distance-correction zones of multi-zone lenses. Multi-zone contact lenses introduced significant myopic defocus on-axis and across the central ±30° retina. However, the magnitude and proportion of defocus were influenced by zone geometry, add power and pupil size.

Myopia Control Dose Delivered to Treated Eyes by a Dual-focus Myopia-control Contact Lens.

PURPOSE: This study examined the optical impact of a DF contact lens during near viewing in a sample of habitual DF lens wearing children. METHODS: Seventeen myopic children aged 14 to 18 years who had completed 3 or 6 years of treatment with a DF contact lens (MiSight 1 Day; CooperVision, Inc., San Ramon, CA) were recruited and fit bilaterally with the DF and a single-vision (Proclear 1 Day; CooperVision, Inc.) contact lens. Right eye wavefronts were measured using a pyramidal aberrometer (Osiris; CSO, Florence, Italy) while children accommodated binocularly to high-contrast letter stimuli at five target vergences. Wavefront error data were used to compute pupil maps of refractive state. RESULTS: During near viewing, children wearing single-vision lenses accommodated on average to achieve approximate focus in the pupil center but, because of combined accommodative lag and negative spherical aberration, experienced up to 2.00 D of hyperopic defocus in the pupil margins. With DF lenses, children accommodated similarly achieving approximate focus in the pupil center. When viewing three near distances (0.48, 0.31, and 0.23 m), the added +2.00 D within the DF lens treatment optics shifted the mean defocus from +0.75 to -1.00 D. The DF lens reduced the percentage of hyperopic defocus (≥+0.75 D) in the retinal image from 52 to 25% over these target distances, leading to an increase in myopic defocus (≤-0.50 D) from 17 to 42%. CONCLUSIONS: The DF contact lens did not alter the accommodative behavior of children. The treatment optics introduced myopic defocus and decreased the amount of hyperopically defocused light in the retinal image.

Retrospective review of the effectiveness of orthokeratology versus soft peripheral defocus contact lenses for myopia management in an academic setting.

PURPOSE: To evaluate the relative efficacy of peripheral defocus contact lenses (PDCLs) and orthokeratology (OK) in a real-world clinical population, and compare these results with previous randomised controlled clinical trials. METHODS: Records from a university practice were reviewed to identify children who were treated with OK or PDCLs. The analysed sample contained 273 visits from 77 patients. Annualised rates of axial length (AL) progression were calculated and used as the response variable in both linear mixed-effects (LME) and nonlinear regression models. RESULTS: On average, children were 10.7 years of age at baseline (p = 0.14 between treatments), and most patients were female. More Asian children wore OK lenses compared with PDCLs (p < 0.01). At baseline, children had ~3.00 D of myopia and 0.75 D of astigmatism in both treatment groups (p > 0.20 between treatments). LME regression models using only baseline covariates showed no evidence that the annualised change in AL differed between treatments, with or without the inclusion of age, race, sex, baseline AL or spherical equivalent refractive error. Across all possible subsets of models, age at baseline was the best predictor of annualised AL change. There was no statistical difference between parameters of an exponential decay model fitted within treatment using follow-up age as a time-varying predictor, indicating that the rate of annualised change in AL was similar for OK and PDCL. CONCLUSIONS: Retrospective analysis of real-world clinical data found no difference in annualised AL growth between PDCL and OK. Importantly, the AL progression from this clinical setting is consistent with that reported in randomised clinical trials. Therefore, continued research of real-world performance is warranted to understand the safety and efficacy of modern myopia control treatments in the broader population.

Maternal Serotonergic Antidepressant Use in Pregnancy and Risk of Seizures in Children.

OBJECTIVE: To evaluate whether children born to women who use serotonergic antidepressants during pregnancy have higher risk of neonatal seizures and epilepsy. METHODS: We used Swedish register-based data to examine associations between maternal-reported use of selective-serotonin reuptake inhibitor (SSRI) and selective serotonin-norepinephrine reuptake inhibitors (SNRI) in pregnancy and diagnosis of neonatal seizures and/or epilepsy in over 1.2 million children. To account for systematic differences between exposed and unexposed children we adjusted for a wide range of measured confounders. After first evaluating the role of maternal indication for SSRI/SNRI use (i.e., depression and anxiety) and parental epilepsy, we adjusted for remaining parental background factors (e.g., age, co-morbidities, education, and family socioeconomic indices) and pregnancy-specific characteristics (e.g., maternal use of other psychotropic medications and tobacco smoking in early pregnancy). RESULTS: Compared with all other children, children of women that reported use of SSRI/SNRI in pregnancy had an elevated risk of neonatal seizures and epilepsy (risk ratio [RR]=1.41, 95% confidence interval [CI]=1.03-1.94; hazard ratio [HR]=1.21, 95% CI=1.03-1.43 respectively). The estimates of association were attenuated by adjustment for maternal indications for SSRI/SNRI use (RR=1.30, 95% CI=0.94-1.79; HR = 1.13, 95% CI = 0.95-1.33), but not by additional adjustment for parental history of epilepsy. Full adjustment for all measured parental and pregnancy-specific factors resulted in substantial attenuation of the remaining associations (RR = 1.10, 95% CI = 0.79-1.53; HR = 0.96, 95% CI = 0.81-1.14). CONCLUSIONS: The present study found no support for the concern that maternal SSRI/SNRI use in pregnancy increases children's risk for neonatal seizures or epilepsy. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that exposure to SSRI/SNRI's in the first trimester of pregnancy is not associated with an increased incidence of neo-natal seizures/epilepsy.

Initiation of Opioid Prescription and Risk of Suicidal Behavior Among Youth and Young Adults.

BACKGROUND AND OBJECTIVES: Opioids are involved in an increasing proportion of suicide deaths. This study examined the association between opioid analgesic prescription initiation and suicidal behavior among young people. METHODS: We analyzed Swedish population-register data on 1 895 984 individuals ages 9 to 29 years without prior recorded opioid prescriptions. We identified prescriptions dispensed from January 2007 onward and diagnosed self-injurious behavior and death by suicide through December 2013. We first compared initiators with demographically matched noninitiators. To account for confounding, we applied an active comparator design, which examined suicidal behavior among opioid initiators relative to prescription nonsteroidal antiinflammatory drug (NSAID) initiators while inverse-probability-of-treatment weighting with individual and familial covariates. RESULTS: Among the cohort, 201 433 individuals initiated opioid prescription. Relative to demographically matched noninitiators, initiators (N = 180 808) had more than doubled risk of incident suicidal behavior (hazard ratio = 2.64; 95% confidence interval [CI], 2.47-2.81). However, in the active comparator design, opioid initiators (N = 86 635) had only 19% relatively greater risk of suicidal behavior compared with NSAID initiators (N = 255 096; hazard ratio = 1.19; 95% CI,: 1.11-1.28), corresponding to a weighted 5-year cumulative incidence of 2.2% (95% CI, 2.1-2.4) for opioid and 1.9% (95% CI, 1.9-2.0) for NSAID initiators. Most sensitivity analyses produced comparable results. CONCLUSIONS: Opioid initiation may make only a small contribution to the elevated risk of suicidal behavior among young people receiving pharmacologic pain management. In weighing benefits and harms of opioid initiation, our results suggest that increased risk of suicidal behavior may not be a major concern.

Associations of opioid prescription dose and discontinuation with risk of substance-related morbidity in long-term opioid therapy.

ABSTRACT: Efforts to reduce opioid-related harms have decreased opioid prescription but have provoked concerns about unintended consequences, particularly for long-term opioid therapy (LtOT) recipients. Research is needed to address the knowledge gap regarding how risk of substance-related morbidity changes across LtOT and its discontinuation. This study used nationwide commercial insurance claims data and a within-individual design to examine associations of LtOT dose and discontinuation with substance-related morbidity. We identified 194,839 adolescents and adults who initiated opioid prescription in 2010 to 2018 and subsequently received LtOT. The cohort was followed for a median of 965 days (interquartile range, 525-1550), of which a median of 176 days (119-332) were covered by opioid prescription. During follow-up, there were 17,582 acute substance-related morbidity events, defined as claims for emergency visits, inpatient hospitalizations, and ambulance transportation with substance use disorder or overdose diagnoses. Relative to initial treatment, risk was greater within individual during subsequent periods of >60 to 120 (adjusted odds ratio [OR], 1.29; 95% CI, 1.12 to 1.49) and >120 (OR, 1.48; 95% CI, 1.24-1.76) daily morphine milligram equivalents. Risk was also greater during days 1 to 30 after discontinuations than during initial treatment (OR, 1.19; 95% CI, 1.05-1.35). However, it was no greater than during the 30 days before discontinuations, indicating that the risk may not be wholly attributable to discontinuation itself. Results were supported by a negative control pharmacotherapy analysis and additional sensitivity analyses. They suggest that LtOT recipients may experience increased substance-related morbidity risk during treatment subsequent to initial opioid prescription, particularly in periods involving higher doses.

A Nation-Wide Swedish Cohort Study on Early Maternal Age at First Childbirth and Risk for Offspring Deaths, Accidents, and Suicide Attempts.

In a sample of over one million Swedish first-born offspring, we examined associations between early maternal age at first childbirth (MAFC; i.e., < 20 and 20-24 vs 25-29 years) and offspring non-accidental deaths, accidental deaths, deaths by suicide, non-fatal accidents, and suicide attempts. We included year of birth and several maternal and paternal characteristics as covariates and conducted maternal cousin comparisons to adjust for unmeasured confounding. Early MAFC (e.g., teenage childbearing) was associated with all outcomes, with the most pronounced risk elevation for accidental deaths [Hazard Ratio (HR) < 20 2.50, 95% confidence interval (CI) 2.23, 2.80], suicides (HR < 20 2.08, 95% CI 1.79, 2.41), and suicide attempts (HR < 20 2.85, 95% CI 2.71, 3.00). Adjusting for covariates and comparing cousins greatly attenuated associations (e.g., accidental deaths HR < 20 1.61, 95% CI 1.22, 2.11; suicides HR < 20 1.01, 95% CI 0.69, 1.47; and suicide attempts HR < 20 1.35, 95% CI 1.19, 1.52). A similar pattern emerged for non-accidental deaths and non-fatal accidents. Therefore, results indicated maternal background factors may be largely responsible for observed associations.

A nation-wide Swedish study of opioid analgesic prescribing patterns during pregnancy and associated preexisting mental health conditions.

INTRODUCTION: Research has consistently shown individuals with mental health conditions are more likely to be prescribed opioid analgesic medications and to engage in heavier utilization. However, it is unclear whether these findings apply to pregnant women. STUDY DESIGN: We explored opioid analgesic prescription in 689,400 pregnancies occurring in Sweden between 2007 and 2013. We investigated prescription patterns across time and type of source clinic for any opioid analgesic and for strong and weak opioid analgesics. We further evaluated the extent to which receipt of opioid analgesic medications was associated with previous mental health diagnoses and prescriptions of other psychoactive medications. RESULTS: The prevalence of pregnant women who filled prescriptions for opioid analgesics (4.5%) was relatively stable across the assessed years. However, among pregnant women who filled opioid analgesic prescriptions, there was a large increase in strong opioid analgesic prescriptions-from 6.1% in 2007 to 17.1% in 2013. The main source of opioid analgesic prescriptions were primary care and obstetrics and gynecology clinics-38.7% of all filled prescriptions originated from primary care providers and 25.3% from obstetrics and gynecology practitioners. Compared to pregnant women who did not fill any opioid analgesic prescriptions, those who did were more likely to have a wide range of preexisting mental health diagnoses (e.g. anxiety disorder odds ratio [OR] = 3.13, 95% confidence interval [CI]:2.98,3.29) and to utilize a wide range of other psychoactive medications (e.g. benzodiazepines OR = 4.26, 95% CI:4.10,4.43). Similarly, those who received strong opioids were more likely to have a wide range of mental health diagnoses and be prescribed a wide range of psychoactive medications compared to those who received weak opioids. CONCLUSIONS: These results highlight the need for physicians treating pregnant women and women of childbearing age for painful conditions to obtain detailed histories of mental health problems, screen for symptoms of mental health problems, and facilitate integrated care and evidence-based mental health interventions if needed.

Risk factors and child outcomes associated with short and long interpregnancy intervals.

Previous research assessing consequences of interpregnancy intervals (IPIs) on child development is mixed. Utilizing a population-based US sample (n=5,339), we first estimated the associations between background characteristics (e.g., sociodemographic and maternal characteristics) and short (≤ 1 year) and long (> 3 years) IPI. Then, we estimated associations between IPI and birth outcomes, infant temperament, cognitive ability, and externalizing symptoms. Several background characteristics, such as maternal age at childbearing and previous pregnancy loss, were associated with IPI, indicating research on the putative effects of IPI must account for background characteristics. After covariate adjustment, short IPI was associated with poorer fetal growth and long IPI was associated with lower infant activity level; however, associations between short and long IPI and the other outcomes were neither large nor statistically significant. These findings indicate that rather than intervening to modify IPI, at-risk families may benefit from interventions aimed at other modifiable risk factors.

A population-based study of concurrent prescriptions of opioid analgesic and selective serotonin reuptake inhibitor medications during pregnancy and risk for adverse birth outcomes.

BACKGROUND: Pregnant women with painful conditions often have mental health problems, including depression and anxiety. Co-morbid conditions may cause pregnant women to use multiple medications, although safety of such practice is poorly understood. OBJECTIVES: We investigated the influence of combined prescriptions of opioid analgesics and selective serotonin reuptake inhibitors (SSRIs) during pregnancy on two adverse birth outcomes. METHODS: We analysed Swedish population-based births (n = 688 914) between 2007 and 2013. Using national registers, we obtained data on filled medication prescriptions, birth outcomes, and a wide range of parental characteristics. We estimated preterm birth and small-for-gestational-age risk following independent or combined prescriptions of the two medications compared with no filled prescriptions for either medication. We adjusted for confounders using inverse probability of treatment weights. RESULTS: After adjusting for confounders, preterm birth risk was higher among women with opioid analgesic prescriptions only (5.9%; risk ratio [RR] 1.27, 95% confidence interval [CI] 1.22, 1.33), SSRIs only (6.2%; RR 1.34, 95% CI 1.27, 1.42), and both medications (7.8%; RR 1.70, 95% CI 1.47, 1.96) compared with unexposed women (4.6%). The interaction between the medications on preterm birth was small (risk difference [RD] 0.4%, 95% CI -0.8%, 1.6%); relative excess risk due to interaction [RERI] 0.09, 95% CI -0.17, 0.34; RR 1.00, 95% CI 0.85, 1.17). For small for gestational age, risk was approximately 2% across all groups, and there was no interaction between the medications (RD 0.3%, 95% CI -0.4%, 1.1%); RERI 0.15, 95% CI -0.16, 0.47; RR 1.15, 95% CI 0.87, 1.52). CONCLUSIONS: Compared with unexposed pregnancies, those with either medication alone had a small increased risk for preterm birth but no increased risk for small for gestational age. The magnitude of associations with combined exposure to both medications were not greater than the sum of the associations with each medication considered individually.

Time-course of the visual Impact on presbyopes of a low dose miotic.

PURPOSE: To examine the pupil and visual impact of a single early morning drop of a low concentration miotic. METHODS: Pupil size, refraction, visual acuity (VA), near reading performance and intraocular pressure were monitored for 8 h at a wide range of light levels following bilateral instillation of single drops of 0.1% brimonidine tartate in 19 early presbyopes (40-50 years) and 11 mature presbyopes (>50 years). RESULTS: Pupil miosis did not alter distance VA or refraction. Significant pupil miosis peaked at 1-2 h after dosing, which expanded the depth of focus of mature presbyopes with the mean improvement in near logMAR VA of -0.15, -0.07 and -0.03, at 20, 200 and 2000 lux, respectively. One hour after instillation, near reading speed improved by 21, 24 and 5 words per min for text size commonly seen in US newspaper and cellphone text messages, 18, 21 and 19 words per min for text size of grocery labels and 12, 13 and 30 words per min for text size of over-the-counter medications at light levels of 20, 200 and 2000 lux, respectively. No such improvements in near VA and near reading speed were observed in the young presbyopes having some residual accommodation. Most of the pupil miosis remained 8 h after instillation, whereas near VA improvements disappeared after 4 h. CONCLUSION: Low dose miotics can enhance near vision in presbyopic subjects while retaining high quality distance vision over a wide range of light levels. Significant improvements in near vision were observed only during the 1-2 h period after dosing when miosis peaked.

Ocular symptoms associated with digital device use in contact lens and non-contact lens groups.

PURPOSE: Previous reports indicate that "eye fatigue" occurs in roughly 60 % of the adult population using digital devices and may negatively impact quality of life. However, the construct of eye fatigue remains poorly understood. The goal of this study was to quantify the relationship among symptoms most frequently associated with eye fatigue in those using digital devices. METHODS: Six hundred and two soft contact lens (SCL) wearers and 127 non-contact lens (non-CL) wearers who reported using digital devices at least 4 hours per day completed a questionnaire assessing the frequency and severity of ten symptoms commonly associated with digital device-related eye fatigue. Subjective ratings were made separately for each symptom using unipolar, five-point Likert scales. RESULTS: From the initial pool of respondents, 89 % of the SCL wearers reported experiencing eye fatigue more than once per month, while over 60 % reported more than once per week. Notably, eye fatigue frequency did not differ between the soft contact and non-contact lens groups. Although eye strain/pain, dryness, and tired eyes were the most frequently endorsed symptoms by both groups, only dryness and eye irritation were significant factors that discriminated the SCL from the non-CL wearers on the basis of frequency and severity. Principal component analysis indicated that eye strain/pain, soreness, tired eyes, and headaches may comprise a "primary sensations" factor, whereas burning, eye irritation, tearing and dryness comprise a "secondary or surface sensations" factor, and blurred/double vision and words move/float comprise a "visual sensations" factor. Confirmatory factor analysis (CFA) of frequency and severity ratings for SCL wearers yielded excellent fits (RMSEA = 0.046 and 0.050, respectively) with construct reliabilities ranging from 0.729 to 0.824. CONCLUSION: Frequent and severe eye fatigue is highly prevalent among both soft contact lens and non-contact lens wearers. Those utilizing SCL do not experience symptoms at higher frequency or severity. Key descriptors of digital eye fatigue have been identified and may then be used to help identify and evaluate specific causative, palliative, or ameliorating factors.

Antiseizure medication use during pregnancy and risk of ASD and ADHD in children.

OBJECTIVE: To determine whether children born to women who use antiseizure medications (ASMs) during pregnancy have higher risk of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) independent of confounding factors. METHODS: We used Swedish register data (n = 14,614 children born 1996-2011 and followed up through 2013) to examine associations in children of women with epilepsy, using the largest sample to date and adjusting for a range of measured confounders. We examined maternal-reported first-trimester use of any ASM (22.7%) and the 3 most commonly reported individual drugs (valproic acid 4.8%, lamotrigine 6.8%, and carbamazepine 9.7%). We identified ASD with ICD-10 diagnoses and ADHD with ICD-10 diagnoses or filled prescriptions of ADHD medication. RESULTS: Examination of individual drugs revealed that after adjustment for confounding, use of valproic acid was associated with ASD (hazard ratio [HR] 2.30, 95% confidence interval [CI] 1.53-3.47) and ADHD (HR 1.74, 95% CI 1.28-2.38). Whereas a small, nonstatistically significant association with ASD (HR 1.25, 95% CI = 0.88-1.79) and ADHD (HR 1.18, 95% CI 0.91-1.52) remained for reported use of carbamazepine, confounding explained all of the associations with lamotrigine (HRASD 0.86, 95% CI 0.67-1.53; HRADHD 1.01, 95% CI 0.67-1.53). CONCLUSIONS: We found no evidence of risk related to exposure to lamotrigine, whereas we observed elevated risk of ASD and ADHD related to maternal use of valproic acid. Associations with carbamazepine were weak and not statistically significant. Our findings add to a growing body of evidence that suggests that certain ASMs may be safer than others in pregnancy.

Association of Opioid Prescription Initiation During Adolescence and Young Adulthood With Subsequent Substance-Related Morbidity.

Importance: Concerns about adverse outcomes associated with opioid analgesic prescription have led to major guideline and policy changes. Substantial uncertainty remains, however, regarding the association between opioid prescription initiation and increased risk of subsequent substance-related morbidity. Objective: To examine the association of opioid initiation among adolescents and young adults with subsequent broadly defined substance-related morbidity. Design, Setting, and Participants: This cohort study analyzed population-register data from January 1, 2007, to December 31, 2013, on Swedish individuals aged 13 to 29 years by January 1, 2013, who were naive to opioid prescription. To account for confounding, the analysis compared opioid prescription recipients with recipients of nonsteroidal anti-inflammatory drugs as an active comparator, compared opioid-recipient twins and other multiple birth individuals with their nonrecipient co-multiple birth offspring (co-twin control), examined dental prescription as a specific indication, and included individual, parental, and socioeconomic covariates. Data were analyzed from March 30, 2019, to January 22, 2020. Exposures: Opioid prescription initiation, defined as first dispensed opioid analgesic prescription. Main Outcomes and Measures: Substance-related morbidity, assessed as clinically diagnosed substance use disorder or overdose identified from inpatient or outpatient specialist records, substance use disorder or overdose cause of death, dispensed pharmacotherapy for alcohol use disorder, or conviction for substance-related crime. Results: Among the included cohort (n = 1 541 862; 793 933 male [51.5%]), 193 922 individuals initiated opioid therapy by December 31, 2013 (median age at initiation, 20.9 years [interquartile range, 18.2-23.6 years]). The active comparator design included 77 143 opioid recipients without preexisting substance-related morbidity and 229 461 nonsteroidal anti-inflammatory drug recipients. The adjusted cumulative incidence of substance-related morbidity within 5 years was 6.2% (95% CI, 5.9%-6.5%) for opioid recipients and 4.9% (95% CI, 4.8%-5.1%) for nonsteroidal anti-inflammatory drug recipients (hazard ratio, 1.29; 95% CI, 1.23-1.35). The co-twin control design produced comparable results (3013 opioid recipients and 3107 nonrecipients; adjusted hazard ratio, 1.43; 95% CI, 1.02-2.01), as did restriction to analgesics prescribed for dental indications and additional sensitivity analyses. Conclusions and Relevance: Among adolescents and young adults analyzed in this study, initial opioid prescription receipt was associated with an approximately 30% to 40% relative increase in risk of subsequent substance-related morbidity in multiple designs that adjusted for confounding. These findings suggest that this increase may be smaller than previously estimated in some other studies.